松村 到(マツムラ イタル)
学長/短期大学部学長 | 教授/主任 |
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J-Global ID
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- 血液内科学 Hematology
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- Kazuya Shimoda; Norio Komatsu; Itaru Matsumura; Kazuhiko Ikeda; Masayuki Hino; Michihiro Hidaka; Yoshinobu Maeda; Takeshi Kondo; Tomoaki Fujisaki; Keita Shoshi; Kyoichi Azuma; Ryuichi Fukushima; Jun Kawashima; Hiroshi KosugiInternational journal of hematology 2024年08月Momelotinib, an oral Janus kinase (JAK) 1/2 and activin A receptor type 1 inhibitor, improved symptoms, splenomegaly, and anemia in patients with myelofibrosis (MF). This sub-analysis of SIMPLIFY-1 evaluated the efficacy and safety of momelotinib versus ruxolitinib in Japanese patients with JAK inhibitor (JAKi)-naïve MF. Patients were randomized 1:1 to receive momelotinib 200 mg once daily or ruxolitinib 20 mg twice daily (or modified based on label) for 24 weeks, after which patients could receive open-label momelotinib. The primary endpoint was splenic response rate (SRR; ≥ 35% reduction in spleen volume) at 24 weeks; main secondary endpoints were total symptom score (TSS) response (≥ 50% reduction) and transfusion independence (TI) rates. Fifteen Japanese patients (momelotinib, n = 6; ruxolitinib, n = 9) were enrolled; all completed treatment. At Week 24, SRR was 50.0% with momelotinib and 44.4% with ruxolitinib. TSS response rates were 33.3% and 0%, and TI rates were 83.3% and 44.4%. Any-grade treatment-related adverse event (TRAE) rates were 83.3% with momelotinib and 88.9% with ruxolitinib. Grade 3/4 TRAE rates were 0% and 55.6%, with specific events being anemia (55.6%) and vertigo (11.1%) with ruxolitinib. Momelotinib was well tolerated, improved spleen and symptom responses, and reduced transfusion requirements in Japanese patients with JAKi-naïve MF.
- Keiki Nagaharu; Eiko Ohya; Yoko Edahiro; Yoshinori Hashimoto; Tomoki Ito; Akihiko Gotoh; Mika Nakamae; Fumihiko Kimura; Michiaki Koike; Keita Kirito; Hideho Wada; Kensuke Usuki; Takayuki Tanaka; Takehiko Mori; Satoshi Wakita; Toshiki I Saito; Akiko M Saito; Kazuya Shimoda; Toshiro Kurokawa; Akihiro Tomita; Hitoshi Kiyoi; Koichi Akashi; Itaru Matsumura; Katsuto Takenaka; Norio Komatsu; Kohshi Ohishi; Isao Tawara; Yuka SugimotoAnnals of hematology 2024年07月Thrombosis in myeloproliferative neoplasms (MPNs) is an important clinical problem, and risk-stratified management is essential. To identify the clinical characteristics of thrombosis in patients with MPNs, a nationwide multi-institutional retrospective analysis (JSH-MPN-R18) was conducted. The aim of the present study was to perform a sub-analysis of JSH-MPN-R18 findings to clarify the predictive parameters for thrombosis among complete blood count (CBC) results. Among the patients enrolled in JSH-MPN-R18, those with essential thrombocythemia (ET; n = 1152) and polycythemia vera (PV; n = 456) were investigated. We analyzed and compared CBC parameters between patients with and those without any thrombotic events using Welch's T-test. Statistical analyses were performed using the R statistical software. Thrombotic events were observed in 74 patients with ET. In multivariate analysis, only the neutrophil ratio was slightly but significantly higher for ET patients with thrombosis than for those without (p < 0.05). Of note, the absolute neutrophil count (aNeu) was considered a useful predictive tool for thrombosis among patients classified as low-risk according to the revised International Prognostic Score of Thrombosis for Essential Thrombocythemia. Among PV patients, those with thrombosis showed significantly higher hematocrit and aNeu than did those without thrombosis. As a thrombosis-associated factor, the neutrophil ratio was slightly but significantly elevated in patients with ET. This myeloid skew might reflect a higher value of JAK2 V617F allelic frequency in patients with ET with thrombosis; this was not clarified in JSH-MPN-R18. Further accumulation of evidence, including genetic information for JAK2 and other passenger mutations, is warranted.
- Yuji Nozaki; Hisaya Akiba; Hiroki Akazawa; Hirotaka Yamazawa; Kaori Ishimura; Koji Kinoshita; Itaru MatsumuraClinical and experimental immunology 2024年07月Members of the T-cell immunoglobulin and mucin (TIM) family, which is crucial for T-cell function, are implicated in autoimmunity. TIM-1 and -3 play distinct roles in autoimmunity, with TIM-1 acting as a costimulatory molecule and TIM-3 regulating Th1 responses. We investigated the therapeutic potential of anti-TIM-1 (RMT1-10) and anti-TIM-3 (RMT3-23) antibodies in an autoimmune arthritis model. Zymosan A was used to induce arthritis in female SKG mice. The arthritis scores, histology, mRNA expression, cytokine levels, micro-CT, and flow cytometry results were obtained. The application of RMT1-10 reduced the arthritis scores, histological damage, and CD4+T cell infiltrations, and it suppressed interleukin (IL)-6 and -17A and reduced TIM-3 mRNA expressions. RMT3-23 also lowered arthritis severity, improved histology, and reduced serum levels of tumor necrosis factor (TNF)-α and IL-17A. RMT3-23 inhibited intracellular TNF-α and IL-6 and early apoptosis. An amelioration of autoimmune arthritis was achieved by blocking the TIM-1 and -3 signaling pathways via RMT1-10 and RMT3-23 administration, leading to a widespread decrease in inflammatory cytokines. Both antibodies exhibited therapeutic effects, suggesting TIM-1 and -3 as potential targets for rheumatoid arthritis.
- Itaru Matsumura; Shigeki Ohtake; Yoshiko Atsuta; Mio Kurata; Yosuke Minami; Naoto Takahashi; Chiaki Nakaseko; Noriyoshi Iriyama; Katsumichi Fujimaki; Kazuhiko Kakihana; Yoji Ogasawara; Takaaki Ono; Masaya Okada; Tetsuzo Tauchi; Toshihiro Miyamoto; Kazunori Ohnishi; Emiko Sakaida; Shin Fujisawa; Yukio Kobayashi; Norio Asou; Tomoki Naoe; Hitoshi Kiyoi; Yasushi MiyazakiBlood advances 2024年07月Treatment-free remission (TFR) is a new therapeutic goal for chronic myeloid leukemia in chronic phase (CML-CP). Deep molecular response (DMR) is a prerequite condition for TFR. The Japan Adult Leukemia Study Group (JALSG) conducted a multicentral prospective randomized phase 3 CML212 study for de novo CML-CP to compare the cumulative achievement of MR4.5 (international scale [IS] BCR::ABL1≤0.0032%) by 18 months between nilotinib and dasatinib as a primary endpoint. A total of 454 patients were randomly assigned to the nilotinib 300 mg, bid arm or dasatinib 100 mg, qd arm (both, n=227). BCR::ABL1 mRNA levels were monitored every three months. Study treatment was stopped if the patients were judged as failure by the European LekemiaNet (ELN) 2009 criteria or showed intolerance. The cumulative achievement rates of MR4.5 by 18 months were 32.6% (95% confidence interval [CI]: 26.5-39.1%) in the nilotinib arm and 30.8% (95% CI: 24.9-37.3%) in the dasatinib arm with no significant difference (p=0.66). Also, the cumulative achievement rates of early molecular response (EMR), complete cytogenetic response (CCyR) and major molecular response (MMR), MR4.0 by 12, 18, 24, and 36 months were almost the same between the two arms. At 36 months, 66.5% and 65.0% patients continued nilotinib and dasatinib, respectively (p=0.76). There was no significant difference in progression-free survival (PFS) or overall survival (OS) between the two arms by log-rank tests (PFS, p=0.58; OS, p=0.64). These results suggest that nilotinib and dasatinib would be equally effective for de novo CML-CP patients with similar continuity. UMIN Clinical Trials Registry (#UMIN000007909).
- Yosuke Minami; Noriko Doki; Hiroshi Matsuoka; Takafumi Yokota; Akihiro Tomita; Naoto Takahashi; Kohmei Kubo; Tatsunori Goto; Keita Kirito; Akio Maki; Makoto Aoki; Meryem Ktiouet Dawson; Itaru MatsumuraInternational journal of hematology 2024年06月Asciminib is a first-in-class BCR::ABL1 inhibitor that Specifically Targets the ABL1 Myristoyl Pocket (STAMP). It is approved worldwide and in Japan for chronic myeloid leukemia in chronic phase (CML-CP) with resistance or intolerance to previous tyrosine kinase inhibitor (TKI) therapy. In the Phase 3 ASCEMBL study, patients with CML-CP who received ≥ 2 prior ATP-competitive TKIs were randomized (2:1) to asciminib 40 mg twice-daily or bosutinib 500 mg once-daily. Here, we report the 96-week results of the subgroup analysis of Japanese patients (asciminib, n = 13; bosutinib, n = 3) in the ASCEMBL study. The MMR rate at Week 96 was 46.2% in asciminib-treated patients, increasing from Weeks 24 and 48. Patients who achieved MMR at Week 24 remained in MMR up to the Week 96 cutoff. While a high proportion of patients treated with asciminib remained on treatment at cutoff, none randomized to bosutinib were on treatment at Week 96. Despite the longer duration of exposure to asciminib, its safety and tolerability continued to be favorable with no new or worsening safety findings. Overall, the efficacy and safety outcomes in the Japanese subgroup were comparable with the ASCEMBL global study population, which supports the use of asciminib in Japanese patients with previously treated CML-CP.
- Koji Kato; Koji Izutsu; Momoko Nishikori; Hirohiko Shibayama; Yoshinobu Maeda; Kenichi Yoshimura; Ukihide Tateishi; Toshihiro Miyamoto; Yasufumi Matsuda; Jun Ishikawa; Shinya Rai; Tsutomu Takahashi; Takahiro Yamauchi; Itaru Matsumura; Koichi Akashi; Yuzuru Kanakura; Junji SuzumiyaInternational journal of hematology 119 6 677 - 685 2024年06月Response determined by 18[F]-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET)-CT after induction therapy can predict progression-free survival (PFS) in follicular lymphoma (FL). However, little prospective research has examined the significance of PET after second-line therapy. We conducted a prospective multicenter phase II trial (W-JHS NHL01) of bendamustine plus rituximab (BR) without rituximab maintenance for FL in first relapse. This study aimed to evaluate the usefulness of end-of-treatment (EOT)-PET for predicting PFS in FL patients in first relapse. EOT-PET examinations were performed between 6 and 8 weeks from the start of the last BR cycle. The primary endpoint was 1-year PFS. Key secondary endpoints were overall response rate (ORR), complete response rate (CRR), and 1-year overall survival (OS). Seventy-five patients were enrolled, and 8 were excluded from analysis. ORR was 86.6% and CRR was 59.7%. One-year PFS was 88.9% (95% confidence interval [CI] 80.7-94.3%) and 1-year OS in 75 patients was 97.3% (95% CI 89.6-99.3%). One-year PFS was significantly inferior in EOT-PET-positive patients (n = 9) compared with PET-negative patients (n = 58) (77.8% vs. 93.1%; p = 0.02). We confirmed that EOT-PET after second-line BR therapy could predict early progression in FL patients in first relapse.
- Akira Kawasaki; Kiyohiko Hatake; Itaru Matsumura; Koji Izutsu; Tomohiro Hoshino; Ayumi Akamatsu; Akito Kakuuchi; Kensei TobinaiInternational journal of hematology 119 6 667 - 676 2024年06月Nivolumab was approved for relapsed/refractory classic Hodgkin lymphoma (cHL) in Japan in 2016. After its approval, a prospective, non-interventional, observational post-marketing surveillance was initiated to evaluate the safety and effectiveness of nivolumab treatment for up to 12 months in patients with relapsed/refractory cHL. Of 304 registered patients, 288 were included in safety analyses and 282 in effectiveness analyses. There were 191 (66.3%) male patients, median age was 64.0 years, and 54 patients (18.8%) had performance status ≥ 2. Treatment-related adverse events (TRAEs) were reported in 183 (63.5%) patients, with grade 3-5 TRAEs in 86 (29.9%). The most common TRAEs were infusion reaction (14.6%), hepatic function abnormal (5.9%), interstitial lung disease (ILD) (5.6%), and hypothyroidism (5.2%). TRAEs of special interest in ≥ 5% of patients were infusion reaction (15.6%), hepatic failure/hepatic dysfunction/hepatitis/cholangitis sclerosing (13.2%), thyroid dysfunction (9.7%), and ILD (7.3%). In multivariable analyses, prior allogeneic hematopoietic stem cell transplantation was a risk factor for hepatic failure/hepatic dysfunction/hepatitis/cholangitis sclerosing, and prior thyroid gland disorders was a risk factor for thyroid dysfunction. The overall response rate was 61.7%. In conclusion, nivolumab showed a similar safety profile and comparable effectiveness to that reported in clinical trials for relapsed/refractory cHL (CheckMate 205, ONO-4538-15).
- Yutaka Shimazu; Junya Kanda; Yoshiyuki Onda; Shin-Ichi Fuchida; Kensuke Ohta; Yuji Shimura; Satoru Kosugi; Ryosuke Yamamura; Mitsuhiro Matsuda; Hitoshi Hanamoto; Yoko Adachi; Naoyuki Anzai; Masaaki Hotta; Kentaro Fukushima; Hideo Yagi; Satoshi Yoshihara; Yasuhiro Tanaka; Teruhito Takakuwa; Hirokazu Tanaka; Hirohiko Shibayama; Nobuhiko Uoshima; Naoki Hosen; Tomoki Ito; Chihiro Shimazaki; Itaru Matsumura; Junya Kuroda; Akifumi Takaori-Kondo; Masayuki HinoCancer immunology, immunotherapy : CII 73 7 135 - 135 2024年05月BACKGROUND: Isatuximab, an anti-CD38 antibody, has been widely used in treatments for patients with relapsed/refractory multiple myeloma (MM). Despite its high efficacy, not all patients achieve a lasting therapeutic response with isatuximab. OBJECTIVE: We tried to identify biomarkers to predict the effectiveness of isatuximab by focusing on the host's immune status before treatment. METHODS: We retrospectively analyzed the cases of 134 relapsed/refractory MM patients in the Kansai Myeloma Forum database who had received only a first isatuximab treatment. RESULTS: Among the 134 patients, an isatuximab, pomalidomide and dexamethasone (Isa-PD) regimen, isatuximab, carfilzomib and dexamethasone (Isa-KD) regimen and isatuximab and/or dexamethasone (Isa-D) regimen were used in 112, 15 and 7 patients, respectively. The median age at treatment, number of prior treatment regimens, and progression-free survival (PFS) were 71, 6, and 6.54 months, respectively. Multivariate analysis showed that the PFS under the Isa-PD regimen was longer in patients with higher lymphocyte/monocyte ratio (LMR ≥ 4), fewer prior treatment regimens (< 6), and no use of prior daratumumab treatment. The OS under the Isa-PD regimen was longer in patients with higher white blood cell counts (WBC counts ≥ 3000/μL) and higher LMR. The PFS under the Isa-D regimen was longer in patients with fewer prior treatment regimens in univariate analysis, but no parameters were correlated with PFS/OS under the Isa-KD regimen. CONCLUSION: We found that the patients with higher LMR (≥ 4) could obtain longer PFS and OS under the Isa-PD regimen. Other cohort studies of isatuximab treatment might be necessary to substantiate our results.
- Ayumi Kondo; Hirokazu Tanaka; Shinya Rai; Hiroshi Shima; Itaru Matsumura; Toshio WatanabeExperimental hematology 133 104205 - 104205 2024年05月Protein phosphatase 6 (PP6) is a serine/threonine (Ser/Thr) protein phosphatase, and its catalytic subunit is Ppp6c. PP6 forms the PP2A subfamily with PP2A and PP4. The diverse phenotypes observed following small interfering RNA (siRNA)-based knockdown of Ppp6c in cultured mammalian cells suggest that PP6 plays roles in cell growth and DNA repair. There is also evidence that PP6 regulates nuclear factor kappa B (NF-κB) signaling and mitogen-activated protein kinases and inactivates transforming growth factor-β-activated kinase 1 (TAK1). Loss of Ppp6c causes several abnormalities, including those of T cell and regulatory T cell function, neurogenesis, oogenesis, and spermatogenesis. PP2A has been reported to play an important role in erythropoiesis. However, the roles of PP6 in other hematopoietic cells have not been investigated. We generated Ppp6cfl/fl;Tie2-Cre (Ppp6cTKO) mice, in which Ppp6c was specifically deleted in hematopoietic and vascular endothelial cells. Ppp6cTKO mice displayed embryonic lethality. Ppp6c deficiency increased the number of dead cells and decreased the percentages of erythroid and monocytic cells during fetal hematopoiesis. By contrast, the number of Lin-Sca-1+c-Kit+ cells, which give rise to all hematopoietic cells, was slightly increased, but their colony-forming cell activity was markedly decreased. Ppp6c deficiency also increased phosphorylation of extracellular signal-regulated kinase 1/2 and c-Jun amino (N)-terminal kinase in fetal liver hematopoietic cells.
- Satoshi Nishiwaki; Isamu Sugiura; Shin Fujisawa; Yoshihiro Hatta; Yoshiko Atsuta; Noriko Doki; Shingo Kurahashi; Yasunori Ueda; Nobuaki Dobashi; Tomoya Maeda; Itaru Matsumura; Masatsugu Tanaka; Shinichi Kako; Tatsuo Ichinohe; Takahiro Fukuda; Shigeki Ohtake; Yuichi Ishikawa; Yasushi Miyazaki; Hitoshi KiyoiAmerican journal of hematology 99 5 806 - 815 2024年05月This study aimed to investigate the usefulness of allogeneic stem cell transplantation (allo-SCT) for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) in the first complete remission (CR1) with complete molecular remission (CMR). We compared the outcomes between Ph+ALL patients who did or did not undergo allo-SCT in CR1. We included patients enrolled in the prospective clinical studies in the tyrosine kinase inhibitor era conducted by the Japan Adult Leukemia Study Group, who achieved CMR within 3 months. A total of 147 patients (allo-SCT: 101; non-SCT: 46) were eligible for this analysis. In the multivariate analyses, allo-SCT was significantly associated with both superior overall survival (OS) (adjusted hazard ratio (aHR): 0.54; 95% CI: 0.30-0.97; p = .04) and relapse-free survival (RFS) (aHR: 0.21; 95% CI: 0.12-0.38; p < .001). The 5-year adjusted OS and RFS were 73% and 70% in the allo-SCT cohort, whereas they were 50% and 20% in the non-SCT cohort. Despite the higher non-relapse mortality (aHR: 3.49; 95% CI: 1.17-10.4; p = .03), allo-SCT was significantly associated with a lower relapse rate (aHR: 0.10; 95% CI: 0.05-0.20; p < .001). In addition, allo-SCT was also associated with superior graft-versus-host disease-free, relapse-free survival (aHR: 0.43; 95% CI: 0.25-0.74; p = .002). Propensity score-matched analyses confirmed the results of the multivariate analyses. In patients who achieved CMR within 3 months, allo-SCT in CR1 had superior survival and lower relapse compared with the non-SCT cohort.
- Hirohiko Shibayama; Mitsuhiro Itagaki; Hiroshi Handa; Akihiro Yokoyama; Akio Saito; Satoru Kosugi; Shuichi Ota; Makoto Yoshimitsu; Yasuhiro Tanaka; Shingo Kurahashi; Shin-Ichi Fuchida; Masaki Iino; Takayuki Shimizu; Yukiyoshi Moriuchi; Kohtaro Toyama; Kinuko Mitani; Yutaka Tsukune; Akiko Kada; Hideto Tamura; Masahiro Abe; Hiromi Iwasaki; Junya Kuroda; Hiroyuki Takamatsu; Kazutaka Sunami; Masahiro Kizaki; Tadao Ishida; Toshiki Saito; Itaru Matsumura; Koichi Akashi; Shinsuke IidaInternational journal of hematology 119 6 707 - 721 2024年03月The emergence of novel drugs has significantly improved outcomes of patients with plasma cell neoplasms (PCN). The Japanese Society of Hematology conducted a prospective observational study in newly diagnosed PCN patients between 2016 and 2021. The analysis focused on 1385 patients diagnosed with symptomatic PCN between 2016 and 2018. The primary endpoint was the 3-year overall survival (OS) rate among patients requiring treatment (n = 1284), which was 70.0% (95%CI 67.4-72.6%). Approximately 94% of these patients received novel drugs as frontline therapy. The 3-year OS rate was 90.3% (95%CI 86.6-93.1%) in the 25% of patients who received upfront autologous stem cell transplantation (ASCT), versus just 61.4% (95%CI 58.0-64.6%) in those who did not receive upfront ASCT. The only unfavorable prognostic factor that affected OS in ASCT recipients was an age of 65 or higher. For patients who did not receive ASCT, independent unfavorable prognostic factors included frontline treatment with conventional chemotherapies, international staging system score of 2/3, extramedullary tumors, and Freiberg comorbidity index of 2/3. This study unequivocally demonstrates that use of novel drugs improved OS in Japanese myeloma patients, and underscores the continued importance of upfront ASCT as the standard of care in the era of novel drugs.
- Naokazu Nakamura; Nobuyoshi Arima; Teruhito Takakuwa; Satoshi Yoshioka; Kazunori Imada; Kentaro Fukushima; Masaaki Hotta; Shin-Ichi Fuchida; Junya Kanda; Nobuhiko Uoshima; Yuji Shimura; Hirokazu Tanaka; Kensuke Ohta; Satoru Kosugi; Hideo Yagi; Satoshi Yoshihara; Ryosuke Yamamura; Yoko Adachi; Hitoshi Hanamoto; Hirohiko Shibayama; Naoki Hosen; Tomoki Ito; Chihiro Shimazaki; Akifumi Takaori-Kondo; Junya Kuroda; Itaru Matsumura; Masayuki HinoAnnals of hematology 2024年03月Elotuzumab-based regimens are sometimes selected for multiple myeloma treatment after daratumumab-based regimens. However, there has been insufficient discussion on the efficacy of elotuzumab after daratumumab. We used Kansai Myeloma Forum registration data in a multicenter retrospective evaluation of the efficacy of elotuzumab after daratumumab. Overall survival (OS) rate and time to next treatment (TTNT) were significantly worse in the cohort given elotuzumab after daratumumab (Dara cohort, n = 47) than in the cohort with no history of daratumumab administration before elotuzumab (No-Dara cohort, n = 80, OS: P = 0.03; TTNT: P = 0.02; best response: P < 0.01). In the Dara cohort, OS and TTNT rates were worse with sequential elotuzumab use after daratumumab than with non-sequential (OS: P = 0.02; TTNT: P = 0.03). In patients given elotuzumab < 180 days after daratumumab, OS (P = 0.08) and best response (P = 0.21) tended to be worse, and TTNT was significantly worse (P = 0.01), than in those given elotuzumab after ≥ 180 days. These findings were confirmed by subgroup analyses and multivariate analyses. Monoclonal-antibody-free treatment might be preferable after daratumumab-based regimens. If possible, elotuzumab-based regimens should be considered only ≥ 180 days after daratumumab use.
- Daisuke Minakata; Tomoyuki Uchida; Aya Nakano; Ken Takase; Nodoka Tsukada; Hiroshi Kosugi; Eri Kawata; Takahiko Nakane; Hiroyuki Takahashi; Tomoyuki Endo; Satoshi Nishiwaki; Hideaki Fujiwara; Akiko M Saito; Toshiki I Saito; Koichi Akashi; Itaru Matsumura; Kinuko MitaniInternational journal of hematology 119 2 183 - 195 2024年02月The Japanese Society of Hematology performed an observational cross-sectional study to clarify the morbidity, prognosis, and prognostic factors in patients with COVID-19 with hematological diseases (HDs) in Japan. The study included patients with HDs who enrolled in our epidemiological survey and had a COVID-19 diagnosis and a verified outcome of up to 2 months. The primary endpoints were characteristics and short-term prognosis of COVID-19 in patients with HDs. A total of 367 patients from 68 institutes were enrolled over 1 year, and the collected data were analyzed. The median follow-up among survivors was 73 days (range, 1-639 days). The 60-day overall survival (OS) rate was 86.6%. In the multivariate analysis, albumin ≤ 3.3 g/dL and a need for oxygen were independently associated with inferior 60-day OS rates (hazard ratio [HR] 4.026, 95% confidence interval (CI) 1.954-8.294 and HR 14.55, 95% CI 3.378-62.64, respectively), whereas 60-day survival was significantly greater in patients with benign rather than malignant disease (HR 0.095, 95% CI 0.012-0.750). Together, these data suggest that intensive treatment may be necessary for patients with COVID-19 with malignant HDs who have low albumin levels and require oxygen at the time of diagnosis.
- Kensuke Usuki; Shigeki Ohtake; Sumihisa Honda; Mitsuhiro Matsuda; Atsushi Wakita; Yuichiro Nawa; Ken Takase; Akio Maeda; Nobuo Sezaki; Hisayuki Yokoyama; Satoru Takada; Daiki Hirano; Tatsuki Tomikawa; Masahiko Sumi; Shingo Yano; Hiroshi Handa; Shuichi Ota; Hiroyuki Fujita; Katsumichi Fujimaki; Atsuko Mugitani; Kensuke Kojima; Tomohiro Kajiguchi; Ko Fujimoto; Norio Asou; Noriko Usui; Yuichi Ishikawa; Akira Katsumi; Itaru Matsumura; Yasushi Miyazaki; Hitoshi KiyoiInternational journal of hematology 119 2 130 - 145 2024年02月We conducted a multicenter, prospective observational study of acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and chronic myelomonocytic leukemia (CMML) in Japan. From August 2011 to January 2016, we enrolled 6568 patients. Herein, we report the results for MDS (n = 2747) and CMML (n = 182). The percentage of patients aged 65 years or older was 79.5% for MDS and 79.7% for CMML. The estimated overall survival (OS) rate and cumulative incidence of AML evolution at 5 years were 32.3% (95% confidence interval: 30.2-34.5%) and 25.7% (23.9-27.6%) for MDS, and 15.0% (8.9-22.7%) and 39.4% (31.1-47.6%) for CMML. Both diseases were more common in men. The most common treatment for MDS was azacitidine, which was used in 45.4% of higher-risk and 12.7% of lower-risk MDS patients. The 5-year OS rate after treatment with azacitidine was 12.1% (9.5-15.1%) for of higher-risk MDS patients and 33.9% (25.6-42.4%) for lower-risk patients. The second most common treatment was erythropoiesis-stimulating agents, given to just 20% of lower-risk patients. This is the first paper presenting large-scale, Japanese data on survival and clinical characteristics in patients with MDS and CMML.
- Kensuke Usuki; Shigeki Ohtake; Sumihisa Honda; Mitsuhiro Matsuda; Atsushi Wakita; Yuichiro Nawa; Ken Takase; Akio Maeda; Nobuo Sezaki; Hisayuki Yokoyama; Satoru Takada; Daiki Hirano; Tatsuki Tomikawa; Masahiko Sumi; Shingo Yano; Hiroshi Handa; Shuichi Ota; Hiroyuki Fujita; Katsumichi Fujimaki; Atsuko Mugitani; Kensuke Kojima; Tomohiro Kajiguchi; Ko Fujimoto; Norio Asou; Noriko Usui; Yuichi Ishikawa; Akira Katsumi; Itaru Matsumura; Hitoshi Kiyoi; Yasushi MiyazakiInternational journal of hematology 119 1 24 - 38 2024年01月This report covers acute myeloid leukemia (AML) results from a multicenter, prospective observational study of AML, myelodysplastic syndromes, and chronic myelomonocytic leukemia in Japan. From August 2011 to January 2016, 3728 AML patients were registered. Among them, 42% were younger than 65, and the male-to-female ratio was 1.57:1. With a median follow-up time of 1807 days (95% confidence interval [CI]: 1732-1844 days), the estimated 5-year overall survival (OS) rate in AML patients (n = 3707) was 31.1% (95% CI: 29.5-32.8%). Trial-enrolled patients had a 1.7-fold higher OS rate than non-enrolled patients (5-year OS, 58.9% [95% CI: 54.5-63.1%] vs 35.5% [33.3-37.8%], p < 0.0001). Women had a higher OS rate than men (5-year OS, 34% [95% CI; 31.4-36.7%] vs 27.7% [25.7-29.7%], p < 0.0001). The OS rate was lower in patients aged 40 and older than those under 40, and even lower in those over 65 (5-year OS for ages < 40, 40-64, 65-74, ≥ 75: 74.5% [95% CI; 69.3-79.0%] vs 47.5% [44.4-50.6%] vs 19.3% [16.8-22.0%] vs 7.3% [5.5-9.4%], respectively). This is the first paper to present large-scale data on survival and clinical characteristics in Japanese AML patients.
- Noriharu Nakagawa; Ken Ishiyama; Kensuke Usuki; Satoru Takada; Tatsuki Tomikawa; Hiroshi Handa; Yuna Katsuoka; Daiki Hirano; Nobuo Sezaki; Masahiko Sumi; Shin Fujisawa; Yasuhiro Taniguchi; Atsuko Mugitani; Takuro Yoshimura; Eiichi Ohtsuka; Ken Takase; Youko Suehiro; Shuichi Ota; Tomohiro Kajiguchi; Tomoya Maeda; Masahide Yamamoto; Shigeki Ohtake; Akira Katsumi; Hitoshi Kiyoi; Itaru Matsumura; Yasushi MiyazakiAnnals of hematology 103 1 307 - 320 2024年01月Allogeneic hematopoietic stem cell transplantation (allo-SCT) is the sole curative therapy for myelodysplastic syndrome (MDS). However, whether bridging therapy (BRT) including azacitidine (AZA) and combination chemotherapy (CCT) prior to allo-SCT should be performed is unclear. We analyzed BRT and the outcomes of patients with myelodysplastic syndrome with excess blasts (MDS-EB) who were ≤ 70 years old at the time of registration for a prospective observational study to clarify the optimal allo-SCT strategy for high-risk MDS. A total of 371 patients were included in this study. Among 188 patients (50.7%) who were considered for allo-SCT, 141 underwent allo-SCT. Among the patients who underwent allo-SCT, 64 received AZA, 29 received CCT, and 26 underwent allo-SCT without BRT as the initial treatment. Multivariate analysis identified BRT as an independent factor influencing overall survival (AZA vs. without BRT, hazard ratio [HR] 3.33, P = 0.005; CCT vs. without BRT, HR 3.82, P = 0.003). In multivariate analysis, BRT was independently associated with progression-free survival (AZA vs. without BRT: HR, 2.23; P = 0.041; CCT vs. without BRT: HR, 2.94; P = 0.010). Transplant-eligible patients with MDS-EB should undergo allo-SCT when clinically acceptable, and upfront allo-SCT without BRT may be superior to AZA or CCT.
- Kinuko Mitani; Jong Wook Lee; Jun-Ho Jang; Yoshiaki Tomiyama; Koji Miyazaki; Koji Nagafuji; Kensuke Usuki; Nobuhiko Uoshima; Tomoaki Fujisaki; Hiroshi Kosugi; Itaru Matsumura; Ko Sasaki; Masahiro Kizaki; Masashi Sawa; Michihiro Hidaka; Naoki Kobayashi; Satoshi Ichikawa; Yuji Yonemura; Kenta Murotani; Mami Shimizu; Akira Matsuda; Keiya Ozawa; Shinji NakaoBlood advances 8 6 1415 - 1419 2023年12月
- Michihiro Hidaka; Koiti Inokuchi; Nobuhiko Uoshima; Naoto Takahashi; Nao Yoshida; Shuichi Ota; Hirohisa Nakamae; Hiromi Iwasaki; Kenichiro Watanabe; Yoshiyuki Kosaka; Norio Komatsu; Kuniaki Meguro; Yuho Najima; Tetsuya Eto; Takeshi Kondo; Shinya Kimura; Chikashi Yoshida; Yuichi Ishikawa; Masashi Sawa; Tomoko Hata; Keizo Horibe; Hiroatsu Iida; Takeshi Shimomura; Nobuaki Dobashi; Isamu Sugiura; Junya Makiyama; Naoyuki Miyagawa; Asuka Sato; Ryuta Ito; Itaru Matsumura; Yuzuru Kanakura; Tomoki NaoeJapanese journal of clinical oncology 54 2 153 - 159 2023年11月OBJECTIVE: Minimal residual disease assessment of BCR-ABL messenger ribonucleic acid levels is crucial in Philadelphia chromosome-positive acute lymphoblastic leukemia for prognosis and treatment planning. However, accurately quantifying minor BCR-ABL transcripts, which comprise 70% of Philadelphia chromosome-positive acute lymphoblastic leukemia cases, lacks a national-approved method. METHODS: We developed the "Otsuka" minor BCR-ABLmessenger ribonucleic acid assay kit with exceptional precision (0.00151%). Minor BCR-ABL messenger ribonucleic acid levels were analyzed in 175 adults, 36 children with acute lymphoblastic leukemia and 25 healthy individuals to evaluate the kit's performance. RESULTS: The "Otsuka" kit showed high concordance with a commonly used chimeric gene screening method, indicating reliable detection of positive cases. Quantitative results demonstrated a robust correlation with both a laboratory-developed test and a diagnostic research product. The "Otsuka" kit performs comparably or even surpass to conventional products, providing valuable insights into Philadelphia chromosome-positive acute lymphoblastic leukemia pathology. CONCLUSIONS: The 'Otsuka" minor BCR-ABL messenger ribonucleic acid assay kit exhibits excellent performance in quantifying minor BCR-ABL transcripts in Philadelphia chromosome-positive acute lymphoblastic leukemia patients. Our results align well with established screening methods and show a strong correlation with laboratory-developed tests and diagnostic research products. The "Otsuka" kit holds great promise as a valuable tool for understanding Philadelphia chromosome-positive acute lymphoblastic leukemia pathology and guiding effective treatment strategies.
- Ayaka Yamada; Sayaka Torihata; Takeshi Shimoide; Atsushi‐Doksa Lee; Yuko Kinoshita; Miku Kawaguchi; Takashi Ashida; Itaru Matsumura; Akifumi EnomotoOral Science International 2023年10月Abstract Aim Oral cGVHD is one of the phenotypes of organ involvement of cGVHD and is a complex, frequent, and highly impactful complication of allogeneic hematopoietic cell transplantation (HSCT). Few studies have compared the incidences and risk factors of oral cGVHD, and they have not been discussed. We performed to evaluate the risk factors for oral cGVHD after allogeneic HSCT in a single center. Methods A retrospective study of clinical hematological data of all consecutive patients who underwent HSCT for malignant hematologic disease and then developed oral chronic graft versus host disease (cGVHD) in a single center from 2012 to the present was performed to evaluate the risk factors for oral cGVHD. Allogeneic HSCT was performed for 179 patients. Assessment of individual risk factors (age, sex, primary diagnosis, stem cell source, human leukocyte antigen [HLA] matching, regimen, donor age, and status after remission induction therapy) was completed to identify the effects of covariates of the independent variables. Results Seventy‐two (40.2%) patients were considered to have oral cGVHD within 36 months after HSCT. Statistical analysis showed that age, sex, stem cell source, HLA matching, regimen, donor age, and status after remission induction therapy were not significant factors related to oral cGVHD, whereas the primary disease was significant. Conclusion The primary disease was a significant risk factor for oral cGVHD. The oral cGVHD was more common in myeloid neoplasms (MNs) patients than in lymphoid neoplasms (LNs) patients.
- Yuji Shimura; Hirohiko Shibayama; Aya Nakaya; Ryosuke Yamamura; Kazunori Imada; Hitomi Kaneko; Hitoshi Hanamoto; Shin-Ichi Fuchida; Hirokazu Tanaka; Satoru Kosugi; Miki Kiyota; Toshimitsu Matsui; Junya Kanda; Masato Iida; Mitsuhiro Matsuda; Nobuhiko Uoshima; Masaru Shibano; Takahiro Karasuno; Tsuneyoshi Hamada; Kensuke Ohta; Tomoki Ito; Hideo Yagi; Satoshi Yoshihara; Chihiro Shimazaki; Shosaku Nomura; Masayuki Hino; Akifumi Takaori-Kondo; Itaru Matsumura; Yuzuru Kanakura; Junya KurodaInternational journal of hematology 2023年09月To investigate the real-world clinical outcomes and management of novel drug-containing therapies for newly diagnosed multiple myeloma (MM) patients, we retrospectively analyzed data on the first-line treatment for newly diagnosed transplant-ineligible MM patients from Kansai Myeloma Forum, a registry network in Japan. A total of 598 patients treated with novel drugs between March 2007 and February 2018 were analyzed. Regimens used were VD (n = 305), Rd (n = 103), VMP (n = 97), VCD (n = 71), and VRd (n = 22). Younger patients tended to receive VRd or VCD, whereas the regimen with the highest median patient age was Rd. More than three-quarters of patients in the Rd group received a reduced dose of lenalidomide. The Rd and VRd groups had a relatively high incidence of infection and skin complications, and the VMP group had the highest incidence of peripheral neuropathy. Overall response rate did not differ significantly between regimens. Multivariate analysis in all patients revealed several poor prognostic factors, such as poor performance status. Novel drug-containing regimens for newly diagnosed MM showed a durable response with manageable AEs in the real-world setting.
- Takahiro Haeno; Shinya Rai; Yoshiaki Miyake; Maiko Inoue; Ko Fujimoto; Aki Fujii; Yoshio Iwata; Shuji Minamoto; Takahide Taniguchi; Hiroaki Kakutani; Hiroaki Inoue; Takahiro Kumode; Kentaro Serizawa; Yasuhiro Taniguchi; Chikara Hirase; Yasuyoshi Morita; Hirokazu Tanaka; Yoichi Tatsumi; Takashi Ashida; Itaru MatsumuraJournal of clinical and experimental hematopathology : JCEH 63 2 99 - 107 2023年06月We retrospectively evaluated long-term outcomes of high dose chemotherapy followed by autologous stem cell transplant (HDC/ASCT) in patients with diffuse large B-cell lymphoma (DLBCL). Between 2004 and 2020, 46 DLBCL patients received HDC/ASCT in our institution, including 12 patients (26.1%), who received as an upfront setting (UFS). At a median follow-up time of 69 months (range, 2-169 months), the 5-year progression-free survival (PFS) rates were 82.5% (95%CI, 46.1-95.3%) in the UFS, and 57.8% (95%CI, 38.1-73.2%) in the relapsed or refractory (R/R) patients (n=34), respectively. The 5-year PFS rates were 62.3% (95%CI, 34.0-81.3%) in primary resistant (n=13) or early relapsing (within 1 year from the initial diagnosis) patients (n=4), and 53.3% (95%CI, 25.9-74.6%) in those relapsing >1 year after the initial diagnosis (n=17), with no statistically significant difference (p=0.498). In R/R patients, multivariate analysis showed that the remission status before HDC/ASCT was an independent poor prognostic factor for progression-free survival (hazard ratio [HR], 17.0; 95%CI, 3.35-86.6; p=0.000630) and high-risk category in the international prognostic index for OS (HR, 9.39; 95%CI, 1.71-51.6; p=0.0100). The incidence of non-relapse mortality by 5 years, and 10 years were 12.2%, and 15.2%, respectively. Eleven patients (23.9%) developed second malignancies, which was the most frequent late complication after HDC/ASCT, with 5-year, and 10-year cumulative incidence of 16.9%, 22.5%, respectively. In conclusion, HDC/ASCT is effective for chemo-sensitive R/R DLBCL regardless of the timing and lines of therapy. However, careful observation is required, considering the long-term complications such as secondary malignancies.
- Atsushi Sato; Yoshihiro Hatta; Chihaya Imai; Koichi Oshima; Yasuhiro Okamoto; Takao Deguchi; Yoshiko Hashii; Takashi Fukushima; Toshinori Hori; Nobutaka Kiyokawa; Motohiro Kato; Shoji Saito; Kenichi Anami; Tatsuhiro Sakamoto; Yoshiyuki Kosaka; Souichi Suenobu; Toshihiko Imamura; Akiko Kada; Akiko M Saito; Atsushi Manabe; Hitoshi Kiyoi; Itaru Matsumura; Katsuyoshi Koh; Arata Watanabe; Yasushi Miyazaki; Keizo HoribeThe Lancet. Haematology 10 6 e419-e432 2023年06月BACKGROUND: T-cell acute lymphoblastic leukaemia has distinct biological characteristics and a poorer prognosis than B-cell precursor acute lymphoblastic leukaemia. This trial aimed to reduce the rate of radiation and haematopoietic stem-cell transplantation (HSCT) while improving outcomes by adding nelarabine, intensified L-asparaginase, and protracted intrathecal therapy in the Berlin-Frankfurt-Münster (BFM)-type treatment. METHODS: In this nationwide, multicenter, phase 2 trial, we enrolled patients with newly diagnosed T-cell acute lymphoblastic leukaemia (age <25 years at diagnosis) conducted by Japan Children's Cancer Group and Japan Adult Leukemia Study Group. Patients were stratified into standard-risk, high-risk, and very-high-risk groups according to prednisolone response, CNS status, and end-of-consolidation minimal residual disease. We used the Associazione Italiana di Ematologia Oncologia Pediatrica (AIEOP)-BFM-ALL 2000-backbone chemotherapy. Nelarabine (650 mg/m2 per day for 5 days) was given to high-risk and very high-risk patients. All patients received, until the measurement of end-of-consolidation minimal residual disease, an identical therapy schedule, which included the prednisolone pre-phase remission induction therapy with dexamethasone (10 mg/m2 per day, for 3 weeks [for patients <10 years] or for 2 weeks including a 7-day off interval [for patients ≥10 years]) instead of prednisolone, and consolidation therapy added with Escherichia coli-derived L-asparaginase. On the basis of the stratification, patients received different intensities of treatment; L-asparaginase-intensified standard BFM-type therapy for standard risk and nelarabine-added high risk BFM-type therapy for high risk. In the very high-risk group, patients were randomly assigned (1:1) to group A (BFM-based block therapy) and group B (another block therapy, including high-dose dexamethasone) stratified by hospital, age (≥18 years or <18 years), and end-of-induction bone marrow blast percentage of M1 (<5%) or M2 (≥5%, <25%)+M3 (≥25%). Cranial radiotherapy was limited to patients with overt CNS disease at diagnosis (CNS3; >5 white blood cells per μL with blasts) and patients with no evidence of CNS disease received protracted triple intrathecal therapy. Only very high-risk patients were scheduled to receive HSCT. The primary endpoint was 3-year event-free survival for the entire cohort and the proportion of patients with disappearance of minimal residual disease between randomly assigned groups A and B in the very high-risk group. Secondary endpoints were overall survival, remission induction rate, and occurrence of adverse events. 3 years after the completion of patient accrual, a primary efficacy analysis was performed in the full analysis set and the per-protocol set. This study is registered with the Japan Registry of Clinical Trials, jRCTs041180145. FINDINGS: Between Dec 1, 2011, and Nov 30, 2017, of 349 eligible patients (median age 9 years [IQR 6-13]), 238 (68%) were male, and 28 (8%) patients had CNS3 status. 168 (48%) patients were stratified as standard risk, 103 (30%) as high risk, 39 (11%) as very high risk, and 39 (11%) as no risk (patients who had off protocol treatment before risk assessment. The composite complete remission (complete remission plus complete remission in suppression) rate after remission induction therapy was 89% (298 of 335 patients). HSCT was performed in 35 (10%) of 333 patients. With a median follow-up of 5·2 years (IQR 3·6-6·7), 3-year event-free survival was 86·4% (95% CI 82·3-89·7%) and 3-year overall survival was 91·3% (87·7-93·8%). The proportion of minimal residual disease disappearance was 0·86 (12 of 14 patients; 95% CI 0·57-0·98) in group A and 0·50 (6 of 12 patients, 0·21-0·79) in group B. Grade 3 peripheral motor neuropathy was seen in 11 (3%) of 349 patients and sensory neuropathy was seen in 6 (2%) patients. The most common grade 3 or worse adverse event was febrile neutropenia (294 [84%] of 349 patients). Treatment-related death occurred in three patients due to sepsis, gastric perforation, or intracranial haemorrhage during remission induction. INTERPRETATION: The ALL-T11 protocol produced encouraging outcomes with acceptable toxicities despite limited cranial radiotherapy and HSCT use. FUNDING: Ministry of Health, Labor and Welfare of Japan, and Japan Agency for Medical Research and Development. TRANSLATION: For the Japanese translation of the abstract see Supplementary Materials section.
- Satoshi Nishiwaki; Isamu Sugiura; Shin Fujisawa; Yoshihiro Hatta; Yoshiko Atsuta; Noriko Doki; Shingo Kurahashi; Yasunori Ueda; Nobuaki Dobashi; Tomoya Maeda; Yasuhiro Taniguchi; Masatsugu Tanaka; Shinichi Kako; Tatsuo Ichinohe; Takahiro Fukuda; Shigeki Ohtake; Yuichi Ishikawa; Hitoshi Kiyoi; Itaru Matsumura; Yasushi MiyazakiHemaSphere 7 6 e899 2023年06月
- 田中 宏和; 芹澤 憲太郎; 松村 到日本臨床 81 6 806 - 812 (株)日本臨床社 2023年06月
- Yukino Kojima; Fumika Kawashima; Takahiko Yasuda; Koya Odaira; Yuichiro Inagaki; Chiharu Yamada; Ami Muraki; Mina Noura; Shuichi Okamoto; Shogo Tamura; Eisuke Iwamoto; Masashi Sanada; Itaru Matsumura; Yasushi Miyazaki; Tetsuhito Kojima; Hitoshi Kiyoi; Shinobu Tsuzuki; Fumihiko HayakawaInternational journal of hematology 118 1 65 - 74 2023年05月Gene aberrations of B-cell regulators and growth signal components such as the JAK-STAT pathway are frequently found in B-cell acute lymphoblastic leukemia (B-ALL). EBF1 is a B-cell regulator that regulates the expression of PAX5 and co-operates with PAX5 to regulate B-cell differentiation. Here, we analyzed the function of the fusion protein of EBF1 and JAK2, EBF1-JAK2 (E-J). E-J caused constitutive activation of JAK-STAT and MAPK pathways and induced autonomous cell growth in a cytokine-dependent cell line. E-J did not affect the transcriptional activity of EBF1 but inhibited that of PAX5. Both the physical interaction of E-J with PAX5 and kinase activity of E-J were required for E-J to inhibit PAX5 function, although the detailed mechanism of inhibition remains unclear. Importantly, gene set enrichment analysis using the results of our previous RNA-seq data of 323 primary BCR-ABL1-negative ALL samples demonstrated repression of the transcriptional target genes of PAX5 in E-J-positive ALL cells, which suggests that E-J also inhibited PAX5 function in ALL cells. Our results shed new light on the mechanisms of differentiation block by kinase fusion proteins.
- Yuji Nozaki; Takuya Kotani; Tohru Takeuchi; Toshihiko Hidaka; Hirofumi Miyake; Kazuhiro Hatta; Yoichi Kurosawa; Masanori Sudo; Satoshi Ito; Koji Kinoshita; Itaru MatsumuraFrontiers in bioscience (Landmark edition) 28 4 68 - 68 2023年04月BACKGROUND: Infliximab is a human-murine chimeric monoclonal IgG antibody against tumor necrosis factor that is used in combination with methotrexate for the treatment of moderate to severe rheumatoid arthritis (RA). The trough concentration of serum infliximab required to control disease activity in RA is ≥1 μg/mL, and we investigated whether this trough concentration can predict the effectiveness of RA treatment. METHODS: We retrospectively analyzed the cases of 76 patients with RA. The REMICHECK Q® (REMIQ) is a kit that can check for serum infliximab concentrations. Infliximab concentrations >1 μg/mL at 14 weeks after an initial infliximab induction is considered REMIQ-positive, otherwise considered REMIQ-negative. Here, we determined the retention rates and investigated the clinical and serologic features of REMIQ-positive and REMIQ-negative patients. RESULTS: At 14 weeks, significantly more of the REMIQ-positive patients (n = 46) were responders compared to the non-responders (n = 30). The retention rate at 54 weeks was also significantly higher in the REMIQ-positive group versus the negative group. After 14 weeks, more patients in the REMIQ-negative group were considered inadequate responders, and their infliximab doses were escalated. At baseline, the REMIQ-positive group had significantly lower C-reactive protein (CRP) levels compared to the negative group. Cox regression analysis with multiple variables showed that the positivity of REMIQ (hazard ratio [HR] 2.10 and 95% confidence interval [CI]: 1.55-5.71) at baseline was associated with the achievement of low disease activity. The positivities of rheumatoid factor and anti-CCP antibody at baseline were associated with the achievement of remission with infliximab treatment (HR 0.44, 95% CI: 0.09-0.82 and HR 0.35, 95% CI: 0.04-0.48, respectively). CONCLUSIONS: The results of this study suggest that the control of RA disease activity may be facilitated by using the REMIQ kit at 14 weeks to check whether it is necessary to increase a patient's infliximab dose to ensure a therapeutic blood concentration that will help the patient achieve low disease activity.
- Yutaka Shimazu; Junya Kanda; Satoru Kosugi; Tomoki Ito; Hitomi Kaneko; Kazunori Imada; Yuji Shimura; Shin-Ichi Fuchida; Kentaro Fukushima; Hirokazu Tanaka; Satoshi Yoshihara; Kensuke Ohta; Nobuhiko Uoshima; Hideo Yagi; Hirohiko Shibayama; Ryosuke Yamamura; Yasuhiro Tanaka; Hitoji Uchiyama; Yoshiyuki Onda; Yoko Adachi; Hitoshi Hanamoto; Ryoichi Takahashi; Mitsuhiro Matsuda; Takashi Miyoshi; Teruhito Takakuwa; Masayuki Hino; Naoki Hosen; Shosaku Nomura; Chihiro Shimazaki; Itaru Matsumura; Akifumi Takaori-Kondo; Junya KurodaScientific reports 13 1 5159 - 5159 2023年03月Novel therapeutic drugs have dramatically improved the overall survival of patients with multiple myeloma. We sought to identify the characteristics of patients likely to exhibit a durable response to one such drug, elotuzumab, by analyzing a real-world database in Japan. We analyzed 179 patients who underwent 201 elotuzumab treatments. The median time to next treatment (TTNT) with the 95% confidence interval was 6.29 months (5.18-9.20) in this cohort. Univariate analysis showed that patients with any of the following had longer TTNT: no high risk cytogenic abnormalities, more white blood cells, more lymphocytes, non-deviated κ/λ ratio, lower β2 microglobulin levels (B2MG), fewer prior drug regimens, no prior daratumumab use and better response after elotuzumab treatment. A multivariate analysis showed that TTNT was longer in patients with more lymphocytes (≥ 1400/μL), non-deviated κ/λ ratio (0.1-10), lower B2MG (< 5.5 mg/L) and no prior daratumumab use. We proposed a simple scoring system to predict the durability of the elotuzumab treatment effect by classifying the patients into three categories based on their lymphocyte counts (0 points for ≥ 1400/μL and 1 point for < 1400/μL) and κ/λ ratio (0 points for 0.1-10 and 1 point for < 0.1 or ≥ 10) or B2MG (0 points for < 5.5 mg/L and 1 point for ≥ 5.5 mg/L). The patients with a score of 0 showed significantly longer TTNT (p < 0.001) and better survival (p < 0.001) compared to those with a score of 1 or 2. Prospective cohort studies of elotuzumab treatment may be needed to validate the usefulness of our new scoring system.
- 成人スチル病・ベーチェット病 成人Still病に合併するマクロファージ活性化症候群の診断におけるHScoreの有用性の検討志賀 俊彦; 土本 早紀; 山澤 広嵩; 芦田 千聖; 冨田 大介; 伊丹 哲; 樋野 尚一; 岸本 和也; 杉山 昌史; 野崎 祐史; 木下 浩二; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 67回 651 - 651 (一社)日本リウマチ学会 2023年03月
- 高齢者に対する生物学的製剤 生物学的製剤を導入した高齢発症関節リウマチの大関節,小関節における関節エコー改善所見の比較冨田 大介; 野崎 祐史; 山澤 広嵩; 石村 香織; 赤澤 宗輝; 芦田 千聖; 岡田 晃典; 伊丹 哲; 志賀 俊彦; 岸本 和也; 木下 浩二; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 67回 688 - 688 (一社)日本リウマチ学会 2023年03月
- Takaaki Ono; Naoto Takahashi; Masahiro Kizaki; Tatsuya Kawaguchi; Ritsuro Suzuki; Kazuhito Yamamoto; Kazunori Ohnishi; Tomoki Naoe; Itaru MatsumuraCancer science 114 3 995 - 1006 2023年03月Age and comorbidities are important factors to be considered in the selection of tyrosine kinase inhibitors (TKIs) for first-line treatment in patients with chronic myeloid leukemia in chronic phase (CML-CP). However, it is yet unclear whether TKI selection, particularly, imatinib versus second-generation TKIs (2GTKIs), impacts treatment outcomes in the clinical practice. To address this, we compared the clinical outcomes of prospectively registered 452 patients with CML-CP treated with imatinib and 2GTKIs, taking into consideration their age and/or comorbidities. A total of 136 patients (30.1%) were classified into an older cohort (≥65 years) and 316 (69.9%) into a younger cohort (18-64 years). The TKI selection did not vary based on age (70.6% received 2GTKIs in the younger cohort and 66.2% in the older cohort). The median follow-up period was 5.4 years. Treatment responses including the cumulative incidence of deep molecular response (BCR-ABL1 international scale ≤0.0032%) at any time were similar between the two age cohorts regardless of the type of TKI. The 5-year overall survival (OS) in the older cohort was lower than that in the younger cohort (95.9% vs 83.8%; p < 0.0001), whereas the 5-year OS in patients treated with 2GTKIs was not influenced by age factors and comorbidities. Therefore, our results suggest that the selection of 2GTKIs as first-line treatment is an effective option for both younger and older CML-CP patients with or without comorbidities. This trial was registered at UMIN-CTR as 00003581.
- 田中 宏和; 芹澤 憲太郎; 松村 到血液内科 86 2 266 - 271 (有)科学評論社 2023年02月
- Hiroki Akazawa; Yuji Nozaki; Hirotaka Yamazawa; Kaori Ishimura; Chisato Ashida; Akinori Okada; Koji Kinoshita; Itaru MatsumuraFrontiers in medicine 10 1293132 - 1293132 2023年Psoriasis is an immune-mediated inflammatory disease of the skin, which is characterized by epidermal hyperkeratosis and neutrophil infiltration. The interleukin (IL)-17/IL-23 pathway and associated cytokines play major roles in the pathogenesis and exacerbation of psoriasis. The IL-18/IL-18 receptor (R) α signaling pathway is important for Th1 cytokine production and differentiation of Th1 cells; however, its role in the pathogenesis of psoriasis remains unknown. In this study, we investigated the effect of the IL-18Rα-mediated signaling pathway in the pathogenesis of psoriasis in Il18ra-deficient mice (Il18ra-/-) and wild-type imiquimod (IMQ)-induced psoriatic dermatitis model mice. Blocking this pathway exacerbated IMQ-induced psoriatic skin inflammation. Il18ra deficiency led to significant increases in the levels of IL-1β, IL-6, IL-8, IL-17A, IL-23, and chemokine (C-X-C motif) ligand 2 in skin lesions. Gr1-positive cells highly infiltrated psoriatic skin lesions in Il18ra-/- mice compared to those in wild-type mice. Citrullinated histone H3-positive area was relatively broad in Il18ra-/- mice. These results suggest that IL-18Rα-mediated signaling pathways may inhibit psoriatic skin inflammation by regulating infiltration and activation of neutrophil and other innate immune cells.
- Aya Nakaya; Hirohiko Shibayama; Nobuhiko Uoshima; Ryosuke Yamamura; Satoshi Yoshioka; Kazunori Imada; Yuji Shimura; Masaaki Hotta; Toshimitsu Matsui; Satoru Kosugi; Hitoshi Hanamoto; Hitoji Uchiyama; Satoshi Yoshihara; Shin-Ichi Fuchida; Yoshiyuki Onda; Yasuhiro Tanaka; Kensuke Ohta; Mitsuhiro Matsuda; Junya Kanda; Adachi Yoko; Miki Kiyota; Eri Kawata; Ryoichi Takahashi; Kentaro Fukushima; Hirokazu Tanaka; Hideo Yagi; Teruhito Takakuwa; Naoki Hosen; Tomoki Ito; Chihiro Shimazaki; Akifumi Takaori-Kondo; Junya Kuroda; Itaru Matsumura; Masayuki HinoLeukemia research reports 20 100395 - 100395 2023年To evaluate the specific prognostic value of CAs, we conducted an analysis of 923 symptomatic multiple myeloma patients. Among this cohort, 480 patients had complete data set of high-risk CAs by interphase fluorescent in situ hybridization at diagnosis. In the high-risk group analysis, the median OS of patients without CAs (n = 338, 72 %) was 6.5 years, patients with del(17p) (n = 42, 9 %) was 4.4 years, patients with t(4;14) or t(14;16) (n = 72, 15 %) was 4.4 years, and patients with double-positive CAs(del(17p) and t(4;14) or t(14;16)) (n = 18, 4 %) was 2.1 years (p = 0.032). Patients with double-positive CAs had a significantly worse prognosis.
- Jinhai Li; Yuji Nozaki; Hiroki Akazawa; Kazuya Kishimoto; Koji Kinoshita; Itaru MatsumuraCurrent issues in molecular biology 44 11 5655 - 5665 2022年11月The pathogenesis of acute kidney injury (AKI) is complex and involves various immune and inflammatory responses. Antigen-presenting cells such as macrophages and dendritic cells (DCs) were recently reported to have diverse functions in AKI depending on the pathogenesis and disease phase. Herein, we intraperitoneally administered liposomal clodronate (LC) to lipopoly-saccharide (LPS)-induced AKI model mice in order to deplete antigen-presenting cells (e.g., macrophages and DCs). After the LPS injection, the mice were divided into LC-treated (LPS + LC) and saline-treated groups (LPS), and the immune responses of macrophages and DCs in the acute and recovery phases were evaluated. The LPS + LC-treated group exhibited significantly suppressed renal macrophages and DC infiltration at 18 h and improved survival at 120 h after LPS injection. Via the depletion of macrophages and DC infiltrations, the serum and renal tissue inflammatory cytokines/chemokines were suppressed at 18 h and reversed at 120 h. Tubular kidney injury molecule-1 expression was decreased at 18 h and increased at 120 h. These findings indicate that LC administration suppressed tubular and interstitial injury in the acute phase of AKI and affected delayed tissue repair in the recovery phase. They are important for understanding innate and acquired immune responses in the therapeutic strategy for LPS-induced AKI.
- Koya Odaira; Takahiko Yasuda; Kentaro Okada; Takuya Shimooka; Yukino Kojima; Mina Noura; Shogo Tamura; Shingo Kurahashi; Eisuke Iwamoto; Masashi Sanada; Itaru Matsumura; Yasushi Miyazaki; Tetsuhito Kojima; Hitoshi Kiyoi; Shinobu Tsuzuki; Fumihiko HayakawaCancer science 114 3 781 - 792 2022年11月CEBPA-IGH, a fusion gene of the immunoglobulin heavy-chain locus (IGH) and the CCAAT enhancer-binding protein α (C/EBPα) gene, is recurrently found in B-ALL cases and causes aberrant expression of C/EBPα, a master regulator of granulocyte differentiation, in B cells. Forced expression of C/EBPα in B cells was reported to cause loss of B-cell identity due to the inhibition of Pax5, a master regulator of B-cell differentiation; however, it is not known whether the same mechanism is applicable for B-ALL development by CEBPA-IGH. It is known that a full-length isoform of C/EBPα, p42, promotes myeloid differentiation, whereas its N-terminal truncated isoform, p30, inhibits myeloid differentiation through the inhibition of p42; however, the differential role between p42 and p30 in ALL development has not been clarified. In the present study, we examined the effect of the expression of p42 and p30 in B cells by performing RNA-seq of mRNA from LCL stably transfected with p42 or p30. Unexpectedly, suppression of PAX5 target genes was barely observed. Instead, both isoforms suppressed the target genes of MEF2 family members (MEF2s), other regulators of B-cell differentiation. Similarly, MEF2s target genes rather than PAX5 target genes were suppressed in CEBP-IGH-positive ALL (n = 8) compared with other B-ALL (n = 315). Furthermore, binding of both isoforms to MEF2s target genes and the reduction of surrounding histone acetylation were observed in ChIP-qPCR. Our data suggest that the inhibition of MEF2s by C/EBPα plays a role in the development of CEBPA-IGH-positive ALL and that both isoforms work co-operatively to achieve it.
- Yuji Nozaki; Toshihiko Shiga; Chisato Ashida; Daisuke Tomita; Tetsu Itami; Kazuya Kishimoto; Koji Kinoshita; Itaru MatsumuraLupus 32 1 54 - 62 2022年10月Objective Biomarkers of disease activity in lupus nephritis (LN) are in demand. This is because they may be useful in patients who are unable to undergo invasive kidney biopsy, as predictors of renal function, and for early detection of LN recurrence. The focus is on the measurement of urinary chemokines and cytokines, especially in urinary biomarkers, which are non-invasive and simple. In our previous report, we reported that kidney injury molecule-1 (KIM-1) is expressed in injured tubules and that the number of tubular-KIM-expressing positive cells correlates with renal pathology findings and also with urinary (u)-KIM-1 levels. However, there have been no reports examining the effect of u-KIM-1 levels on response to therapy, correlation with renal pathology, and usefulness as a predictor of renal function. Methods U-KIM-1 levels were measured by ELISA in 61 SLE patients. In 38 active LN who underwent renal biopsy, we also examined whether u-KIM-1 levels affected LN disease activity, renal histological findings, and predictors of renal function. Results In SLE patients, proteinuria and u-KIM-1 levels were elevated in active LN compared to inactive LN. U-KIM-1 and proteinuria decreased with intensified treatment. U-KIM-1 levels also correlated with the percentage of glomerular crescent formation in renal pathology. In addition, patients with higher baseline u-KIM-1 levels had significantly higher eGFR and lower LN disease activity at 12 months after treatment intensification. Conclusions These data suggest that u-KIM-1 levels correlate with LN disease activity and renal histopathology findings and may be used as a predictor of treatment response.
- PV、ETの治療と血栓、出血イベント発症との関連性の検討 JSH-MPN-R18の二次分析大矢 瑛子; 永春 圭規; 杉本 由香; 大石 晃嗣; 俵 功; 伊藤 量基; 後藤 明彦; 中前 美佳; 木村 文彦; 小池 通明; 桐戸 敬太; 和田 秀穂; 臼杵 憲祐; 田中 孝幸; 森 毅彦; 脇田 知志; 齋藤 俊樹; 嘉田 晃子; 齋藤 明子; 下田 和哉; 黒川 敏郎; 冨田 章裕; 枝廣 陽子; 橋本 由徳; 清井 仁; 赤司 浩一; 松村 到; 竹中 克斗; 小松 則夫日本血液学会学術集会 84回 277 - 277 2022年10月
- 日本のAYA世代の真性多血症と本態性血小板血症の臨床的特徴 JSH-MPN-R18の二次分析研究杉本 由香; 永春 圭規; 大矢 瑛子; 大石 晃嗣; 俵 功; 伊藤 量基; 後藤 明彦; 中前 美佳; 木村 文彦; 小池 道明; 桐戸 敬太; 和田 秀穂; 臼杵 憲祐; 田中 孝幸; 森 毅彦; 脇田 知志; 齋藤 俊樹; 嘉田 晃子; 齋藤 明子; 下田 和哉; 黒川 敏郎; 冨田 章裕; 枝廣 陽子; 橋本 由徳; 清井 仁; 赤司 浩一; 松村 到; 竹中 克斗; 小松 則夫日本血液学会学術集会 84回 279 - 279 2022年10月
- Junichiro Yuda; Noriko Doki; Hiroshi Matsuoka; Takafumi Yokota; Akihiro Tomita; Naoto Takahashi; Itaru Matsumura; Kohmei Kubo; Tatsunori Goto; Keita Kirito; Akio Maki; Makoto Aoki; Alex Allepuz; Yosuke MinamiCancer medicine 12 3 2990 - 2998 2022年09月Asciminib, a first-in-class, allosteric inhibitor of BCR-ABL1 that acts by STAMP (Specifically Targeting the ABL Myristoyl Pocket), is a novel therapeutic option for patients with chronic myeloid leukemia (CML). In the global, phase 3, open-label ASCEMBL study in patients with CML in chronic phase (CML-CP) pretreated with ≥2 tyrosine kinase inhibitors (TKIs) (NCT03106779), asciminib (40 mg twice-daily) demonstrated significant superiority over the ATP-competitive TKI bosutinib (500 mg once daily) for the primary endpoint of major molecular response (MMR; BCR::ABL1 transcript levels on the international scale [BCR::ABL1IS ] ≤0.1%) at week 24. Here, we report results from a descriptive subgroup analysis of Japanese patients enrolled in ASCEMBL study (data cut-off: May 25, 2020). Overall, 16 Japanese patients were randomized (asciminib, n = 13; bosutinib, n = 3). At week 24, the MMR rate with asciminib was 30.8% (4/13; 95% confidence interval [CI], 9.09-61.43). BCR::ABL1IS ≤1% and complete cytogenic response (CCyR) at week 24 were 61.5% (8/13 patients) and 50.0% (4/8 patients), respectively. In the bosutinib group, no patient achieved MMR, CCyR, or BCR::ABL1IS ≤1%, but results were limited by the low number of patients. The safety profile of asciminib was comparable to that previously observed in the overall study population. Findings from this Japanese subgroup analysis of the ASCEMBL study support the use of asciminib for the treatment of Japanese patients with CML-CP previously treated with ≥2 TKIs. ClinicalTrials.gov Identifier: NCT03106779.
- Takaaki Ono; Masayuki Hino; Itaru Matsumura; Shin Fujisawa; Kenichi Ishizawa; Emiko Sakaida; Naohiro Sekiguchi; Chiho Ono; Mana Aizawa; Yusuke Tanetsugu; Yuichiro Koide; Naoto TakahashiInternational journal of hematology 116 6 871 - 882 2022年08月Bosutinib has been evaluated for treatment of chronic-phase chronic myeloid leukemia (CP-CML) in several clinical studies, including in Japan. This open-label, single-arm, phase 2 study evaluated the efficacy and safety of bosutinib at a starting dose of 400 mg once daily in Japanese patients (n = 60) with newly diagnosed CP-CML. The minimum follow-up period was 3 years and median duration of treatment was 35.9 months. At study completion, 60% of patients were still on treatment. Cumulative rates of major molecular response (MMR), molecular response4 (MR4), and MR4.5 at any time were 70.0%, 53.3%, and 48.3%, respectively. No patient who achieved MMR or MR4 had a confirmed loss of response. No patient experienced on-treatment transformation to accelerated/blast phase or died within 28 days of the last bosutinib dose. Any-grade treatment-emergent adverse events (TEAEs) occurred in 100% (grade ≥ 3: 81.7%) of patients. The most common TEAEs were diarrhea (86.7%), increased alanine aminotransferase (55.0%), and increased aspartate aminotransferase (46.7%). No new safety signals emerged during the follow-up period. Bosutinib continues to demonstrate a favorable benefit/risk profile and is an important treatment option for Japanese patients with newly diagnosed CP-CML. Optimal management of TEAEs during initial treatment with bosutinib should be prioritized.Trial Registration: ClinicalTrials.gov ID: NCT03128411.
- Ryosuke Fujiwara; Yasuhiro Taniguchi; Shinya Rai; Yoshio Iwata; Aki Fujii; Ko Fujimoto; Takahiro Kumode; Kentaro Serizawa; Yasuyoshi Morita; J Luis Espinoza; Hirokazu Tanaka; Hitoshi Hanamoto; Itaru MatsumuraBiochemical and biophysical research communications 626 156 - 166 2022年08月We previously reported that the antipsychotic drug chlorpromazine (CPZ), which inhibits the formation of clathrin-coated vesicles (CCVs) essential for endocytosis and intracellular transport of receptor tyrosine kinase (RTK), inhibits the growth/survival of acute myeloid leukemia cells with mutated RTK (KIT D816V or FLT3-ITD) by perturbing the intracellular localization of these molecules. Here, we examined whether these findings are applicable to epidermal growth factor receptor (EGFR). CPZ dose-dependently inhibited the growth/survival of the non-small cell lung cancer (NSCLC) cell line, PC9 harboring an EGFR-activating (EGFR exon 19 deletion). In addition, CPZ not only suppressed the growth/survival of gefitinib (GEF)-resistant PC9ZD cells harboring T790 M, but also restored their sensitivities to GEF. Furthermore, CPZ overcame GEF resistance caused by Met amplification in HCC827GR cells. As for the mechanism of CPZ-induced growth suppression, we found that although CPZ hardly influenced the phosphorylation of EGFR, it effectively reduced the phosphorylation of ERK and AKT. When utilized in combination with trametinib (a MEK inhibitor), dabrafenib (an RAF inhibitor), and everolimus (an mTOR inhibitor), CPZ suppressed the growth of PC9ZD cells cooperatively with everolimus but not with trametinib or dabrafenib. Immunofluorescent staining revealed that EGFR shows a perinuclear pattern and was intensely colocalized with the late endosome marker, Rab11. However, after CPZ treatment, EGFR was unevenly distributed in the cells, and colocalization with the early endosome marker Rab5 and EEA1 became more apparent, indicating that CPZ disrupted the intracellular transport of EGFR. These results suggest that CPZ has therapeutic potential for NSCLC with mutated EGFR by a novel mechanism different from conventional TKIs alone or in combination with other agents.
- Yasuyoshi Morita; Yasuhito Nannya; Motoshi Ichikawa; Hitoshi Hanamoto; Hirohiko Shibayama; Yoshinobu Maeda; Tomoko Hata; Toshihiro Miyamoto; Hiroshi Kawabata; Kazuto Takeuchi; Hiroko Tanaka; Junji Kishimoto; Satoru Miyano; Itaru Matsumura; Seishi Ogawa; Koichi Akashi; Yuzuru Kanakura; Kinuko MitaniInternational journal of hematology 116 5 659 - 668 2022年07月Darbepoetin alfa (DA) is used to treat anemia in lower-risk (IPSS low or int-1) myelodysplastic syndromes (MDS). However, whether mutations can predict the effectiveness of DA has not been examined. The present study aimed to determine predictive gene mutations. The primary endpoint was a correlation between the presence of highly frequent (≥ 10%) mutations and hematological improvement-erythroid according to IWG criteria 2006 by DA (240 μg/week) until week 16. The study included 79 patients (age 29-90, median 77.0 years; 52 [65.8%] male). Frequently (≥ 10%) mutated genes were SF3B1 (24 cases, 30.4%), TET2 (20, 25.3%), SRSF2 (10, 12.7%), ASXL1 (9, 11.4%), and DNMT3A (8, 10.1%). Overall response rate to DA was 70.9%. Multivariable analysis including baseline erythropoietin levels and red blood cell transfusion volumes as variables revealed that erythropoietin levels and mutations of ASXL1 gene were significantly associated with worse response (odds ratio 0.146, 95% confidence interval 0.042-0.503; p = 0.0023, odds ratio 0.175, 95% confidence interval 0.033-0.928; p = 0.0406, respectively). This study indicated that anemic patients who have higher erythropoietin levels and harbor ASXL1 gene mutations may respond poorly to DA. Alternative strategies are needed for the treatment of anemia in this population. Trial registration number and date of registration: UMIN000022185 and 09/05/2016.
- Yoko Edahiro; Tomoki Ito; Akihiko Gotoh; Mika Nakamae; Fumihiko Kimura; Michiaki Koike; Keita Kirito; Hideho Wada; Kensuke Usuki; Takayuki Tanaka; Takehiko Mori; Satoshi Wakita; Toshiki I Saito; Akiko Kada; Akiko M Saito; Kazuya Shimoda; Yuka Sugimoto; Toshiro Kurokawa; Akihiro Tomita; Yoshinori Hashimoto; Koichi Akashi; Itaru Matsumura; Katsuto Takenaka; Norio KomatsuInternational journal of hematology 116 5 696 - 711 2022年07月The presence of a JAK2 V617F or JAK2 exon 12 mutation is one of the three major criteria listed for the diagnosis of polycythemia vera (PV) in the 2017 World Health Organization Classification. However, a nationwide study has not yet been conducted in Japan since the discovery of JAK2 mutations. Therefore, the Japanese Society of Hematology (JSH) retrospectively analyzed the clinical characteristics of 596 Japanese patients with PV diagnosed between April 2005 and March 2018. Among the 473 patients with complete data on JAK2 mutations available, 446 (94.3%) and 10 (2.1%) were positive for the JAK2 V617F and JAK2 exon 12 mutations, respectively. During a median follow-up of 46 months (range: 0-179 months), 47 (7.9%) deaths occurred. The major causes of death were secondary malignancies (23.4%), acute leukemia (12.8%), non-leukemic progressive disease (10.6%) and thrombotic (6.4%) and hemorrhagic complications (6.4%). Thrombotic and hemorrhagic events occurred during the clinical course in 4.0% (n = 24) and 3.5% (n = 21) of patients, respectively. These results show that the international PV prognostic score (age, venous thrombosis and leukocytosis) is applicable to Japanese patients with PV.
- コロナ禍の多職種連携教育における仮想空間実施の影響池田 行宏; 木村 貴明; 三井 良之; 藤田 貢; 梶 博史; 赤木 將男; 松村 到; 井上 知美; 細見 光一; 大鳥 徹; 小竹 武; 岩城 正宏医学教育 53 Suppl. 233 - 233 (一社)日本医学教育学会 2022年07月
- コロナ禍の多職種連携教育における仮想空間実施の影響池田 行宏; 木村 貴明; 三井 良之; 藤田 貢; 梶 博史; 赤木 將男; 松村 到; 井上 知美; 細見 光一; 大鳥 徹; 小竹 武; 岩城 正宏医学教育 53 Suppl. 233 - 233 (一社)日本医学教育学会 2022年07月
- Takahide Taniguchi; Shoko Nakayama; Hirokazu Tanaka; Shinya Rai; Chikara Hirase; Yasuyoshi Morita; Yoichi Tatsumi; Takashi Ashida; Mitsuhiro Matsuda; Shigeo Hashimoto; Itaru MatsumuraBritish journal of haematology 198 2 360 - 372 2022年07月We previously reported that a novel haemoglobin-platelet index (HPI) based on anaemia and thrombocytopenia was useful to predict the prognosis of patients with diffuse large B-cell lymphoma not otherwise specified (DLBCL NOS). Here, we analyse the utility of HPI in a new validation cohort with DLBCL NOS (n = 94). As a result, we confirm that HPI was effective for differentiating progression-free survival (PFS) and overall survival in this validation cohort. So, we further compare the utility of HPI with previously reported prognostic markers such as the National Comprehensive Center Network-International Prognostic Index (NCCN-IPI), Glasgow prognostic score (GPS), and platelet-albumin (PA) score, using a larger number of 160 patients consisting of the derivation cohort (n = 66) and a validation cohort (n = 94). As a result, the patients with a higher HPI score had significantly worse outcomes, and HPI predicted the prognosis of DLBCL NOS independently of NCCN-IPI. HPI was more sensitive than GPS and almost the same as PA score in predicting PFS. Moreover, the patients whose lymphoma cells were positive for interleukin-6 (IL-6) (75/111 cases) judged by immunohistochemical staining had significantly lower haemoglobin levels and platelet counts than IL-6-negative cases (36/111 cases), suggesting the involvement of IL-6 produced by lymphoma cells in anaemia and thrombocytopenia in DLBCL NOS patients.
- Yuji Nozaki; Motohiro Oribe; Daisuke Tomita; Tetsu Itami; Shinya Hayashi; Toshihisa Maeda; Koji Fukuda; Ryosuke Kuroda; Keiko Funahashi; Tsukasa Matsubara; Koji Kinoshita; Itaru MatsumuraModern rheumatology 33 3 472 - 480 2022年06月OBJECTIVES: Methotrexate (MTX) is recommended as a first-line conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) for treating rheumatoid arthritis (RA). No studies have established which csDMARDs are useful as add-on drugs for RA patients with an inadequate response (IR) to MTX. This retrospective study sought to identify an add-on csDMARD treatment strategy for RA patients with MTX-IR. PATIENTS AND METHODS: We collected the cases of RA patients treated with salazosulfapyridine (SASP) or iguratimod (IGU) as the additional csDMARD for MTX-IR during a 24-month follow-up at four institutions in Japan. We performed propensity score matching to evaluate the retention rate, clinical efficacy, and safety profile (n=54, each group). RESULTS: The retention rates at 24 months of combination therapy in the patients with any-reason discontinuations were 38.5% (MTX+SASP group) and 67.8% (MTX+IGU group). At 3 and 6 months of follow-up, the MTX+IGU group's DAS28-CRP was significantly decreased versus the MTX+SASP group, and at 3 months the MTX+IGU group's good-responder percentage (22.9%) was significantly higher versus the MTX+SASP group's (10.7%). Conversely, compared to the MTX+SASP group, the MTX+IGU group showed a greater reduction in the eGFR from baseline after 3 months during follow-up. CONCLUSIONS: IGU is a useful add-on csDMARD for RA patients with MTX-IR; its high retention rate and good clinical response make it a useful combination therapy for controlling RA disease activity. However, the renal function of these patients should be monitored during follow-up.
- 【血液疾患のすべて】血液学の基礎知識 骨髄系腫瘍の発症機構松村 到日本医師会雑誌 151 特別1 S51 - S52 (公社)日本医師会 2022年06月
- Naoto Takahashi; Jorge E Cortes; Emiko Sakaida; Kenichi Ishizawa; Takaaki Ono; Noriko Doki; Itaru Matsumura; Valentín García-Gutiérrez; Gianantonio Rosti; Chiho Ono; Masayuki Ohkura; Yusuke Tanetsugu; Andrea Viqueira; Tim H BrümmendorfInternational journal of hematology 115 6 838 - 851 2022年06月Bosutinib has been investigated in multiple clinical trials globally, including Japan, for treatment of chronic myeloid leukemia (CML). A pooled analysis of seven Pfizer-sponsored clinical trials evaluated the safety of bosutinib in Japanese (n = 138) vs non-Japanese (n = 1210) patients with CML. First-line bosutinib was administered in 54.3% vs 41.4% of patients, and second-line or later bosutinib in the remainder. Median treatment duration was 1.4 vs 2.3 years, and median relative dose intensity 78.1% vs 90.0%. Any-grade treatment-emergent adverse events (TEAEs) occurred in 100.0% vs 98.9% (grade ≥ 3: 81.9% vs 75.2%). In both groups, the most common TEAEs relevant to bosutinib were gastrointestinal (92.8% vs 84.7%), liver function (72.5% vs 34.8%), rash (63.8% vs 37.4%), and myelosuppression (55.1% vs 50.7%). TEAEs led to dose reduction in 65.2% vs 50.6%, dose interruption in 78.3% vs 68.8%, and permanent treatment discontinuation in 30.4% vs 25.4% of patients. The safety profile of bosutinib in Japanese patients was generally consistent with that in non-Japanese patients, despite a higher incidence of gastrointestinal, liver function, and rash events. TEAEs were largely manageable with dose modifications and supportive care in both groups. These data may help optimize TEAE management and outcomes in Japanese patients receiving bosutinib for CML. Trial registration ClinicalTrials.gov: NCT02130557, NCT03128411, NCT00574873, NCT00261846, NCT01903733, NCT00811070, NCT02228382.
- Yasushi Miyazaki; Toru Kiguchi; Shinya Sato; Kensuke Usuki; Ken Ishiyama; Yoshikazu Ito; Takahiro Suzuki; Jun Taguchi; Shigeru Chiba; Nobuaki Dobashi; Akihiro Tomita; Hironori Harada; Hiroshi Handa; Shigeo Horiike; Tomoya Maeda; Mitsuhiro Matsuda; Motoshi Ichikawa; Tomoko Hata; Sumihisa Honda; Satoshi Iyama; Hitoshi Suzushima; Yukiyoshi Moriuchi; Toshiro Kurokawa; Kenichi Yokota; Shigeki Ohtake; Takahiro Yamauchi; Itaru Matsumura; Hitoshi Kiyoi; Tomoki NaoeInternational journal of hematology 116 2 228 - 238 2022年05月The hypomethylating agent azacitidine (AZA) significantly extends overall survival (OS) in patients with higher risk myelodysplastic syndromes (MDS), when compared with other conventional care regimens, including supportive care and low-dose and intensive chemotherapy. However, the effects of 5- and 7-day treatment schedules of AZA (AZA-5 and AZA-7, respectively) on the OS of MDS patients had not been compared prospectively. We started a phase 3 trial comparing the effects of AZA-7 and AZA-5 on MDS patients with refractory anemia with excess blasts (RAEB) and RAEB in transformation (RAEB-T). However, this trial was prematurely terminated because of poor recruitment. Using all data, there was no significant difference in the OS of patients between AZA-7 (92 patients) and AZA-5 (95 patients), with the 2-year OS rates of AZA-7 and AZA-5 at 36.4% and 25.8%, respectively (P = 0.293). Adverse event profiles were similar between the two groups. Interestingly, data of the centrally diagnosed RAEB and RAEB-T cases showed that AZA-7 significantly prolonged the time to leukemia transformation compared with AZA-5 (P = 0.022), confirmed by multivariate analysis. Although this trial could not provide definite evidence, the results support the use of AZA-7 for RAEB and RAEB-T. (UMIN Clinical Trials Registry UMIN000009633).
- Yu-Ting Dai; Fan Zhang; Hai Fang; Jian-Feng Li; Gang Lu; Lu Jiang; Bing Chen; Dong-Dong Mao; Yuan-Fang Liu; Jin Wang; Li-Jun Peng; Chong Feng; Hai-Feng Chen; Jun-Xi Mu; Qun-Ling Zhang; Hao Wang; Hany Ariffin; Tan Ah Moy; Jing-Han Wang; Yin-Jun Lou; Su-Ning Chen; Qian Wang; Hong Liu; Zhe Shan; Itaru Matsumura; Yasushi Miyazaki; Takahiko Yasuda; Li-Ping Dou; Xiao-Jing Yan; Jin-Song Yan; Allen Eng-Juh Yeoh; De-Pei Wu; Hitoshi Kiyoi; Fumihiko Hayakawa; Jie Jin; Sheng-Yue Wang; Xiao-Jian Sun; Jian-Qing Mi; Zhu Chen; Jin-Yan Huang; Sai-Juan ChenProceedings of the National Academy of Sciences of the United States of America 119 15 e2120787119 2022年04月T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy of T cell progenitors, known to be a heterogeneous disease in pediatric and adult patients. Here we attempted to better understand the disease at the molecular level based on the transcriptomic landscape of 707 T-ALL patients (510 pediatric, 190 adult patients, and 7 with unknown age; 599 from published cohorts and 108 newly investigated). Leveraging the information of gene expression enabled us to identify 10 subtypes (G1–G10), including the previously undescribed one characterized by GATA3 mutations, with GATA3R276Q capable of affecting lymphocyte development in zebrafish. Through associating with T cell differentiation stages, we found that high expression of LYL1/LMO2/SPI1/HOXA (G1–G6) might represent the early T cell progenitor, pro/precortical/cortical stage with a relatively high age of disease onset, and lymphoblasts with TLX3/TLX1 high expression (G7–G8) could be blocked at the cortical/postcortical stage, while those with high expression of NKX2-1/TAL1/LMO1 (G9–G10) might correspond to cortical/postcortical/mature stages of T cell development. Notably, adult patients harbored more cooperative mutations among epigenetic regulators, and genes involved in JAK-STAT and RAS signaling pathways, with 44% of patients aged 40 y or above in G1 bearing DNMT3A/IDH2 mutations usually seen in acute myeloid leukemia, suggesting the nature of mixed phenotype acute leukemia.
- Yasunori Ueda; Kensuke Usuki; Jiro Fujita; Itaru Matsumura; Nobuyuki Aotsuka; Naohiro Sekiguchi; Tomonori Nakazato; Hiromi Iwasaki; Mariko Takahara-Matsubara; Saori Sugimoto; Masashi Goto; Tomoki Naoe; Masahiro Kizaki; Yasushi Miyazaki; Koichi AakashiCancer science 113 4 1377 - 1392 2022年04月DSP-7888 is an immunotherapeutic cancer vaccine derived from the Wilms' tumor gene 1 (WT1) protein. This phase 1/2 open-label study evaluated the safety and efficacy of DSP-7888 dosing emulsion in patients with myelodysplastic syndromes (MDS). DSP-7888 was administered intradermally (3.5 or 10.5 mg) every 2 weeks for 6 months and then every 2-4 weeks until lack of benefit. Twelve patients were treated in phase 1 (3.5 mg, n = 6; 10.5 mg, n = 6), with no dose-limiting toxicities reported. Thus, the 10.5 mg dose was selected as the recommended phase 2 dose, and 35 patients were treated in phase 2. Forty-seven patients received ≥1 dose of the study drug and comprised the safety analysis set. The most common adverse drug reaction (ADR) was injection site reactions (ISR; 91.5%). Grade 3 ISR were common (58.8%) in phase 1 but occurred less frequently in 2 (22.9%) following implementation of risk minimization strategies. Other common ADR were pyrexia (10.6%) and febrile neutropenia (8.5%). In the efficacy analysis set, comprising patients with higher-risk MDS after azacitidine failure in phases 1 and 2 (n = 42), the disease control rate was 19.0%, and the median overall survival (OS) was 8.6 (90% confidence interval [CI], 6.8-10.3) months. Median OS was 10.0 (90% CI, 7.6-11.4) months in patients with a WT1-specific immune response (IR; n = 33) versus 4.1 (90% CI, 2.3-8.1) months in those without a WT1-specific IR (n = 9; P = .0034). The acceptable safety and clinical activity findings observed support the continued development of DSP-7888 dosing emulsion.
- Takahiko Yasuda; Masashi Sanada; Masahito Kawazu; Shinya Kojima; Shinobu Tsuzuki; Hiroo Ueno; Eisuke Iwamoto; Yuka Iijima-Yamashita; Tomomi Yamada; Takashi Kanamori; Rieko Nishimura; Yachiyo Kuwatsuka; Satoru Takada; Masatsugu Tanaka; Shuichi Ota; Nobuaki Dobashi; Etsuko Yamazaki; Asao Hirose; Tohru Murayama; Masahiko Sumi; Shinya Sato; Naoyuki Tange; Yukinori Nakamura; Yuna Katsuoka; Emiko Sakaida; Toyotaka Kawamata; Hiroatsu Iida; Yuichi Shiraishi; Yasuhito Nannya; Seishi Ogawa; Masafumi Taniwaki; Norio Asou; Yoshihiro Hatta; Hitoshi Kiyoi; Itaru Matsumura; Keizo Horibe; Hiroyuki Mano; Tomoki Naoe; Yasushi Miyazaki; Fumihiko HayakawaBlood 139 12 1850 - 1862 2022年03月The genetic basis of leukemogenesis in adults with B-cell acute lymphoblastic leukemia (B-ALL) is largely unclear, and its clinical outcome remains unsatisfactory. This study aimed to advance the understanding of biological characteristics, improve disease stratification, and identify molecular targets of adult B-ALL. Adolescents and young adults (AYA) (15 to 39 years old, n = 193) and adults (40 to 64 years old, n = 161) with Philadelphia chromosome-negative (Ph-) B-ALL were included in this study. Integrated transcriptomic and genetic analyses were used to classify the cohort into defined subtypes. Of the 323 cases included in the RNA sequencing analysis, 278 (86.1%) were classified into 18 subtypes. The ZNF384 subtype (22.6%) was the most prevalent, with 2 novel subtypes (CDX2-high and IDH1/2-mut) identified among cases not assigned to the established subtypes. The CDX2-high subtype (3.4%) was characterized by high expression of CDX2 and recurrent gain of chromosome 1q. The IDH1/2-mut subtype (1.9%) was defined by IDH1 R132C or IDH2 R140Q mutations with specific transcriptional and high-methylation profiles. Both subtypes showed poor prognosis and were considered inferior prognostic factors independent of clinical parameters. Comparison with a previously reported pediatric B-ALL cohort (n = 1003) showed that the frequencies of these subtypes were significantly higher in AYA/adults than in children. We delineated the genetic and transcriptomic landscape of adult B-ALL and identified 2 novel subtypes that predict poor disease outcomes. Our findings highlight the age-dependent distribution of subtypes, which partially accounts for the prognostic differences between adult and pediatric B-ALL.
- SLEの治療(ステロイドの減量・中止) 当院における全身性エリテマトーデスに対するベリムマブの治療効果とステロイド減量についての検討冨田 大介; 野崎 祐史; 山澤 広嵩; 石村 香織; 芦田 千聖; 岡田 晃典; 伊丹 哲; 酒井 健史; 志賀 俊彦; 岸本 和也; 木下 浩二; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 66回 445 - 445 (一社)日本リウマチ学会 2022年03月
- JAK阻害薬とDMARDsの併用療法についての検討伊丹 哲; 冨田 大介; 志賀 俊彦; 岸本 和也; 野崎 祐史; 木下 浩二; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 66回 607 - 607 (一社)日本リウマチ学会 2022年03月
- Kentaro Serizawa; Hirokazu Tanaka; Takeshi Ueda; Ayano Fukui; Hiroaki Kakutani; Takahide Taniguchi; Hiroaki Inoue; Takahiro Kumode; Yasuhiro Taniguchi; Shinya Rai; Chikara Hirase; Yasuyoshi Morita; J Luis Espinoza; Yoichi Tatsumi; Takashi Ashida; Itaru MatsumuraInternational journal of hematology 115 3 336 - 349 2022年03月Side population (SP) is known to include therapy-resistant cells in various cancers. Here, we analyzed SP using multiple myeloma (MM) samples. The SP accounted for 2.96% in MM cells from newly diagnosed MM (NDMM). CD34 was expressed in 47.8% of SP cells, but only in 2.11% of bulk MM cells. CD34+ MM cells expressed more immature cell surface markers and a gene signature than CD34- MM cells. CD34+ but not CD34- MM cells possessed clonogenic activities and showed long-term self-renewal activities in xenotransplantation assays. Similarly, whereas 2.20% of MM cells were CD34+ in NDMM (n = 38), this proportion increased to 42.6% in minimal residual disease (MRD) samples (n = 16) (p < 0.001) and to 17.7% in refractory/relapsed MM (RRMM) (n = 30) (p < 0.01). Cell cycle analysis showed that 24.7% of CD34+ MM cells from NDMM were in G0 phase while this proportion was 54.9% in MRD (p < 0.05) and 14.5% in RRMM, reflecting the expansion of MM. Together, CD34+ MM cells with long-term self-renewal activities persist as MRD in cell cycle quiescence or remain as therapy-resistant cells in RRMM, substantiating the necessity of targeting this population to improve clinical outcomes of MM.
- Shinichi Kako; Fumihiko Hayakawa; Koichi Miyamura; Junji Tanaka; Kiyotoshi Imai; Junya Kanda; Satoko Morishima; Naoyuki Uchida; Noriko Doki; Kazuhiro Ikegame; Yukiyasu Ozawa; Satoru Takada; Noriko Usui; Shigeki Ohtake; Hitoshi Kiyoi; Itaru Matsumura; Yasushi Miyazaki; Tatsuo Ichinohe; Takahiro Fukuda; Yoshiko Atsuta; Yoshinobu KandaTransplantation and cellular therapy 28 3 161.e1-161.e10 2022年03月An HLA-matched relative is the first-choice donor for patients with Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL) in first complete remission (CR1). The most promising alternative donor is thought to be an HLA-matched unrelated donor (MUD) in patients who do not have an HLA-matched related donor. Cord blood transplantation (CBT) is an alternative option. Higher rates of engraftment failure and nonrelapse mortality (NRM) are significant problems, but the ready availability of cord blood can be an advantage, because patients can immediately undergo transplantation before progression. This study was conducted to identify an appropriate alternative donor in patients with Ph-negative ALL in CR1 who do not have an HLA-matched related donor (MRD). Decision analyses using a Markov model were performed to compare immediate CBT, in which CBT was performed at 1 month after the achievement of CR1, with elective unrelated bone marrow transplantation (uBMT) from an 8/8 MUD (8/8 uBMT) or uBMT from a 7/8 MUD (7/8 uBMT), in which uBMT was performed at 4 months, in patients age 16 to 55 years with Ph-negative ALL in CR1 who did not have an MRD. We constructed a decision tree. The cycle length was set at 3 months, and analyses were performed for 19 cycles for uBMT and 20 cycles for CBT, resulting in evaluation of the 5-year life expectancy after both decisions. Transition probabilities (TPs) and utilities were estimated from prospective and retrospective Japanese studies and the registry database of Japan. Subgroup analyses were performed according to risk stratification based on WBC count and cytogenetics at diagnosis and according to age stratification, with a cutoff of 25 years. One-way sensitivity analyses for TPs and utilities were performed as well. The baseline analyses showed that 8/8 uBMT or 7/8 uBMT had superior results to CBT, with quality-adjusted life years (QALYs) of 2.86 in 8/8 uBMT, 2.84 in 7/8 uBMT, and 2.75 in CBT. One-way sensitivity analyses showed that the results of the baseline analyses were reversed if the probability of NRM in CBT improved. Subgroup analyses showed similar results in younger, older, and high-risk patients. However, QALY was worse in 8/8 uBMT compared with CBT in standard-risk patients. In one-way sensitivity analyses, the probabilities of NRM in uBMT and CBT affected the baseline results in all analyses except for comparisons between 8/8 uBMT and CBT in younger and high-risk patients. In these 2 populations, the superiority of 8/8 uBMT was consistently demonstrated throughout the one-way sensitivity analyses. For patients with Ph-negative ALL in CR1 who decide to undergo transplantation from an alternative donor, elective uBMT from either an 8/8 MUD or a 7/8 MUD is expected to yield a better outcome than immediate CBT. Nonetheless, CBT is a viable option, and improvements to reduce the risk of NRM in CBT may change these results.
- Takahiro Kumode; Hirokazu Tanaka; Jorge Luis Esipinoza; Shinya Rai; Yasuhiro Taniguchi; Ryosuke Fujiwara; Keigo Sano; Kentaro Serizawa; Yoshio Iwata; Yasuyoshi Morita; Itaru MatsumuraInternational journal of hematology 115 3 310 - 321 2022年03月C-type lectin-like receptor 2 (CLEC-2) expressed on megakaryocytes plays important roles in megakaryopoiesis. We found that CLEC-2 was expressed in about 20% of phenotypical long-term hematopoietic stem cells (LT-HSCs), which expressed lower levels of HSC-specific genes and produced larger amounts of megakaryocyte-related molecules than CLEC-2low LT-HSCs. Although CLEC-2high LT-HSCs had immature clonogenic activity, cultured CLEC-2high LT-HSCs preferentially differentiated into megakaryocytes. CLEC-2high HSCs yielded 6.8 times more megakaryocyte progenitors (MkPs) and 6.0 times more platelets 2 weeks and 1 week after transplantation compared with CLEC-2low LT-HSCs. However, platelet yield from CLEC-2high HSCs gradually declined with the loss of MkPs, while CLEC-2low HSCs self-renewed long-term, indicating that CLEC-2high LT-HSCs mainly contribute to early megakaryopoiesis. Treatment with pI:C and LPS increased the proportion of CLEC-2high LT-HSCs within LT-HSCs. Almost all CLEC-2low LT-HSCs were in the G0 phase and barely responded to pI:C. In contrast, 54% of CLEC-2high LT-HSCs were in G0, and pI:C treatment obliged CLEC-2high LT-HSCs to enter the cell cycle and differentiate into megakaryocytes, indicating that CLEC-2high LT-HSCs are primed for cell cycle entry and rapidly yield platelets in response to inflammatory stress. In conclusion, CLEC-2high LT-HSCs appear to act as a reserve for emergent platelet production under stress conditions.
- Shinobu Tsuzuki; Takahiko Yasuda; Masahito Kawazu; Toshihide Ueno; Sivasundaram Karnan; Akinobu Ota; Masashi Sanada; Hirokazu Nagai; Akihiro Tomita; Yoshiyuki Takahashi; Yasushi Miyazaki; Itaru Matsumura; Hitoshi Kiyoi; Yoshitaka Hosokawa; Hiroyuki Mano; Fumihiko HayakawaCANCER SCIENCE 113 1236 - 1236 2022年02月
- Yoshinori Hashimoto; Tomoki Ito; Akihiko Gotoh; Mika Nakamae; Fumihiko Kimura; Michiaki Koike; Keita Kirito; Hideho Wada; Kensuke Usuki; Takayuki Tanaka; Takehiko Mori; Satoshi Wakita; Toshiki I Saito; Akiko Kada; Akiko M Saito; Kazuya Shimoda; Yuka Sugimoto; Toshiro Kurokawa; Akihiro Tomita; Yoko Edahiro; Koichi Akashi; Itaru Matsumura; Katsuto Takenaka; Norio KomatsuInternational journal of hematology 115 2 208 - 221 2022年02月We conducted a large-scale, nationwide retrospective study of Japanese patients who were diagnosed with essential thrombocythemia based on the diagnostic criteria in the World Health Organization classification. We investigated clinical characteristics, survival rates, and the incidence of thrombohemorrhagic events as well as risk factors for these events. A total of 1152 patients were analyzed in the present study. Median age at diagnosis was 65 years, the median platelet count was 832 × 109/L, and the positive mutation rates of JAK2V617F, CALR, and MPL were 62.8, 25.1, and 4.1%, respectively. Compared with European and American patients, Japanese patients were more likely to have cardiovascular risk factors and less likely to have systemic symptoms including palpable splenomegaly. Thrombocytosis was identified as a risk factor for hemorrhagic events and prognosis, but not for thrombotic events. The prognostic factors and risk classifications reported in Europe and the United States were generally applicable to Japanese patients. Regarding transformations, secondary myelofibrosis progressed in a time-dependent manner, but progression to acute leukemia was low in "true" ET patients. Skin cancers were less common and gastrointestinal cancers more common as secondary malignancies in Japanese patients, suggesting ethnic differences.
- Shinya Rai; Hiroaki Inoue; Kazuko Sakai; Hitoshi Hanamoto; Mitsuhiro Matsuda; Yasuhiro Maeda; Takahiro Haeno; Yosaku Watatani; Takahiro Kumode; Kentaro Serizawa; Yasuhiro Taniguchi; Chikara Hirase; J Luis Espinoza; Yasuyoshi Morita; Hirokazu Tanaka; Takashi Ashida; Yoichi Tatsumi; Kazuto Nishio; Itaru MatsumuraCancer science 113 2 660 - 673 2022年02月We previously examined the utility of rituximab-bendamustine (RB) in patients with follicular lymphoma (FL) exhibiting less than optimal responses to 2 cycles of the R-CHOP chemotherapy regimen. The aim of this study was to identify molecular biomarkers that can predict prognosis in RB-treated patients in the context of the prospective cohort. We first analyzed the mutational status of 410 genes in diagnostic tumor specimens by target capture and Sanger sequencing. CREBBP, KMT2D, MEF2B, BCL2, EZH2, and CARD11 were recurrently mutated as reported before, however none was predictive for progression-free survival (PFS) in the RB-treated patients (n = 34). A gene expression analysis by nCounter including 800 genes associated with carcinogenesis and/or the immune response showed that expression levels of CD8+ T-cell markers and half of the genes regulating Th1 and Th2 responses were significantly lower in progression of disease within the 24-mo (POD24) group (n = 8) than in the no POD24 group (n = 31). Collectively, we selected 10 genes (TBX21, CXCR3, CCR4, CD8A, CD8B, GZMM, FLT3LG, CD3E, EOMES, GZMK), and generated an immune infiltration score (IIS) for predicting PFS using principal component analysis, which dichotomized the RB-treated patients into immune IIShigh (n = 19) and IISlow (n = 20) groups. The 3-y PFS rate was significantly lower in the IISlow group than in the IIShigh group (50.0% [95% CI: 27.1-69.2%] vs. 84.2% [95% CI: 58.7-94.6%], P = .0237). Furthermore, the IIS was correlates with absolute lymphocyte counts at diagnosis (r = 0.460, P = .00355). These results suggest that the T-cell-associated immune markers could be useful to predict prognosis in RB-treated FL patients. (UMIN:000 013 795, jRCT:051 180 181).
- Yasuaki Hirooka; Saki Okuda; Masafumi Sugiyama; Toshihiko Shiga; Yuji Nozaki; Koji Kinoshita; Masanori Funauchi; Itaru MatsumuraFrontiers in Immunology 13 2022年01月The rare systemic inflammatory disorder ‘adult-onset Still’s disease (AOSD)’ is characterized by recurrent fever, evanescent rash, arthralgia, and leukocytosis with neutrophilia. The Yamaguchi criteria are widely used to diagnose AOSD; these criteria can be used for diagnosis after a wide range of infectious, rheumatic, and neoplastic diseases have been excluded. AOSD generally does not overlap with other rheumatic diseases. We present the rare case of an 80-year-old Japanese woman who presented with arthralgia, fever, and skin rash during treatment for systemic lupus erythematosus (SLE), which was finally diagnosed as an overlap of AOSD. Blood tests revealed leukocytosis with neutrophilia, high C-reactive protein (CRP), and liver dysfunction. Her anti-ds-DNA antibody titer and serum complement titer were at the same level as before and remained stable. We suspected AOSD based on the high serum ferritin level but hesitated to diagnose AOSD because of the patient’s SLE history. We measured serum interleukin (IL)-18; it was extremely high at 161,221 pg/mL, which was strongly suggestive of AOSD. We thus diagnosed AOSD complicated during the course of treatment for SLE. The patient’s arthralgia and high CRP level persisted after we increased her oral prednisolone dose and added oral methotrexate, but her symptoms eventually improved with the addition of intravenous tocilizumab. We note that the presence of autoantibodies or other rheumatic diseases cannot be absolutely ruled out in the diagnosis of AOSD. Although high serum IL-18 levels are not specific for AOSD, the measurement of serum IL-18 may aid in the diagnosis of AOSD in similar rare cases.
- Kazuhito Yamamoto; Atsushi Shinagawa; Courtney D DiNardo; Keith W Pratz; Kenichi Ishizawa; Toshihiro Miyamoto; Norio Komatsu; Yasuhiro Nakashima; Chikashi Yoshida; Noriko Fukuhara; Kensuke Usuki; Takahiro Yamauchi; Noboru Asada; Norio Asou; Ilseung Choi; Yasushi Miyazaki; Hideyuki Honda; Sumiko Okubo; Misaki Kurokawa; Ying Zhou; Jiuhong Zha; Jalaja Potluri; Itaru MatsumuraJapanese journal of clinical oncology 52 1 29 - 38 2022年01月BACKGROUND: The phase 3 VIALE-A trial (NCT02993523) reported that venetoclax-azacitidine significantly prolonged overall survival compared with placebo-azacitidine in patients with newly diagnosed acute myeloid leukemia ineligible for intensive chemotherapy. Herein, efficacy and safety of venetoclax-azacitidine are analyzed in the Japanese subgroup of VIALE-A patients. METHODS: Eligible Japanese patients were randomized 2:1 to venetoclax-azacitidine (N = 24) or placebo-azacitidine (N = 13). Primary endpoints for Japan were overall survival and complete response (CR) + CR with incomplete hematologic recovery (CRi). Venetoclax (target dose 400 mg) was given orally once daily. Azacitidine (75 mg/m2) was administered subcutaneously or intravenously on Days 1-7 of each 28-day cycle. RESULTS: Median follow-up was 16.3 months (range, 1.0-20.3). Median overall survival was not reached with venetoclax-azacitidine (hazard ratio 0.409 and 95% confidence interval: 0.151, 1.109); overall survival estimate was higher with venetoclax-azacitidine than placebo-azacitidine at 12 (67 and 46%) and 18 months (57 and 31%), respectively. CR and CRi rates were 67% with venetoclax-azacitidine and 15% with placebo-azacitidine. Most common any-grade adverse events were febrile neutropenia (79 and 39%), thrombocytopenia (54 and 77%), constipation (54 and 54%) and decreased appetite (54 and 38%) in the venetoclax-azacitidine and placebo-azacitidine arms, respectively. Only 1 patient in the venetoclax-azacitidine arm, and no patients in the placebo-azacitidine arm, had grade 4 febrile neutropenia that led to treatment discontinuation. CONCLUSIONS: This Japanese subgroup analysis of VIALE-A demonstrates comparable safety and efficacy outcomes compared with the global study and supports venetoclax-azacitidine as first-line standard-of-care for Japanese treatment-naive patients with acute myeloid leukemia who are ineligible for intensive chemotherapy.
- Yutaka Shimazu; Junya Kanda; Hitomi Kaneko; Kazunori Imada; Ryosuke Yamamura; Satoru Kosugi; Yuji Shimura; Tomoki Ito; Shin-Ichi Fuchida; Hitoji Uchiyama; Kentaro Fukushima; Satoshi Yoshihara; Hitoshi Hanamoto; Hirokazu Tanaka; Nobuhiko Uoshima; Kensuke Ohta; Hideo Yagi; Hirohiko Shibayama; Yoshiyuki Onda; Yasuhiro Tanaka; Yoko Adachi; Mitsuhiro Matsuda; Masato Iida; Takashi Miyoshi; Toshimitsu Matsui; Ryoichi Takahashi; Teruhito Takakuwa; Masayuki Hino; Naoki Hosen; Shosaku Nomura; Chihiro Shimazaki; Itaru Matsumura; Akifumi Takaori-Kondo; Junya KurodaTherapeutic advances in hematology 13 20406207221142487 - 20406207221142487 2022年BACKGROUND: Daratumumab is one of the most widely used treatments for relapsed/refractory multiple myeloma (MM) patients. However, not all patients achieve a lasting therapeutic response with daratumumab. OBJECTIVES: We hypothesized that a durable response to daratumumab could be predicted by the balance between the MM tumor burden and host immune status. DESIGN: We conducted a retrospective study using the real-world data in the Kansai Myeloma Forum (KMF) database. METHODS: We retrospectively analyzed 324 relapsed/refractory MM patients who were treated with daratumumab in the KMF database. RESULTS: In this study, 196 patients were treated with daratumumab, lenalidomide, and dexamethasone (DLd) regimen and 128 patients were treated with daratumumab, bortezomib, and dexamethasone (DBd) regimen. The median age at treatment, number of prior treatment regimens and time-to-next-treatment (TTNT) were 68, 4 and 8.02 months, respectively. A multivariate analysis showed that the TTNT under the DLd regimen was longer with either higher monocyte counts (analysis 1), higher white blood cell (WBC) counts (analysis 2), lower β2 microglobulin (B2MG < 5.5 mg/L) or fewer prior regimens (<4). No parameters were correlated with TTNT under the DBd regimen. CONCLUSION: We propose a simple scoring model to predict a durable effect of the DLd regimen by classifying patients into three categories based on either monocyte counts (0 points for ⩾200/μl; 1 point for <200/μl) or WBC counts (0 points for ⩾3500/μl; 1 point for <3500/μl) plus B2MG (0 points for <5.5 mg/L; 1 point for ⩾5.5 mg/L). Patients with a score of 0 showed significantly longer TTNT and significantly better survival compared to those with a score of 1 or 2 (both p < 0.001). To confirm this concept, our results will need to be validated in other cohorts.
- 山本敦弘; 山本敦弘; 山澤広嵩; 石村香織; 芦田千聖; 赤澤宗輝; 冨田大介; 岡田晃典; 伊丹哲; 酒井健史; 李進海; 李進海; 志賀俊彦; 岸本和也; 野崎祐史; 木下浩二; 松村到日本リウマチ学会総会・学術集会プログラム・抄録集 66th 2022年
- 石村香織; 志賀俊彦; 山澤広嵩; 赤澤宗輝; 芦田千聖; 岡田晃典; 冨田大介; 伊丹哲; 酒井健史; 岸本和也; 野崎祐史; 木下浩二; 船内正憲; 松村到日本リウマチ学会総会・学術集会プログラム・抄録集 66th 2022年
- 山澤広嵩; 志賀俊彦; 石村香織; 赤澤宗輝; 芦田千聖; 岡田晃典; 冨田大介; 伊丹哲; 酒井健史; 岸本和也; 野崎祐史; 木下浩二; 船内正憲; 松村到日本リウマチ学会総会・学術集会プログラム・抄録集 66th 2022年
- 赤澤宗輝; 山澤広嵩; 石村香織; 芦田千聖; 池田房代; 山本敦弘; 岡田晃典; 冨田大介; 伊丹哲; 酒井健史; 志賀俊彦; 岸本和也; 野崎祐史; 木下浩二; 船内正憲; 松村到日本リウマチ学会総会・学術集会プログラム・抄録集 66th 2022年
- 山本敦弘; 山澤広嵩; 石村香織; 芦田千聖; 赤澤宗輝; 冨田大介; 岡田晃典; 伊丹哲; 酒井健史; 李進海; 李進海; 志賀俊彦; 岸本和也; 野崎祐史; 木下浩二; 松村到日本リウマチ学会総会・学術集会プログラム・抄録集 66th 2022年
- 岸本和也; 山澤広嵩; 石村香織; 芦田千聖; 赤澤宗輝; 山本敦弘; 池田房代; 岡田晃典; 冨田大介; 伊丹哲; 志賀俊彦; 野崎祐史; 木下浩二; 松村到日本リウマチ学会総会・学術集会プログラム・抄録集 66th 2022年
- 赤澤宗輝; 山澤広嵩; 石村香織; 芦田千聖; 岡田晃典; 冨田大介; 伊丹哲; 酒井健史; 志賀俊彦; 岸本和也; 野崎祐史; 木下浩二; 船内正憲; 松村到日本リウマチ学会総会・学術集会プログラム・抄録集 66th 2022年
- 田中宏和; 芹澤憲太郎; 松村到月刊血液内科 84 4 2022年
- 松村到週刊日本医事新報 5109 2022年
- Yasuaki Hirooka; Saki Okuda; Masafumi Sugiyama; Toshihiko Shiga; Yuji Nozaki; Koji Kinoshita; Masanori Funauchi; Itaru MatsumuraFrontiers in immunology 13 822169 - 822169 2022年The rare systemic inflammatory disorder 'adult-onset Still's disease (AOSD)' is characterized by recurrent fever, evanescent rash, arthralgia, and leukocytosis with neutrophilia. The Yamaguchi criteria are widely used to diagnose AOSD; these criteria can be used for diagnosis after a wide range of infectious, rheumatic, and neoplastic diseases have been excluded. AOSD generally does not overlap with other rheumatic diseases. We present the rare case of an 80-year-old Japanese woman who presented with arthralgia, fever, and skin rash during treatment for systemic lupus erythematosus (SLE), which was finally diagnosed as an overlap of AOSD. Blood tests revealed leukocytosis with neutrophilia, high C-reactive protein (CRP), and liver dysfunction. Her anti-ds-DNA antibody titer and serum complement titer were at the same level as before and remained stable. We suspected AOSD based on the high serum ferritin level but hesitated to diagnose AOSD because of the patient's SLE history. We measured serum interleukin (IL)-18; it was extremely high at 161,221 pg/mL, which was strongly suggestive of AOSD. We thus diagnosed AOSD complicated during the course of treatment for SLE. The patient's arthralgia and high CRP level persisted after we increased her oral prednisolone dose and added oral methotrexate, but her symptoms eventually improved with the addition of intravenous tocilizumab. We note that the presence of autoantibodies or other rheumatic diseases cannot be absolutely ruled out in the diagnosis of AOSD. Although high serum IL-18 levels are not specific for AOSD, the measurement of serum IL-18 may aid in the diagnosis of AOSD in similar rare cases.
- Yoshiyuki Onda; Junya Kanda; Hitomi Kaneko; Yuji Shimura; Shin-Ichi Fuchida; Aya Nakaya; Tomoki Itou; Ryosuke Yamamura; Hirokazu Tanaka; Hirohiko Shibayama; Yutaka Shimazu; Hitoji Uchiyama; Satoshi Yoshihara; Yoko Adachi; Mitsuhiro Matsuda; Hitoshi Hanamoto; Nobuhiko Uoshima; Satoru Kosugi; Kensuke Ohta; Hideo Yagi; Yuzuru Kanakura; Itaru Matsumura; Masayuki Hino; Shosaku Nomura; Chihiro Shimazaki; Akifumi Takaori-Kondo; Junya KurodaTherapeutic advances in hematology 13 20406207221104584 - 20406207221104584 2022年Background: Little is known about the real-world survival benefits and safety profiles of carfilzomib-lenalidomide-dexamethasone (KRd) and carfilzomib-dexamethasone (Kd). Methods: We performed a retrospective analysis to evaluate their efficacy and safety in 157 patients registered in the Kansai Myeloma Forum database. Results: A total of 107 patients received KRd. Before KRd, 99% of patients had received bortezomib (54% were refractory disease), and 82% had received lenalidomide (57% were refractory disease). The overall response rate (ORR) was 68.2%. The median progression-free survival (PFS) and overall survival (OS) were 8.8 and 29.3 months, respectively. Multivariate analysis showed that reduction of the carfilzomib dose and non-IgG M protein were significantly associated with lower PFS and reduction of the carfilzomib dose and refractoriness to prior bortezomib-based regimens were significantly associated with lower OS. A total of 50 patients received Kd. Before Kd, 96% of patients had received bortezomib (54% were refractory disease). The ORR was 62.0%. The median PFS and OS were 7.1 and 20.9 months, respectively. Based on the multivariate analysis, reduction of the carfilzomib dose and International Staging System Stage III (ISS III) were significantly associated with lower PFS. Grade III or higher adverse events were observed in 48% of KRd cases and 54% of Kd cases. Cardiovascular events, cytopenia, and infections were frequent, and 4 KRd patients died due to heart failure, arrhythmia, cerebral hemorrhage, and pneumonia. Conclusion: Our analysis showed that an adequate dose of carfilzomib is important for achieving the best survival benefits in a real-world setting. Adverse effects after KRd and Kd therapy should also be considered.
- Yuki Fujioka; Daisuke Sugiyama; Itaru Matsumura; Yosuke Minami; Masatomo Miura; Yoshiko Atsuta; Shigeki Ohtake; Hitoshi Kiyoi; Yasushi Miyazaki; Hiroyoshi Nishikawa; Naoto TakahashiCancers 13 23 2021年11月Treatment-free remission (TFR) has become a therapeutic goal in chronic myeloid leukemia (CML), and approximately half of the patients with chronic phase-CML (CML-CP) with deep molecular remission (DMR) by tyrosine-kinase inhibitors (TKIs) have achieved TFR. However, the mechanism of continuous TFR is still unclear, as there are "fluctuate" patients who have BCR-ABL-positive leukemia cells but do not observe obvious relapse. We focused on the immune response and conducted an immune analysis using clinical samples from the imatinib discontinuation study, JALSG-STIM213. The results showed that, in the group that maintained TFR for 3 years, changes in regulatory T (Treg) cells were observed early after stopping imatinib treatment. The effector Treg (eTreg) cells increased transiently at 1 month after stopping imatinib and then returned to baseline at 3 months after stopping imatinib treatment. There was no difference in the Treg phenotype, and CD8+ T cells in the TFR group were relatively activated. High concentrations of imatinib before stopping were negatively correlated with eTreg cells after stopping imatinib. These data suggest immunological involvement in the maintenance of the TFR, and that Treg cells after stopping imatinib might be a biomarker for TFR. Furthermore, high imatinib exposure may have a negative immunological impact on the continuous TFR.
- Noriharu Nakagawa; Ken Ishiyama; Kensuke Usuki; Satoru Takada; Tatsuki Tomikawa; Hiroshi Handa; Yuna Katsuoka; Daiki Hirano; Nobuo Sezaki; Masahiko Sumi; Shin Fujisawa; Yasuhiro Taniguchi; Takuro Yoshimura; Eiichi Ohtsuka; Ken Takase; Youko Suehiro; Shuichi Ota; Tomohiro Kajiguchi; Tomoya Maeda; Masahide Yamamoto; Shigeki Ohtake; Akira Katsumi; Hitoshi Kiyoi; Itaru Matsumura; Yasushi MiyazakiBLOOD 138 2021年11月0
- Aya Nakaya; Hirohiko Shibayama; Eiji Nakatani; Yuji Shimura; Satoru Kosugi; Hirokazu Tanaka; Shin-Ichi Fuchida; Junya Kanda; Nobuhiko Uoshima; Hitomi Kaneko; Kazunori Imada; Kensuke Ohta; Tomoki Ito; Hideo Yagi; Satoshi Yoshihara; Masayuki Hino; Chihiro Shimazaki; Akifumi Takaori-Kondo; Junya Kuroda; Itaru Matsumura; Yuzuru Kanakura; Shosaku NomuraEJHaem 2 4 765 - 773 2021年11月A total of 129 symptomatic patients with multiple myeloma (MM) who underwent high-dose chemotherapy with autologous stem cell transplantation (HDT/ASCT) were analyzed. The 4-year overall survival (OS) of patients with maintenance (n = 82) was 80%, whereas that of patients without maintenance (n = 47) was 72% (p = 0.426). The 4-year progression-free survival (PFS) of patients with maintenance was 38%, whereas that of patients without maintenance was 27% (p = 0.088). Multivariate analysis revealed that an International Staging System score ≥2 was associated with worse PFS (hazard ratio 1.62, p = 0.043). Among the 129 patients, two were excluded owing to early relapse, 50 patients achieved complete response (CR), and 77 patients failed to achieve CR. Patients who achieved CR showed better 4-year PFS than those who failed to achieve CR (41% vs. 30%, p = 0.027); however, 4-year OS was not different (76% vs. 82%, p = 0.971). In patients who achieved CR, 4-year OS with/without maintenance was 74%/81% (p = 0.357), 4-year PFS with/without maintenance was 42%/40% (p = 0.954). In patients who failed to achieve CR, the 4-year OS with/without maintenance was 97%/91% (p = 0.107), and 4-year PFS with/without maintenance was 36%/16% (p < 0.001). In patients who failed to achieve CR, maintenance significantly improved the PFS. Maintenance after HDT/ASCT can prolong PFS in patients who fail to achieve CR in real-world settings.
- Toshihiko Shiga; Yuji Nozaki; Daisuke Tomita; Kazuya Kishimoto; Yasuaki Hirooka; Koji Kinoshita; Masanori Funauchi; Itaru MatsumuraFrontiers in Immunology 12 2021年10月
Background Interleukin (IL)-18 is markedly elevated in systemic inflammatory diseases that cause the ‘cytokine storm’ such as adult-onset Still’s disease (AOSD) and hemophagocytic lymphohistiocytosis (HLH). The differences in IL-18 between AOSD and HLH, especially in adults, is uncertain. Macrophage activation syndrome (MAS), a form of secondary HLH, is often difficult to differentiate cases of AOSD that include MAS from other secondary HLH. In this case-control study, we investigated whether serum IL-18 levels could be a useful biomarker for the differential diagnosis of AOSD with or without MAS (AOSD group) and other secondary HLH in adults (adult HLH group).Patients and Methods We enrolled 46 patients diagnosed with AOSD including 9 patients with MAS and 31 patients in the adult HLH group, which excluded AOSD-associated MAS. The clinical features and laboratory data were compared between the AOSD and adult HLH groups. In addition, we subdivided the AOSD group (with or without MAS) and the adult HLH group (whether lymphoma-associated or not) and compared the four groups. A logistic regression analysis was used to identify factors with high efficacy in differentiating the two groups, followed by a receiver operating characteristic (ROC) curve analysis to evaluate the differential diagnostic ability of IL-18. We analyzed the correlation between IL-18 and various laboratory parameters in the AOSD group.Results Serum IL-18 levels of patients in the AOSD groups were significantly higher than those of the adult HLH groups, and were closely correlated with ferritin, soluble interleukin-2 receptor (sIL-2R), and other laboratory data. Univariate and multivariate logistic regression analyses revealed that IL-18, sIL-2R, and ‘arthralgia or arthritis’ are independent factors useful in the differential diagnosis of AOSD from adult HLH. In the differential diagnosis of both groups, the area under the curve obtained from the ROC curve of IL-18 with a cutoff value of 18,550 pg/mL was 0.91 (95% confidence interval 0.83–1.00; sensitivity 90.3%, specificity 93.5%), and the differential diagnosis ability of IL-18 was superior to that of other laboratory data.Conclusions IL-18 could be a useful biomarker for the differential diagnosis of AOSD and adult HLH. - Kazuya Kishimoto; Yuji Nozaki; Toshiharu Sakurai; Koji Kinoshita; Masanori Funauchi; Itaru MatsumuraLife (Basel, Switzerland) 11 10 2021年09月We report a 14-year-old man with Crohn's disease (CD) who developed right upper arm pain while being treated with the anti-tumor necrosis factor (TNF)-alpha monoclonal antibody, infliximab. There were no symptoms suggestive of active CD, but the inflammatory response was high, and a contrast-enhanced CT showed the occlusion of the right brachial artery. We diagnosed the patient as having Takayasu's arteritis (TA) and started treatment with corticosteroids, then tapered off the steroids as the symptoms of TA resolved. Later, TA flared up, and his treatment was changed from infliximab to an anti-IL-6 receptor antibody, tocilizumab. The change to TCZ stabilized TA, but exacerbated CD. It is difficult to control both diseases at the same time, and the choice of biologics for treatment must be carefully considered.
- Yasuaki Hirooka; Yuji Nozaki; Saki Okuda; Masafumi Sugiyama; Koji Kinoshita; Masanori Funauchi; Itaru MatsumuraFrontiers in Endocrinology 12 2021年09月
Objectives In our previous 24-month study, we observed that teriparatide had some advantages over denosumab for bone mineral density (BMD) in glucocorticoid-induced osteoporosis (GIO) patients with prior bisphosphonate treatment. We conducted this extension study to investigate whether the advantage of teriparatide obtained in the first 2 years would be maintained after the switch to denosumab.Materials and Methods We switched patients who had completed 24-month daily teriparatide treatment to denosumab (switch group, n=18) and compared their BMD every 6 months up to 48 months with the group who continued to receive denosumab (denosumab group, n=16).Results At 48 months, the lumbar spine BMD was significantly increased from baseline in both groups (denosumab: 10.4 ± 8.7%, p<0.001; switch: 14.2 ± 6.8%, p<0.001). However, a significant increase in femoral neck BMD from baseline occurred only in the switch group (11.2 ± 14.6%, p<0.05); denosumab (4.1 ± 10.8%). The total hip BMD increased significantly from baseline in both groups (denosumab: 4.60 ± 7.4%, p<0.05; switch: 7.2 ± 6.9%, p<0.01). Femoral neck BMD was significantly increased in the switchversus the denosumab group (p<0.05).Conclusion In GIO patients with prior bisphosphonate treatment, the advantage of teriparatide may be maintained after the treatment period. A continuous increase in BMD can be expected with teriparatide followed by denosumab. - Saki Okuda; Yasuaki Hirooka; Tetsu Itami; Yuji Nozaki; Masafumi Sugiyama; Koji Kinoshita; Masanori Funauchi; Itaru MatsumuraLife (Basel, Switzerland) 11 9 2021年09月Relapsing polychondritis (RP) is a rare autoimmune inflammatory disease characterized by recurrent inflammation and destruction of cartilage. Although auricular chondritis is a characteristic finding in RP, it can be difficult to diagnose in the absence of auricular symptoms. A 64-year-old Japanese male was referred to our hospital with fever and respiratory distress. Contrast-enhanced computed tomography (CT) revealed bronchial wall thickening and we suspected RP; however, he had no auricular symptoms and did not meet the diagnostic McAdam criteria for RP, so we used 18F-fluorodeoxyglucose positron emission tomography/CT (FDG-PET/CT) to search for other cartilage lesions. This analysis revealed FDG accumulation not only in the bronchial walls, but also in the left auricle. Instead of a bronchial biopsy using a bronchoscope, we performed a biopsy of the left auricular cartilage, which is considered a relatively less invasive site. Even though the auricle was asymptomatic, the pathology results revealed chondritis. He was diagnosed with RP, and his symptoms rapidly improved with corticosteroid therapy. A biopsy of asymptomatic auricular cartilage may be useful in the diagnosis of RP. FDG-PET/CT is a powerful tool for the early diagnosis of RP, identifying inflammatory areas even in the absence of symptoms, and guiding the selection of appropriate biopsy sites.
- A nationwide survey on Japanese patients with essential thrombocythemia: JSH-MPN-R18 study(和訳中)橋本 由徳; 枝廣 陽子; 伊藤 量基; 後藤 明彦; 中前 美佳; 木村 文彦; 小池 道明; 桐戸 敬太; 和田 秀穂; 臼杵 憲祐; 田中 孝幸; 森 毅彦; 脇田 知志; 齋藤 俊樹; 嘉田 晃子; 齋藤 明子; 下田 和哉; 杉本 由香; 黒川 敏郎; 冨田 章裕; 赤司 浩一; 松村 到; 竹中 克斗; 小松 則夫日本血液学会学術集会 83回 OS3 - 3 2021年09月
- Efficacy of elotuzumab plus lenalidomide and dexamethasone for MM: A retrospective analysis from KMF(和訳中)淵田 真一; 伊藤 量基; 小杉 智; 太田 健介; 内山 人二; 島津 裕; 恩田 佳幸; 金子 仁臣; 足立 陽子; 高桑 輝人; 諫田 淳也; 魚嶋 伸彦; 柴山 浩彦; 福島 健太郎; 田中 宏和; 志村 勇司; 今田 和典; 八木 秀男; 吉原 哲; 日野 雅之; 保仙 直毅; 高折 晃史; 松村 到; 野村 昌作; 島崎 千尋; 黒田 純也日本血液学会学術集会 83回 OS1 - 4 2021年09月
- 前向き観察研究に登録された骨髄異形成症候群における同種移植までの橋渡し治療と移植成績の検討(Outcomes of SCT for MDS pts registered in a prospective observational study; JALSG-CS-11-MDS-SCT)中川 紀温; 石山 謙; 臼杵 憲祐; 高田 覚; 富川 武樹; 半田 寛; 勝岡 優奈; 平野 大希; 瀬崎 伸夫; 住 昌彦; 藤澤 信; 谷口 康博; 市原 弘善; 吉村 卓朗; 大塚 英一; 高瀬 謙; 末廣 陽子; 太田 秀一; 梶口 智弘; 前田 智也; 山本 正英; 大竹 茂樹; 勝見 章; 清井 仁; 松村 到; 宮崎 泰司日本血液学会学術集会 83回 OS1 - 2 2021年09月
- Very elderly patients with myeloma: a multicenter retrospective analysis from Kansai Myeloma Forum(和訳中)岡山 裕介; 高桑 輝人; 志村 勇司; 金子 仁臣; 今田 和典; 小杉 智; 伊藤 量基; 淵田 真一; 田中 宏和; 魚嶋 伸彦; 吉原 哲; 諫田 淳也; 柴山 浩彦; 福島 健太郎; 太田 健介; 八木 秀男; 野村 昌作; 島崎 千尋; 松村 到; 高折 晃史; 保仙 直毅; 日野 雅之; 黒田 純也日本血液学会学術集会 83回 OS1 - 1 2021年09月
- Secondary malignancies in Japanese patients with myeloproliferative neoplasms: JSH-MPN-R18 study(和訳中)落合 友則; 橋本 由徳; 枝廣 陽子; 伊藤 量基; 後藤 明彦; 中前 美佳; 木村 文彦; 小池 道明; 桐戸 敬太; 和田 秀穂; 臼杵 憲祐; 田中 孝幸; 森 毅彦; 脇田 知志; 齋藤 俊樹; 嘉田 晃子; 齋藤 明子; 下田 和哉; 杉本 由香; 黒川 敏郎; 冨田 章裕; 赤司 浩一; 松村 到; 竹中 克斗; 小松 則夫日本血液学会学術集会 83回 OS3 - 4 2021年09月
- AYA世代のがん研究における最新の知見 Pre-B細胞性急性リンパ球性白血病における転写制御ネットワーク都築 忍; 安田 貴彦; 河津 正人; 上野 敏秀; カルナン・シバスンダラン; 太田 明伸; 真田 昌; 永井 宏和; 冨田 章裕; 高橋 義行; 宮崎 泰司; 松村 到; 清井 仁; 細川 好孝; 間野 博行; 早川 文彦日本癌学会総会記事 80回 [SST5 - 2] 2021年09月
- Novel web application predicting patient-specific prognosis in MM from KMF using machine learning(和訳中)高桑 輝人; 岡村 浩史; 島津 裕; 金子 仁臣; 今田 和典; 伊藤 量基; 山村 亮介; 太田 健介; 小杉 智; 田中 宏和; 淵田 真一; 志村 勇司; 諫田 淳也; 魚嶋 伸彦; 柴山 浩彦; 吉原 哲; 八木 秀男; 日野 雅之; 金倉 譲; 黒田 純也; 高折 晃史; 島崎 千尋; 松村 到; 野村 昌作日本血液学会学術集会 83回 OS1 - 2 2021年09月
- Shinya Rai; Hiroaki Inoue; Hitoshi Hanamoto; Mitsuhiro Matsuda; Yasuhiro Maeda; Yusuke Wada; Takahiro Haeno; Yosaku Watatani; Takahiro Kumode; Chikara Hirase; J Luis Espinoza; Yasuyoshi Morita; Hirokazu Tanaka; Yoichi Tatsumi; Itaru MatsumuraInternational journal of hematology 114 2 205 - 216 2021年08月The aim of this trial is to evaluate the utility of rituximab-bendamustine (R-B) for untreated advanced follicular lymphoma (FL) showing non-optimal response (nOR) to R-CHOP, and to identify clinical prognostic factors for FL patients receiving R-B. Patients who failed to achieve complete response/complete response unconfirmed (CR/CRu) [nOR-group] after 2 cycles of R-CHOP subsequently received 6 cycles of R-B. The primary endpoint was the 3-year progression-free survival (PFS) rate. Secondary endpoints included determination of prognostic factors. Fifty-six patients initially received R-CHOP, 43/56 patients (76.8%) were judged as nOR, and 33/43 patients (76.7%) completed 6 cycles of R-B. At a median follow-up of 50.6 months in the nOR-group, the 3-year PFS rate was 69.0%, and the 3-year overall survival (OS) rate was 92.7%. The most common toxicities associated with R-B were grade 3-4 lymphopenia (93.0%) and neutropenia (74.4%), both of which were manageable. A multivariate analysis including dose intensity, serum soluble interleukin-2 receptor, and FL international prognostic index-2 revealed low absolute lymphocyte count (< 869/μL) at diagnosis was an independent poor prognostic factor for both PFS and OS in the R-B-treated nOR-group. This result was further confirmed in validation cohorts including R-B-treated de novo (n = 40) and relapsed (n = 49) FL patients.
- Shinichi Kako; Fumihiko Hayakawa; Kiyotoshi Imai; Junji Tanaka; Shuichi Mizuta; Satoshi Nishiwaki; Heiwa Kanamori; Junichi Mukae; Yukiyasu Ozawa; Tadakazu Kondo; Takahiro Fukuda; Tatsuo Ichinohe; Shuichi Ota; Yoshinori Tanaka; Tohru Murayama; Shingo Kurahashi; Toru Sakura; Noriko Usui; Shigeki Ohtake; Hitoshi Kiyoi; Itaru Matsumura; Yasushi Miyazaki; Yoshiko AtsutaInternational journal of hematology 114 5 608 - 619 2021年07月The optimal treatment for Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL) in first complete remission (CR1) has not been established in the high-intensity chemotherapy era. The outcomes of patients with Ph-negative ALL who underwent allogeneic hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen-matched related or unrelated donor in CR1 (HSCT-MRD group and HSCT-MUD group) were obtained from a Japanese registry database. Patients aged 16-24 years and 25-65 years were analyzed separately, and their outcomes were compared to those of patients who continued high-intensity chemotherapy in CR1 in studies (202U group and 202O group) by the Japan Adult Leukemia Study Group (JALSG). In the HSCT-MRD group, patients younger than 25 years had lower overall survival (OS) than the 202U group, presumably due to the higher non-relapse mortality (NRM) in the HSCT-MRD group. Patients 25 years and older had similar OS to the 202O group. The lower relapse rate was counterbalanced by higher NRM in the HSCT-MRD group. In the HSCT-MUD group, patients in both age groups had similar OS to their corresponding groups in the JALSG studies. In conclusion, high-intensity chemotherapy may change the role of HSCT for Ph-negative ALL.
- Takahiro Yamauchi; Chikashi Yoshida; Kensuke Usuki; Satoru Takada; Itaru Matsumura; Nobuaki Dobashi; Yasushi Miyazaki; Toshihiro Miyamoto; Hiroatsu Iida; Norio Asou; Junya Kuroda; Satoshi Ichikawa; Norio Komatsu; Wellington Mendes; Hideyuki Honda; Sumiko Okubo; Misaki Kurokawa; Qi Jiang; Andrew Wei; Kenichi IshizawaJapanese journal of clinical oncology 51 9 1372 - 1382 2021年07月BACKGROUND: In a multinational phase 3 trial (VIALE-C), venetoclax plus low-dose cytarabine prolonged overall survival vs placebo plus low-dose cytarabine in patients with newly diagnosed acute myeloid leukaemia ineligible for intensive chemotherapy, although it was not statistically significant. Herein, we assess the benefit of venetoclax plus low-dose cytarabine in the Japanese subgroup of VIALE-C patients (n = 27). METHODS: VIALE-C, a randomized (2:1), double-blind study (NCT03069352), enrolled untreated patients (≥18 years) with acute myeloid leukaemia. Patients received venetoclax (600 mg days 1-28, 4-day ramp-up in cycle 1) or placebo in 28-day cycles with low-dose cytarabine (20 mg/m2 days 1-10). The primary endpoint was median overall survival. RESULTS: In the Japanese subgroup, at a 6-month follow-up from the primary analysis, median overall survival for venetoclax (n = 18) and placebo (n = 9), plus low-dose cytarabine, was 4.7 and 8.1 months, respectively (hazard ratio, 0.928, 95% confidence intervals : 0.399, 2.156). The rate of complete remission plus complete remission with incomplete blood count recovery was higher with venetoclax plus low-dose cytarabine (44.4%) vs placebo plus low-dose cytarabine (11.1%). All patients experienced at least 1 adverse event. The most common grade ≥3 adverse events with venetoclax or placebo, plus low-dose cytarabine, were febrile neutropenia (50.0% vs 44.4%, respectively) and thrombocytopenia (27.8% vs 44.4%, respectively). Serious adverse events were reported in 50.0 and 33.3% of patients in the venetoclax and placebo, plus low-dose cytarabine arms, respectively; pneumonia was the most common (22.2% each). CONCLUSIONS: Limited survival benefit in the Japanese subgroup can be attributed to small patient numbers and to baseline imbalances observed between treatment arms, with more patients in the venetoclax plus low-dose cytarabine arm presenting poor prognostic factors. Venetoclax plus low-dose cytarabine was well tolerated in Japanese patients with acute myeloid leukaemia ineligible for intensive chemotherapy.
- COVID-19パンデミック下における学生相談形態の変化池田 行宏; 藤田 貢; 三井 良之; 梶 博史; 磯貝 典孝; 赤木 將男; 松村 到医学教育 52 Suppl. 141 - 141 (一社)日本医学教育学会 2021年07月
- Akinori Okada; Yuji Nozaki; Shinya Rai; Koji Kinoshita; Masanori Funauchi; Itaru MatsumuraLife (Basel, Switzerland) 11 6 2021年05月A 35-year-old male was referred to our hospital with dysesthesia of the lower extremities that had begun six months earlier. A blood test revealed the presence of various antibodies, suggesting a collagen-related peripheral neuropathy. However, a history of repeated shingles and sex with males was noted, and the patient was tested for and diagnosed with human immunodeficiency virus (HIV) infection. Based on the manifestations and laboratory data, including the results of immunological and urinary tests, he was further diagnosed with concomitant systemic lupus erythematosus (SLE). The activity of SLE improved with antiretroviral therapy. There is currently no established treatment for AIDS complicated with SLE. Indeed, because HIV treatment involves the activation of immune function and SLE treatment involves immunosuppression, any treatments for the two conditions would be in conflict. It is thus necessary to select a treatment strategy based on the condition of the individual patient. In addition, because HIV infection is relatively rare in Japan compared to other countries, rheumatologists in Japan must keep HIV infection in mind as a differential diagnosis for autoimmune diseases.
- Kotaro Miyao; Seitaro Terakura; Yukiyasu Ozawa; Masashi Sawa; Akio Kohno; Senji Kasahara; Hiroatsu Iida; Kazuko Ino; Shigeru Kusumoto; Masanobu Kasai; Akiyoshi Takami; Shingo Kurahashi; Tomohiro Kajiguchi; Takanobu Morishita; Tetsuya Nishida; Makoto MurataTransplantation and cellular therapy 27 4 342.e1-342.e10 2021年04月 [査読有り]
Ganciclovir (GCV) and foscarnet (FCN) are effective anti-cytomegalovirus (CMV) preemptive therapies; however, the impact of the 2 agents on various clinical outcomes of allogeneic hematopoietic stem cell transplantation (HSCT) remains unclear. We retrospectively analyzed data on 532 patients undergoing allogeneic HSCT from unrelated donors and administered FCN (n = 86) or GCV (n = 446) as first-line anti-CMV preemptive therapy. Overall survival, relapse, and nonrelapse mortality (NRM) did not differ between the FCN and GCV groups, whereas the GCV group had a higher risk of chronic graft-versus-host disease (cGVHD) (hazard ratio [HR], 2.38; 95% confidence interval [CI], 1.28 to 4.39; P = .006) and extensive cGVHD (HR, 3.94; 95% CI, 1.43 to 10.9; P = .008). All 13 patients with cGVHD in the FCN group survived. Switching to the other agent was done mainly due to hematologic adverse events in the GCV group and mainly due to insufficient efficacy in the FCN group. The incidence of end-organ CMV disease was similar in the 2 groups. Selection of FCN or GCV as first-line preemptive anti-CMV therapy did not affect survival, relapse, or NRM. Physicians can select either of the agents, depending on the clinical situation; however, the selection may influence the cGVHD-related clinical course in HSCT recipients. - Teruhito Takakuwa; Ryosuke Yamamura; Kensuke Ohta; Hitomi Kaneko; Kazunori Imada; Aya Nakaya; Shin-Ichi Fuchida; Hirohiko Shibayama; Mitsuhiro Matsuda; Yutaka Shimazu; Yoko Adachi; Satoru Kosugi; Hitoji Uchiyama; Hirokazu Tanaka; Hitoshi Hanamoto; Yuji Shimura; Junya Kanda; Yoshiyuki Onda; Nobuhiko Uoshima; Hideo Yagi; Satoshi Yoshihara; Masayuki Hino; Chihiro Shimazaki; Akifumi Takaori-Kondo; Junya Kuroda; Itaru Matsumura; Yuzuru Kanakura; Shosaku NomuraEuropean journal of haematology 106 4 555 - 562 2021年04月OBJECTIVES: This study aimed to investigate real-world data of ixazomib plus lenalidomide and dexamethasone (IRd) therapy for patients with relapsed and refractory multiple myeloma (RRMM). METHODS: We retrospectively analyzed 122 patients treated with IRd at 16 centers from May 2017 to January 2019 by using the Kansai Myeloma Forum database. RESULT: At the start of IRd, the median age was 72 years, 66.7% of patients had IgG type, and the median number of prior therapies was 4, comprising bortezomib (85.4%) and lenalidomide (89.3%)-based regimens. Disease progression and adverse events accounted for treatment discontinuation in 46 and 32 patients, respectively. The median overall survival (OS) was not reached, and the median progression-free survival (PFS) was 11.9 months. Sensitivity to bortezomib did not affect the PFS, whereas lenalidomide-refractory patients had significantly lower PFS than lenalidomide-sensitive patients, who were comparable to TOURMALINE-MM1 study. The patients with IgG type had significantly better PFS and OS than those with non-IgG type. CONCLUSION: This study presents the largest real-world data of patients treated with IRd in Asia. However, in real clinical practice, the patient background is different from the TOURMALINE-MM1 study, and IRd showed poor efficacy, especially in the non-IgG type and lenalidomide-refractory patients with RRMM.
- Teruhito Takakuwa; Kensuke Ohta; Eiji Nakatani; Tomoki Ito; Hitomi Kaneko; Shin-Ichi Fuchida; Yuji Shimura; Hideo Yagi; Hirohiko Shibayama; Junya Kanda; Hitoji Uchiyama; Satoru Kosugi; Hirokazu Tanaka; Eri Kawata; Nobuhiko Uoshima; Jun Ishikawa; Masaru Shibano; Takahiro Karasuno; Maki Shindo; Yoshifumi Shimizu; Kazunori Imada; Yuzuru Kanakura; Junya Kuroda; Masayuki Hino; Shosaku Nomura; Akifumi Takaori-Kondo; Chihiro Shimazaki; Itaru MatsumuraHematological oncology 39 3 349 - 357 2021年03月The plateau phase emerging during the treatment of multiple myeloma (MM) is known to last steadily for a certain period, even without treatment. Therefore, the treatment started at plateau phase is expected to be associated with a better outcome. In this study, this hypothesis was evaluated retrospectively for previously treated MM patients in Kansai Myeloma Forum database who received lenalidomide (LEN) with or without dexamethasone for the first time. Disease stability index (DSI) was defined as (maximum - minimum values of M protein during the 90 days before the start of LEN) divided by M-protein values at the start of LEN. The patients were classified into three groups: stable (S), DSI ≤ 0.25; increasing (I), DSI > 0.25 with increasing M protein; decreasing (D), DSI > 0.25 with decreasing M protein. In univariate analysis of 352 patients, DSI group "I", non-IgG type, serum albumin<3.5 g/dL, and age≥70 were statistically significant prognostic factors for both progression-free survival and overall survival. In multivariate analysis, the former 3 risk factors were statistically significant for poor overall survival. Thus, DSI is an independent prognostic factor for the treatment with LEN for previously treated MM.
- 関節リウマチ患者におけるJAK Failure症例の考察伊丹 哲; 志賀 俊彦; 岸本 和也; 野崎 祐史; 木下 浩二; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 65回 597 - 597 (一社)日本リウマチ学会 2021年03月
- SLE・抗リン脂質抗体症候群(臨床):ステロイド 全身性エリテマトーデスに対する当科におけるベリムマブの治療やステロイド減量効果についての検討冨田 大介; 野崎 祐史; 石村 香織; 芦田 千聖; 山本 敦弘; 岡田 晃典; 伊丹 哲; 酒井 健史; 李 進海; 志賀 俊彦; 岸本 和也; 木下 浩二; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 65回 373 - 373 (一社)日本リウマチ学会 2021年03月
- Takeshi Saito; Yoshihiro Hatta; Fumihiko Hayakawa; Tsutomu Takahashi; Maki Hagihara; Hiroatsu Iida; Koichiro Minauchi; Etsuko Yamazaki; Isamu Sugiura; Tohru Murayama; Toru Sakura; Naoki Mori; Kiyotoshi Imai; Yuichi Yahagi; Yoshiko Atsuta; Akiko Moriya Saito; Akihiro Hirakawa; Hitoshi Kiyoi; Itaru Matsumura; Yasushi MiyazakiInternational journal of hematology 113 3 395 - 403 2021年03月This phase 1/2 study aimed to identify the maximum tolerated dose, the recommended phase 2 dose (RP2D), and efficacy of the clofarabine, etoposide, and cyclophosphamide combination regimen in adult patients with relapsed/refractory acute lymphoblastic leukemia (ALL). Patients aged ≥ 15 years with relapsed/refractory ALL were enrolled. Escalating doses of clofarabine (20-30 mg/m2/day × 5 days), etoposide (50-100 mg/m2/day × 5 days), and cyclophosphamide (200-440 mg/m2/day × 5 days) were administered. Dose-limiting toxicity was defined as Grade 3 or more non-hematological toxicities and others. A total of 18 patients (B-ALL; n = 13, T-ALL; n = 5) were recruited in phase 1; however, the protocol was amended to close study without proceeding to phase 2. Three patients were enrolled in cohort 1, three in cohort 2, six in cohort 3, and six in cohort 4. The RP2D of clofarabine, etoposide, and cyclophosphamide was 30, 100, and 440 mg/m2 daily, respectively. Complete remission (CR) was achieved in four patients (22%) and CR without platelet recovery in four patients (22%), with an overall response rate of 44%. The RP2D of the combination therapy was successfully determined in this study.
- Yoichi Naito; Hiroyuki Aburatani; Toraji Amano; Eishi Baba; Toru Furukawa; Tetsu Hayashida; Eiso Hiyama; Sadakatsu Ikeda; Masashi Kanai; Motohiro Kato; Ichiro Kinoshita; Naomi Kiyota; Takashi Kohno; Shinji Kohsaka; Keigo Komine; Itaru Matsumura; Yuji Miura; Yoshiaki Nakamura; Atsushi Natsume; Kazuto Nishio; Katsutoshi Oda; Naoyuki Oda; Natsuko Okita; Kumiko Oseto; Kuniko Sunami; Hideaki Takahashi; Masayuki Takeda; Shimon Tashiro; Shinichi Toyooka; Hideki Ueno; Shinichi Yachida; Takayuki Yoshino; Katsuya TsuchiharaInternational journal of clinical oncology 26 2 233 - 283 2021年02月BACKGROUND: To promote precision oncology in clinical practice, the Japanese Society of Medical Oncology, the Japanese Society of Clinical Oncology, and the Japanese Cancer Association, jointly published "Clinical practice guidance for next-generation sequencing in cancer diagnosis and treatment" in 2017. Since new information on cancer genomic medicine has emerged since the 1st edition of the guidance was released, including reimbursement for NGS-based multiplex gene panel tests in 2019, the guidance revision was made. METHODS: A working group was organized with 33 researchers from cancer genomic medicine designated core hospitals and other academic institutions. For an impartial evaluation of the draft version, eight committee members from each society conducted an external evaluation. Public comments were also made on the draft. The finalized Japanese version was published on the websites of the three societies in March 2020. RESULTS: The revised edition consists of two parts: an explanation of the cancer genomic profiling test (General Discussion) and clinical questions (CQs) that are of concern in clinical practice. Particularly, patient selection should be based on the expectation that the patient's post-test general condition and organ function will be able to tolerate drug therapy, and the optimal timing of test should be considered in consideration of subsequent treatment plans, not limited to treatment lines. CONCLUSION: We expect that the revised version will be used by healthcare professionals and will also need to be continually reviewed in line with future developments in cancer genome medicine.
- Hirohisa Nakamae; Masahide Yamamoto; Emiko Sakaida; Yoshinobu Kanda; Ken Ohmine; Takaaki Ono; Itaru Matsumura; Maho Ishikawa; Makoto Aoki; Akio Maki; Hirohiko ShibayamaInternational Journal of Hematology 2021年In the 10-year analysis of Japanese patients with newly diagnosed CML-CP in the ENESTnd trial, nilotinib yielded higher cumulative response rates. There were no new occurrences of disease progression or deaths since the 5-year analysis. Cumulative 10-year rates of MMR and MR4.5 were higher in the nilotinib arms [300 mg twice daily (BID), 86.2% and 69.0%, respectively 400 mg BID, 78.3% and 69.6%, respectively] than the imatinib arm (400 mg once daily, 60.0% and 48.0%, respectively). Nasopharyngitis (85.7%, 77.3%, 79.2%), rash (50.0%, 68.2%, 37.5%), headache (39.3%, 45.5%, 25.0%), and back pain (39.3%, 50.0%, 29.2%) were the most frequently reported all-grade adverse events (AEs) for nilotinib 300 and 400 mg BID and imatinib, respectively. Cardiovascular AEs were more common with nilotinib than with imatinib. More patients on nilotinib had pre-diabetic and diabetic levels of HbA1c (300 mg BID, 17.9% and 10.7%, respectively 400 mg BID, 22.7% and 18.2%, respectively) compared with imatinib (4.2% each). Overall, 10-year results from the Japanese cohort are consistent with prior results from the full ENESTnd cohort and the Japanese subgroup, and continue to support the long-term use of nilotinib in Japanese patients with newly diagnosed CML-CP, but with proper monitoring and management of comorbidities.
- 山本敦弘; 石村香織; 赤澤宗輝; 芦田千聖; 岡田晃典; 冨田大介; 伊丹哲; 酒井健史; 李進海; 志賀俊彦; 岸本和也; 野崎祐史; 木下浩二; 船内正憲; 松村到日本リウマチ学会総会・学術集会プログラム・抄録集 65th 2021年
- 赤澤宗輝; 山澤広嵩; 石村香織; 芦田千聖; 池田房代; 山本敦弘; 岡田晃典; 冨田大介; 伊丹哲; 酒井健史; 李進海; 志賀俊彦; 岸本和也; 野崎祐史; 木下浩二; 船内正憲; 松村到日本リウマチ学会総会・学術集会プログラム・抄録集 65th 2021年
- 石村香織; 酒井健史; 赤澤宗輝; 芦田千聖; 山本敦弘; 岡田晃典; 冨田大介; 伊丹哲; 李進海; 志賀俊彦; 岸本和也; 野崎祐史; 木下浩二; 船内正憲; 松村到日本リウマチ学会総会・学術集会プログラム・抄録集 65th 2021年
- 奥田早紀; 伊丹哲; 白井里香; 森本祐美; 石村香織; 赤澤宗輝; 芦田千聖; 山本敦弘; 岡田晃典; 冨田大介; 酒井健史; 李進海; 志賀俊彦; 岸本和也; 野崎祐史; 木下浩二; 船内正憲; 松村到日本リウマチ学会総会・学術集会プログラム・抄録集 65th 2021年
- 岸本和也; 野崎祐史; 石村香織; 赤澤宗輝; 芦田千聖; 岡田晃典; 伊丹哲; 酒井健史; 李進海; 志賀俊彦; 樋野尚一; 廣岡靖章; 杉山昌史; 木下浩二; 船内正憲; 松村到日本リウマチ学会総会・学術集会プログラム・抄録集 65th 2021年
- 李進海; 野崎祐史; 石村香織; 赤澤宗輝; 芦田千聖; 山本敦弘; 岡田晃典; 冨田大介; 伊丹哲; 酒井健史; 志賀俊彦; 岸本和也; 木下浩二; 舟橋惠子; 松原司; 船内正憲; 松村到日本リウマチ学会総会・学術集会プログラム・抄録集 65th 2021年
- 白井里香; 森本祐美; 奥田早紀; 石村香織; 山本敦弘; 芦田千聖; 赤澤宗輝; 冨田大介; 岡田晃典; 伊丹哲; 酒井健史; 李進海; 志賀俊彦; 岸本和也; 野崎祐史; 木下浩二; 船内正憲; 松村到日本リウマチ学会総会・学術集会プログラム・抄録集 65th 2021年
- 森本祐美; 酒井健史; 奥田早紀; 白井里香; 石村香織; 山本敦弘; 芦田千聖; 赤澤宗輝; 冨田大介; 岡田晃典; 伊丹哲; 李進海; 志賀俊彦; 岸本和也; 野崎祐史; 木下浩二; 船内正憲; 松村到日本リウマチ学会総会・学術集会プログラム・抄録集 65th 2021年
- Yasuaki Hirooka; Yuji Nozaki; Saki Okuda; Masafumi Sugiyama; Koji Kinoshita; Masanori Funauchi; Itaru MatsumuraFrontiers in endocrinology 12 753185 - 753185 2021年Objectives: In our previous 24-month study, we observed that teriparatide had some advantages over denosumab for bone mineral density (BMD) in glucocorticoid-induced osteoporosis (GIO) patients with prior bisphosphonate treatment. We conducted this extension study to investigate whether the advantage of teriparatide obtained in the first 2 years would be maintained after the switch to denosumab. Materials and Methods: We switched patients who had completed 24-month daily teriparatide treatment to denosumab (switch group, n=18) and compared their BMD every 6 months up to 48 months with the group who continued to receive denosumab (denosumab group, n=16). Results: At 48 months, the lumbar spine BMD was significantly increased from baseline in both groups (denosumab: 10.4 ± 8.7%, p<0.001; switch: 14.2 ± 6.8%, p<0.001). However, a significant increase in femoral neck BMD from baseline occurred only in the switch group (11.2 ± 14.6%, p<0.05); denosumab (4.1 ± 10.8%). The total hip BMD increased significantly from baseline in both groups (denosumab: 4.60 ± 7.4%, p<0.05; switch: 7.2 ± 6.9%, p<0.01). Femoral neck BMD was significantly increased in the switch versus the denosumab group (p<0.05). Conclusion: In GIO patients with prior bisphosphonate treatment, the advantage of teriparatide may be maintained after the treatment period. A continuous increase in BMD can be expected with teriparatide followed by denosumab.
- Toshihiko Shiga; Yuji Nozaki; Daisuke Tomita; Kazuya Kishimoto; Yasuaki Hirooka; Koji Kinoshita; Masanori Funauchi; Itaru MatsumuraFrontiers in immunology 12 750114 - 750114 2021年Background: Interleukin (IL)-18 is markedly elevated in systemic inflammatory diseases that cause the 'cytokine storm' such as adult-onset Still's disease (AOSD) and hemophagocytic lymphohistiocytosis (HLH). The differences in IL-18 between AOSD and HLH, especially in adults, is uncertain. Macrophage activation syndrome (MAS), a form of secondary HLH, is often difficult to differentiate cases of AOSD that include MAS from other secondary HLH. In this case-control study, we investigated whether serum IL-18 levels could be a useful biomarker for the differential diagnosis of AOSD with or without MAS (AOSD group) and other secondary HLH in adults (adult HLH group). Patients and Methods: We enrolled 46 patients diagnosed with AOSD including 9 patients with MAS and 31 patients in the adult HLH group, which excluded AOSD-associated MAS. The clinical features and laboratory data were compared between the AOSD and adult HLH groups. In addition, we subdivided the AOSD group (with or without MAS) and the adult HLH group (whether lymphoma-associated or not) and compared the four groups. A logistic regression analysis was used to identify factors with high efficacy in differentiating the two groups, followed by a receiver operating characteristic (ROC) curve analysis to evaluate the differential diagnostic ability of IL-18. We analyzed the correlation between IL-18 and various laboratory parameters in the AOSD group. Results: Serum IL-18 levels of patients in the AOSD groups were significantly higher than those of the adult HLH groups, and were closely correlated with ferritin, soluble interleukin-2 receptor (sIL-2R), and other laboratory data. Univariate and multivariate logistic regression analyses revealed that IL-18, sIL-2R, and 'arthralgia or arthritis' are independent factors useful in the differential diagnosis of AOSD from adult HLH. In the differential diagnosis of both groups, the area under the curve obtained from the ROC curve of IL-18 with a cutoff value of 18,550 pg/mL was 0.91 (95% confidence interval 0.83-1.00; sensitivity 90.3%, specificity 93.5%), and the differential diagnosis ability of IL-18 was superior to that of other laboratory data. Conclusions: IL-18 could be a useful biomarker for the differential diagnosis of AOSD and adult HLH.
- 松村到週刊日本医事新報 5049 2021年
- Jun Ho Jang; Yoshiaki Tomiyama; Koji Miyazaki; Koji Nagafuji; Kensuke Usuki; Nobuhiko Uoshima; Tomoaki Fujisaki; Hiroshi Kosugi; Itaru Matsumura; Ko Sasaki; Masahiro Kizaki; Masashi Sawa; Michihiro Hidaka; Naoki Kobayashi; Satoshi Ichikawa; Yuji Yonemura; Kouki Enokitani; Akira Matsuda; Keiya Ozawa; Kinuko Mitani; Jong Wook Lee; Shinji NakaoBritish journal of haematology 192 1 190 - 199 2021年01月A previous dose-finding study has suggested that romiplostim is effective in patients with refractory aplastic anaemia (AA) and 10 µg/kg once weekly was recommended as a starting dose. In this Phase II/III, multicentre, open-label study, romiplostim was administered subcutaneously at a fixed dose of 10 µg/kg once weekly for 4 weeks (weeks 1-4) followed by weekly doses (5, 10, 15 and 20 µg/kg) titrated by platelet response for up to 52 weeks (weeks 5-52). A total of 31 patients with AA who were refractory to immunosuppressive therapy (IST) and thrombocytopenia (platelet count of ≤30 × 109 /l) were enrolled. The primary efficacy endpoint of the proportion of patients achieving any haematological (platelet, neutrophil and erythrocyte) response at week 27 was 84% [95% confidence interval (CI) 66-95%]. Trilineage response was 39% (95% CI 22-58%) at week 53. The most common treatment-related adverse events (AEs) were headache and muscle spasms (each 13%). All AEs were mild or moderate except for three patients with Grade 3 hepatic AEs; no AEs necessitated romiplostim discontinuation. Two patients developed cytogenetic abnormalities, of whom one returned to normal karyotype at last follow-up. High-dose romiplostim is effective and well tolerated in the treatment of patients with AA refractory to IST.
- Yuji Nozaki; Toshihiko Hidaka; Jinhai Ri; Tetsu Itami; Daisuke Tomita; Akinori Okada; Chisato Ashida; Fusayo Ikeda; Atsuhiro Yamamoto; Keiko Funahashi; Koji Kinoshita; Tsukasa Matsubara; Masanori Funauchi; Itaru MatsumuraFrontiers in medicine 8 643459 - 643459 2021年Objective: Rheumatoid arthritis (RA) treatments have markedly advanced with the introduction of biological agents, e. g., tumor necrosis factor (TNF) inhibitors. TNF inhibitors are demonstrated to be quite effective in combination with methotrexate (MTX), and sufficient doses of both agents are important to control RA's disease activity. However, not all RA patients can be treated with high-dose MTX due to contraindications related to the antimetabolite action of MTX or to tolerability concerns. In daily practice, this has resulted in reduced effectiveness of TNF inhibitors. We sought to determine whether the concomitant use of dose of MTX affected the clinical effectiveness, retention rate, and side effects of certolizumab pegol (CZP) for treating RA in a real-world setting. CZP is a pegylated-conjugated Fab' fragment of a humanized anti-TNF antibody that has high affinity to TNF. Patients and Methods: We divided Japanese RA patients treated with CZP (n = 95, 25-83 years old) into groups based on those with (n = 65) and without (n = 30) concomitant MTX and those treated with a high dose (≥8 mg, n = 41) or low dose (1- <8 mg, n = 24) of MTX. We retrospectively analyzed the concomitant MTX doses' effects and side effects and the patient retention rate. Results: There were no significant differences among the CZP groups with and without MTX or the groups receiving the high vs. low MTX doses in the retention rate, the low disease activity rate, or the inhibitory effect in radiographic joint damage. Conclusion: CZP has the potential to be a useful biological agent to control RA's disease activity and the bone destruction in patients who cannot tolerate a sufficient MTX dose.
- Shinya Rai; Hirokazu Tanaka; J Luis Espinoza; Takahiro Kumode; Itaru MatsumuraLeukemia research reports 15 100256 - 100256 2021年Acute myeloid leukemia (AML) is a heterogeneous disease often associated with poor prognosis. We previously showed that the localization of KIT-D816V at endolysosomes is critical to activate aberrant Akt signaling and Chlorpromazine (CPZ) perturbs the intracellular localization, leading to cell death in AML cells with KIT-D816V. We report that daily administration of CPZ, prescribed for controlling anxiety disorder in patient with AML harboring KIT-D816V, led to a dramatic reduction in AML cells. In vitro and in vivo experiments showed that CPZ inhibited the growth and survival of the patient-derived AML cells, implying potent efficacy of CPZ in AML with KIT-D816V.
- Yoriaki Komeda; Toshiharu Sakurai; Kazuko Sakai; Yasuyoshi Morita; Arito Hashimoto; Tomoyuki Nagai; Satoru Hagiwara; Itaru Matsumura; Kazuto Nishio; Masatoshi KudoWorld journal of clinical cases 8 24 6389 - 6395 2020年12月BACKGROUND: Concomitant ulcerative colitis (UC) and idiopathic thrombocytopenic purpura (ITP) is a rare phenomenon. The management of UC with ITP can be challenging, since a decreased platelet count augments UC. CASE SUMMARY: A 24-year-old man with UC and steroid-resistant ITP experienced UC flare. Although continuous infusion of cyclosporine was initiated, UC did not improve. The administration of tofacitinib subsequently led to the induction of remission. The patient has maintained remission of UC and ITP for over one year on tofacitinib treatment. Whole transcriptomic sequencing was performed for inflamed rectal mucosae obtained before and after the initiation of Janus kinase (JAK) inhibitor, suggesting that distinct molecular signatures seemed to be regulated by JAK inhibitors and other conventional therapies including tumor necrosis factor lockers. CONCLUSION: Tofacitinib should be considered in refractory cases of UC with ITP.
- Yasuaki Hirooka; Yuji Nozaki; Asuka Inoue; Jinhai Li; Toshihiko Shiga; Kazuya Kishimoto; Masafumi Sugiyama; Koji Kinoshita; Masanori Funauchi; Itaru MatsumuraBone reports 13 100293 - 100293 2020年12月 [査読有り]
Introduction: Osteoporosis is one of the serious adverse effects associated with glucocorticoid therapy. Although bisphosphonates have been used for glucocorticoid-induced osteoporosis (GIO), some patients have shown an inadequate response. In such cases, denosumab or teriparatide are used. However, there is no consensus on which of these two drugs is superior. We prospectively compared denosumab's and teriparatide's effects on the bone mineral density (BMD) in GIO patients with prior bisphosphonate treatment. Materials and methods: After receiving oral bisphosphonates for ≥2 years, GIO patients with low T-score BMD (<-2.5) were switched from bisphosphonates to denosumab (n = 20) or daily teriparatide (n = 21). We measured the BMD (lumbar spine, femoral neck, and total hip) in both groups every 6 months for 24 months. Results: At 24 months of treatment, the lumbar spine BMD increased significantly from baseline in both the denosumab and teriparatide groups (baseline vs. denosumab and teriparatide; 5.9 ± 5.6%, P < 0.001 and 7.9 ± 5.4%, P < 0.001). A significant increase in femoral neck BMD from baseline occurred only in the teriparatide group (6.6 ± 10.8%, P < 0.05); denosumab (1.5 ± 5.0%). No significant changes occurred in the total hip BMD from baseline in either group (-0.1 ± 5.6% and 3.3 ± 7.5%, respectively). There was no significant difference between the denosumab and teriparatide groups at 24 months in lumbar spine and femoral neck BMD, but was significantly higher in the teriparatide group at 12 months (P < 0.01 and P < 0.05 in the lumbar spine and femoral neck, respectively). Conclusion: Teriparatide might have some advantages over denosumab and be a good alternative for treating GIO patients with prior bisphosphonate treatment. - Hitoshi Minamiguchi; Hiroyuki Fujita; Yoshiko Atsuta; Norio Asou; Toru Sakura; Yasunori Ueda; Masashi Sawa; Nobuaki Dobashi; Yasuhiro Taniguchi; Rikio Suzuki; Yoshihito Uchino; Akihiro Tomita; Shigehisa Tamaki; Maki Hagihara; Katsumichi Fujimaki; Masamitsu Yanada; Yoshinobu Maeda; Masako Iwanaga; Noriko Usui; Yukio Kobayashi; Shigeki Ohtake; Hitoshi Kiyoi; Itaru Matsumura; Yasushi Miyazaki; Tomoki Naoe; Akihiro TakeshitaAnnals of hematology 99 12 2787 - 2800 2020年12月 [査読有り]
Significant advancements have been achieved with regard to the outcomes of acute promyelocytic leukemia (APL) patients through the introduction of all-trans retinoic acid; however, early hemorrhagic death and differentiation syndrome remain the major causes of remission induction failure in patients with APL. To investigate early death, serious hemorrhage, and differentiation syndrome during remission induction therapy in terms of incidence, risk factors, influence on outcomes, and prophylactic effects of several new anticoagulants, the results of 344 patients enrolled in the Acute Promyelocytic Leukemia 204 study conducted by the Japan Adult Leukemia Study Group were analyzed. Early death was observed in 16 patients (4.7%), of whom 14 had serious hemorrhage and 2 had differentiation syndrome. Serious hemorrhage and differentiation syndrome of grade 2 or higher were observed in 21 and 54 patients, respectively. Patients who achieved complete remission had a 7-year disease-free survival of 84.8% if they did not experience serious hemorrhage and 40.0% if they experienced serious hemorrhage during remission induction therapy (P = 0.001). Risk factor analyses showed that higher white blood cell count was associated with early death, higher white blood cell count and lower platelet count with serious hemorrhage, and leukocytosis during induction therapy and higher body surface area with differentiation syndrome. In conclusion, these results indicate that patients with such high-risk features may benefit from more intensive supportive care. The hemorrhagic risk was not relieved by the introduction of new anticoagulants. Further studies are required to establish the predictive impact of body surface area on differentiation syndrome. This trial is registered with UMIN-CTR as C000000154 on September 13, 2005. - Naoki Takezako; Hiroshi Kosugi; Morio Matsumoto; Shinsuke Iida; Takayuki Ishikawa; Yukio Kondo; Kiyoshi Ando; Hirokazu Miki; Itaru Matsumura; Kazutaka Sunami; Takanori Teshima; Hiromi Iwasaki; Yasushi Onishi; Masahiro Kizaki; Koji Izutsu; Dai Maruyama; Kensei Tobinai; Razi Ghori; Mohammed Farooqui; Jason Liao; Patricia Marinello; Kenji Matsuda; Yasuhiro Koh; Takashi Shimamoto; Kenshi SuzukiInternational journal of hematology 112 5 640 - 649 2020年11月 [査読有り]
The global, randomized, open-label KEYNOTE-185 study closed early after an interim analysis showed an unfavorable benefit-risk profile with pembrolizumab plus lenalidomide and low-dose dexamethasone (Rd) versus Rd alone in treatment-naive, transplant-ineligible multiple myeloma. This subgroup analysis reported outcomes in the Japanese population. Patients were randomly assigned (1:1) to pembrolizumab plus Rd or Rd alone, stratified by age and International Staging System. The primary end point was progression-free survival (PFS). Fifty-two Japanese patients were randomly assigned to pembrolizumab plus Rd (n = 27) or Rd (n = 25). The median follow-up was 7.2 months (range, 0.4-13.8). The median PFS was not reached (NR); 6-month PFS was 91.2% versus 86.2% with pembrolizumab plus Rd versus Rd [hazard ratio (HR), 0.31; 95% CI, 0.06-1.63]. The median overall survival (OS) was NR; 6-month OS was 96.2% versus 95.7% with pembrolizumab plus Rd versus Rd (HR, 0.33; 95% CI, 0.03-3.72). With pembrolizumab plus Rd versus Rd, grade 3-5 adverse events occurred in 70.4% versus 69.6% of patients; serious adverse events occurred in 40.7% versus 52.5%. Although in the Japanese subgroup of KEYNOTE-185 adding pembrolizumab to Rd did not show an unfavorable risk-benefit, the analysis is limited by short follow-up and small sample size, affecting generalizability of the results. - Shun-Ichi Kimura; Yoshinobu Kanda; Masaki Iino; Takahiro Fukuda; Emiko Sakaida; Tatsuo Oyake; Hiroki Yamaguchi; Shin-Ichiro Fujiwara; Yumi Jo; Akinao Okamoto; Hiroyuki Fujita; Yasushi Takamatsu; Yoshio Saburi; Itaru Matsumura; Jun Yamanouchi; Souichi Shiratori; Moritaka Gotoh; Shingen Nakamura; Kazuo TamuraInternational journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases 100 292 - 297 2020年11月 [査読有り]
OBJECTIVES: The D-index is defined as the area over the neutrophil curve during neutropenia. The CEDMIC trial confirmed the noninferiority of D-index-guided early antifungal therapy (DET) using micafungin to empirical antifungal therapy (EAT). In this study, we evaluated the efficacy and safety of micafungin in these settings. METHODS: From the CEDMIC trial, we extracted 67 and 113 patients who received micafungin in the DET and EAT groups, respectively. Treatment success was defined as the fulfilment of all components of a five-part composite end point. Fever resolution was evaluated at seven days after the completion of therapy. RESULTS: The proportion of high-risk treatments including induction chemotherapy for acute leukemia and allogeneic hematopoietic stem cell transplantation was significantly higher in the DET group than in the EAT group (82.1% vs. 52.2%). The efficacy of micafungin was 68.7% (95%CI: 56.2-79.4) and 79.6% (71.0-86.6) in the DET and EAT groups, respectively. When we focused on high-risk treatments, the efficacy was 69.1% (55.2-80.9%) and 78.0% (65.3-87.7%), respectively (P = 0.30). There was no significant difference in any of the 5 components between the two groups. CONCLUSIONS: The efficacy of micafungin in patients undergoing high-risk treatment was not strongly impaired in DET compared to that in EAT. - Asuka Inoue; Yuji Nozaki; Yasuaki Hirooka; Koji Kinoshita; Yasutaka Chiba; Masanori Funauchi; Itaru MatsumuraLife (Basel, Switzerland) 10 11 2020年10月(1) Background: We evaluated the clinical response of iguratimod (IGU) in patients with rheumatoid arthritis (RA) being treated with or without methotrexate (MTX) over 54 weeks. (2) Methods: 106 patients with RA undergoing IGU were retrospectively observed. RA patients were divided into those treated with MTX+IGU (n = 35) and those treated with IGU (n = 71). The primary endpoint was the clinical response of the Disease Activity Score assessing 28 joints with C-reactive protein (DAS28-CRP) differences in the changes from baseline to 54 weeks between MTX+IGU and IGU groups. Secondary endpoints, such as the clinical response, retention rate, and safety, were evaluated. (3) Results: The DAS28-CRP difference in the changes between the two groups were -0.2. DAS28-CRP were significantly reduced from the baseline in the MTX+IGU and IGU groups (-1.43 and -1.20 from baseline, respectively). The retention rates were 71.4% in the MTX+IGU groups and 59.2% in the IGU groups (p = 0.16). Adverse events were observed in a total of 6 (17.1%) MTX+IGU patients and 20 (28.2%) IGU patients (p = 0.21). (4) Conclusions: IGU therapy may be a useful treatment option for patients who cannot be treated with MTX.
- Takaaki Ono; Naoto Takahashi; Masahiro Kizaki; Tatsuya Kawaguchi; Ritsuro Suzuki; Kazuhito Yamamoto; Kazunori Ohnishi; Tomoki Naoe; Itaru MatsumuraCancer science 111 10 3714 - 3725 2020年10月Comorbidities at diagnosis among patients with chronic myeloid leukemia in chronic phase (CML-CP) may affect their overall survival (OS) rate even in the tyrosine kinase inhibitor (TKI) era. However, the prognostic impact of comorbidities in patients with CML-CP treated with a second-generation TKI (2GTKI) has not been elucidated. We evaluated the effect of comorbidities on survival using the Charlson Comorbidity Index (CCI) in patients with CML-CP treated with imatinib or a 2GTKI (nilotinib and dasatinib). From April 2010 to March 2013, 506 patients with CML-CP were registered for the population-based cohort study, and 452 with a median age of 56 y were assessable. Treatment groups included 139 patients receiving imatinib, 169 receiving nilotinib, and 144 receiving dasatinib. Comorbidities were diagnosed in 99 patients. CCI scores were stratified as follows: 2, 353 patients; 3, 72 patients; and ≥4, 27 patients. Treatment response did not vary relative to CCI scores. However, across the entire cohort, the OS rate was significantly lower among patients with higher CCI scores than in those with a CCI score of 2 (94.4% in score 2, 89.0% in score 3, and 72.8% in score ≥4; P < .001). Multivariate analysis identified a CCI score of ≥4 as a strong adverse prognostic factor for OS rather than the disease-specific risk factor, older age, performance status, or selection of TKI (Wald test, P < .01). Our results demonstrated that comorbidities at diagnosis were the most important predictive factor for successful treatment, regardless of the TKI type used in CML-CP. This trial was registered at UMIN-CTR as 00003581.
- Aya Nakaya; Takae Kohara; Hirohiko Shibayama; Yoshiyuki Onda; Junya Kanda; Hitomi Kaneko; Kazunori Imada; Toru Kida; Satoru Kosugi; Jun Ishikawa; Ryosuke Yamamura; Yutaka Shimazu; Hirokazu Tanaka; Shin-Ichi Fuchida; Yuji Shimura; Miki Kiyota; Katsuya Wada; Tomoki Ito; Nobuhiko Uoshima; Hideo Yagi; Satoshi Yoshihara; Kensuke Ohta; Chihiro Shimazaki; Masayuki Hino; Akifumi Takaori-Kondo; Junya Kuroda; Itaru Matsumura; Yuzuru Kanakura; Shosaku NomuraInternational journal of hematology 112 4 435 - 438 2020年10月 [査読有り]
We retrospectively analyzed the clinical features and outcomes in a real-world cohort of adolescents and the young adult (AYA) patients (age between 16 and 39 years) with symptomatic multiple myeloma (MM) registered with the Kansai Myeloma Forum. 26 patients had been diagnosed as symptomatic MM out of 3284 patients. The prevalence of AYA-MM was 0.8% in this cohort. 81% of the patients was received stem cell transplantation, which may improve outcome. Anemia and hypercalcemia might be prognostic factors, however International Staging System failed to predict overall survival. Five patients developed late-onset adverse events which were serious and life-threatening. The 5-year overall survival was 71.0%. We need to develop the new strategy to overcome AYA-MM. - Shun-Ichi Kimura; Hiroyuki Fujita; Hiroshi Handa; Nobuhiro Hiramoto; Naoko Hosono; Hitoshi Minamiguchi; Tsutomu Takahashi; Hideaki Kato; Takaaki Ono; Yoshinobu Kanda; Hitoshi Kiyoi; Itaru Matsumura; Yasushi MiyazakiInternational journal of hematology 112 3 409 - 417 2020年09月 [査読有り]
We conducted a nationwide questionnaire-based survey in 2019 following 2001, 2007 and 2013 surveys to clarify the real-world management of infection during chemotherapy for acute leukemia in Japan. An online questionnaire was sent through SurveyMonkey® to member institutions of the Japan Adult Leukemia Study Group in June 2019. The questionnaire consisted of 52 multiple-choice questions covering prophylactic measures, screening and diagnostic tests, empirical antibiotic therapy, antifungal management, the usage of granulocyte-colony stimulating factor, and vaccinations against influenza and pneumococcus during intensive chemotherapy for acute leukemia. Questions associated with antimicrobial stewardship were also included. Usable responses were received from 163 of 218 (74.8%) institutions. Approximately, half (52.2%) of the institutes did not have infectious disease department. As antibiotic prophylaxis, fluoroquinolones (62%) were most commonly used in induction chemotherapy for acute myeloid leukemia. No prophylaxis accounted for 19% of the institutions, which has gradually increased compared to previous surveys. In empirical antibiotic therapy for febrile neutropenia, monotherapy with β-lactam antibiotics was the most commonly used first-line therapy. De-escalation was not considered in 42.2% of the institutions. In conclusion, this study clarified the real-world management of infection during intensive chemotherapy for acute leukemia in 2019 and raised future issues in Japan. - Shinya Rai; Hirokazu Tanaka; Mai Suzuki; J Luis Espinoza; Takahiro Kumode; Akira Tanimura; Takafumi Yokota; Kenji Oritani; Toshio Watanabe; Yuzuru Kanakura; Itaru MatsumuraNature communications 11 1 4147 - 4147 2020年08月 [査読有り]
Mutated receptor tyrosine kinases (MT-RTKs) such as internal tandem duplication of FMS-like tyrosine kinase 3 (FLT3 ITD) and a point mutation KIT D816V are driver mutations for acute myeloid leukemia (AML). Clathrin assembly lymphoid myeloid leukemia protein (CALM) regulates intracellular transport of RTKs, however, the precise role for MT-RTKs remains elusive. We here show that CALM knock down leads to severely impaired FLT3 ITD- or KIT D814V-dependent cell growth compared to marginal influence on wild-type FLT3- or KIT-mediated cell growth. An antipsychotic drug chlorpromazine (CPZ) suppresses the growth of primary AML samples, and human CD34+CD38- AML cells including AML initiating cells with MT-RTKs in vitro and in vivo. Mechanistically, CPZ reduces CALM protein at post transcriptional level and perturbs the intracellular localization of MT-RTKs, thereby blocking their signaling. Our study presents a therapeutic strategy for AML with MT-RTKs by altering the intracellular localization of MT-RTKs using CPZ. - Aya Nakaya; Hirokazu Tanaka; Hideo Yagi; Kensuke Ohta; Hirohiko Shibayama; Takae Kohara; Junya Kanda; Maki Shindo; Yuji Shimura; Satoru Kosugi; Toru Kida; Hitomi Kaneko; Kazunori Imada; Takahiro Karasuno; Mitsuhiro Matsuda; Masato Iida; Yoko Adachi; Shin-Ichi Fuchida; Nobuhiko Uoshima; Hitoji Uchiyama; Ryoichi Takahashi; Toshimitsu Matsui; Katsuya Wada; Miki Kiyota; Chihiro Shimazaki; Masayuki Hino; Junya Kuroda; Yuzuru Kanakura; Akifumi Takaori-Kondo; Shosaku Nomura; Itaru MatsumuraInternational journal of hematology 112 5 666 - 673 2020年08月 [査読有り]
We retrospectively analyzed 51 patients with solitary plasmacytoma diagnosed from October 2002 to September 2018 from a cohort of 3575 patients with plasma cell dyscrasias registered in the Kansai Myeloma Forum. Twenty-seven patients had solitary bone plasmacytoma (SBP) and 24 had extramedullary plasmacytoma (EMP), with prevalence of 0.8% and 0.7%, respectively. The most frequent M protein was IgG (40%) in SBP, whereas non-secretory proteins were most frequent (50%) in EMP. Five-year overall survival was 78.2% in SBP and 80.8% in EMP (P = 0.894). Among patients with SBP, 44% progressed to MM with a median time of 10.5 months (2.4-93.3 months), whereas 8% of EMP patients progressed to MM with a median time of 18.6 months (13.0-24.2 months). The most frequent treatment was radiotherapy (41%) or observation (41%) in SBP, and chemotherapy (54%) in EMP. No statistically significant difference was observed upon univariate analysis of prognostic factors including age, sex, performance status, and IgG M protein. Our results suggest that there are biological differences between SBP and EMP in real-world settings. - Masayuki Hino; Itaru Matsumura; Shin Fujisawa; Kenichi Ishizawa; Takaaki Ono; Emiko Sakaida; Naohiro Sekiguchi; Yusuke Tanetsugu; Kei Fukuhara; Masayuki Ohkura; Yuichiro Koide; Naoto TakahashiInternational journal of hematology 112 1 24 - 32 2020年07月 [査読有り]
This open-label, single-arm, phase 2 study (ClinicalTrials.gov, NCT03128411) evaluated the efficacy, safety, and pharmacokinetics of bosutinib at a starting dose of 400 mg once daily (QD) in Japanese patients with newly diagnosed chronic phase chronic myeloid leukemia (CP CML). The primary endpoint was major molecular response (MMR) at Month 12 in the modified as-treated population (Philadelphia chromosome-positive [Ph+] patients with e13a2/e14a2 transcripts). Sixty Japanese patients with CP CML were treated with bosutinib; median age was 55 years (range 20-83), 60.0% were males, and all were Ph+ and had e13a2/e14a2 transcripts. After median follow-up of 16.6 months (range 11.1-21.9), 41 (68.3%) patients remained on bosutinib. The MMR rate at Month 12 was 55.0% (2-sided 90% confidence interval: 44.4-65.6). There were no on-treatment transformations to accelerated/blast phase, and no patient died on treatment or within 28 days of the last bosutinib dose. The most common treatment-emergent adverse events were diarrhea (86.7%), increased alanine aminotransferase (55.0%), and increased aspartate aminotransferase (46.7%). The primary objective of this phase 2 study was met, and there were no new safety signals for bosutinib. These data suggest bosutinib is an effective first-line treatment option for Japanese patients with newly diagnosed CP CML. - Naomi Kawashima; Yuichi Ishikawa; Yoshiko Atsuta; Masashi Sawa; Yukiyasu Ozawa; Masaki Hayashi; Akio Kohno; Akihiro Tomita; Tomoya Maeda; Emiko Sakaida; Kensuke Usuki; Maki Hagihara; Heiwa Kanamori; Hiroshi Matsuoka; Miki Kobayashi; Norio Asou; Shigeki Ohtake; Itaru Matsumura; Yasushi Miyazaki; Tomoki Naoe; Hitoshi KiyoiCancer science 111 7 2472 - 2481 2020年07月 [査読有り]
In this phase II multicenter study (JALSG AML209-FLT3-SCT), we aimed to prospectively elucidate the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) at first complete remission (CR1) for FLT3-internal tandem duplication (ITD)-positive AML. Newly diagnosed de novo AML patients with FLT3-ITD were enrolled at the achievement of CR1 and received allo-HSCT as soon as possible after the first consolidation therapy. Mutations of 57 genes in AML cells at diagnosis were also analyzed. Among 48 eligible patients with a median age of 38.5 (17-49) years, 36 (75%) received allo-HSCT at a median of 108 days after CR1. The median follow-up was 1726 days. The primary end-point, 3-year disease-free survival (DFS) based on an intent to treat analysis, was 43.8% (95% confidence interval [CI], 30%-57%), suggesting the efficacy of this treatment because the lower limit of the 95% CI exceeded the threshold response rate of 20%. The 3-year overall survival, post-transplant DFS, and non-relapse mortality rates were 54.2% (95% CI, 39%-67%), 58.3% (95% CI, 41%-72%), and 25.0% (95% CI, 12%-40%), respectively. The median ITD allelic ratio (AR) was 0.344 (0.006-4.099). Neither FLT3-ITD AR nor cooccurring genetic alterations was associated with a poor DFS. This prospective study indicated the efficacy and safety of allo-HSCT for FLT3-ITD AML patients in CR1. This study was registered at: www.umin.ac.jp/ctr/ as #UMIN000003433. - Shinobu Tsuzuki; Takahiko Yasuda; Shinya Kojima; Masahito Kawazu; Koshi Akahane; Takeshi Inukai; Masue Imaizumi; Takanobu Morishita; Koichi Miyamura; Toshihide Ueno; Sivasundaram Karnan; Akinobu Ota; Toshinori Hyodo; Hiroyuki Konishi; Masashi Sanada; Hirokazu Nagai; Keizo Horibe; Akihiro Tomita; Kyogo Suzuki; Hideki Muramatsu; Yoshiyuki Takahashi; Yasushi Miyazaki; Itaru Matsumura; Hitoshi Kiyoi; Yoshitaka Hosokawa; Hiroyuki Mano; Fumihiko HayakawaBlood Cancer Discovery 1 1 82 - 95 2020年06月 [査読有り]
UNLABELLED: The cellular context that integrates gene expression, signaling, and metabolism dictates the oncogenic behavior and shapes the treatment responses in distinct cancer types. Although chimeric fusion proteins involving transcription factors (TF) are hallmarks of many types of acute lymphoblastic leukemia (ALL), therapeutically targeting the fusion proteins is a challenge. In this work, we characterize the core regulatory circuitry (CRC; interconnected autoregulatory loops of TFs) of B-ALL involving MEF2D-fusions and identify MEF2D-fusion and SREBF1 TFs as crucial CRC components. By gene silencing and pharmacologic perturbation, we reveal that the CRC integrates the pre-B-cell receptor (BCR) and lipid metabolism to maintain itself and govern malignant phenotypes. Small-molecule inhibitors of pre-BCR signaling and lipid biosynthesis disrupt the CRC and silence the MEF2D fusion in cell culture and show therapeutic efficacy in xenografted mice. Therefore, pharmacologic disruption of CRC presents a potential therapeutic strategy to target fusion protein-driven leukemia. SIGNIFICANCE: Cancer type-specific gene expression is governed by transcription factors involved in a highly interconnected autoregulatory loop called CRC. Here, we characterized fusion protein-driven CRC and identified its pharmacologic vulnerabilities, opening therapeutic avenues to indirectly target fusion-driven leukemia by disrupting its CRC.See related commentary by Sadras and Müschen, p. 18. This article is highlighted in the In This Issue feature, p. 5. - 木下 浩二; 船内 正憲; 松村 到臨床リウマチ 32 2 140 - 145 2020年06月症例は38歳男性。幼少期より気管支喘息と診断されステロイド薬による治療を受けていた。5年前に両側大腿骨頭壊死の既往あり。1年前から多関節痛あり関節リウマチ疑いにて当科受診。当初はリウマチとして抗リウマチ薬による治療を開始し、一時症状の改善を認めたが、その後痛みが再燃したためMRI検査を施行したところ多数の関節に骨壊死を認めたため、喘息治療で使用されていたステロイド薬による多発骨壊死と診断した。その後ステロイド薬を漸減、中止し、骨壊死に対し保存的治療を行った。(著者抄録)
- 【血液疾患と消化器系の異常】造血器腫瘍に対する新規分子標的薬による肝障害の留意点田中 宏和; 松村 到血液内科 80 6 849 - 855 (有)科学評論社 2020年06月 [査読有り]
- Akihiro Takeshita; Norio Asou; Yoshiko Atsuta; Hiroaki Furumaki; Toru Sakura; Yasunori Ueda; Masashi Sawa; Nobuaki Dobashi; Yasuhiro Taniguchi; Rikio Suzuki; Masaru Nakagawa; Shigehisa Tamaki; Maki Hagihara; Katsumichi Fujimaki; Hitoshi Minamiguchi; Hiroyuki Fujita; Masamitsu Yanada; Yoshinobu Maeda; Noriko Usui; Yukio Kobayashi; Hitoshi Kiyoi; Shigeki Ohtake; Itaru Matsumura; Tomoki Naoe; Yasushi Miyazaki; The Japan Adult Leukemia Study GroupCancers 12 6 1444 - 1444 2020年06月 [査読有り]
BACKGROUND: After long-term analysis of the JALSG-APL204 study we recently reported that maintenance therapy with tamibarotene was more effective than all-trans retinoic acid (ATRA) by reducing relapse in APL patients. Here, the clinical significance of other important prognostic factors was evaluated with multivariate analyses. PATIENTS AND METHODS: Newly diagnosed acute promyelocytic leukemia (APL) patients were registered with the study. Induction was composed of ATRA and chemotherapy. Patients who achieved molecular remission after consolidation were randomly assigned to maintenance with tamibarotene or ATRA. RESULTS: Of the 344 eligible patients, 319 (93%) achieved complete remission (CR). After completing consolidation, 269 patients underwent maintenance random assignment-135 to ATRA, and 134 to tamibarotene. By multivariate analysis, overexpression of CD56 in blast was an independent unfavorable prognostic factor for relapse-free survival (RFS) (p = 0.006) together with more than 10.0 × 109/L WBC counts (p = 0.001) and the ATRA arm in maintenance (p = 0.028). Of all phenotypes, CD56 was related most clearly to an unfavorable prognosis. The CR rate, mortality rate during induction and overall survival of CD56+ APL were not significantly different compared with CD56- APL. CD56 is continuously an independent unfavorable prognostic factor for RFS in APL patients treated with ATRA and chemotherapy followed by ATRA or tamibarotene maintenance therapy. - Masatoshi Sakurai; Shinichiro Okamoto; Itaru Matsumura; Satsuki Murakami; Makiko Takizawa; Masato Waki; Daiki Hirano; Reiko Watanabe-Nakaseko; Naoki Kobayashi; Masaki Iino; Hideki Mitsui; Yuichi Ishikawa; Naoto Takahashi; Tatsuya Kawaguchi; Ritsuro Suzuki; Kazuhito Yamamoto; Masahiro Kizaki; Kazunori Ohnishi; Tomoki Naoe; Koichi AkashiInternational journal of hematology 111 6 812 - 825 2020年06月 [査読有り]
We herein report the results of the New TARGET study 2nd-line, which collected data on patients with chronic-phase (CP) chronic myeloid leukemia (CML) who received a 2nd-line tyrosine kinase inhibitor (TKI) because of resistance and/or to a 1st-line TKI. A total of 98 patients were enrolled intolerance between April 2010 and March 2013, and 82 patients were analyzed. The median age was 54 years (range 22-88 years). Seventy-six patients (93%) received imatinib as the 1st-line TKI. Forty-five (55%) and 37 (45%) patients began nilotinib and dasatinib treatments at entry, respectively. First-line TKI treatment achieved complete hematological response in 79 patients (96%) and complete cytogenetic response (CCyR) in 49 patients (60%), respectively. Nine patients (11%) had BCR-ABL1 kinase domain point mutations at enrollment. The estimated 3-year progression-free-survival rate after enrollment was 98.7% (95% CI 91.1-99.8%). Overall, the probabilities of achieving CCyR and a major molecular response were 89.3% (95% CI 81.4-94.8%) and 87.2% (95% CI 78.1-93.8%), respectively. There were no new safety issues. This study demonstrated that CML-CP patients in Japan who are resistant and/or intolerant to a 1st-line TKI can achieve an extremely good outcome by 2nd-line TKI treatment. - Hiroaki Inoue; Shinya Rai; Hirokazu Tanaka; J Luis Espinoza; Yosaku Watatani; Takahiro Kumode; Kentaro Serizawa; Shoko Nakayama; Yasuhiro Taniguchi; Yasuyoshi Morita; Yoichi Tatsumi; Takashi Ashida; Itaru MatsumuraBritish journal of haematology 191 2 243 - 252 2020年05月 [査読有り]
Despite duodenal-type follicular lymphoma (DTFL) being morphologically, immunophenotypically and genetically indistinguishable from nodal FL (nFL), this entity typically shows a significantly better prognosis. Here, we analysed the tumour immune microenvironments of diagnostic specimens from patients with DTFL (n = 30), limited-stage FL (LSFL; n = 19) and advanced-stage FL (ASFL; n = 31). The mean number of CD8+ tumour-infiltrating lymphocytes (TILs) in the neoplastic follicles was higher in DTFL (1,827/mm2 ) than in LSFL (1,150/mm2 ) and ASFL (1,188/mm2 ) (P = 0·002, P = 0·002, respectively). In addition, CD8+ PD1- T cells with non-exhausting phenotype were more abundant in the peripheral blood (PB) of DTFL than in LSFL and ASFL, indicating that DTFL may exhibit a better and longer-lasting T cell-mediated immune response. Moreover, whereas FOXP3+ CTLA-4+ effector regulatory T cells (eTregs) were rarely observed in the neoplastic follicles of DTFL (mean: 12/mm2 ), they were more abundant in LSFL (78/mm2 ) and ASFL (109/mm2 ) (P = 2·80 × 10-5 , P = 4·74 × 10-8 , respectively), and the numbers of eTregs correlated inversely with those of CD8+ TILs (r = -0267; P = 0·018). Furthermore, DTFL showed significantly fewer circulating FOXP3hi CD45RA- CD25hi eTregs (0·146%) than ASFL (0·497%) and healthy controls (0·639%) (P = 0·0003, P = 6·79 × 10-7 , respectively). These results suggest that the augmented anti-tumour immune reactions may contribute to a better prognosis on DTFL. - Hiroaki Inoue; Shinya Rai; Hirokazu Tanaka; J Luis Espinoza; Maiko Komori-Inoue; Hiroaki Kakutani; Shuji Minamoto; Takahiro Kumode; Shoko Nakayama; Yasuhiro Taniguchi; Yasuyoshi Morita; Takeshi Okuda; Yoichi Tatsumi; Takashi Ashida; Itaru MatsumuraViruses 12 4 2020年04月 [査読有り]
Aplastic anemia is a rare blood disease characterized by the destruction of the hematopoietic stem cells (HSC) in the bone marrow that, in the majority of cases, is caused by an autoimmune reaction. Patients with aplastic anemia are treated with immunosuppressive drugs and some of them, especially younger individuals with a donor available, can be successfully treated with hematopoietic stem cell transplantation (HSCT). We report here a rare case of post-transplant lymphoproliferative disorder (PTLD) associated with Epstein-Barr virus (EBV) reactivation in a 30-year-old female patient who underwent allogeneic HSCT for severe aplastic anemia. The PTLD, which was diagnosed 230 days after transplantation, was localized exclusively in the central nervous system (specifically in the choroid plexus) and manifested with obvious signs of intracranial hypertension. After receiving three cycles of high dose methotrexate (HD-MTX) combined with rituximab, the patient achieved a complete clinical recovery with normalization of blood cell counts, no evidence of EBV reactivation, and no associated neurotoxicity. - Yuji Nozaki; Jinhai Ri; Kenji Sakai; Kaoru Niki; Masanori Funauchi; Itaru MatsumuraInternational journal of molecular sciences 21 7 2020年04月 [査読有り]
Thrombomodulin (TM) is a single transmembrane, multidomain glycoprotein receptor for thrombin, and is best known for its role as a cofactor in a clinically important natural anticoagulant pathway. In addition to its anticoagulant function, TM has well-defined anti-inflammatory properties. Soluble TM levels increase significantly in the plasma of septic patients; however, the possible involvement of recombinant human soluble TM (rTM) transduction in the pathogenesis of lipopolysaccharide (LPS)-induced nephrotoxicity, including acute kidney injury (AKI), has remained unclear. Mice were injected intraperitoneally with 15 mg/kg LPS. rTM (3 mg/kg) or saline was administered to the animals before the 3 and 24 h LPS-injection. At 24 and 48 h, blood urea nitrogen, the inflammatory cytokines in sera and kidney, and histological findings were assessed. Cell activation and apoptosis signal was assessed by Western blot analysis. In this study using a mouse model of LPS-induced AKI, we found that rTM attenuated renal damage by reducing both cytokine and cell activation and apoptosis signals with the accumulation of CD4+ T-cells, CD11c+ cells, and F4/80+ cells via phospho c-Jun activations and Bax expression. These findings suggest that the mechanism underlying these effects of TM may be mediated by a reduction in inflammatory cytokine production in response to LPS. These molecules might thereby provide a new therapeutic strategy in the context of AKI with sepsis. - Yoshinobu Kanda; Shun-Ichi Kimura; Masaki Iino; Takahiro Fukuda; Emiko Sakaida; Tatsuo Oyake; Hiroki Yamaguchi; Shin-Ichiro Fujiwara; Yumi Jo; Akinao Okamoto; Hiroyuki Fujita; Yasushi Takamatsu; Yoshio Saburi; Itaru Matsumura; Jun Yamanouchi; Souichi Shiratori; Moritaka Gotoh; Shingen Nakamura; Kazuo TamuraJournal of clinical oncology : official journal of the American Society of Clinical Oncology 38 8 815 - 822 2020年03月 [査読有り]
PURPOSE: Empiric antifungal therapy (EAT) is recommended for persistent febrile neutropenia (FN), but in most patients, it is associated with overtreatment. The D-index, calculated as the area surrounded by the neutrophil curve and the horizontal line at a neutrophil count of 500/μL, reflects both the duration and depth of neutropenia and enables real-time monitoring of the risk of invasive fungal infection in individual patients at no cost. We investigated a novel approach for patients with persistent FN called D-index-guided early antifungal therapy (DET), in which antifungal treatment is postponed until a D-index reaches 5,500 or the detection of positive serum or imaging tests, and compared it with EAT in this multicenter open-label noninferiority randomized controlled trial. PATIENTS AND METHODS: We randomly assigned 423 patients who underwent chemotherapy or hematopoietic stem-cell transplantation for hematologic malignancies to the EAT or DET group. The prophylactic use of antifungal agents other than polyenes, echinocandins, or voriconazole was allowed. Micafungin at 150 mg per day was administered as EAT or DET. RESULTS: In an intent-to-treat analysis of 413 patients, the incidence of probable/proven invasive fungal infection was 2.5% in the EAT group and 0.5% in the DET group, which fulfilled the predetermined criterion of noninferiority of the DET group (-2.0%; 90% CI, -4.0% to 0.1%). The survival rate was 98.0% versus 98.6% at day 42 and 96.4% versus 96.2% at day 84. The use of micafungin was significantly reduced in the DET group (60.2% v 32.5%; P < .001). CONCLUSION: A novel strategy, DET, decreased the use and cost of antifungal agents without increasing invasive fungal infections and can be a reasonable alternative to empiric or preemptive antifungal therapy. - Shigeto Yanagihara; Naoki Oiso; Yasuyo Ohyama; Hiroaki Masaie; Itaru Matsumura; Akira KawadaEUROPEAN JOURNAL OF DERMATOLOGY 30 2 185 - 187 2020年03月 [査読有り]
- Shoko Nakayama; Yasuyoshi Morita; Jorge Luis Espinoza; Shinya Rai; Yasuhiro Taniguchi; Takahide Taniguchi; Yoshiaki Miyake; Hirokazu Tanaka; Takashi Ashida; Itaru MatsumuraAnnals of hematology 99 2 381 - 383 2020年02月 [査読有り]
- Yuichi Ishikawa; Naomi Kawashima; Yoshiko Atsuta; Isamu Sugiura; Masashi Sawa; Nobuaki Dobashi; Hisayuki Yokoyama; Noriko Doki; Akihiro Tomita; Toru Kiguchi; Shiro Koh; Heiwa Kanamori; Noriyoshi Iriyama; Akio Kohno; Yukiyoshi Moriuchi; Noboru Asada; Daiki Hirano; Kazuto Togitani; Toru Sakura; Maki Hagihara; Tatsuki Tomikawa; Yasuhisa Yokoyama; Norio Asou; Shigeki Ohtake; Itaru Matsumura; Yasushi Miyazaki; Tomoki Naoe; Hitoshi KiyoiBlood advances 4 1 66 - 75 2020年01月 [査読有り]
The prognostic impact of KIT mutation on core-binding factor acute myeloid leukemia (CBF-AML) remains controversial. We registered 199 newly diagnosed de novo CBF-AML patients, aged 16 to 64 years, who achieved complete remission. They received 3 courses of high-dose cytarabine therapy and no further treatment until hematological relapse. Mutations in exons 8, 10-11, and 17 of the KIT gene were analyzed. Furthermore, we analyzed mutations in 56 genes that are frequently identified in myeloid malignancies and evaluated minimal residual disease (MRD). The primary end point was relapse-free survival (RFS) according to KIT mutations. The RFS in KIT-mutated patients was inferior to that in unmutated patients (hazard ratio, 1.92; 95% confidence interval, 1.23-3.00; P = .003). Based on subgroup analysis, KIT mutations had a prognostic impact in patients with RUNX1-RUNX1T1, but not in those with CBFB-MYH11, and only exon 17 mutation had a significant prognostic impact. Multivariate Cox regression analysis with stepwise selection revealed that the KIT exon 17 mutation and the presence of extramedullary tumors in patients with RUNX1-RUNX1T1, and loss of chromosome X or Y and NRAS mutation in patients with CBFB-MYH11 were poor prognostic factors for RFS. MRD was evaluated in 112 patients, and it was associated with a poorer RFS in the patients with CBFB-MYH11, but not in those with RUNX1-RUNX1T1. These results suggested that it is necessary to separately evaluate AML with RUNX1-RUNX1T1 or CBFB-MYH11 according to appropriate prognostic factors. This study was registered at www.umin.ac.jp/ctr/ as #UMIN000003434. - 岸本和也; 野崎祐史; 石村香織; 赤澤宗輝; 芦田千聖; 岡田晃典; 伊丹哲; 酒井健史; 李進海; 志賀俊彦; 樋野尚一; 廣岡靖章; 杉山昌史; 木下浩二; 船内正憲; 松村到日本リウマチ学会総会・学術集会プログラム・抄録集 64th (CD-ROM) 2020年
- Yasuaki Hirooka; Yuji Nozaki; Kaoru Niki; Asuka Inoue; Masafumi Sugiyama; Koji Kinoshita; Masanori Funauchi; Itaru MatsumuraFrontiers in medicine 7 604656 - 604656 2020年Renal interstitial fibrosis is a common lesion in the process of various progressive renal diseases. Interleukin (IL)-18 is a proinflammatory cytokine that plays an important role in the induction of Th1 responses and is associated with renal interstitial fibrosis, but the mechanism of fibrosis remains unclear. Here we used IL-18 receptor alpha knockout (IL-18Rα KO) mice to investigate the role of an IL-18Rα signaling pathway in renal fibrosis in a murine model of unilateral ureteral obstruction. IL-18 Rα KO mice showed decreased renal interstitial fibrosis and increased infiltration of CD4+ T cells and Foxp3+ regulatory T cells (Tregs) compared to wildtype (WT) mice. The expression of renal transforming growth factor beta 1 (TGF-β1, which is considered an important cytokine in renal interstitial fibrosis) was not significantly different between WT and IL-18Rα KO mice. The adoptive transfer of CD4+ T cells from the splenocytes of IL-18Rα KO mice to WT mice reduced renal interstitial fibrosis and increased the number of Foxp3+ Tregs in WT mice. These results demonstrated that Foxp3+ Tregs have a protective effect in renal interstitial fibrosis via an IL-18R signaling pathway.
- Yasuhiro Taniguchi; Naoto Takahashi; Masatomo Miura; Chikara Hirase; Sanae Sueda; Jorge Luis Espinoza; Shinya Rai; Shoko Nakayama; Kentaro Serizawa; Takahiro Kumode; Yosaku Watatani; Yasuyoshi Morita; Hirokazu Tanaka; Itaru MatsumuraINTERNAL MEDICINE 59 21 2745 - 2749 2020年 [査読有り]
We recently treated a chronic myeloid leukemia (CML) patient with liver and renal dysfunction, who was undergoing hemodialysis (HD). He was treated with 50 mg dasatinib (DAS) once daily just before HD. The maximum plasma concentration of DAS was 227 ng/mL on a non-HD day and 46.9 ng/mL on a HD day. He was subsequently treated with 200 mg bosutinib (BOS) once daily. The plasma concentration of BOS changed from 74.5 ng/mL before HD to 58.8 ng/mL after HD. Our results indicate that close monitoring of the plasma tyrosine kinase inhibitor concentrations should be considered in CML patients with organ impairment. - Takahiro Kumode; Shinya Rai; Hirokazu Tanaka; J Luis Espinoza; Hiroaki Kakutani; Yosaku Watatani; Shuji Minamoto; Yasuhiro Taniguchi; Shoko Nakayama; Yasuyoshi Morita; Takashi Ashida; Itaru MatsumuraLeukemia research reports 14 100219 - 100219 2020年 [査読有り]
We report a case with extramedullary tumors affecting the supraclavicular region that presented as a relapse of acute myeloid leukemia (AML) with FLT3-ITD mutation after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Treatment with gilteritinib resulted in remarkable response with disappearance of both the medullary and extramedullary tumors. Subsequently, a 2nd allo-HSCT was performed in an attempt to cure his AML and complete molecular response has been sustained with gilteritinib resumption without worsening GVHD. Targeted therapy with gilteritinib for medullary and extramedullary relapse of FLT3-ITD AML could be effective and suitable as a bridging therapy for allo-HSCT. - Shigeto Yanagihara; Naoki Oiso; Yasuyoshi Morita; Yoshiaki Miyake; Maiko Kato; Itaru Matsumura; Akira KawadaJOURNAL OF DERMATOLOGY 47 1 E4 - E5 2020年01月 [査読有り]
- Yuji Nozaki; Jinhai Ri; Kenji Sakai; Kaoru Niki; Koji Kinoshita; Masanori Funauchi; Itaru MatsumuraCells 9 1 2019年12月 [査読有り]
Interleukin (IL)-18 expression in synovial tissue correlates with the severity of joint inflammation and the levels of pro-inflammatory cytokines. However, the role of the IL-18/IL-18 receptor-alpha (Rα) signaling pathway in autoimmune arthritis is unknown. Wild-type (WT) and IL-18Rα knockout (KO) mice were immunized with bovine type II collagen before the onset of arthritis induced by lipopolysaccharide injection. Disease activity was evaluated by semiquantitative scoring and histologic assessment. Serum inflammatory cytokine and anticollagen antibody levels were quantified by an enzyme-linked immunosorbent assay. Joint cytokine and matrix metalloproteinases-3 levels were determined by a quantitative polymerase chain reaction. Splenic suppressors of cytokine signaling (SOCS) were determined by Western blot analysis as indices of systemic immunoresponse. IL-18Rα KO mice showed lower arthritis and histological scores in bone erosion and synovitis due to reductions in the infiltration of CD4+ T cells and F4/80+ cells and decreased serum IL-6, -18, TNF, and IFN-γ levels. The mRNA expression and protein levels of SOCS3 were significantly increased in the IL-18Rα KO mice. By an up-regulation of SOCS, pro-inflammatory cytokines were decreased through the IL-18/IL-18Rα signaling pathway. These results suggest that inhibitors of the IL-18/IL-18Rα signaling pathway could become new therapeutic agents for rheumatoid arthritis. - 冨田 大介; 志賀 俊彦; 田崎 知江美; 野崎 祐史; 船内 正憲; 松村 到臨床リウマチ 31 4 307 - 313 (一社)日本臨床リウマチ学会 2019年12月症例30歳、男性。5年前頃から皮疹と関節痛の増悪と改善を繰り返し、3週間前から増悪を認め入院となった。血球貪食症候群を認め、全身性エリテマトーデス(SLE)等の膠原病が疑われたが各種自己抗体は抗核抗体を含め陰性であった。しかし、皮膚ループスバンドテスト(LBT)の陽性所見からSLEと診断された。本例のように血清抗核抗体が陰性だが、臨床的にSLEが疑われる場合は、LBTを含む病理組織学的検査を施行することが重要と考えられた。(著者抄録)
- Koji Nagafuji; Itaru Matsumura; Takayuki Shimose; Tatsuya Kawaguchi; Junya Kuroda; Hirohisa Nakamae; Toshihiro Miyamoto; Norimitsu Kadowaki; Jun Ishikawa; Yutaka Imamura; Hirohito Yamazaki; Koichi Akashi; Yuzuru KanakuraInternational journal of hematology 110 6 675 - 682 2019年12月 [査読有り]
The aim of this multicenter phase 2 trial, Stop Nilotinib (NILSt), was to examine the safety and efficacy of discontinuation of nilotinib in patients with chronic phase (CP)-chronic myelogenous leukemia (CML). Patients with CP-CML who had achieved molecular response (MR4.5) after initiation of imatinib or nilotinib therapy received consolidation therapy with nilotinib 300-400 mg twice daily for up to 24 months. Patients who maintained MR4.5 at 24 months of consolidation therapy proceeded to discontinuation of nilotinib. The study enrolled 149 patients; 112 patients proceeded to consolidation therapy with nilotinib; 90 patients maintained MR4.5 with consolidation therapy, and 87 proceeded to discontinuation of nilotinib. The treatment-free remission (TFR) (MR4.5) rate at both 1 and 3 years after discontinuation of nilotinib was the same, at 60.9% (90% CI 51.6-69.7). Among 34 patients with molecular relapse, nilotinib was resumed in 33 patients; all of them attained MR4.5. There was no significant association between molecular relapse and age, sex, Sokal score, previous interferon-α exposure, duration of tyrosine kinase inhibitors treatment, or trough concentration of nilotinib. With nilotinib, it might be possible to avoid prognostic factors for TFR that exist with imatinib discontinuation. Cessation of nilotinib after two years of consolidation was safe and feasible.Trial registration UMIN000007141. - Shoko Nakayama; Yasuyoshi Morita; Jorge Luis Espinoza; Shinya Rai; Yasuyo Oyama; Takahide Taniguchi; Yoshiaki Miyake; Hirokazu Tanaka; Itaru MatsumuraLeukemia & lymphoma 62 2 1 - 3 2019年09月 [査読有り]
- 田中 宏和; 松村 到腫瘍内科 = Clinical oncology 24 3 276 - 284 科学評論社 2019年09月 [査読有り]
- Shigeru Kawai; Takeshi Okuda; Ayano Fukui; Yasuhiro Sanada; Keisuke Yoshikawa; Miyuki Morikawa; Motoi Kuwahara; Osamu Maenishi; Yasuyoshi Morita; Shuichi Izumoto; Amami Kato; Itaru Matsumura; Susumu KusunokiInternal medicine (Tokyo, Japan) 58 14 2085 - 2089 2019年07月 [査読有り]
Intravascular lymphoma (IVL) is a malignant lymphoma that lacks the expression of cell surface adhesion molecules so that cells fluidly migrate within the blood vessels. The patient in the present study had restricted eye movement caused by IVL, mimicking a cavernous sinus tumor. Because the cavernous sinus lumen is divided into multiple compartments by trabeculae and venous channels, IVL tumor cells were trapped in these compartments, thus forming a mass, which subsequently extended into the contralateral cavernous sinus via the anterior and posterior intercavernous sinuses. This is a rare case of IVL forming a mass inside the cavernous sinus. - Masashi Kono; Toshiharu Sakurai; Kazuki Okamoto; Tomoyuki Nagai; Yoriaki Komeda; Hiroshi Kashida; Kosuke Minaga; Ken Kamata; Mamoru Takenaka; Satoru Hagiwara; Tomohiro Watanabe; Naoshi Nishida; Eisuke Enoki; Hiroaki Inoue; Itaru Matsumura; Masatoshi KudoInternal medicine (Tokyo, Japan) 58 14 2029 - 2033 2019年07月 [査読有り]
Autoimmune diseases including inflammatory bowel disease (IBD) occur in association with myelodysplastic syndrome (MDS). MDS-associated IBD frequently demonstrates a complicated course. We herein report the first case with MDS-associated IBD that was successfully treated with ustekinumab (UST), an anti-interleukin (IL) 12/23p40 monoclonal antibody. A 63-year-old man with a 7-year history of MDS was referred for examination of diarrhea, abdominal pain and fever. A blood examination revealed a marked elevation of C-reactive protein. Colonoscopy showed multiple ulcers in the terminal ileum. He was resistant to anti-tumor necrosis factor (TNF)-α antibody and azacitidine. Subsequently, UST treatment reduced colonic IL-17 and IL-6 expression and the patient currently maintains a state of remission. - 岩田 吉生; 森田 泰慶; 辻 潔; 頼 晋也; 田崎 貴之; 井上 宏昭; 谷口 康博; 藤本 昂; 田中 宏和; 芦田 隆司; 加藤 天美; 松村 到PNH Frontier 6 46 - 49 (株)メディカルレビュー社 2019年07月症例は35歳女性で、17歳時に再生不良性貧血-発作性夜間ヘモグロビン尿症(PNH)症候群と診断され、無治療で経過観察されていた。今回、感冒症状が出現し、全身倦怠感・褐色尿などの増悪を認めていた。自室で昏睡状態になっているのを家人が発見し救急要請された。頭部CTでは脳の正中偏移を伴う左前頭葉脳浮腫所見を認め、CT Venographyで上矢状静脈洞の描出欠損を認めた。以上より、上矢状静脈洞血栓症による脳梗塞に起因する意識障害と診断され緊急入院となった。第1病日夜間に意識レベル低下、瞳孔不同の症状が出現し、頭部CTで左前頭葉脳浮腫の増悪を認めたため、緊急開頭減圧術を実施した。さらに、術後侵襲による補体活性化と溶血再燃を抑制する目的で、術後第2病日に髄膜炎菌ワクチンとエクリズマブ投与を開始した。ワルファリンとエクリズマブ投与を継続し、溶血発作の再燃を認めることはなく、第53病日に退院となった。
- Isao Yoshida; Kazuo Tamura; Toshihiro Miyamoto; Mototsugu Shimokawa; Yasushi Takamatsu; Yasuhito Nanya; Itaru Matsumura; Moritaka Gotoh; Tadahiko Igarashi; Tsutomu Takahashi; Keisuke Aiba; Kyoya Kumagai; Kenichi Ishizawa; Naoki Kurita; Noriko Usui; Kiyohiko HatakeIN VIVO 33 4 1355 - 1362 2019年07月 [査読有り]
Background/Aim: Although neurokinin- 1 receptor antagonists are approved chemotherapy drugs in Japan, no nationwide surveys have been performed to validate chemotherapy-induced nausea and vomiting (CINV) guidelines in clinical practice. This study evaluated CINV in patients with haematological malignancies starting first-time chemotherapy. Patients and Methods: A nationwide CINV survey on patients with haematological malignancies was conducted at 118 institutions. Patients undergoing moderately emetic chemotherapy (n=17) and highly emetic chemotherapy (HEC; n=180) were compared. Results: Forty-one patients undergoing HEC received triple antiemetics. Female gender and young age were risk factors for early-phase nausea, while female gender remained a risk factor for late-phase nausea and vomiting. Among 125 patients receiving CHOP (doxorubicin, cyclophosphamide, vincristine, prednisone)-like regimens, complete response and complete control were increased in patients receiving triple antiemetics, compared to those with double antiemetics. Conclusion: Guideline compliance was very low. Although not statistically significant, there was a trend for reduced CINV and improved disease control for triple versus double antiemetics, suggesting that triple antiemetics should be considered for HEC, especially in young female patients with non-Hodgkin lymphoma receiving CHOP-like regimens. - Takehiko Mori; Yasushi Onishi; Yukiyasu Ozawa; Chiaki Kato; Tatsuyuki Kai; Yoshinobu Kanda; Mineo Kurokawa; Masatsugu Tanaka; Takashi Ashida; Yasushi Sawayama; Takahiro Fukuda; Tatsuo Ichinohe; Yoshiko Atsuta; Hirohito YamazakiInternational journal of hematology 109 6 711 - 717 2019年06月 [査読有り]
Outcomes of allogeneic hematopoietic stem cell transplantation (HSCT) for hepatitis-associated aplastic anemia have not been fully evaluated. In the present study, the outcomes of 37 adult patients with hepatitis-associated aplastic anemia who underwent allogeneic HSCT were retrospectively analyzed using the registry database of Japan Society for Hematopoietic Cell Transplantation. The median age of the patients was 24 years (range, 16-61). The median period between diagnosis of hepatitis-associated aplastic anemia and HSCT was 6.0 months (range, 0.5-430.8). Stem cell sources were bone marrow (N = 19) or peripheral blood stem cells (N = 5) from an HLA-identical sibling or bone marrow (N = 11) and cord blood (N = 2) from an unrelated donor. The majority of conditioning regimens were fludarabine-based or high-dose cyclophosphamide-based. In all but 2 cases of early death, neutrophil engraftment was achieved. At the time of analysis, 32 patients were alive, with a median follow-up of 54.1 months. Five-year overall and failure-free survival rates were 86.0% (95% CI, 69.4-93.9%) and 75.0% (95% CI, 57.4-86.2%), respectively. Despite the heterogeneity in transplant procedures in a small number of patients, these results suggest that allogeneic HSCT is safe for use in hepatitis-associated aplastic anemia with a low rate of transplant-related mortality. - 松村 到日本病院薬剤師会雑誌 55 6 707 - 711 (一社)日本病院薬剤師会 2019年06月
- 田中 宏和; 松村 到血液内科 78 5 579 - 586 (有)科学評論社 2019年05月
- 松村 到血液内科 78 5 605 - 611 (有)科学評論社 2019年05月
- 田中 宏和; 松村 到血液内科 78 5 579 - 586 (有)科学評論社 2019年05月
- Masahiro Kizaki; Naoto Takahashi; Noriyoshi Iriyama; Shinichiro Okamoto; Takaaki Ono; Noriko Usui; Koiti Inokuchi; Chiaki Nakaseko; Mineo Kurokawa; Masahiko Sumi; Fumihiko Nakamura; Tatsuya Kawaguchi; Ritsuro Suzuki; Kazuhito Yamamoto; Kazunori Ohnishi; Itaru Matsumura; Tomoki NaoeInternational journal of hematology 109 4 426 - 439 2019年04月 [査読有り]
We report the results of a multicenter observational study using the New TARGET system, in which the effectiveness and safety of tyrosine kinase inhibitors (TKIs) were evaluated in newly diagnosed chronic-phase chronic myeloid leukemia (CML) patients. A total of 506 patients were enrolled between April 2010 and March 2013. Median age was 56 (range 18-92) years; 35% of patients were females. As the first-line therapy, 139 (27.9%), 169 (33.9%) and 144 (28.9%) patients were treated with imatinib, nilotinib, and dasatinib, respectively. Five-year progression-free survival (PFS) and overall survival (OS) were 93.8% and 94.5%, respectively. The OS curve was significantly superior for patients treated with second-generation TKIs than imatinib (P = 0.0068), and an early molecular response (EMR) at 3 months (BCR-ABL1 < 10%) was detected in 328 of 377 patients evaluated for molecular response. The PFS curve was significantly superior for patients with EMR than without (P < 0.0001). Although 12 patients experienced vascular adverse events, no new safety issues were observed in patients with adverse events. The results of this observational study demonstrated that treating newly diagnosed CML-CP patients with TKI results in satisfactory and reliable outcomes. - Hirokazu Tanaka; J Luis Espinoza; Ryosuke Fujiwara; Shinya Rai; Yasuyoshi Morita; Takashi Ashida; Yuzuru Kanakura; Itaru MatsumuraCells 8 3 2019年03月 [査読有り]
Iron overload is the accumulation of excess iron in the body that may occur as a result of various genetic disorders or as a consequence of repeated blood transfusions. The surplus iron is then stored in the liver, pancreas, heart and other organs, which may lead to chronic liver disease or cirrhosis, diabetes and heart disease, respectively. In addition, excessive iron may impair hematopoiesis, although the mechanisms of this deleterious effect is not entirely known. In this study, we found that ferrous ammonium sulfate (FeAS), induced growth arrest and apoptosis in immature hematopoietic cells, which was mediated via reactive oxygen species (ROS) activation of p38MAPK and JNK pathways. In in vitro hematopoiesis derived from embryonic stem cells (ES cells), FeAS enhanced the development of dysplastic erythroblasts but inhibited their terminal differentiation; in contrast, it had little effect on the development of granulocytes, megakaryocytes, and B lymphocytes. In addition to its directs effects on hematopoietic cells, iron overload altered the expression of several adhesion molecules on stromal cells and impaired the cytokine production profile of these cells. Therefore, excessive iron would affect whole hematopoiesis by inflicting vicious effects on both immature hematopoietic cells and stromal cells. - Satoshi Yamasaki; Dai Chihara; Sung-Won Kim; Takahito Kawata; Shuichi Mizuta; Hiroatsu Ago; Takaaki Chou; Takahisa Yamane; Hitoji Uchiyama; Tatsuo Oyake; Katsuhiro Miura; Bungo Saito; Hirofumi Taji; Hirohisa Nakamae; Toshihiro Miyamoto; Takahiro Fukuda; Junya Kanda; Yoshiko Atsuta; Ritsuro SuzukiInternational journal of hematology 109 2 175 - 186 2019年02月 [査読有り]
High-dose chemotherapy with autologous stem cell transplantation (HDC-ASCT) is an option for patients with peripheral T-cell lymphoma (PTCL); however, neither prospective nor retrospective studies support proceeding with ASCT upfront, and the timing of HDC-ASCT remains controversial. We retrospectively analyzed the risk factors for outcomes of 570 patients with PTCL, including PTCL not otherwise specified (PTCL-NOS) and angioimmunoblastic T-cell lymphoma (AITL), who received ASCT for frontline consolidation (n = 98 and 75, respectively) or alternative therapies after either relapse (n = 112 and 75) or primary induction failure (PIF; n = 127 and 83) between 2000 and 2015. Significant risk factors for overall survival (OS) after upfront ASCT were a ≥ 2 prognostic index for T-cell lymphoma (P < 0.001) and partial response (PR) at ASCT (P = 0.041) in PTCL-NOS patients, and > 60 years of age (P = 0.0028) and PR at ASCT (P = 0.0013) in AITL patients. Performance status of ≥ 2 at ASCT (P < 0.001), receiving ≥ 3 regimens before ASCT (P = 0.018), and PR at ASCT (P = 0.018) in PTCL-NOS patients and > 60 years of age at ASCT (P = 0.0077) in AITL patients were risk factors for OS after ASCT with a chemosensitive PIF status. Strategies that carefully select PTCL patients may allow identification of individuals suitable for ASCT. - びまん性大細胞型B細胞性リンパ腫治療中にムーコル脳塞栓を発症した1例波江野 高大; 口分田 貴裕; 森田 泰慶; 芦田 隆司; 松村 到; 高島 康利; 木村 雅友臨床血液 60 1 66 - 66 (一社)日本血液学会-東京事務局 2019年01月
- 谷口 貴英; 中山 聖子; 森田 泰慶; 頼 晋也; 大山 泰世; 三宅 義昭; 田中 宏和; 辰巳 陽一; 芦田 隆司; 松村 到臨床血液 60 1 65 - 66 (一社)日本血液学会-東京事務局 2019年01月
- 宮崎泰司; 宮崎泰司; 松村到; 松村到; 清井仁; 清井仁月刊腫瘍内科 23 2 88 - 93 (有)科学評論社 2019年
- Sakai K; Nozaki Y; Murao Y; Yano T; Ri J; Niki K; Kinoshita K; Funauchi M; Matsumura ILaboratory investigation; a journal of technical methods and pathology 99 5 671 - 683 2019年01月 [査読有り]
Interleukin (IL)-10, a cytokine with anti-inflammatory effects, is produced by blood cells and cells of various organs. Ischemia-reperfusion injury (IRI) is a systemic inflammatory disease caused by a systemic circulation of pro-inflammatory cytokines and chemokines produced from blood cells or organs damaged by ischemia. Apoptosis, a key event after IRI, is correlated with the degree of injury. Here we investigated the effects and mechanism of IL-10 in renal IRI. Compared to wild-type (WT) mice with a renal IRI, IL-10 knockout (IL-10 KO) mice with IRI demonstrated decreased renal function as represented by blood urea nitrogen and serum creatinine, upregulated early acute kidney injury (AKI) biomarkers such as kidney injury molecule-1 (Kim-1), increased mRNA expression of the pro-inflammatory cytokines IL-1β, IL-6, and IL-18 and a chemokine (regulated on activation, normal T cell expressed and secreted; RANTES), and increased expression of the pro-apoptosis factors Bax and cleaved caspase-3. When tubular epithelial cells (TECs) from IL-10 KO mice were put in a hypoxic state and added with recombinant IL-10, their expression of Bax decreased. Our findings demonstrated that IL-10 suppressed the production of pro-inflammatory cytokines, renal dysfunction, and the expression of pro-apoptosis factors after IRI. - Nozaki Y; Inoue A; Kinoshita K; Funauchi M; Matsumura IModern rheumatology 30 2 1 - 23 2019年01月 [査読有り]
Objectives: We retrospectively evaluated the retention rate and clinical responses following treatment for rheumatoid arthritis (RA) with iguratimod (IGU) vs. salazosulfapyridine (SASP) as the first-line conventional synthetic disease-modifying antirheumatic drug (csDMARD).Methods: We analyzed 197 RA patients who were treated with IGU or SASP as the initial treatment in the 3-year study period. The retention rate, clinical response, the dosage and percent user of prednisolone (PSL), and safety profiles were evaluated.Results: At month 36, the retention rates of the IGU and SASP groups were 52.4 vs. 32.1%. The rate of responders (good or moderate response) at month 36 was 85.8 vs. 65.2% in the IGU and SASP groups, respectively. At month 36 for the IGU and SASP groups, the percentages of PSL users were 16.7 vs. 46.7%, and the PSL dosage was 0.3 mg/d vs. 2.0 mg/d, respectively. The cumulative rates of any adverse event (AE) at month 36 were 19.8 vs. 29.2% in the IGU and SASP groups, respectively.Conclusion: IGU is a useful first-line csDMARD treatment for RA patients, showing a high retention rate and good efficacy without an increased risk of serious AEs, including serious infections. Our findings also indicate a PSL dose-sparing effect of IGU treatment. - Nakayama S; Taniguchi T; Tanaka H; Espinoza JL; Rai S; Matsumura IBritish journal of haematology 184 2 122 - 122 2019年01月 [査読有り]
- Takahide Taniguchi; Shoko Nakayama; Yasuyoshi Morita; Shinya Rai; Jorge L. Espinoza; Itaru MatsumuraBRITISH JOURNAL OF HAEMATOLOGY 184 2 121 - 121 2019年01月 [査読有り]
- Kawashima N; Akashi A; Nagata Y; Kihara R; Ishikawa Y; Asou N; Ohtake S; Miyawaki S; Sakura T; Ozawa Y; Usui N; Kanamori H; Ito Y; Imai K; Suehiro Y; Kitamura K; Sakaida E; Takeshita A; Suzushima H; Naoe T; Matsumura I; Miyazaki Y; Ogawa S; Kiyoi H; Japan Adult Leukemia Study Group (JALSGAnnals of hematology 98 1 83 - 91 2019年01月 [査読有り]
- 窪田 愛恵; 伊木 雅之; 赤木 將男; 松村 到; 池田 行宏; 甲田 勝康; 岡田 満; 三井 良之; 奥村 二郎; 平出 敦近畿大学医学雑誌 43 3-4 111 - 115 近畿大学医学会 2018年12月本学出身の研修医が、本学以外の医療機関でどのように評価されているかを調査した。方法としては、本学の卒業生が研修する医療機関にアンケートを郵送し、臨床研修センター長もしくは研修担当の医師から回答いただき、その内容を分析した。卒業時までに修得すべき本学のアウトカム10項目のうち、「コミュニケーション能力」については、回答を寄せた27病院のうち21病院で、本学出身の研修医がよくできていると評価された。また、「チーム医療」に関しても「チームに溶け込む」といった表現で代表されるように、評価が高かった。一方、不十分であると評価された項目で最も頻度が高かったのは「国際化に対応できる教養と英語力」であり、7病院がとりあげていた。記述回答をテキストマイニングの手法で感性分析したところ、本学の全般的なイメージについては本学出身の研修医や医師に関する印象をあげた記載が多かった。内容としては、好感がもてる、元気、明るいというポジティブな表現が多かった。ネガティブな表現は少なかったが、本学出身者が学術活動に消極的という回答が該当した。これらの結果は今後の本学の教育プログラムを改善していく上で、貴重な資料になると考えられる。(著者抄録)
- 谷口 康博; 松村 到腫瘍内科 22 6 658 - 666 (有)科学評論社 2018年12月
- 松村 到腫瘍内科 22 6 692 - 699 (有)科学評論社 2018年12月
- Li JF; Dai YT; Lilljebjörn H; Shen SH; Cui BW; Bai L; Liu YF; Qian MX; Kubota Y; Kiyoi H; Matsumura I; Miyazaki Y; Olsson L; Tan AM; Ariffin H; Chen J; Takita J; Yasuda T; Mano H; Johansson B; Yang JJ; Yeoh AE; Hayakawa F; Chen Z; Pui CH; Fioretos T; Chen SJ; Huang JYProceedings of the National Academy of Sciences of the United States of America 115 50 E11711 - E11720 2018年12月 [査読有り]
- Takeshita Akihiro; Asou Norio; Atsuta Yoshiko; Furumaki Hiroaki; Sakura Toru; Ueda Yasunori; Sawa Masashi; Dobashi Nobuaki; Suzuki Rikio; Taniguchi Yasuhiro; Nakagawa Masaru; Tamaki Shigehisa; Hagihara Maki; Fujimaki Katsumichi; Yokoyama Yasuhisa; Fujita Hiroyuki; Yanada Masamitsu; Maeda Yoshinobu; Usui Noriko; Kobayashi Yukio; Kiyoi Hitoshi; Ohtake Shigeki; Matsumura Itaru; Naoe Tomoki; Miyazaki YasushiBLOOD 132 2018年11月 [査読有り]
- Kawashima, Naomi; Ishikawa, Yuichi; Atsuta, Yoshiko; Sugiura, Isamu; Sawa, Masashi; Dobashi, Nobuaki; Yokoyama, Hisayuki; Doki, Noriko; Tomita, Akihiro; Kiguchi, Toru; Koh, Shiro; Kanamori, Heiwa; Iriyama, Noriyoshi; Kohno, Akio; Moriuchi, Yukiyoshi; Asada, Noboru; Hirano, Daiki; Togitani, Kazuto; Sakura, Toru; Hagihara, Maki; Tomikawa, Tatsuki; Yokoyama, Yasuhisa; Asou, Norio; Ohtake, Shigeki; Matsumura, Itaru; Miyazaki, Yasushi; Naoe, Tomoki; Kiyoi, HitoshiBLOOD 132 1 AMER SOC HEMATOLOGY 2018年11月0
- Yoshiaki Tomiyama; Jun Ho Jang; Jong-Wook Lee; Koji Miyazaki; Koji Nagafuji; Kensuke Usuki; Nobuhiko Uoshima; Tomoaki Fujisaki; Hiroshi Kosugi; Itaru Matsumura; Ko Sasaki; Masahiro Kizaki; Masashi Sawa; Michihiro Hidaka; Naoki Kobayashi; Satoshi Ichikawa; Yuji Yonemura; Hiroyuki Keta; Akira Matsuda; Keiya Ozawa; Kinuko Mitani; Shinji NakaoBLOOD 132 2018年11月 [査読有り]
0 - Takahiko Yasuda; Dai Nishijima; Shinya Kojima; Masahito Kawazu; Toshihide Ueno; Shinobu Tsuzuki; Hitoshi Kiyoi; Itaru Matsumura; Yasushi Miyazaki; Keizo Horibe; Hiroyuki Mano; Tomoki Naoe; Masashi Sanada; Fumihiko HayakawaBLOOD 132 2018年11月 [査読有り]
0 - Anas Younes; Laurie H. Sehn; Peter Johnson; Pier Luigi Zinzani; Xiaonan Hong; Jun Zhu; Olga Samoilova; Cheolwon Suh; Itaru Matsumura; Andres Lopez-Hernandez; Ulrich Duehrsen; Catherine Thieblemont; Jodi Carey; Grace Liu; S. Martin Shreeve; Steven Sun; Jessica Vermeulen; Louis M. Staudt; Wyndham H. WilsonBLOOD 132 2018年11月 [査読有り]
0 - A 5-day regimen of azacitidine for lower-risk myelodysplastic syndromes (RA or RARS): a prospective single-arm phase 2 trial.Morita Y; Maeda Y; Yamaguchi T; Urase F; Kawata S; Hanamoto H; Tsubaki K; Ishikawa J; Shibayama H; Matsumura I; Matsuda MCancer Science 2018年10月 [査読有り]
- 異常なRTKの細胞内輸送阻害は急性骨髄性白血病における有望な治療標的である頼 晋也; 田中宏和; 鈴木麻衣; Luis Espinoza; 谷村 朗; 森田泰慶; 辰巳陽一; 横田貴史; 織谷健司; 渡邊俊雄; 金倉 譲; 松村 到第80回日本血液学会学術集会 2018年10月 [査読有り]
- KMFに登録されたボルテゾミブとIMiDs両剤に抵抗性の再発骨髄腫の予後解析藤原亮介; 田中宏和; 芹澤憲太郎; 金子仁臣; 志村勇司; 太田健介; 淵田真一; 中谷 綾; 諫田淳也; 八木秀男; 和田勝也; 小杉智; 魚嶋伸彦; 柴山浩彦; 小原尚恵; 中谷英仁; 内山人二; 足立陽子; 飯田正人; 濱田常義; 松田光弘; 高折晃史; 野村昌作; 島崎千尋; 日野雅之; 黒田純也; 谷脇雅史; 今田和典; 金倉譲; 松村到第80回日本血液学会学術集会 2018年10月 [査読有り]
- 形質細胞腫の後方視的多施設共同研究(関西骨髄腫フォーラム)中谷 綾; 田中宏和; 八木秀男; 太田健介; 柴山浩彦; 諫田淳也; 新堂真紀; 志村勇司; 小杉 智; 木田 亨; 金子仁臣; 今田和典; 烏野隆博; 松田光弘; 飯田正人; 足立陽子; 淵田真一; 魚嶋伸彦; 内山人二; 高橋良一; 松井利充; 和田勝也; 清田実希; 島崎 千尋; 日野雅之; 黒田純也; 金倉 譲; 高折晃史; 野村昌作; 松村到第80回日本血液学会学術集会 2018年10月 [査読有り]
- 症候性骨髄腫1414例の後方視的解析:関西骨髄腫フォーラムからの最新報告田中宏和; 芹澤憲太郎; 中谷 綾; 金子仁臣; 太田健介; 小杉 智; 八木秀男; 花本 仁; 淵田真一; 志村勇司; 柴山浩彦; 小原尚恵; 中谷英仁; 諫田淳也; 魚嶋伸彦; 和田勝也; 烏野隆博; 松井利充; 内山人二; 松田光弘; 足立陽子; 高折晃史; 黒田純也; 谷脇雅史; 島崎千尋; 日野雅之; 今田和典; 野村昌作; 金倉 譲; 松村 到第80回日本血液学会学術集会 2018年10月 [査読有り]
- RRMM患者に対するKRD療法およびKD療法の後方視的解析(関西骨髄腫フォーラム)恩田佳幸; 諫田淳也; 金子仁臣; 柴山浩彦; 志村勇司; 太田健介; 田中宏和; 淵田真一; 中谷 綾; 魚嶋伸彦; 小杉 智; 松田光弘; 足立陽子; 八木秀男; 内山人二; 新堂真紀; 今田和典; 日野雅之; 野村昌作; 島崎千尋; 黒田純也; 金倉 譲; 高折晃史; 松村 到第80回日本血液学会学術集会 2018年10月 [査読有り]
- サリドマイド単剤治療を施行した症候性骨髄腫230例の後方視的解析(関西骨髄腫フォーラム)金子仁臣; 柴山浩彦; 八木秀男; 諫田淳也; 中谷 綾; 小杉 智; 木田 亨; 田中宏和; 志村勇司; 淵田真一; 足立陽子; 和田勝也; 清田実希; 魚嶋伸彦; 太田健介; 小原尚恵; 濱田常義; 小林正行; 内山人二; 烏野隆博; 黒田純也; 今田和典; 高折晃史; 島崎千尋; 金倉 譲; 日野雅之; 野村昌作; 松村 到第80回日本血液学会学術集会 2018年10月 [査読有り]
- Satoshi Yamasaki; Dai Chihara; Sung-Won Kim; Koji Izutsu; Kouji Iwato; Takahiro Fukuda; Naoyuki Uchida; Itsuto Amano; Hideyuki Nakazawa; Junya Kuroda; Hisako Hashimoto; Tatsuo Ichinohe; Yoshinobu Kanda; Yoshiko Atsuta; Junji Suzumiya; Ritsuro SuzukiAnnals of hematology 97 10 2013 - 2014 2018年10月 [査読有り]
The original version of this article contained a mistake in fig. 1a. "Autologous HCT(n=111)" should be changed to "Allogeneic HCT (n=51)". Correct figure is presented below. - Yasuyoshi Morita; Yasuhiro Maeda; Terufumi Yamaguchi; Fumiaki Urase; Shuhei Kawata; Hitoshi Hanamoto; Kazuo Tsubaki; Jun Ishikawa; Hirohiko Shibayama; Itaru Matsumura; Mitsuhiro MatsudaCancer science 109 10 3209 - 3215 2018年10月 [査読有り]
Although azacitidine is the first-line drug for higher-risk myelodysplastic syndrome (MDS) patients, its efficacy for lower-risk MDS remains unestablished. Therefore, we conducted a prospective study to examine the efficacy and safety of a 5-day regimen of azacitidine (AZA-5) for lower-risk MDS. The primary endpoint was hematological improvement (HI) after 4 courses of therapy. A total of 51 patients with lower-risk MDS based on the French-American-British (FAB) classification (44 patients with refractory anemia [RA] and 7 patients with refractory anemia with ringed sideroblasts [RARS]) were enrolled from 6 centers in Japan. The median age was 75 years (range: 51-88). These patients received AZA-5 (75 mg/m2 ; once daily for 5 sequential days). The median number of AZA-5 courses was 8 (range: 1-57), and 45 patients (88.2%) received more than 4 courses. HI and transfusion independency were seen in 24 patients (47.1%) and 11 patients (39.2%), respectively. A total of 11 patients (21.6%) achieved complete remission or marrow remission. WT1 mRNA levels were not significantly correlated with therapy response. Grade 3 or 4 neutropenia and thrombocytopenia occurred in 26 (51.0%) and 11 (21.5%) patients, respectively. Nonhematological grade 3 or 4 adverse events were observed in 9 patients (17.6%). Together, these results indicate that AZA-5 is feasible and effective for lower-risk MDS patients as well as for higher-risk MDS patients. - 平瀬 主税; 松村 到日本血栓止血学会誌 29 5 473 - 486 (一社)日本血栓止血学会 2018年10月現在、抗悪性腫瘍剤として臨床応用されているチロシンキナーゼ阻害薬(TKI)の多くは、阻害すべき標的分子に加えて、種々のoff-target分子を阻害することが知られている。慢性骨髄性白血病(CML)に対するTKI治療では、標的であるBCR-ABL以外に血管新生等に関与する血管内皮細胞、血小板、マクロファージ、肥満細胞等に発現しているoff-targetが阻害されることにより、様々な心血管イベント(CVE)としての血栓塞栓症が発症する。その劇的かつ持続的な臨床的有用性のため、CMLに対するTKI投与は、長期間となり、治療継続に問題となるCVE等に関する知見も蓄積されている。CMLの治療では、TKI投与開始前に、十分な糖尿病、高血圧等の心血管系のリスク評価を行い、投与開始後は心電図、心エコーなどの適切なモニタリングを継続的に実施する必要がある。(著者抄録)
- Shinya Rai; Hirokazu Tanaka; Ko Fujimoto; Takahiro Kumode; Hiroaki Inoue; Yasuhiro Taniguchi; Yasuyoshi Morita; J Luis Espinoza; Yoichi Tatsumi; Takashi Ashida; Ryota Matsuoka; Yukie Yara Kikuti; Naoya Nakamura; Itaru MatsumuraCancers 10 9 2018年09月 [査読有り]
A 62-year-old male was diagnosed with chronic lymphocytic leukemia (CLL) and treated with a fludarabine-containing regimen which maintained the disease in a partial response. Nine years after diagnosis, a rapidly growing systemic lymphadenopathy was observed, and a biopsy specimen revealed the presence of typical Hodgkin/Reed-Sternberg (HRS) cells, surrounded by T-lymphocytes and CLL cells. Sequencing analysis of the germline complementary determining region 3 (CDR3) region of the immunoglobulin heavy chain (IGH) gene showed that the Hodgkin/Reed-Sternberg cells were clonally unrelated to the preexisting CLL cells and the HRS cells were composed of five different clones, leading to the molecular diagnosis of de novo lymphocyte-rich classic Hodgkin lymphoproliferative diseases (LPDs) with small lymphocytic lymphoma (SLL). As the initial treatment was neither effective for classic Hodgkin LPDs nor for SLL, Bendamustine, Rituximab (BR) was started and complete remission was achieved, which has continued for more than one year so far. BR may be a good therapeutic option for both entities without causing hematological toxicity. - 松村 到臨床血液 59 9 1405 - 1405 2018年09月
- Prognostic Analysis According to the 2017 ELN Risk Stratification by Genetics in Adult Acute Myeloid Leukemia Patients Treated in The Japan Adult Leukemia Study Group (JALSG) AML201 studyHarada Yasuhiko; Nagata Yasunobu; Kihara Rika; Ishikawa Yuichi; Asou Norio; Ohtake Shigeki; Miyawaki Shuichi; Sakura Toru; Ozawa Yukiyasu; Usui Noriko; Kanamori Heiwa; Ito Yoshikazu; Imai Kiyotoshi; Suehiro Youko; Kobayashi Shinichi; Kitamura Kunio; Sakaida Emiko; Onizuka Makoto; Takeshita Akihiro; Ishida Fumihiro; Suzushima Hitoshi; Ishizawa Kenichi; Naoe Tomoki; Matsumura Itaru; Miyazaki Yasushi; Ogawa Seishi; Kiyoi HitoshiCLINICAL LYMPHOMA MYELOMA & LEUKEMIA 18 S196-S196 2018年09月 [査読有り]
- Espinoza JL; Ai S; Matsumura IPathogens (Basel, Switzerland) 7 3 2018年09月 [査読有り]
- Nozaki Y; Ri J; Sakai K; Shiga T; Inoue A; Nagare Y; Funauchi M; Matsumura IImmunological medicine 41 3 129 - 135 2018年09月 [査読有り]
OBJECTIVE: Ultrasound (US) is more sensitive and reliable than a clinical examination, and is better correlated with the disease activity in rheumatoid arthritis (RA). We conducted the present study to assess the value of US as a screening tool to predict therapeutic responses in RA patients treated with anti-tumor necrosis factor (TNF) drugs. METHODS: We retrospectively analyzed the cases of 86 consecutive RA patients who were classified by their DAS28-CRP scores at the 54th week. We assessed two US findings (i.e., the synovial hypertrophy index [SHI] and synovial vascularization) by grey-scale imaging and the Doppler synovitis index (DSI). RESULTS: When we applied cut-off points determined by a ROC curve analysis, patients with a lower total SHI (≤34) or DSI (≤7) at baseline were significantly more likely to reach remission (44 patients, 51.2%) as shown by the DAS28-CRP at 54 weeks. On the basis of these cut-off values, we dichotomized all variables and performed a logistic regression analysis using the 54-weeks data; the only predictive factors of remission with anti-TNF therapy were the patients' baseline DAS28-CRP ≤2.7 as low disease activity/remission, and the SHI. CONCLUSION: An ultrasound assessment would be a highly useful predictor of the achievement of clinical remission. - Satoshi Yamasaki; Dai Chihara; Sung-Won Kim; Koji Izutsu; Kouji Iwato; Takahiro Fukuda; Naoyuki Uchida; Itsuto Amano; Hideyuki Nakazawa; Junya Kuroda; Hisako Hashimoto; Tatsuo Ichinohe; Yoshinobu Kanda; Yoshiko Atsuta; Junji Suzumiya; Ritsuro SuzukiAnnals of hematology 97 8 1445 - 1452 2018年08月 [査読有り]
Rituximab has been shown to improve outcomes in patients with B-cell lymphoma. However, patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL) still have a poor prognosis, and the choice between high-dose therapy with autologous hematopoietic cell transplantation (HCT) and allogeneic HCT remains controversial in these patients. We retrospectively analyzed the risk factors for outcomes in 162 R/R MCL patients who received autologous (n = 111) or allogeneic (n = 51) HCT between 2004 and 2014. The median overall survival (OS) rates were 48 and 65 months in the autologous and allogeneic HCT groups, respectively (P = 0.20). Significant risk factors for overall survival in R/R MCL patients after autologous HCT were > 60 years of age at HCT (P = 0.017), higher score of HCT-specific comorbidity index at HCT (P = 0.033), and receiving MCEC (ranimustine + carboplatin + etoposide + cyclophosphamide) regimen (P = 0.017), while higher performance status at HCT (P = 0.011) and longer interval from diagnosis to HCT (P = 0.0054) were risk factors after allogeneic HCT. Strategies that carefully select R/R MCL patients for autologous HCT may allow the identification of individuals suitable for allogeneic HCT. - Takeshita A; Asou N; Atsuta Y; Sakura T; Ueda Y; Sawa M; Dobashi N; Taniguchi Y; Suzuki R; Nakagawa M; Tamaki S; Hagihara M; Fujimaki K; Furumaki H; Obata Y; Fujita H; Yanada M; Maeda Y; Usui N; Kobayashi Y; Kiyoi H; Ohtake S; Matsumura I; Naoe T; Miyazaki Y; the Japanese Adult Leukemia; Study GroupLeukemia 33 2 358 - 370 2018年08月 [査読有り]
Between April 2004 and December 2010, we conducted a prospective randomized controlled study comparing tamibarotene with all-trans retinoic acid (ATRA) in the maintenance therapy of newly diagnosed acute promyelocytic leukemia (APL), and here report the final results of this study with a median follow-up of 7.3 years. Of 344 eligible patients who had received ATRA and chemotherapy, 319 (93%) achieved complete remission (CR). After completion of three courses of consolidation chemotherapy, 269 patients in molecular remission underwent maintenance randomization, 135 to ATRA (45 mg/m2 daily), and 134 to tamibarotene (6 mg/m2 daily) for 14 days every 3 months for 2 years. The primary endpoint was relapse-free survival (RFS). The 7-year RFS was 84% in the ATRA arm and 93% in the tamibarotene arm (p = 0.027, HR = 0.44, 95% CI, 0.21 to 0.93). The difference was prominent in high-risk patients with initial leukocytes ≥ 10.0 × 109/L (62% vs. 89%; p = 0.034). Tamibarotene was significantly superior to ATRA by decreasing relapse in high-risk patients. Overall survival after randomization did not differ (96% vs. 97%; p = 0.520). Secondary hematopoietic disorders developed in nine patients, secondary malignancies in 11, and grade 3 or more late cardiac comorbidities in three. These late complications did not differ between the two arms. - 頼 晋也; 松村 到日本内科学会雑誌 107 7 1316 - 1323 (一社)日本内科学会 2018年07月
- Nakayama S; Matsuda M; Adachi T; Sueda S; Ohashi Y; Awaji S; Hashimoto S; Matsumura IPlatelets 30 5 1 - 9 2018年07月 [査読有り]
- Sueda S; Nakayama S; Adachi T; Ohashi Y; Awaji S; Hashimoto S; Matsumura I; Matsuda MAnnals of hematology 2018年07月 [査読有り]
- Kato R; Hayashi H; Sano K; Handa K; Kumode T; Ueda H; Okuno T; Kawakami H; Matsumura I; Kudo M; Nakagawa KJournal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 13 12 e239 - e241 2018年07月 [査読有り]
- 【分子標的薬の新しいバイオマーカー】 バイオマーカーの最近のtopics中川 和彦; 各務 博; 松村 到; 岩田 広治がん分子標的治療 16 2 146 - 153 (株)メディカルレビュー社 2018年07月分子標的薬や免疫チェックポイント阻害薬ががん治療に浸透していくなかで、より適切で効果的な治療開発に向け、バイオマーカーの研究も進んでいる。たとえば、免疫チェックポイント阻害薬においては、腫瘍細胞におけるPD-L1発現が進行非小細胞肺がんに対するペムブロリズマブのコンパニオン診断として使われている。しかしながら、がん種によってPD-L1発現のバイオマーカーとしての臨床的意義が異なっていたり、腫瘍細胞に発現するPD-L1が重要なのか、それとも腫瘍組織に浸潤した細胞傷害性Tリンパ球(CTL)に発現されるPD-L1か、どちらをみるべきかといった議論もあり、今後解決すべき課題は多い。一方で、腫瘍細胞のtumor mutation burdenやCD62Lが新たなバイオマーカーとして注目されている。一方、分子標的薬のバイオマーカーとしては、肺がん領域において上皮成長因子受容体(EGFR)の遺伝子変異やALK、ROS1、BRAFの融合遺伝子の有無が治療方針の決定に用いられている。最近では第3世代のEGFRチロシンキナーゼ阻害薬(TKI)であるオシメルチニブのコンパニオン診断としてEGFR遺伝子変異T790Mの臨床導入も行われている。血液がんでは慢性骨髄性白血病(CML)のBCR-ABL融合遺伝子がイマチニブ治療の診断薬ならびに効果判定の指標として使用されている。乳がんでは古くからエストロゲン受容体(ER)やプロゲステロン(PG)の蛋白発現の有無がホルモン療法の有効性のバイオマーカーとして用いられてきた。トラスツズマブ治療の診断薬の指標としてのヒト上皮成長因子受容体(HER)2蛋白の過剰発現は固形がんの分子標的治療の先駆けとして有名である。近年はPI3Kの遺伝子変異や生殖細胞のBRCA変異による患者選択が臨床開発されている。本座談会では、がん治療各領域におけるトップリーダーをお招きしてバイオマーカー研究の最近のtopicsを総括した。(著者抄録)
- Hideaki Kato; Hiroyuki Fujita; Nobu Akiyama; Shun-ichi Kimura; Nobuhiro Hiramoto; Naoko Hosono; Tsutomu Takahashi; Kazuyuki Shigeno; Hitoshi Minamiguchi; Junichi Miyatake; Hiroshi Handa; Yoshinobu Kanda; Minoru Yoshida; Shuichi Miyawaki; Shigeki Ohtake; Tomoki Naoe; Hitoshi Kiyoi; Itaru Matsumura; Yasushi Miyazaki; Japan Adult Leukemia Study GroupSupportive Care in Cancer 1 - 12 2018年06月 [査読有り]
Purpose: The Japan Adult Leukemia Study Group (JALSG) AML201 protocols are regimens for remission induction and consolidation chemotherapy of acute myeloid leukemia (AML) and have been widely accepted in Japan since 2001. Management of infectious complications during chemotherapy has a key role in the supportive care of AML patients. Methods: By using case report forms collected in December 2001 and December 2005, we retrospectively analyzed the infectious complications in adult patients treated by using the JALSG AML201 protocols against AML (excluding promyelocytic leukemia). Results: Of 980 patients, 80.2% experienced febrile neutropenia (FN), 8.3% bacteremia/fungemia, and 10.3% pulmonary infection at least once during remission-induction chemotherapy. Gram-positive bacteremia accounted for 65.1% of bacteremia/fungemia in 2001–2005, compared with 38.2% in 1987–1991 and 45.9% in 1992–1995. Of 750 patients, 81.9% experienced FN, 21.9% bacteremia/fungemia, and 9.1% pulmonary infection at least once during consolidation chemotherapy. During consolidation chemotherapy, bacteremia/fungemia and pulmonary infection were significantly more frequent in the high-dose cytarabine (HDAC) arm than in the conventional multiagent arm (25.9 vs. 17.9% and 12.7 vs. 7.7%, respectively). Invasive pulmonary aspergillosis accounted for 15.8% of pulmonary infections during remission induction and 19.7% during consolidation chemotherapy. Conclusions: Our data suggest that patterns of infectious complications have changed between 1987 and 2005, possibly because of chemoprophylaxis with oral fluoroquinolones and improved diagnosis of invasive pulmonary aspergillosis by serum antigen analysis. - Kohei Yamauchi; Naoki Oiso; Takashi Iwanaga; Yoichi Tatsumi; Itaru Matsumura; Yuji Tohda; Akira KawadaJOURNAL OF DERMATOLOGY 45 6 E150 - E151 2018年06月 [査読有り]
- Shoko Nakayama; Mitsuhiro Matsuda; Tatsuya Adachi; Sanae Sueda; Yuka Ohashi; Sumie Awaji; Shigeo Hashimoto; Itaru MatsumuraAnnals of Hematology 97 6 1095 - 1096 2018年06月 [査読有り]
- Junichi Miyatake; Hiroaki Inoue; Kentarou Serizawa; Yasuyoshi Morita; J L Espinoza; Hirokazu Tanaka; Takahiro Shimada; Yoichi Tatsumi; Takashi Ashida; Itaru MatsumuraInternal medicine (Tokyo, Japan) 57 10 1445 - 1453 2018年05月 [査読有り]
Patients with mycosis fungoides (MF), the most common subtype of primary cutaneous T-cell lymphoma, have an increased risk of developing secondary malignancies. We herein report two rare cases of MF concurring with diffuse large B cell lymphoma (B lymphoid lineage) and acute myeloid leukemia (myeloid lineage) in two otherwise healthy elderly patients. Potential etiologic factors, including the impact of the therapy-associated inflammatory response on the development of secondary tumors in patients with MF, are discussed. Further clinical, experimental and genetic studies are needed to elucidate possible physiopathogenic associations among the three concurrent malignancies occurring in the cases presented here. - Jun Ishikawa; Itaru Matsumura; Tatsuya Kawaguchi; Junya Kuroda; Hirohisa Nakamae; Toshihiro Miyamoto; Ken-Ichi Matsuoka; Hirohiko Shibayama; Masayuki Hino; Chikara Hirase; Tomohiko Kamimura; Takayuki Shimose; Koichi Akashi; Yuzuru KanakuraInternational journal of hematology 107 5 535 - 540 2018年05月 [査読有り]
We evaluated the efficacy and safety of switching to nilotinib in CML-CP patients who had achieved MMR with continuous detectable BCR-ABL1 transcript levels after long-term imatinib treatment. Patients who had achieved MMR, but not deep molecular response (DMR), after > 18 months from the initiation of imatinib received nilotinib 400 mg twice daily for up to 24 months. BCR-ABL1 transcript levels were assessed every 3 months. Thirty-eight patients with a median age of 57.5 years (range 22-76 years) were evaluated. Twenty-seven patients completed 24 months of nilotinib treatment; 11 discontinued nilotinib due to retraction of consent (three patients), loss of MMR (1), intolerance (3) or AEs (5). Twenty patients [52.6%, (90% CI 38.2-66.7%)] achieved DMR. The cumulative incidence of achieving DMR by the time of 3, 6, 9, 12, 15, 18, and 21 months was 22.9, 37.7, 47.0, 53.7, 53.7, 53.7, and 53.7%, respectively. Adverse events were consistent with those reported in other nilotinib studies. Patients experienced each of the following cardiovascular complications: atrial fibrillation (G2), chest tightness and dyspnea (G1), myocardial infarction (G2) and heart failure (G3) (n = 1 for each complication). This study indicates nilotinib achieves strong, rapid induction of DMR for patients who achieved MMR after long-term imatinib therapy. - Yayoi Matsumura-Kimoto; Junya Kuroda; Hitomi Kaneko; Yuri Kamitsuji; Shin-Ichi Fuchida; Aya Nakaya; Hirohiko Shibayama; Nobuhiko Uoshima; Isao Yokota; Hitoji Uchiyama; Hideo Yagi; Satoru Kosugi; Toshimitsu Matsui; Jun Ishikawa; Mitsuhiro Matsuda; Kensuke Ohta; Masato Iida; Hirokazu Tanaka; Masayuki Kobayashi; Katsuya Wada; Chihiro Shimazaki; Shosaku Nomura; Kazunori Imada; Masayuki Hino; Itaru Matsumura; Yuzuru Kanakura; Akifumi Takaori-KondoInternational journal of hematology 107 5 541 - 550 2018年05月 [査読有り]
Determinants of the efficacy and safety of pomalidomide (POM) monotherapy or POM plus dexamethasone (DEX) (POM/DEX) for relapsed and refractory multiple myeloma (RRMM) were examined retrospectively in a real-world clinical practice setting in Japan. The subjects were 108 patients registered with the Kansai Myeloma Forum, who were treated with either POM or POM/DEX. Of these, 79 (73%), 73 (68%), and 58 (54%) were resistant to bortezomib (BTZ), lenalidomide (LEN), and both BTZ and LEN, respectively. The median overall survival (OS) was not reached. The median time to treatment failure (TTF) was 4.4 months. The best response was recorded in 96 patients, with a 31% overall response rate (ORR) and a 79% rate of achieving at least stable disease. Number of pre-POM regimens ≥ 5, non-IgG-type M-protein, and time from initial therapy to POM or POM/DEX therapy < 2 years were associated with shorter TTF and OS. Frequent (> 10%) severe adverse events included neutropenia (55.1%), thrombocytopenia (33.7%), anemia (30.6%), febrile neutropenia (12.2%), fatigue (11.2%), and anorexia (10.2%). In conclusion, POM and POM/DEX showed substantial efficacy against RRMM, but new combination therapies with POM are needed to improve efficacy further without causing hematologic toxicities. - Masashi Kono; Yoriaki Komeda; Toshiharu Sakurai; Ayana Okamoto; Kosuke Minaga; Ken Kamata; Satoru Hagiwara; Hiroaki Inoue; Eisuke Enoki; Itaru Matsumura; Tomohiro Watanabe; Masatoshi KudoJournal of Crohn's and Colitis 12 4 499 - 502 2018年03月 [査読有り]
- Hirohisa Nakamae; Tetsuya Fukuda; Chiaki Nakaseko; Yoshinobu Kanda; Ken Ohmine; Takaaki Ono; Itaru Matsumura; Akira Matsuda; Makoto Aoki; Kazuo Ito; Hirohiko ShibayamaInternational Journal of Hematology 107 3 327 - 336 2018年03月 [査読有り]
In the ongoing, international, phase 3 study Evaluating Nilotinib Efficacy and Safety in Clinical Trials–Newly Diagnosed Patients (ENESTnd), nilotinib 300 and nilotinib 400 mg, both twice daily, are compared with imatinib 400 mg once daily for the treatment of newly diagnosed chronic myeloid leukemia in the chronic phase (CML-CP). Results for the overall population in ENESTnd (n = 846) showed that nilotinib resulted in higher response rates vs. imatinib and was well tolerated. Outcomes among Japanese patients in ENESTnd were specifically analyzed after 1 year of follow-up, and showed similar trends to the overall population we present updated analysis of the Japanese subgroup based on 5 years of follow-up. Among Japanese patients in the nilotinib 300-mg (n = 29), nilotinib 400-mg (n = 23), and imatinib (n = 25) arms, 86.2, 78.3, and 60.0%, respectively, achieved major molecular response [BCR-ABL1 ≤ 0.1% on the International Scale (BCR-ABL1IS)] by 5 years, and 65.5, 69.6, and 40.0%, respectively, achieved MR4.5 (BCR-ABL1IS ≤ 0.0032%). Safety results were consistent with prior reports. In this subgroup, one death occurred during treatment in the nilotinib 400-mg twice-daily arm (unknown cause), and one patient in each arm progressed to accelerated phase/blast crisis by the data cutoff. - Yasuhiko Harada; for the Japan Adult Leukemia Study Group JALSG; Yasunobu Nagata; Rika Kihara; Yuichi Ishikawa; Norio Asou; Shigeki Ohtake; Shuichi Miyawaki; Toru Sakura; Yukiyasu Ozawa; Noriko Usui; Heiwa Kanamori; Yoshikazu Ito; Kiyotoshi Imai; Youko Suehiro; Shinichi Kobayashi; Kunio Kitamura; Emiko Sakaida; Makoto Onizuka; Akihiro Takeshita; Fumihiro Ishida; Hitoshi Suzushima; Kenichi Ishizawa; Tomoki Naoe; Itaru Matsumura; Yasushi Miyazaki; Seishi Ogawa; Hitoshi KiyoiLeukemia Research 66 20 - 27 2018年03月 [査読有り]
Many genetic alterations that are associated with the prognosis of acute myeloid leukemia (AML) have been identified, and several risk stratification systems based on the genetic status have been recommended. The European LeukemiaNet (ELN) first proposed the risk stratification system for AML in 2010 (ELN-2010), and recently published the revised system (ELN-2017). We validated the long-term prognosis and clinical characteristics of each ELN-2017 risk category in Japanese adult AML patients who were treated in the Japan Adult Leukemia Study Group (JALSG) AML-201 study. We demonstrated that the 3-risk category system of the ELN-2017 successfully discriminated the overall survival and complete remission rates in our cohort in comparison with the 4-risk category of the ELN-2010. However, there were still genetic categories in which stratification of patients into favorable or intermediate risk categories was controversial the low allelic ratio of FLT3-ITD was not necessarily associated with a better prognosis in patients with FLT3-ITD, and cytogenetic abnormalities may affect the prognosis in patients with favorable genetic lesions such as NPM1 and CEBPA mutations. As many molecular targeting agents, such as FLT3 inhibitors, have been developed, we must continue to modify the genetic risk stratification system to match the progression of therapeutic strategies. - 難治性血栓症を伴うI型クリオグロブリン血症を合併したリンパ形質細胞性リンパ腫の1例國田 裕貴; 口分田 貴裕; 波江野 高大; 森田 泰慶; 嶋田 高広; 田中 宏和; 辰巳 陽一; 芦田 隆司; 松村 到臨床血液 59 2 239 - 240 (一社)日本血液学会-東京事務局 2018年02月
- 複数の免疫異常を合併した脾辺縁帯リンパ腫の1例三宅 義昭; 口分田 貴裕; 波江野 高大; 森田 泰慶; 嶋田 高広; 田中 宏和; 辰巳 陽一; 芦田 隆司; 松村 到臨床血液 59 2 240 - 240 (一社)日本血液学会-東京事務局 2018年02月
- Naoto Takahashi; Tetsuzo Tauchi; Kunio Kitamura; Koichi Miyamura; Yoshio Saburi; Yoshihiro Hatta; Yasuhiko Miyata; Shinichi Kobayashi; Kensuke Usuki; Itaru Matsumura; Yosuke Minami; Noriko Usui; Tetsuya Fukuda; Satoru Takada; Maho Ishikawa; Katsumichi Fujimaki; Hiroshi Gomyo; Osamu Sasaki; Kohshi Ohishi; Takaaki Miyake; Kiyotoshi Imai; Hitoshi Suzushima; Hideki Mitsui; Kazuto Togitani; Toru Kiguchi; Yoshiko Atsuta; Shigeki Ohtake; Kazunori Ohnishi; Yukio Kobayashi; Hitoshi Kiyoi; Yasushi Miyazaki; Tomoki NaoeInternational journal of hematology 107 2 185 - 193 2018年02月 [査読有り]
The objective of this prospective clinical trial (JALSG-STIM213, UMIN000011971) was to evaluate treatment-free remission (TFR) rates after discontinuation of imatinib in chronic myeloid leukemia (CML). CML patients who received imatinib treatment for at least 3 years and sustained deep molecular response for at least 2 years were eligible. Molecular recurrence was defined as loss of major molecular response (MMR). Of the 68 eligible patients, 38.2% were women, the median age was 55.0 years, and the median duration of imatinib treatment was 97.5 months. The 12-month TFR rate was 67.6%. Patients who lost MMR were immediately treated with imatinib again; all re-achieved MMR. Three-year treatment-free survival (TFS) was estimated as 64.6% using the Kaplan-Meier method. Undetectable molecular residual disease (UMRD) was defined as no BCR-ABL1 in > 100,000 ABL1 control genes using international scale polymerase chain reaction. UMRD at the study baseline was found to be predictive of continuation of TFR. Our findings suggest that CML patients who meet all the eligibility criteria that have commonly been used in the TFR trials are able to discontinue imatinib use safely. TFR may thus be valuable as a new goal for CML treatment in Japan. - J. Luis Espinoza; Ayumi Matsumoto; Hirokazu Tanaka; Itaru MatsumuraCancer Letters 414 147 - 152 2018年02月 [査読有り]
The complex diversity of nonpathogenic microbes that colonize the human body, known as microbiota, exert considerable effects on physiological homeostasis, and immune regulation. Helicobacter pylori (H. pylori) is a bacterium that frequently colonizes human stomach and is a major pathogenic agent for peptic ulcer diseases, gastric cancer, and mucosa-associated lymphoid tissue (MALT) lymphoma. Due to its acidic pH and peristaltic movements, the stomach has been considered a hostile environment for most microorganisms, however various commensal microorganisms are capable of colonizing the stomach to form a stomach niche. Recent pieces of evidence indicate that commensal gastric microbes or their metabolites influence the capability of H. pylori to colonize the stomach and directly modulate its pathogenicity and carcinogenic potential. In this article, we present an overview of recent advances in the understanding of H. pylori-commensal interactions in the pathogenesis and clinical evolution of H. pylori-associated gastric malignancies. - 嶋田高広; 松村到がん分子標的治療 15 4 451‐454 2018年01月
- Kaito Harada; Noriko Doki; Takeshi Hagino; Shuichi Miyawaki; Shigeki Ohtake; Hitoshi Kiyoi; Yasushi Miyazaki; Hiroyuki Fujita; Noriko Usui; Hirokazu Okumura; Koichi Miyamura; Chiaki Nakaseko; Atsushi Fujieda; Tadashi Nagai; Takahisa Yamane; Hisashi Sakamaki; Kazunori Ohnishi; Tomoki Naoe; Ryuzo Ohno; Kazuteru OhashiAnnals of hematology 97 1 73 - 81 2018年01月 [査読有り]
Recent studies have described various impacts of obesity and being overweight on acute myeloid leukemia (AML) outcomes in adult patients, but little is known about the impact of being underweight. We compared the outcomes of underweight patients to those of normal weight and overweight patients. Adult patients with AML who registered in the JALSG AML201 study (n = 1057) were classified into three groups: underweight (body mass index [BMI] < 18.5, n = 92), normal weight (BMI 18.5-25, n = 746), and overweight (BMI ≥ 25, n = 219). With the exception of age and male/female ratio, patient characteristics were comparable among the three groups. Rates of complete remission following induction chemotherapy were similar among the three groups (p = 0.68). We observed a significant difference in overall survival (OS), disease-free survival (DFS), and non-relapse mortality (NRM) between underweight and normal weight patients (3-year OS 34.8 vs. 47.7%, p = 0.01; DFS 28.6 vs. 39.8%, p = 0.02; 1-year NRM 6.2 vs. 2.6%, p = 0.05), but not between underweight and overweight patients. In multivariate analysis, underweight was an independent adverse prognostic factor for OS (p < 0.01), DFS (p = 0.01), and NRM (p = 0.04). During the first induction chemotherapy, the incidences of documented infection (DI) and severe adverse events (AEs) were higher in underweight patients than those in normal weight patients (DI 16 vs. 8.1%, p = 0.04; AE 36 vs. 24%, p = 0.05). In conclusion, underweight was an independent adverse prognostic factor for survival in adult AML patients. - Kentaro Serizawa; Hirokazu Tanaka; Yasuyoshi Morita; Takahide Taniguchi; Takashi Ashida; Itaru MatsumuraFrontiers in oncology 8 204 - 204 2018年 [査読有り]
Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal disorders of hematopoietic stem cells, characterized by dysplastic hematopoiesis and dysregulated immune system resulting in various clinical conditions. Paraneoplastic inflammatory syndromes, which are well known to be associated with MDS, show response to immune-modulated therapy and often disappear during the course of hematologic management. Azacitidine (5-Aza) was shown to prolong survival of high-risk MDS patients, however, the effects of 5-Aza on paraneoplastic inflammation in MDS have yet to be elucidated. 5-Aza was administered to a 60-year-old man with MDS accompanying Sweet's syndrome at a dose of 75 mg/m2/daily subcutaneously for 7 days every 28 days. 5-Aza was not only effective in controlling systemic symptoms caused by paraneoplastic inflammation, but hematologic improvements were also observed after four cycles of the 5-Aza treatment. Immune profiling in peripheral blood before and after 5-Aza treatment revealed that the effector and naive regulatory T cells in lymphocytes drastically increased after the 5-Aza treatment, i.e., 5-Aza might induce a shift in lymphocytic populations toward immunosuppression in this patient. Our results raised the immune-mediated effect of 5-Aza on both dysplastic hematopoiesis and paraneoplastic inflammation in myelodyplastic syndromes. - Nakayama S; Matsuda M; Adachi T; Sueda S; Ueda K; Kawahara K; Ohashi Y; Awaji S; Hashimoto S; Matsumura ILeukemia research reports 10 1 - 3 2018年 [査読有り]
- Aya Nakaya; Hideo Yagi; Hitomi Kaneko; Satoru Kosugi; Toru Kida; Yoko Adachi; Hirohiko Shibayama; Takae Kohara; Yuri Kamitsuji; Shin-Ichi Fuchida; Nobuhiko Uoshima; Eri Kawata; Hitoji Uchiyama; Yuji Shimura; Takayuki Takahashi; Fumiaki Urase; Kensuke Ohta; Tsuneyoshi Hamada; Kazue Miyamoto; Masayuki Kobayashi; Maki Shindo; Hirokazu Tanaka; Chihiro Shimazaki; Masayuki Hino; Junya Kuroda; Yuzuru Kanakura; Akifumi Takaoari-Kondo; Shosaku Nomura; Itaru MatsumuraLeukemia research reports 10 7 - 10 2018年 [査読有り]
We retrospectively analyzed twenty-six patients with primary plasma cell leukemia (pPCL) registered from May 2005 until April 2015 by the Kansai Myeloma Forum. Twenty patients received novel agents (bortezomib or lenalidomide), and their median survival of was 34 months. The median survival of patients who underwent autologous stem cell transplantation (SCT) was 40 months, those undergoing allogeneic SCT 55 months, and those undergoing both types of SCT (auto-allo) 61 months; whereas for those who did not undergo SCT it was 28 months (p = 0.845). The only statistically significant risk factor identified by multivariate analysis was hypercalcemia. - Matsumura I[Rinsho ketsueki] The Japanese journal of clinical hematology 59 1 13 - 26 2018年 [査読有り]
- 平瀬主税; 松村到日本血栓止血学会誌 29 5 473‐486(J‐STAGE) 2018年
- Nozaki Y; Nagare Y; Ashida C; Tomita D; Okada A; Inoue A; Kinoshita K; Funauchi M; Matsumura IBiologics : targets & therapy 12 171 - 182 2018年 [査読有り]
Purpose: We evaluated the clinical responses and radiographic outcomes of 90 patients with rheumatoid arthritis (RA) undergoing continuous or dose-adjusted infliximab treatment over 104 weeks. Patients and methods: Patients received 3 mg/kg infliximab continuously (the contin group; n=50), or the dose escalation and de-escalation of infliximab (3, 6, and 10 mg/kg) from week 14 (the adjusted group; n=40) based on the patient's Disease Activity Score in 28 joints (DAS28). The retention rate, clinical response, and radiographic assessment were determined at week 104. Results: The contin and adjusted groups' retention rates at week 104 were 56.8 and 66.7%, and the groups' low disease activity in the DAS28 was 39.1 and 66.7%, respectively. Remission based on the DAS28 and the American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) Boolean-based criteria was significantly increased in the adjusted group. In the radiographic assessment, there was also a significant reduction in the mean changes in total Sharp score. The cumulative rates of any adverse effects showed no significant difference between the groups. Conclusion: In an assessment of adequate DAS28 results, the RA patients who did not respond to the initial dose of infliximab showed improved clinical responses and radiographic assessment after a dose adjustment of infliximab, without an increased risk of serious adverse events. - Shinya Rai; J Luis Espinoza; Yasuyoshi Morita; Hirokazu Tanaka; Itaru MatsumuraFrontiers in immunology 9 3031 - 3031 2018年 [査読有り]
Myelodysplastic syndromes (MDS) are a heterogeneous group clonal disorders of hematopoietic stem cells (HSC) characterized by ineffective hematopoiesis that lead to variable grades of impaired blood cell production. Chromosomal aberrations are often detected in MDS patients and thus cytogenetic analysis is useful for the diagnosis of these disorders. Common recurring chromosomal defects, such as the -5/5q- and -7/7q- are relatively well characterized cytogenetic abnormalities in MDS, however, the biological significance of uncommon cytogenetic alterations is unknown. We report here, two cases of peripheral blood and bone marrow hypereosinophilia in patients with MDS harboring the unbalanced translocation der(1;7)(q10;p10), a poorly characterized cytogenetic abnormality that is found in certain myeloid malignancies, including MDS. The patients reported here presented hypereosinophilia that was refractory to steroids and cytotoxic therapy, leading to severe target tissue damage that ultimately resulted in fatal end-organ failure. Potential roles of the der(1;7)(q10;p10) aberrations in the pathogenesis of aggressive eosinophilia and disease prognosis are discussed here. - Koji Kawamura; Hideki Nakasone; Saiko Kurosawa; Kazuki Yoshimura; Yukiko Misaki; Ayumi Gomyo; Jin Hayakawa; Masaharu Tamaki; Yu Akahoshi; Machiko Kusuda; Kazuaki Kameda; Hidenori Wada; Yuko Ishihara; Miki Sato; Kiriko Terasako-Saito; Misato Kikuchi; Shun-ichi Kimura; Aki Tanihara; Shinichi Kako; Heiwa Kanamori; Takehiko Mori; Satoshi Takahashi; Shuichi Taniguchi; Yoshiko Atsuta; Yoshinobu KandaBiology of Blood and Marrow Transplantation 24 7 1521 - 1526 2018年 [査読有り]
The aim of this study was to develop a new composite endpoint that accurately reflects the long-term success of allogeneic hematopoietic stem cell transplantation (allo-HSCT), as the conventional graft-versus-host disease (GVHD)–free, relapse-free survival (GRFS) overestimates the impact of GVHD. First, we validated current GRFS (cGRFS), which recently was proposed as a more accurate endpoint of long-term transplant success. cGRFS was defined as survival without disease relapse/progression or active chronic GVHD at a given time after allo-HSCT, calculated using 2 distinct methods: a linear combination of a Kaplan-Meier estimates approach and a multistate modelling approach. Next, we developed a new composite endpoint, refractory GRFS (rGRFS). rGRFS was calculated similarly to conventional GRFS treating grade III to IV acute GVHD, chronic GVHD requiring systemic treatment, and disease relapse/progression as events, except that GVHD that resolved and did not require systemic treatment at the last evaluation was excluded as an event in rGRFS. The 2 cGRFS curves obtained using 2 different approaches were superimposed and both were superior to that of conventional GRFS, reflecting the proportion of patients with resolved chronic GVHD. Finally, the curves of cGRFS and rGRFS overlapped after the first 2 years of post-transplant follow-up. These results suggest that cGRFS and rGRFS more accurately reflect transplant success than conventional GRFS. Especially, rGRFS can be more easily calculated than cGRFS and analyzed with widely used statistical approaches, whereas cGRFS more accurately represents the burden of GVHD-related morbidity in the first 2 years after transplantation. - Yuji Nozaki; Shoichi Hino; Jinhai Ri; Kenji Sakai; Yasuaki Nagare; Mai Kawanishi; Kaoru Niki; Masanori Funauchi; Itaru MatsumuraInternational Journal of Molecular Sciences 18 12 2017年12月 [査読有り]
The proinflammatory cytokine interleukin (IL)-18 is an important mediator of the organ failure induced by endotoxemia. IL-18 (known as an interferon-gamma (IFN-γ) inducing factor), and other inflammatory cytokines have important roles in lipopolysaccharide (LPS)-induced acute kidney injury (AKI). We investigated the effect of inflammatory cytokines and Toll-like receptor 4 (TLR4) expression, an event that is accompanied by an influx of monocytes, including CD4+ T cells and antigen-presenting cells (APCs) in IL-18Rα knockout (KO) mice and wild-type (WT) mice after LPS injection. In the acute advanced phase, the IL-18Rα KO mice showed a higher survival rate and a suppressed increase of blood urea nitrogen, increased levels of proinflammatory cytokines such as IFN-γ and IL-18, the infiltration of CD4+ T cells and the expression of kidney injury molecule-1 as an AKI marker. In that phase, the renal mRNA expression of the M1 macrophage phenotype and C-C chemokine receptor type 7 as the maturation marker of dendritic cells (DCs) was also significantly decreased in the IL-18Rα KO mice, although there were small numbers of F4/80+ cells and DCs in the kidney. Conversely, there were no significant differences in the expressions of mRNA and protein TLR4 after LPS injection between the WT and IL-18Rα KO groups. Our results demonstrated that the IL-18Rα-mediated signaling pathway plays critical roles in CD4+ T cells and APCs and responded more quickly to IFN-γ and IL-18 than TLR4 stimulation in the pathogenesis of LPS-induced AKI. - 松村到日本臨床内科医会会誌 32 4 580‐585 2017年12月
- Takeshita Akihiro; Asou Norio; Yanada Masamitsu; Sakura Toru; Ueda Yasunori; Sawa Masashi; Dobashi Nobuaki; Onizuka Makoto; Taniguchi Yasuhiro; Nakagawa Masaru; Tamaki Shigehisa; Hagihara Maki; Fujimaki Katsumichi; Furumaki Hiroaki; Fujita Hiroyuki; Usui Noriko; Kobayashi Yukio; Kiyoi Hitoshi; Ohtake Shigeki; Atsuta Yoshiko; Matsumura Itaru; Naoe Tomoki; Miyazaki YasushiBLOOD 130 2017年12月 [査読有り]
- Gotoh T; Takechi K; Oiso N; Matsumura I; Iki MActa Med Kindai Univ 42 2 57 - 62 2017年12月 [査読有り]
- Satoshi Nishiwaki; Isamu Sugiura; Yasuhiko Miyata; Shigeki Saito; Masashi Sawa; Tetsuya Nishida; Koichi Miyamura; Yachiyo Kuwatsuka; Akio Kohno; Masaaki Yuge; Masanobu Kasai; Hiroatsu Iida; Shingo Kurahashi; Masahide Osaki; Tatsunori Goto; Seitaro Terakura; Makoto Murata; Hiroyoshi Nishikawa; Hitoshi KiyoiMedicine 96 52 e9568 2017年12月 [査読有り]
INTRODUCTION: The prognosis of Philadelphia chromosome positive acute lymphoblastic leukemia (Ph + ALL) has been dramatically improved since the introduction of tyrosine kinase inhibitors (TKIs). Although allogeneic hematopoietic cell transplantation (allo-HCT) is a major treatment option, the role of autologous peripheral blood stem cell transplantation (auto-PBSCT) has been reconsidered, especially in patients who achieved early molecular remission. METHODS AND ANALYSIS: This is a multicenter exploratory study for Ph + ALL patients aged between 55 and 70 years who achieved complete molecular remission within 3 cycles of chemotherapy. The target sample size is 5, and the registration period is 2 years. The primary endpoint is Day100- mortality after transplantation, and the secondary endpoints are survival, relapse rate, nonrelapse mortality, and adverse events.This study is divided into 3 phases: peripheral blood stem cell harvest, transplantation, and maintenance. Chemomobilization is performed using a combination of cyclophosphamide (CPM), doxorubicin, vincristine (VCR), and prednisolone (PSL). As a preparative regimen, the LEED regimen is used, which consists of melphalan, CPM, etoposide, and dexamethasone. Twelve cycles of maintenance therapy using a combination of VCR, PSL, and dasatinib are performed.In association with relapse, the minimal residual disease (MRD) of BCR-ABL chimeric gene and T-cell subsets are analyzed both before and after auto-PBSCT. ETHICS AND DISSEMINATION: The protocol was approved by the institutional review board of Nagoya University Hospital and all the participating hospitals. Written informed consent was obtained from all patients before registration, in accordance with the Declaration of Helsinki. Results of the study will be disseminated via publications in peer-reviewed journals. TRIAL REGISTRATION: Trial registration number UMIN000026445. - 芹澤 憲太郎; 芦田 隆司; 谷口 貴英; 谷口 康博; 森田 泰慶; 田中 宏和; 嶋田 高広; 辰巳 陽一; 松村 到臨床血液 58 12 2386 - 2391 (一社)日本血液学会-東京事務局 2017年12月急性骨髄性白血病に対する同種骨髄移植後に一旦造血機能の回復を認めたものの汎血球減少を来し、二次性生着不全と判断してドナーリンパ球輸注(donor lymphocyte infusion,DLI)を施行したところ著効を示した症例を経験したので報告する。症例は64歳女性。急性骨髄性白血病の部分寛解に対して非血縁者間同種骨髄移植を施行した。速やかに生着し、complete remission with incomplete blood count recovery(CRi)に到達したが、day 110から汎血球減少症が出現した。血液検査および骨髄穿刺では、再発や血球貪食症候群は認めないものの、キメリズム解析でドナー比率が経時的に低下したため、二次性生着不全と診断した。Granulocyte-colony stimulating factor(G-CSF)の投与と輸血にて経過観察したが、造血の改善は認めなかった。患者が再移植を希望しなかったため、DLIを施行した(CD3陽性細胞:1.0×107/kg、単回投与)ところ、有害事象を認めることなく、血球は速やかに改善した。(著者抄録)
- 花本仁; 松村到月刊腫瘍内科 20 5 389‐397 - 397 科学評論社 2017年11月
- Junichiro Yuda; Toshihiro Miyamoto; Jun Odawara; Yasuyuki Ohkawa; Yuichiro Semba; Masayasu Hayashi; Koichi Miyamura; Mitsune Tanimoto; Kazuhito Yamamoto; Masafumi Taniwaki; Koichi AkashiCANCER SCIENCE 108 11 2204 - 2212 2017年11月 [査読有り]
Treatment with tyrosine kinase inhibitors (TKI) may sequentially induce TKI-resistant BCR-ABL mutants in chronic myeloid leukemia (CML). Conventional PCR monitoring of BCR-ABL is an important indicator to determine therapeutic intervention for preventing disease progression. However, PCR cannot separately quantify amounts of BCR-ABL and its mutants, including alternatively spliced BCR-ABL with an insertion of 35 intronic nucleotides (BCR-ABL(Ins35bp)) between ABL exons 8 and 9, which introduces the premature termination and loss of kinase activity. To assess the clinical impact of BCR-ABL mutants, we performed deep sequencing analysis of BCR-ABL transcripts of 409 samples from 37 patients with suboptimal response to frontline imatinib who were switched to nilotinib. At baseline, TKI-resistant mutations were documented in 3 patients, whereas BCR-ABL(Ins35bp) was detected in all patients. After switching to nilotinib, both BCR-ABL and BCR-ABL(Ins35bp) became undetectable in 3 patients who attained complete molecular response (CMR), whereas in the remaining all 34 patients, BCR-ABL(Ins35bp) was persistently detected, and minimal residual disease (MRD) fluctuated at low but detectable levels. PCR monitoring underestimated molecular response in 5 patients whose BCR-ABL(Ins35bp) was persisted, although BCR-ABL(Ins35bp) does not definitively mark TKI resistance. Therefore, quantification of BCR-ABL(Ins35bp) is useful for evaluating functional MRD and determining the effectiveness of TKI with accuracy. - 安藤 潔; 張 高明; 鈴木 憲史; 品川 篤司; 内田 俊樹; 谷脇 雅史; 平田 大二; 石澤 賢一; 末永 孝生; 岡本 真一郎; 大塚 眞紀; 松本 守生; 飯田 真介; 松村 到; 池田 宇次; 竹迫 直樹; 大柿 友美; 緑川 修一; Houck Vanessa; Ervin-Haynes Annette; 照井 康仁臨床血液 58 11 2219 - 2226 (一社)日本血液学会-東京事務局 2017年11月造血幹細胞移植非適応の未治療多発性骨髄腫患者に対するlenalidomideとdexamethasoneの併用(Rd)療法の本邦第II相臨床試験(MM-025)では、追跡期間中央値14.2ヵ月の時点で同療法の有効性および安全性が確認された。今回、本試験の追跡データを含めて解析を行った。追跡期間中央値31.3ヵ月の時点で全26例が治療を終了しており、治療期間中央値は約25ヵ月であった。全奏効率は87.5%、complete response率は20.8%であった。奏効期間および無増悪生存期間の中央値はそれぞれ30.7ヵ月、31.6ヵ月で、全生存期間は中央値に未到達であった。23例(88.5%)にグレード3/4の有害事象が発現し、18例(69.2%)に重篤な有害事象が認められた。治療関連死は認められなかった。以上より、移植非適応の日本人の未治療多発性骨髄腫患者に対するRd療法の有効性および安全性が今回の追跡期間においても確認された。(著者抄録)
- Yasuhiro Taniguchi; Hirokazu Tanaka; Espinoza J. Luis; Kazuko Sakai; Takahiro Kumode; Keigo Sano; Kentarou Serizawa; Shinya Rai; Yasuyoshi Morita; Hitoshi Hanamoto; Kazuo Tsubaki; Kazuto Nishio; Itaru MatsumuraINTERNATIONAL JOURNAL OF HEMATOLOGY 106 5 691 - 703 2017年11月 [査読有り]
Myeloproliferative neoplasms (MPNs), including polycythemia vera and essential thrombocythemia, are frequently associated with thrombotic complications. Prevention of thrombotic events is thus a primary aim of the current treatment for these disorders. Although it is known that microparticles (MPs), which are small vesicles released from cell membranes and circulate in the blood, directly contribute to thrombosis via their procoagulant activity, potential associations between plasma levels of MPs and the risk of thrombotic events in MPNs have not been reported. In the present study, we characterized plasma levels of MPs and assessed their potential association with the occurrence of thrombotic events in 59 patients with MPNs. Plasma levels of procoagulant MPs expressing tissue factor (TF+ MPs) were significantly higher in patients suffering thrombotic events than in patients without such events (median/mu l plasma: 33.8 vs 47.2, p = 0.02). Among patients who developed thrombotic events, irrespective of patients' blood counts, TF+ MP were significantly higher in patients without cytoreductive therapy than in those receiving cytoreductive therapy (101.2 vs. 42.5, p < 0.001). These results suggest that elevated levels of TF+ MP may be considered as a novel surrogate marker for thrombotic events in MPN patients. Further studies are needed to clarify the mechanism involved. - くも膜下出血を合併した好酸球性多発血管炎性肉芽腫の1例渡辺 圭子; 森田 玲子; 柳原 茂人; 大磯 直毅; 川田 暁; 長束 一紘; 大槻 俊輔; 加藤 天美; 井上 明日香; 永禮 靖章; 船内 正憲; 松村 到; 岩永 賢司; 東田 有智皮膚の科学 16 5 379 - 380 日本皮膚科学会-大阪地方会・京滋地方会 2017年10月
- 廣川 誠; 藤島 直仁; 澤田 賢一; 張替 秀郎; 松田 晃; 小松 則夫; 通山 薫; 米村 雄士; 中尾 眞二; 齋藤 明子; 松村 到; 荒井 俊也; 黒川 峰夫臨床血液 58 9 1567 - 1567 (一社)日本血液学会-東京事務局 2017年09月
- Arinobu Tojo; Taiichi Kyo; Kazuhito Yamamoto; Hirohisa Nakamae; Naoto Takahashi; Yukio Kobayashi; Tetsuzo Tauchi; Shinichiro Okamoto; Koichi Miyamura; Kiyohiko Hatake; Hiromi Iwasaki; Itaru Matsumura; Noriko Usui; Tomoki Naoe; Meera Tugnait; Narayana I. Narasimhan; Stephanie Lustgarten; Heinrich Farin; Frank Haluska; Kazuma OhyashikiINTERNATIONAL JOURNAL OF HEMATOLOGY 106 3 385 - 397 2017年09月 [査読有り]
In this ongoing Phase 1/2 study (NCT01667133), we evaluated ponatinib and assessed its recommended dose in Japanese patients with chronic myeloid leukemia (CML) resistant/intolerant to dasatinib or nilotinib, or with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL) resistant/intolerant to ae1 tyrosine kinase inhibitor (TKI). The primary endpoints were safety of the recommended dose (Phase 1) and major cytogenetic response (MCyR) by 12 months in chronic-phase CML (CP-CML) patients or major hematologic response (MaHR) by 6 months in patients with advanced phase disease (Phase 2). MCyR was achieved/maintained by 12 months in 65% of CP-CML patients; MaHR was achieved by 6 months in 61% of patients with advanced phase disease. The most common nonhematologic grade 3/4 treatment-emergent adverse event (AE) was hypertension (37%); common hematologic grade 3/4 AEs were thrombocytopenia (57%), neutropenia (34%), and leukopenia (26%). Overall, five (14%) patients experienced arterial occlusive events (AOEs); no grade 5 AOEs were reported. The steady-state accumulation ratio of ponatinib (based on area under the curve) ranged from 2.6 (15 mg/day) to 1.3 (45 mg/day). In summary, ponatinib demonstrated efficacy in Japanese patients with CML and Ph(+)ALL resistant/intolerant to prior TKI treatment; safety data support a recommended starting dose of 45 mg/day in these patients. - Naoto Takahashi; Chiaki Nakaseko; Yukio Kobayashi; Koichi Miyamura; Chiho Ono; Yuichiro Koide; Yosuke Fujii; Kazunori OhnishiINTERNATIONAL JOURNAL OF HEMATOLOGY 106 3 398 - 410 2017年09月 [査読有り]
This long-term follow-up of a completed phase 1/2 study assessed the safety and efficacy of bosutinib in Japanese Philadelphia chromosome-positive, chronic phase (CP) or advanced phase (ADV) chronic myeloid leukemia patients who were resistant/refractory or intolerant to prior tyrosine kinase inhibitor treatment. This analysis included 63 patients with a median bosutinib follow-up of 132 weeks (range 3aEuro'372). In the CP second-line (2L) cohort, the cumulative major cytogenetic response (MCyR) and major molecular response (MMR) rates throughout the study were 73 and 53%, respectively. In the CP third-line (3L) cohort, the cumulative MCyR and MMR rates throughout the study were 70 and 40%, respectively. Of the eight ADV patients, MCyR was attained or maintained by 50% of patients, and complete hematologic response was attained or maintained by 25% of patients. Progression-free survival rate and overall survival rate at 96 weeks were, respectively, 91 and 98% in CP2L, 88 and 100% in CP3L, and 33 and 50% in ADV patients. The most common adverse events (> 50%) reported were diarrhea (95%), nasopharyngitis (57%), and rash (57%). Bosutinib demonstrated durable efficacy and a manageable tolerability profile over long-term use in Japanese patients. ClinicalTrials.gov: NCT00811070. - 田中宏和; 松村到月刊血液内科 75 2 163‐168 - 136 科学評論社 2017年08月
- T. Kumode; H. Tanaka; R. Fujiwara; K. Sano; K. Serizawa; Y. Taniguchi; S. Rai; I. MatsumuraHAEMATOLOGICA 102 452 - 453 2017年06月
- 腎虚血再灌流モデルの病態におけるIL-10の意義についての研究酒井 健史; 李 進海; 岸本 和也; 永禮 靖章; 野崎 祐史; 杉山 昌史; 船内 正憲; 松村 到日本腎臓学会誌 59 3 289 - 289 (一社)日本腎臓学会 2017年04月
- 腎間質線維化病態におけるIL-18Rの役割の検討永禮 靖章; 岡田 晃典; 冨田 大介; 酒井 健史; 李 進海; 井上 明日圭; 志賀 俊彦; 岸本 和也; 野崎 祐史; 船内 正憲; 松村 到日本腎臓学会誌 59 3 353 - 353 (一社)日本腎臓学会 2017年04月
- ANCA関連腎炎に対する抗IL7R抗体の治療効果について岸本 和也; 酒井 健二; 李 進海; 野崎 祐史; 船内 正憲; 松村 到日本腎臓学会誌 59 3 360 - 360 (一社)日本腎臓学会 2017年04月
- E. Togasaki; J. Takeda; K. Yoshida; Y. Shiozawa; M. Takeuchi; M. Oshima; A. Saraya; A. Iwama; K. Yokote; E. Sakaida; C. Hirase; A. Takeshita; K. Imai; H. Okumura; Y. Morishita; N. Usui; N. Takahashi; S. Fujisawa; Y. Shiraishi; K. Chiba; H. Tanaka; H. Kiyoi; K. Ohnishi; S. Ohtake; N. Asou; Y. Kobayashi; Y. Miyazaki; S. Miyano; S. Ogawa; I. Matsumura; C. Nakaseko; T. NaoeBLOOD CANCER JOURNAL 7 4 e559 2017年04月 [査読有り]
Although tyrosine kinase inhibitors (TKIs) have significantly improved the prognosis of chronic myeloid leukemia (CML), the ability of TKIs to eradicate CML remains uncertain and patients must continue TKI therapy for indefinite periods. In this study, we performed whole-exome sequencing to identify somatic mutations in 24 patients with newly diagnosed chronic phase CML who were registered in the JALSG CML212 study. We identified 191 somatic mutations other than the BCR-ABL1 fusion gene (median 8, range 1-17). Age, hemoglobin concentration and white blood cell counts were correlated with the number of mutations. Patients with mutations >= 6 showed higher rate of achieving major molecular response than thoseo6 (P = 0.0381). Mutations in epigenetic regulator, ASXL1, TET2, TET3, KDM1A and MSH6 were found in 25% of patients. TET2 or TET3, AKT1 and RUNX1 were mutated in one patient each. ASXL1 was mutated within exon 12 in three cases. Mutated genes were significantly enriched with cell signaling and cell division pathways. Furthermore, DNA copy number analysis showed that 2 of 24 patients had uniparental disomy of chromosome 1p or 3q, which disappeared major molecular response was achieved. These mutations may play significant roles in CML pathogenesis in addition to the strong driver mutation BCR-ABL1. - 血管炎 ANCA関連腎炎に対する抗IL7R抗体の治療効果について岸本 和也; 酒井 健史; 李 進海; 野崎 祐史; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 61回 430 - 430 (一社)日本リウマチ学会 2017年03月
- その他の膠原病 トシリズマブに治療抵抗性であった間質性肺炎を合併した成人発症Still病に対しIVCY療法が奏功した一例冨田 大介; 志賀 俊彦; 岡田 晃典; 伊丹 哲; 酒井 健史; 李 進海; 田崎 知江美; 井上 明日圭; 樋野 尚一; 岸本 和也; 永禮 靖章; 野崎 祐史; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 61回 468 - 468 (一社)日本リウマチ学会 2017年03月
- 骨粗鬆症と骨代謝/変形性関節症・軟骨 治療抵抗性のステロイド性骨粗鬆症患者におけるデノスマブとテリパラチドの治療効果について永禮 靖章; 岡田 晃典; 冨田 大介; 酒井 健史; 井上 明日圭; 李 進海; 志賀 俊彦; 岸本 和也; 野崎 祐史; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 61回 544 - 544 (一社)日本リウマチ学会 2017年03月
- 関節リウマチの治療 有効性・寛解 関節リウマチ患者におけるTNF阻害薬での寛解導入予測因子としての関節エコーの有用性について野崎 祐史; 酒井 健史; 李 進海; 井上 明日圭; 志賀 俊彦; 岸本 和也; 永禮 靖章; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 61回 569 - 569 (一社)日本リウマチ学会 2017年03月
- リウマチ性疾患の合併症 自己免疫疾患を合併する骨髄異形成症候群の臨床的特徴の検討志賀 俊彦; 岡田 晃典; 富田 大介; 酒井 健史; 李 進海; 井上 明日圭; 岸本 和也; 永禮 靖章; 野崎 祐史; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 61回 587 - 587 (一社)日本リウマチ学会 2017年03月
- SLE・抗リン脂質抗体症候群 精神神経症状を呈した全身性エリテマトーデス症例での髄液IL-6高値群と低値群の比較検討酒井 健史; 岡田 晃典; 冨田 大介; 井上 明日圭; 李 進海; 志賀 俊彦; 岸本 和也; 永禮 靖章; 野崎 祐史; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 61回 594 - 594 (一社)日本リウマチ学会 2017年03月
- 多彩な自己抗体陽性を認め、HAART治療により改善したHIV脳症の一例岡田 晃典; 船内 正憲; 野崎 祐史; 永禮 靖章; 岸本 和也; 志賀 俊彦; 李 進海; 酒井 健史; 井上 明日圭; 冨田 大介; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 61回 746 - 746 (一社)日本リウマチ学会 2017年03月
- 全身性エリテマトーデス(SLE)モデルマウスの腎炎発症におけるIL-18Rαの役割李 進海; 野崎 祐史; 酒井 健史; 岸本 和也; 永禮 靖章; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 61回 781 - 781 (一社)日本リウマチ学会 2017年03月
- 関節リウマチ患者におけるイグラチモド継続率とメトトレキサート併用について井上 明日圭; 野崎 祐史; 岡田 晃典; 冨田 大介; 酒井 健史; 李 進海; 志賀 俊彦; 岸本 和也; 永禮 靖章; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 61回 793 - 793 (一社)日本リウマチ学会 2017年03月
- 岡田 晃典; 伊丹 哲; 志賀 俊彦; 野崎 祐史; 船内 正憲; 松村 到臨床リウマチ 29 1 52 - 58 (一社)日本臨床リウマチ学会 2017年03月84歳、男性。1週間前から高熱と咳嗽、喀痰に続き多関節痛が出現し、気管支炎の診断で抗生剤が投与された。しかし、気管支炎の改善後も発熱と頸部痛を含む多関節痛と高度の炎症反応が持続した。頸部のCT検査からCrowned dens syndrome(CDS)、環軸椎に生じた偽痛風と診断し、非ステロイド性消炎剤にて改善した。以上、偽痛風と炎症性疾患の関連性を鑑別することは有用であると考えられた。(著者抄録)
- 岡田 晃典; 伊丹 哲; 志賀 俊彦; 野崎 祐史; 船内 正憲; 松村 到臨床リウマチ 29 1 52 - 58 (一社)日本臨床リウマチ学会 2017年03月84歳、男性。1週間前から高熱と咳嗽、喀痰に続き多関節痛が出現し、気管支炎の診断で抗生剤が投与された。しかし、気管支炎の改善後も発熱と頸部痛を含む多関節痛と高度の炎症反応が持続した。頸部のCT検査からCrowned dens syndrome(CDS)、環軸椎に生じた偽痛風と診断し、非ステロイド性消炎剤にて改善した。以上、偽痛風と炎症性疾患の関連性を鑑別することは有用であると考えられた。(著者抄録)
- リツキシマブによる間質性肺炎をきたしたDLBCLの1例小森 舞子; 井上 宏昭; 角谷 宏明; 頼 晋也; 森田 泰慶; 芦田 隆司; 松村 到臨床血液 58 1 47 - 47 (一社)日本血液学会-東京事務局 2017年01月
- Ando K; Chou T; Suzuki K; Shinagawa A; Uchida T; Taniwaki M; Hirata H; Ishizawa K; Matsue K; Okamoto S; Otsuka M; Matsumoto M; Iida S; Matsumura I; Ikeda T; Takezako N; Ogaki Y; Midorikawa S; Houck V; Ervin-Haynes A; Terui Y[Rinsho ketsueki] The Japanese journal of clinical hematology 58 11 2219 - 2226 一般社団法人 日本血液学会 2017年 [査読有り]
造血幹細胞移植非適応の未治療多発性骨髄腫患者に対するlenalidomideとdexamethasoneの併用(Rd)療法の本邦第II相臨床試験(MM-025)では,追跡期間中央値14.2ヶ月の時点で同療法の有効性および安全性が確認された。今回,本試験の追跡データを含めて解析を行った。追跡期間中央値31.3ヶ月の時点で全26例が治療を終了しており,治療期間中央値は約25ヶ月であった。全奏効率は87.5%,complete response率は20.8%であった。奏効期間および無増悪生存期間の中央値はそれぞれ30.7ヶ月,31.6ヶ月で,全生存期間は中央値に未到達であった。23例(88.5%)にグレード3/4の有害事象が発現し,18例(69.2%)に重篤な有害事象が認められた。治療関連死は認められなかった。以上より,移植非適応の日本人の未治療多発性骨髄腫患者に対するRd療法の有効性および安全性が今回の追跡期間においても確認された。
- 照井康仁; 照井康仁; 張高明; 鈴木憲史; 品川篤司; 内田俊樹; 谷脇雅史; 平田大二; 石澤賢一; 末永孝生; 岡本真一郎; 大塚眞紀; 松本守生; 飯田真介; 松村到; 池田宇次; 竹迫直樹; 大柿友美; 緑川修一; HOUCK Vanessa; ERVIN‐HAYNES Annette; 安藤潔International Journal of Myeloma (Web) 7 1 ROMBUNNO.O2‐3 (WEB ONLY) 2017年
- Serizawa K; Ashida T; Taniguchi T; Taniguchi Y; Morita Y; Tanaka H; Shimada T; Tatsumi Y; Matsumura I[Rinsho ketsueki] The Japanese journal of clinical hematology 58 12 2386 - 2391 2017年 [査読有り]
Here we report a case of secondary graft failure that was effectively treated with donor lymphocyte infusion (DLI). A 64-year-old female patient with acute myeloid leukemia obtained partial remission with azacitidine therapy and subsequently underwent unrelated allogeneic bone marrow transplantation (BMT). After confirming successful engraftment and achieving complete remission with incomplete blood count recovery, she was subsequently followed up at an outpatient clinic. A routine test performed by day 110 after BMT revealed the presence of pancytopenia. A bone marrow aspirate did not reveal any evidence of disease relapse or hemophagocytic syndrome but demonstrated hematopoietic insufficiency. Donor chimerism also declined over time; thus, the patient was diagnosed with secondary graft failure. Supportive treatment, including granulocyte-colony stimulating factor and blood transfusion, failed to improve the blood parameters. Because the patient refused a second BMT, we performed DLI on day 147 after BMT (CD3+ cells: 1.0×107/kg, single dose). Consequently, the blood cell count improved promptly and dramatically without adverse events. Following this, we discussed the case and analyzed the related literature. - 井上 宏昭; 森田 泰慶; 頼 晋也; 角谷 宏明; 大山 泰世; 谷口 康博; 田中 宏和; 嶋田 高広; 辰巳 陽一; 芦田 隆司; 松村 到臨床血液 58 2 138 - 142 (一社)日本血液学会-東京事務局 2017年固形臓器移植後の免疫抑制療法は,骨髄異形成症候群(MDS)の発症リスクとなることが知られている。我々は,固形臓器移植後に発症した低リスクMDSに対して移植臓器の拒絶などの悪影響がなく,安全にアザシチジン(AZA)を投与することが可能で,血液学的改善が得られた2症例を経験したので報告する。1例目は肝移植後の74歳の男性である。免疫抑制療法として,シクロスポリンとプレドニゾロンを投与されていた。肝移植9年後,MDS(RCMD)と診断された。2例目は死体腎移植後の47歳の女性である。免疫抑制療法として,シクロスポリン,アザチオプリンおよびプレドニゾロンを投与されていた。腎移植27年後,MDS(RA)と診断された。両患者は,AZA治療(75mg/m2,5日間,28日間隔,点滴注射)を受けた。両者とも,2コース後にグレード3/4以上の非血液学的毒性を認めず,血液学的改善(国際ワーキンググループ2006年分類)が得られた。さらに,両患者に対するAZA治療は,移植臓器に対する拒絶などの悪影響を及ぼさなかった。固形臓器移植後に発症したMDSに対するAZA治療は,安全かつ有効である。しかしながら,真の安全性と有効性を確かめるために経過を長期間追跡することが必要である。(著者抄録)
- Norimitsu Kadowaki; Tatsuya Kawaguchi; Junya Kuroda; Hirohisa Nakamae; Itaru Matsumura; Toshihiro Miyamoto; Jun Ishikawa; Koji Nagafuji; Yutaka Imamura; Hirohito Yamazaki; Mototsugu Shimokawa; Koichi Akashi; Yuzuru KanakuraBLOOD 128 22 2016年12月
- Hirohiko Shibayama; Tatsuya Kawaguchi; Junya Kuroda; Hirohisa Nakamae; Itaru Matsumura; Toshihiro Miyamoto; Jun Ishikawa; Tomohiko Kamimura; Kentaro Fukushima; Yutaka Imamura; Tetsuya Eto; Kazutaka Sunami; Mototsugu Shimokawa; Koichi Akashi; Yuzuru KanakuraBLOOD 128 22 2016年12月
- 【白血病学(下)-最新の基礎、臨床研究-】 白血病の基礎研究と臨床研究の動向 白血病における遺伝子ゲノム研究の動向 慢性骨髄性白血病における遺伝子異常松村 到日本臨床 74 増刊10 白血病学(下) 462 - 467 (株)日本臨床社 2016年12月
- 【白血病学(下)-最新の基礎、臨床研究-】 白血病の基礎研究と臨床研究の動向 臨床研究の動向 ピオグリタゾンによるCML治療田中 宏和; 松村 到日本臨床 74 増刊10 白血病学(下) 526 - 530 (株)日本臨床社 2016年12月
- Koichi Miyamura; Toshihiro Miyamoto; Mitsune Tanimoto; Kazuhito Yamamoto; Shinya Kimura; Tatsuya Kawaguchi; Itaru Matsumura; Tomoko Hata; Hisashi Tsurumi; Shigeki Saito; Masayuki Hino; Seiji Tadokoro; Kuniaki Meguro; Hideo Hyodo; Masahide Yamamoto; Kohmei Kubo; Junichi Tsukada; Midori Kondo; Makoto Aoki; Hikaru Okada; Masamitsu Yanada; Kazuma Ohyashiki; Masafumi TaniwakiLEUKEMIA RESEARCH 51 11 - 18 2016年12月 [査読有り]
Optimal management of patients with chronic myeloid leukemia in chronic phase with suboptimal molecular response (MR) to frontline imatinib is undefined. We report final results from SENSOR, which evaluated efficacy/safety of nilotinib in this setting. A substudy assessed whether BIM polymorphisms impacted response to nilotinib. In this single-arm, multicenter study, Japanese patients with suboptimal MR per European LeukemiaNet 2009 criteria (complete cytogenetic response, but not major MR [MMR]) after >= 18 months of frontline imatinib received nilotinib 400 mg twice daily for 24 months. MR, BCR-ABL1 mutations/variants, and BIM polymorphisms were evaluated in a central laboratory. Primary endpoint was the MMR rate at 12 months (null hypothesis of 40%). Of 45 patients (median exposure, 22.08 months), 39 completed the study and six discontinued. At 12 and 24 months, 51.1% (95% CI, 35.8%-66.3%) and 66.7% (95% CI, 51.0%-80.0%) achieved MMR, respectively. Cumulative MMR incidence by 24 months was 75.6%. Of 40 patients analyzed, 10 of 12 (83.3%) with and 17 of 28 (60.7%) without BIM polymorphisms achieved MMR at 24 months. The safety profile was manageable with dose reductions and interruptions. Nilotinib provided clinical benefit for patients with suboptimal response to imatinib, and BIM polymorphisms did not influence MMR achievement. (C) 2016 Elsevier Ltd. All rights reserved. - Nakamine H; Yamakawa M; Yoshino T; Fukumoto T; Enomoto Y; Matsumura IJournal of clinical and experimental hematopathology : JCEH 56 2 118 - 118 日本リンパ網内系学会 2016年12月 [査読有り]
Langerhans cell (LC) histiocytosis (LCH) and LC sarcoma (LCS) are proliferative processes consisting of cells having morphologic and phenotypic features of Langerhans cells (LCs), although the latter may have lost some of these features. Because neoplastic nature of LCH as well as LCS is more likely by recent studies, a category of LC hyperplasia can be better characterized. LCH and LCS are rarely seen in daily pathology practice, but it is important to accurately characterize these lesions. For this purpose, an outline covering proliferations of LC and related cells was constructed. The scheme of this outline is based especially on evaluating borderline lesions, neoplastic trans-differentiation, and degree of similarity with the normal counter-parts. In addition, the organization and update of the current classification scheme for histiocytic and dendritic-cell proliferations is presented.
- Haruhiko Ninomiya; Naoshi Obara; Shigeru Chiba; Kensuke Usuki; Kaichi Nishiwaki; Itaru Matsumura; Tsutomu Shichishima; Shinichiro Okamoto; Jun-ichi Nishimura; Kazuma Ohyashiki; Shinji Nakao; Kiyoshi Ando; Yoshinobu Kanda; Tatsuya Kawaguchi; Hideki Nakakuma; Daisuke Harada; Hirozumi Akiyama; Taroh Kinoshita; Keiya Ozawa; Mitsuhiro Omine; Yuzuru KanakuraINTERNATIONAL JOURNAL OF HEMATOLOGY 104 5 548 - 558 2016年11月 [査読有り]
Data characterizing the safety and effectiveness of eculizumab in patients with paroxysmal nocturnal hemoglobinuria (PNH) are limited. We describe the safety and effectiveness of eculizumab in PNH patients enrolled in a post-marketing surveillance study. Types and frequencies of observed adverse events were similar to those reported in previous clinical trials and no meningococcal infection was reported. Effectiveness outcomes included the reduction of intravascular hemolysis, the change in hemoglobin (Hb) level, the withdrawal of transfusion and corticosteroids, the change of renal function, and overall survival. The effect of eculizumab on intravascular hemolysis was demonstrated by a reduction in lactate dehydrogenase levels at all measurements after baseline. Significant increases in Hb levels from baseline were also observed after 1 month's treatment with eculizumab (p < 0.01). Of those who were transfusion-dependent at baseline, the median number of transfusions decreased significantly from 18 to 0 unit/year after 1 year of treatment with eculizumab (p < 0.001). An increase in Hb and a high rate of transfusion independence were observed, especially in patients with platelet count aeyen150 x 10(9)/L. Approximately 97 % of patients showed maintenance or improvement of renal function. Overall survival rate was about 90 % (median follow-up 1.9 years). These results suggest an acceptable safety profile and favorable prognosis after eculizumab intervention. - 【新しいチロシンキナーゼ阻害薬】 各臓器がんに対する新しいチロシンキナーゼ阻害薬 造血器腫瘍(CML、CLL、その他)谷口 康博; 松村 到がん分子標的治療 14 3 284 - 289 (株)メディカルレビュー社 2016年10月さまざまながん種でdriver oncogeneが発見され、その変異であるdriver mutationが治療標的として重要視されている。Driver mutationに伴うチロシンキナーゼの恒常的活性化に対する阻害薬(TKI)は各臓器がんで臨床応用され、造血器腫瘍においても開発が進んでいる。慢性骨髄性白血病(CML)に対し用いられるイマチニブ(IM)は最も早く臨床応用されたTKIである。そのほか、B細胞性リンパ腫におけるブルトン型チロシンキナーゼ(BTK)、骨髄増殖性腫瘍(MPN)におけるJAK2、急性骨髄性白血病(AML)におけるFMS様チロシンキナーゼ-3(FLT3)など、さまざまなチロシンキナーゼを治療標的に多くの薬剤が開発され、すでに一部の薬剤は臨床応用されている。チロシンキナーゼによる治療は作用機序がこれまでの抗がん剤と異なることから、劇的な治療効果が得られる可能性や、副作用が軽減できる可能性があり、今後重要な治療選択肢となっていくことが期待される。現在開発中のものも含めた造血器腫瘍におけるTKIについて概説する。(著者抄録)
- 【白血病学(上)-最新の基礎、臨床研究-】 白血病・骨髄異形成症候群・骨髄増殖性腫瘍のWHO分類 骨髄異形成症候群森田 泰慶; 松村 到日本臨床 74 増刊8 白血病学(上) 396 - 401 (株)日本臨床社 2016年10月
- Koji Kawamura; Takashi Ikeda; Shotaro Hagiwara; Takehiko Mori; Atsushi Shinagawa; Kaichi Nishiwaki; Kazuteru Ohashi; Shiro Kubonishi; Takahiro Fukuda; Toshiro Ito; Naoto Tomita; Tatsuo Ichinohe; Koji Kato; Yasuo Morishima; Yoshiko Atsuta; Kazutaka Sunami; Yoshinobu KandaLEUKEMIA & LYMPHOMA 57 9 2077 - 2083 2016年09月 [査読有り]
Autologous hematopoietic stem cell transplantation (auto-HCT) is considered a standard therapy for transplant-eligible patients with multiple myeloma, while allogeneic HCT (allo-HCT) is controversial. We retrospectively analyzed 765 patients with myeloma who underwent tandem transplantation between 1998 and 2012 using Japanese registry data. We evaluated the clinical outcomes of tandem auto-HCT (n=676) and auto/allo-HCT (n=89). To adjust for a selection bias, we compared overall survival (OS) between the two groups by a propensity score analysis. The probability of OS at six years was 58.5% for the tandem auto-HCT group and 54.4% for the tandem auto/allo-HCT group (p=0.47). In a matched-pair analysis based on the propensity score, the difference in survival between the two groups was not statistically significant, although the survival curve appeared to reach a plateau beyond five years in the auto/allo group. Further strategies to reduce treatment-related mortality and enhance a graft-versus-myeloma effect are necessary to improve OS. - 【骨髄増殖性腫瘍のマネジメントと最近の展開】 ELN基準に基づいた慢性骨髄性白血病の治療効果判定とモニタリング谷口 康博; 松村 到血液内科 73 3 316 - 320 (有)科学評論社 2016年09月
- 李 進海; 野崎 祐史; 酒井 健史; 岸本 和也; 永禮 靖章; 船内 正憲; 松村 到日本臨床免疫学会会誌 39 4 409 - 409 (一社)日本臨床免疫学会 2016年08月
- 酒井 健史; 岡田 晃典; 冨田 大介; 伊丹 哲; 李 進海; 井上 明日圭; 田崎 知江美; 志賀 俊彦; 朝戸 佳世; 樋野 尚一; 岸本 和也; 永禮 靖章; 野崎 祐史; 船内 正憲; 松村 到日本臨床免疫学会会誌 39 4 409 - 409 (一社)日本臨床免疫学会 2016年08月
- M. Kato; T. Yamashita; R. Suzuki; K. Matsumoto; H. Nishimori; S. Takahashi; K. Iwato; C. Nakaseko; T. Kondo; K. Imada; F. Kimura; T. Ichinohe; Y. Hashii; K. Kato; Y. Atsuta; S. Taniguchi; T. FukudaLEUKEMIA 30 8 1742 - 1745 2016年08月 [査読有り]
- 【慢性骨髄性白血病の治療戦略2016】 (序)CML治療の歴史,現状と今後松村 到血液フロンティア 26 8 1071 - 1075 (株)医薬ジャーナル社 2016年07月慢性骨髄性白血病(CML)は,BCR-ABLが病因遺伝子として同定され,BCR-ABL蛋白を標的としたチロシンキナーゼ阻害薬(TKI)が開発された。第一世代TKIのイマチニブによりCMLの予後は劇的に改善し,多くの患者が余命を全うできるようになった。さらに,第二世代TKIも臨床応用されている。今後のCML治療は,すべての症例で病期進行による死亡を回避するのみでなく,長期にわたるQOLの低下や経済的な問題を解決するために,STOP試験や新規薬剤を用いた治癒に向けた新たな戦略の確立に期待したい。(著者抄録)
- 小杉 智; 柴山 浩彦; 中谷 英仁; 木田 亨; 太田 健介; 金子 仁臣; 八木 秀男; 田中 宏和; 淵田 真一; 中谷 綾; 小林 正行; 黒田 純也; 上辻 由里; 魚嶋 伸彦; 足立 陽子; 通堂 満; 島崎 千尋; 野村 昌作; 日野 雅之; 松村 到; 谷脇 雅史; 金倉 譲; 高折 晃史臨床血液 57 7 839 - 847 (一社)日本血液学会-東京事務局 2016年07月新規薬剤により骨髄腫患者の生存が延長すると共に,二次がん発生が問題になっている。今回,関西骨髄腫フォーラム(KMF)データベースを用い,2012年11月〜2015年3月に登録された骨髄腫および関連疾患1571例について二次がん発生を解析した。観察期間(中央値31ヵ月)内に血液腫瘍が10例,固形がんが36例に発生していた(5年累積発生率:血液腫瘍1.0%,固形がん3.7%)。未治療の無症候性骨髄腫およびMGUS症例では,固形がん発生を認める一方で血液腫瘍発生は認めなかったが,累積発生率においては治療例との間に有意差を認めなかった。一方,melphalan,bortezomib,lenalidomideおよびthalidomideの4剤それぞれの投与歴を見た場合,血液腫瘍発生への影響は統計学的に認められない一方,レナリドマイド投与歴のある患者で固形がん発生が多く認められた。より詳細な検討には,本データベースへのさらなる症例数の蓄積と,長期の観察が必要と考える。(著者抄録)
- 腎間質線維化病態におけるIL-18Rの役割の検討永禮 靖章; 伊丹 哲; 酒井 健史; 李 進海; 田崎 知江美; 井上 明日圭; 志賀 俊彦; 朝戸 佳世; 樋野 尚一; 岸本 和也; 野崎 祐史; 船内 正憲; 松村 到日本腎臓学会誌 58 3 364 - 364 (一社)日本腎臓学会 2016年05月
- Kenshi Suzuki; Atsushi Shinagawa; Toshiki Uchida; Masafumi Taniwaki; Hirokazu Hirata; Kenichi Ishizawa; Kosei Matsue; Yoshiaki Ogawa; Takayuki Shimizu; Maki Otsuka; Morio Matsumoto; Shinsuke Iida; Yasuhito Terui; Itaru Matsumura; Takashi Ikeda; Naoki Takezako; Yumi Ogaki; Shuichi Midorikawa; Vanessa Houck; Annette Ervin-Haynes; Takaaki ChouCANCER SCIENCE 107 5 653 - 658 2016年05月 [査読有り]
In the FIRST trial (MM-020), lenalidomide plus low-dose dexamethasone (Rd) reduced the risk of disease progression or death compared with combination melphalan-prednisone-thalidomide. As the FIRST trial did not include any Japanese patients, the efficacy and safety of continuous treatment with Rd was evaluated in 26 Japanese patients with newly diagnosed multiple myeloma (NDMM) in a singlearm, multicenter, open-label phase II trial (MM-025). Patients received lenalidomide on days 1-21 of each 28-day cycle, with a starting dose of 25 mg/day (dose adjusted for renal impairment), and 40 mg/day dexamethasone (dose adjusted for age) on days 1, 8, 15 and 22 of each 28-day cycle until disease progression or discontinuation for any reason. In the efficacy evaluable population, overall response rate was 87.5%, including 29.2% of patients who achieved a complete response/very good partial response. Median durations of response, progressionfree survival and overall survival have not been reached. The most common grade 3-4 adverse events were neutropenia (23%) and anemia (19%). The efficacy and safety of Rd were consistent with data from larger studies, including the FIRST trial, thereby supporting the use of Rd continuous in Japanese patients with NDMM who are ineligible for stem cell transplantation. - Chikashi Yoshida; Hirohisa Nakamae; Linda Fletcher; Daisuke Koga; Takayuki Sogabe; Itaru Matsumura; Yuzuru Kanakura; Susan Branford; Tomoki NaoeSPRINGERPLUS 5 1 2016年05月 [査読有り]
Background: Detection and quantitation of BCR-ABL1 transcripts are crucial for managing patients with chronic myeloid leukemia (CML). Although real-time quantitative polymerase chain reaction (RT-qPCR) can be measured on an International Scale (IS), this has not become fully universal. By using a WHO international standard panel established for calibrating secondary standards based on the IS, we have previously developed an RT-qPCR kit, ODK-1201, for quantification of major BCR-ABL1.Results: In this study, the reliability of kit-specific conversion factor 1.12 was validated by exchanging patients' samples between three local clinical laboratories and a reference laboratory. The mean bias of the local method after IS conversion was 1.6 fold lower than the reference method. The clinically-useful sensitivity of the kit was further evaluated for monitoring patients with deep molecular response. Based on the correlation of the IS values between ODK-1201 and the reference laboratory method, the detection level of the kit was estimated as 0.0032 % BCR-ABL1(IS).Conclusions: ODK-1201 is a highly sensitive one-step RT-qPCR system for detecting BCR-ABL1 on the IS in 2 h after RNA extraction, thus contributing to standardization of molecular monitoring in CML. - 芹澤 憲太郎; 森田 泰慶; 口分田 貴裕; 田中 宏和; 山田 枝里佳; 芦田 隆司; 松村 到日本輸血細胞治療学会誌 62 2 272 - 272 (一社)日本輸血・細胞治療学会 2016年04月
- 【遺伝子解析に基づく新しい分子標的治療】 遺伝子解析に基づく新しい分子標的治療南 博信; 中島 貴子; 間野 博行; 松村 到がん分子標的治療 14 1 68 - 75 (株)メディカルレビュー社 2016年04月遺伝子解析に基づいた分子標的治療により、個別化治療が実臨床でも行われるようになっている。乳がんではヒト上皮成長因子受容体(HER)2に対するトラスツズマブやラパチニブが使われ、また予後因子かつ効果予測因子であるOncotype DXなどが開発されている。大腸がんでもOncotype DXやColoPrintが開発されているが、まだ実臨床レベルには至っていない。大腸がんではRAS遺伝子変異が抗上皮成長因子受容体(EGFR)抗体の効果予測因子であり、最近では予後不良因子であることも示唆されている。また、予後不良因子であるBRAF遺伝子変異例に対する3剤併用療法や、マイクロサテライト不安定性(MSI)のある大腸がんに対する免疫チェックポイント阻害薬の開発が注目されている。血液がん領域では早くから遺伝子解析に基づく個別化治療が行われてきた。BCR-ABLキメラ型遺伝子に対してイマチニブを筆頭にチロシンキナーゼ阻害薬(TKI)が、またFMS様チロシンキナーゼ3(FLT3)などの活性型遺伝子変異についても開発が進められている。全ゲノム解析によって造血器腫瘍は多様なクローンからなることが明らかになり、いかに有効に分子標的薬を組み合わせてそれに対応するかが課題となっている。肺がんでは、EML4-ALK融合遺伝子の発見によりALK阻害薬の開発が一気に進み、EGFR遺伝子変異とともに、遺伝子解析による個別化治療が行われている。ただし、分子標的薬による耐性が出現した際にはリキッドバイオプシーを含め、その都度検体を採取して解析することが重要である。また、今後は複数の遺伝子を同時に検査できる体制の構築が求められる。(著者抄録)
- その他の膠原病 リウマチ性多発筋痛症における関節エコー所見とMMP-3の変化に関する検討井上 明日圭; 野崎 祐史; 伊丹 哲; 酒井 健史; 田崎 知江美; 李 進海; 湯本 妙子; 朝戸 佳世; 志賀 俊彦; 樋野 尚一; 矢野 智洋; 岸本 和也; 永禮 靖章; 嶋津 秀紀; 木下 浩二; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 60回 320 - 320 (一社)日本リウマチ学会 2016年03月
- その他の膠原病 成人発症スティル病10例を含む膠原病患者におけるプロカルシトニンの検討酒井 健史; 伊丹 哲; 井上 明日圭; 田崎 知江美; 李 進海; 湯本 妙子; 朝戸 佳世; 志賀 俊彦; 樋野 尚一; 矢野 智洋; 岸本 和也; 嶋津 秀紀; 永禮 靖章; 野崎 祐史; 木下 浩二; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 60回 323 - 323 (一社)日本リウマチ学会 2016年03月
- その他の膠原病 成人発症Still病における血清IL-18濃度測定の臨床的有用性の検討志賀 俊彦; 伊丹 哲; 酒井 健史; 井上 明日圭; 田崎 知江美; 李 進海; 朝戸 佳世; 樋野 尚一; 岸本 和也; 永禮 靖章; 野崎 祐史; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 60回 323 - 323 (一社)日本リウマチ学会 2016年03月
- SLE・抗リン脂質抗体症候群 ループス腎炎 ループス腎炎におけるKim-1の治療反応効果に対する意義野崎 祐史; 伊丹 哲; 酒井 健史; 李 進海; 田崎 知江美; 井上 明日圭; 志賀 俊彦; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 60回 351 - 351 (一社)日本リウマチ学会 2016年03月
- リウマチ性疾患の画像 関節リウマチにおける症状の日内変動と関節超音波所見との関連性について李 進海; 伊丹 哲; 酒井 健史; 井上 明日圭; 田崎 知江美; 朝戸 佳世; 志賀 俊彦; 樋野 尚一; 岸本 和也; 永禮 靖章; 野崎 祐史; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 60回 438 - 438 (一社)日本リウマチ学会 2016年03月
- ビスホスホネート治療抵抗性の骨量減少・骨粗鬆症患者におけるデノスマブの治療効果について永禮 靖章; 伊丹 哲; 酒井 健史; 李 進海; 田崎 知江美; 井上 明日圭; 志賀 俊彦; 朝戸 佳世; 矢野 智洋; 樋野 尚一; 岸本 和也; 野崎 祐史; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 60回 574 - 574 (一社)日本リウマチ学会 2016年03月
- IgG4関連疾患に類似した好酸球性肉芽腫性血管炎の1例伊丹 哲; 酒井 健史; 井上 明日圭; 田崎 知江美; 李 進海; 朝戸 佳世; 志賀 俊彦; 樋野 尚一; 岸本 和也; 永禮 靖章; 野崎 祐史; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 60回 660 - 660 (一社)日本リウマチ学会 2016年03月
- 疾患と検査値の推移 慢性骨髄性白血病松村 到検査と技術 44 1 48 - 56 (株)医学書院 2016年01月<Point>慢性期の慢性骨髄性白血病(CML-CP)を無治療で放置する,あるいは治療効果が不十分であると,移行期(AP),急性転化期(BP)へと病期が進行し,極めて予後不良となる.CML-CPにおいて病期進行を回避するためには,より早期にCML細胞を減少させることが必要である.治療効果は,血液学的検査,細胞遺伝学的(染色体)検査,分子遺伝学的(BCR-ABL mRNAの定量)検査によって評価される.CML-CPをチロシンキナーゼ阻害薬(TKI)で治療開始した際には,治療開始後各時期での治療目標が設定されている.(著者抄録)
- Tomoyuki Sasano; Takuji Tomimatsu; Jun-ichi Nishimura; Itaru Matsumura; Yuzuru Kanakura; Tadashi KimuraBLOOD COAGULATION & FIBRINOLYSIS 27 1 109 - 112 2016年01月 [査読有り]
Paroxysmal nocturnal haemoglobinuria (PNH) is a rare acquired disorder of haematopoietic stem cells characterized by intravascular haemolysis, cytopenias and thrombophilia. Thrombophilia is the leading cause of mortality in patients with PNH. As the risk of thrombogenesis further increases during pregnancy and the postpartum period, an anticoagulant therapy is generally recommended for pregnant women with PNH. However, there are no standardized criteria for determining the appropriate dose of anticoagulant therapy. We describe the case of a PNH patient with who was managed with anticoagulant therapy at different doses during two consecutive pregnancies. A prophylactic dose of heparin was administered during her first pregnancy and a therapeutic dose, during her second pregnancy. Both pregnancies resulted in uncomplicated vaginal deliveries without thrombosis. Interestingly, not only D-dimer (as a thrombotic marker) but also lactate dehydrogenase (as a haemolytic marker) levels were lower during her second pregnancy when a therapeutic dose of heparin was used. Blood Coagul Fibrinolysis 27: 109-112 Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved. - Yuji Nozaki; Koji Kinoshita; Jinhai Ri; Kenji Sakai; Toshihiko Shiga; Shoichi Hino; Yasuaki Hirooka; Masahumi Sugiyama; Masanori Funauchi; Itaru MatsumuraMODERN RHEUMATOLOGY 26 2 265 - 270 2016年 [査読有り]
Objective: Gastroesophageal reflux disease (GERD) is one of the most common comorbidity in many diseases, but the frequency in rheumatic disease has not been well understood. Methods: We investigated the prevalence of GERD by GerdQ in 530 rheumatic patients [systematic lupus erythematosus (SLE; n = 120), rheumatoid arthritis (RA; n = 117), polymyalgia rheumatica (PMR; n = 40), dermatomyositis and polymyositis (PM/DM; n = 38), systemic scleroderma (SSc; n = 37), mixed connective tissue disease (MCTD; n = 18), Behc, et disease (BD; n = 17), adult onset still disease (AOSD; n = 14), and other rheumatic diseases (n = 129)]. Results: The mean GerdQ scores of patients was 6.2 +/- 1.8, respectively, and no significant differences were observed between all patients. However, the GERD prevalence in SSc and BD was increased compared to that in SLE, RA, PMR, PM/DM, MCTD, and AOSD. In no medication of proton pump inhibitors (PPIs), a significant increase in the risk of GERD symptoms was 2.5 times compared with that in the medication of PPIs in all patients by multivariable regression analysis. On the other hand, there were no increased risks of GERD symptoms with corticosteroids. Conclusion: In rheumatic diseases, GerdQ would be the useful tool of diagnosis GERD, regardless whether the patients complain or not about gastrointestinal (GI) symptoms. - Sato M; Oiso N; Shiga T; Morita R; Kimura M; Funauchi M; Matsumura I; Kawada AActa dermato-venereologica 96 4 568 - 569 2016年 [査読有り]
- 松村 到血液内科 71 6 759 - 764 (有)科学評論社 2015年12月
- Kentaro Serizawa; Yasuyoshi Morita; Yosaku Watatani; Yasuyo Oyama; Chikara Hirase; Hirokazu Tanaka; Junichi Miyatake; Yoichi Tatsumi; Takashi Ashida; Itaru MatsumuraANNALS OF ONCOLOGY 26 108 - 108 2015年11月 [査読有り]
- 【造血器腫瘍の分子標的治療の進歩】 序 分子標的治療の歴史と今後松村 到血液フロンティア 25 12 1715 - 1719 (株)医薬ジャーナル社 2015年11月分子標的療法は従来の抗がん剤とは異なり、腫瘍化に関わる分子あるいは腫瘍細胞に強く発現する分子を標的とする。2001年に初めて登場したImatinib、Rituximabは、慢性骨髄性白血病、悪性リンパ腫に対して、従来の抗がん剤では期待できないほどの画期的な治療効果を示し、現在ではほぼすべての造血器腫瘍に対して分子標的療法が臨床応用されている。今後は、分子標的療法の併用、近年脚光を浴びている抗腫瘍免疫療法との併用も期待される。(著者抄録)
- Isamu Sugiura; Satomi Terabe; Tomohiro Kinoshita; Kazuhito Yamamoto; Masashi Sawa; Yukiyasu Ozawa; Yoshiko Atsuta; Ritsuro Suzuki; Kazuyuki ShimizuINTERNATIONAL JOURNAL OF HEMATOLOGY 102 4 434 - 440 2015年10月 [査読有り]
The present study was conducted to determine the recommended dose (RD) of cyclophosphamide (CPM) in the CBD regimen, a triplet combination of CPM, bortezomib (BTZ), and dexamethasone (Dex), for relapsed and/or refractory multiple myeloma (RRMM). Patients received intravenous CPM on days 1 and 8 at one of three dose levels: 300, 400, or 500 mg/m(2), with dose escalation in a 3 + 3 design. BTZ at 1.3 mg/m(2) was given twice weekly in 3-week cycles, with Dex at 20 mg/m(2) on the day of and day after BTZ. Of 16 patients enrolled, 15 eligible patients were allocated to the study. Dose-limiting toxicities (DLTs) were seen in two patients: one in dose level 1 with increased gamma-GTP and the other in dose level 3 with increased gamma-GTP and ALT. Both patients spontaneously recovered from DLT. Neither therapy-related mortality nor severe adverse events were reported during the study. Therefore, the RD of CPM was determined as 500 mg/m(2). Overall, 2 (13.3 %), 1 (6.7 %), and 8 (53.3 %) patients achieved CR, VGPR, and PR, respectively. The regimen was well tolerated and showed promising activity in patients with RRMM. - Takaaki Konuma; Satoshi Takahashi; Naoyuki Uchida; Yachiyo Kuwatsuka; Satoshi Yamasaki; Jun Aoki; Yasushi Onishi; Nobuyuki Aotsuka; Kazuteru Ohashi; Takehiko Mori; Masayoshi Masuko; Hirohisa Nakamae; Kouichi Miyamura; Koji Kato; Yoshiko Atsuta; Seiko Kato; Shigetaka Asano; Akiyoshi Takami; Yasushi MiyazakiBIOLOGY OF BLOOD AND MARROW TRANSPLANTATION 21 9 1632 - 1640 2015年09月 [査読有り]
Granulocyte colony stimulating factor (G-CSF) increases the susceptibility of dormant malignant or nonmalignant hematopoietic cells to cytarabine arabinoside (Ara-C) through the induction of cell cycle entry. Therefore, G-CSF combined conditioning before allogeneic stem cell transplantation might positively contribute to decreased incidences of relapse and graft failure without having to increase the dose of cytotoxic drugs. We conducted a retrospective nationwide study of 336 adult patients with myelodysplastic syndrome (MDS) and secondary acute myeloid leukemia (sAML) after single-unit cord blood transplantation (CBT) who underwent 4 different kinds of conditioning regimens: total body irradiation (TBI) >= 8 Gy + Ara-C/G-CSF + cyclophosphamide (CY) (n = 65), TBI >= 8 Gy + Ara-C + CY (n = 119), TBI >= 8 Gy +other (n = 104), or TBI < 8 Gy or non-TBI (n = 48). The TBI >= 8 Gy + Ara-C/G-CSF + CY regimen showed significantly higher incidence of neutrophil engraftment (hazard ratio, 1.52; 95% confidence interval [CI], 1.10 to 2.08; P = .009) and lower overall mortality (hazard ratio, .46; 95% CI, .26 to .82; P = .008) rates compared with those without a G-CSF regimen. This retrospective study shows that the G-CSF combined conditioning regimen provides better engraftment and survival results. in CBT for adults with MDS and sAML. (C) 2015 American Society for Blood and Marrow Transplantation. - Shinya Rai; Hirokazu Tanaka; Toshio Watanabe; Yuzuru Kanakura; Itaru MatsumuraEXPERIMENTAL HEMATOLOGY 43 9 S90 - S90 2015年09月 [査読有り]
- Hirokazu Tanaka; Shinya Rai; Toshio Watazzabe; Yuzuru Kanakura; Itaru MatsumuraEXPERIMENTAL HEMATOLOGY 43 9 S98 - S98 2015年09月 [査読有り]
- 松村 到最新医学 70 9 1877 - 1883 (株)最新医学社 2015年09月慢性期の慢性骨髄性白血病(CML)の現在の治療目標は治癒させることである.このためにCML幹細胞において機能する細胞内シグナル伝達,自己複製,細胞周期,代謝,立体構造,オートファジーの制御分子などを標的とした新規分子標的薬剤の臨床試験が進んでいる.また,インターフェロン,ワクチン,PD-1/PD-L1などの免疫チェック機構を標的とした抗腫瘍免疫機構を活性化する治療法の開発も進んでいる.(著者抄録)
- 酒井 健史; 野崎 祐史; 伊丹 哲; 李 進海; 井上 明日圭; 田崎 知江美; 志賀 俊彦; 朝戸 佳世; 樋野 尚一; 矢野 智洋; 岸本 和也; 船内 正憲; 松村 到臨床リウマチ 27 3 205 - 211 (一社)日本臨床リウマチ学会 2015年09月43歳、女性。発熱、顔面と体幹部の紅斑、関節痛を示す成人発症スティル病に対して、プレドニゾロンの投与が行われたが、治療抵抗性であり、播種性血管内凝固を併発した。血漿交換を施行、シクロフォスファミド、シクロスポリンを追加し、病状は改善した。その後、寛解維持目的としてトシリズマブを導入し、疾患活動性の低下を認めた。プレドニゾロン、シクロスポリンを漸減、中止したが寛解状態は維持できた。トシリズマブの寛解維持における意義について検討した。(著者抄録)
- Hirohisa Nakamae; Chikashi Yoshida; Yasuhiko Miyata; Michihiro Hidaka; Naokuni Uike; Daisuke Koga; Takayuki Sogabe; Itaru Matsumura; Yuzuru Kanakura; Tomoki NaoeINTERNATIONAL JOURNAL OF HEMATOLOGY 102 3 304 - 311 2015年09月 [査読有り]
The current first-line therapy of chronic myeloid leukemia (CML) is based on tyrosine kinase inhibitors. Diagnostic kits that are capable of identifying at least a 4.5 log reduction in the international scale % BCR-ABL/ABL (IS % BCR-ABL/ABL) are needed for use in the clinical evaluation of deeper molecular response to treatment and to determine the timing of dose selection or treatment interruption during the course of treatment. In this study, we evaluated the performance of a new diagnostic kit, ODK-1201, designed to be capable of performing reverse transcription and quantitative PCR in a single tube for the quantitation of major BCR-ABL mRNA. The kit demonstrated excellent assay performance (limit of detection 0.0007 %) and a broader detection range of BCR-ABL mRNA in peripheral blood compared to a commercially available kit for CML (Amp-CML). ODK-1201 was also shown to be as sensitive as Ipsogen and Molecular MD kits in the same assay. Results obtained in this study indicate evidences that ODK-1201 was capable of identifying at least a 4.5 log reduction in the IS % BCR-ABL/ABL. - Mami Sumiyoshi; Narumi Masuda; Nobuhiro Tanuma; Honami Ogoh; Eri Imai; Mizuki Otsuka; Natsuki Hayakawa; Kinuyo Ohno; Yasuhisa Matsui; Kanae Hara; Risa Gotoh; Mai Suzuki; Shinya Rai; Hirokazu Tanaka; Itaru Matsumura; Hiroshi Shima; Toshio WatanabeFEBS LETTERS 589 19 2754 - 2762 2015年09月 [査読有り]
In mammals, the small Arf GTPase-activating protein (SMAP) subfamily of An GTPase-activating proteins consists of closely related members, SMAP1 and SMAP2. These factors reportedly exert distinct functions in membrane trafficking, as manifested by different phenotypes seen in single knockout mice. The present study investigated whether SMAP proteins interact genetically. We report for the first time that simultaneous loss of SMAP1 and SMAP2 promotes apoptosis in the distal region of E7.5 mouse embryos, likely resulting in embryonic lethality. Thus, at least one SMAP gene, either SMAP1 or SMAP2, is required for proper embryogenesis. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. - Midori Yanagihara; Naoki Oiso; Hirokazu Tanaka; Tomohiko Narita; Eisuke Enoki; Masatomo Kimura; Hirokazu Nakamine; Itaru Matsumura; Akira KawadaJOURNAL OF DERMATOLOGY 42 8 844 - 845 2015年08月 [査読有り]
- Osamu Hirata; Satoshi Okada; Miyuki Tsumura; Shuhei Karakawa; Itaru Matsumura; Yujiro Kimura; Toshiro Maihara; Shin'ichiro Yasunaga; Yoshihiro Takihara; Osamu Ohara; Masao KobayashiJOURNAL OF CLINICAL IMMUNOLOGY 35 5 512 - 516 2015年07月 [査読有り]
Purpose To confirm and characterize mosaicism of the cyclic neutropenia (CyN)-related mutation in the ELANE gene identified in the asymptomatic mother of patients with CyN. Methods We identified sibling cases with CyN due to a novel heterozygous splicing site mutation, IVS4 +5SD G > T, in the ELANE gene, resulting in an internal in-frame deletion of 30 nucleotides (corresponding to a ten amino acid deletion, V161-F170). The mutated allele was also detected in their asymptomatic mother but at low frequency. We measured the frequency of the mutant allele from peripheral blood leukocytes (PBLs) by subcloning, and confirmed the allelic frequency of mosaicism in various cell types by massively parallel DNA sequencing (MPS) analysis. Results In the subcloning analysis, the mutant allele was identified in 21.36 % of PBLs from the asymptomatic mother, compared with 54.72 % of PBLs from the CyN patient. In the MPS analysis, the mutant allele was observed in approximately 30 % of mononuclear cells, CD3(+) T cells, CD14(+) monocytes and the buccal mucosa. Conversely, it was detected in low frequency in polymorphonuclear leukocytes (PLMLs) (3-4 %) and CD16(+) granulocytes (2-3 %). Conclusions Mosaicism of the ELANE mutation has only previously been identified in one confirmed and one unconfirmed case of SCN. This is the first report of mosaicism of the ELANE mutation in a case of CyN. The MPS results suggest that this de novo mutation occurred during the two-cell stage of embryogenesis. PLMLs expressing the ELANE mutation were found to be actively undergoing apoptosis. - Hino Shoichi; Nozaki Yuji; Nagare Yasuaki; Kinoshita Koji; Funauchi Masanori; Matsumura ItaruACTA MEDICA KINKI UNIVERSITY = The Kinki University Medical Association 40 1 15 - 22 Kinki University Medical Association 2015年06月
Interleukin (IL)-18 has important roles in the pathogenesis of organ failure caused by endotoxemia. To determine whether IL-18 receptor(R)αsignaling ameliorates or deteriorates the renal function in lipopolysaccharide (LPS)-induced acute kidney injury(AKI), we compared IL-18Rα knockout (KO) mice with wild-type (WT) mice following LPS injection. As the results, IL-18Rα deficiency ameliorated the renal function and reduced the serum level of pro-inflammatory cytokines, such as tumor necrosis factor (TNF), interferon-gamma (IFN-γ), and IL-18. The renal suppressor of cytokine signaling 1(SOCS1) mRNA expression was also significantly reduced in IL-18Rα KO mice compared with WT mice. In addition, the adoptivetransfer of splenocytes from WT mice into IL-18Rα KO mice increased their serum pro-inflammatory cytokine levels and deteriorated the renal function In conclusion, IL-18Rα deficiency ameliorated the release of systemic pro-inflammatory cytokines and renal function in mice with LPS-induced AKI. Thus, IL-18Rα affects renal injury through the pro-inflammatory cytokine signaling pathway in the pathogenesis of LPS-induced AKI. - 頼 晋也; 豊嶋 崇徳; 福原 規子; 飛内 賢正; 畠 清彦; 下山 達; 安藤 潔; 内田 俊樹; 永井 宏和; 谷脇 雅史; 柴山 浩彦; 中前 博久; 松村 到; 石川 隆之; 一戸 辰夫; 加藤 光次; 日高 道弘日本リンパ網内系学会会誌 55 108 - 108 (一社)日本リンパ網内系学会 2015年06月
- 和田 裕介; 樋口 智紀; 藤田 貢; 頼 晋也; 前倉 俊治; 浦瀬 文明; 松村 到; 義江 修近畿大学医学雑誌 = Medical Journal of Kinki University 40 1 23 - 29 近畿大学医学会 2015年06月 [査読有り]
[抄録] びまん性大細胞型B細胞性リンパ腫(diffuse large B-cell lymphoma/DLBCL)は非ホジキンリンパ腫の中で最頻のサブタイプである. 本疾患に対しては, シクロホスファミド, ドキソルビシン, ビンクリスチン, およびプレドニゾロンの併用療法, いわゆるCHOP療法が長きにわたり標準治療法であった. しかし近年, CD20を標的としたキメラIgG1モノクローナル抗体であるリツキシマブがDLBCLに著効することが示され, これを加えたR-CHOPが現在では実質的標準治療となっている. 一方SOX4はSOXファミリーに属する転写因子である. これは未熟B/Tリンパ球の分化増殖に関わることが知られ, さらに成人T細胞白血病リンパ腫をはじめとする複数の悪性腫瘍においては癌遺伝子として作用する. しかしながらDLBCLとSOX4との関連については未だ不明である. そこで本研究ではDLBCLにおけるSOX4発現と治療応答性および予後との相関について検証した. 我々の集めたDLBCL 70症例の検討から, SOX4のタンパクおよびmRNAレベルでの発現量はともにR-CHOP応答性と負の相関を示した. また予後解析によりSOX4発現量はDLBCL患者の予後不良とも相関を示した. これらの結果よりSOX4がDLBCLの予後予測因子として有用である可能性が示された. - 【Ph陰性骨髄増殖性腫瘍〜分子病態と治療の最前線〜】 好酸球増加症(増加症候群)の病態と治療田中 宏和; 松村 到血液フロンティア 25 7 977 - 986 (株)医薬ジャーナル社 2015年06月好酸球増加をきたす疾患は多岐にわたるが、大きく腫瘍性、反応性、特発性に分類される。その原因によらず、好酸球増加が持続すると、浸潤した組織に炎症、線維化が生じ、結果として臓器障害が引き起こされる。特に、心合併症が重篤である。診断は、反応性好酸球増加の鑑別、造血器腫瘍の有無、クロナリティ、および異常T細胞の検索により行う。PDGFRA/B遺伝子異常を有する好酸球増加に対しては、イマチニブ投与により劇的な予後の改善が得られるため、より的確な診断が求められる。(著者抄録)
- 急性腎障害におけるRho kinaseシグナル抑制経路を介した抗炎症・アポトーシス効果について野崎 祐史; 木下 浩二; 樋野 尚一; 矢野 智洋; 廣岡 靖明; 船内 正憲; 松村 到日本腎臓学会誌 57 3 538 - 538 (一社)日本腎臓学会 2015年04月
- Yuji Nozaki; Koji Kinoshita; Shoichi Hino; Tomohiro Yano; Kaoru Niki; Yasuaki Hirooka; Kazuya Kishimoto; Masanori Funauchi; Itaru MatsumuraAMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY 308 8 F899 - F909 2015年04月 [査読有り]
Nephrotoxicity is a frequent complication of cisplatin-induced chemotherapy, in which T cells are known to promote acute kidney injury (AKI). Apoptosis and necrosis of tubules and inflammatory events also contribute to the nephrotoxicity. A delineation of the mechanisms that underlie the inappropriate renal and tubular inflammation can thus provide important insights into potential therapies for cisplatin-induced AKI. Rho-kinases are known to act as molecular switches controlling several critical cellular functions, including cell migration, cytokine production, and apoptosis. Here, we show that the Rho-kinase inhibitor fasudil attenuated cisplatin nephrotoxicity, resulting in less histological damage, improved renal function, and the infiltration of fewer leukocytes into the kidney. Renal nuclear factor-kappa B activation and apoptosis were reduced, and the expressions of proinflammatory renal cytokine and chemokine mRNA were decreased. Urinary and renal kidney injury molecule-1 (Kim-1) expression was also reduced, a finding that is consistent with diminished kidney injury. In the current study, we also showed that fasudil could be protective of the impaired tubules. In vitro, fasudil reduced the apoptosis (annexin-V + PI cells) and cytokine production (tumor necrosis factor+ cells) in T cells and the apoptosis (annexin-V + PI cells) and tubular damage (Kim-1 + cells) in proximal tubular cells by flow cytometric analysis. As Rho-kinase plays an important role in promoting cisplatin nephrotoxicity, inhibiting Rho-kinase may be a therapeutic strategy for preventing cisplatin-induced AKI. - 【がん分子標的治療の副作用と対策】 薬剤別副作用対策 造血器腫瘍に対する分子標的薬田中 宏和; 松村 到がん分子標的治療 13 1 37 - 45 (株)メディカルレビュー社 2015年04月造血器腫瘍領域では、白血病、リンパ腫、骨髄腫などに対して、低分子化合物や抗体製剤などの分子標的薬が他に先駆けて臨床応用され、画期的な成果を挙げている。一方で、分子標的薬投与により従来の抗がん薬とは異なる特異的な副作用が出現し、多くの場合に投与量の規定因子となることも明らかになってきている。今後も数多くの新規分子標的薬の登場が期待されるが、投与時の副作用は治療薬を選択するうえでも重要な因子であり、その使用にあたっては十分な理解と経験が求められる。また多くの薬剤は、十分な治療効果を達成し、維持するために長期間の投与を必要とすることから、長期安全性にも十分な注意が必要である。本稿では、造血器腫瘍に対する代表的な分子標的薬であるチロシンキナーゼ阻害薬(TKI)、抗体製剤(抗CD20抗体、抗CCR4抗体)、プロテアソーム阻害薬、免疫調節薬(IMiDs)の主な副作用とその対策について概説する。(著者抄録)
- その他の膠原病 成人発症Still病とリンパ腫関連血球貪食症候群における血清IL-18測定の臨床的意義志賀 俊彦; 伊丹 哲; 酒井 健史; 井上 明日圭; 田崎 知江美; 李 進海; 湯本 妙子; 朝戸 佳世; 樋野 尚一; 矢野 智洋; 岸本 和也; 永禮 靖章; 嶋津 秀紀; 野崎 祐史; 木下 浩二; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 59回 343 - 343 (一社)日本リウマチ学会 2015年03月
- 関節リウマチの治療評価と予測 生物学的製剤導入前における関節超音波所見の治療反応予測因子としての有用性について野崎 祐史; 酒井 健史; 李 進海; 井上 明日圭; 田崎 知江美; 朝戸 佳世; 志賀 俊彦; 矢野 智洋; 樋野 尚一; 永禮 靖章; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 59回 361 - 361 (一社)日本リウマチ学会 2015年03月
- RA関連特殊病態 リウマチ性多発筋痛症に対する関節エコーの有用性について井上 明日圭; 野崎 祐史; 伊丹 哲; 酒井 健史; 田崎 智江美; 李 進海; 湯本 妙子; 朝戸 佳世; 志賀 俊彦; 樋野 尚一; 矢野 智洋; 岸本 和也; 永禮 靖章; 嶋津 秀紀; 木下 浩二; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 59回 420 - 420 (一社)日本リウマチ学会 2015年03月
- 当科の膠原病患者におけるプロカルシトニンの検討酒井 健史; 伊丹 哲; 井上 明日圭; 田崎 知江美; 李 進海; 湯本 妙子; 志賀 俊彦; 朝戸 佳世; 矢野 智洋; 樋野 尚一; 岸本 和也; 嶋津 秀紀; 永禮 靖章; 野崎 祐史; 木下 浩二; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 59回 528 - 528 (一社)日本リウマチ学会 2015年03月
- 関節リウマチにおける症状の日内変動と関節超音波所見との関連性について李 進海; 伊丹 哲; 酒井 健史; 井上 明日圭; 田崎 知江美; 朝戸 佳世; 志賀 俊彦; 矢野 智洋; 樋野 尚一; 岸本 和也; 永禮 靖章; 野崎 祐史; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 59回 545 - 545 (一社)日本リウマチ学会 2015年03月
- ビスホスホネートからデノスマブへ変更することによるQOLと骨密度変化に与える影響について永禮 靖章; 伊丹 哲; 酒井 健史; 井上 明日圭; 田崎 知江美; 李 進海; 湯本 妙子; 朝戸 佳世; 志賀 俊彦; 樋野 尚一; 矢野 智洋; 岸本 和也; 嶋津 秀紀; 野崎 祐史; 木下 浩二; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 59回 572 - 572 (一社)日本リウマチ学会 2015年03月
- 早期診断から集学的治療を行い、救命し得た劇症型抗リン脂質抗体症候群の1例伊丹 哲; 酒井 健史; 李 進海; 田崎 知江美; 井上 明日圭; 湯本 妙子; 志賀 俊彦; 朝戸 佳世; 矢野 智洋; 樋野 尚一; 岸本 和也; 嶋津 秀紀; 永禮 靖章; 野崎 祐史; 木下 浩二; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 59回 643 - 643 (一社)日本リウマチ学会 2015年03月
- Kohei Hanaoka; Makoto Hosono; Yoichi Tatsumi; Kazunari Ishii; Sung-Woon Im; Norio Tsuchiya; Kenta Sakaguchi; Itaru MatsumuraEJNMMI RESEARCH 5 1 2015年03月 [査読有り]
Background: The purpose of this study was to quantitatively evaluate the tumor accumulation and heterogeneity of In-111-ibritumomab tiuxetan (Zevalin (R)) and tumor accumulation of F-18-fluoro-deoxyglucose (FDG) and compare them to the tumor response in B-cell non-Hodgkin's lymphoma patients receiving Y-90-ibritumomab tiuxetan (Zevalin (R)) therapy. Methods: Sixteen patients with histologically confirmed non-Hodgkin's B-cell lymphoma who underwent Y-90-ibritumomab tiuxetan therapy along with In-111-ibritumomab tiuxetan single-photon emission computerized tomography (SPECT)/CT and FDG positron emission tomography (PET)/CT were enrolled in this retrospective study. On pretherapeutic FDG PET/CT images, the maximum standardized uptake value (SUVmax) was measured. On SPECT/CT images, a percentage of the injected dose per gram (%ID/g) and SUVmax of In-111-ibritumomab tiuxetan were measured at 48 h after its administration. The skewness and kurtosis of the voxel distribution were calculated to evaluate the intratumoral heterogeneity of tumor accumulation. As another intratumoral heterogeneity index, cumulative SUV-volume histograms describing the percentage of the total tumor volume above the percentage thresholds of pretherapeutic FDG and In-111-ibritumomab tiuxetan SUVmax (area under the curve of the cumulative SUV histograms (AUC-CSH)) were calculated. All lesions (n = 42) were classified into responders and non-responders lesion-by-lesion on pre- and post-therapeutic CT images. Results: A positive correlation was observed between the FDG SUVmax and accumulation of In-111-ibritumomab tiuxetan in lesions. A significant difference in pretherapeutic FDG SUVmax was observed between responders and non-responders, while no significant difference in In-111-ibritumomab tiuxetan SUVmax was observed between the two groups. In contrast, voxel distribution of FDG demonstrated no significant differences in the three heterogeneity indices between responders and non-responders, while In-111-ibritumomab tiuxetan demonstrated skewness of 0.58 +/- 0.16 and 0.73 +/- 0.24 (p < 0.05), kurtosis of 2.39 +/- 0.32 and 2.78 +/- 0.53 (p < 0.02), and AUC-CSH of 0.37 +/- 0.04 and 0.34 +/- 0.05 (p < 0.05) for responders and non-responders. Conclusions: Pretherapeutic FDG accumulation was predictive of the tumor response in Y-90-ibritumomab tiuxetan therapy. The heterogeneity of the intratumoral distribution rather than the absolute level of In-111-ibritumomab tiuxetan was correlated with the tumor response. - Chiaki Nakaseko; Naoto Takahashi; Kenichi Ishizawa; Yukio Kobayashi; Kazuteru Ohashi; Yasunori Nakagawa; Kazuhito Yamamoto; Koichi Miyamura; Masafumi Taniwaki; Masaya Okada; Tatsuya Kawaguchi; Atsushi Shibata; Yosuke Fujii; Chiho Ono; Kazunori OhnishiINTERNATIONAL JOURNAL OF HEMATOLOGY 101 2 154 - 164 2015年02月 [査読有り]
This phase 1/2 study evaluated the safety and pharmacokinetics (part 1) and efficacy and safety (part 2) of bosutinib in Japanese Philadelphia chromosome-positive (Ph+) chronic-phase (CP) or advanced-phase chronic myeloid leukemia (CML) patients resistant/intolerant to previous imatinib (2L) or imatinib+dasatinib/nilotinib (3L). Based on dose-limiting toxicities and previous studies, the part 2 bosutinib starting dose was 500 mg/day (n = 63). For CP CML 2L (n = 28), the cumulative major cytogenetic response (MCyR) rate by week 24 was 36 % (primary endpoint); the cumulative major molecular response (MMR) rate through the study was 43 %. Transformation to accelerated/blast phase (AP/BP) was observed in one patient. Progression-free survival (PFS) and overall survival (OS) rates at 96 weeks were 94 and 96 %, respectively. Of seven advanced-phase 2L patients, one had confirmed complete hematologic response at week 84, and one had AP/BP transformation. PFS and OS rates at week 96 were 21 and 43 %. For 3L (n = 11), cumulative MCyR rate by week 24 was 18 %; cumulative MMR rate was 18 %; no transformations occurred. Common non-hematologic adverse events (AEs) were diarrhea (95 %), rash (57 %), and nasopharyngitis (51 %). Sixteen patients discontinued due to adverse events; no deaths occurred within 30 days of the last dose. Bosutinib 500 mg/day demonstrated efficacy and manageable toxicity in Japanese Ph+ CML patients resistant/intolerant to imatinib. - 平瀬 主税; 田中 宏和; 松村 到血液内科 70 2 140 - 148 科学評論社 2015年02月 [査読有り]
- Tanaka H; Hirase C; Matsumura I[Rinsho ketsueki] The Japanese journal of clinical hematology 56 2 139 - 149 2015年02月 [査読有り]
Tyrosine kinase inhibitors (TKIs) have dramatically improved the clinical outcomes of patients with chronic myeloid leukemia (CML) in the chronic phase. However, even if these patients achieve and maintain marked molecular responses such as a complete molecular response (BCR-ABL/ABL≤0.032% by international scale), discontinuation of TKI treatment results in early molecular relapse in most cases. Although several factors such as the Sokal score and the duration of TKI treatment have been identified as being related to treatment-free remission (TFR), identification of more definite factors or clinical conditions that would enable us to select patients who can maintain TFR is required. Relapse after TKI discontinuation is considered to be attributable to CML stem cells surviving even in patients who maintain marked molecular responses. A number of in vitro experiments have shown that TKI by itself cannot kill CML stem cells. Also, CML stem cells are resistant to TKI in a manner dependent on self-renewal factors (Hh, Wnt/β-catenin), cell cycle regulators (PML), metabotropic factors (FOXO3, Alox5), and adhesion molecules (CXCR4). In addition, surface markers specific for CML stem cells such as IL-1RAP and CD26 have been identified. New therapeutic strategies targeting these molecules in combination with TKI hold promise of achieving a more effective strategy for curing CML. - Itaru MatsumuraMolecular Pathogenesis and Treatment of Chronic Myelogenous Leukemia 29 - 52 2015年01月 [査読有り]
Chronic myelogenous leukemia (CML) is caused by the reciprocal chromosomal translocation t(9:22)(q34 q11). This translocation yields BCR-ABL fusion gene on derivative chromosome 22 called as Philadelphia (Ph) chromosome. Although several forms of BCR-ABL are generated according to the breakpoints in the BCR gene, p210 BCR-ABL is observed in more than 95 % of CML patients. In contrast to the nuclear localization of c-ABL, BCR-ABL is localized in the cytoplasm and acts as a constitutively active tyrosine kinase as a tetramer. BCR-ABL has several functional domains, through which it interacts with downstream signaling molecules and transmits leukemogenic signals: a coiled-coil motif, SH2 domain, Y177, and Dbl homology domain from BCR and SH3, SH2, SH1(kinase), CRKL-binding, and actin-binding domains from c-ABL. Through these domains, BCR-ABL activates Ras/MAPK, PI3K/Akt, and STATs, each of which contributes to excessive cell growth, survival, and consequent leukemic transformation. In addition, SHP-2, c-Cbl, Gab2, and CRKL are involved in the leukemogenic activities of BCR-ABL. Although tyrosine kinase inhibitors (TKIs) have dramatically improved the prognosis of CML patients in chronic phase, a small proportion of patients show resistance to TKIs due to point mutations of the BCR-ABL gene and/or BCR-ABL-independent activation of Src family tyrosine kinases such as Lyn and HCK. In addition, CML stem cells are known to resistant to TKIs, in which JAK2, Wnt/β-catenin, and Sonic hedgehog pathways are activated in a BCR-ABL independent manner and contribute to TKI resistance. - 松村 到日本臨床 73 1 80 - 84 (株)日本臨床社 2015年01月
- Yano T; Nozaki Y; Kinoshita K; Hino S; Hirooka Y; Niki K; Shimazu H; Kishimoto K; Funauch M; Matsumura ILaboratory investigation; a journal of technical methods and pathology 95 1 78 - 91 2015年01月 [査読有り]
Interleukin (IL)-18 is a proinflammatory cytokine produced by leukocytes and parenchymal cells (eg, tubular epithelial cells (TECs), mesangial cells, and podocytes). IL-18 receptor (IL-18R) is expressed on these cells in the kidney during ischemia/reperfusion injury (IRI), but its role in this injury is unknown. Fas/Fas ligand (FasL) is also involved in the pathogenesis of renal IRI via tubular apoptosis. In addition, IL-18 enhances the expression of FasL on TECs, but the mechanism underlying this enhancement is not known. Here we used IL-18R alpha-deficient mice to explore the pathological role of IL-18R alpha in renal IRI. We found that compared to wild-type (WT) mice with renal IRI as an acute kidney injury (AKI), the IL-18R alpha-deficient mice demonstrated decreased renal function (as represented by blood urea nitrogen), tubular damage, an increased accumulation of leukocytes (CD4+ T cells, neutrophils, and macrophages), upregulated early AKI biomarkers (ie, urinary kidney injury molecule-1 levels), and increased mRNA expressions of proinflammatory cytokines (IL-1 beta, IL-12p40, and IL-18) and chemokines (intercellular adhesion molecule-1 and CCL2/monocyte chemoattractant protein-1). The mRNA expression of FasL in the kidney was increased in the IL-18R alpha-deficient mice compared to the WT mice. The adoptive transfer of splenocytes by WT mice led to decreased renal IRI compared to the IL-18R alpha-deficient mice. In vitro, the mRNA expression of FasL on TECs was promoted in the presence of recombinant IL-18. These data reveal that IL-18R alpha has an anti-inflammatory effect in IRI-induced AKI. Above all, IL-18 enhanced the inflammatory mechanisms and the apoptosis of TECs through the Fas/FasL pathway by blocking IL-18R alpha. - Tsutomu Kobayashi; Junya Kuroda; Shin-ichi Fuchida; Hitomi Kaneko; Hideo Yagi; Hirohiko Shibayama; Hirokazu Tanaka; Satoru Kosugi; Nobuhiko Uoshima; Masayuki Kobayashi; Yoko Adachi; Kensuke Ohta; Kazuyoshi Ishii; Hitoji Uchiyama; Mitsuhiro Matsuda; Eiji Nakatani; Mitsuru Tsudo; Chihiro Shimazaki; Akifumi Takaori-Kondo; Shosaku Nomura; Itaru Matsumura; Masafumi Taniwaki; Yuzuru KanakuraINTERNATIONAL JOURNAL OF HEMATOLOGY 101 1 37 - 45 2015年01月 [査読有り]
We retrospectively investigated the prognostic factor of lenalidomide plus low-dose dexamethasone (Rd) in Japanese patients with refractory or relapsed multiple myeloma (RRMM) registered in the Kansai Myeloma Forum from January 2006 to December 2013. A total of 140 patients were analyzed. The median age was 66 years. The overall response rate was 68.6 %, including 33.1 % with a better than very good partial response. At 13.0 months median follow-up, the median overall survival (OS) and progression-free survival (PFS) were 34.2 and 17.0 months, respectively. In univariate analyses, patients with one or two prior therapies had significantly longer OS (41.2 vs. 21.5 months; P = 0.002) and PFS (29.0 vs. 13.0 months; P = 0.006) than patients treated with three or more prior therapies. Prior use of thalidomide was associated with significantly shorter PFS (19.0 vs. 16.0 months; P = 0.045). The prior use of bortezomib or high-dose therapy with stem cell transplantation, and the International Staging System had no impact on long-term outcome. Multivariate analysis showed that only the number of prior therapies was a significant predictor of both OS and PFS. Our findings suggest that greater benefit may occur when Rd therapy is used at the first or second relapse in RRMM. - Yuji Nozaki; Koji Kinoshita; Shoichi Hino; Tomohiro Yano; Kaoru Niki; Yasuaki Hirooka; Kazuya Kishimoto; Masanori Funauchi; Itaru MatsumuraAmerican Journal of Physiology - Renal Physiology 308 8 F899 - F909 2015年 [査読有り]
Nephrotoxicity is a frequent complication of cisplatin-induced chemotherapy, in which T cells are known to promote acute kidney injury (AKI). Apoptosis and necrosis of tubules and inflammatory events also contribute to the nephrotoxicity. A delineation of the mechanisms that underlie the inappropriate renal and tubular inflammation can thus provide important insights into potential therapies for cisplatin-induced AKI. Rho-kinases are known to act as molecular switches controlling several critical cellular functions, including cell migration, cytokine production, and apoptosis. Here, we show that the Rhokinase inhibitor fasudil attenuated cisplatin nephrotoxicity, resulting in less histological damage, improved renal function, and the infiltration of fewer leukocytes into the kidney. Renal nuclear factor-_B activation and apoptosis were reduced, and the expressions of proinflammatory renal cytokine and chemokine mRNA were decreased. Urinary and renal kidney injury molecule-1 (Kim-1) expression was also reduced, a finding that is consistent with diminished kidney injury. In the current study, we also showed that fasudil could be protective of the impaired tubules. In vitro, fasudil reduced the apoptosis (annexin-V_PI cells) and cytokine production (tumor necrosis factor_ cells) in T cells and the apoptosis (annexin-V_PI cells) and tubular damage (Kim-1_ cells) in proximal tubular cells by flow cytometric analysis. As Rho-kinase plays an important role in promoting cisplatin nephrotoxicity, inhibiting Rho-kinase may be a therapeutic strategy for preventing cisplatin-induced AKI. - Yasuyoshi Morita; Masakatsu Emoto; Kentaro Serizawa; Shinya Rai; Chikara Hirase; Yoshitaka Kanai; Yasuyo Ohyama; Toshihiko Shiga; Hirokazu Tanaka; Junichi Miyatake; Yoichi Tatsumi; Takashi Ashida; Masatomo Kimura; Masafumi Ito; Itaru MatsumuraINTERNAL MEDICINE 54 11 1393 - 1396 2015年 [査読有り]
A 68-year-old man was referred to our hospital due to a high fever and pancytopenia. Neither tumors nor infectious lesions were detected. Hemophagocytosis was observed on the bone marrow (BM) smear, although without abnormal cells. Prednisolone therapy was ineffective for the patient's high fever. Later on, we obtained the results of a BM biopsy indicating the presence of infiltration of atypical Reed-Sternberg cells, leading to a diagnosis of HIV-negative primary bone marrow Hodgkin lymphoma (PBMHL). However, the patient died of multiple organ failure before receiving chemotherapy. As the clinical course of PBMHL is rapid, physicians must keep in mind its possibility in similar cases. - Mitsune Tanimoto; Koichi Miyamura; Toshihiro Miyamoto; Kazuhito Yamamoto; Masafumi Taniwaki; Shinya Kimura; Kazuma Ohyashiki; Tatsuya Kawaguchi; Itaru Matsumura; Tomoko Hata; Hisashi Tsurumi; Shigeki Saito; Masayuki Hino; Seiji Tadokoro; Kuniaki Meguro; Hideo Hyodo; Masahide Yamamoto; Kohmei Kubo; Junichi Tsukada; Midori Kondo; Makoto Aoki; Hikaru Okada; Masamitsu YanadaBLOOD 124 21 2014年12月 [査読有り]
- Miwa Adachi; Akihiro Takeshita; Tomohiko Taki; Shigeki Ohtake; Katsuji Shinagawa; Hitoshi Kiyoi; Mitsuhiro Matsuda; Masatomo Takahashi; Nobuhiko Emi; Yukio Kobayashi; Koichi Miyamura; Hiroyuki Fujita; Toru Sakura; Masako Iwanaga; Noriko Usui; Shuichi Miyawaki; Norio Asou; Kazunori Ohnishi; Yasushi Miyazaki; Tomoki NaoeBLOOD 124 21 2014年12月 [査読有り]
- Taiichi Kyo; Arinobu Tojo; Kazuhito Yamamoto; Naoto Takahashi; Hirohisa Nakamae; Yukio Kobayashi; Tetsuzo Tauchi; Shinichiro Okamoto; Koichi Miyamura; Hiromi Iwasaki; Kiyohiko Hatake; Itaru Matsumura; Noriko Usui; Kumiko Yanase; Simin Hu; Tomoki Naoe; Kazuma OhyashikiBLOOD 124 21 2014年12月 [査読有り]
- 加藤 祐子; 福島 靖幸; 川野 亜美; 山田 枝里佳; 井手 大輔; 菅野 知恵美; 金光 靖; 芦田 隆司; 松村 到近畿大学医学雑誌 = Medical Journal of Kinki University 39 3 21A1 - 21A1 近畿大学医学会 2014年12月 [査読有り]
- 松村 到腫瘍内科 14 6 585 - 588 (有)科学評論社 2014年12月
- 李 進海; 朝戸 佳世; 酒井 健史; 井上 明日圭; 田崎 知江美; 志賀 俊彦; 樋野 尚一; 矢野 智洋; 岸本 和也; 野崎 祐史; 船内 正憲; 松村 到; 西坂 文章; 赤木 將男臨床リウマチ 26 4 305 - 309 (一社)日本臨床リウマチ学会 2014年12月RAを発症し、サラゾスルファピリジンに抵抗性を示したため、エタネルセプトが投与され、3ヵ月後から発熱、皮疹、口内炎が出現し、ループス腎炎を伴うSLEを発症した症例(35歳、女性)を経験した。抗TNF-α製剤の投与によってSLEを発症したとする報告が散見されるが、本例のようにループス腎炎を伴う例は少ない。以上、抗TNF-α製剤による治療経過中は抗核抗体やSLEの素因の有無に留意する必要性が示唆された。(著者抄録)
- M. Sakurai; H. Kunimoto; N. Watanabe; Y. Fukuchi; S. Yuasa; S. Yamazaki; T. Nishimura; K. Sadahira; K. Fukuda; H. Okano; H. Nakauchi; Y. Morita; I. Matsumura; K. Kudo; E. Ito; Y. Ebihara; K. Tsuji; Y. Harada; H. Harada; S. Okamoto; H. NakajimaLEUKEMIA 28 12 2344 - 2354 2014年12月 [査読有り]
Somatic mutation of RUNX1 is implicated in various hematological malignancies, including myelodysplastic syndrome and acute myeloid leukemia (AML), and previous studies using mouse models disclosed its critical roles in hematopoiesis. However, the role of RUNX1 in human hematopoiesis has never been tested in experimental settings. Familial platelet disorder (FPD)/AML is an autosomal dominant disorder caused by germline mutation of RUNX1, marked by thrombocytopenia and propensity to acute leukemia. To investigate the physiological function of RUNX1 in human hematopoiesis and pathophysiology of FPD/AML, we derived induced pluripotent stem cells (iPSCs) from three distinct FPD/AML pedigrees (FPD-iPSCs) and examined their defects in hematopoietic differentiation. By in vitro differentiation assays, FPD-iPSCs were clearly defective in the emergence of hematopoietic progenitors and differentiation of megakaryocytes, and overexpression of wild-type (WT)-RUNX1 reversed most of these phenotypes. We further demonstrated that overexpression of mutant-RUNX1 in WT-iPSCs did not recapitulate the phenotype of FPD-iPSCs, showing that the mutations were of loss-of-function type. Taken together, this study demonstrated that haploinsufficient RUNX1 allele imposed cell-intrinsic defects on hematopoietic differentiation in human experimental settings and revealed differential impacts of RUNX1 dosage on human and murine megakaryopoiesis. FPD-iPSCs will be a useful tool to investigate mutant RUNX1-mediated molecular processes in hematopoiesis and leukemogenesis. - 同種移植後再発に対してAzacitidineが有効であった治療関連AML症例河合 栄樹; 和田 裕介; 村上 晴郎; 上田 宏次; 永禮 靖章; 浦瀬 文明; 平瀬 主税; 松村 到臨床血液 55 11 2341 - 2341 (一社)日本血液学会-東京事務局 2014年11月
- 急性前骨髄性白血病の形態学的特徴を示し、t(9;11)(p22;q23)染色体転座を有する治療関連白血病の1症例綿谷 陽作; 山入 望美; 岩永 隆行; 松田 光弘; 松村 到臨床血液 55 11 2345 - 2345 (一社)日本血液学会-東京事務局 2014年11月
- Maiko Kato; Naoki Oiso; Yuji Nozaki; Asuka Inoue; Yuji Hosono; Masanori Funauchi; Tsuneyo Mimori; Itaru Matsumura; Akira KawadaJOURNAL OF DERMATOLOGY 41 11 1034 - 1036 2014年11月 [査読有り]
- 松村 到臨床血液 55 10 1853 - 1859 (一社)日本血液学会-東京事務局 2014年10月
- Shinya Rai; Hirokazu Tanaka; Mai Suzuki; Honami Ogoh; Yasuhiro Taniguchi; Yasuyoshi Morita; Takahiro Shimada; Akira Tanimura; Keiko Matsui; Takafumi Yokota; Kenji Oritani; Kenji Tanabe; Toshio Watanabe; Yuzuru Kanakura; Itaru MatsumuraPLOS ONE 9 10 2014年10月 [査読有り]
CALM is implicated in the formation of clathrin-coated vesicles, which mediate endocytosis and intracellular trafficking of growth factor receptors and nutrients. We previously found that CALM-deficient mice suffer from severe anemia due to the impaired clathrin-mediated endocytosis of transferrin receptor in immature erythroblast. However, CALM has been supposed to regulate the growth and survival of hematopoietic stem/progenitor cells. So, in this study, we focused on the function of CALM in these cells. We here show that the number of Linage(-)Sca-1(+)KIT(+) (LSK) cells decreased in the fetal liver of CALM(-/-) mice. Also, colony forming activity was impaired in CALM(-/-) LSK cells. In addition, SCF, FLT3, and TPO-dependent growth was severely impaired in CALM(-/-) LSK cells, while they can normally proliferate in response to IL-3 and IL-6. We also examined the intracellular trafficking of KIT using CALM(-/-) murine embryonic fibroblasts (MEFs) engineered to express KIT. At first, we confirmed that endocytosis of SCF-bound KIT was not impaired in CALM(-/-) MEFs by the internalization assay. However, SCF-induced KIT trafficking from early to late endosome was severely impaired in CALM(-/-) MEFs. As a result, although intracellular KIT disappeared 30 min after SCF stimulation in wild-type (WT) MEFs, it was retained in CALM(-/-) MEFs. Furthermore, SCF-induced phosphorylation of cytosolic KIT was enhanced and prolonged in CALM(-/-) MEFs compared with that in WT MEFs, leading to the excessive activation of Akt. Similar hyperactivation of Akt was observed in CALM(-/-) KIT+ cells. These results indicate that CALM is essential for the intracellular trafficking of KIT and its normal functions. Also, our data demonstrate that KIT located in the early endosome can activate downstream molecules as a signaling endosome. Because KIT activation is involved in the pathogenesis of some malignancies, the manipulation of CALM function would be an attractive therapeutic strategy. - Kazuteru Ohashi; Tokiko Nagamura-Inoue; Fumitaka Nagamura; Arinobu Tojo; Kouichi Miyamura; Takehiko Mori; Mineo Kurokawa; Shuichi Taniguchi; Jun Ishikawa; Yasuo Morishima; Yoshiko Atsuta; Hisashi SakamakiINTERNATIONAL JOURNAL OF HEMATOLOGY 100 3 296 - 306 2014年09月 [査読有り]
We retrospectively compared transplant outcomes for related bone marrow transplantation (rBMT), related peripheral blood stem cell transplantation (rPBSCT), unrelated bone marrow transplantation (uBMT), and unrelated cord blood transplantation (CBT) in 1,062 patients with chronic myeloid leukemia (CML) aged 20 years or over between January 1, 2000 and December 31, 2009 in Japan. The disease status was as follows: chronic phase 1 (CP1, n = 531), CP 2 or later including accelerated phase (CP2-AP, n = 342) and blastic crisis (BC, n = 189). Graft sources (GS) were rBMT (n = 205), uBMT (n = 507), rPBSCT (n = 226) or CBT (n = 124). In multivariate analysis in CP1, lower overall survival (OS) (relative risk [RR]: 6.01, 95 % confidence interval [CI]: 1.20-29.97, P = 0.029) and leukemia-free survival (LFS) (RR: 4.26, 95 % CI: 1.24-14.62, P = 0.021) were observed in uBMT compared with those in rBMT. For patients in the advanced phase of CML beyond CP1, GS had no significant impact on OS or LFS. Our results support the use of rBMT for adults with CML in CP1, but in contrast to previous reports, the superiority of rPBSCT in advanced stage of CML was not confirmed in our cohorts. - 辻岡 大志; 岡本 紀夫; 芦田 隆司; 國吉 一樹; 松本 長太; 松村 到; 下村 嘉一臨床眼科 68 9 1345 - 1350 (株)医学書院 2014年09月目的:網膜と脈絡膜の循環障害が生じた本態性血小板血症の症例の報告。症例:64歳女性が前日からの右眼の眼痛と視朦で受診した。血小板が増加する本態性血小板血症が7年前からあった。所見:矯正視力は右手動弁,左1.2で,右眼の網膜静脈に口径不同,拡張と蛇行があり,後極部が白濁し,乳頭の発赤腫脹があった。左眼には異常所見はなかった。蛍光眼底造影では,造影開始が遅延し,網膜中心動脈閉塞症と診断した。光干渉断層計と網膜電図の所見もこれと一致した。赤外蛍光造影検査では後極部脈絡膜の循環障害があった。初診時の血小板数は,84.6万/μlであった。3ヵ月後に左眼に視朦が生じた。視力は良好であったが,左眼の網膜静脈の拡張と蛇行があり,乳頭が発赤していた。右眼に乳頭新生血管があり,2ヵ月後に硝子体出血,さらに虹彩ルベオーシスが生じ,眼圧が上昇した。初診から1年後の現在,視力は右手動弁,左1.5で,血小板数は24万/μl前後で安定している。結論:本態性血小板血症は網膜だけでなく,脈絡膜にも循環障害が生じる可能性のあることを,本症例では示している。(著者抄録)
- 松村 到日本内科学会雑誌 103 9 2261 - 2268 (一社)日本内科学会 2014年09月
- 【癌幹細胞】 造血系癌幹細胞 骨髄系の白血病幹細胞田中 宏和; 松村 到医学のあゆみ 250 1 5 - 9 医歯薬出版(株) 2014年07月健常人の造血幹細胞(HSC)にも遺伝子異常は認められ、加齢とともに増加する。このような細胞の一部はpre-白血病幹細胞(LSC)としてクローナルに増殖する。急性骨髄性白血病(AML)の場合、pre-LSCに二次的な遺伝子変異が起こってAMLを発症する。AMLのLSCはもっとも未分化なHSCレベル、あるいは前駆細胞が自己複製能を獲得したものと推定されるが、LSC集団内にも自己複製能において階層が存在する。LSCは正常のHSCと同様に骨髄微小環境内でその特性を維持し、抗癌剤に抵抗性を示す。一方、LSCと正常HSCでは表面抗原やその維持にかかわるシグナル伝達に違いがあり、これらを標的とした新規治療が開発中である。(著者抄録)
- 尿タンパク試験紙にBence Jonesタンパクが反応することの検証井本 真由美; 松村 到; 船内 正憲; 中川 和彦; 鮫島 謙一; 前田 裕弘; 森嶋 祥之; 中江 健市; 上硲 俊法; 工藤 正俊; 櫻林 郁之介臨床化学 43 3 217 - 225 (一社)日本臨床化学会 2014年07月Bence Jonesタンパク(BJP)は尿タンパク試験紙(以下、試験紙)にはほとんど反応しないことが定説となっている。我々はこの説に疑問を持ち、過去約6年間におけるBJP定性試験(Putnam法)陽性で、免疫電気泳動法(IEP)あるいは免疫固定法(IFE)においてBJP陽性が確認されている患者尿の試験紙反応性について調査した結果、BJP含有尿352検体(66症例)中、試験紙陰性はわずかに10検体(2.8%)で、342検体(97.2%)が±以上の反応(±〜4+)であった。試験紙法陰性検体は経過観察中の多発性骨髄腫患者3例のみであった。しかも、尿総タンパク量は、15mg/dL未満であり、試験紙法の検出限界濃度以下であった。またIgGおよびアルブミンが出現していないBJP陽性尿を用い、試験紙が±以上に反応する濃度(検出限界)を求めた結果、アルブミンの検出感度と同等で15mg/dLであった。さらにIgGが試験紙に反応しがたいことを再確認したうえで、IgGを還元処理してL鎖を遊離させた後は、試験紙の反応性が強くなることを確認した。したがって、尿タンパク試験紙がBJPに反応しない(反応しがたい)という説は見直されるべきであると考える。(著者抄録)
- Y. Nozaki; K. Kinoshita; T. Yano; T. Shiga; S. Hino; K. Niki; K. Kishimoto; M. Funauchi; I. MatsumuraLUPUS 23 8 769 - 777 2014年07月 [査読有り]
Objective: Biomarkers of disease activity in lupus nephritis (LN) are needed. Ideally, such biomarkers would be capable of detecting early sub-clinical disease and could be used to gauge response to therapy, thus obviating the need for serial renal biopsies. Much of the focus in the search for LN biomarkers has been on the measurement of urinary chemokines and cytokines in LN patients. However, these have yet to be widely implemented in clinical practice. Kidney injury molecule-1 (Kim-1) is expressed in damaged tubules, but whether urinary (u) and tubular (t)-Kim-1 could serve as a biomarker of active LN is unknown. To investigate the disease activity and histological findings in LN, we evaluated u-Kim-1 levels and t-Kim-1 cells in patients with systemic lupus erythematosus (SLE). Method: We measured u-Kim-1 levels and stained t-Kim-1 expression in 57 patients with LN using an ELISA and immunohistochemistry staining. Patients were classified into two groups (active LN, n = 37; inactive LN, n 20) based on the presence of active renal disease according to the renal SLE disease activity index. correlations of clinical, laboratory data, and histological findings with urinary and t-Kim-1 expression were assessed. Result: The u-Kim-1 levels were significantly correlated with the expression of t-Kim-1 (R = 0.64; P = 0.004) in the SLE patients. The active LN patients exhibited elevated u-Kim-1 levels compared to the inactive LN patients. The number of t-Kim-1 cells was also correlated with histological findings (both glomerular and interstitial inflammation). The u-Kim-1 levels were also correlated with proteinuria and tubular damage in the active LN group. The number of t-Kim-1 cells at baseline was significantly correlated with the estimated glomerular filtration rate (R = 0.72; P = 0.005) and serum creatinine (R = 0.53; P = 0.005) after 6-8 months of treatment. Conclusion: These data suggest the potential use of the u-Kim-1 levels to screen for active LN and for the estimation of t-Kim-1 expression in renal biopsies to predict renal damage, ongoing glomerular nephritis and tubulointerstitial inflammation, and tubular atrophy. - Kanai Yoshitaka; Shimada Takahiro; Taniguchi Yasuhiro; Rai Shinya; Hirase Chikara; Hanamoto Hitoshi; Morita Yasuyoshi; Tanaka Hirokazu; Tatsumi Yoichi; Ashida Takashi; Matsumura ItaruACTA MEDICA KINKI UNIVERSITY = The Kinki University Medical Association 39 1 29 - 37 Kinki University Medical Association 2014年06月[Abstract] Background :Overexpression of Tribbles homolog 1 (Tribl) and Tribbles homolog 2 (Trib2) in hematopoietic stem/progenitor cells evokes acute myeloid leukemia (AML) in murine transplantation models. Degradation of CCAAT-enhancer-binding-protein α (C/EBPα) plays a crucial role in Trib1 or Trib2-induced AML. However, because C/EBPα knockout mice do not develop AML, it is likely that Trib1 and Trib2 influence other signaling pathways besides C/EBPα. Elevated Akt phosphorylation is considered to contribute to the development of AML. In contrast, two groups recently reported that reduced Akt activity is involved in the pathogenesis of leukemia. We performed this study to reveal the role of Akt signaling in Trib family-induced AML.Methods : G-CSF-induced granulocytic differentiation of 32D cells was assessed morphologically and phenotypically. G-CSF-induced signaling wasassessed by Westernblotting. Results : Overexpression of Trib1 or Trib2 inhibited GCSF-induced granulocytic differentiation of 32D cells, which was accompanied by reduced Akt phosphorylation. Also, an Akt inhibitor API-2 blocked G-CSF-induced granulocytic differentiation independently of C/EBPα degradation. Furthermore, retroviral C/EBPα restoration did not completely abolish the differentiation block caused by Trib1 and Trib2. Conclusion :Trib1 and Trib2 block granulocytic differentiation, at least partially, by suppressing Akt phosphorylation.
- ループス腎炎の疾患活動性評価における尿中Kim-1測定の有用性について野崎 祐史; 木下 浩二; 矢野 智洋; 志賀 俊彦; 樋野 尚一; 岸本 和也; 船内 正憲; 松村 到日本腎臓学会誌 56 3 312 - 312 (一社)日本腎臓学会 2014年05月
- 敗血症における急性腎障害に対するIL-18Rαの役割の検討樋野 尚一; 矢野 智洋; 野崎 祐史; 木下 浩二; 船内 正憲; 松村 到日本腎臓学会誌 56 3 342 - 342 (一社)日本腎臓学会 2014年05月
- Makoto Hosono; Kohei Hanaoka; Kazunari Ishii; Kenta Sakaguchi; Sung-Woon Im; Norio Tsuchiya; Yoshihiro Komeya; Yoichi Tatsumi; Itaru MatsumuraJOURNAL OF NUCLEAR MEDICINE 55 2014年05月 [査読有り]
- 移植非適応MM標準治療を考える 診療ガイドラインをふまえて松村 到; 飯田 真介; 柴山 浩彦; 黒田 純也; 山村 亮介; 石井 一慶血液フロンティア 24 6 911 - 916 (株)医薬ジャーナル社 2014年05月
- Akira Tanimura; Hirohiko Shibayama; Yuri Hamanaka; Natsuko Fujita; Tomohiko Ishibashi; Takao Sudo; Takafumi Yokota; Sachiko Ezoe; Hirokazu Tanaka; Itaru Matsumura; Kenji Oritani; Yuzuru KanakuraEXPERIMENTAL HEMATOLOGY 42 5 410 - 422 2014年05月 [査読有り]
Anamorsin (AM) is an antiapoptotic molecule that confers factor-independent survival on hematopoietic cells. AM-deficient (AM(-/-)) mice are embryonic lethal because of a defect in definitive hematopoiesis; however, the significance of AM in embryonic hematopoiesis remains unknown. This study characterized the hematopoietic defects in AM(-/-) fetal livers. The AM(-/-) fetal liver displayed significantly reduced numbers of c-Kit(+)Sca-1(+)Lin(-) (KSL) cells. An in vitro colony-forming unit assay showed that fetal liver cells isolated from AM(-/-) embryos gave rise to fewer colonies in all cell types. The reconstitution activity in AM(-/-) hematopoietic stem cells (HSCs) was markedly reduced in all lineages. Furthermore, the limiting dilution assay revealed that the number of fetal liver HSCs was reduced because of AM deficiency. Retrovirus-mediated AM expression rescued the defective hematopoietic colony-forming activities of AM(-/-) KSL cells. We also investigated the effects of AM deficiency on fetal liver stromal cells, which support hematopoiesis. Interestingly, primary stromal cell cultures from wild type fetal liver supported the growth of AM(-/-) KSL cells, but stromal cultures from AM(-/-) fetal liver provided little support of wild type KSL cell growth. These results demonstrated that AM was essential for both autonomous and extrinsic regulation of fetal liver hematopoiesis. This study provided new insight into the molecular regulation of hematopoiesis. (C) 2014 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. - Yuji Nozaki; A. Richard Kitching; Hisaya Akiba; Hideo Yagita; Koji Kinoshita; Masanori Funauchi; Itaru MatsumuraAMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY 306 10 F1210 - F1221 2014年05月 [査読有り]
The T-cell immunoglobulin mucin 1, also known as kidney injury molecule-1, modulates CD4+ T-cell responses and is also expressed by damaged proximal tubules within the kidney. Both Th subset imbalance (Th1/Th2/Th17) and regulatory T-cell and B-cell alterations contribute to the pathogenesis of autoimmune disease. This study investigated the effects of an inhibitory anti-T-cell immunoglobulin mucin 1 antibody (RMT1-10) in lupus-prone MRL-Fas(lpr) mice. MRL-Fas(lpr) mice were treated with RMT1-10 or a control antibody intraperitoneally twice weekly from 3 mo of age for 16 wk. RMT1-10 treatment significantly improved survival, limited the development of lymphadenopathy and skin lesions, preserved renal function and decreased proteinuria, reduced serum anti-DNA antibody levels, and attenuated renal leukocyte accumulation. Th1 and Th17 cellular responses systemically and intrarenally were reduced, but regulatory T and B cells were increased. RMT1-10 treatment also reduced glomerular immunoglobulin and C3 deposition and suppressed cellular proliferation and apoptosis. Urinary excretion and renal expression of kidney injury molecule-1 was reduced, reflecting diminished interstitial injury. As RMT1-10 attenuated established lupus nephritis, manipulating immune system T-cell immunoglobulin mucin 1 may represent a therapeutic strategy in autoimmune diseases affecting the kidney. - Junya Kuroda; Yuji Shimura; Kensuke Ohta; Hirokazu Tanaka; Hirohiko Shibayama; Satoru Kosugi; Shinichi Fuchida; Masayuki Kobayashi; Hitomi Kaneko; Nobuhiko Uoshima; Kazuyoshi Ishii; Shosaku Nomura; Masafumi Taniwaki; Akifumi Takaori-Kondo; Chihiro Shimazaki; Mitsuru Tsudo; Masayuki Hino; Itaru Matsumura; Yuzuru KanakuraINTERNATIONAL JOURNAL OF HEMATOLOGY 99 4 441 - 449 2014年04月 [査読有り]
We retrospectively investigated clinical outcomes and prognostic factors of 131 patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM) who received melphalan and prednisolone (MP) as first-line therapy from 2006 to 2013. Eighty-one patients received salvage therapies incorporating bortezomib, lenalidomide, and/or thalidomide. The overall response rate to MP was 54.2 %, including 9.2 % of better than very good partial response. With a median follow-up period of 30.2 months, median overall survival (OS) and median time to next treatment (TNT) were 54.4 and 19.0 months, respectively. Univariate analysis revealed that performance status and serum calcium level significantly associated with both OS and TNT, and multivariate analysis revealed that the higher serum calcium level had a significantly unfavorable impact on OS and TNT. Importantly, staging informed by the international staging system (ISS) was not predictive for OS or TNT in the analyzed cohort. Our study revealed that, in the context of first-line MP therapy for NDMM, the salvage therapy incorporating novel agents produced a survival period of > 30 months after the initiation of second-line therapy, suggesting that the predictive value of ISS for OS and TNT may be limited in the era of novel agents. - その他の膠原病・アミロイドーシス 成人発症Still病と血球貪食症候群合併悪性リンパ腫の鑑別診断における血清IL-18測定の有用性の検討志賀 俊彦; 酒井 健史; 井上 明日圭; 田崎 知江美; 李 進海; 湯本 妙子; 朝戸 佳世; 樋野 尚一; 矢野 智洋; 岸本 和也; 永禮 靖章; 嶋津 秀紀; 野崎 祐史; 木下 浩二; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 58回 416 - 416 (一社)日本リウマチ学会 2014年03月
- 線維筋痛症・臨床(内科)・血液浄化療法 NSAIDs(Non-Steroidal Anti-Inflammatory Drugs)またはステロイドを継続服用し、GERD(Gastroesophageal Reflux Disease)症状を有する患者に対するエソメプラゾール(EPZ)の効果李 進海; 酒井 健史; 井上 明日圭; 田崎 知江美; 湯本 妙子; 朝戸 佳世; 志賀 俊彦; 樋野 尚一; 矢野 智洋; 岸本 和也; 永禮 靖章; 嶋津 秀紀; 野崎 祐史; 高田 由紀子; 杉山 昌史; 木下 浩二; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 58回 448 - 448 (一社)日本リウマチ学会 2014年03月
- 増量プロトコールに従ったインフリキシマブ増量の検討永禮 靖章; 酒井 健史; 井上 明日圭; 田崎 知江美; 李 進海; 湯本 妙子; 朝戸 佳世; 志賀 俊彦; 樋野 尚一; 矢野 智洋; 岸本 和也; 嶋津 秀紀; 野崎 祐史; 木下 浩二; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 58回 522 - 522 (一社)日本リウマチ学会 2014年03月
- アダリムマブとトシリズマブ治療の効果判定の指標としての血清MMP-3の有用性について井上 明日圭; 野崎 祐史; 酒井 健史; 田崎 知江美; 李 進海; 湯本 妙子; 朝戸 佳世; 志賀 俊彦; 樋野 尚一; 矢野 智洋; 岸本 和也; 永禮 靖章; 嶋津 秀紀; 木下 浩二; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 58回 524 - 524 (一社)日本リウマチ学会 2014年03月
- ループス腎炎モデルマウスにおけるTim-1の免疫応答と腎炎への影響について野崎 祐史; 矢野 智洋; 樋野 尚一; 岸本 和也; 永禮 靖章; 木下 浩二; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 58回 585 - 585 (一社)日本リウマチ学会 2014年03月
- アダリムマブ投与後に皮膚筋炎を併発した関節リウマチの一例酒井 健史; 井上 明日圭; 田崎 知江美; 李 進海; 湯本 妙子; 志賀 俊彦; 朝戸 佳世; 樋野 尚一; 矢野 智洋; 岸本 和也; 永禮 靖章; 嶋津 秀紀; 野崎 祐史; 木下 浩二; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 58回 610 - 610 (一社)日本リウマチ学会 2014年03月
- M. Murata; T. Nishida; S. Taniguchi; K. Ohashi; H. Ogawa; T. Fukuda; T. Mori; H. Kobayashi; C. Nakaseko; N. Yamagata; Y. Morishima; T. Nagamura-Inoue; H. Sakamaki; Y. Atsuta; R. Suzuki; T. NaoeBONE MARROW TRANSPLANTATION 49 3 355 - 360 2014年03月 [査読有り]
To determine whether a difference in donor source affects the outcome of transplantation for patients with primary myelofibrosis (PMF), a retrospective study was conducted using the national registry data on patients who received first allogeneic hematopoietic cell transplantation (HCT) with related BM (n= 19), related PBSCs (n=25), unrelated BM (n=28) or unrelated umbilical cord blood (UCB; n= 11). The 5-year OS rates after related BM, related PBSC and unrelated BM transplantation were 63%, 43% and 41%, respectively, and the 2-year OS rate after UCB transplantation was 36%. On multivariate analysis, the donor source was not a significant factor for predicting the OS rate. Instead, performance status (PS) >= 2 (vs PS 0-1) predicted a lower OS (P= 0.044), and RBC transfusion >= 20 times before transplantation (vs transfusion <= 9 times) showed a trend toward a lower OS (P= 0.053). No advantage of nonmyeloablative preconditioning regimens in terms of decreasing nonrelapse mortality or increasing OS was found. Allogeneic HCT, and even unrelated BM and UCB transplantation, provides a curative treatment for PMF patients. - 【もう見逃さない!迷わない! 非血液専門医のための血液診療】 この血算の異常を見逃してはいけない 専門医への紹介のタイミング 白血球増加森田 泰慶; 田中 宏和; 松村 到Medicina 51 3 430 - 433 (株)医学書院 2014年03月<ポイント>白血球増加症には,造血器腫瘍による場合と類白血病反応の場合がある.敗血症,粟粒結核などの重篤な感染症時には,末梢血中に種々の分化段階の未熟な顆粒球系細胞の出現を認める.がんの骨髄転移やG-CSF産生腫瘍では,CML様の白血球増多症が認められることがある.(著者抄録)
- 朝戸 佳世; 野崎 祐史; 井上 明日圭; 田崎 知江美; 李 進海; 湯本 妙子; 志賀 俊彦; 樋野 尚一; 矢野 智洋; 岸本 和也; 廣岡 靖章; 嶋津 秀紀; 木下 浩二; 船内 正憲; 松村 到臨床リウマチ 26 1 63 - 68 (一社)日本臨床リウマチ学会 2014年03月症例は66歳女性で、歩行困難、下腿浮腫、体重増加を主訴に、近医にて肝逸脱酵素の上昇を指摘され、紹介受診となった。来院時検査で高度の筋逸脱酵素の上昇を認めたため、精査加療目的で緊急入院となった。採血、画像、生検結果、臨床経過より、亜急性に進行する抗SRP抗体陽性の重症多発筋炎と診断した。メチルプレドニゾロン投与やプレドニゾロン投与、シクロスポリン投与を開始しるも改善せず、IVIGを併用したところ寛解が得られた。
- 【成人白血病に対する治療-治癒を目指して】 慢性白血病に対する薬物治療の実際 慢性骨髄性白血病宮武 淳一; 平瀬 主税; 松村 到臨床腫瘍プラクティス 10 1 43 - 48 (株)ヴァンメディカル 2014年02月<View Points!>慢性期の慢性骨髄性白血病(CML-CP)の治療成績はチロシンキナーゼ阻害薬(TKI)が登場して画期的に改善し、ほとんどの症例で病期進行が回避される。第二世代TKIが克服できなかったT315I変異に対しては第三世代TKIのponatinibが海外で承認され、わが国でも臨床試験中である。分子遺伝学的完全寛解(CMR)を達成し、維持した症例の一部では薬剤中止後もCMRが維持され、CMLは治癒を目指す時代を迎えたと言って過言ではない。(著者抄録)
- Yuji Nozaki; A. Richard Kitching; Hisaya Akiba; Hideo Yagita; Koji Kinoshita; Masanori Funauchi; Itaru MatsumuraAmerican Journal of Physiology - Renal Physiology 306 10 F1210 - F1221 2014年 [査読有り]
The T-cell immunoglobulin mucin 1, also known as kidney injury molecule-1, modulates CD4+ T-cell responses and is also expressed by damaged proximal tubules within the kidney. Both Th subset imbalance (Th1/Th2/Th17) and regulatory T-cell and B-cell alterations contribute to the pathogenesis of autoimmune disease. This study investigated the effects of an inhibitory anti-T-cell immunoglobulin mucin 1 antibody (RMT1-10) in lupus-prone MRL-Faslpr mice. MRL-Faslpr mice were treated with RMT1-10 or a control antibody intraperitoneally twice weekly from 3 mo of age for 16 wk. RMT1-10 treatment significantly improved survival, limited the development of lymphadenopathy and skin lesions, preserved renal function and decreased proteinuria, reduced serum anti-DNA antibody levels, and attenuated renal leukocyte accumulation. Th1 and Th17 cellular responses systemically and intrarenally were reduced, but regulatory T and B cells were increased. RMT1-10 treatment also reduced glomerular immunoglobulin and C3 deposition and suppressed cellular proliferation and apoptosis. Urinary excretion and renal expression of kidney injury molecule-1 was reduced, reflecting diminished interstitial injury. As RMT1-10 attenuated established lupus nephritis, manipulating immune system T-cell immunoglobulin mucin 1 may represent a therapeutic strategy in autoimmune diseases affecting the kidney. © 2014 the American Physiological Society. - 宮武 淳一; 平瀬 主税; 松村 到臨床腫瘍プラクティス 10 1 43 - 48 ヴァン・メディカル 2014年 [査読有り]
- 骨髄系 第三世代チロシンキナーゼ阻害薬ポナチニブの有効性と安全性平瀬 主税; 田中 宏和; 松村 到Annual Review血液 2014 110 - 116 (株)中外医学社 2014年01月慢性期の慢性骨髄性白血病(CML-CP)の治療成績はチロシンキナーゼ阻害薬(TKI)であるイマチニブの登場により画期的に改善した.その後,イマチニブより強力なBCR-ABL阻害作用を有する第二世代TKIのニロチニブ,ダサチニブが開発され,イマチニブ抵抗性・不耐容例のみでなく初発CML-CPに対しても承認された.これらのTKIにより初発CML-CPのほとんどの症例で長期予後が担保されるようになったが,一部の症例は第二世代TKIにも抵抗性を示す.TKI抵抗性の原因として最も高頻度に認められるのはBCR-ABLの点突然変異であり,この中でもT315I変異は第二世代TKIにも抵抗性を示す.ポナチニブは第三世代TKIであり,T315Iを有する症例や第二世代TKIに抵抗性を示す症例にも有効性を示す.欧米では第二世代TKIに抵抗性・不耐容例に承認されており,わが国でも治験が実施されており,承認が待たれるところである.(著者抄録)
- 嶋田 高広; 松村 到日本臨床免疫学会会誌 37 1 33 - 41 日本臨床免疫学会 2014年緑膿菌は水まわりなど自然および生活環境中に広く存在する常在菌の一種であり,代表的な日和見感染症の原因細菌である.免疫能に異常がない個体には通常病原性を示さないため,弱毒細菌に分類されるが,免疫不全患者においては致死的な感染症を引き起こしうる.代表的な院内感染の病原菌でもあり,近年多くの抗菌薬に対して耐性を獲得した多剤耐性緑膿菌が出現し,臨床の場において深刻な問題となっている.緑膿菌の病原性規定因子に関しては種々の遺伝子欠損緑膿菌株の解析などから多くの知見が得られており,緑膿菌はIII型毒素分泌機構,Exoenzyme,バイオフィルム形成などの,宿主の免疫系を障害または回避するさまざまな機構を備えていることが明らかとなってきた.またクオラムセンシングと呼ばれる細菌間情報伝達機構によって,その病原性がコントロールされていることが明らかとなっている.一方,宿主側の緑膿菌の侵入を検出,防御する機構も種々の遺伝子欠損マウスの解析から明らかになってきた.本稿ではこれらの緑膿菌の病原性規定因子とその宿主免疫系障害機構,宿主の緑膿菌認識機構と緑膿菌による宿主免疫系回避機構に関して述べる.(著者抄録)
- 慢性骨髄性白血病平瀨 主税; 松村 到月刊 臨牀と研究 90 11 48 - 56 2013年11月
- 平瀬 主税; 松村 到臨牀と研究 90 11 1472 - 1480 大道学館出版部 2013年11月 [査読有り]
- 【白血病・悪性リンパ腫】 白血病・悪性リンパ腫の治療の最前線 慢性骨髄性白血病平瀬 主税; 松村 到臨牀と研究 90 11 1472 - 1480 大道学館出版部 2013年11月
- 木崎 昌弘; Mateos Maria-Victoria; 松村 到; 小松 則夫; 渡部 玲子血液フロンティア 23 12 1767 - 1772 (株)医薬ジャーナル社 2013年11月
- 末梢性T細胞リンパ腫に合併した続発性赤芽球癆(Secondary pure red cell aplasia associated with peripheral T-cell lymphoma)Watatani Yosaku; Yamairi Nozomi; Hori Yumiko; Ikeda Junichiro; Wada Naoki; Honma Keiichiro; Morii Eiichi; Iwanaga Takayuki; Matsumura Itaru; Matsuda Mitsuhiro臨床血液 54 9 1416 - 1416 2013年09月
- S. Kurosawa; K. Yakushijin; T. Yamaguchi; Y. Atsuta; T. Nagamura-Inoue; H. Akiyama; S. Taniguchi; K. Miyamura; S. Takahashi; T. Eto; H. Ogawa; M. Kurokawa; J. Tanaka; K. Kawa; K. Kato; R. Suzuki; Y. Morishima; H. Sakamaki; T. FukudaBONE MARROW TRANSPLANTATION 48 9 1198 - 1204 2013年09月 [査読有り]
Although recent improvements have been indicated in the outcome after allogeneic hematopoietic cell transplantation (allo-HCT), little information is available on how changes in transplant modalities have affected the outcomes after allo-HCT in non-remission, based on patient age, donor source and disease type. We compared the incidence and causes of non-relapse mortality (NRM) after allo-HCT in non-remission among three consecutive four-year periods using a nationwide transplant outcome registry database. A total of 3308 patients with acute leukemia in non-remission were analyzed. The risk of NRM decreased over the three periods, and the hazard ratios (HRs) in 2001-2004 and 2005-2008 compared with 1997-2000 were 0.86 (95% CI, 0.70-1.06; P = 0.16) and 0.65 (95% CI, 0.53-0.80; P<0.01), respectively. A significant decrease in the HR for overall mortality was also observed in 2005-2008 (HR 0.85; 95% CI, 0.75-0.97; P = 0.02). We found that a decrease in the incidences of death due to GVHD and infection contributed to the reduction in NRM, to which high-resolution donor-recipient HLA matching and other improvements may have contributed. As none of the subgroups showed improved survival without a reduction in NRM, the effective prevention of transplant-related complications appears to be necessary for improving outcomes after allo-HCT in non-remission. - 白血病 白血病の治療松村 到日本癌治療学会誌 48 2 385 - 387 (一社)日本癌治療学会 2013年09月
- Takahiro Kumode; Yasuyo Ohyama; Masaya Kawauchi; Terufumi Yamaguchi; Jun-ichi Miyatake; Yoshihiko Hoshida; Yoichi Tatsumi; Itaru Matsumura; Yasuhiro MaedaLEUKEMIA & LYMPHOMA 54 9 1947 - 1952 2013年09月 [査読有り]
Primary effusion lymphoma (PEL) is a rare type of non-Hodgkin lymphoma that usually develops in immunosuppressed patients infected with human herpes virus-8 (HHV-8) in conjunction with human immunodeficiency virus (HIV) infection. However, there are several reports of HHV-8-related HIV-negative cases and HHV-8-unrelated HIV-negative cases, mainly in immunodeficient and elderly patients. Here, we report one case of HHV-8-related HIV-negative PEL with gastric cancer (case 1) and one case of HHV-8-unrelated HIV-negative effusion-based lymphoma (case 2), both in elderly men. A 73-year-old man and a 79-year-old man were admitted because of lymphomatous effusions, and no mass was detectable in both cases. They were diagnosed as having malignant effusion lymphoma on the basis of cytological findings indicating atypical lymphoid cells and the expression of CD20 and CD79a. To detect evidence of HHV-8 infection in neoplastic cells, immunocytochemical staining for ORF73/latent nuclear antigen-1 (LNA-1) was performed. The results revealed that case 1 was ORF73-positive, and case 2 was ORF73-negative. Rituximab-based chemotherapy (R-THPCOP: rituximab, pirarubicin, cyclophosphamide, vincristine, prednisolone) was administered to both patients and complete remission was achieved in both. Compared to most HIV-positive PEL cases, these two cases showed a good response to chemotherapy. In cases of PEL, we should focus on HHV-8 infection and HIV status for determining prognosis. - 【分子標的治療薬の選び方、使い方】 分子標的治療薬の選び方、使い方 リツキシマブ松村 到臨床腫瘍プラクティス 9 3 218 - 219 (株)ヴァンメディカル 2013年08月
- 【分子標的治療薬の選び方、使い方】 分子標的治療薬の選び方、使い方 ゲムツズマブオゾガマイシン(GO)松村 到臨床腫瘍プラクティス 9 3 220 - 221 (株)ヴァンメディカル 2013年08月
- 【分子標的治療薬の選び方、使い方】 分子標的治療薬の選び方、使い方 トレチノイン松村 到臨床腫瘍プラクティス 9 3 222 - 223 (株)ヴァンメディカル 2013年08月
- 【分子標的治療薬の選び方、使い方】 分子標的治療薬の選び方、使い方 タミバロテン松村 到臨床腫瘍プラクティス 9 3 224 - 225 (株)ヴァンメディカル 2013年08月
- Naoki Oiso; Chikara Hirase; Yasuyoshi Morita; Ayaka Hirao; Shusuke Uchida; Atsushi Sasakawa; Mami Toyomasu; Yoichi Tatsumi; Itaru Matsumura; Akira KawadaAUSTRALASIAN JOURNAL OF DERMATOLOGY 54 3 e67 - e69 2013年08月 [査読有り]
Patients with acquired haemophilia A usually show widespread subcutaneous bleeding. We describe an 86-year-old man with acquired haemophilia A associated with prostate carcinoma, showing initial localised giant haematoma and subsequent widespread subcutaneous bleeding. A localised giant haematoma may present as a first and important sign of acquired haemophilia A. - Yusuke Satoh; Takafumi Yokota; Takao Sudo; Motonari Kondo; Anne Lai; Paul W Kincade; Taku Kouro; Ryuji Iida; Koichi Kokame; Toshiyuki Miyata; Yoko Habuchi; Keiko Matsui; Hirokazu Tanaka; Itaru Matsumura; Kenji Oritani; Terumi Kohwi-Shigematsu; Yuzuru KanakuraImmunity 38 6 1105 - 15 2013年06月 [査読有り]
How hematopoietic stem cells (HSCs) produce particular lineages is insufficiently understood. We searched for key factors that direct HSC to lymphopoiesis. Comparing gene expression profiles for HSCs and early lymphoid progenitors revealed that Satb1, a global chromatin regulator, was markedly induced with lymphoid lineage specification. HSCs from Satb1-deficient mice were defective in lymphopoietic activity in culture and failed to reconstitute T lymphopoiesis in wild-type recipients. Furthermore, Satb1 transduction of HSCs and embryonic stem cells robustly promoted their differentiation toward lymphocytes. Whereas genes that encode Ikaros, E2A, and Notch1 were unaffected, many genes involved in lineage decisions were regulated by Satb1. Satb1 expression was reduced in aged HSCs with compromised lymphopoietic potential, but forced Satb1 expression partly restored that potential. Thus, Satb1 governs the initiating process central to the replenishing of lymphoid lineages. Such activity in lymphoid cell generation may be of clinical importance and useful to overcome immunosenescence. - 慢性骨髄性白血病平瀨 主税; 田中 宏和; 松村 到日本臨牀 23 67 - 72 日本臨牀 2013年05月
- 慢性好酸球性白血病、非特定型田中 宏和; 平瀨 主税; 松村 到日本臨牀 23 80 - 82 日本臨牀 2013年05月
- Camille Abboud; Ellin Berman; Adam Cohen; Jorge Cortes; Daniel DeAngelo; Michael Deininger; Steven Devine; Brian Druker; Amir Fathi; Elias Jabbour; Madan Jagasia; Hagop Kantarjian; Jean Khoury; Pierre Laneuville; Richard Larson; Jeffrey Lipton; Joseph O. Moore; Tariq Mughal; Susan O'Brien; Javier Pinilla-Ibarz; Alfonso Quintas-Cardama; Jerald Radich; Vishnu Reddy; Charles Schiffer; Neil Shah; Paul Shami; Richard T. Silver; David Snyder; Richard Stone; Moshe Talpaz; Ayalew Tefferi; Richard A. Van Etten; Meir Wetzler; Elisabetta Abruzzese; Jane Apperley; Massimo Breccia; Jenny Byrne; Francisco Cervantes; Ekaterina Chelysheva; R. E. Clark; Hugues de Lavallade; Iryna Dyagil; Carlo Gambacorti-Passerini; John Goldman; Ibrahim Haznedaroglu; Henrik Hjorth-Hansen; Tessa Holyoake; Brian Huntly; Philipp le Coutre; Elza Lomaia; Francois-Xavier Mahon; David Marin-Costa; Giovanni Martinelli; Jiri Mayer; Dragana Milojkovic; Eduardo Olavarria; Kimmo Porkka; Johan Richter; Philippe Rousselot; Giuseppe Saglio; Guray Saydam; Jesper Stentoft; Anna Turkina; Paolo Vigneri; Andrey Zaritskey; Alvaro Aguayo; Manuel Ayala; Israel Bendit; Raquel Maria Bengio; Carlos Best; Eduardo Bullorsky; Eduardo Cervera; Carmino DeSouza; Ernesto Fanilla; David Gomez-Almaguer; Nelson Hamerschlak; Jose Lopez; Alicia Magarinos; Luis Meillon; Jorge Milone; Beatriz Moiraghi; Ricardo Pasquini; Carolina Pavlovsky; Guillermo J. Ruiz-Arguelles; Nelson Spector; Christopher Arthur; Peter Browett; Andrew Grigg; Jianda Hu; Xiao-jun Huang; Tim Hughes; Qian Jiang; Saengsuree Jootar; Dong-Wook Kim; Hemant Malhotra; Pankaj Malhotra; Itaru Matsumura; Junia Melo; Kazunori Ohnishi; Ryuzo Ohno; Tapan Saikia; Anthony P. Schwarer; Naoto Takahashi; Constantine Tam; Tetsuzo Tauchi; Kensuke Usuki; Jianxiang Wang; Fawzi Abdel-Rahman; Mahmoud Deeb Saeed Aljurf; Ali Bazarbachi; Dina Ben Yehuda; Naeem Chaudhri; Muheez Durosinmi; Hossam Kamel; Vernon Louw; Bassam FrancisMatti; Arnon Nagler; Pia Raanani; Ziad SalemBLOOD 121 22 4439 - 4442 2013年05月 [査読有り]
As a group of more than 100 experts in chronic myeloid leukemia (CML), we draw attention to the high prices of cancer drugs, with the particular focus on the prices of approved tyrosine kinase inhibitors for the treatment of CML. This editorial addresses the multiple factors involved in cancer drug pricing and their impact on individual patients and health care policies, and argues for the need to (1) lower the prices of cancer drugs to allow more patients to afford them and (2) maintain sound long-term health care policies. - 【血液症候群(第2版)-その他の血液疾患を含めて-】 造血器腫瘍と類縁疾患 骨髄増殖性疾患 慢性骨髄性白血病群 慢性骨髄性白血病平瀬 主税; 田中 宏和; 松村 到日本臨床 別冊 血液症候群第2版III 67 - 72 (株)日本臨床社 2013年05月
- 【血液症候群(第2版)-その他の血液疾患を含めて-】 造血器腫瘍と類縁疾患 骨髄増殖性疾患 慢性好酸球性白血病、非特定型田中 宏和; 平瀬 主税; 松村 到日本臨床 別冊 血液症候群第2版III 80 - 82 (株)日本臨床社 2013年05月
- 芦田 隆司; 川野 亜美; 山田 枝里佳; 井手 大輔; 菅野 知恵美; 加藤 祐子; 椿本 祐子; 伊藤 志保; 峯 佳子; 藤田 往子; 金光 靖; 森嶋 祥之; 森田 泰慶; 田中 宏和; 嶋田 高広; 川西 一信; 宮武 淳一; 辰巳 陽一; 松村 到臨床血液 54 4 365 - 369 一般社団法人 日本血液学会 2013年04月 [査読有り]
今回,単一施設における輸血後鉄過剰症の実態を検討した。2009年と2010年の2年間に年間10単位以上の輸血を受けていた血液疾患患者は合計163例で,およそ半数が骨髄異形成症候群(61例)と再生不良性貧血(18例)であった。赤血球輸血が20単位施行された時点で血清フェリチン値が測定されていた65症例中血清フェリチン値が500 ng/ml以上,1,000 ng/ml以上であった症例の比率はそれぞれ90.8%, 66.2%であった。鉄過剰症に関連すると推測される臓器障害の比率は,全体で56.9%, 血清フェリチンが500~999 ng/mlでは43.8%, 1,000 ng/ml以上では67.4%であった。今回の解析により,「輸血後鉄過剰症の全国実態調査」の結果より早期に輸血後鉄過剰症が起こり,臓器障害も出現することが明らかになった。したがって,赤血球輸血40単位,血清フェリチン値1,000 ng/mlを除鉄療法の開始基準とするわが国のガイドラインより早期に除鉄療法を開始する必要がある可能性が示唆された。 - 白血病田中 宏和; 松村 到Animus Animus 75 11 - 15 アニムス 2013年04月
- 敗血症における急性腎障害に対するIL-18Rαの役割の検討樋野 尚一; 李 進海; 田崎 知江美; 井上 明日圭; 湯本 妙子; 岩永 智陽; 志賀 俊彦; 朝戸 佳世; 岸本 和也; 嶋津 秀紀; 矢野 智洋; 永禮 靖章; 野崎 祐史; 木下 浩二; 船内 正憲; 松村 到日本腎臓学会誌 55 3 311 - 311 (一社)日本腎臓学会 2013年04月
- 腎虚血再灌流障害(IRI)におけるIL-18とFas Ligand(FasL)の関与についての検討矢野 智洋; 野崎 祐史; 船内 正憲; 木下 浩二; 嶋津 秀紀; 岸本 和也; 樋野 尚一; 松村 到日本腎臓学会誌 55 3 370 - 370 (一社)日本腎臓学会 2013年04月
- Ashida T; Kawano A; Yamada E; Ide D; Sugano C; Kato Y; Tsubakimoto Y; Ito S; Mine Y; Fujita M; Kanemitsu Y; Morishima Y; Morita Y; Tanaka H; Shimada T; Kawanishi K; Miyatake J; Tatsumi Y; Matsumura I[Rinsho ketsueki] The Japanese journal of clinical hematology 54 4 365 - 369 2013年04月 [査読有り]
- Yoshinobu Kanda; Kumi Oshima; Shinichi Kako; Takahiro Fukuda; Naoyuki Uchida; Koichi Miyamura; Yukio Kondo; Shinji Nakao; Koji Nagafuji; Toshihiro Miyamoto; Mineo Kurokawa; Yasushi Okoshi; Shigeru Chiba; Yasuo Ohashi; Yoichi Takaue; Shuichi TaniguchiAMERICAN JOURNAL OF HEMATOLOGY 88 4 294 - 300 2013年04月 [査読有り]
We evaluated the efficacy of in vivo T-cell depletion with alemtuzumab in two prospective studies according to the International Conference on Harmonisation (ICH)Good Clinical Practice (ICHGCP) guidelines; one was for patients with aplastic anemia (AA study) and the other was for patients who were undergoing hematopoietic stem cell transplantation (HSCT) from a 2- or 3-antigen-mismatched haploidentical donor (MM study). The final dose of alemtuzumab in these studies was 0.16 mg/kg/day for 6 days. At this dose, all of the 12 and 11 patients in the AA and MM studies, respectively, achieved initial engraftment and the incidences of Grade IIIV acute graft-versus-host disease (GVHD) were 0% and 18%. While cytomegalovirus (CMV) frequently reactivated, none of the patients developed fatal CMV disease. Transplantation-related mortality within 1 year after HSCT was observed in only two and one patients, respectively. The numbers of CD4+ and CD8+ T-cells and T-cell receptor rearrangement excision circles remained low within 1 year after HSCT. These findings suggest that the use of alemtuzumab at this dose in a conditioning regimen enables safe allogeneic HSCT even from a 2- or 3-antigen-mismatched donor. However, the use of a lower dose of alemtuzumab should be explored in future studies to accelerate immune recovery after HSCT. Am. J. Hematol. 88:294300, 2013. (c) 2013 Wiley Periodicals, Inc. - S. Kurosawa; K. Yakushijin; T. Yamaguchi; Y. Atsuta; T. Nagamura-Inoue; H. Akiyama; S. Taniguchi; K. Miyamura; S. Takahashi; T. Eto; H. Ogawa; M. Kurokawa; J. Tanaka; K. Kawa; K. Kato; R. Suzuki; Y. Morishima; H. Sakamaki; T. FukudaBONE MARROW TRANSPLANTATION 48 4 529 - 536 2013年04月 [査読有り]
The outcomes for allogeneic hematopoietic cell transplantation (allo-HCT) are heavily influenced by non-relapse mortality (NRM). We retrospectively assessed the changes in the incidence and causes of NRM after allo-HCT over the past 12 years. NRM, relapse rate and OS were analyzed using the Japan transplant outcome database of 6501 adult patients with acute leukemia or myelodysplastic syndrome who received their first allo-HCT in remission from 1997 through 2008. In multivariate analysis in patients aged 16-49 years, the adjusted hazard ratios (HRs) for NRM for 2001-2004 and 2005-2008 were 0.78 (95% confidence interval, 0.65-0.93) and 0.64 (0.54-0.78), respectively, compared with 1997-2000. The HR for overall mortality in 2005-2008 was 0.81 (0.70-0.93) compared with 1997-2000. In patients aged 50-70 years, the HRs for NRM and overall mortality in 2005-2008 were 0.56 (0.46-0.68) and 0.66 (0.47-0.93), respectively, compared with those in 2001-2004. We found that causes of death that contributed to the changes in NRM varied among subgroups. In conclusion, our study indicated that the incidence of NRM after allo-HCT has significantly decreased over the past 12 years, which has led to an improvement of OS, and also showed reductions in NRM in subgroups consisting of older patients and those who received unrelated cord blood transplantation. Bone Marrow Transplantation (2013) 48, 529-536; doi: 10.1038/bmt.2012.172; published online 10 September 2012 - 骨髄由来細胞によるがん転移の制御機構松村 到BIO Clinica 28 5 493 - 498 (株)北隆館 2013年04月がんの転移は、がん細胞の原発巣からの遊離に始まり、遠隔の転移巣形成まで数多くのステップから構成される。これらのステップが遂行されるためには、がん細胞自身の変異のみでなく、がん細胞の周辺細胞、細胞外マトリックスといった微小環境ががん転移に適した状態に整えられる必要がある。以前から原発巣、転移巣のいずれのがん組織にもマクロファージなどの骨髄由来細胞が多数集簇することが報告されてきたが、この数年の研究でこれらの骨髄由来細胞が、がんの組織内進展、血管新生、前転移ニッチの形成、さらには腫瘍免疫の抑制などがんの浸潤・転移のほとんどのステップに深く関わっていることが明らかとされてきた。とくに最近ではがん転移の促進における骨髄由来細胞の機能やそれに関わる主要な分子が同定され、それらを標的とした新たな治療薬の開発が進められている。(著者抄録)
- 【造血器腫瘍】 白血病田中 宏和; 松村 到アニムス 18 2 11 - 15 アニムス編集委員会 2013年04月
- Successful anticoagulant therapy for two pregnant PNH patients, and prospects for the eculizumab eraYasuyoshi Morita; Jun-Ichi Nishimura; Takahiro Shimada; Hirokazu Tanaka; Kentaro Serizawa; Yasuhiro Taniguchi; Mitsuhiro Tsuritani; Yuzuru Kanakura; Itaru MatsumuraInternational Journal of Hematology 97 4 491 - 497 2013年04月 [査読有り]
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired stem cell disorder characterized by intravascular hemolysis and thrombosis. The most serious complication is thrombosis, the risk of which is augmented by the hyper-coagulable state that occurs during pregnancy despite this risk, however, young female PNH patients often desire to have a baby. We recently experienced two successful deliveries in PNH patients, who were treated with anticoagulant therapy during their pregnancies. Meanwhile, given the potential benefit of eculizumab (Soliris), a humanized monoclonal antibody against C5, in reducing thrombosis and hemolysis, it represents a promising therapeutic option for the treatment of pregnant PNH patients in combination with, or in replacement of, anticoagulant therapy. © The Japanese Society of Hematology 2013. - 関節リウマチでエタネルセプト治療中に発症した全身性エリテマトーデスの1例李 進海; 朝戸 佳世; 井上 明日圭; 田崎 知江美; 志賀 俊彦; 樋野 尚一; 矢野 智洋; 岸本 和也; 野崎 祐史; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会・国際リウマチシンポジウムプログラム・抄録集 57回・22回 491 - 491 (一社)日本リウマチ学会 2013年03月
- PRES(Posterior Reversible Encephalopathy Syndrome)とRCVS(Reversible Cerebral Vasoconstriction Syndrome)を合併した強皮症腎クリーゼの1例志賀 俊彦; 井上 明日圭; 田崎 知江美; 李 進海; 朝戸 佳世; 樋野 尚一; 矢野 智洋; 岸本 和也; 野崎 祐史; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会・国際リウマチシンポジウムプログラム・抄録集 57回・22回 522 - 522 (一社)日本リウマチ学会 2013年03月
- リウマチ性多発筋痛症における関節エコー所見とMMP-3の相関に関する検討井上 明日圭; 野崎 祐史; 田崎 知江美; 李 進海; 湯本 妙子; 岩永 智陽; 朝戸 佳世; 志賀 俊彦; 樋野 尚一; 矢野 智洋; 岸本 和也; 永禮 靖章; 嶋津 秀紀; 木下 浩二; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会・国際リウマチシンポジウムプログラム・抄録集 57回・22回 630 - 630 (一社)日本リウマチ学会 2013年03月
- インフリキシマブ投与時間短縮症例の検討永禮 靖章; 井上 明日圭; 田崎 知江美; 李 進海; 岩永 智陽; 湯本 妙子; 朝戸 佳世; 志賀 俊彦; 樋野 尚一; 矢野 智洋; 岸本 和也; 嶋津 秀紀; 野崎 祐史; 木下 浩二; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会・国際リウマチシンポジウムプログラム・抄録集 57回・22回 638 - 638 (一社)日本リウマチ学会 2013年03月
- 当科におけるニューモシスチス肺炎4例の臨床的検討岸本 和也; 李 進海; 田崎 知江美; 井上 明日圭; 湯本 妙子; 岩永 智陽; 志賀 俊彦; 朝戸 佳世; 矢野 智洋; 樋野 尚一; 永禮 靖章; 嶋津 秀紀; 野崎 祐史; 木下 浩二; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会・国際リウマチシンポジウムプログラム・抄録集 57回・22回 683 - 683 (一社)日本リウマチ学会 2013年03月
- 野村 守弘; 浅野 肇; 讃岐 寛徳; 喜来 美妃; 氏原 淳; 渡邉 達也; 山添 譲; 松村 到臨床薬理 44 2 71 - 76 (一社)日本臨床薬理学会 2013年03月治験に係る業務のなかでもSDV(Source Data Verification)はGCPが定める必須作業であり、臨床現場での開発コストの大きな部分を占める作業でもある。電子的遠隔SDV(以下RSDV)は、現場で実施するSDVを遠隔地点で実施できるようにしたものであるが、単にコンピュータ通信システムを使うといった単純なものではなく、実施にあたって生じる「個人情報保護」「データ保証」「作業労力とコスト」といった問題をクリアして実施されねばならない。今回、RSDVの試行にあたって治験依頼者の協力を得、その成果と課題について検討した。また、RSDVの本実施にあたり依頼者に成果や満足度のアンケートを行ったので、併せて報告した。RSDVの成果として、SDV回数の減少傾向がみられたものの、大幅な削減はできていなかった。しかし、RSDVにて一度見た場合の1回のSDV時間は、現場で初めて見た場合に比べて著明に短縮されており、事前チェックされたデータを現場で再チェックしている機能が顕著であった。
- 慢性骨髄性白血病の診断と治療松村 到日本検査血液学会 14 1 18 日本検査血液学会 2013年02月
- Masamitsu Yanada; Japan Adult Leukemia Study Group; Motohiro Tsuzuki; Hiroyuki Fujita; Katsumichi Fujimaki; Shin Fujisawa; Kazutaka Sunami; Masafumi Taniwaki; Akira Ohwada; Kosuke Tsuboi; Akio Maeda; Akihiro Takeshita; Shigeki Ohtake; Yasushi Miyazaki; Yoshiko Atsuta; Yukio Kobayashi; Tomoki Naoe; Nobuhiko EmiBlood 121 16 3095 - 3102 2013年 [査読有り]
The optimal treatments for relapsed acute promyelocytic leukemia (APL) remain equivocal. We conducted a phase 2 study to evaluate the efficacy and feasibility of a sequential treatment consisting of induction and consolidation with arsenic trioxide (ATO), peripheral blood stem cell (PBSC) harvest after high-dose cytarabine chemotherapy, and autologous hematopoietic cell transplantation (HCT). Between 2005 and 2009, 35 patients (26 with hematologic and 9 with molecular relapse) were enrolled. Induction therapy resulted in complete remission in 81% of those with hematologic relapse, and most patients became negative for PML-RARa after the first ATO consolidation course, but 4 remained positive. Administration of the second ATO consolidation course further decreased the transcript levels in 3 patients. In total, 25 patients proceeded to PBSC harvest, all of whom successfully achieved the target CD341 cell doses, and 23 underwent autologous HCT with PML-RARa–negative PBSC graft. Posttransplant relapse occurred in 3 patients, and there was no transplant-related mortality. With a median follow-up of 4.9 years, the 5-year event-free and overall survival rates were 65% and 77%, respectively. These findings demonstrate the outstanding efficacy and feasibility of the sequential treatment featuring ATO and autologous HCT for relapsed APL. This study was registered at http://www.umin.ac.jp/ctr/ as #C000000302. - 【慢性骨髄性白血病(CML)治療〜残された課題〜】 序 CML治療の到達点と今後松村 到血液フロンティア 23 2 165 - 168 (株)医薬ジャーナル社 2013年01月BCR-ABL阻害薬イマチニブが登場し、慢性期のCML(CML-CP)の治療成績は飛躍的に改善した。また、一部のイマチニブ抵抗性・不耐容例に対して第二世代チロシンキナーゼ阻害薬(TKI)のニロチニブとダサチニブが開発され、第二世代TKIは初発CML-CPに対しても承認された。これら第二世代TKIが無効なT315I変異を克服するための、第三世代TKIであるポナチニブの開発も進んでいる。一方、CML幹細胞はTKI抵抗性であり、TKIは中止できないとされてきた。しかし、STIM試験の結果から、TKI単独投与でもCML-CPが治癒する可能性が示唆されるようになった。すでにTKI単独あるいは他の薬剤との併用によるCML治癒に向けた研究も進行中である。CML治療はすべての症例で病期進行を回避するのみでなく、長期にわたるQOLの低下や経済的な問題を解決するために治癒に向けた戦略の確立が目指されている。(著者抄録)
- 【慢性骨髄性白血病(CML)治療〜残された課題〜】 初発慢性期CMLに対する至適治療とその効果判定平瀬 主税; 松村 到血液フロンティア 23 2 177 - 187 (株)医薬ジャーナル社 2013年01月初発の慢性期慢性骨髄性白血病に対して、第1世代のチロシンキナーゼ阻害剤であるイマチニブよりも強力なBCR-ABL阻害作用を有する第2世代のニロチニブ、ダサチニブが本邦でも承認された。その結果、イマチニブと比較してより早期の深い分子遺伝学的効果の達成、より確実な病期進行の回避が可能となった。また、深い分子遺伝学的効果を達成・維持することで治癒を目指す時代となった。しかし、イマチニブと違って第2世代TKIの長期投与の安全性は、今後確認される必要がある。また、新たな治療効果判定基準の確立という課題も残されている。(著者抄録)
- Shinya Rai; Mitsuhiro Matsuda; Nozomi Yamairi; Go Eguchi; Takayuki Iwanaga; Yasuyoshi Morita; Hirokazu Tanaka; Yoichi Tatsumi; Takashi Ashida; Itaru MatsumuraInternal Medicine 52 2 273 - 276 2013年 [査読有り]
A 32-year-old woman was referred to our hospital due to systemic lymphadenopathy. The patient's peripheral blood showed expansion of CD5+CD20+CD38+CD23- mature lymphocytes. However, the axillary lymph nodes were infiltrated by both CD23+ large lymphocytes and CD23- small lymphocytes. Because the pattern of the rearranged immunoglobulin heavy chain gene was different between the peripheral blood and lymph node samples in a Southern blot analysis, the patient was diagnosed with Richter syndrome, in which diffuse large B-cell lymphoma develops from a clone distinct from B-cell chronic lymphocytic leukemia. After undergoing rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) therapy, the patient was successfully treated with allogeneic hematopoietic transplantation, and no relapse was observed for three years. © 2013 The Japanese Society of Internal Medicine. - 樋野 尚一; 井上 明日圭; 田崎 知江美; 李 進海; 岩永 智陽; 湯本 妙子; 朝戸 佳世; 志賀 俊彦; 矢野 智洋; 廣岡 靖章; 野崎 祐史; 木下 浩二; 船内 正憲; 松村 到; 杉山 昌史臨床リウマチ 24 4 273 - 278 (一社)日本臨床リウマチ学会 2012年12月近年、関節炎、レイノー現象や抗核抗体など、膠原病を示唆する症状や検査所見を認めるものの、特定の膠原病の診断基準を満たさない症例があり、undifferentiated connective tissue diseases(UCTD)と呼ばれている。これらの多くの症例は軽症であり、少量のステロイドで活動性が抑えられている。症例は55歳女性。急速に進行した足趾の皮膚潰瘍は壊死に至った。病理組織では血管炎を認めたが、特定の膠原病の診断基準を満たさず、UCTDと診断した。ステロイド治療が有効であったが、足趾先端の壊死は自然離断した。進行性の血管炎をきたす場合には、病理学的診断を得て早期の鑑別診断と治療方針の決定が重要と考えた。(著者抄録)
- 米矢 吉宏; 細野 眞; 山田 穣; 松木 充; 花岡 宏平; 坂口 健太; 任 誠雲; 柳生 行伸; 石井 一成; 辰巳 陽一; 松村 到; 土屋 典生核医学 49 4 439 - 439 (一社)日本核医学会 2012年11月
- Morita Y; Tanaka H; Matsumura INihon rinsho. Japanese journal of clinical medicine 70 Suppl 8 508 - 512 2012年11月 [査読有り]
- 【分子標的薬-がんから他疾患までの治癒をめざして-】 臨床研究 腫瘍性疾患の分子標的薬 骨髄異形成症候群森田 泰慶; 田中 宏和; 松村 到日本臨床 70 増刊8 分子標的薬 508 - 512 (株)日本臨床社 2012年11月
- A case of intraocular lymphoma with central nervous system involvement and high interleukin-10 levels in both vitreous humor and cerebrospinal fluids:successsful tretment with a combinnation of intravitreal,intrathecal,and systemic therapy宮武 淳一; 川内 超矢; 口分田 貴裕; 山口 晃史; 森田 泰慶; 辰巳 陽一; 松村 到; 前田裕弘; 大黒のぶゆきInt Canc Conf J 2 71 - 75 2012年10月
- 正常核型AMLの遺伝子変異田中 宏和; 松村 到最新医学 67 10 24 - 30 最新医学社 2012年10月
- 急性骨髄性白血病(AML)-病態解明と治療はいかに進歩したか-松村 到; 清井 仁; 黒川峰夫最新医学 67 10 7 - 17 最新医学社 2012年10月
- イマチニブ抵抗性・不耐容の慢性期CMLに対する治療方針田中 宏和; 松村 到EBM血液疾患の治療 2013-2014 中外医学社 2012年10月
- クロマチンおよびDNA修飾を標的とする分子的治療薬の開発:総論田中 宏和; 松村 到造血器腫瘍とエピジェネティクス 160 - 167 医薬ジャーナル社 2012年10月
- CMLの最新治療平瀨 主税; 田中 宏和; 松村 到Current Therapy Current Therapy 30 10 2012年10月
- 松村 到; 清井 仁; 黒川 峰夫最新医学 67 10 2389 - 2399 最新医学社 2012年10月 [査読有り]
- 【白血病治療の最前線-EBMの先にあるもの】 CMLの最新治療平瀬 主税; 田中 宏和; 松村 到カレントテラピー 30 10 1051 - 1056 (株)ライフメディコム 2012年10月
- 【急性骨髄性白血病-分子異常と予後-】 急性骨髄性白血病(AML) 病態解明と治療はいかに進歩したか松村 到; 清井 仁; 黒川 峰夫最新医学 67 10 2389 - 2399 (株)最新医学社 2012年10月
- 【急性骨髄性白血病-分子異常と予後-】 正常核型AMLの遺伝子変異田中 宏和; 松村 到最新医学 67 10 2406 - 2412 (株)最新医学社 2012年10月急性骨髄性白血病(AML)の40〜50%は正常核型を有する.これまでAMLは,細胞増殖・生存にかかわるクラスI変異と細胞分化にかかわるクラスII変異が同時に起こって発症すると考えられてきた.しかし近年,エピジェネティクスにかかわる分子の遺伝子変異が多数明らかにされ,クラスIII変異と呼ばれるようになった.これらの遺伝子異常によって正常核型AMLの予後を層別化し,至適な治療法を確立することが今後の課題である.(著者抄録)
- Nozaki Y; Kinoshita K; Yano T; Asato K; Shiga T; Hino S; Niki K; Nagare Y; Kishimoto K; Shimazu H; Funauchi M; Matsumura IKidney international 82 8 892 - 902 2012年10月 [査読有り]
Interleukin (IL)-18 is produced by leukocytes and renal parenchymal cells (tubular epithelial cells, podocytes, and mesangial cells). The IL-18 receptor (IL-18R) is expressed on these cells in cisplatin-induced acute kidney injury, but the role of IL-18R is unknown. To help define this, we compared IL-18R alpha knockout with wild-type mice in cisplatin-induced acute kidney injury and found deteriorated kidney function, tubular damage, increased accumulation of leukocytes (CD4(+) and CD8(+) T-cells, macrophages, and neutrophils), upregulation of early kidney injury biomarkers (serum TNF, urinary IL-18, and KIM-1 levels), and increased expression of pro-inflammatory molecules downstream of IL-18. In vitro, leukocytes from the spleen and kidneys of the knockout mice produced greater amounts of pro-inflammatory cytokines upon stimulation with concanavalin A compared to that in wild-type mice. Levels of the suppressor of cytokine signaling 1 and 3 (negative regulators of cytokine signaling) were reduced in the spleen and kidneys of IL-18R alpha-deficient compared to wild-type mice. Adoptive transfer of wild-type splenocytes by IL-18R alpha-deficient mice led to decreased cisplatin nephrotoxicity compared to control IL-18R alpha-deficient mice. In contrast, anti-IL-18R alpha and anti-IL-18R beta antibody treatment tended to increase cisplatin nephrotoxicity in wild-type mice. Thus, signaling through IL-18Ra activates both inflammation-suppressing and pro-injury pathways in cisplatin-induced acute kidney injury. Kidney International (2012) 82, 892-902; doi:10.1038/ki.2012.226; published online 6 June 2012 - Recognition of complete response by long-term observation after treatment with 90Y-Ibritumomab tiuxetan for relapsed follicular lymphoma辰巳 陽一; 賴 晋也; 嶋田 高広; 山口 晃史; 森田 泰慶; 川西 一信; 宮武 淳一; 芦田 隆司; 前田 裕弘; 細野 眞; 松村 到Acta Med Kinki Univ 36 2 87 - 89 近畿大学 2012年09月
- 自家SCTとリツキシマブ維持療法によるリクター症候群患者の長期生存例(Richter syndrome with a long-term survival treated with auto-SCT and Rituximab maintenance therapy)Yamairi Nozomi; Eguchi Go; Rai Shinya; Yamagami Tamotsu; Iwanaga Takayuki; Wada Naoki; Ikeda Junichiro; Aozasa Katsuyuki; Matsumura Itaru; Matsuda Mitsuhiro臨床血液 53 9 1244 - 1244 2012年09月
- Shigeo Fuji; Fumiaki Nakamura; Kazuo Hatanaka; Shuichi Taniguchi; Maho Sato; Shin-ichiro Mori; Hisashi Sakamaki; Hiromasa Yabe; Toshihiro Miyamoto; Heiwa Kanamori; Yasunori Ueda; Keisei Kawa; Koji Kato; Ritsuro Suzuki; Yoshiko Atsuta; Toshiharu Tamaki; Yoshinobu KandaBIOLOGY OF BLOOD AND MARROW TRANSPLANTATION 18 9 1407 - 1414 2012年09月 [査読有り]
To compare the different stem cell sources used in salvage transplantation for graft failure (GF) after cord blood transplantation (CBT), we retrospectively analyzed data of 220 patients who developed GF after undergoing CBT between January 2001 and December 2007 and underwent a second hematopoietic stem cell transplantation (HSCT) within 3 months. The donor sources for salvage HSCTwere cord blood (n = 180), peripheral blood stem cells (PBSCs; n = 24), and bone marrow (BM; n = 16). The cumulative incidence of neutrophil engraftment on day 30 after the second HSCTwas 39% with CB, 71% with PBSCs, and 75% with BM. Multivariate analysis revealed that PBSC and BM grafts were associated with a significantly higher engraftment rate than CB (hazard ratio [HR], 7.77; P < .001 and HR, 2.81; P = .016, respectively). Although the incidence of grade II-1V acute graft-versus-host disease was significantly higher in the PBSC group than in the CB group (HR, 2.83; P = .011), the incidence of 1-year nonrelapse mortality was lower in the PBSC group than in the CB group (HR, 0.43; P = .019), and 1-year overall survival was superior in the PBSC group compared with the CB group (HR, 0.45; P = .036). Our results suggest that PBSC is the preferable source of stem cells in salvage HSCT for GF after CBT. Biol Blood Marrow Transplant 18: 1407-1414 (2012) (C) 2012 American Society fir Blood and Marrow Transplantation - 慢性骨髄性白血病の現状と展望松村 到; 木村晋也; 木村文彦; 高橋直人; 三谷絹子Trends in Hematological Malignancies Trends in Hematological Malignancies 4 2 10 - 17 メディカルビュー社 2012年08月
- 志賀 俊彦; 湯本 妙子; 井上 明日圭; 田崎 智江美; 李 進海; 岩永 智陽; 朝戸 佳世; 矢野 智洋; 樋野 尚一; 岸本 和也; 永禮 靖章; 嶋津 秀紀; 野崎 祐史; 木下 浩二; 船内 正憲; 松村 到日本臨床免疫学会会誌 35 4 341 - 341 (一社)日本臨床免疫学会 2012年08月
- 樋野 尚一; 李 進海; 田崎 知江美; 井上 明日圭; 湯本 妙子; 岩永 智陽; 志賀 俊彦; 朝戸 佳世; 矢野 智洋; 岸本 和也; 永禮 靖章; 嶋津 秀紀; 野崎 祐史; 木下 浩二; 船内 正憲; 松村 到日本臨床免疫学会会誌 35 4 348 - 348 (一社)日本臨床免疫学会 2012年08月
- 松村 到; 木村 晋也; 木村 文彦Trends in hematological malignancies 4 2 74 - 81 メディカルレビュー社 2012年08月 [査読有り]
- 慢性骨髄性白血病診療の現状と展望松村 到; 木村 晋也; 木村 文彦; 高橋 直人; 三谷 絹子Trends in Hematological Malignancies 4 2 74 - 81 (株)メディカルレビュー社 2012年08月
- 造血器腫瘍関連遺伝子異常が樹状細胞分化に及ぼす影響の解析藤田 二郎; 水木 満佐央; 大塚 正恭; 江副 幸子; 佐藤 友亮; 福島 健太郎; 徳永 正浩; 田中 宏和; 松村 到; 金倉 譲Cytometry Research 22 Suppl. 65 - 65 (一社)日本サイトメトリー学会 2012年06月
- Kazunori Ohnishi; Chiaki Nakaseko; Jin Takeuchi; Shin Fujisawa; Tadashi Nagai; Hirohito Yamazaki; Tetsuzo Tauchi; Kiyotoshi Imai; Naoki Mori; Fumiharu Yagasaki; Yasuhiro Maeda; Noriko Usui; Yasushi Miyazaki; Koichi Miyamura; Hitoshi Kiyoi; Shigeki Ohtake; Tomoki NaoeCANCER SCIENCE 103 6 1071 - 1078 2012年06月 [査読有り]
A prospective multicenter Phase II study was performed to examine the efficacy and safety of imatinib therapy in newly diagnosed Japanese patients with chronic-phase CML. Patients were scheduled to receive imatinib 400 mg daily. Plasma imatinib concentrations were measured by liquid chromatographytandem mass spectrometry. In 481 evaluable patients, estimated 7-year overall survival (OS) and event-free survival (EFS) at a median follow-up of 65 months were 93% and 87%, respectively. Because imatinib dosage was reduced in many patients due mainly to adverse events, subgroup analysis was performed according to the mean daily dose during the first 24 months of treatment: =360 mg (400-mg group; n = 294), 270359 mg (300-mg group; n = 90) and <270 mg (200-mg group; n = 67). There were no significant differences in OS and EFS between the 300- and 400-mg groups; however, cumulative rates of complete cytogenetic and major molecular responses differed significantly between the two groups. There were no significant differences in mean imatinib trough levels between these two groups for the patients in whom trough levels had been measured. Survival and efficacy in the 200-mg group were markedly inferior to the former two groups. These results suggest that, although a daily dose of 400 mg imatinib is associated with better outcomes, 300 mg imatinib may be adequate for a considerable number of Japanese patients who are intolerant to 400 mg imatinib. Blood level monitoring would be useful to determine the optimal dose of imatinib. (Cancer Sci 2012; 103: 10711078) - Naoki Oiso; Yoichi Tatsumi; Tokuzo Arao; Shinya Rai; Masatomo Kimura; Shigeo Nakamura; Tomoo Itoh; Kazuto Nishio; Itaru Matsumura; Akira KawadaEUROPEAN JOURNAL OF DERMATOLOGY 22 3 393 - 394 2012年05月 [査読有り]
- 白血病松村 到; 平瀨 主税診療ガイドライン UP-TO-DATE 2012-2013 メディカルビュー社 2012年05月
- Naoki Wada; Mona A. A. Zaki; Masaharu Kohara; Hiroyasu Ogawa; Haruo Sugiyama; Shosaku Nomura; Itaru Matsumura; Masayuki Hino; Yuzuru Kanakura; Hiroshi Inagaki; Eiichi Morii; Katsuyuki AozasaHISTOPATHOLOGY 60 6 924 - 932 2012年05月 [査読有り]
Wada N, Zaki M A A, Kohara M, Ogawa H, Sugiyama H, Nomura S, Matsumura I, Hino M, Kanakura Y, Inagaki H, Morii E & Aozasa K (2012) Histopathology 60, 924-932 Diffuse large B cell lymphoma with an interfollicular pattern of proliferation shows a favourable prognosis: a study of the Osaka Lymphoma Study Group Aims: ]Diffuse large B cell lymphoma (DLBCL) occasionally shows an interfollicular pattern of proliferation (DLBCL-IF) preserving lymphoid follicles. In this study, clinicopathological findings in 31 cases of DLBCL-IF were analysed. Methods and results: The study group comprised 20 males and 11 females, with ages ranging from 41 to 87 (median 69) years. The primary site was lymph node in 25 cases, and unknown in six due to advanced stage at diagnosis. Eight cases were clinical Stage I, 10 were Stage II, four Stage III, and nine Stage IV. A polymorphous pattern of proliferation containing large B cells and inflammatory cells was found in about 60% of cases. The overall survival rate of the DLBCL-IF patients was better than that of a DLBCL control group (log-rank test; P < 0.05). Multivariate analysis revealed that an interfollicular pattern of proliferation showed marginal significance for favourable prognosis (P = 0.069). Immunohistochemical double staining with antibodies for HLA-DR/CD68 (markers for M1-tumour-associated macrophage [M1-TAM]) or CD163/CD68 (M2-TAM) revealed that all DLBCL-IF patients with a low M2 count were alive at the end of observation. Conclusions: These findings suggest that DLBCL-IF is a clinicopathological entity distinct from ordinary DLBCL. The possible origin of tumour cells in DLBCL-IF from marginal zone B cells is discussed. - Atsushi Sasakawa; Chikara Hirase; Terufumi Yamaguchi; Yasuyoshi Morita; Jun-ichi Miyatake; Itaru Matsumura; Yasuhiro MaedaHEMATOLOGY 17 3 144 - 150 2012年05月 [査読有り]
The pathogenesis of acquired immunodeficiency syndrome-associated primary central nervous system lymphoma (AIDS-associated PCNSL) remains unclear. However, cell adhesion molecules have been reported to be strongly associated with PCNSL. In this study, we established Epstein-Barr virus (EBV)transformed lymphoblastoid cell lines (LCLs) from HIV-positive patients (LCLHIV) and normal individuals (LCLN). The expression of CD18 antigen by LCLHIV was stronger than that by LCLN. We performed a cell adhesion assay using ISO-HAS, which is the human hemangiosarcoma cell line and expresses intercellular adhesion molecule 1 (CD54). The binding rates of LCLHIV and ISO-HAS without stimulation were higher than those of LCLN. Further, we demonstrated that azidothymidine or simvastatin inhibited the binding rates of LCLHIV and ISO-HAS more significantly than those of LCLN. Further, the levels of interleukin (IL)-8, a CD18 inducer, were higher in LCLHIV than in LCLN. We conclude that interaction between IL-8 and CD18 may be critical to AIDS-related PCNSL. - Yasuhiro Maeda; Masaya Kawauchi; Jun-ichi Miyatake; Chikara Hirase; Terufumi Yamaguchi; Itaru MatsumuraANNALS OF HEMATOLOGY 91 4 629 - 631 2012年04月 [査読有り]
- 腎虚血再灌流障害におけるIL-18Rαの役割の検討矢野 智洋; 野崎 祐史; 嶋津 秀紀; 岸本 和也; 樋野 尚一; 木下 浩二; 船内 正憲; 松村 到日本腎臓学会誌 54 3 229 - 229 (一社)日本腎臓学会 2012年04月
- Kensuke Usuki; Arinobu Tojo; Yasuhiro Maeda; Yukio Kobayashi; Akira Matsuda; Kazuma Ohyashiki; Chiaki Nakaseko; Tatsuya Kawaguchi; Hideo Tanaka; Koichi Miyamura; Yasushi Miyazaki; Shinichiro Okamoto; Kenji Oritani; Masaya Okada; Noriko Usui; Tadashi Nagai; Taro Amagasaki; Aira Wanajo; Tomoki NaoeINTERNATIONAL JOURNAL OF HEMATOLOGY 95 4 409 - 419 2012年04月 [査読有り]
Although the tyrosine kinase inhibitor (TKI) imatinib is often used as first-line therapy for newly diagnosed chronic myelogenous leukemia (CML), some patients fail to respond, or become intolerant to imatinib. Nilotinib is a potent and selective second-generation TKI, with confirmed efficacy and tolerability in patients with imatinib-resistant or -intolerant CML. A phase I/II study was conducted in Japanese patients with imatinib-resistant or -intolerant CML or relapsed/refractory Ph+ acute lymphoblastic leukemia. Thirty-four patients were treated with nilotinib for up to 36 months. Major cytogenetic response was achieved in 15/16 patients (93.8%) with chronic-phase CML within a median of approximately 3 months. Major molecular response was achieved in 13/16 patients (81.3%). These responses were sustained at the time of the most recent evaluation in 13 patients and 11 patients, respectively. Hematologic and cytogenetic responses were also observed in patients with advanced CML. The BCR-ABL mutation associated with the most resistance to available TKIs, T315I, was observed in three patients. Common adverse events included rash, nasopharyngitis, leukopenia, neutropenia, thrombocytopenia, nausea, headache and vomiting. Most adverse events resolved following nilotinib dose interruptions/reductions. These results support the favorable long-term efficacy and tolerability of nilotinib in Japanese patients with imatinib-resistant or -intolerant chronic-phase chronic myeloid leukemia. - 平瀬 主税; 松村 到日本臨床 70 1018 298 - 303 日本臨床社 2012年04月 [査読有り]
- 平瀬 主税; 松村 到日本臨床 70 1018 293 - 297 日本臨床社 2012年04月 [査読有り]
- 【造血器腫瘍学-基礎と臨床の最新研究動向-】 骨髄系腫瘍の臨床 慢性骨髄性白血病 初発慢性期の慢性骨髄性白血病の治療平瀬 主税; 松村 到日本臨床 70 増刊2 造血器腫瘍学 298 - 303 (株)日本臨床社 2012年04月
- 【造血器腫瘍学-基礎と臨床の最新研究動向-】 骨髄系腫瘍の臨床 慢性骨髄性白血病 慢性期の慢性骨髄性白血病の病因・病態平瀬 主税; 松村 到日本臨床 70 増刊2 造血器腫瘍学 293 - 297 (株)日本臨床社 2012年04月
- Kazuma Ohyashiki; Sei-ichiro Katagiri; Tetsuzo Tauchi; Junko H. Ohyashiki; Yasuhiro Maeda; Itaru Matsumura; Tai-ichi KyoBRITISH JOURNAL OF HAEMATOLOGY 157 2 254 - 256 2012年04月 [査読有り]
- Junya Kanda; Hiroh Saji; Takahiro Fukuda; Takeshi Kobayashi; Koichi Miyamura; Tetsuya Eto; Mineo Kurokawa; Heiwa Kanamori; Takehiko Mori; Michihiro Hidaka; Koji Iwato; Takashi Yoshida; Hisashi Sakamaki; Junji Tanaka; Keisei Kawa; Yasuo Morishima; Ritsuro Suzuki; Yoshiko Atsuta; Yoshinobu KandaBLOOD 119 10 2409 - 2416 2012年03月 [査読有り]
To clarify which is preferable, a related donor with an HLA-1 Ag mismatch at the HLA-A, HLA-B, or HLA-DR loci in the graft-versus-host (GVH) direction (RD/1AG-MM-GVH) or an HLA 8/8-allele (HLA-A, HLA-B, HLA-C, and HLA-DRB1)-matched unrelated donor (8/8-MUD), we evaluated 779 patients with acute leukemia, chronic myelogenous leukemia, or myelodysplastic syndrome who received a T cell-replete graft from an RD/1AG-MM-GVH or 8/8-MUD. The use of an RD/1AG-MM-GVH donor was significantly associated with a higher overall mortality rate than the use of an 8/8-MUD in a multivariate analysis (hazard ratio, 1.49; P<.001), and this impact was statistically significant only in patients with standard-risk diseases (P=.001). Among patients with standard-risk diseases who received transplantation from an RD/1AG-MM-GVH donor, the presence of an HLA-B Ag mismatch was significantly associated with a lower overall survival rate than an HLA-DR Ag mismatch because of an increased risk of treatment-related mortality. The HLA-C Ag mismatch or multiple allelic mismatches were frequently observed in the HLA-B Ag-mismatched group, and were possibly associated with the poor outcome. In conclusion, an 8/8-MUD should be prioritized over an RD/1AG-MM-GVH donor during donor selection. In particular, an HLA-B Ag mismatch in the GVH direction has an adverse effect on overall survival and treatment-related mortality in patients with standard-risk diseases. (Blood. 2012;119(10):2409-2416) - 笹川 淳; 前田 裕弘; 頼 晋也; 平瀬 主税; 山口 晃史; 森田 泰慶; 松村 到近畿大学医学雑誌 = Medical journal of Kinki University 37 1 45 - 52 近畿大学医学会 2012年03月 [査読有り]
[抄録] HIV感染者は, Epstein-Barrウイルス(EBV)陽性の悪性リンパ腫を高率に発症し, 非HIV感染者に発症する悪性リンパ腫と比較すると節外性, 特に中枢神経原発の悪性リンパ腫(primary central nervous system lymphoma, PCNSL)の頻度が高い.その機序を解明するため我々は, HIV感染者および健常者から, EBV陽性のBリンパ芽球細胞株(B-LCL)を樹立し, 細胞表面の接着分子の発現をフローサイトメーターで解析した.リンパ球機能関連抗原-1(lymphocyte function-associated antigen-1, LFA-1)のβ鎖であるCD18の発現は, HIV感染者由来のB-LCL(B-LCL_HIV)と健常者由来のB-LCL(B-LCL_N)の何れにおいても, EBV感染前のB細胞と比較して増強していた.また, B-LCL_HIVはB-LCL_NよりCD18を強く発現していた.B-LCL_はB-LCL_Nに比較し, LFA-1のリガンドである細胞接着分子-1(intercellular adhesion molecule-1, ICAM-1)を発現するヒト頭部血管肉腫細胞株(ISO-HAS)により高率に接着した.CD18の発現強度と, ISO-HASの接着率は正に相関しており, 細胞接着にCD18が関与していることが示唆された.さらに, B-LCL_HIVの培養上清中では, B-LCL_Nの培養上清に比べIL-8が有意に増加しており, この培養上清を添加することでB-LCL_NのCD18発現が増強した.本研究は, AIDS関連悪性リンパ腫細胞が, EBVの活性化, さらにオートクラインあるいはパラクラインのIL-8の刺激により, CD18の発現を亢進し, 血管内皮細胞により強く接着する可能性を示唆するものである. - Keiko Matsui; Sachiko Ezoe; Kenji Oritani; Masaru Shibata; Masahiro Tokunaga; Natsuko Fujita; Akira Tanimura; Takao Sudo; Hirokazu Tanaka; Michael W. McBurney; Itaru Matsumura; Yuzuru KanakuraBIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 418 4 811 - 817 2012年02月 [査読有り]
Sir2 has been shown to be essential for transcriptional silencing and longevity provided by calorie restriction in Saccharomyces cerevisiae and Caenorhabditis elegans. In this study, we investigated the role for its mammalian homologue, SIRT1, in hematopoietic cells. SIRT1 inhibitor, nicotinamide (NA), promoted and its activator, resveratrol, inhibited the differentiation of murine bone marrow c-Kit(high)Sca-1(+)Lineage(-) (KSL) cells during the culture system ex vivo. To further clarify the roles of SIRT1 in hematopoietic cells, we isolated KSL cells from fetal liver of SIRT1 knockout (KO) mice and cultured them for 5 days, because SIRT1 KO mice die shortly after the delivery. In agreement with the results from the experiments using NA and resveratrol, KSL cells isolated from SIRT1 KO mice more apparently differentiated and lost the KSL phenotype than those from wild-type (WT) mice. Furthermore, in each of colony assay, replating assay, or serial transplantation assay, SIRT1 KO KSL cells lost earlier the characteristics of stem cells than WT KSL cells. In addition, we found that SIRT1 maintains prematurity of hematopoietic cells through ROS elimination, FOXO activation, and p53 inhibition. These results suggest that SIRT1 suppresses differentiation of hematopoietic stem/progenitor cells and contributes to the maintenance of stem cell pool. (C) 2012 Elsevier Inc. All rights reserved. - Mai Suzuki; Hirokazu Tanaka; Akira Tanimura; Kenji Tanabe; Natsuko Oe; Shinya Rai; Syunsuke Kon; Manabu Fukumoto; Kohji Takei; Takaya Abe; Itaru Matsumura; Yuzuru Kanakura; Toshio WatanabePLOS ONE 7 2 2012年02月 [査読有り]
Phosphatidylinositol binding clathrin assembly protein (PICALM), also known as clathrin assembly lymphoid myeloid leukemia protein (CALM), was originally isolated as part of the fusion gene CALM/AF10, which results from the chromosomal translocation t(10;11)(p13;q14). CALM is sufficient to drive clathrin assembly in vitro on lipid monolayers and regulates clathrin-coated budding and the size and shape of the vesicles at the plasma membrane. However, the physiological role of CALM has yet to be elucidated. Here, the role of CALM in vivo was investigated using CALM-deficient mice. CALM-deficient mice exhibited retarded growth in utero and were dwarfed throughout their shortened life-spans. Moreover, CALM-deficient mice suffered from severe anemia, and the maturation and iron content in erythroid precursors were severely impaired. CALM-deficient erythroid cells and embryonic fibroblasts exhibited impaired clathrin-mediated endocytosis of transferrin. These results indicate that CALM is required for erythroid maturation and transferrin internalization in mice. - 慢性骨髄性白血病松村 到; 田中 宏和血液フロンティア 22 3 33 - 41 医薬ジャーナル社 2012年02月
- Y. Satoh; I. Matsumura; H. Tanaka; H. Harada; Y. Harada; K. Matsui; M. Shibata; M. Mizuki; Y. KanakuraLEUKEMIA 26 2 303 - 311 2012年02月 [査読有り]
Loss-of-function mutations of RUNX1 have been found in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDSs). Although several reports have suggested roles for RUNX1 as a tumor suppressor, its precise function remains unknown. Because gene alterations of RUNX1 by themselves do not lead to the development of leukemia in mouse models, additional mutation(s) would be required for leukemia development. Here, we report that the C-terminal deletion mutant of RUNX1, RUNX1dC, attenuates DNA-damage repair responses in hematopoietic stem/progenitor cells. gamma H2AX foci, which indicate the presence of DNA double-strand breaks, were more abundantly accumulated in RUNX1dC-transduced lineage(-)Sca1(+)c-kit(+) (LSK) cells than in mock-transduced LSK cells both in a steady state and after gamma-ray treatment. Expression profiling by real-time -PCR array revealed RUNX1dC represses the expression of Gadd45a, a sensor of DNA stress. Furthermore, bone marrow cells from MDS/AML patients harboring the RUNX1-C-terminal mutation showed significantly lower levels of GADD45A expression compared with those from MDS/AML patients with wild-type RUNX1. As for this mechanism, we found that RUNX1 directly regulates the transcription of GADD45A and that RUNX1 and p53 synergistically activate the GADD45A transcription. Together, these results suggest Gadd45a dysfunction due to RUNX1 mutations can cause additional mutation(s) required for multi-step leukemogenesis. Leukemia (2012) 26, 303-311; doi:10.1038/leu.2011.202; published online 12 August 2011 - 田中 宏和; 松村 到腫瘍内科 9 2 186 - 190 科学評論社 2012年02月
- 【血液病ガイドラインupdate〜造血器腫瘍〜】 慢性骨髄性白血病田中 宏和; 松村 到血液フロンティア 22 3 355 - 363 (株)医薬ジャーナル社 2012年02月慢性期の慢性骨髄性白血病(CML-CP)の治療成績は、チロシンキナーゼ阻害薬(TKI)が登場して画期的に改善した。イマチニブ投与時の治療効果判定およびその後の治療選択については、エビデンスが蓄積されてきた。第二世代TKIはイマチニブ抵抗性・不耐容例のみでなく、初発CML-CPに対してもイマチニブより高い治療効果を示すが、長期予後を含めたエビデンスの確立が今後の課題である。一方、移行期、急性転化期のCMLに対してはTKI単独では十分でなく、化学療法、同種造血幹細胞移植が必要とされる。CML治療においてはEuropean Leukemia Net(ELN)の推奨およびNCCNのガイドラインが一般に用いられている。(著者抄録)
- 田中 宏和; 松村 到腫瘍内科 9 2 186 - 190 (有)科学評論社 2012年02月
- Sachiko Sakamoto; Naoki Oiso; Masakatsu Emoto; Shusuke Uchida; Ayaka Hirao; Yoichi Tatsumi; Itaru Matsumura; Akira KawadaCase Reports in Dermatology 4 1 47 - 49 2012年01月Patients with hematologic malignancies are immunosuppressive and may develop cutaneous or invasive infections as a primary sign of immune suppression. Acute promyelocytic leukemia (acute myeloid leukemia M3) is caused by translocation of reciprocal chromosomal rearrangement t(15 17), which produces an oncogenic protein. We herein describe a 71-year-old man having cellulitis with leukocytopenia as a first sign of acute promyelocytic leukemia. Dermatologists and hematologists should keep in mind that patients with a hematologic malignancy, such as acute promyelocytic leukemia, can develop cellulitis with leukocytopenia. Copyright © 2012 S. Karger AG, Basel.
- 慢性骨髄性白血病松村 到今日の治療指針 582 - 584 医学書院 2012年01月
- Kazunobu Kawanishi; Yasuyo Ohyama; Yoshitake Kanai; Tikara Hirase; Hirokazu Tanaka; Junichi Miyatake; Youichi Tatsumi; Takashi Ashida; Hirokazu Nakamine; Itaru MatsumuraINTERNAL MEDICINE 51 15 2015 - 2020 2012年 [査読有り]
Here we report the first case of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), who initially presented with peripheral neuropathy. Nerve conduction, cerebral spinal fluid studies and his clinical course were compatible with sub-acute demyelinating polyradiculoneuropathy. In addition, left cervical lymph node swelling was observed on admission. Diagnosis of PTCL-NOS was made by the histological, immuno-histochemical, and Southern blot analyses on the biopsy specimen from the enlarged lymph node. Combination chemotherapy composed of cyclophosphamide, vincristine, doxorubicin and prednisolone (CHOP) was effective for polyneuropathy as well as for lymphoma. Several antibodies relating to paraneoplastic syndrome such as Ma1, Ma2, Amphiphysin, CV2, Ri, Yo and Hu were all negative. Because sural nerve biopsy performed prior to CHOP therapy revealed no infiltration of lymphoma cells, immune dysfunction mediated by some cytokine or unidentified autoantibody related to PTCL-NOS was thought to be involved in the polyradiculoneuropathy. - Cytokine profiles in relapsed multiple myeloma patients undergoing febrile reactions to lenalidomideYasuyoshi Morita; Takahiro Shimada; Terufumi Yamaguchi; Shinya Rai; Chikara Hirase; Masakatsu Emoto; Kentaro Serizawa; Yasuhiro Taniguchi; Mayuko Ojima; Yoichi Tatsumi; Takashi Ashida; Itaru MatsumuraINTERNATIONAL JOURNAL OF HEMATOLOGY 94 6 583 - 584 2011年12月 [査読有り]
- 松村 到血液内科 63 6 698 - 701 (有)科学評論社 2011年12月
- Akira Tanimura; Yuri Kondo; Hirokazu Tanaka; Itaru Matsumura; Tomohiko Ishibashi; Takao Sudo; Yusuke Satoh; Takafumi Yokota; Sachiko Ezoe; Kenji Oritani; Hirohiko Shibayama; Yuzuru KanakuraBLOOD 118 21 922 - 923 2011年11月 [査読有り]
- Yusuke Satoh; Takafumi Yokota; Motonari Kondo; Paul W. Kincade; Taku Kouro; Ryuji Iida; Koichi Kokame; Toshiyuki Miyata; Takao Sudo; Hirokazu Tanaka; Itaru Matsumura; Kenji Oritani; Terumi Kohwi-Shigematsu; Yuzuru KanakuraBLOOD 118 21 179 - 179 2011年11月 [査読有り]
- Kazuma Ohyashiki; Sei-ichiro Katagiri; Tetsuzo Tauchi; Junko H. Ohyashiki; Yasuhiro Maeda; Itaru Matsumura; Taiichi KyoBLOOD 118 21 739 - 739 2011年11月 [査読有り]
- 【がん分子標的治療の現状と展望】 臨床で分子標的薬を使用する際のポイントと課題 造血器腫瘍 白血病・悪性リンパ腫・多発性骨髄腫芹澤 憲太郎; 松村 到Progress in Medicine 31 11 2631 - 2635 (株)ライフ・サイエンス 2011年11月
- 【がん分子標的治療の現状と展望】 分子標的薬耐性とその克服 造血器腫瘍における分子標的薬 薬剤耐性機構と開発中の新薬芹澤 憲太郎; 松村 到Progress in Medicine 31 11 2581 - 2586 (株)ライフ・サイエンス 2011年11月
- 松村 到臨床血液 52 10 1610 - 1618 (一社)日本血液学会-東京事務局 2011年10月慢性期の慢性骨髄性白血病(CML)の治療成績はBCR-ABL阻害薬イマチニブの登場で画期的に改善したが、イマチニブ抵抗性或いは不耐容を示す症例も存在する。これに対応するため第二世代チロシンキナーゼ阻害薬(TKI)が開発された。ニロチニブはイマチニブに比べ20倍、ダサチニブは325倍、ボスチニブは50〜200倍高いBCR-ABL阻害効果を示す。慢性期、移行期および急性転化期CMLに対する第二世代TKIの有効性について概説した。
- Masaru Shibata; Sachiko Ezoe; Kenji Oritani; Keiko Matsui; Masahiro Tokunaga; Natsuko Fujita; Yuri Saito; Takayuki Takahashi; Masayuki Hino; Itaru Matsumura; Yuzuru KanakuraLEUKEMIA RESEARCH 35 9 1205 - 1211 2011年09月 [査読有り]
It would be of great value to predict the efficacy of tyrosine kinase inhibitors (TKIs) in the treatment of individual CML patients. We propose an immunoblot system for detecting the phosphorylation of Crkl, a major target of Bcr-Abl, in blood samples after in vitro incubation with TKIs. When the remaining phosphorylated Crkl after treatment with imatinib was evaluated as the "residual index (RI)", high values were found in accordance with imatinib resistance. Moreover, RI reflected the outcome of imatinib- as well as second generation TKIs with a high sensitivity and specificity. Therefore, this system should be useful in the selection of TKIs. (C) 2011 Elsevier Ltd. All rights reserved. - Antimicrobials for the treatment of febrile neutropenia clinical useffulness of antimicrobial cycling辰巳 陽一; 金丸 昭久; 松村 到Acta Med. Kinki Univ. 37 1 9 - 18 近畿大学 2011年08月
- 嶋田 高広; 松村 到検査と技術 39 8 593 - 598 (株)医学書院 2011年08月
- Hirofumi Akagi; Itaru MatsumuraIEEE TRANSACTIONS ON INDUSTRY APPLICATIONS 47 4 1741 - 1748 2011年07月 [査読有り]
This paper presents an intensive discussion on an overvoltage appearing at the motor terminals of an adjustable-speed drive that consists of a voltage-source pulsewidth-modulated inverter, an induction motor, and a three-phase symmetric long cable. It describes a design procedure for a simple passive electromagnetic-interference filter based on parallel connection of an inductor and a resistor, which is intended for mitigating the overvoltage at the motor terminals. The modeling of the cable and the motor is characterized by focusing on the natural frequency or ringing frequency inherent in the cable used, which is inversely proportional to cable length. Impedance mismatch at the inverter and motor terminals causes the overvoltage that may reach double the inverter dc-link voltage. The effectiveness and validity of the simple design procedure of the filter are confirmed on the 400-V 15-kW experimental system with either a 100- or 200-m-long cable, as well as on computer simulation based on the modeling of the cable and the motor. - 平瀬 主税; 松村 到診断と治療 99 7 1132 - 1136 診断と治療社 2011年07月
- 平瀬 主税; 松村 到診断と治療 99 7 1132 - 1136 (株)診断と治療社 2011年07月
- Naoki Oiso; Yoichi Tatsumi; Shinya Rai; Itaru Matsumura; Akira KawadaEUROPEAN JOURNAL OF DERMATOLOGY 21 4 636 - 638 2011年07月 [査読有り]
- Yasuhiro Maeda; Masaya Kawauchi; Chikara Hirase; Terufumi Yamaguchi; Jun-ichi Miyatake; Itaru MatsumuraRetrovirology 8 S1 2011年06月
- 松村 到内科 107 6 1328 - 1336 南江堂 2011年06月
- 松村 到内科 107 6 1328 - 1336 (株)南江堂 2011年06月
- Yuri Saito; Hirohiko Shibayama; Hirokazu Tanaka; Akira Tanimura; Itaru Matsumura; Yuzuru KanakuraBIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 408 2 329 - 333 2011年05月 [査読有り]
Anamorsin (AM) (also called CIAPIN-1) is a cell-death-defying factor. AM deficient mice die during late gestation; AM deficient embryos are anemic and very small compared to wild type (WT) embryos. It is thought that AM plays crucial roles in hematopoiesis and embryogenesis. To clarify the mechanisms of AM functions, we performed the yeast-two-hybrid assay to identify AM-interacting molecules; we found that PICOT (PKC theta interacting cousin of thioredoxin) preferentially bound to AM. We also showed that the N-terminal regions of both AM and PICOT were essential for their bindings and the inhibition of interaction of both molecules might lead to the cell growth retardation. Both PICOT and the yeast homolog of AM are known to be iron-sulfur proteins. The phenotype of PICOT deficient mice is very similar to that of anamorsin deficient mice; both mice are embryonic lethal. These data suggest that AM and PICOT might play cooperatively essential roles in embryogenesis as iron-sulfur cluster proteins. (C) 2011 Elsevier Inc. All rights reserved. - Minako Iida; Takahiro Fukuda; Kazuhiro Ikegame; Satoshi Yoshihara; Hiroyasu Ogawa; Shuichi Taniguchi; Akiyoshi Takami; Yasunobu Abe; Masayuki Hino; Tetsuya Etou; Yasunori Ueda; Toshiaki Yujiri; Toshimitsu Matsui; Atsuo Okamura; Junji Tanaka; Yoshiko Atsuta; Yoshihisa Kodera; Ritsuro SuzukiINTERNATIONAL JOURNAL OF HEMATOLOGY 93 4 523 - 531 2011年04月 [査読有り]
We evaluated the use of mycophenolate mofetil (MMF) after hematopoietic stem cell transplantation (HSCT) in Japan from 1999 to 2008. MMF was administered to 301 patients, including 157 for the prevention of graft-versus-host disease (GVHD), 94 for the treatment of acute GVHD and 50 for the treatment of chronic GVHD. The three most common doses were 500 mg twice daily, 250 mg three times daily and 1,000 mg twice daily, given to 63, 54 and 45 patients, respectively. The incidence of grade II-IV acute GVHD was 30.0% and grade III-IV was 20.0% in the GVHD prevention group. Among treated patients, disappearance or improvement of subjective symptoms occurred in 57.0% of acute GVHD patients and in 52.0% of chronic GVHD patients. With regard to safety, the following major adverse events (grade 3 or more) were recorded: 31 infections, 31 neutropenia, 28 thrombocytopenia, 25 diarrhea and 1 renal disorder. A total of 116 patients developed grade 3 or 4 adverse events, but 79 were successfully treated with supportive treatment. Thus, our findings suggest that MMF is safe and effective for the prevention and treatment of GVHD in patients who have received an allogeneic stem cell transplant. - Jiro Fujita; Masao Mizuki; Masayasu Otsuka; Sachiko Ezoe; Hirokazu Tanaka; Yusuke Satoh; Kentaro Fukushima; Masahiro Tokunaga; Itaru Matsumura; Yuzuru KanakuraIMMUNOLOGY LETTERS 136 1 61 - 73 2011年04月 [査読有り]
Dendritic cells (DCs) play important roles in tumor immunology. Leukemic cells in patients with myeloid neoplasms can differentiate into DCs in vivo (referred to as in vivo leukemic DCs), which are postulated to affect anti-leukemia immune responses. We established a reproducible culture system of in vitro FLT3 ligand-mediated DC (FL-DC) differentiation from murine lineage(-) Sca-1(+) c-Kit(high) cells (LSKs), which made it possible to analyse the effects of target genes on steady-state DC differentiation from hematopoietic stem/progenitor cells. Using this system, we analysed the effects of various myeloid neoplasm-related gene abnormalities, termed class I and class II mutations, on FL-DC differentiation from LSKs. All class II mutations uniformly impaired FL-DC differentiation maintaining a plasmacytoid DC (pDC)/conventional DC (cDC) ratio comparable to the control cells. In contrast, class I mutations differentially affected FL-DC differentiation from LSKs. FLT3-ITD and a constitutively active form of Ras (CA-N-Ras) yielded more FL-DCs than the control, whereas the other class I mutations tested yielded less FL-DCs. Both FLT3-ITD and FLT3-tyrosine kinase domain (TKD) mutation showed a comparable pDC/cDC ratio as the control. CA-N-Ras, c-Kit-TKD, TEL/PDGFR beta, and FIP1L1 /PDGFR alpha showed a severe decrease in the pDC/cDC ratio. CA-STAT5 and CA-MEK1 severely inhibited pDC differentiation. FLT3-ITD, CA-N-Ras, and TEL/PDGFR beta aberrantly induced programmed death ligand-1 (PD-L1)-expressing DCs. In conclusion, we have established a simple, efficient, and reproducible in vitro FL-DC differentiation system from LSKs. This system could uncover novel findings on how myeloid neoplasm-related gene abnormalities differentially affect FL-DC differentiation from murine hematopoietic stem/progenitor cells in a gene-specific manner. (C) 2011 Elsevier B.V. All rights reserved. - Takeshi Chihara; Naoki Wada; Junichiro Ikeda; Shigeki Fujita; Yumiko Hori; Hiroyasu Ogawa; Haruo Sugiyama; Shosaku Nomura; Itaru Matsumura; Masayuki Hino; Yuzuru Kanakura; Eiichi Morii; Katsuyuki AozasaJOURNAL OF HEMATOLOGY & ONCOLOGY 4 2011年04月 [査読有り]
- 白血病松村 到今日の診療のために ガイドライン外来診療2011 439 - 441 日経メディカル開発 2011年03月
- 右頬部皮下硬結で初発したblastic plasmacytoid dendritic cell neoplasm大磯 直毅; 辰巳 陽一; 荒尾 徳三; 大山 雄一; 木村 雅友; 中村 栄男; 西尾 和人; 松村 到; 東 禹彦; 川田 暁日本皮膚科学会雑誌 121 3 614 - 614 (公社)日本皮膚科学会 2011年03月
- S. Kako; S. Morita; H. Sakamaki; H. Ogawa; T. Fukuda; S. Takahashi; H. Kanamori; M. Onizuka; K. Iwato; R. Suzuki; Y. Atsuta; T. Kyo; T. Sakura; I. Jinnai; J. Takeuchi; Y. Miyazaki; S. Miyawaki; K. Ohnishi; T. Naoe; Y. KandaLEUKEMIA 25 2 259 - 265 2011年02月 [査読有り]
Clinical studies using genetic randomization cannot accurately answer whether adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia (ALL) who have a human leukocyte antigen (HLA)-matched sibling should undergo allogeneic hematopoietic stem cell transplantation (HSCT) or chemotherapy in first remission, as, in these studies, patients without a sibling donor undergo alternative donor transplantation or chemotherapy alone after a relapse. Therefore, we performed a decision analysis to identify the optimal strategy in this setting. Transition probabilities and utilities were estimated from prospective studies of the Japan Adult Leukemia Study Group, the database of the Japan Society for Hematopoietic Cell Transplantation and the literature. The primary outcome measure was the 10-year survival probability with or without quality of life (QOL) adjustments. Subgroup analyses were performed according to risk stratification on the basis of white blood cell count and cytogenetics, and according to age stratification. In analyses without QOL adjustments, allogeneic HSCT in first remission was superior in the whole population (48.3 vs 32.6%) and in all subgroups. With QOL adjustments, a similar tendency was conserved (44.9 vs 31.7% in the whole population). To improve the probability of long-term survival, allogeneic HSCT in first remission is recommended for patients who have an HLA-matched sibling. Leukemia (2011) 25, 259-265; doi:10.1038/leu.2010.260; published online 12 November 2010 - Shigeki Ohtake; Shuichi Miyawaki; Hiroyuki Fujita; Hitoshi Kiyoi; Katsuji Shinagawa; Noriko Usui; Hirokazu Okumura; Koichi Miyamura; Chiaki Nakaseko; Yasushi Miyazaki; Atsushi Fujieda; Tadashi Nagai; Takahisa Yamane; Masafumi Taniwaki; Masatomo Takahashi; Fumiharu Yagasaki; Yukihiko Kimura; Norio Asou; Hisashi Sakamaki; Hiroshi Handa; Sumihisa Honda; Kazunori Ohnishi; Tomoki Naoe; Ryuzo OhnoBLOOD 117 8 2358 - 2365 2011年02月 [査読有り]
We conducted a multi-institutional randomized study to determine whether high-dose daunorubicin would be as effective as standard-dose idarubicin in remission-induction therapy for newly diagnosed adult patients younger than 65 years of age with acute myeloid leukemia. Of 1064 patients registered, 1057 were evaluable. They were randomly assigned to receive either daunorubicin (50 mg/m(2) daily for 5 days) or idarubicin (12 mg/m(2) daily for 3 days) in combination with 100 mg/m(2) of cytarabine by continuous infusion daily for 7 days as induction therapy. Complete remission was achieved in 407 (77.5%) of 525 patients in the daunorubicin group and 416 (78.2%) of 532 in the idarubicin group (P = .79). Patients achieving complete remission received intensive postremission therapy that consisted of either 3 courses of high-dose cytarabine or 4 courses of standarddose therapy. Overall survival rates at 5 years were 48% for the daunorubicin group and 48% for the idarubicin group (P = .54), and relapse-free survival rates at 5 years were 41% and 41% (P = .97), respectively. Thus, high-dose daunorubicin and standard-dose idarubicin were equally effective for the treatment of adult acute myeloid leukemia, achieving a high rate of complete remission and good long-term efficacy. This study is registered at http://www.umin.ac.jp/ctrj/as C000000157. (Blood. 2011;117(8):2358-2365) - Shuichi Miyawaki; Shigeki Ohtake; Shin Fujisawa; Hitoshi Kiyoi; Katsuji Shinagawa; Noriko Usui; Toru Sakura; Koichi Miyamura; Chiaki Nakaseko; Yasushi Miyazaki; Atsushi Fujieda; Tadashi Nagai; Takahisa Yamane; Masafumi Taniwaki; Masatomo Takahashi; Fumiharu Yagasaki; Yukihiko Kimura; Norio Asou; Hisashi Sakamaki; Hiroshi Handa; Sumihisa Honda; Kazunori Ohnishi; Tomoki Naoe; Ryuzo OhnoBLOOD 117 8 2366 - 2372 2011年02月 [査読有り]
We conducted a prospective randomized study to assess the optimal postremission therapy for adult acute myeloid leukemia in patients younger than 65 years in the first complete remission. A total of 781 patients in complete remission were randomly assigned to receive consolidation chemotherapy of either 3 courses of high-dose cytarabine (HiDAC, 2 g/m(2) twice daily for 5 days) alone or 4 courses of conventional standard-dose multiagent chemotherapy (CT) established in the previous JALSG AML97 study. Five-year disease-free survival was 43% for the HiDAC group and 39% for the multiagent CT group (P = .724), and 5-year overall survival was 58% and 56%, respectively (P = .954). Among the favorable cytogenetic risk group (n = 218), 5-year diseasefree survival was 57% for HiDAC and 39% for multiagent CT (P = .050), and 5-year overall survival was 75% and 66%, respectively (P = .174). In the HiDAC group, the nadir of leukocyte counts was lower, and the duration of leukocyte less than 1.0 x 10(9)/L longer, and the frequency of documented infections higher. The present study demonstrated that the multiagent CT regimen is as effective as our HiDAC regimen for consolidation. Our HiDAC regimen resulted in a beneficial effect on disease-free survival only in the favorable cytogenetic leukemia group. This trial was registered at www.umin.ac.jp/ctr/as #C000000157. (Blood. 2011;117(8):2366-2372) - 嶋田 高広; 松村 到血液内科 62 2 151 - 158 科学評論社 2011年02月
- 【細胞死と造血器腫瘍】 急性白血病におけるアポトーシス抑制嶋田 高広; 松村 到血液内科 62 2 151 - 158 (有)科学評論社 2011年02月
- Yasuhiro Maeda; Atsushi Sasakawa; Chikara Hirase; Terufumi Yamaguchi; Yasuyoshi Morita; Jun-ichi Miyatake; Fumiaki Urase; Shosaku Nomura; Itaru MatsumuraLEUKEMIA & LYMPHOMA 52 1 150 - 152 2011年01月 [査読有り]
- Pathogenetic and clinical significance of genetic abnormalities in acute myeloid leukemia松村 到近畿大学医学会誌 35 2 87 - 96 近畿大学 2011年
- Yasuyoshi Morita; Yuichi Ohyama; Shinya Rai; Masaya Kawauchi; Terufumi Yamaguchi; Takahiro Shimada; Yoichi Tatsumi; Takashi Ashida; Yasuhiro Maeda; Itaru MatsumuraINTERNAL MEDICINE 50 16 1737 - 1740 2011年 [査読有り]
We report a rare case of chronic myelomonocytic leukemia (CMML) with pericardial effusion. After receving the diagnosis of CMML, she had been successfully treated with hydroxycarbamide (HU). However, she was admitted to our hospital due to pericardial effusion. The majority of the cells in the pericardial fluid were monocytes. We made the diagnosis of pericardial involvement with CMML cells and intravenously administered etoposide (100 mg/body daily for 5 days). Although CMML cells disappeared from the peripheral blood, the pericardial effusion still persisted. This case indicates that pericardial effusion is a possible and life-threatening complication in CMML patients despite stably controlled leukocytes. - S. Mizuta; K. Matsuo; F. Yagasaki; T. Yujiri; Y. Hatta; Y. Kimura; Y. Ueda; H. Kanamori; N. Usui; H. Akiyama; Y. Miyazaki; S. Ohtake; Y. Atsuta; H. Sakamaki; K. Kawa; Y. Morishima; K. Ohnishi; T. Naoe; R. OhnoLEUKEMIA 25 1 41 - 47 2011年01月 [査読有り]
A high complete remission (CR) rate has been reported in newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) following imatinib-based therapy. However, the overall effect of imatinib on the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is undetermined. Between 2002 and 2005, 100 newly diagnosed adult patients with Ph+ALL were registered to a phase II study of imatinib-combined chemotherapy (Japan Adult Leukemia Study Group Ph+ALL202 study) and 97 patients achieved CR. We compared clinical outcomes of 51 patients who received allo-HSCT in their first CR (imatinib cohort) with those of 122 historical control patients in the pre-imatinib era (pre-imatinib cohort). The probability of overall survival at 3 years after allo-HSCT was 65% (95% confidence interval (CI), 49-78%) for the imatinib cohort and 44% (95% CI, 35-52%) for the pre-imatinib cohort. Multivariate analysis confirmed that this difference was statistically significant (adjusted hazard ratio, 0.44, P = 0.005). Favorable outcomes of the imatinib cohort were also observed for disease-free survival (P = 0.007) and relapse (P = 0.002), but not for non-relapse mortality (P = 0.265). Imatinib-based therapy is a potentially useful strategy for newly diagnosed patients with Ph+ALL, not only providing them more chance to receive allo-HSCT, but also improving the outcome of allo-HSCT. Leukemia (2011) 25, 41-47; doi: 10.1038/leu.2010.228; published online 14 October 2010 - 森田 泰慶; 松村 到血液内科 62 1 63 - 70 科学評論社 2011年01月
- 森田 泰慶; 松村 到血液内科 62 1 63 - 70 (有)科学評論社 2011年01月
- 白血球系 がん性疼痛における造血因子の役割山口 晃史; 松村 到Annual Review血液 2011 116 - 122 (株)中外医学社 2011年01月がん性疼痛はがん患者のQOLを著しく低下させ,社会的に大きな問題となっている.これまでにがん性疼痛に関わる分子としてブラジキニン,セロトニンなどの分子が同定されてきた.最近,がん組織にはG-CSFやGM-CSFが大量に存在し,これらのサイトカインが神経線維上の受容体に結合して細胞内にシグナルを伝達することにより,神経細胞に肥大や分枝を誘導するのみでなく,疼痛刺激に対する感受性を亢進させることが明らかとなった(著者抄録)
- Itaru Matsumura; Yasuhito Nannya; Tadashi Nagai; Kazuki Tanimoto; Kazuhisa Fujikawa; Masanobu Kasai; Yoko Inaguma; Makoto Takeuchi; Hiromasa Niimi; Hirokazu Kashiwagi; Yutaka Imamura; Toshinari Yagi; Erina Sakamoto; Masahiro Okabe; Go Aoki; Takuji Katayama; Masaya Okada; Yoko Adachi; Yoshio Saburi; Masahiro Kizaki[Rinsho ketsueki] The Japanese journal of clinical hematology 51 12 1762 - 8 2010年12月The response criteria proposed by European Leukemia Net are useful to predict the prognosis of de novo chronic myeloid leukemia (CML) patients in the chronic phase (CP) treated with imatinib. However, the clinical significance of late suboptimal response, which is defined as the achievement of CCgR without MMR after 18 months, is controversial. In this study, we retrospectively analyzed the clinical courses of 16 CML-CP patients, who satisfied the criteria for late suboptimal response. The median duration of imatinib treatment was 62 (25∼87) months. The median starting dose of imatinib was 400 mg/day. Imatinib dose was escalated to 600∼800 mg/day in 10 patients for various reasons. Among 4 patients who continued high-dose imatinib for late suboptimal response, 2 patients subsequently achieved MMR, and BCR-ABL mRNA transcript levels were decreasing in 2 patients. However, imatinib was kept at 300 or 400 mg/day in 6 patients. Among these six patients, 4 patients achieved MMR, while 2 failed to achieve MMR. None of 16 patients progressed to the acute phase or blast phase. Imatinib dose escalation was effective for late suboptimal response. Furthermore, a second tyrosine kinase inhibitor such as nilotinib may be more potent to reduce the risk of disease progression by achieving earlier MMR.
- 松村 到; 南谷 泰仁; 永井 正; 谷本 一樹; 藤川 一壽; 笠井 雅信; 稲熊 容子; 竹内 誠; 新美 寛正; 柏木 浩和; 今村 豊; 屋木 敏也; 坂本 恵利奈; 岡部 雅弘; 青木 剛; 片山 卓爾; 岡田 昌也; 足立 陽子; 佐分利 能生; 木崎 昌弘臨床血液 51 12 1762 - 1768 (一社)日本血液学会-東京事務局 2010年12月European Leukemia Netの判定基準は慢性期の慢性骨髄性白血病をイマチニブ(IM)で治療した際の予後推定に有用であるが18ヵ月以降のLate Suboptimal Response(CCgR達成,MMR未達成:LSR)の評価には異論がある。本研究では国内のLSR16例を解析した。IMの投与期間中央値は62(25?87)ヵ月,開始量中央値は400mg/日,10例で種々の理由により600?800mg/日に増量された。LSRに対してIMが増量,継続された4例中2例はMMRを達成,残り2例も分子遺伝学的な改善を示した。IMを増量しなかった6例では4例のみがその後MMRを達成した。今回の16例では病期進行はなかった。以上よりLSR例のMMR達成にはIM増量が有効と考えられた。ただし,ニロチニブなどの第二世代TKIは,より早期にMMRを達成し病期進行のリスクを軽減することも期待される。(著者抄録)
- 松村 到細胞 42 14 582 - 585 (株)ニュー・サイエンス社 2010年12月慢性期の慢性骨髄性白血病(CML-CP)の治療成績はBCR-ABL阻害薬Imatinibの登場により画期的に改善した。しかし、一部の症例はImatinib抵抗性あるいは不耐容を示す。これらに対して第二世代チロシンキナーゼ阻害薬(TKI)であるNilotinib、Dasatinibが市販され、その有効性が臨床試験のみでなく、日常臨床においても確認されつつある。さらに、未治療CML-CPに対してNilotinib、DasatinibがImatinibに勝る効果を示すことがそれぞれのランダム化比較試験で示されている。今後、未治療CML-CPに対して第二世代TKIをFirst Lineで投与することが承認されればCML-CPの治療成績はさらに改善することが期待される。一方、移行期、急性転化期の症例にはTKI単独での効果は限定的であり、移植可能例には依然として同種造血幹細胞移植が必要である。(著者抄録)
- Jiro Fujita; Masao Mizuki; Masayasu Otsuka; Sachiko Ezoe; Hirokazu Tanaka; Yusuke Satoh; Kentaro Fukushima; Masahiro Tokunaga; Itaru Matsumura; Yuzuru KanakuraBLOOD 116 21 1592 - 1592 2010年11月 [査読有り]
- Satoshi Nishiwaki; Yoshihiro Inamoto; Hisashi Sakamaki; Mineo Kurokawa; Hiroatsu Iida; Hiroyasu Ogawa; Takahiro Fukuda; Yukiyasu Ozawa; Naoki Kobayashi; Masanobu Kasai; Takehiko Mori; Koji Iwato; Takashi Yoshida; Makoto Onizuka; Keisei Kawa; Yasuo Morishima; Ritsuro Suzuki; Yoshiko Atsuta; Koichi MiyamuraBLOOD 116 20 4368 - 4375 2010年11月 [査読有り]
To identify factors to improve the outcomes of related and unrelated allogeneic stem cell transplantations (allo-SCT) for Philadelphia chromosome-negative acute lymphocytic leukemia (Ph(-) ALL) in the first complete remission (CR1), we retrospectively analyzed 1139 Ph(-) ALL patients using the registry data, particularly the details of 641 patients transplanted in CR1. Overall survival was significantly superior among patients transplanted in CR1, but no significant difference was observed between related and unrelated allo-SCTs (related vs unrelated: 65% vs 62% at 4 years, respectively; P = .19). Among patients transplanted in CR1, relapse rates were significantly higher in related allo-SCT compared with unrelated allo-SCT, and multivariate analysis demonstrated that less than 6 months from diagnosis to allo-SCT alone was associated with relapse. On the other hand, nonrelapse mortality (NRM) was significantly higher in unrelated allo-SCT compared with related allo-SCT, and multivariate analysis demonstrated that 10 months or longer from diagnosis to allo-SCT, human leukocyte antigen mismatch, and abnormal karyotype were associated with NRM. In conclusion, our study showed comparable survival rates but different relapse rates, NRM rates, and risk factors between related and unrelated allo-SCTs. After a close consideration of these factors, the outcome of allo-SCT for adult Ph(-) ALL in CR1 could be improved. (Blood. 2010;116(20):4368-4375) - BCR-ABL but Not JAK2 V617F Inhibits Erythropoiesis through the Ras Signal by Inducing p21(CIP1/WAF1)Masahiro Tokunaga; Sachiko Ezoe; Hirokazu Tanaka; Yusuke Satoh; Kentaro Fukushima; Keiko Matsui; Masaru Shibata; Akira Tanimura; Kenji Oritani; Itaru Matsumura; Yuzuru KanakuraJOURNAL OF BIOLOGICAL CHEMISTRY 285 41 31774 - 31782 2010年10月 [査読有り]
BCR-ABL is a causative tyrosine kinase (TK) of chronic myelogenous leukemia (CML). In CML patients, although myeloid cells are remarkably proliferating, erythroid cells are rather decreased and anemia is commonly observed. This phenotype is quite different from that observed in polycythemia vera (PV) caused by JAK2 V617F, whereas both oncogenic TKs activate common downstream molecules at the level of hematopoietic stem cells (HSCs). To clarify this mechanism, we investigated the effects of BCR-ABL and JAK2 V617F on erythropoiesis. Enforced expression of BCR-ABL but not of JAK2 V617F in murine LSK (Lineage(-)Sca-1(hi)CD117(hi)) cells inhibited the development of erythroid cells. Among several signaling molecules downstream of BCR-ABL, an active mutant of N-Ras (N-RasE12) but not of STAT5 or phosphatidylinositol 3-kinase (PI3-K) inhibited erythropoiesis, while N-RasE12 enhanced the development of myeloid cells. BCR-ABL activated Ras signal more intensely than JAK2 V617F, and inhibition of Ras by manumycin A, a farnesyltransferase inhibitor, ameliorated erythroid colony formation of CML cells. As for the mechanisms of Ras-induced suppression of erythropoiesis, we found that GATA-1, an erythroid-specific transcription factor, blocked Ras-mediated mitogenic signaling at the level of MEK through the direct interaction. Furthermore, enforced expression of N-RasE12 in LSK cells derived from p53-, p16(INK4a)/p19(ARF)-, and p21(CIP1/WAF1)-null/wild-type mice revealed that suppressed erythroid cell growth by N-RasE12 was restored only by p21(CIP1/WAF1) deficiency, indicating that a cyclin-dependent kinase (CDK) inhibitor, p21(CIP1/WAF1), plays crucial roles in Ras-induced suppression of erythropoiesis. These data would, at least partly, explain why respective oncogenic TKs cause different disease phenotypes. - Yuichi Ishikawa; Hitoshi Kiyoi; Keisuke Watanabe; Koichi Miyamura; Yasuyuki Nakano; Kunio Kitamura; Akio Kohno; Isamu Sugiura; Toshiya Yokozawa; Akitoshi Hanamura; Kazuhito Yamamoto; Hiroatsu Iida; Nobuhiko Emi; Ritsuro Suzuki; Kazunori Ohnishi; Tomoki NaoeCANCER SCIENCE 101 10 2186 - 2192 2010年10月 [査読有り]
Pharmacokinetic (PK) factors have been suggested to be involved in the unfavorable clinical responses of chronic myeloid leukemia (CML) patients treated with imatinib. The purpose of this study was to clarify prognostic implications of PK factors in CML patients treated with imatinib. The plasma trough (C(min)) level of imatinib and serum alpha(1)-acid glycoprotein (AGP) level were measured on two different days in 65 CML patients treated with imatinib for more than 12 months. We further examined whether the C(min) level of imatinib actually reflects inhibitory activity against BCR-ABL kinase using the plasma inhibitory activity (PIA) assay. Since the differences of five patients were statistically rejected by the Smirnov-Grubbs' test, we excluded them for further analysis. The C(min) level was strongly associated with the achievement of MMR at the 12th month, and ROC analysis demonstrated C(min) levels and their discrimination potential for major molecular response (MMR) with the best sensitivity (63.2%) and specificity (68.2%) at a C(min) threshold of 974 ng/mL. The alpha(1)-Acid glycoprotein (AGP) level was within the normal range in 57 of 60 patients, indicating little impact of AGP on our study. There was a weak correlation between PIA against phospho (P)-BCR-ABL and the C(min) level of imatinib (r2 = 0.2501, P = 0.0007), and patient plasma containing > 974 ng/mL imatinib sufficiently inhibited P-BCR-ABL. These results collectively indicated that maintaining similar to 1000 ng/mL of C(min) was clinically and biologically important for the optimal response in CML patients treated with imatinib. A prospective intervention study is required to establish PK-based management in CML patients treated with imatinib. (Cancer Sci 2010). - 松村 到臨床血液 51 10 1386 - 1394 (一社)日本血液学会-東京事務局 2010年10月
- 宮武淳一; 松村到血液フロンティア 20 S-1 1533 - 1540 2010年09月
- Maiko Asakura; Kazuhiro Ikegame; Satoshi Yoshihara; Shuichi Taniguchi; Takehiko Mori; Tetsuya Etoh; Akiyoshi Takami; Takashi Yoshida; Takahiro Fukuda; Kazuo Hatanaka; Heiwa Kanamori; Toshiaki Yujiri; Yoshiko Atsuta; Hisashi Sakamaki; Ritsuro Suzuki; Hiroyasu OgawaINTERNATIONAL JOURNAL OF HEMATOLOGY 92 2 351 - 359 2010年09月 [査読有り]
Foscarnet is an active agent against cytomegalovirus (CMV) infection after hematopoietic stem cell transplantation (HSCT), as well as ganciclovir. We investigated the usefulness of foscarnet in patients who underwent related allogeneic HSCT. Foscarnet was used in 320 patients with a median age of 45 years (range 15-72). The purpose of administration was CMV disease in 65, preemptive use in 248 and prophylaxis in 7. Totally, 194 patients had a history of prior ganciclovir treatment. The reason for foscarnet use was insufficient therapeutic effect of prior ganciclovir in 99, and adverse event including myelosuppression in 95. The response rate in symptom was 52% for the CMV disease patients. Antigenemia disappeared in 77% of the preemptive treatment and improved in 13% of the patients. No outbreak of CMV disease was recognized. The total effectiveness of therapeutic and preemptive use was significantly higher for patients without prior ganciclovir (91 vs. 76%, P = 0.001). Adverse events of grade 3 or higher were recognized in 24%, including electrolyte abnormalities in 11%, neutropenia in 8%, and thrombocytopenia in 8%. Renal damage was only observed in 3% of patients. Foscarnet was concluded to be a safe and effective anti-CMV agent and to be a suitable alternative to ganciclovir. - 非炎症状態の樹状細胞分化における白血病関連遺伝子異常の役割(Leukemia-related gene abnormalities affect steady-state dendritic cell differentiation)藤田 二郎; 水木 満佐央; 江副 幸子; 田中 宏和; 佐藤 友亮; 福島 健太郎; 徳永 正浩; 松村 到; 金倉 譲日本癌学会総会記事 69回 161 - 161 2010年08月
- 抗細胞死分子アナモルシンは、p38MAPKを不活化し細胞増殖をもたらす(A cell-death-defying factor, anamorsin, yields cell growth through inactivation of p38 MAPK)斉藤 有理; 柴山 浩彦; 田中 宏和; 谷村 朗; 松村 到; 金倉 譲日本癌学会総会記事 69回 168 - 168 2010年08月
- 川西一信; 松村到内科 106 2 305 - 309 南江堂 2010年08月
- 松村到Bio Clinica 25 7 568 - 573 2010年07月
- 森田泰慶; 松村到月刊メディカル・サイエンス・ダイジェスト 36 7 868 - 871 2010年06月
- 嶋田高広; 松村到月刊血液・腫よう科 60 6 771 - 776 科学評論社 2010年06月
- 慢性骨髄性白血病の治療戦略松村 到Bio Clinica 25 7 18 - 23 北隆堂 2010年06月慢性骨髄性白血病の治療成績はチロシンキナーゼ阻害薬イマチニブの登場により、画期的に改善した。しかし、一部の症例は抵抗性を示し問題となる。このような抵抗性例に対し第二世代チロシンキナーゼ阻害薬が開発され、良好な治療成績を示している。
- 口分田 貴裕; 頼 晋也; 辰巳 陽一; 大山 雄一; 金井 良高; 平瀬 主税; 山口 晃史; 森田 泰慶; 嶋田 高広; 川西 一信; 宮武 淳一; 芦田 隆司; 前田 裕弘; 松村 到; 金丸 昭久日本リンパ網内系学会会誌 50 106 - 106 (一社)日本リンパ網内系学会 2010年05月
- 頼 晋也; 辰巳 陽一; 口分田 貴裕; 大山 雄一; 金井 良高; 平瀬 主税; 山口 晃史; 森田 泰慶; 嶋田 高広; 川西 一信; 宮武 淳一; 芦田 隆司; 前田 裕弘; 松村 到; 松田 光弘; 金丸 昭久日本リンパ網内系学会会誌 50 123 - 123 (一社)日本リンパ網内系学会 2010年05月
- 松村 到; 金倉 譲血液・腫瘍科 60 4 395 - 401 科学評論社 2010年04月
- 松村 到臨床検査 54 3 271 - 279 医学書院 2010年03月
- 松村到; 金倉譲Medical Practice 27 2 196 - 202 2010年02月
- 松村到; 金倉譲Annual Review 血液 2010 107 - 113 (株)中外医学社 2010年01月癌の転移は,癌細胞の癌組織からの遊離に始まって,転移巣の形成まで数多くのステップから構成される.これらのステップが遂行されるためには,癌細胞自身の遺伝子変化のみでなく,癌細胞の周辺細胞,細胞外マトリックスといった微小環境が癌転移に適した状態に整えられる必要がある.以前から原発巣,転移巣のいずれの癌組織にもマクロファージなどの骨髄由来細胞が多数集簇することが報告されてきたが,この数年の研究でこれらの骨髄由来細胞が,癌の組織内進展,血管新生,前転移ニッチの形成など癌転移のためのほとんどのステップに深く関わり,癌の浸潤・転移に寄与することが明らかとされてきた.骨髄由来細胞による癌転移の促進にはケモカイン,serum amyloid A3などの化学遊走因子,自然免疫に関わるToll-like受容体,低酸素に反応して分泌されるlysyl oxidaseなどが関与することが明らかとされ,新たな治療標的として注目が集まっている.(著者抄録)
- 松村 到臨床血液 52 10 198 - 206 日本血液学会 2010年
- CML治療の現状と展望松村 到細胞 42 14 14 - 17 ニューサイエンス社 2010年
- イマチニブで治療中の慢性CML患者.ELNの基準でsuboptimal responseである.今後の治療をどうしよう?賴 晋也; 松村 到造血器腫瘍治療 2版 95 - 98 中外医学社 2010年ELNの基準でsuboptimal responseの予後については明らかではない。しかし、各治療時期別にみると予後不良の場合と良好の場合があり、それぞれに応じた治療戦略が必要である。
- 急性白血病松村 到; 金倉 譲疾病と治療Ⅱ 南江堂 2010年急性白血病はクラス1と呼ばれる増殖・生存シグナルを促進する分子の異常と分解場をきたすクラス2の遺伝子異常があいまって発症する。
- 松村到WHO血液腫瘍分類〜WHO分類2008をうまく活用するために〜 38 - 45 医薬ジャーナル社 2010年
- Hirofumi Akagi; Itaru Matsumura2010 IEEE Energy Conversion Congress and Exposition, ECCE 2010 - Proceedings 862 - 869 2010年 [査読有り]
This paper presents an intensive discussion on an overvoltage appearing at the motor terminals of an adjustable-speed drive that consists of a voltage-source PWM inverter, an induction motor, and a three-phase symmetric long cable. It describes a design procedure for a simple passive EMI filter based on parallel connection of an inductor and a resistor, which is intended for mitigating the overvoltage at the motor terminals. The modeling of the cable and the motor are prominent in focusing on the natural frequency or ringing frequency inherent in the cable used, which is inversely proportional to cable length. Impedance mismatch at the inverter and motor terminals causes the overvoltage that may reach double the inverter dclink voltage. The effectiveness and validity of the simple design procedure of the filter are confirmed on the 400-V, 15-kW experimental system with either a 100-m or 200-m-long cable, as well as on computer simulation based on the modeling of the cable and the motor. © 2010 IEEE. - 田中宏和; 金倉譲; 松村到新たな移植細胞療法に向けた造血幹細胞のex vivo増幅技術の開発と応用 平成21年度 総括・分担研究報告書 43 - 49 2010年
- 松村到臨床血液 51 10 1386-1394 (J-STAGE) 2010年
- Hiroyuki Murota; Yukiko Shoda; Tomohiko Ishibashi; Hiroyuki Sugahara; Itaru Matsumura; Ichiro KatayamaJOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY 61 6 1070 - 1075 2009年12月 [査読有り]
Schnitzler syndrome is a rare condition defined by chronic urticaria, osteosclerotic bone lesions, and monoclonal IgM gammopathy. Schnitzler syndrome can precede the onset of a true lymphoproliferative disorder including Waldenstrom macroglobulinemia and rarely systemic marginal zone B-cell lymphoma. We describe a case of intractable chronic urticaria accompanied by a retroperitoneal neoplasm. IgM monoclonal gammopathy, lumber pain, intermittent fever, and elevation of C-reactive protein were the clues for the diagnosis of Schnitzler syndrome. An evaluation for malignancy using systemic Computed tomography scan and fluorodeoxyglucose Positron emission tomography revealed the retroperitoneal tumor, and a subsequent bone-marrow aspirate confirmed the diagnosis of B-cell lymphoma. Combined rituximab and radiotherapy ameliorated the skin symptoms. This case indicates that a detailed search for malignant neoplasms might be required for the long-term management of Schnitzler syndrome, and that B-cell lymphomas may contribute to the pathogenesis of this condition. (J Am Acad Dermatol 2009;61:1070-5.) - Yusuke Satoh; Itaru Matsumura; Hirokazu Tanaka; Hironori Harada; Yuka Harada; Yuzuru KanakuraBLOOD 114 22 80 - 81 2009年11月 [査読有り]
- 松村 到臨床血液 50 10 1389 - 1400 (一社)日本血液学会-東京事務局 2009年10月
- Jun Ishikawa; Tetsuo Maeda; Itaru Matsumura; Masato Yasumi; Hidetoshi Ujiie; Hiroaki Masaie; Tsuyoshi Nakazawa; Nobuo Mochizuki; Satoshi Kishino; Yuzuru KanakuraANTIMICROBIAL AGENTS AND CHEMOTHERAPY 53 10 4559 - 4562 2009年10月 [査読有り]
We have evaluated the antifungal activity of micafungin in serum by using the disk diffusion method with serum-free and serum-added micafungin standard curves. Serum samples from micafungin-treated patients have been shown to exhibit adequate antifungal activity, which was in proportion to both the applied dose and the actual concentration of micafungin measured by high-performance liquid chromatography. The antifungal activity of micafungin in serum was also confirmed with the broth microdilution method. - 田中宏和; 松村到; 金倉譲Biotherapy (Tokyo) 23 5 364 - 370 (株)癌と化学療法社 2009年09月がん組織は多様な細胞集団から構成されるが、白血病など多くの腫瘍において腫瘍のなかの一部の細胞集団のみがNOD/SCIDマウスに移植した際に、元の腫瘍に類似した腫瘍を作ることが示されてきた。この概念は骨髄性白血病においても最も理解されており、これらの細胞が白血病幹細胞として定義されている。白血病幹細胞は正常造血幹細胞と同様に未分化な表面形質を示し、自己複製能と分化能を有することで白血病幹細胞集団を維持しつつ、白血病組織を構成する多様な分化段階にあるすべての白血病細胞を生みだす。正常造血幹細胞と同様に、白血病幹細胞も「白血病ニッチ」と呼ばれる微小環境を必要とし、その場で自己複製、生存に必要なNotch、Wnt/β-catenin、Sonic hedgehogなどからのシグナルを伝達される。白血病幹細胞の起源としては、もともと自己複製能を有していた正常造血幹細胞に遺伝子異常が起こった可能性と、自己複製能を有さない前駆細胞レベルに自己複製能を寄与する遺伝子異常が起こった可能性がある。白血病組織を形成する白血病幹細胞以外の白血病細胞は限られた分裂能しか有さず、いずれアポトーシスを起こしていくので、白血病を治癒させるには白血病幹細胞のみを死滅させれば十分である。しかし、白血病幹細胞は正常造血幹細胞と同様に細胞周期の静止期にあることから、通常の白血病治療には抵抗性であると想定されている。現在、自己複製能を阻害する薬剤などが開発中であるが、これらの薬剤は正常造血道細胞を阻害することは免れない。したがって、白血病幹細胞を選択的に死滅させる薬剤の開発が必要である。そのためには、抗体療法のための白血病幹細胞特異的抗原の同定や、直接の治療標的となる白血病幹細胞においてのみ活性化している分子、白血病幹細胞の自己複製や生存にのみかかわっている分子の同定が有用である。(著者抄録)
- 松村到; 金倉譲血液フロンティア 19 10 1507 - 1515 2009年09月
- 松村 到; 金倉 譲綜合臨床 58 8 1708 - 1712 永井書店 2009年08月
- 松村到; 金倉譲月刊血液・腫よう科 59 1 59 - 63 科学評論社 2009年07月
- 松村 到; 赤司 浩一; 薄井 紀子Trends in hematological malignancies 1 1 8 - 16 メディカルレビュー社 2009年07月
- Arinobu Tojo; Kensuke Usuki; Akio Urabe; Yasuhiro Maeda; Yukio Kobayashi; Itsuro Jinnai; Kazuma Ohyashiki; Miki Nishimura; Tatsuya Kawaguchi; Hideo Tanaka; Koichi Miyamura; Yasushi Miyazaki; Timothy Hughes; Susan Branford; Shinichiro Okamoto; Jun Ishikawa; Masaya Okada; Noriko Usui; Hiromi Tanii; Taro Amagasaki; Hiroko Natori; Tomoki NaoeINTERNATIONAL JOURNAL OF HEMATOLOGY 89 5 679 - 688 2009年06月 [査読有り]
Nilotinib is a second-generation BCR-ABL kinase inhibitor with improved potency and selectivity compared to imatinib. A Phase I/II dose-escalation study was designed to evaluate the efficacy, safety, and pharmacokinetics of nilotinib in Japanese patients with imatinib-resistant or -intolerant Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) or relapsed/refractory Ph+ acute lymphoblastic leukemia (ALL). A total of 34 patients were evaluated in this analysis and had a median duration of drug exposure of 293 (range 13-615) days. All 6 CML-CP patients without complete hematologic response (CHR) at baseline rapidly achieved CHR. A major cytogenetic response was achieved in 94% of patients with CML-CP, including a complete cytogenetic response in 69%. A major molecular response was achieved by 56%. These responses were also observed in patients with CML in advanced stages and Ph+ ALL. Non-hematologic adverse events were mostly mild to moderate. Grade 3 or 4 neutropenia and thrombocytopenia occurred in 50 and 28% of patients, respectively. Overall, the results of this study suggest that nilotinib induced significant responses in imatinib-resistant or -intolerant patients with CML-CP and CML in advanced stages and Ph+ ALL. The results of this study confirmed the efficacy and safety of nilotinib in Japanese patients. - 松村到; 金倉譲綜合臨床 58 1125 - 1129 永井書店 2009年04月
- 松村到; 金倉譲月刊細胞 41 3 104 - 107 ニューサイエンス社 2009年03月
- 松村 到; 金倉 譲細胞 41 3 104 - 107 ニューサイエンス社 2009年03月
- Kentaro Fukushima; Itaru Matsumura; Sachiko Ezoe; Masahiro Tokunaga; Masato Yasumi; Yusuke Satoh; Hirohiko Shibayama; Hirokazu Tanaka; Atsushi Iwama; Yuzuru KanakuraJOURNAL OF BIOLOGICAL CHEMISTRY 284 12 7719 - 7732 2009年03月 [査読有り]
Although leukemogenic tyrosine kinases (LTKs) activate a common set of downstream molecules, the phenotypes of leukemia caused by LTKs are rather distinct. Here we report the molecular mechanism underlying the development of hypereosinophilic syndrome/chronic eosinophilic leukemia by FIP1L1-PDGFR alpha. When introduced into c-Kit(high)Sca-1(+)Lineage(-) cells, FIP1L1-PDGFR alpha conferred cytokine-independent growth on these cells and enhanced their self-renewal, whereas it did not immortalize common myeloid progenitors in in vitro replating assays and transplantation assays. Importantly, FIP1L1-PDGFR alpha but not TEL-PDGFR beta enhanced the development of Gr-1(+)IL-5R alpha(+) eosinophil progenitors from c-Kit(high)Sca-1(+)Lineage(-) cells. FIP1L1-PDGFR alpha also promoted eosinophil development from common myeloid progenitors. Furthermore, when expressed in megakaryocyte/erythrocyte progenitors and common lymphoid progenitors, FIP1L1-PDGFR alpha not only inhibited differentiation toward erythroid cells, megakaryocytes, and B-lymphocytes but aberrantly developed eosinophil progenitors from megakaryocyte/erythrocyte progenitors and common lymphoid progenitors. As for the mechanism of FIP1L1-PDGFR alpha-induced eosinophil development, FIP1L1-PDGFR alpha was found to more intensely activate MEK1/2 and p38MAPK than TEL-PDGFR beta. In addition, a MEK1/2 inhibitor and a p38MAPK inhibitor suppressed FIP1L1-PDGFR alpha-promoted eosinophil development. Also, reverse transcription-PCR analysis revealed that FIP1L1-PDGFR alpha augmented the expression of C/EBP alpha, GATA-1, and GATA-2, whereas it hardly affected PU.1 expression. In addition, short hairpin RNAs against C/EBP alpha and GATA-2 and GATA-3KRR, which can act as a dominant-negative form over all GATA members, inhibited FIP1L1-PDGFR alpha-induced eosinophil development. Furthermore, FIP1L1-PDGFR alpha and its downstream Ras inhibited PU.1 activity in luciferase assays. Together, these results indicate that FIP1L1-PDGFR alpha enhances eosinophil development by modifying the expression and activity of lineage-specific transcription factors through Ras/MEK and p38MAPK cascades. - 松村 到; 金倉 譲血液・腫瘍科 58 2 146 - 151 科学評論社 2009年02月
- 松村到; 金倉譲Annual Review 血液 2009 110 - 116 2009年01月
- Itaru Matsumura; Hirofumi AkagiIEEJ Transactions on Industry Applications 129 8 9 - 851 2009年 [査読有り]
This paper presents an intensive discussion on modeling an adjustable-speed motor drive system consisting of a voltage-source PWM inverter and an induction motor that are connected by a three-phase symmetric, long cable with a grounding wire lead. Then, it describes a design procedure for a parallel-connected R-L filter in each phase that can mitigate the overvoltage appearing at the motor terminals. The model developed in this paper focuses on the inherent "ringing frequency" of the cable, where the ringing frequency is inversely proportional to cable length. When no filter is used, the so-called "impedance mismatch" causes the reflection of a voltage-traveling wave at both the inverter and the motor terminals. As a result, the impedance mismatch generates an overvoltage that may reach twice the inverter dc-link voltage at the motor terminals. The overvoltage may damage the motor-winding insulation, and may cause it to breakdown. Although an R-L filter installed on the ac side of the inverter can reduce the overvoltage, it would be difficult to design the filter effectively for long cables of different lengths. The effectiveness and validity of the simple design procedure described in this paper are confirmed on a 400-V, 15-kW experimental system with either a 100-m or 200-m-long cable. © 2009 The Institute of Electrical Engineers of Japan. - 松村 到; 金倉 譲綜合臨床 58 0 1125 - 1129 永井書店 2009年
- 松村 到; 金倉 譲血液・腫瘍科 58 1 8 - 13 科学評論社 2009年01月
- 田中宏和; 金倉譲; 松村到新たな移植細胞療法に向けた造血幹細胞のex vivo増幅技術の開発と応用 平成20年度 総括・分担研究報告書 65 - 71 2009年
- 小澤敬也; 鈴木隆浩; 朝長万左男; 宮崎泰司; 中尾眞二; 大屋敷一馬; 松村到; 高後裕; 新津洋司郎; 小島勢二特発性造血障害に関する調査研究 平成20年度 総括・分担研究報告書 86 - 105 2009年
- 松村到; 金倉譲血液フロンティア 18 12 1843 - 1855 2008年11月
- Hirokazu Tanaka; Itaru Matsumura; Yusuke Satoh; Sachiko Ezoe; Tatsutoshi Nakahata; Yuzuru KanakuraBLOOD 112 11 847 - 847 2008年11月 [査読有り]
- 松村到三共生命科学研究振興財団研究報告集 24 187 - 195 三共生命科学研究振興財団 2008年10月
- 松村 到; 金倉 譲医学のあゆみ 227 1 5 - 9 医歯薬出版 2008年10月
- 松村到; 金倉譲医学のあゆみ 227 1 5 - 9 医歯薬出版 2008年10月
- Yusuke Satoh; Itaru Matsumura; Hirokazu Tanaka; Sachiko Ezoe; Kentaro Fukushima; Masahiro Tokunaga; Masato Yasumi; Hirohiko Shibayama; Masao Mizuki; Takumi Era; Tsukasa Okuda; Yuzuru KanakuraJOURNAL OF BIOLOGICAL CHEMISTRY 283 44 30045 - 30056 2008年10月 [査読有り]
In this study, we analyzed the roles for AML1/RUNX1 in the regulation of the c-mpl promoter. Wild-type AML1 activated the c-mpl promoter through the proximal AML-binding site in luciferase assays using 293T and HeLa cells. In accord with this result, electrophoretic mobility shift assay and chromatin immunoprecipitation assays demonstrated that AML1 bound to this site. Next, we analyzed the function of AML1 using a mutant of AML1 lacking the C terminus (AML1dC), which was originally found in a patient with myelodysplastic syndromes. AML1dC dominant-negatively suppressed transcriptional activity of wild-type AML1. However, unexpectedly, AML1dC-transduced murine c-Kit(+)Sca1(+)Lineage(-) cells expressed c-mpl mRNA and c-Mpl protein more abundantly than mock-transduced cells, which led to the enhanced thrombopoietin-mediated proliferation. Moreover, when AML1dC was induced to express during the development of hematopoietic cells from embryonic stem (ES) cells, AML1dC augmented the c-Mpl expression on hematopoietic stem/progenitor cells. Furthermore, we found that early hematopoietic cells that derived from AML1(-/-) ES cells expressed c-Mpl more intensely than those that developed from wild-type ES cells. In contrast, AML1dC hardly affected c-Mpl expression and maturation of megakaryocytes. As for the mechanism of the different roles of AML1 in the regulation of the c-mpl promoter, we found that AML1 forms a complex with a transcription repressor mSin3A on the c-mpl promoter in hematopoietic stem/progenitor cells, although it forms a complex with a transcription activator p300 on the same promoter in megakaryocytic cells. Together, these data indicate that AML1 can regulate the c-mpl promoter both positively and negatively by changing the binding partner according to cell types. - Takahiro Suzuki; Masao Tomonaga; Yasushi Miyazaki; Shinji Nakao; Kazuma Ohyashiki; Itaru Matsumura; Yutaka Kohgo; Yoshiro Niitsu; Seiji Kojima; Keiya OzawaINTERNATIONAL JOURNAL OF HEMATOLOGY 88 1 30 - 35 2008年07月 [査読有り]
Many patients with bone marrow failure syndromes need frequent transfusions of red blood cells, and most of them eventually suffer from organ dysfunction induced by excessively accumulated iron. The only way to treat transfusion-induced iron overload is iron chelating therapy. However, most patients have not been treated effectively because daily/continuous administration of deferoxamine is difficult for outpatients. Recently, a novel oral iron chelator, deferasirox, has been developed, and introduction of the drug may help many patients benefit from iron chelation therapy. In this review, we will discuss the current status of iron overload in transfusion-dependent patients, and the development of Japanese guidelines for the treatment of iron overload in Japan, which were established by the National Research Group on Idiopathic Bone Marrow Failure Syndromes in Japan. - 松村到; 金倉譲カレントテラピー 26 6 526 - 530 2008年06月
- H. Sasaki; J. Hayakawa; Y. Terai; M. Kanemura; A. Tanabe-Kimura; H. Kamegai; H. Seino-Noda; S. Ezoe; I. Matsumura; Y. Kanakura; M. Sakata; K. Tasaka; M. OhmichiOncogene 27 19 2737 - 2745 2008年04月 [査読有り]
Although there is growing evidence that estrogens promote tumor progression in epithelial ovarian cancer, the molecular mechanisms accounting for this are still unclear. Selective estrogen receptor modulators (SERMs) mimic estrogen action in certain tissues while opposing it in others. The molecular mechanisms of the effects of SERMs such as raloxifene on the tumor progression of epithelial ovarian cancer are also still unclear. Here, we show that various genomic actions of estrogen differ from those of raloxifene in human ovarian cancer cell lines expressing estrogen receptor α (ERα). 17β-Estradiol (E2) induced the gene expression of c-Myc and IGF-1 and increased the binding of ERα to the AP1 site of the promoters of c-Myc and IGF-1. ERα silencing abolished the E2-stimulated c-Myc expression. E2 induced the recruitment of co-activators such as SRC-1, SRC-3 and CBP to the promoters of c-Myc and IGF-1, and SRC-1 silencing abolished both the E2-stimulated c-Myc expression and cell-cycle progression. In contrast, although raloxifene increased the binding of ERα to the AP1 site of the promoters of c-Myc and IGF-1, raloxifene had no effect on the gene expression of c-Myc or IGF-1. Raloxifene induced the recruitment of co-repressors such as HDAC2, N-CoR and SMRT to the promoter of IGF-1. Thus, the difference between the genomic actions exerted by estrogen and raloxifene in human ovarian cancer cell lines expressing ERα appear to be dependent on the recruitment of co-regulators. © 2008 Nature Publishing Group All rights reserved. - 松村到; 金倉譲綜合臨床 57 1089 - 1090 2008年04月
- 松村 到; 金倉 譲綜合臨床 57 4 666 - 674 永井書店 2008年04月
- 松村到; 金倉譲綜合臨床 57 4 666 - 674 永井書店 2008年04月
- 松村 到; 金倉 譲日本臨床 66 3 535 - 539 日本臨床社 2008年03月
- 松村到; 金倉譲日本臨床 66 3 535 - 539 日本臨床社 2008年03月
- Itaru Matsumura; Masao Mizuki; Yuzuru KanakuraCANCER SCIENCE 99 3 479 - 485 2008年03月 [査読有り]
Growth, survival and differentiation of hematopoietic cells are regulated by the interactions between hematopoietic growth factors and their receptors. The defect in these interactions results in a failure of hematopoiesis, while aberrantly elevated and/or sustained activation of these signals cause hematologic malignancies. Among them, constitutively activating mutations of the receptor tyrosine kinases (RTKs), such as c-Kit, platelet-derived growth factor receptor (PDGFR) and FLT3, are often involved in the pathogenesis of various types of hematologic malignancies. Constitutive activation of RTKs is provoked by several mechanisms including chromosomal translocations and various mutations involving their regulatory regions. Chromosomal translocations commonly generate chimeric proteins consisting of the cytoplasmic domain of RTKs and the dimerization or multimerization motif of the fusion partner, resulting in the constitutive dimerization of RTKs. On the other hand, missense, insertion or deletion mutations in the regulatory regions, such as juxtamembrane domain, activation loop, and extracellular domain, also cause constitutive activation of RTKs mainly by preventing the auto-inhibitory regulation. Oncogenic RTKs activate downstream signaling molecules such as Ras/MAPK, PI3-K/Akt/mTOR, and STATs as well as ligand-activated wild type RTKs. However, their signals are quantitatively and qualitatively different from wild type RTKs. Based on these findings, several agents that target oncogenic RTKs or their downstream molecules have been developed: imatinib and FLT3 inhibitors for RTKs themselves, farnesyltransferase inhibitors, mTOR inhibitors and MEK inhibitors for the downstream signaling molecules. As promising results have been obtained in several clinical trials using these agents, the establishment of these molecular targeted agents is expected. - 松村到; 金倉譲月刊血液・腫よう科 56 1 120 - 126 科学評論社 2008年01月
- 松村到がん研究に係わる特定領域研究研究報告集録 平成19年度 98 2008年
- 田中宏和; 金倉譲; 松村到サイトカインによる増幅培養臍帯血による臍帯血移植の臨床試験 平成19年度 総括・分担研究報告書 59 - 68 2008年
- Takae Shizusawa; Hirohiko Shibayama; Shinsuke Murata; Yuri Saitoh; Yuna Sugimoto; Itaru Matsumura; Hiroyasu Ogawa; Haruo Sugiyama; Shirou Fukuhara; Masayuki Hino; Akihisa Kanamaru; Amane Yamauchi; Katsuyuki Aozasa; Yuzuru KanakuraLEUKEMIA & LYMPHOMA 49 1 113 - 121 2008年 [査読有り]
Anamorsin is a cell-death-defying factor, which was originally isolated as a molecule that conferred resistance to apoptosis induced by growth factor starvation. In order to evaluate anamorsin expression levels in malignant lymphoma, we immunostained paraffin-embedded sections with anti-anamorsin monoclonal antibodies. About 40% (89/234) of sections from patients with diffuse large B cell lymphoma (DLBCL) showed strong anamorsin expression. Comparing the level of anamorsin expression in DLBCL patients with their clinical features (i.e., overall survival rate, International Prognostic Index (IPI) parameters, and treatment response) revealed no significant correlation between anamorsin expression levels and these clinical features. However, anamorsin expression in DLBCL patients with a low IPI was shown to be an unfavorable biomarker, especially in the patients who received chemotherapy without rituximab. It is suggested that anamorsin might play some roles in the abnormal growth of DLBCL. - Kentaro Fukushima; Itaru Matsumura; Sachiko Ezoe; Hirohiko Shibayama; Michiko Ichii; Takafumi Yokota; Hirokazu Tanaka; Yuzuru KanakuraBLOOD 110 11 300A - 300A 2007年11月 [査読有り]
- Takafumi Yokota; Kenji Oritani; Karla P. Garrett; Taku Kouro; Makoto Nishida; Isao Takahashi; Michiko Ichii; Itaru Matsumura; Paul W. Kincade; Yuzuru KanakuraBLOOD 110 11 188A - 189A 2007年11月 [査読有り]
- 松村到; 金倉譲Med Pract 24 11 1922 - 1928 2007年11月
- 松村到; 金倉譲血液フロンティア 17 11 1659 - 1666 2007年10月
- 松村到; 金倉譲生体の科学 58 5 460 - 461 2007年10月
- 腫瘍性チロシンキナーゼによる病型決定機構 FIP1L1/PDGFRαによる好酸球系細胞への選択的誘導福島 健太郎; 松村 到; 江副 幸子; 佐藤 友亮; 水木 満佐央; 田中 宏和; 織谷 健司; 金倉 譲臨床血液 48 9 917 - 917 (一社)日本血液学会-東京事務局 2007年09月
- 身近な話題・世界の話題 新しい血小板増加因子松村 到; 金倉 譲血液フロンティア 17 9 1390 - 1396 (株)医薬ジャーナル社 2007年08月血小板産生における最も重要な造血因子トロンボポエチン(TPO)が単離されてから10年以上経つ。この間に行われたPEG化TPOの臨床試験はTPOに対する中和抗体の出現で頓挫してしまい、その後血小板増加因子の開発が進まなかった。しかし、この数年TPO類似化合物やTPO受容体結合ペプチドなどが開発され、特にAMG531は特発性血小板減少症に有効なことが報告された。経口投与可能な薬剤も開発されており、今後、種々の血小板減少症に対する臨床応用が期待される。(著者抄録)
- 癌幹細胞と分子標的療法松村 到; 金倉 譲Biotherapy 21 4 209 - 216 (株)癌と化学療法社 2007年07月癌組織は多様な細胞集団から構成されるが、白血病、乳癌、脳腫瘍など多くの腫瘍において腫瘍のなかの一部の細胞集団のみがNOD/SCIDマウスに移植した際に、元の腫瘍に類似した腫瘍を作ることが示されてきた。そして、現在このような細胞が癌幹細胞として定義されている。癌幹細胞は正常幹細胞と同様に未分化な表面形質を示し、自己複製能と分化能を有し、癌幹細胞集団を維持しつつ、癌組織を構成する多様な分化段階にあるすべての癌細胞を生みだす。正常幹細胞と同様に、癌幹細胞も原発巣、転移巣のいずれにおいても「癌ニッチ」と呼ばれる微小環境を必要とし、その場で自己複製、生存に必要なNotch,Wnt/β-catenin,Sonic hedgehogなどからのシグナルを伝達される。癌幹細胞の起源としては、もともと自己複製能を有していた正常幹細胞に遺伝子異常が起こった可能性と、自己複製能を有さない前駆細胞レベルに自己複製能を寄与する遺伝子異常が起こった可能性がある。癌組織を形成する癌幹細胞以外の癌細胞は限られた分裂能しか有さずいずれアポトーシスを起こしていくので、癌を治癒させるには癌幹細胞のみを死滅させれば十分である。しかし、癌幹細胞は正常幹細胞と同様に細胞周期の静止期にあり、薬剤排出能も高いことから通常の癌治療には抵抗性であると想定されている。現在、自己複製能を阻害する薬剤などが開発中であるが、これらの薬剤は正常幹細胞を阻害することは免れない。したがって、癌幹細胞を選択的に死滅させる薬剤の開発が必要である。そのためには、抗体療法のための癌幹細胞特異的抗原の同定や、直接の治療標的となる癌幹細胞においてのみ活性化している分子、癌幹細胞の自己複製や生存にのみかかわっている分子の同定が有用である。(著者抄録)
- Hyper eosinophilic syndrome 病態と治療松村 到; 金倉 譲BIO Clinica 22 7 628 - 633 (株)北隆館 2007年07月従来、寄生虫感染やアレルギー性疾患などの基礎疾患がない原因不明の持続性の好酸球増加症がHypereosinophilic syndrome(HES)とされてきた。しかし、一部の症例では異常T細胞クローンによる過剰なIL-5産生や染色体4q12上でのinterstitial deletionによるFIP1L1-PDGFRαの融合チロシンキナーゼの形成が好酸球増加の原因であることが明らかにされた。これらの症例では、発症機構に基づいた抗IL-5抗体やimatinibなどの分子標的療法が極めて有効である。(著者抄録)
- 松村 到; 金倉 譲血液・腫瘍科 54 6 635 - 640 科学評論社 2007年06月
- Shinichi Ozawa; Chiaki Nakaseko; Miki Nishimura; Atsuo Maruta; Ryuko Cho; Chikako Ohwada; Hisashi Sakamaki; Hiroshi Sao; Shin-ichiro Mori; Shinichiro Okamoto; Kouichi Miyamura; Shunichi Kato; Takakazu Kawase; Yasuo Morishima; Yoshihisa KoderaBRITISH JOURNAL OF HAEMATOLOGY 137 2 142 - 151 2007年04月 [査読有り]
Chronic graft-versus-host disease (GVHD) remains the major cause of late morbidity and mortality after allogeneic stem cell transplantation. We retrospectively analysed 2937 patients who underwent bone marrow transplantation from an unrelated donor (UR-BMT) facilitated by the Japan Marrow Donor Program (JMDP) and survived beyond day 100 after transplantation. The cumulative incidence of chronic GVHD (limited + extensive) or extensive chronic GVHD at 5 years post-transplant was 45.8% and 28.2%, respectively. On multivariate analysis, seven variables predicting chronic GVHD were identified: recipient age over 20 years, donor age over 30 years, primary diagnosis of chronic myeloid leukaemia, human leucocyte antigen (HLA)-A or -B mismatch, total body irradiation-containing regimen, platelet count not having reached 50 x 10(9)/l by day 100, and prior acute GVHD. Among 2609 patients with haematological malignancy, overall survival was significantly higher in patients with limited chronic GVHD but lower in patients with extensive chronic GVHD compared with those without chronic GVHD. The cumulative incidence of relapse among patients with limited or extensive chronic GVHD was significantly lower than that among patients without chronic GVHD. Our results suggest that limited chronic GVHD provides a survival benefit to patients with haematological malignancies by reducing the risk of relapse without increasing the risk of death from chronic GVHD. - 松村 到綜合臨床 56 増刊 1373 - 1377 (株)永井書店 2007年04月
- 松村 到; 金倉 譲医学のあゆみ 220 9 765 - 770 医歯薬出版 2007年03月
- 松村到; 金倉譲月刊血液・腫よう科 54 2 158 - 166 科学評論社 2007年02月
- 松村 到; 金倉 譲血液・腫瘍科 54 2 158 - 166 科学評論社 2007年02月
- Potential target molecules for Ex Vivo expansion of hematopoietic stem cells and their roles in normal hematopoiesisHirokazu Tanaka; Itaru Matsumura; Yuzuru KanakuraJournal of Stem Cells 2 3 167 - 183 2007年Hematopoietic stem cells (HSCs) are characterized by two distinct abilities, that is, self-renewal ability and multipotency. To keep homeostasis of hematopoiesis and protect exhaustion of HSCs throughout the life, most of HSCs are kept quiescent and only a limited number of HSCs enter cell cycle to supply mature blood cells. Cell cycle state of HSCs is crucially regulated by external factors such as cytokines, adhesion molecules, Notch ligands, and Wnt signals in the bone marrow (BM) microenvironment, so called hematopoietic niche. In addition, intrinsic molecules expressed in HSCs such as transcription factors and cell cycle regulatory molecules also control their growth and differentiation. To utilize HSCs more efficiently and to develop new therapeutic strategies for various diseases, it is of particular interest to expand HSCs ex vivo. At present, three clinical studies, in which cord blood HSCs were ex vivo expanded by cytokines and transplanted into patients with hematologic malignancies, have been performed. However, the expanded HSCs did not shorten the recovery of hematopoiesis. So, further novel strategies to expand HSCs more efficiently and to fasten hematopoiesis from HSCs are required by mo ifying the function of the molecules that regulate self-renewal of HSCs. © 2007 Nova Science Publishers, Inc.
- 松村 到綜合臨床 56 0 1373 - 1377 永井書店 2007年
- 松村 到; 金倉 譲日本臨床 65 0 100 - 104 日本臨床社 2007年01月
- 松村到がん研究に係わる特定領域研究研究報告集録 平成18年度 98 2007年
- 田中宏和; 金倉譲; 松村到サイトカインによる増幅培養臍帯血による臍帯血移植の臨床試験 平成18年度 総括・分担研究報告書 71 - 78 2007年
- 松村到上原記念生命科学財団研究報告集 20 335 - 337 2006年11月
- Hirokazu Tanaka; Itaru Matsumura; Kazuki Nakao; Takumi Era; Yuzuru KanakuraBLOOD 108 11 339A - 339A 2006年11月 [査読有り]
- Hirokazu Tanaka; Itaru Matsumura; Kiminari Itoh; Asako Hatsuyama; Masayuki Shikamura; Yusuke Satoh; Toshio Heike; Tatsutoshi Nakahata; Yuzuru KanakurabSTEM CELLS 24 11 2592 - 2602 2006年11月 [査読有り]
HOX transcription factors play important roles in the self-renewal of hematopoietic cells. HOX proteins interact with the non-HOX homeobox protein PBX1 to regulate, both positively and negatively, the expression of target genes. In this study, we synthesized a decoy peptide containing the YPWM motif from HOX proteins ( decoy HOX [decHOX]), which was predicted to act as a HOX mimetic, and analyzed its effects on self-renewal of human cord blood CD34(+) cells. We were able to deliver decHOX into approximately 70% of CD34(+) cells. By examining the expression of HOX target genes c-myc and p21(waf1/cip1), we confirmed that decHOX enhanced HOX functions. After 7 days of culture in serum-free medium containing a cytokine cocktail, cultures treated with decHOX had approximately twofold-increased numbers of CD34(+) cells and primitive multipotent progenitor cells compared with control cells. Furthermore, decHOX-treated cells reconstituted hematopoiesis in nonobese diabetic/severe combined immunodeficiency mice more rapidly and more effectively ( more than twofold greater efficiency, as determined by a limiting dilution method) than control cells. decHOX-treated cells were also able to repopulate secondary recipients. Together, these results indicate that in combination with growth factors and/or other approaches, decHOX might be a useful new tool for the ex vivo expansion of hematopoietic stem/progenitor cells. - 松村到; 金倉譲Mebio 23 9 55 - 69 2006年09月
- 老化制御因子Sirt1が造血幹細胞の未分化性維持にはたす役割についての解析江副 幸子; 松村 到; 津森 洋; 佐藤 友亮; 石川 淳; 水木 満佐央; 織谷 健司; 金倉 譲臨床血液 47 9 1045 - 1045 (一社)日本血液学会-東京事務局 2006年09月
- Anamorsinトランスジェニックマウスの作製と解析沈沢 尚恵; 柴山 浩彦; 村田 信介; 水木 満佐央; 松村 到; 青笹 克之; 金倉 譲日本癌学会総会記事 65回 121 - 122 (一社)日本癌学会 2006年09月
- 松村 到; 金倉 譲日本内科学会雑誌 95 7 1375 - 1381 一般社団法人 日本内科学会 2006年07月造血器腫瘍の分野においては分子標的療法という言葉がもてはやされる以前からATRAによるAPLの治療が行われてきた. また, 他の分野に先駆けてCMLにimatinib, B細胞悪性リンパ腫にrituximabが臨床応用されてきた. 両薬剤は, 共に際立った有効性を示し, 現在ではそれぞれの疾患の治療に欠くことのできないキードラッグである. 昨年, この2剤に引き続き, 亜砒酸, Am80, 抗CD33抗体が保険認可された. 既に悪性リンパ腫に対する<sup>90</sup>Y-ibritumomabの臨床試験は終了しており, imatinib耐性CMLに対する新規BCR-ABL阻害剤AMN107, BMS354825の臨床治験も始まっている. 更に, プロテアソーム阻害剤bortezomibも近く認可される予定である. 今後, 更に分子標的療法が進歩し, 造血器腫瘍の治療成績が更に改善されることを期待したい.
- 松村到; 金倉譲月刊血液・腫よう科 52 6 683 - 688 2006年06月
- 松村到; 金倉譲綜合臨床 55 6 1609 - 1615 2006年06月
- 松村到; 金倉譲綜合臨床 55 6 1624 - 1628 2006年06月
- 松村到; 金倉譲血液フロンティア 16 5 701 - 707 2006年04月
- 松村到; 金倉譲医学のあゆみ 3 689 - 693 2006年04月
- 松村到; 金倉譲血液フロンティア 16 3 377 - 385 2006年02月
- 松村到; 金倉譲Annual Review 血液 2006 56 - 63 2006年01月
- 松村到がん研究に係わる特定領域研究研究報告集録 平成17年度 98 2006年
- 田中宏和; 金倉譲; 松村到サイトカインによる増幅培養臍帯血移植の臨床試験 平成17年度 総括・分担研究報告書 76 - 83 2006年
- 松村到; 金倉謙実験医学 23 20 3176 - 3181 2005年12月
- J Ishiko; M Mizuki; Matsumura, I; H Shibayama; H Sugahara; G Scholz; H Serve; Y KanakuraONCOGENE 24 55 8144 - 8153 2005年12月FLT3 tyrosine kinase domain ( TKD) mutations are detected in similar to 7% of acute myeloid leukemia patients, and suggested to correlate with poor prognosis and confer resistance to FLT3 inhibitors. To explore activation mechanism of FLT3 TKD mutation, we analysed critical tyrosine residues for the constitutive activation and downstream signaling of the mutant by generating a series of single Tyr -> Phe substitution mutant of all 22 cytoplasmic tyrosine residues of murine FLT3 TKD-mutant (mFLT3(Asp838Val)). Tyr845Phe, Tyr892Phe and Tyr922Phe substitutions suppressed the phosphorylation of mFLT3(Asp838Val) itself, the activation of Erk1/2, STAT3 and STAT5, and the factor-independent cell proliferation and survival. In contrast, these three Tyr -> Phe mutations partially suppressed but maintained the ligand-dependent activation and anti-apoptotic activity of wild-type FLT3, suggesting that these tyrosine residues were more critical for the constitutive activation and signaling of mFLT3(Asp838Val). These three Tyr -> Phe mutations also inhibited the constitutive activation of other FLT3 mutants bearing internal tandem duplication, Asp838Tyr or Ile839del. The suppression of mFLT3(Asp838Val) activation and signaling by these substitutions was partially recovered by shifting the culture temperature from 37 to 33 degrees C, or by the introduction of Cdc37 and Hsp90. Taken together, Tyr(845), Tyr(892) and Tyr(922) are the critical residues in mFLT3(Asp838Val) activation, possibly through stabilizing the active conformation of mFLT3(Asp838Val).
- 松村到; 金倉譲内科 96 6 1028 - 1036 南江堂 2005年12月
- 松村到; 金倉譲医学のあゆみ 48 - 51 2005年09月
- 松村到綜合臨床 54 6 1799 - 1804 2005年06月
- S Ezoe; Matsumura, I; K Gale; Y Satoh; J Ishikawa; M Mizuki; S Takahashi; N Minegishi; K Nakajima; M Yamamoto; T Enver; Y KanakuraJOURNAL OF BIOLOGICAL CHEMISTRY 280 13 13163 - 13170 2005年04月Although GATA-1 and GATA-2 were shown to be essential for the development of hematopoietic cells by gene targeting experiments, they were also reported to inhibit the growth of hematopoietic cells. Therefore, in this study, we examined the effects of GATA-1 and GATA-2 on cytokine signals. A tamoxifen-inducible form of GATA-1 (GATA-1/ERT) showed a minor inhibitory effect on interleukin-3 (IL-3)-dependent growth of an IL3-dependent cell line Ba/F3. On the other hand, it drastically inhibited TPO-dependent growth and gp130-mediated growth/survival of Ba/F3. Similarly, an estradiol-inducible form of GATA-2 (GATA-2/ER) disrupted thrombopoietin (TPO)-dependent growth and gp130-mediated growth/survival of Ba/F3. As for this mechanism, we found that both GATA-1 and GATA-2 directly bound to STAT3 both in vitro and in vivo and inhibited its DNA-binding activity in gel shift assays and chromatin immunoprecipitation assays, whereas they hardly affected STAT5 activity. In addition, endogenous GATA-1 was found to interact with STAT3 in normal megakaryocytes, suggesting that GATA-1 may inhibit STAT3 activity in normal hematopoietic cells. Furthermore, we found that GATA-1 suppressed STAT3 activity through its N-zinc finger domain. Together, these results suggest that, besides the roles as transcription factors, GATA family proteins modulate cytokine signals through protein-protein interactions, thereby regulating the growth and survival of hematopoietic cells.
- 松村到; 金倉譲Mebio 22 2 74 - 80 2005年02月
- E Ishiko; Matsumura, I; S Ezoe; K Gale; J Ishiko; Y Satoh; H Tanaka; H Shibayama; M Mizuki; T Era; T Enver; Y KanakuraJOURNAL OF BIOLOGICAL CHEMISTRY 280 6 4929 - 4939 2005年02月The effects of Notch signals on the erythroid/ imegakaryocytic differentiation of hematopoietic cells were examined. Activation of Notch signals by the intracellular Notch1 or an estradiol-inducible form of Notch1/ER suppressed the expression of the erythroid marker glycophorin A in an erythroid/megakaryocytic cell line K562. Although Mock-transfected K562 cells underwent megakaryocytic differentiation in response to '12-O-tetradecanoylphorbol-13-acetate (TPA), estradiol-activated Notch1/ER induced apoptosis during TPA treatment in the transfectant, which was accompanied by the reduced expression of an antiapoptotic molecule Bcl-XL. Even when apoptosis was prevented by the overexpression of Bcl-XL, activated Notch signals still inhibited TPA-induced megakaryocytic differentiation. As for this mechanism, Notch1/recombination signal binding protein J-kappa-induced HES1 but not HES5 was found to inhibit the function of an erythroid/megakaryocytic lineage-specific transcription factor GATA-1. Although HES1 did not affect the DNA binding activity of GATA-1 in gel shift and chromatin immunoprecipitation assays, it directly bound to GATA-1 and dissociated a critical transcriptional cofactor, p300, from GATA-1. Furthermore, overexpressed HES1 inhibited the development of erythroid and megakaryocytic cells in colony assays. Also, the Notch ligand Jagged1 expressed on NIH3T3 cells suppressed the development of erythroid and megakaryocytic cells from cocultured Lin(-)Sca-1(+) hematopoietic stem/progenitor cells. These results suggest that Notch1 inhibits the development of erythroid/ megakaryocytic cells by suppressing GATA-1 activity through HES1.
- 松村到; 金倉譲月刊血液・腫よう科 50 1 42 - 52 2005年01月
- 松村到Annual Review 血液 2005 151 - 162 2005年01月
- S Nakata; Matsumura, I; H Tanaka; S Ezoe; Y Satoh; J Ishikawa; T Era; Y KanakuraJOURNAL OF BIOLOGICAL CHEMISTRY 279 53 55578 - 55586 2004年12月 [査読有り]
examine the roles for NF-kappaB family proteins in hematopoiesis, we first expressed dominant negative Rel/NF-kappaB (IkappaBSR) in a factor-dependent cell line, Ba/F3. Although IkappaBSR neither affected thrombopoietindependent nor gp130-mediated growth, it suppressed interleukin-3- and erythropoietin-dependent growth at low concentrations. In addition, IkappaBSR enhanced factor-deprived apoptosis through the accumulation of reactive oxygen species (ROS). When expressed in normal hematopoietic stem/progenitor cells, IkappaBSR induced apoptosis even in the presence of appropriate cytokines by accumulating ROS. We also expressed IkappaBSR in an inducible fashion at various stages of hematopoiesis using the OP9 system, in which hematopoietic cells are induced to develop from embryonic stem cells. When IkappaBSR was expressed at the stage of Flk-1(+) cells (putative hemangioblasts), IkappaBSR inhibited the development of primitive hematopoietic progenitor cells by inducing apoptosis through the ROS accumulation. Furthermore, when IkappaBSR was expressed after the development of hematopoietic progenitor cells, it inhibited their terminal differentiation toward erythrocytes, megakaryocytes, and granulocytes by inducing apoptosis through the ROS accumulation. These results indicate that NF-kappaB is required for preventing apoptosis at multiple steps of hematopoiesis by eliminating ROS. - 造血幹細胞の自己複製におけるc-Mycの役割佐藤 友亮; 松村 到; 田中 宏和; 水木 満佐央; 金倉 譲日本血液学会・日本臨床血液学会総会プログラム・抄録集 66回・46回 788 - 788 日本臨床血液学会 2004年09月
- D Watanabe; S Ezoe; M Fujimoto; A Kimura; Y Saito; H Nagai; Tachibana, I; Matsumura, I; T Tanaka; H Kanegane; T Miyawaki; M Emi; Y Kanakura; Kawase, I; T Naka; T KishimotoBRITISH JOURNAL OF HAEMATOLOGY 126 5 726 - 735 2004年09月The aim of this study was to investigate whether the suppressor of cytokine signalling (SOCS)-1 can act as a tumour suppressor when functioning as a negative regulator of the Janus family tyrosine kinases (JAKs), which have been reported to play important roles in leukaemogenesis. For this purpose, we carried out molecular analysis of the SOCS-1 gene in human acute myeloid leukaemia (AML) and human haematopoietic cell lines. Sequencing alterations in the coding region were found in two of 90 primary AML samples and one of 17 cell lines. Hypermethylation of the SOCS-1 gene was also observed in 72% of primary cases and 52% of cell lines and aberrant methylation strongly correlated with reduced expression. Transfection of SOCS-1 into Jurkat cells harbouring the mutation and methylation suppressed cell growth at a low serum concentration. These findings indicate that SOCS-1 is frequently silenced in haematopoietic malignancies, mainly as a result of hypermethylation, and suggest that SOCS-1 may be able to function as a tumour suppressor.
- 松村到; 金倉譲綜合臨床 53 7 2071 - 2074 2004年07月
- Y Satoh; Matsumura, I; H Tanaka; S Ezoe; H Sugahara; M Mizuki; H Shibayama; E Ishiko; J Ishiko; K Nakajima; Y KanakuraJOURNAL OF BIOLOGICAL CHEMISTRY 279 24 24986 - 24993 2004年06月Notch and HOXB4 have been reported to expand hematopoietic stem cells (HSCs) in vitro. However, their critical effector molecules remain undetermined. We found that the expression of c-myc, cyclin D2, cyclin D3, cyclin E, and E2F1 was induced or enhanced during Notch1- or HOXB4-induced self-renewal of murine HSCs. Since c-Myc can act as a primary regulator of G(1)/S transition, we examined whether c-Myc alone can induce self-renewal of HSCs. In culture with stem cell factor, FLT3 ligand, and IL-6, a 4-hydroxytamoxifen-inducible form of c-Myc (Myc/ERT) enabled murine Lin(-) Sca-1(+) HSCs to proliferate with the surface phenotype compatible with HSCs for more than 28 days. c-Myc activated by 4-hydroxytamoxifen augmented telomerase activities and increased the number of CFU-Mix about 2-fold in colony assays. Also, in reconstitution assays, HSCs expanded by c-Myc could reconstitute hematopoiesis for more than 6 months. As for the mechanism of c-myc induction by Notch1, we found that activated forms of Notch1 (NotchIC) and its downstream effector recombination signal-binding protein-J kappa (RBP-VP16) can activate the c-myc promoter through the element between -195 bp and -161 bp by inducing the DNA-binding complex. Together, these results suggest that c-Myc can support self-renewal of HSCs as a downstream mediator of Notch and HOXB4.
- S Ezoe; Matsumura, I; Y Satoh; H Tanaka; Y KanakuraCELL CYCLE 3 3 314 - 318 2004年03月 [査読有り]
Hematopoietic stem cells (HSCs) are characterized by pluripotentiality and a capacity for self-renewal. In order to both maintain a supply of mature blood cells and not to exhaust HSCs throughout the lifespan of the organism, most HSCs remain quiescent and only a limited number enter the cell cycle. In HSCs, the cell cycle is crucially regulated by external factors such as cytokines and interactions with stromal cells and the extracellular matrix (ECM) in the bone marrow (BM) microenvironment. In addition, intrinsic transcription factors expressed in HSCs, including c-Myb, GATA-2, HOX family proteins, and Bmi-1, also control their growth through their effect on gene transcription. In terms of the particular roles in regulation of the cell-cycle, p21(WAF1) (p21) and p27(KIP1) (p27) were shown to maintain the quiescence of HSCs and of progenitor cells, respectively, thereby governing their available pool sizes. Also, p16(INK4A) (p16) and p15(INK4B) ( p15) are thought to act as tumor suppressors, since their inactivation and/or deletion are observable in various types of hematologic malignancies. These results make evident that appropriate cell cycle control, particularly at the early stage of stem/progenitor cells, is required for maintaining normal hematopoiesis. - H Shibayama; E Takai; Matsumura, I; M Kouno; E Morii; Y Kitamura; J Takeda; Y KanakuraJOURNAL OF EXPERIMENTAL MEDICINE 199 4 581 - 592 2004年02月 [査読有り]
Many growth factors and cytokines prevent apoptosis. Using an expression cloning method, we identified a novel antiapoptotic molecule named Anamorsin, which does not show any homology to known apoptosis regulatory molecules such as Bcl-2 family, caspase fan-lily, or signal transduction molecules. The expression of Anamorsin was completely dependent on stimulation with growth factors such as interleukin 3, stem cell factor, and thrombopoietin in factor-dependent hematopoietic cell lines, and forced expression of Anamorsin conferred resistance to apoptosis caused by growth factor deprivation in vitro. Furthermore, Anamorsin was found to act as an antiapoptotic molecule in vivo because Anamorsin(-/-) mice die in late gestation due to defective definitive hematopoiesis in the fetal liver (FL). Although the number of hematopoietic stem/progenitor cells in the FL did not decrease in these mice, myeloid, and particularly erythroid colony formation in response to cytokines, was severely disrupted. Also, Anamorsin(-/-) erythroid cells initiated apoptosis during terminal maturation. As for the mechanism of Anamorsin-mediated cell survival, a microarray analysis revealed that the expression of Bcl-xL and Jak2 was severely impaired in the FL of Anamorsin(-/-) mice. Thus, Anamorsin is considered to be a necessary molecule for hematopoiesis that mediates antiapoptotic effects of various cytokines. - Mizuki M; Ueda S; Matsumura I; Ishiko J; Kanakura YGastrointestinal Stromal Tumor (GIST): From Pathology to Molecular Target Therapy, pp91-105 53 91 - 105 2004年
- Y Kataoka; Matsumura, I; S Ezoe; S Nakata; E Takigawa; Y Sato; A Kawasaki; T Yokota; K Nakajima; A Felsani; Y KanakuraJOURNAL OF BIOLOGICAL CHEMISTRY 278 45 44178 - 44187 2003年11月 [査読有り]
The development of myoblasts is regulated by various growth factors as well as by intrinsic muscle-specific transcriptional factors. In this study, we analyzed the roles for STAT3 in the growth and differentiation of myoblasts in terms of cell cycle regulation and interaction with MyoD using C2C12 cells. Here we found that STAT3 inhibited myogenic differentiation induced by low serum or MyoD as efficiently as the Ras/mitogen-activated protein kinase cascade. As for this mechanism, we found that STAT3 not only promoted cell cycle progression through the induction of c-myc but also inhibited MyoD activities through direct interaction. STAT3 inhibited not only DNA binding activities of MyoD but also its transcriptional activities. However, the inhibited transcriptional activities were restored by the supplement of p300/CBP and PCAF, suggesting that STAT3 might deprive MyoD of these transcriptional cofactors. In addition, we found that MyoD inhibited DNA binding activities of STAT3, thereby inhibiting STAT3-dependent cell growth and survival of Ba/F3 cells. These results suggest that the development of muscle cells is regulated by the coordination of cytokine signals and intrinsic transcription factors. - Activation loop変異Flt3の恒常的活性化機構の解析石河 純; 水木 満佐央; 上田 周二; 松村 到; 金倉 譲臨床血液 44 8 652 - 652 (一社)日本血液学会-東京事務局 2003年08月
- PMLがRas/MAPKのシグナル伝達に及ぼす影響についての解析江副 幸子; 松村 到; 菅原 浩之; 水木 満佐央; 柴山 浩彦; 金倉 譲臨床血液 44 8 778 - 778 (一社)日本血液学会-東京事務局 2003年08月
- Rhoファミリー分子によるヘアリーセル白血病細胞の増殖と形態制御についての解析張 弦; 待井 隆志; 松村 到; 菅原 浩之; 柴山 浩彦; 水木 満佐央; 金倉 譲臨床血液 44 8 827 - 827 (一社)日本血液学会-東京事務局 2003年08月
- 造血器腫瘍患者の化学療法後の好中球減少時におけるアンフォテリシンBシロップとイトラコナゾールカプセルの真菌感染予防効果の比較菅原 浩之; 中田 壮一; 片岡 良久; 山城 賢太郎; 石河 純; 滝川 江里; 柴山 浩彦; 水木 満佐央; 松村 到; 金倉 譲血液フロンティア 13 6 806 - 810 (株)医薬ジャーナル社 2003年05月カンジダ属,アスペルギルス属共に広く抗菌活性を持つitraconazole(ITCZ)に注目しamphotericin-B(AMPH-B)シロップとの比較検討を行った.化学療法後に好中球減少が予想される患者をITCZカプセル内服群とAMPH-Bシロップ内服群の2群に順次振り分けた.両群の発熱頻度に有意差を認めず,感染症に伴う死亡例もなかった.深在性真菌症の確診例は両群共に認めず,AMPH-B群で疑診1例を認めた.ITCZ群で咽頭・便からのカンジダ属の検出率が低い傾向がみられた.肝・腎障害等の副作用は両群共に認めなかった.ITCZはAMPH-Bより格段に内服しやすく,薬剤血中濃度や併用薬との相互作用に注意して用いれば造血器腫瘍患者の治療時のQOLを改善すると考えた
- A Kawasaki; Matsumura, I; Y Kataoka; E Takigawa; K Nakajima; YR KanakuraBLOOD 101 9 3668 - 3673 2003年05月 [査読有り]
Promyelocytic leukemia protein PML acts as a tumor suppressor, whereas its chimeric mutant promyelocytic leukemia/retinoic acid receptoralpha (PML/RARalpha) causes acute promyelocytic leukemia (APL). Because PML has, been shown to form transcription-regulatory complexes With various molecules, we speculated that PML and/or PML/RARalpha might affect signal transducer and activator of transcription 3 (STAT3) activity, which plays a crucial role in granulocyte colony-stimulating factor (G-CSF)-induced growth and survival of myeloid cells. In luciferase assays, PML inhibited STAT3 activity in NIH3T3,293T, HepG2, and 32D cells. PML formed a complex with STAT3 through B-box and COOH terminal regions in vitro and in vivo, thereby inhibiting its DNA binding activity. Although PML/RARalpha did not interact with STAT3, it dissociated PML from STAT3 and restored its activity suppressed by PML. To assess the biologic significance of these findings, we introduced PML and PML/RARalpha, into interleukin-3 (IL-3)-dependent Ba/F3 cells expressing the chimeric receptor composed of extracellular domain of G-CSF-R and cytoplasmic domain of gp130, in which gp130-mediated growth is essentially dependent on STAT3 activity. Neither PML nor PML/RARalpha affected IL-3-dependent growth of these clones. By contrast, gp130-mediated growth was abrogated by PML, whereas it was enhanced. by PML/RARalpha. These results reveal new functions of PML and PML/RARalpha, and suggest that dysregulated STAT3 activity by PML/RARalpha may participate in the pathogenesis of APL. (C) 2003 by The American Society of Hematology. - M Mizuki; J Schwable; C Steur; C Choudhary; S Agrawal; B Sargin; B Steffen; Matsumura, I; Y Kanakura; FD Bohmer; C Muller-Tidow; WE Berdel; H ServeBLOOD 101 8 3164 - 3173 2003年04月The receptor tyrosine kinase Flt3 is expressed and functionally important in early myeloid progenitor cells and in the majority of acute myeloid leukeimia (AML) blasts. Internal tandem duplications (ITDs) in the juxtamembrane domain of the receptor occur in 25% of AML cases. Previously, we have shown that these mutations activate the receptor and induce leukemic transformation. In this study, we performed genome-wide parallel expression analyses of 32Dcl3 cells stably transfected with either wild-type or 3 different ITD isoforms of Flt3. Comparison of microarray expression analyses revealed that 767 of 6586 genes differed in expression between FLT3-WT- and FLT3-ITD-expressing cell lines. The target genes of mutationally activated Flt3 resembled more closely those of the interleukin 3 (IL-3) receptor than those of ligand-activated FIt3. The serine-threonine kinase Pim-2 was up-regulated on the mRNA and the protein level in Flt3-ITD-expressing cells. Further experiments indicated that Pim-2 function was important for clonal growth. of 32D cells. Several genes repressed by the mutations were found to be involved in myeloid gene regulation. Pu.1 and C/EBPalpha, both induced by ligand-activation of wild-type Flt3, Were suppressed in their expression and function by the FIt3 mutations. In conclusion, internal tandem duplication mutations of Flt3 activate transcriptional programs that partially mimic IL-3 activity. Interestingly, other parts of the transcriptional program involve novel, IL-3-independent pathways that antagonize differentiation-inclucing effects of wildtype FIt3. The identification of the transcriptional program induced by ITD mutations should ease the development of specific therapies. (C) 2003 by The American Society of Hematology.
- Zhang, X; T Machii; Matsumura, I; S Ezoe; A Kawasaki; H Tanaka; S Ueda; H Sugahara; H Shibayama; M Mizuki; Y KanakuraINTERNATIONAL JOURNAL OF HEMATOLOGY 77 3 263 - 273 2003年04月 [査読有り]
Hairy cell leukemia (HCL) is a rare type of chronic B-cell leukemia characterized by the hairy morphology of the leukemia cells. All of 5 HCL samples and an HCL-derived cell line, BNBH-I, showed serrated edges and hairlike projections in May-Grunwald Giemsa stain and protruding actin spikes and lamellipodia in phalloidin stain. These structures were hardly detected on B-cell chronic lymphocytic leukemia (B-CLL) and precursor B-cell acute lymphocytic leukemia (B-ALL) cells. Because Rho guanosine triphosphatases (GTPases) regulate the formation of these structures, we examined the expression levels and activation states of Rho GTPases in HCL cells. RhoA, Rac1, and Cdc42 were overexpressed and constitutively activated in HCL samples and BNBH-I cells but not in B-CLL or precursor B-ALL cells. Next we overexpressed dominant-negative (DN)-RhoA, DN-Rac1, and DN-Cdc42 in BNBH-I. As a result, each DN mutant repressed the growth of BNBH-I cells by more than 50% and inhibited actin spike formation, but only DN-Rac1 suppressed lamellipodia formation. We also found that enforced expression of constitutively active-RhoA, Rac, or Cdc42 in the proB-cell line Ba/F3 was sufficient to induce actin spike formation, whereas none of these molecules produced lamellipodia. These results indicated that constitutively activated Rho GTPases regulate the growth and unique morphology of HCL cells. (C) 2003 The Japanese Society of Hematology. - 急性骨髄性白血病の予後不良因子,internal tandem duplication変異Flt3によるSTAT標的遺伝子の発現誘導と骨髄系転写因子の発現抑制水木 満佐央; 松村 到; 上田 周二; 石河 純; Joachim Schwaeble; Hubert Serve; 金倉 譲日本内科学会雑誌 92 Suppl. 145 - 145 (一社)日本内科学会 2003年02月
- K Hashimoto; Matsumura, I; T Tsujimura; DK Kim; H Ogihara; H Ikeda; S Ueda; M Mizuki; H Sugahara; H Shibayama; Y Kitamura; Y KanakuraBLOOD 101 3 1094 - 1102 2003年02月 [査読有り]
Substitution of valine (Val) for aspartic acid (Asp) at codon 814 constitutively activates murine c-kit receptor tyrosine kinase (KIT), and Asp816Val mutation, corresponding to murine Asp814Val mutation, is found in patients with mastocytosis and acute myelocytic leukemia. However, the signal transduction pathways responsible for oncogenesis by the Asp814Val mutant (KlT(Val814)) are not fully understood. To examine the oncogenic signal transduction of KITVal814, we converted 20 tyrosine (Tyr) residues to phenylalanine (Phe) in the cytoplasmic domain of KITVal814 or deleted the C-terminal region containing 2 other tyrosine residues (Del). Among various KITVal814_ derived mutants, KITVal814-Tyr719Phe and KITVal814-Del severely impaired receptor tyrosine phosphorylation and association with the p85 subunit of phosphatidylinositol 3'-kinase (p85 (P13-K)). Moreover, KITVal814-Tyr719Phe and KITVal814-Del failed to induce ligand-independent growth in Ba/F3 cells, indicating that Tyr719, the binding site for p85(PI3-K), and the C-terminal region are indispensable for factor-independent growth by KITVal814. Although the C-terminal region was also required for ligand-dependent growth by wild-type KIT (KITWT), the Tyr719Phe substitution had negligible effects on ligand-dependent growth by KITWT. Furthermore, dominant-negative P13-K significantly inhibited ligand-independent growth by KITVal814. These results demonstrate that Tyr719 is crucial for constitutive activation of KITVal814, but not for the ligand-induced activation of KIT (WT), and that the downstream signaling of P13-K plays an important role in ligand-independent growth and tumorigenicity by KITVal814, thereby suggesting that KITVal814 is a unique activating mutation that leads to a distinguishable function from the effects of KITWT. (C) 2003 by The American Society of Hematology. - 松村 到; 田中 宏和; 金倉 譲細胞工学 22 1 46 - 49 秀潤社 2003年01月
- Constitutive active receptor tyrosine kinase in hematological neoplasiaMizuki M; Ueda S; Matsumura I; Schwaeble J; Ishiko J; Serve H; Kanakura YRec. Res. Dev. in Mol. & Cell. Biol. 4:85-100 2003年
- Roles for E2F1 and c-Myc in the regulation of cell growth and survivalMatsumura I; Tanaka H; Kanakura YCell Cycle 2:333-338 2003年
- Molecular mechanisms of E2F1- and c-Myc-enhanced apoptosisMatsumura I; Tanaka H; Mizuki M; Sugahara H; Kanakura YRec. Res. Dev. in Mol. & Cell. Biol. 4:311-324 2003年
- Itaru Matsumura; Hirokazu Tanaka; Yuzuru KanakuraCELL CYCLE 2 4 333 - 338 2003年 [査読有り]
Cell cycle machinery controls not only cell growth but also cell survival and death. For example, overexpression of c-Myc or E2F1, which are involved in G(1)/S transition, causes apoptosis under certain conditions. Furthermore, endogenous E2F1 also participates in apoptosis, as evidenced by the defect of apoptosis in E2F1-deficient mice. Candidate molecules that mediate c-Myc-and E2F1-enhanced apoptosis include p14/p19(ARF), ornithine decarboxylase and lactate degydrogenase-A (for c-Myc) as well as p14/p19(ARF), p73, Apaf-1 and caspase-3 (for E2F1). c-Myc also activates the CD95/Fas-FADD-mediated death signal. c-Myc and E2F1 inhibit NF-kappa B activities induced by TNF alpha or reactive oxygen species. Therefore, c-Myc and E2F1 regulate cell growth and death not only by inducing transcription but also by modulating signal transduction pathways. - S Ueda; H Ikeda; M Mizuki; J Ishiko; Matsumura, I; H Tanaka; H Shibayama; H Sugahara; E Takai; Zhang, X; T Machii; Y KanakuraINTERNATIONAL JOURNAL OF HEMATOLOGY 76 5 427 - 435 2002年12月The c-kit receptor tyrosine kinase (KIT) is constitutively activated by 2 types of naturally occurring mutations, the Val559-->Gly (G559) mutation in the juxtamembrane domain and the Asp814-->Val (V814) mutation in the catalytic domain. We evaluated the effects of the tyrosine kinase inhibitors STI571 and AG1296 on BaF3 cells expressing wild-type KIT (KITWT) or activating mutants of KIT (KITG559 and KITV814) in the presence or absence of the KIT ligand, stem cell factor (SCF). Both STI571 and AG1296 inhibited SCF-dependent activation of KITWT and SCF-independent activation of KITG559 more efficiently, whereas SCF-independent activation of KITV814 was scarcely affected. Furthermore, both inhibitors inhibited SCF-dependent growth of BaF3-KITWT cells and, with higher potencies, SCF-independent growth of BaF3-KITG559 cells through the induction of apoptosis. In contrast, the inhibitors had little or no effect on SCF-independent growth of BaF3-KITV814 cells or on IL-3-dependent growth of BaF3-Mock cells. These results suggested that both inhibitors may be effective therapeutic agents for oncogenic KIT with the juxtamembrane domain mutation, but not with the catalytic domain mutation, and that the activation mechanism of the catalytic domain mutant KIT is complex and entirely different from that of the wild-type KIT or the juxtamembrane domain mutant KIT. (C)2002 The Japanese Society of Hematology.
- 【p53経路とRB経路 ここまでわかった細胞癌化のメカニズム】 E2F1とMycによるアポトーシス誘導のメカニズム松村 到; 田中 宏和; 金倉 譲細胞工学 22 1 46 - 49 (株)学研メディカル秀潤社 2002年12月E2F1とMycによるアポトーシス誘導機構について概説した.一般に,E2F1やMycなどの過剰発現は細胞のアポトーシス感受性を高める.この機構として,E2F1やMycが転写因子としてp19ARFなど種々のアポトーシス促進分子の発現を誘導することが報告されてきた.最近,著者等は,これらの細胞では活性酸素種が蓄積され,更に,過剰なE2F1により抗アポトーシス分子NF-κBの機能が阻害されることにより,細胞のアポトーシス感受性が亢進することを明らかにした
- S Ezoe; Matsumura, I; S Nakata; K Gale; K Ishihara; N Minegishi; T Machii; T Kitamura; M Yamamoto; T Enver; Y KanakuraBLOOD 100 10 3512 - 3520 2002年11月GATA-2 is considered to be essential for the development, maintenance, and function of hematopoietic stem cells (HSCs). However, it was also reported that GATA-2 Inhibits the growth of HSCs. To examine the role of GATA-2 in the growth of hematopoietic cells, we introduced an estradiol-inducible form of GATA-2 (GATA-2/estrogen receptor [ER]) into interleukin 3 (IL-3)-dependent cell lines, Ba/F3, 32D, and FDC-P1. Estradiol-induced GATA-2 suppressed c-myc mRNA expression and inhibited IL-3-dependent growth in these clones. As for this mechanism, GATA-2 was found to inhibit ubiquitin/proteasome-dependent degradation of p21(WAF1) and p27(Kip1) and to induce their accumulation by repressing the expression of Skp2 and Cul1, both of which are components of the ubiquitin ligase for p21(WAF1) and p27(Kip1). Overexpression of c-myc restored the expression of Skp2 and Cul1 mRNA, reduced the amounts of p21(WAF1) and p27(Kip1) proteins, and canceled GATA-2-induced growth suppression, suggesting that down-regulation of c-myc expression may be primarily responsible for GATA-2-induced growth suppression. Next, we transduced retrovirus containing GATA-2/ER into murine bone marrow mononuclear cells (MNCs) and stem/progenitor (Sca-1(+)Lin(-)) cells. GATA-2/ER suppressed cytokine-dependent growth of MNCs and Sca-1(+)Lin(-) cells by about 70%, which was also accompanied by the reduced expression of c-myc, Skp2, and Cull mRNA and the accumulation of p21(WAF1) and p27(Kip1) proteins. In addition, the amount of GATA-2 protein was found to decline in hematopoietic stem/progenitor cells that were promoted to enter cell cycle by the stimulation with cytokines. These results suggest that GATA-2 may regulate expression levels of p21(WAF1) and p27(Kip1), thereby contributing to the quiescence of hematopoietic stem/progenitor cells.
- 松村到; 金倉譲臨床検査 46 11 1194 - 1202 2002年10月
- 水木満佐央; 松村到; 上田周二; 金倉譲臨床医 28 10 2152 - 2154 (株)中外医学社 2002年10月
- c-Kit受容体を介した細胞遊走シグナルの解析 Tyr567,Tyr719の重要性上田 周二; 水木 満佐央; 池田 弘和; 辻村 亨; 松村 到; 柴山 浩彦; 菅原 浩之; 待井 隆志; 金倉 譲日本癌学会総会記事 61回 82 - 82 (一社)日本癌学会 2002年10月
- AMLの予後不良因子,internal tandem duplication変異Flt3の腫瘍化シグナルの解析水木 満佐央; 松村 到; 上田 周二; Serve Hubert; 金倉 譲日本臨床分子医学会記録 39 22 - 22 日本臨床分子医学会 2002年09月
- R Nanbu-Wakao; Y Morikawa; Matsumura, I; Y Masuho; MA Muramatsu; E Senba; H WakaoMOLECULAR ENDOCRINOLOGY 16 7 1565 - 1576 2002年07月Signal transducer and activator of transcription 5 (Stat5) mediates signaling of many cytokines and growth factors. Here we show that Stat5 functions as an initial mediator of adipogenesis. The preadipocyte cell line 3T3-L1 undergoes adipocyte differentiation upon appropriate hormonal induction. We found that Stat5A and Stat5B were strongly activated at an early stage of 3T3-L1 differentiation. To investigate physiological roles of Stat5 in adipogenesis, we have constructed 3T3-L1 cell lines in which either an exogenous wild type (wt) or dominant negative (dn) form of Stat5A expression was controlled under the doxycycline-regulatable promoter. Precocious induction of wt-Stat5A in adipocyte differentiation promoted accumulation of triglycerides within the cells. In contrast, induction of dn-Stat5A attenuated lipid accumulation. Northern blot analyses revealed that the expression of proadipogenic transcription factors was influenced in a complementary fashion by ectopic expression of either wt- or dn-Stat5A. Notably, Stat5 regulated expression of peroxisome proliferator-activated receptor-gamma, which plays crucial roles in adipogenesis. We have also generated transgenic mice in which dn-Stat5A is expressed in an adipose tissue-specific fashion and found attenuation of peroxisome proliferator-activated receptor-gamma and of many adipocyte-related genes. These results high-light a novel role of Stat5 in adipocyte differentiation.
- Matsumura, I; Y KanakuraINTERNATIONAL JOURNAL OF HEMATOLOGY 75 5 473 - 483 2002年06月Megakaryopoiesis and subsequent thrombopoicsis occur through complex biologic steps: megakaryocyte precursors that developed from hematopoietic stem cells initially proliferate, then differentiate into mature polyploid megakaryocytes, and finally release platelets. Although a number of growth factors can augment megakaryopoiesis in vitro, thrombopoietin is a physiologic and the most potent regulator of megakaryopoiesis in vitro and in vivo. Thrombopoietin induces the growth of megakaryocyte precursors through activation of multiple signaling cascades, including Ras/mitogen-activated protein kinase (MAPK), signal transducers and activators of transcription 5 (STAT5), phosphatidylinositol 3-kinase (PI3-K)/Akt, and protein kinase C, whereas it induces megakaryocytic maturation primarily through the Ras/MAPK pathway. During the maturation step, megakaryocytes undergo polyploidization characterized by repeated rounds of DNA replication without concomitant cell division. During these rounds of replication, cytokinesis is neglected because of the down-regulated expression of AIM-1, and DNA replication occurs through the increased expression of D-type cyclins. As for transcriptional regulation during megakaryopoiesis, GATA-1 plays a central role in the lineage commitment of hematopoietic stem cells toward erythroid/megakaryocytic lineage and subsequent maturation. p45 NF-E2 is essential for platelet release from terminally differentiated megakaryocytes. At present, mutations of GATA-1, AML-1 and HOXA11 genes have been found in hereditary diseases accompanying thrombocytopenia among humans. (C) 2002 The Japanese Society of Hematology.
- Q Yang; K Yamagata; K Fukui; Y Cao; T Nammo; H Iwahashi; HY Wang; Matsumura, I; T Hanafusa; R Bucala; CB Wollheim; J Miyagawa; Y MatsuzawaDIABETES 51 6 1785 - 1792 2002年06月 [査読有り]
Maturity-onset diabetes of the young type 3 (MODY3) is characterized by impaired insulin secretion. Heterozygous mutations in the gene encoding hepatocyte nuclear factor (HNF)-1a are the cause of MODY3. Transgenic mice overexpressing dominant-negative HNF-1alpha mutant in pancreatic beta-cells and HNF-1alpha. knockout mice are animal models of MODY3. These mice exhibit defective glucose-stimulated insulin secretion and have reduced beta-cell mass and beta-cell proliferation rate. Here we examined the effect of HNF-1alpha on beta-cell proliferation by overexpressing a human naturally occurring dominant-negative mutation P291fsinsC in INS-1 cells under the control of doxycycline-induction system. INS-1 cells overexpressing P291fsinsC showed apparent growth impairment. The proliferation rate estimated by [H-3]thymidine incorporation was significantly reduced in P291fsinsC-expressing INS-1 cells compared with non-induced or wild-type HNF-1alpha-overexpressing INS-1 cells. Growth inhibition occurred at the transition from G1 to S cell cycle phase, with reduced expression of cyclin E and upregulation of p27. cDNA array analysis revealed that the expression levels of IGF-1, a major growth factor for beta-cells, and macrophage migration inhibitory factor (MIF), a cytokine expressed in pancreatic beta-cells, were reduced in P291fsinsC-HNF-1alpha-expressing INS-1 cells. Although MIF seemed to have proliferative function, blockade of MIF action by anti-MIF antibody stimulated INS-1 cell proliferation, excluding its direct role in the growth impairment. However, addition of IGF-1 to P291fsinsC-expressing INS-1 cells rescued the growth inhibition. Our data suggest that HNF-1alpha is critical for modulating pancreatic beta-cell growth by regulating IGF-1 expression. IGF-1 might be a potential therapeutic target for the treatment of MODY3. - 松村到; 金倉譲綜合臨床 51 1704 - 1708 2002年05月
- 松村到; 金倉譲綜合臨床 51 1696 - 1699 2002年05月
- S Ueda; M Mizuki; H Ikeda; T Tsujimura; Matsumura, I; K Nakano; H Daino; ZI Honda; J Sonoyama; H Shibayama; H Sugahara; T Machii; Y KanakuraBLOOD 99 9 3342 - 3349 2002年05月Stem cell factor (SCF) has crucial roles In proliferation, survival, and differentiation of hematopoietic stem cells and mast cells through binding to c-Kit receptor (KIT). Chemotaxis Is another unique function of SCF. However, little Is known about the Intracellular signaling pathway of SCF/KIT-mediated cell migration. To Investigate the signaling cascade, we made a series of 22 KIT mutants, In which tyrosine (Y) residue was substituted for phenylalanine (F) In the cytoplasmic domain, and Introduced Into BAF3 cells or 293T cells. On stimulation with SCF, BAF3 expressing KITWT(WT) showed cell migration and Ca2+ mobilization. Among 22 YF mutants, Y567F, Y569F, and Y719F showed significantly reduced cell migration and Ca2+ mobilization compared to WT. In Y567F, Lyn activation on SCIF stimulation decreased and C-terminal Src kinase (Csk) suppressed KIT-mediated Ca2+ Influx and cell migration, suggesting that Y567-mediated Src family kinase (SFK) activation leads to Ca2+ Influx and migration. Furthermore, we found that p38 mitogen-activated protein kinase (p38 MAPK) and Erk1/2 were also regulated by Y567/SFK and Involved In cell migration, and that p38 MAPK induced Ca2+ Influx, thereby leading to Erk1/2 activation. In Y719F, the binding of phosphatidylinositol 3'-kinase (PI3K) to KIT was lost and KIT-mediated cell migration and Ca2+ mobilization were suppressed by PI3K chemical Inhibitors or dominant-negative PI3K, suggesting the Involvement of Y719-mediated PI3K pathway In cell migration. Combination of Csk and the PI3K Inhibitor synergistically reduced cell migration, suggesting the cooperation of SFK and PI3K. Taken together, these results Indicate that 2 major KIT signaling pathways lead to cell migration, one Is Y567-SFK-p38 MAPK-Ca2+ influx-Erk and the other Is Y719-PI3K-Ca2+ influx. (C) 2002 by The American Society of Hematology.
- S Ueda; M Mizuki; H Ikeda; T Tsujimura; Matsumura, I; K Nakano; H Daino; ZI Honda; J Sonoyama; H Shibayama; H Sugahara; T Machii; Y KanakuraBLOOD 99 9 3342 - 3349 2002年05月 [査読有り]
Stem cell factor (SCF) has crucial roles In proliferation, survival, and differentiation of hematopoietic stem cells and mast cells through binding to c-Kit receptor (KIT). Chemotaxis Is another unique function of SCF. However, little Is known about the Intracellular signaling pathway of SCF/KIT-mediated cell migration. To Investigate the signaling cascade, we made a series of 22 KIT mutants, In which tyrosine (Y) residue was substituted for phenylalanine (F) In the cytoplasmic domain, and Introduced Into BAF3 cells or 293T cells. On stimulation with SCF, BAF3 expressing KITWT(WT) showed cell migration and Ca2+ mobilization. Among 22 YF mutants, Y567F, Y569F, and Y719F showed significantly reduced cell migration and Ca2+ mobilization compared to WT. In Y567F, Lyn activation on SCIF stimulation decreased and C-terminal Src kinase (Csk) suppressed KIT-mediated Ca2+ Influx and cell migration, suggesting that Y567-mediated Src family kinase (SFK) activation leads to Ca2+ Influx and migration. Furthermore, we found that p38 mitogen-activated protein kinase (p38 MAPK) and Erk1/2 were also regulated by Y567/SFK and Involved In cell migration, and that p38 MAPK induced Ca2+ Influx, thereby leading to Erk1/2 activation. In Y719F, the binding of phosphatidylinositol 3'-kinase (PI3K) to KIT was lost and KIT-mediated cell migration and Ca2+ mobilization were suppressed by PI3K chemical Inhibitors or dominant-negative PI3K, suggesting the Involvement of Y719-mediated PI3K pathway In cell migration. Combination of Csk and the PI3K Inhibitor synergistically reduced cell migration, suggesting the cooperation of SFK and PI3K. Taken together, these results Indicate that 2 major KIT signaling pathways lead to cell migration, one Is Y567-SFK-p38 MAPK-Ca2+ influx-Erk and the other Is Y719-PI3K-Ca2+ influx. (C) 2002 by The American Society of Hematology. - H Tanaka; Matsumura, I; S Ezoe; Y Satoh; T Sakamaki; C Albanese; T Machii; RG Pestell; Y KanakuraMOLECULAR CELL 9 5 1017 - 1029 2002年05月 [査読有り]
Overexpression of c-Myc or E2F1 sensitizes host cells to various types of apoptosis. Here, we found that overexpressed c-Myc or E2F1 induces accumulation of reactive oxygen species (ROS) and thereby enhances serum-deprived apoptosis in NIH3T3 and Saos-2. During serum deprivation, MnSOD mRNA was induced by NF-kappaB in mock-transfected NIH3T3, while this induction was inhibited in NIH3T3 overexpressing c-Myc or E2F1. In these clones, E2F1 inhibited NF-kappaB activity by binding to its subunit p65 in competition with a heterodimeric partner p50. In addition to overexpressed E2F1, endogenous E2F1 released from Rb was also found to inhibit NF-kappaB activity in a cell cycle-dependent manner by using E2F1(+/+) and E2F1(-/-) murine embryonic fibroblasts. These results indicate that E2F1 promotes apoptosis by inhibiting NF-kappaB activity. - 水木満佐央; 松村到; 池田弘和; 上田周二; 園山順子; 小田嶋純子; 金倉譲臨床血液 43 4 239 - 242 日本臨床血液学会 2002年04月
- 松村到; 金倉譲月刊細胞 34 4 150 - 153 ニュー・サイエンス社 2002年04月
- AMLの予後不良因子,internal tandem duplication変異Flt3の腫瘍化シグナルの解析水木 満佐央; 松村 到; 上田 周二; 金倉 譲; Serve Hubert日本臨床分子医学会学術総会プログラム・抄録集 39回 28 - 28 日本臨床分子医学会 2002年03月
- J Sonoyama; Matsumura, I; S Ezoe; Y Satoh; Zhang, X; Y Kataoka; E Takai; M Mizuki; T Machii; H Wakao; Y KanakuraJOURNAL OF BIOLOGICAL CHEMISTRY 277 10 8076 - 8082 2002年03月 [査読有り]
BCR/ABL tyrosine kinase generated from the chromosomal translocation t(9;22) causes chronic myelogenous leukemia and acute lymphoblastic leukemia. To examine the roles of BCR/ABL-activated individual signaling molecules and their cooperation in leukemogenesis, we inducibly expressed a dominant negative (DN) form of Ras, phosphatidylinositol 3-kinase, and STAT5 alone or in combination in p210 BCR/ABL-positive K562 cells. The inducibly expressed DN Ras (N17), STAT5 (694F), and DN phosphatidylinositol 3-kinase (Deltap85) inhibited the growth by 90, 55, and 40%:, respectively. During the growth inhibition, the expression of cyclin D2 and cyclin D3 was suppressed by N17, 694F, or Deltap85; that of cyclin E by N17; and that of cyclin A by Deltap85. In addition, N17 induced apoptosis in a small proportion of K562, whereas 694F and DeltapS5 were hardly effective. In contrast, coexpression of two DN mutants in any combinations induced severe apoptosis. During these cultures, the expression of Bcl-2 was suppressed by N17, 694F, or Deltap85, and that of Bcl-XL by N17. Furthermore, although K562 was resistant to interferon-alpha- and dexamethasone-induced apoptosis, disruption of one pathway by N17, 694F, or Deltap85 sensitized K562 to these reagents. These results suggested that cooperation among these molecules is required for full leukemogenic activities of BCR/ABL. - Hepatocyte nuclear factor-1a modulates pancreatic beta-cell growth by regulating the expression of insulin-like growth factor-1 in INS-1 cellsYang Q; Yamagata K; Fukui K; Cao Y; Nammo T; Iwahashi H; Wang H; Matsumura I; Hanafusa T; Bucala R; Wollheim CB; Miyagawa J; Matsuzawa YDiabetes 51:1785-1792 2002年
- 金倉譲; 松村到日本臨床 59 12 2304 - 2307 日本臨床社 2001年12月
- Internal tandem duplication変異flt3による腫瘍化シグナルの解析水木 満佐央; 松村 到; 金倉 譲日本癌学会総会記事 60回 505 - 505 (一社)日本癌学会 2001年09月
- 松村到; 金倉譲血液フロンティア 11 5 547 - 557 2001年05月
- 松村到; 金倉譲血液フロンティア 11 4 405 - 417 2001年04月
- 松村到; 台野華子; 金倉譲月刊血液・腫よう科 42 3 271 - 277 2001年03月
- Oncogenic tyrosine kinase in hematological malignancy ミ signal transduction and targeting therapy-Mizuki M; Ueda S; Matsumura I; Kanakura YRes. Adv. in Blood 1:35-46 2001年
- A Kawasaki; Matsumura, I; J Miyagawa; S Ezoe; H Tanaka; Y Terada; M Tatsuka; T Machii; H Miyazaki; Y Furukawa; Y KanakuraJOURNAL OF CELL BIOLOGY 152 2 275 - 287 2001年01月During the late phase of megakaryopoiesis, megakaryocytes undergo polyploidization, which is characterized by DNA duplication without concomitant cell division. However, it remains unknown by which mechanisms this process occurs. AIM-1 and STK15 belong to the Aurora/increase-in-ploidy (Ip1)1 serine/threonine kinase family and play key roles in mitosis. In a human interleukin-3-dependent cell line, F-36P, the expressions of AIM-1 and STK15 mRNA were specifically observed at G2/M phase of the cell cycle during proliferation. In contrast, the expressions of AIM-1 and STK15 were continuously repressed during megakaryocytic polyploidization of human erythro/megakaryocytic cell lines (F-36P, K562, and CMK) treated with thrombopoietin, activated ras (H-ras(G12V)), or phorbol ester. Furthermore, their expressions were suppressed during thrombopoietin-induced polyploidization of normal human megakaryocytes. Activation of AIM-1 by the induced expression of AIM-l(wild-type) canceled TPA-induced polyploidization of K562 cells significantly, whereas that of STK15 did not. Moreover, suppression of AIM-1 by the induced expression of AIM-1 (K/R, dominant-negative type) led to polyploidization in 25% of K562 cells, whereas STK15(K/R) showed no effect. Also, the induced expression of AIM-1(K/R) in CMK cells provoked polyploidization up to 32N. These results suggested that downregulation of AIM-1 at M phase may be involved in abortive mitosis and polyploid formation of megakaryocytes.
- Molecular mechanisms of megakaryopoiesis and thrombopoiesis and their dysregulation in hematologic disordersMatsumura I; Zhang X; Takai E; Kanakura YRes. Adv. in Blood 1:23-34 2001年
- M Mizuki; R Fenski; H Halfter; Matsumura, I; R Schmidt; C Muller; R Gruning; K Kratz-Abers; S Serve; C Steur; T Buchner; J Kienast; Y Kanakura; WE Berdel; H ServeBLOOD 96 12 3907 - 3914 2000年12月Somatic mutations of the receptor tyrosine kinase Flt3 consisting of internal tandem duplications (ITD) occur in 20% of patients with acute myeloid leukemia. They are associated with a poor prognosis of the disease. In this study, we characterized the oncogenic potential and signaling properties of Flt3 mutations. We constructed chimeric molecules that consisted of the murine Flt3 backbone and a 510-base pair human Flt3 fragment, which contained either 4 different ITD mutants or the wild-type coding sequence, Flt3 isoforms containing ITD mutations (Flt3-ITD) induced factor-independent growth and resistance to radiation-induced apoptosis in 32D cells. Cells containing Flt3-ITD, but not those containing wild-type Flt3 (Flt3-WT), formed colonies in methylcellulose. Injection of 32D/Flt3-ITD induced rapid development of a leukemia-type disease in syngeneic mice. Flt3-ITD mutations exhibited constitutive autophosphorylation of the immature form of the Flt3 receptor. Analysis of the involved signal transduction pathways revealed that Flt3-ITD only slightly activated the MAP kinases Erk1 and 2 and the protein kinase B (Akt) in the absence of ligand and retained ligand-induced activation of these enzymes, However, Flt3-ITD led to strong factor-independent activation of STAT5. The relative importance of the STAT5 and Ras pathways for ITD-induced colony formation was assessed by transfection of dominant negative (dn) forms of these proteins: transfection of dnSTAT5 inhibited colony formation by 50%, Despite its weak constitutive activation by Flt3D-ITD, dnRas also strongly inhibited Flt3-ITD-mediated colony formation. Taken together, Flt3-ITD mutations induce factor-independent growth and leukemogenesis of 32D cells that are mediated by the Ras and STAT5 pathways. (C) 2000 by The American Society of Hematology.
- 松村到; 金倉譲日本医師会雑誌 124 8 34 - 38 2000年10月
- Matsumura, I; A Kawasaki; H Tanaka; J Sonoyama; S Ezoe; N Minegishi; K Nakajima; M Yamamoto; Y KanakuraBLOOD 96 7 2440 - 2450 2000年10月Lineage-specific transcription factors play crucial roles in the development of hematopoietic cells. In a previous study, it was demonstrated that Has activation was involved in thrombopoietin-induced megakaryocytic differentiation. In this study, constitutive Has activation by H-ras(G12V) evoked megakaryocytic maturation of erythroleukemia cell lines F-36P and K562, but not of myeloid cell line 32D c13 that lacks GATA-1. However, the introduction of GATA-1 led to reprogramming of 32D c13 toward erythrocytic/megakaryocytic lineage and enabled it to undergo megakaryocytic differentiation in response to H-ras(G12V). In contrast, the overexpression of PU.1 and c-Myb changed the phenotype of K562 from erythroid to myeloid/monocytic lineage and rendered K562 to differentiate into granulocytes and macrophages in response to H-ras(G12V), respectively. In GATA-1-transfected 32D c13, the endogenous expression of PU.1 and c-Myb was easily detectable, but their activities were reduced severely. Endogenous GATA-1 activities were markedly suppressed in PU.1-transfected and c-myb-transfected K562. As for the mechanisms of these reciprocal inhibitions, GATA-1 and PU.1 were found to associate through their DNA-binding domains and to inhibit the respective DNA-binding activities of each other. In addition, c-Myb bound to GATA-1 and inhibited its DNA-binding activities. Mutant GATA-1 and PU.1 that retained their own transcriptional activities but could not inhibit the reciprocal partner were less effective in changing the lineage phenotype of 32D c13 and K562. These results suggested that GATA-1 activities may be crucial for Has-mediated megakaryocytic differentiation and that its activities may be regulated by the direct interaction with other lineage-specific transcription factors such as PU.1 and c-Myb. (Blood. 2000;96:2440-2450) (C) 2000 by The American Society of Hematology.
- 松村到; 金倉譲綜合臨床 49 10 2553 - 2558 2000年10月
- 松村到; 金倉譲分子細胞治療 1 5 454 - 460 2000年10月
- 松村到; 金倉譲実験医学 18 15 2167 - 2174 2000年09月
- M Ogawa; T Nishiura; K Oritani; H Yoshida; M Yoshimura; Y Okajima; J Ishikawa; K Hashimoto; Matsumura, I; Y Tomiyama; Y MatsuzawaCANCER RESEARCH 60 15 4262 - 4269 2000年08月A new human myeloma cell line, OPM-6, was established from the peripheral blood of a patient with advanced IgG-kappa plasma cell leukemia. Cytogenetic and phenotypic analysis confirmed that the cells were derived from the patient's Leukemic cells. Insulin-like growth factor-1 (IGF-1) acts as an autocrine growth factor in these cells. In addition, OPM-6 cells were particularly sensitive to dexamethasone (DEX), when endogenous IGF-1 was blocked. Under these conditions, >95% of the DEX-treated cells died within 36 h. Therefore, OPM-6 represents a potentially powerful tool for the analysis of the molecular mechanisms of DEX-induced apoptosis, because it is possible to easily analyze the direct effects of DEX using this system. Using this culture system of OPM-6, we demonstrated that the treatment with DEX plus a monoclonal antibody to the human IGF-1 receptor (alpha IGF-1R) leads to the down-regulation of the gene expression of Bcl-xL, an antiapoptotic gene, and the activation of CPP32 during this apoptotic process. IFN-alpha as well as IL-6 prevented DEX plus alpha IGF-1R-induced apoptosis, and this prevention was blocked by the mitogen-activated protein kinase kinase inhibitor, PD098059, or the phosphatidylinositol 3-kinase inhibitor, wortmannin. Therefore, both IL-6 and IFN-alpha blocked DEX plus alpha IGF-1R-induced apoptosis through activation of the mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways.
- J Odajima; Matsumura, I; J Sonoyama; H Daino; A Kawasaki; H Tanaka; N Inohara; T Kitamura; J Downward; K Nakajima; T Hirano; Y KanakuraJOURNAL OF BIOLOGICAL CHEMISTRY 275 31 24096 - 24105 2000年08月Tyrosine kinase oncoproteins cause simultaneous activation of multiple intracellular signaling pathways. However, the precise mechanisms by which individual pathways induce oncogenesis are not well understood. We have investigated the roles of individual signaling pathways in v-Src-dependent cell growth and survival by inhibiting one particular pathway. v-Src induced constitutive activation of signal transducers and activators of transcription 3 (STAT3), phosphatidylinositol 3-kinase, and Res in murine Ba/F3 cells and led to factor-independent proliferation. Dominant-negative mutants of STAT3 (STAT3D) and phosphatidylinositol 3-kinase (Delta p85) inhibited v-Src-dependent growth by similar to 60 and similar to 40%, respectively. Moreover, dominant-negative Res (N17) induced severe apoptosis, which was accompanied by down regulation of Bcl-2 and activation of caspase-3. Although cells overexpressing Bcl-2 or caspase-3 inhibitors remained viable even when N17 was expressed, the growth was reduced by similar to 85%. During N17- and STAT3D-induced growth suppression, expression of cyclin D2, cyclin D3, c-myc, and c-fos was suppressed by N17, whereas that of cyclin D2, cyclin E, and c-myc was suppressed by STAT3D, Thus, v-Src-activated Ras and STAT3 are involved in distinct but partly overlapping transcriptional regulation of cell cycle regulatory molecules. These results suggest that the full oncogenic activity of v-Src requires simultaneous activation of multiple signalings, in which Ras is particularly required for survival.
- H Yoshida; Y Tomiyama; J Ishikawa; K Oritani; Matsumura, I; M Shiraga; T Yokota; Y Okajima; M Ogawa; J Miyagawa; T Nishiura; Y MatsuzawaBLOOD 96 1 234 - 241 2000年07月Cell migration requires a dynamic interaction between the cell, its substrate, and the cytoskeleton-associated motile apparatus. Integrin-associated protein (IAP)/ CD47 is a 50-kd cell surface protein that is physically associated with beta 3 integrins and that modulates the functions of beta 3 integrins in various cells. However, in B-lymphocytes that express beta 1 integrins but few beta 3 integrins, the roles of IAP/ CD47 remain to be determined. Cross-linking of IAP/CD47 by the immobilized anti-IAP/CD47 monoclonal antibody (mAb) B6H12, but not 2D3, produced signals to promote polarization with lamellipodia, a characteristic morphology during leukocyte migration, in pre-B and mature B-cell lines (BALL, Nalm6, ONHL-1, Daudi), but not in myeloma cell lines (RPM18226, OPM-2). In the presence of the immobilized fibronectin (FN), soluble B6H12 could increase the rate of the polarization and activate migratory activity of BALL cells to FN in a transwell filter assay. Furthermore, the dominant-negative form of CDC42 completely blocked B6H12-induced morphologic and functional changes without inhibiting phorbol 12-myristate 13-acetate-induced spreading on FN in BALL cells, whereas the dominant-negative form of Rac1 inhibited all these changes. These findings demonstrate that in B lymphocytes, IAP/CD47 may transduce the signals to activate the migratory activity, in which CDC42 may be specifically involved, end that IAP/ CD47 shows synergistic effect with alpha 4 beta 1 on B cell migration. These findings would provide new insight into the role of IAP/CD47 on B-cell function. (Blood. 2000; 96:234-241) (C) 2000 by The American Society of Hematology.
- H Daino; Matsumura, I; K Takada; J Odajima; H Tanaka; S Ueda; H Shibayama; H Ikeda; M Hibi; T Machii; T Hirano; Y KanakuraBLOOD 95 8 2577 - 2585 2000年04月The ubiquitin-proteasome pathway is responsible for selective degradation of short-lived cellular proteins and is critical for the regulation of many cellular processes. We previously showed that ubiquitin (Ub) secreted from hairy cell leukemia cells had inhibitory effects on clonogenic growth of normal hematopoietic progenitor cells. In this study, we examined the effects of exogenous Ub on the growth and survival of a series of human hematopoietic cells, including myeloid cell lines (HL-60 and U937), a B-cell line (Daudi), and T-cell lines (KT-3, MT-4, YTC-3, and MOLT-4), Exogenous Ub inhibited the growth of Various hematopoietic cell lines tested, especially of KT-3 and HL-60 cells. The growth-suppressive effects of Ub on KT-3 and HL-60 cells were almost completely abrogated by the proteasome inhibitor PSI or MG132, suggesting the involvement of the proteasome pathway in this process. Furthermore, exogenous Ub evoked severe apoptosis of KT-3 and HL-60 cells through the activation of caspase-3, In interleukin-6 (IL-6)-dependent KT-3 cells, STAT3 was found to be conjugated by exogenous biotinylated Ub and to be degraded in a proteasome-dependent manner, whereas expression levels of STAT1, STAT5, or mitogen-activated protein kinase were not affected. Moreover, IL-6-induced the up-regulation of Bcl-2 and c-myc, and JunB was impaired in Ub-treated KT-3 cells, suggesting that the anti-apoptotic and mitogenic effects of IL-6 were disrupted by Ub, These results suggest that extracellular Ub was incorporated into hematopoietic cells and mediated their growth suppression and apoptosis through proteasome-dependent degradation of selective cellular proteins such as STAT3, (Blood, 2000;95:2577-2585) (C) 2000 by The American Society of Hematology.
- H Tanaka; Matsumura, I; K Nakajima; H Daino; J Sonoyama; H Yoshida; K Oritani; T Machii; M Yamamoto; T Hirano; Y KanakuraBLOOD 95 4 1264 - 1273 2000年02月Cytokines exert pleiotropic effects on target cells in a manner dependent on the cell type or stage of differentiation. To determine how instinctive cell properties affect biological effects of cytokine, we introduced an erythroid/megakaryocyte lineage-specific transcription factor, GATA-1, into a murine myeloid cell line MI, which is known to undergo macrophage differentiation in response to interleukin 6 (IL-6). Overexpression of GATA-1 changed the phenotype of M1 cells from myeloid to megakaryocytic lineage. Furthermore, GATA-1 blocked both IL-6-induced macrophage differentiation and apoptosis of M1 cells. Although STAT3 is essential for IL-6-induced macrophage differentiation of M1 cells, GATA-1 had little or no effect on tyrosine phosphorylation, DNA binding, and transcriptional activities of STAT3 in Western blot analysis, electropholic mobility shift assay (EMSA), and luciferase assays. During IL-6-induced macrophage differentiation of M1 cells, IL-6 down-regulated cyclin D1 expression and induced p19(INK4D) expression, reading to reduction in cdk4 activities. In contrast, sustained expression of cyclin Dt and a significantly lesser amount of p19(INK4D) induction were observed in IL-6-treated M1 cells overexpressing GATA-1. Furthermore, although bcl-2 expression was severely reduced by IL-6 in M1 cells, it was sustained in GATA-1-introduced M1 cells during the culture with IL-6, Both IL-6-induced macrophage differentiation and apoptosis were significantly abrogated by coexpression of cyclin D1 and bcl-2, whereas overexpressions of cyclin D1 or bcl-2 inhibited only differentiation or apoptosis, respectively. These results suggested that GATA-1 may not only reprogram the lineage phenotype of M1 cells but also disrupt the biologic effects of IL-6 through the sustained expression of cyclin D1 and bcl-2. (C) 2000 by The American Society of Hematology.
- Matsumura, I; H Tanaka; A Kawasaki; J Okajima; H Daino; K Hashimoto; H Wakao; K Nakajima; T Kato; H Miyazaki; Y KanakuraJOURNAL OF BIOLOGICAL CHEMISTRY 275 8 5553 - 5559 2000年02月At the late phase of megakaryocytopoiesis, megakaryocytes undergo endomitosis, which is characterized by DNA replication without cell division. Although a number of cell. cycle regulatory molecules have been identified, the precise roles of these molecules in megakaryocytic endomitosis are largely unknown. In a human interleukin-3-dependent cell line transfected with the thrombopoietin (TPO) receptor c-mpl (F-36P-mpl), either treatment with TPO or the overexpression of activated ras (Ha-Ras(G12V)) induced megakaryocytic maturation with polyploid formation, We found that TPO stimulation or Ha-Ras(G12V) expression led to up-regulation of cyclin D1, cyclin D2, and cyclin D3 expression. In addition, expression levels of cyclin A and cyclin B were reduced during the total course of both TPO- and Ha-Ras(G12V)-induced megakaryocytic differentiation, thereby leading to decreased cdc2 kinase activity. Neither the induced expression of cyclin DI, cyclin D2, or cyclin D3 nor the expression of a dominant negative form of cdc2 alone could induce megakaryocytic differentiation of F-36P-mpl cells. In contrast, overexpression of dominant negative cdc2 together with cyclin D1, cyclin D2, or cyclin D3 facilitated megakaryocytic differentiation in the absence of TPO. These results suggest that both D-type cyclin expression and decreased cdc2 kinase activity may participate in megakaryocytic differentiation.
- 松村到; 金倉譲Annual Review 血液 2000 58 - 63 2000年01月
- K Uozumi; M Otsuka; N Ohno; T Moriyama; S Suzuki; S Shimotakahara; Matsumura, I; S Hanada; T ArimaLEUKEMIA 14 1 142 - 152 2000年01月A new factor-independent megakaryoblastic cell line, designated SET-2, was established from the peripheral blood of a patient with leukemic transformation of essential thrombocythemia (ET), SET-2 expressed CD 4, 7, 13, 33, 34, 36, 38, 41, 61, 71, 117, 126, 130 and c-mpl, In addition, it spontaneously produced numerous platelet-like particles in liquid culture. These particles were shown to be the same size as normal platelets, and to express CD 36, 38, 41, 61 and 71, Proliferation of SET-2 was not influenced by thrombopoietin (TPO) and other hemopoietic cytokines, SET-2 was found to express the platelet-specific proteins such as platelet factor 4 and P-thromboglobulin. The levels of expression were not altered by TPO, SET-2 also secreted interleukin-6 into the supernatants, as well as normal megakaryocytes, These results suggest that SET-P spontaneously matures to megakaryocytes and produces platelet-like particles. These findings indicate that SET-2 may be useful for investigating the proliferation and differentiation mechanisms of leukemia cells and the role of c-mpl on megakaryoblasts, megakaryocytes, and platelets in ET.
- 松村到; 金倉譲日本内科学会雑誌 88 12 2487 - 2492 (一社)日本内科学会 1999年12月トロンボポエチン(TPO)は,血小板産生を促進する造血因子としてクローニングされ,数多くのin vitroの研究やノックアウトマウスの結果から, TPOは巨核球系細胞の増殖・分化制御において最も重要な造血因子であることが明らかとなってきた.最近, TPO受容体c-mplは巨核球系細胞のみでなく,造血系を再構築する能力のある多能性造血幹細胞(PHSC)にも発現していることが証明された.また, TPOは単独あるいはIL-3, SCFなどの造血因子と協調してPHSCをPHSCの性格を維持したまま増幅させる能力を有していた.更に, TPOのin vivoへの投与は,抗癌剤などによる骨髄抑制後の血小板数の回復ばかりでなく,貧血や白血球数の回復にも有効であること,末梢血への幹細胞の動員作用も有していることが示された.今後, TPOは血小板増加促進因子としてのみでなく, in vitro, in vivoでの造血幹細胞に対する増殖誘導因子としてもその臨床応用が期待される.
- 松村到; 金倉譲血液フロンティア 9 12 1389 - 1391 1999年12月
- 松村到臨床血液 40 4 275 - 279 日本臨床血液学会 1999年04月
- 松村到; 金倉譲Medicina 36 4 630 - 631 1999年04月
- Matsumura, I; T Kitamura; H Wakao; H Tanaka; K Hashimoto; C Albanese; J Downward; RG Pestell; Y KanakuraEMBO JOURNAL 18 5 1367 - 1377 1999年03月STAT5 is a member of a family of transcription factors that participate in the signal transduction pathways of many hormones and cytokines, Although STAT5 is suggested to play a crucial role in the biological effects of cytokines, its downstream target(s) associated with cell growth control is largely unknown. In a human interleukin-3 (IL-3)-dependent cell line F-36P-mpl, the induced expression of dominant-negative (dn)-STAT5 and of dn-ras led to inhibition of IL-3-dependent cell growth, accompanying the reduced expression of cyclin D1 mRNA. Also, both constitutively active forms of STAT5A (1*6-STAT5A) and ras (H-ras(G12V)) enabled F-36P-mpl cells to proliferate without added growth factors. In NIH 3T3 cells, 1*6-STAT5A and N-ras(G12V) individually and cooperatively transactivated the cyclin D1 promoter in luciferase assays. Both dn-STAT5 and dn-ras suppressed IL-3-induced cyclin D1 promoter activities in F-36P-mpl cells, Using a series of mutant cyclin DI promoters, 1*6-STAT5A was found to transactivate the cyclin D1 promoter through the potential STAT-binding sequence at -481 bp, In electrophoretic mobility shift assays, STAT5 bound to the element in response to IL-3, Furthermore, the inhibitory effect of dn-STAT5 on IL-3-dependent growth was restored by expression of cyclin DI, Thus STAT5, in addition to ras signaling, appears to mediate transcriptional regulation of cyclin D1, thereby contributing to cytokine-dependent growth of hematopoietic cells.
- 松村到; 金倉譲血液フロンティア 9 3 261 - 267 1999年03月
- T Tsujimura; K Hashimoto; H Kitayama; H Ikeda; H Sugahara; Matsumura, I; T Kaisho; N Terada; Y Kitamura; Y KanakuraBLOOD 93 4 1319 - 1329 1999年02月The c-kit receptor tyrosine kinase (KIT) is constitutively activated by naturally occurring mutations in either the juxtamembrane domain or the kinase domain. Although the juxtamembrane domain mutations led to ligand-independent KIT dimerization, the kinase domain mutations (Asp(814)-->Val or Tyr) did not. In an effort to determine if the kinase domain mutant could transfer oncogenic signaling without receptor dimerization. we have constructed the truncated types of c-kit(Wild) and c-kitTyr(814) cDNAs (c-kit(Del-Wild) and c-kit(Del-Tyr814) cDNAs, respectively), in which ligand-binding and ligand-induced dimerization domains were deleted. When c.kit(Del-Wild) and c-kit(Del-Tyr814) genes were introduced into a murine interleukin-3 (IL-3)-dependent cell line Ba/F3, KITDel-Tyr814 was constitutively phosphorylated on tyrosine and activated, whereas KITDel-Wild was not. In addition, Ba/F3 cells expressing KITDel-Tyr814 (Ba/F3(Del-Tyr814)) grew in suspension culture without the addition of exogenous growth factor, whereas Ba/F3 cells expressing KITDel-Wild (Ba/F3(Del-Wild)) required IL-3 for growth. The factor-independent growth of Ba/F3(Del-Tyr814) cells was virtually abrogated by coexpression of KITW42 that is a dominant-negative form of KIT, but not by that of KITWild, suggesting that KITDel-Tyr814 may not function as a monomer but may require receptor dimerization for inducing factor-independent growth. Furthermore, KITDel-Tyr814 was found to be coimmunoprecipitated with KITWild Or KITW42 by an ACK2 monoclonal antibody directed against the extracellular domain of KIT. Moreover, KITW42 was constitutively associated with a chimeric FMS/KITTyr814 receptor containing the ligand-binding and receptor dimerization domain of c-fms receptor (FMS) fused to the transmembrane and cytoplasmic domain of KITTyr814. but not with a chimeric FMS/KITWild receptor even after stimulation with FMS-ligand. These results suggest that constitutively activating mutation of c-kit at the Asp(814) codon may cause a conformation change that leads to receptor self-association not in the extracellular domain and that the receptor self-association of the Asp(814) mutant may be important for activation of downstream effecters that are required for factor-independent growth and tumorigenicity. (C) 1999 by The American Society of Hematology.
- K Oritani; Y Tomiyama; PW Kincade; K Aoyama; T Yokota; Matsumura, I; Y Kanakura; K Nakajima; T Hirano; Y MatsuzawaBLOOD 93 4 1346 - 1354 1999年02月A unique subclone of a bone marrow-derived stromal cell line, BMS2.4, produces soluble factors that inhibit proliferation of several types of hematopoietic cell lines. An understanding of these molecules may be informative about negative regulatory circuits that can potentially limit blood cell formation. We used expression cloning to identify interleukin-g (IL-6) as one factor that suppressed growth of a pre-B-cell variant line, 1A9-M. Moreover, IL-6 induced macrophage-differentiation and apoptosis of 1A9-M cells. During this process, IL-6 downregulated expression of BCL2 in 1A9-M cells and stimulated BCL-XL expression, but had no effect on p53, Bar, or Bak gene expression. Mechanisms for transduction of IL-6-induced signals were then evaluated in Il-Gi-stimulated 1A9-M cells. Whereas the signal transducer and activator of transcription 3 (Stat3) was phosphorylated and activated, there was no effect on either Stat1 or Stat5. The importance of BCL2 and Stat3 on Ib-fi-induced macrophage-differentiation and apoptosis was studied with 1A9-M cells expressing human BCL2 or a dominant-negative form of Stat3, respectively. IL-6-induced apoptosis, but not macrophage-differentiation, was blocked by continuously expressed BCL2. A dominant-negative form of Stat3 inhibited both macrophage-differentiation and apoptosis induced by IL-6. However, diminished Stat3 activity did not prevent IL-6-induced downregulation of the BCL2 gene. Therefore, activation of Stat3 is essential for IL-6-induced macrophage-differentiation and programmed cell death in this model. Whereas overexpression of BCL2 abrogates the apoptotic response, Stat3-independent signals appear to downregulate expression of the BCL2 gene. (C) 1999 by The American Society of Hematology.
- 松村到; 金倉譲Annual Review 血液 1999 173 - 177 1999年01月
- T Nagase; S Kawata; H Nakajima; S Tamura; E Yamasaki; K Fukui; K Yamamoto; J Miyagawa; Matsumura, I; T Matsuda; Y MatsuzawaINTERNATIONAL JOURNAL OF CANCER 80 1 126 - 133 1999年01月A series of studies using farnesyltransferase (FTase) inhibitors that the inhibition of FTase function suppresses the growth of res-transformed cells in vitro and in vivo, However, whether FTase is directly involved in the regulation of cell proliferation remains to be demonstrated, To investigate whether overexpression of FTase results in altered cell growth and transformation, we thus used NIH3T3 cells transfected with cDNA constructs of both alpha and beta subunits of human FTase, FTase-overexpressing cells resulted in a 3- to 13-fold increase in the expression of the alpha and beta subunit protein of FTase and a 1.5- to 3-fold increase in the level of the enzyme activity compared with untransfected NIH3T3 cells or vector-transfected cells. Further investigations using metabolic labeling indicated that farnesylation of Ras was enhanced in FTase-overexpressing cells. Insulin-like growth factor-1, platelet-derived growth factor (PDCF), and basic fibroblast growth factor (bFCF) more potently enhanced DNA synthesis and anchorage-dependent growth in FTase-overexpressing cells than in control cells, in a dose-dependent manner. In particular, PDGF and bFGF also induced dose-dependently enhanced colony formation in soft agar in FTase-overexpressing cells. Furthermore, in FTase-transfectants, bFGF stimulated high activation of mitogen-activated protein kinase. Interestingly, FTase transfectants developed progressive tumors in nude mice. Light and electron microscopy showed that the tumors were characteristic of fibrosarcoma, which were distinct from v-ros-induced tumors. Overexpression of FTase in NIH3T3 cells thus amplifies growth-factor-mediated cell growth and transformation, and FTase-overexpressing cells form tumors in nude mice. (C) 1999 Wiley-Liss, Inc.
- Matsumura, I; Y Horikawa; Y KanakuraLEUKEMIA & LYMPHOMA 32 3-4 351 - 358 1999年01月Thrombopoietin (TPO) is implicated as a primary regulator of megakaryopoiesis and thrombopoiesis through binding to the cytokine receptor c-Mpl (the product of the c-mpl-proto-oncogene). In addition to its physiologic role, the TPO-c-mpl system has been suggested to participate in the pathophysiology of essential thrombocythemia (ET) which is a clonal disorder characterized by a sustained elevation of the circulating platelet count and bane-marrow hyperplasia with excessive proliferation of megakaryocytes. Recent studies have demonstrated that serum TPO levels are slightly elevated or within normal range in ET patients, whereas serum TPO levels tend to be inversely correlated with platelet mass. Flow cytometric, Western blot, and Northern blot analyses have revealed that the expression of platelet c-Mpl is strikingly reduced in all of patients with ET,possibly due to the decreased expression of c-mpl mRNA. These results suggest that normal or slightly elevated levels of serum TPO in ET patients may be attributable to the impaired uptake and catabolism of TPO owing to the low c-Mpl expression. Furthermore, immunoblotting with anti-phosphotyrosine antibody showed that no aberrant protein-tyrosine phosphorylation was observed in platelets of ET patients before treatment with TPO, and the levels of TPO-induced protein-tyrosine phosphorylation, including c-Mpl-tyrosyl phosphorylation, roughly paralleled those of c-Mpl expression, suggesting that c-Mpl-mediated Signaling pathway was not constitutively activated in platelets of ET patients. Although activating mutation in the TPO gene, which leads to overexpression of TPO mRNA, has been reported in familial thrombocythemia, these results suggest that TPO-c-Mpl system may not be directly linked to pathogenesis of sporadic ET.
- 金倉譲; 松村到; 池田弘和; 北山等血液系疾患調査研究班特発性造血障害分科会 平成10年度研究業績報告書 52 1999年
- 金倉譲; 松村到再生不良性貧血について治療薬の組み合わせを評価する多施設共同研究 平成10年度研究業績報告書 厚生省重点研究事業 33 1999年
- 松村到; 金倉譲綜合臨床 48 1 187 - 188 1999年01月
- H Yoshida; T Nishiura; T Karasuno; Matsumura, I; J Ishikawa; M Yoshimura; T Yokota; Y Okajima; M Ogawa; Y Kanakura; Y Tomiyama; Y MatsuzawaBRITISH JOURNAL OF HAEMATOLOGY 103 3 804 - 812 1998年12月Very late antigen (VLA)-4 integrin has been suggested to play an important role in haemopoiesis. However, little is known concerning the roles of the fibronectin (FN)/VLA-4 interaction in the proliferation of human B cells, In this study we investigated the effect of immobilized FN on the proliferation of various B-cell lines, including a newly-established B-cell line, OPM-3, and human tonsillar B cells, that primarily express VLA-4 but not VLA-5. Immobilized FN significantly promoted the proliferation of OPM-3 cells and normal B cells via VLA-4. The cross-linking of beta 1 integrins of OPM-3 cells resulted in the phosphorylation of the focal adhesion kinase (FAK) associated 90 kD protein, an increase in FAK-associated kinase activity and the phosphorylation of Raf-l. Furthermore, the MEK1 inhibitor, PD98059, inhibited the FN-promoted proliferation of OPM-3 cells. These results demonstrate that the FN/VLA-4 interaction transmits the growth signal(s) which may be mediated by Ras pathway in OPM-3 cells, and suggest that OPM-3 cells may be of great value in studying the roles of the FN/VLA-4 interaction in human B-cell growth.
- M Ogawa; T Nishiura; M Yoshimura; Y Horikawa; H Yoshida; Y Okajima; Matsumura, I; J Ishikawa; H Nakao; Y Tomiyama; Y Kanayama; Y Kanakura; Y MatsuzawaEUROPEAN JOURNAL OF CLINICAL INVESTIGATION 28 11 937 - 943 1998年11月Background L-Arginine (L-Arg), one of the essential amino acids, has been reported to have an immunomodulatory effect. The precise mechanism of the L-Arg-induced natural killer (NK) cell activation remains unresolved,and the effect of L-Arg on NK cells in chronic fatigue syndrome (CFS) patients has not been estimated. Methods NK cell function was evaluated in 20 subjects with CFS and compared with that in 21 healthy individuals. Results In healthy control subjects, NK activity was significantly increased after treatment with L-Arg, an NK function enhancer, for 24h, whereas the same treatment failed to enhance NK activity in the CFS patients. We thus focused on L-Arg metabolism, which involves nitric oxide (NO) production through NO synthase (NOS). The expression of inducible NO synthase (iNOS) transcripts in peripheral blood mononuclear cells was not significantly different between healthy control subjects and CFS patients. The L-Arg-mediated NK cell activation was abolished by addition of N-G-monomethyl-L-arginine, an inhibitor for iNOS. Furthermore, incubation with S-nitroso-N-acetyl-penicillamine, an NO donor, stimulated NK activity in healthy control subjects but not in CFS patients. Conclusion These results demonstrate that the L-Arg-induced activation of NK activity is mediated by NO and that a possible dysfunction exists in the NO-mediated NK Cell activation in CFS patients.
- 金倉譲; 西村純一; 池田弘和; 松村到最新医学 53 2462 - 2474 1998年10月
- Y Okajima; Matsumura, I; T Nishiura; K Hashimoto; H Yoshida; J Ishikawa; H Wakao; A Yoshimura; Y Kanakura; Y Tomiyama; Y MatsuzawaJOURNAL OF BIOLOGICAL CHEMISTRY 273 36 22877 - 22883 1998年09月Insulin-like growth factor (IGF-I) is known to synergistically stimulate the proliferation of hematopoietic cells in combination with other hematopoietic growth factors. However, the precise mechanism underlying the cooperative effects of IGF-I is unknown. In a human interleukin-3 or erythropoietin (EPO)-dependent cell line, F-36P, IGF-I alone failed to stimulate DNA synthesis but did augment the EPO dependent DNA synthesis of F-36P cells. The treatment of F-36P cells with a combination of EPO and IGF-I (EPO/IGF-I) was found to enhance EPO-induced tyrosine phosphorylation of STATE, whereas IGF-I alone did not. Furthermore, c-CIS mRNA expression, one of the target molecules of STATE, was more effectively induced by EPO/IGF-I than by EPO alone. To examine the mechanisms of the EPO- and EPO/ IGF-I-induced proliferation of F-36P cells, we expressed dominant negative (dn) mutants of STATE and Ras in an inducible system. The EPO-induced DNA synthesis and the cooperative effect of EPO/IGF-I were significantly inhibited by the inducible expression of dn-STAT5 or dn-Ras. In addition, the inducible expression of dn-Ras abolished the IGF-I-enhanced tyrosine phosphorylation of STATE. These results suggest that IGF-I may augment EPO-induced proliferation by enhancing tyrosine phosphorylation of STATE and raise the possibility that Ras may be involved in the augmentation of STATE tyrosyl phosphorylation.
- Matsumura, I; K Nakajima; H Wakao; S Hattori; K Hashimoto; H Sugahara; T Kato; H Miyazaki; T Hirano; W KanakuraMOLECULAR AND CELLULAR BIOLOGY 18 7 4282 - 4290 1998年07月Thrombopoietin (TPO) is a hematopoietic growth factor that plays fundamental roles is both megakaryopoiesis and thrombopoiesis through binding to its receptor, c-mpl. Although TPO has been shown to activate various types of intracellular signaling molecules, such as the Janus family of protein tyrosine kinases, signal transducers and activators of transcription (STATs), and ras, the precise mechanisms underlying TPO-induced proliferation and differentiation remain unknown. In an effort to clarify the mechanisms of TPO-induced proliferation and differentiation, c-mpl was introduced into F-36P, a human interleukin-3 (IL-3)dependent erythroleukemia cell line, and the effects of TPO on the c-mpl-transfected F-36P (F-36P-mpl) cells were investigated. F-36P-mpl cells were found to proliferate and differentiate at a high rate into mature megakaryocytes in response to TPO. Dominant-negative (dn) forms of STAT1, STAT3, STAT5, and ras were inducibly expressed in F-36P-mpl cells, and their effects on TPO-induced proliferation and megakaryocytic differentiation were analyzed. Among these dn molecules, both dn res and dn STAT5 reduced TPO- or IL-3-induced proliferation of F-36P-mpl cells by similar to 30%, and only dn ras could inhibit TPO-induced megakaryocytic differentiation. In accord with this result, overexpression of activated ras (H-ras(G12V)) for 5 days led to megakaryocytic differentiation of F-36P-mpl cells. In a time course analysis on (H-ras(G12V)-induced differentiation, activation of the ras pathway for 24 to 28 h was required and sufficient to induce megakaryocytic differentiation. Consistent with this result, the treatment of F-36P-mpl cells with TPO was able to induce prolonged activation of ras for more than 24 h, whereas IL-3 had only a transient effect. These results suggest that prolonged ras activation may be involved in TPO-induced megakaryocytic differentiation.
- 金倉譲; 北山等; 池田弘和; 松村到現代医療 30 7 1783 - 1787 現代医療社 1998年07月
- T Yokota; K Oritani; H Mitsui; K Aoyama; J Ishikawa; H Sugahara; Matsumura, I; S Tsai; Y Tomiyama; Y Kanakura; Y MatsuzawaBLOOD 91 9 3263 - 3272 1998年05月Fibronectin (FN) is supposed to play important roles in various aspects of hematopoiesis through binding to very late antigen 4 (VLA4) and VLA5. However, effects of FN on hematopoietic stem cells are largely unknown. In an effort to determine if FN had a growth-supporting activity on hematopoietic stem cells, human CD34(+)/VLA4(bright)/VLA5(dull) hematopoietic stem cells and a murine stem cell factor (SCF)dependent multipotent cell line, EML-C1, were treated with or without FN in a serum and growth-factor-deprived medium, and then subjected to clonogenic assay in the presence of hematopoietic growth factors. The pretreatment of the CD34(+) cells with FN gave rise to significantly increased numbers of granulocyte-macrophage colony-forming units (CFU-GM), erythroid burst colony-forming units, and mixed erythroid-myeloid colony-forming units. In addition, the numbers of blast colony-forming units and CFU-GM that developed after culture of EML-C1 cells with SCF and the combination of SCF and interleukin-l, respectively, were augmented by the pretreatment with FN. The augmented colony formation by FN was completely abrogated by the addition of CS1 fragment, but not of GRGDSP peptide, suggesting an essential role of FN-VLA4 interaction in the FN effects. Furthermore, the effects of various FN fragments consisting of RGDS-containing cell-binding domain (CBD), heparin-binding domain (HBD), and/or CS1 portion were tested on clonogenic growth of CD34(+) cells. Increased colony formation was induced by CBD-CS1 and CBD-HBD-CS1 fragments, but not with other fragments lacking CBD or CS1 domains, suggesting that both CS1 and CBD of FN were required for the augmentation of clonogenic growth of hematopoietic stem/progenitor cells in vitro. In addition to the in vitro effects, the in vivo administration of CBD-CS1 fragment into mice was found to increase the numbers of hematopoietic progenitor cells in bone marrow and spleen in a dose-dependent manner. Thus, FN may function on hematopoietic stem/progenitor cells as a growth-supporting factor in vitro and in vivo. (C) 1998 by The American Society of Hematology.
- 金倉譲; 池田弘和; 北山等; 松村到; 橋本光司; 北村幸彦血液系疾患調査研究班特発性造血障害分科会 平成9年度研究業績報告書 42 - 43 1998年
- 松村到; 金倉譲Mol Med 35 276 - 277 1998年
- Y Horikawa; Matsumura, I; K Hashimoto; M Shiraga; S Kosugi; S Tadokoro; T Kato; H Miyazaki; Y Tomiyama; Y Kurata; Y Matsuzawa; Y KanakuraBLOOD 90 10 4031 - 4038 1997年11月Thrombopoietin (TPO) is implicated as a primary regulator of megakaryopoiesis and thrombopoiesis through binding to the cytokine receptor c-Mpl (the product of the c-mpl proto-oncogene). in an effort to determine the pathophysiological role of TPO-c-Mpl system in essential thrombocythemia (ET), we have examined the levels of serum TPO and the expression and function of platelet c-Mpl in 17 patients with ET. In spite of extreme thrombocytosis, serum TPO levels were slightly elevated or within normal range in most, if not all, patients with ET (mean +/- SD, 1.31 +/- 1.64 fmol/mL), as compared with normal subjects (0.76 +/- 0.21 fmol/mL). Flow cytometric and Western blot analyses revealed that the expression of platelet c-Mpl was strikingly reduced in all patients with ET. Furthermore, the expression of platelet c-mpl mRNA was found to be significantly decreased in the ET patients tested. In contrast, almost identical levels of GPIIb/IIIa protein and mRNA were expressed in platelets from ET patients and normal controls. In addition to expression level, activation state of platelet c-Mpl was investigated in ET patients. Immunoblotting with anti-phosphotyrosine antibody showed that no aberrant protein-tyrosine phosphorylation was observed in platelets of ET patients before treatment with TPO, and the levels of TPO-induced protein-tyrosine phosphorylation, including c-Mpl-tyrosyl phosphorylation, roughly paralleled those of c-Mpl expression, suggesting that c-Mpl-mediated signaling pathway was not constitutively activated in platelets of ET patients. These results suggested that the TPO-c-Mpl system may not be directly linked to pathogenesis of ET, and that gene(s) mutated in ET may be important in regulating the levels of c-mpl gene expression in addition to the growth and differentiation of multipotential hematopoietic stem cells. (C) 1997 by The American Society of Hematology.
- Matsumura, I; J Ishikawa; K Nakajima; K Oritani; Y Tomiyama; JI Miyagawa; T Kato; H Miyazaki; Y Matsuzawa; Y KanakuraMOLECULAR AND CELLULAR BIOLOGY 17 5 2933 - 2943 1997年05月Although thrombopoietin (TPO) is known to play a fundamental role in both megakaryopoiesis and thrombopoiesis, the molecular mechanism of TPO-induced megakaryocytic differentiation is not known. In a human megakaryoblastic leukemia cell line, CMK, that showed some degree of megakaryocytic differentiation after culture with TPO, the cyclin-dependent kinase (Cdk) inhibitor p21(WAF1/Cipl), but not p27(Kip1), p16(INK4A) p15(INK4B), Or p18(INK4C), found to be upregulated in an immediately early response to TPO. The expression of p21 was found to be sustained over a period of 5 days by treatment with TPO in large polyploid cells that developed in response to TPO, but not in small undifferentiated cells, indicating a close correlation between the ligand-induced differentiation and p21 induction in CR IK cells. To examine potential roles of Cdk inhibitors in megakaryocytic differentiation, CMK cells were transfected with the p21, p27, or p16 gene, together with a marker gene, beta-galactosidase, and were cultured with medium alone for i days. The ectopic expression of p21 or p27 hut not of p16 led to induction of megakaryocytic differentiation of CR IK cells, Overexpression of the N-terminal domain (amino acids [aa] 1 to 75) of p21 was sufficient to induce megakaryocytic differentiation, whereas that of the C-terminal domain (aa 76 to 164) had little or no effect on morphological features, Furthermore, we found that although TPO induced tyrosine phosphorylation of both STAT3 and STAT5 in CR IK cells, only STAT5 showed binding activities to potential STAT-binding sites that locate in the promoter region of p21 gene (p21-SIE sites), thereby leading to transactivation of p21. These results suggested that p21 induction, possibly mediated through activated STAT5, could play an important role in TPO-induced megakaryocytic differentiation.
- 造血器腫瘍と遺伝子異常 治療の標的として サイトカイン受容体異常と造血器腫瘍松村 到; 金倉 譲血液・免疫・腫瘍 2 2 147 - 152 (株)メディカルレビュー社 1997年04月
- 松村到; 金倉譲臨床検査 41 3 291 - 295 1997年03月
- 松村到; 金倉譲最新医学 52 2 184 - 189 1997年02月
- 松村到; 金倉譲Annual Review 血液 1997 79 - 87 1997年
- 松村到; 金倉譲日常診療と血液 7 1 33 - 41 1997年01月
- Matsumura, I; H Ikeda; Y KanakuraLEUKEMIA & LYMPHOMA 23 5-6 533 - 538 1996年11月Thrombopoietin (TPO) is a novel hematopoietic growth factor that was cloned as a ligand for c-mpl proto-oncogene. The c-mpl proto-oncogene is expressed on various types of human leukemia cell lines derived from erythroid, megakaryocytic, and stem-cell leukemia cells. Also, c-mpl mRNA is detectable on blast cells in about half of acute myeloblastic leukemia (AML) cases regardless of French-American-British (FAB) classification. In the cases with myelodysplastic syndrome, c-mpl is expressed in a substantial fraction of refractory anemia with excess of blast (RAEB), RAEB in trasformation, and chronic myelomonocytic leukemia cells, but not in refractory anemia or sideroblastic anemia. Little or no expression of c-mpl mRNA is observed in human lymphoid cell lines and blast cells of acute lymphoblastic leukemia cases. The in vitro treatment of AML cells with TPO resulted in proliferation in about 70% of c-mpl-positive AML cases. The proliferative responses of AML cells to TPO were observed not only in M7-type, but also in the other subtypes of AML cases. Furthermore, the TPO-induced proliferation of AML cells was augmented by the addition of the other hematopoietic growth factors such as interleukin-3 (IL-3), IL-6, stem cell factor, or granulocyte macrophage colony-stimulating factor. In addition to proliferation, TPO appeared to induce megakaryocytic differentiation in a small part of AML cells. These results suggested that TPO/c-mpl system might contribute, at least in part, to abnormal growth and differentiation of AML cells.
- Matsumura, I; Y Kanakura; T Kato; H Ikeda; Horikawa, V; J Ishikawa; H Kitayama; T Nishiura; Y Tomiyama; H Miyazaki; Y MatsuzawaBLOOD 88 8 3074 - 3082 1996年10月Thrombopoietin (TPO) is implicated as a primary regulator of megakaryopoiesis and thrombopoiesis. However, the biologic effects of TPO on human acute myeloblastic leukemia (AML) cells are largely unknown. To determine if recombinant human (rh) TPO has proliferation-supporting and differentiation-inducing activities in AML cells, 15 cases of AML cells that were exclusively composed of undifferentiated leukemia cells and showed growth response to rhTPO in a short-term culture (72 hours) were subjected to long-term suspension culture with or without rhTPO. Of 15 cases, rhTPO supported proliferation of AML cells for 2 to 4 weeks in 4 cases whose French-American-British subtypes were M0, M2, M4, and M7, respectively. In addition to the proliferation-supporting activity, rhTPO was found to induce AML cells to progress to some degree of megakaryocytic differentiation at both morphologic and surface-phenotypic levels in 2 AML cases with M0 and M7 subtypes. The treatment of AML cells with rhTPO resulted in rapid tyrosine phosphorylation of the TPO-receptor, c-mpl, and STAT3 in all of cases tested. By contrast, the expression of erythroid/megakaryocyte-specific transcription factors (GATA-1, GATA-2, and NF-E2) was markedly induced or enhanced in only 2 AML cases that showed megakaryocytic differentiation in response to rhTPO. These results suggested that, at least in a fraction of AML cases, TPO could not only support the proliferation of AML cells irrespective of AML subtypes, but could also induce megakaryocytic differentiation, possibly through activation of GATA-1, GATA-2, and NF-E2. (C) 1996 by The American Society of Hematology.
- 松村到; 金倉譲治療学 30 10 1093 - 1096 1996年10月
- H Kitayama; T Tsujimura; Matsumura, I; K Oritani; H Ikeda; J Ishikawa; M Okabe; M Suzuki; K Yamamura; Y Matsuzawa; Y Kitamura; Y KanakuraBLOOD 88 3 995 - 1004 1996年08月The c-kit proto-oncogene encodes a receptor tyrosine kinase that is crucial to hematopoiesis, melanogenesis, and garnetogeneis. Although the enzymatic activity of the c-kit product (KIT) is regulated by its ligand, both the Val559 --> Gly (G559) mutation in the juxtamembrane domain and the Asp814 --> Val (V814) mutation in the phosphotransferase domain lead to constitutive activation of KIT. By retroviral infection of hematopoietic progenitor cells with KITG559 Or KITV814, KITG559 induced development of granulocyte/macrophage and mast-cell colonies in vitro without the addition of exogenous growth factors. KITV814 induced factor-independent growth of various types of hematopoietic progenitor cells, resulting in the development of mixed erythroid/myeloid colonies in addition to granulocyte/macrophage and mast-cell colonies. Furthermore, transplantation of KITG559 and KITV814-infected bone marrow cells led to development of acute leukemia in one of 10 and six of 10 transplanted mice, respectively. No mice developed hematologic malignancies after transplantation of wild-type KIT-infected cells. Furthermore, transgenic mice expressing KITV814 developed acute leukemia or malignant lymphoma. These results demonstrate a direct role of the mutant KITs, particularly KITV814, in tumorigenesis of hematopoietic cells and suggest that similar mutations may contribute to the development of human hematologic malignancies. (C) 1996 by The American Society of Hematology.
- 松村到; 金倉譲月刊血液・腫よう科 33 1 36 - 42 1996年07月
- Matsumura, I; Y Kanakura; H Ikeda; Ishikawa, I; H Yoshida; Y Horikawa; T Nishiura; T Tahara; T Kato; H Miyazaki; Y MatsuzawaLEUKEMIA 10 1 91 - 94 1996年01月Thrombopoietin (TPO) is a recently identified hematopoietic growth factor that is essential for the growth and development of megakaryocytes. We have previously shown that TPO induces proliferation of acute myeloblastic leukemia (AML) cells in vitro. In this study, we have examined the expression of TPO and its receptor c-mpl in a series of AML cases and human leukemia cell lines. The mRNA transcripts of TPO were detectable in 18 of 50 AML cases and in some myeloid leukemia cell lines (HEL, M07E and CMK) by means of reverse transcriptase polymerase chain reaction (RT-PCR). In addition, TPO transcripts were coexpressed with c-mpl transcripts in 10 of 50 AML cases and in HEL, M07E and CMK cells. With regard to the French-American-British (FAB) classification, coexpression of TPO and c-mpl was observed with high frequency in AML cases of M7-type. Despite the TPO expression in a substantial fraction of leukemia cells, biological activity of TPO was not found in the conditioned medium that was obtained from cultivation of TPO mRNA-positive leukemia cells. These results suggest that TPO may not commonly participate in the abnormal growth of AML cells as an extracellular autocrine growth factor.
- I. Matsumura; Y. Kanakura; T. Kato; H. Ikeda; J. Ishikawa; Y. Horikawa; K. Hashimoto; Y. Moriyama; T. Tsujimura; T. Nishiura; H. Miyazaki; Y. MatsuzawaBlood 86 2 703 - 709 1995年Thrombopoietin (TPO) is e newly identified hematopoietic growth factor that stimulates both megakaryopoiesis and thrombopoiesis through its interaction with a specific cell surface receptor encoded by the c-mpl proto- oncogene. In an effort to investigate the effect of TPO on human myeloid leukemia cells, the expression of c-mpl and the proliferative response to recombinant human (rh) TPO were investigated in a series of patients with acute myeloblastic leukemia (AML). Of 50 cases of AML, the c-mpl mRNA was detectable by means of Northern blot analysis in 26 cases, and the in vitro treatment with rhTPO led to proliferation of AML cells in 22 cases. The c- mpl expression and proliferative response to rhTPO was observed in all subtypes of AML and did not correlate with French-American-British classification, whereas all cases of M7-type AML cells expressed c-mpl and proliferated in response to rhTPO. Furthermore, rhTPO-induced proliferation of AML cells was augmented with the addition of interleukin-3 (IL-3), IL-6, stem cell factor, or granulocyte-macrophage colony-stimulating factor. These results suggested that c-mpl may be functional in terms of supporting proliferation of various types of AML cells and that TPO may contribute, at least in part, to abnormal growth of the cells, especially in combination with other hematopoietic growth factors.
- T TAMAKI; Y KANAKURA; A KURIU; H IKEDA; H MITSUI; H YAGURA; MATSUMURA, I; B DRUKER; JD GRIFFIN; Y KANAYAMA; T YONEZAWACANCER RESEARCH 52 3 566 - 570 1992年02月The protooncogene product, Raf-1, is a serine/threonine kinase and has been implicated as an intermediate in signal transduction mechanisms. We examined neoplastic and normal B cells for phosphorylation and activation of Raf-1 protein in response to anti-immunoglobulin antibody (anti-Ig). Anti-Ig induced rapid phosphorylation of Raf-1 protein in both neoplastic B-cells of hairy cell leukemia and normal tonsillar B-cells which proliferated well in response to anti-Ig. The increase in phosphorylation was due primarily to an increase in phosphoserine. The immune complex kinase assay using Histone V-S as an exogenous substrate also showed an increase in Raf-1-associated kinase activity. An inhibitor of protein kinase C, H7, inhibited the proliferation as well as the Raf-1 phosphorylation in response to the proliferative signal of anti-Ig. Further, downregulation of protein kinase C by the treatment with 12-phorbol 13-myristic acid significantly abrogated the induction of Raf-1 phosphorylation. These results suggest that, in human B-cells, Raf-1 protein may be involved in the signal transduction pathway mediated by surface immunoglobulin, and that it may be, at least partially, phosphorylated by activated PKC.
- 松村到; 平野俊夫病理と臨床 10 1 119 - 121 1992年01月
- 松村到; 木曾真一; 多胡基; 川上房男; 伏見博彰; 青笹克之; 金倉譲; 玉値俊治; 垂井清一郎臨床血液 32 3 266 - 271 1991年03月
- H MITSUI; H YAGURA; T TAMAKI; H IDEKA; MATSUMURA, I; Y KANAKURA; T YONEZAWA; S TARUIIMMUNOLOGY LETTERS 27 2 105 - 112 1991年02月The role of phorbol myristate acetate (PMA: a protein kinase-C (PKC) activator) and calcium ionophore A23187 in the induction mechanism of the interleukin 2 receptor (IL2R) on B-cell chronic lymphocytic leukemia (B-CLL) cells was studied. B-CLL cells from five patients were cultured with PMA or A23187 for 72 h and used for the following experiments. Interleukin 2 (IL2) cross-linking assays showed that PMA induced the expression of IL2R subunits (p55 and p70/75) in all cases examined, but that A23187 induced neither subunit. Radiolabeled IL2 binding assays also demonstrated that PMA induced both high-affinity IL2R (HA-IL2R) and low-affinity IL2R (LA-IL2R) on B-CLL cells, but that A23187 did not. After treatment with PMA, three of five cases did not respond to IL2 even though they expressed HA-IL2R, suggesting impaired signal transduction. No cases responded to IL2 after treatment with A23187. In conclusion, PMA but not A23187 stimulates B-CLL cells to induce the expression of p55 and p70/75, indicating that the PKC pathway plays a more important role than the calcium pathway in the induction of IL2R subunits in B-CLL cells.
- MATSUMURA, I; T TAMAKI; S KATAGIRI; M TANIWAKI; N TOMINAGA; K ORITANI; M IIDA; H YAGURA; T YONEZAWA; S TARUIINTERNATIONAL JOURNAL OF CANCER 46 6 1107 - 1111 1990年12月
- 木曽真一; 柏原たけし; 藤森永二郎; 橋本光司; 伊藤俊雄; 松村到; 大木篤; 川上房男; 奥野ぎ一Gastroenterol Endosc 32 10 2407 - 2415 1990年10月
- 児島雄三; 山田美津子; 西川吉伸; 山中忠; 加藤宗寛; 松村到; 天野利男産婦人科の実際 39 6 973 - 976 1990年06月
- K ORITANI; S KATAGIRI; N TOMINAGA; M IIDA; T AMANO; T KARASUNO; MATSUMURA, I; H MITSUI; Y KANAYAMA; T YONEZAWA; S TARUIBRITISH JOURNAL OF HAEMATOLOGY 75 1 10 - 15 1990年05月
- 木曽真一; 柏原たけし; 藤森永二郎; 大木篤; 川上房男; 多胡基; 奥野ぎ一; 木戸良明; 松村到Gastroenterol Endosc 32 7 1685 - 1691 1990年We report a case of hepatic coproporphyria. He was a 24-year-old male who visited our hospital complaining of abdominal pain and convulsion. Eight months ago, he had suffered from cerebral contusion and had been administered phenobarbital and sodium valproate. On admission, the urine was wine-colored and liver function tests were almost normal, δ-aminolevulinic acid (26 mg/24 hr), porphobilinogen (5.9 mg/24hr), uroporphyrin (1,296 μg/24hr) and coproporphyrin (7,290 μg/24 hr) (I: III= 1: 15.5) of urine, and fecal coproporphyrin (1,490 μg/g dw) were markedly increased. Uroporphyrin and protoporphyrin of feces, and uroporphyrin, coproporphyrin and protoporphyrin of erythrocyte were not increased. Laparoscopic findings revealed that the liver surface was almost flat, but had a map-like appearance with reddish-brown areas and slightly depressed dark purple areas. Needle biopsy of the liver showed red fluorescence under ultraviolent light. H. E. staining revealed hydropic degeneration and the presence of brown granules (partially positive for iron staining) in the hepatocytes as well as slight lymphocyte infiltration and fibrosis of the Glisson's sheath. Schmorl's staining revealed needle-shaped crystalline enclosures as long as a hepatocytic nucleus. © 1990, Japan Gastroenterological Endoscopy Society. All rights reserved.
- 正名好之; 池田宏也; 藤本康裕; 松村到; 川上房男; 森信太郎; 有田憲生; 生塩之敬Neurol Med Chir 30 11 853 - 857 1990年The patients was a 27-year-old female, gravida 0, para 0, with complaint of headache and visual disturbance for about 1 month. Ophthalmological examination showed impaired visual acuity and enlargement of Mariotte's spot on the left. A computed tomography scan disclosed an enhanced mass in the sellar and suprasellar region. Endocrinological examination revealed slight elevation of thyroxin, growth hormone, and prolactin. A trans-sphenoidal hypophysectomy was carried out with a preoperative diagnosis of nonfunctioning pituitary adenoma. Histological examination showed a marked infiltration of lymphocytes and interstitial fibrosis, diagnosed as lymphocytic adenohypophysitis. She received hormone-replacement therapy owing to postoperative hypopituitarism. Twenty-eight cases of lymphocytic adenohypophysitis including the authors' are classified clinically into two types fluminant type and chronic type. The former type occurs frequently with disturbance of consciousness because of the end organ insufficiency and proceeds to death in a fluminant course. The latter type occurs frequently with headache and visual disturbances, closely related to pregnancy and the postpartum period and survival occurs with hormone replacement therapy. This disease should be kept in mind in the diagnosis of sellar and suprasellar mass lesions. © 1990, The Japan Neurosurgical Society. All rights reserved.
- 松村到; 宮田哲; 多胡基; 川上房雄; 奥野ぎ一; 冨永信彦; 片桐修一; 金山良男; 米沢毅臨床血液 30 4 491 - 496 1989年04月
- 松村 到; 宮田 哲; 多胡 基; 大木 篤; 川上 房男; 奥野 巍一日本内科学会雑誌 78 4 567 - 568 The Japanese Society of Internal Medicine 1989年症例は発熱を主訴に入院した35才の男性.超音波, CTで肝内に多数の低吸収域を認め,超音波下穿刺で得られた膿よりK. pneumoniae肝膿瘍と診断した.肝膿瘍の基礎疾患として,慢性骨髄性白血病が発見された.肝膿瘍はしばしば致死的な疾患であるが,超音波下ドレナージと抗生物質の全身および局所投与により治療に成功した.本例では,顆粒球の遊走能, NBT還元能の低下が認められ,肝膿瘍の発症に関与した可能性が考えられた.
- 宮田哲; 松村到; 大木篤; 柴本茂樹; 作山欽治; 柏原たけし; 川上房男; 多胡基; 奥野ぎ一超音波医学 14 6 619 - 625 1987年12月
MISC
- 波江野高大; 三宅義昭; 井上舞子; 藤本昂; 角谷宏明; 藤井晶; 源周治; 口分田貴裕; 芹澤憲太郎; 谷口康博; 頼晋也; 平瀬主悦; 森田泰慶; 田中宏和; 辰巳陽一; 芦田隆司; 松村到 日本造血・免疫細胞療法学会総会プログラム・抄録集 44th 2022年
- 井上宏昭; 頼晋也; 口分田貴裕; 芹澤憲太郎; 谷口康博; 中山聖子; 森田泰慶; LUIS Espinoza J; 田中宏和; 辰巳陽一; 芦田隆司; 松村到 日本リンパ網内系学会会誌 59 2019年
- 脳静脈洞血栓症を合併し、開頭減圧術・術後エクリズマブ投与が有効であったPNHの一例(Post-operative treatment with eculizumab for PNH presenting as cerebral venous sinus thrombosis)岩田 吉生; 森田 泰慶; 辻 潔; 頼 晋也; 田崎 貴之; 井上 宏昭; 谷口 康博; 藤本 昂; 田中 宏和; 芦田 隆司; 加藤 天美; 松村 到 臨床血液 59 (9) 1765 -1765 2018年09月
- KMFに登録されたボルテゾミブとIMiDs両剤に抵抗性の再発骨髄腫の予後解析(Clinical outcomes of relapsed myeloma, dual refractory to bortezomib and IMiDs in KMF registry)藤原 亮介; 田中 宏和; 芹澤 憲太郎; 金子 仁臣; 志村 勇司; 太田 健介; 淵田 真一; 中谷 綾; 諫田 淳也; 八木 秀男; 和田 勝也; 小杉 智; 魚嶋 伸彦; 柴山 浩彦; 小原 尚恵; 中谷 英仁; 内山 人二; 足立 陽子; 飯田 正人; 濱田 常義; 松田 光弘; 高折 晃史; 野村 昌作; 島崎 千尋; 日野 雅之; 黒田 純也; 谷脇 雅史; 今田 和典; 金倉 譲; 松村 到 臨床血液 59 (9) 1739 -1739 2018年09月
- 症候性骨髄腫1414例の後方視的解析 関西骨髄腫フォーラムからの最新報告(Retrospective analyses of 1,414 symptomatic multiple myeloma cases: update from Kansai Myeloma Forum)田中 宏和; 芹澤 憲太郎; 中谷 綾; 金子 仁臣; 太田 健介; 小杉 智; 八木 秀男; 花本 仁; 淵田 真一; 志村 勇司; 柴山 浩彦; 小原 尚恵; 中谷 英仁; 諫田 淳也; 魚嶋 伸彦; 和田 勝也; 烏野 隆博; 松井 利充; 内山 人二; 松田 光弘; 足立 陽子; 高折 晃史; 黒田 純也; 谷脇 雅史; 島崎 千尋; 日野 雅之; 今田 和典; 野村 昌作; 金倉 譲; 松村 到 臨床血液 59 (9) 1510 -1510 2018年09月
- 小森舞子; 井上宏昭; 角谷宏明; 大山泰世; 森田泰慶; 芦田隆司; 松村到 日本造血細胞移植学会総会プログラム・抄録集 39th 2017年
- 芦田隆司; 芦田隆司; 小森舞子; 波江野高大; 斎藤花往里; 藤本昴; 角谷宏明; 谷口貴英; 佐野圭吾; 大山泰世; 井上宏昭; 口分田貴裕; 森田泰慶; 地守慶亮; 前田朋子; 中野勝彦; 福島靖幸; 川野亜美; 井手大輔; 前田岳宏; 松村到 日本造血細胞移植学会総会プログラム・抄録集 40th 2017年
- 小森舞子; 井上宏昭; 角谷宏明; 大山泰世; 口分田貴裕; 森田泰慶; 田中宏和; 芦田隆司; 田崎貴之; 奥田武司; 松村到 日本造血細胞移植学会総会プログラム・抄録集 40th 2017年
- 孤発性皮膚myeloid sarcomaの1例齋藤 花往里; 頼 晋也; 岩田 吉生; 田中 宏和; 辰巳 陽一; 芦田 隆司; 松村 到; 柳原 緑; 大磯 直毅; 川田 暁 臨床血液 57 (2) 197 -198 2016年02月
- 藤本昂; 頼晋也; 岩田吉生; 平瀬主税; 森田泰慶; 田中宏和; 辰巳陽一; 芦田隆司; 松村到 臨床血液 57 (2) 2016年
- 芦田隆司; 芦田隆司; 角谷宏明; 末田早苗; 岩田吉生; 福井彩乃; 大山泰世; 井上宏昭; 頼晋也; 平瀬主税; 森田泰慶; 中野勝彦; 福島靖幸; 川野亜美; 山田枝里佳; 井手大輔; 前田岳宏; 菅野知恵美; 椿本祐子; 金光靖; 松村到; 松村到 日本造血細胞移植学会総会プログラム・抄録集 38th 2016年
- 芹澤憲太郎; 森田泰慶; 谷口貴英; 岩田吉生; 源周治; 大山泰世; 川内超矢; 金井良高; 頼晋也; 平瀬主税; 田中宏和; 宮武淳一; 辰巳陽一; 芦田隆司; 松村到 日本造血細胞移植学会総会プログラム・抄録集 37th 2015年
- 口分田貴裕; 岩田吉夫; 谷口貴秀; 源周治; 大山泰世; 佐野圭吾; 川内超矢; 芹澤憲太郎; 谷口康博; 頼晋也; 金井良高; 平瀬主税; 森田泰慶; 田中宏和; 宮武淳一; 辰巳陽一; 芦田隆司; 松村到 日本造血細胞移植学会総会プログラム・抄録集 37th 2015年
- 宮武淳一; 岩田吉生; 谷口貴英; 源周治; 大山泰世; 川内超矢; 佐野圭吾; 口分田貴裕; 芹澤憲太郎; 谷口康博; 頼晋也; 金井良高; 平瀬主税; 森田泰慶; 田中宏和; 辰巳陽一; 芦田隆司; 松村到 日本造血細胞移植学会総会プログラム・抄録集 37th 2015年
- 芦田隆司; 芦田隆司; 岩田吉生; 谷口貴英; 源周治; 芹沢憲太郎; 川内超矢; 大山泰世; 金井良高; 頼晋也; 平瀬主税; 森田泰慶; 竹中孝子; 福島靖幸; 川野亜美; 山田枝里佳; 井手大輔; 菅野知恵美; 加藤祐子; 椿本祐子; 松村到; 松村到 日本造血細胞移植学会総会プログラム・抄録集 37th 2015年
- 芦田隆司; 芦田隆司; 福井彩乃; 大山泰世; 芹沢憲太郎; 頼晋也; 平瀬主税; 中野勝彦; 福島靖幸; 川野亜美; 山田枝里佳; 井手大輔; 前田岳宏; 菅野知恵美; 加藤祐子; 椿本祐子; 金光靖; 松村到; 松村到 日本輸血細胞治療学会誌 61 (2) 2015年
- 芹澤憲太郎; 森田泰慶; 江本正克; 大山泰世; 福井彩乃; 井上宏昭; 川内超矢; 金井良高; 平瀬主税; 田中宏和; 嶋田高広; 宮武淳一; 辰巳陽一; 芦田隆司; 松村到 日本造血細胞移植学会総会プログラム・抄録集 36th 2014年
- 川西一信; 綿谷陽作; 谷口康博; 川内超矢; 芹澤憲太郎; 江本正克; 金井良高; 頼晋也; 平瀬主税; 森田泰慶; 田中宏和; 嶋田高広; 宮武淳一; 辰巳陽一; 芦田隆司; 松村到 日本造血細胞移植学会総会プログラム・抄録集 35th 2013年
- 芹澤憲太郎; 綿谷陽作; 谷口康博; 森田泰慶; 川内超矢; 江本正克; 平瀬主税; 田中宏和; 嶋田高広; 川西一信; 宮武淳一; 辰巳陽一; 芦田隆司; 松村到 日本造血細胞移植学会総会プログラム・抄録集 35th 2013年
- 芹澤憲太郎; 川西一信; 大山泰世; 尾嶋真由子; 井上宏昭; 口分田貴裕; 江本正克; 谷口康博; 金井良高; 頼晋也; 笹川淳; 平瀬主税; 山口晃史; 森田泰慶; 田中宏和; 嶋田高広; 辰巳陽一; 芦田隆司; 松村到 日本造血細胞移植学会総会プログラム・抄録集 34th 2012年
- 芦田隆司; 川野亜美; 山田枝里佳; 井手大輔; 菅野知恵美; 加藤祐子; 椿本祐子; 伊藤志保; 峯佳子; 藤田往子; 井上宏昭; 口分田貴裕; 芹澤憲太郎; 江本正克; 平瀬主税; 山口晃史; 森田泰慶; 川西一信; 辰巳陽一; 松村到; 松村到 日本造血細胞移植学会総会プログラム・抄録集 34th 2012年
- 笹川淳; 前田裕弘; 平瀬主税; 山口晃史; 森田泰慶; 松村到 日本エイズ学会誌 12 (4) 2010年
- FIP1L1/PDGFRaは造血幹細胞/前駆細胞の好酸球系への分化を誘導する(FIP1L1/PDGFRa imposes commitment towards eosinophic lineage on hematopoietic stem/progenitor cells)福島 健太郎; 松村 到; 江副 幸子; 佐藤 友亮; 安見 正人; 田中 宏和; 金倉 譲 日本癌学会総会記事 66回 299 -299 2007年08月
- Cancer stem cells as a target of molecular therapeuticsItaru Matsumura; Yuzuru Kanakura Biotherapy 21 (4) 209 -216 2007年07月
- Itaru Matsumura; Yuzuru Kanakura Nippon rinsho. Japanese journal of clinical medicine 65 100 -104 2007年
書籍等出版物
- 松村, 到; 張替, 秀郎; 神田, 善伸 南江堂 2022年10月 ISBN: 9784524233687 vi, 335p
- 松村, 到 中外医学社 2020年12月 ISBN: 9784498225220 vi, 297p
- 直江 知樹; 小澤 敬也; 中尾 真二; 松村 到 南江堂 2017年02月 ISBN: 9784524254224
- 松村, 到 南江堂 2016年06月 ISBN: 9784524258758 xiv, 368p
- 松村, 到 医薬ジャーナル社 2015年11月 ISBN: 9784753227662 227p
- 金倉, 譲; 伊豆津, 宏二; 冨山, 佳昭; 松村, 到; 山崎, 宏人 中山書店 2015年10月 ISBN: 9784521742793 xii, 560p
- 松村, 到 中外医学社 2015年04月 ISBN: 9784498125889 iii, 280p
- 直江 知樹; 小澤 敬也; 中尾 真二; 松村 到 南江堂 2014年01月 ISBN: 9784524267996 380
- 松村, 到 中山書店 2013年10月 ISBN: 9784521737775 xiv, 340p
- 造血器腫瘍とエピジェネティスク-治療への応用と新たな展開-田中宏和; 松村 到 (担当:共著範囲:クロマチンおよびDNA修飾を標的とする分子標的治療薬の開発:総論)2012年
- EBM 血液疾患の治療 2013-2014田中宏和; 松村 到 (担当:共著範囲:イマチニブ抵抗性・不耐容の慢性期CMLに対する治療方針)2012年
- 今日の治療指針松村 到 (担当:共著範囲:慢性骨髄性白血病)2012年
- 血管新生阻害薬のベストマネジメント, ニロチニブ松村 到 (担当:単著範囲:)金原出版㈱ 2011年11月
- 骨髄異形成症候群(MDS)診療up-to-date, 鉄キレート療法松村 到 (担当:単著範囲:)中外医学社 2011年10月
- 松村, 到 中外医学社 2011年10月 ISBN: 9784498125681 xii, 386p
- 血液専門医テキスト松村 到 (担当:共著範囲:造血幹細胞、血球産生と分化)日本血液学会 2011年
- ニロチニブ松村 到 (担当:共著範囲:血管新生阻害薬のベストマネジメント)金原出版 2011年
- 押味, 和夫; 木崎, 昌弘; 松村, 到 中外医学社 2010年10月 ISBN: 9784498125353 5, 361p
- 直江, 知樹; 小澤, 敬也; 中尾, 真二; 松村, 到; 神田, 善伸 南江堂 2010年10月 ISBN: 9784524260713 冊
- 内科, 白血病治療における新規分子標的治療薬川西 一信; 松村 到 (担当:共著範囲:)南江堂 2010年08月正常細胞を傷害することなく、白血病細胞のみを死滅させるには白血病細胞特異的に発現するあるいは活性化している分子を治療標的とすることが必要である。本稿では白血病、とくに急性骨髄性白血病に対して開発中の新規分子標的薬を中心に概説する。
- 松村, 到; 高橋, 聡; 宮崎, 泰司 (担当:分担執筆範囲:)中外医学社 2009年11月 ISBN: 9784498125544 viii, 351p
- 和光大学総合文化研究所; 松枝, 到 言叢社 2006年03月 ISBN: 4862090079 586p
- 松村, 到 [松村到] 2006年03月 105p
- 松村 到 [松村到] 2004年03月 98p
- 松村, 到 [松村到] 2002年03月 78p
- 松村, 到 [松村到] 2000年 65p
- 文藝春秋 1982年 ISBN: 4165071102 19冊
講演・口頭発表等
- JSH-MPN-R18データを用いた血栓症リスク因子の検索永春 圭規; 大矢 瑛子; 杉本 由香; 大石 晃嗣; 俵 功; 伊藤 量基; 後藤 明彦; 中前 美佳; 木村 文彦; 小池 道明; 桐戸 敬太; 和田 秀穂; 臼杵 憲祐; 田中 孝幸; 森 毅彦; 脇田 知志; 齋藤 俊樹; 嘉田 晃子; 齋藤 明子; 下田 和哉; 黒川 敏郎; 冨田 章裕; 枝廣 陽子; 橋本 由徳; 清井 仁; 赤司 浩一; 松村 到; 竹中 克斗; 小松 則夫日本血液学会学術集会 2022年10月 (一社)日本血液学会
- びまん性大細胞型 B 細胞リンパ腫に対する自家末梢血幹細胞移植併用大量化学療法につ いての後方視的解析波江野高大; 三宅義昭; 井上舞子; 藤本昂; 角谷宏明; 藤井晶; 源周治; 口分田貴裕; 芹澤憲太郎; 谷口康博; 賴晋也; 平瀬主税; 森田泰慶; 田中宏和; 辰巳陽一; 芦田隆司; 松村到第44回日本造血・免疫細胞療法学会総会 2022年05月 口頭発表(一般)
- TKIの免疫作用はTKI中止後の免疫応答を変化させ再発率にも影響する.藤岡優樹; 髙橋直人; 熱田由子; 南陽介; 清井仁; 宮崎泰司; 松村到第80回日本癌学会学術総会. 2021年09月
- 成人発症スティル病に対するトシリズマブの使用経験杉山 昌史; 廣岡 靖章; 井上 明日圭; 木下 浩二; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 2021年03月 (一社)日本リウマチ学会
- FDG-PETが診断に有用であった再発性多発軟骨炎の一例奥田 早紀; 伊丹 哲; 白井 里香; 森本 祐美; 石村 香織; 赤澤 宗輝; 芦田 千聖; 山本 敦弘; 岡田 晃典; 冨田 大介; 酒井 健史; 李 進海; 志賀 俊彦; 岸本 和也; 野崎 祐史; 木下 浩二; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 2021年03月 (一社)日本リウマチ学会
- 形質細胞腫とIgG4関連疾患との鑑別を要した腰椎硬膜外腫瘤の一例石村 香織; 酒井 健史; 赤澤 宗輝; 芦田 千聖; 山本 敦弘; 岡田 晃典; 冨田 大介; 伊丹 哲; 李 進海; 志賀 俊彦; 岸本 和也; 野崎 祐史; 木下 浩二; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 2021年03月 (一社)日本リウマチ学会
- 急性の神経症状が先行し、診断に難渋した脳幹脳炎を伴うシェーグレン症候群の一例森本 祐美; 酒井 健史; 奥田 早紀; 白井 里香; 石村 香織; 山本 敦弘; 芦田 千聖; 赤澤 宗輝; 冨田 大介; 岡田 晃典; 伊丹 哲; 李 進海; 志賀 俊彦; 岸本 和也; 野崎 祐史; 木下 浩二; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 2021年03月 (一社)日本リウマチ学会
- IL-5がEGPAとの鑑別に有用であった好酸球増多症の一例白井 里香; 森本 祐美; 奥田 早紀; 石村 香織; 山本 敦弘; 芦田 千聖; 赤澤 宗輝; 冨田 大介; 岡田 晃典; 伊丹 哲; 酒井 健史; 李 進海; 志賀 俊彦; 岸本 和也; 野崎 祐史; 木下 浩二; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 2021年03月 (一社)日本リウマチ学会
- 関節リウマチ患者におけるJAK Failure症例の考察伊丹 哲; 志賀 俊彦; 岸本 和也; 野崎 祐史; 木下 浩二; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 2021年03月 (一社)日本リウマチ学会
- 52週後におけるサリルマブの有効性と安全性について岸本 和也; 野崎 祐史; 石村 香織; 赤澤 宗輝; 芦田 千聖; 岡田 晃典; 伊丹 哲; 酒井 健史; 李 進海; 志賀 俊彦; 樋野 尚一; 廣岡 靖章; 杉山 昌史; 木下 浩二; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 2021年03月 (一社)日本リウマチ学会
- 関節リウマチにおけるセルトリズマブペゴルのメトトレキサート用量別の治療効果について李 進海; 野崎 祐史; 石村 香織; 赤澤 宗輝; 芦田 千聖; 山本 敦弘; 岡田 晃典; 冨田 大介; 伊丹 哲; 酒井 健史; 志賀 俊彦; 岸本 和也; 木下 浩二; 舟橋 惠子; 松原 司; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 2021年03月 (一社)日本リウマチ学会
- 生物学的製剤で治療された関節リウマチ患者における腎予後予測赤澤 宗輝; 山澤 広嵩; 石村 香織; 芦田 千聖; 池田 房代; 山本 敦弘; 岡田 晃典; 冨田 大介; 伊丹 哲; 酒井 健史; 李 進海; 志賀 俊彦; 岸本 和也; 野崎 祐史; 木下 浩二; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 2021年03月 (一社)日本リウマチ学会
- インフリキシマブ導入14週後の血中トラフ濃度における治療効果予測因子としての有用性野崎 祐史; 芦田 千聖; 岡田 晃典; 伊丹 哲; 酒井 健史; 李 進海; 志賀 俊彦; 岸本 和也; 木下 浩二; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 2021年03月 (一社)日本リウマチ学会
- 成人スチル病の特性 血球貪食症候群を対照とした成人Still病の診断における血清IL-18測定の有用性の検討志賀 俊彦; 岸本 和也; 野崎 祐史; 木下 浩二; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 2021年03月 (一社)日本リウマチ学会
- 大型血管炎:高安動脈炎 当院における高安動脈炎に対するトシリズマブ長期投与した症例についての検討山本 敦弘; 石村 香織; 赤澤 宗輝; 芦田 千聖; 岡田 晃典; 冨田 大介; 伊丹 哲; 酒井 健史; 李 進海; 志賀 俊彦; 岸本 和也; 野崎 祐史; 木下 浩二; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 2021年03月 (一社)日本リウマチ学会
- SLE・抗リン脂質抗体症候群(臨床):ステロイド 全身性エリテマトーデスに対する当科におけるベリムマブの治療やステロイド減量効果についての検討冨田 大介; 野崎 祐史; 石村 香織; 芦田 千聖; 山本 敦弘; 岡田 晃典; 伊丹 哲; 酒井 健史; 李 進海; 志賀 俊彦; 岸本 和也; 木下 浩二; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 2021年03月 (一社)日本リウマチ学会
- CMML様の病型移行を来したMDSに対してアザシチジンが有効であった1例角谷宏明; 口分田貴裕; 源周治; 頼晋也; 森田泰慶; 田中宏和; 芦田隆司; 松村到臨床血液 2021年 (一社)日本血液学会-東京事務局
- 専門医試験とJ-Oslarについて松村到日本臨床腫瘍学会学術集会(CD-ROM) 2021年
- 同種造血幹細胞移植におけるレテルモビルの有用性の検討谷口康博; 平瀬主税; 芦田隆司; 波江野高大; 角谷宏明; 源周治; 綿谷陽作; 口分田貴裕; 芹澤憲太郎; 頼晋也; 森田泰慶; 田中宏和; 辰巳陽一; 松村到日本造血細胞移植学会総会プログラム・抄録集 2021年
- 同種移植後髄外再発に対してギルテリチニブが奏功したFLT3-ITD変異陽性急性骨髄性白血病口分田貴裕; 頼晋也; 波江野高大; 角谷宏明; 源周治; 綿谷陽作; 芹澤憲太郎; 谷口康博; 森田泰慶; 田中宏和; 芦田隆司; 松村到日本造血細胞移植学会総会プログラム・抄録集 2021年
- フロントラインダサチニブ後のCML-CP患者における治療フリー寛解:JALSG D-STOP216【JST・京大機械翻訳】|||南陽介; 松村到; 高橋直人; 大竹茂樹; 熱田由子; 倉田美穂; 矢野真吾; 入山規良; 上田恭典; 小澤幸泰; 堺田恵美子; 近藤健; 山本正英; 小野孝明; 藤巻克通; 中世古知昭; 宮本敏浩; 麻生規雄; 清井仁; 宮崎泰司日本血液学会学術集会抄録(Web) 2021年
- フロントラインニロチニブ後のCML-CP患者における治療フリー寛解:JALSG N-STOP 216【JST・京大機械翻訳】|||高橋直人; 松村到; 南陽介; 小野孝明; 波多智子; 大竹茂樹; 熱田由子; 倉田美穂; 藤巻克通; 長尾俊景; 中世古知昭; 入山規良; 宮本敏浩; 麻生範雄; 清井仁; 宮崎泰司日本血液学会学術集会抄録(Web) 2021年
- 前向き観察研究で登録されたMDS ptsに対するSCTの転帰;JALSG-CS-11-MDS-SCT【JST・京大機械翻訳】|||中川紀温; 中川紀温; 石山謙; 臼杵憲祐; 高田覚; 富川武樹; 半田寛; 勝岡優奈; 平野大希; 瀬崎伸夫; 住昌彦; 藤澤信; 谷口康博; 市原弘善; 吉村卓朗; 大塚英一; 高瀬謙; 末廣陽子; 太田秀一; 梶口智弘; 前田智也; 山本正英; 大竹茂樹; 勝見章; 清井仁; 松村到; 宮崎泰司日本血液学会学術集会抄録(Web) 2021年
- Pre-B細胞性急性リンパ球性白血病における転写制御ネットワーク都築忍; 安田貴彦; 河津正人; 上野敏秀; シバスンダラン カルナン; 太田明伸; 真田昌; 永井宏和; 冨田章裕; 高橋義行; 宮崎泰司; 松村到; 清井仁; 細川好孝; 間野博行; 早川文彦日本癌学会学術総会抄録集(Web) 2021年
- Retrospective Multi-center Study of Adolescent and Young Adult (AYA) Multiple Myeloma in Kansai Myeloma Forum RegistryAya Nakaya; Takae Kohara; Hirohiko Shibayama; Yoshiyuki Onda; Junya Kanda; Hitomi Kaneko; Kazunori Imada; Toru Kida; Satoru Kosugi; Jun Ishikawa; Ryosuke Yamamura; Yutaka Shimazu; Hirokazu Tanaka; Shin-Ichi Fuchida; Yuji Shimura; Miki Kiyota; Katsuya Wada; Tomoki Ito; Nobuhiko Uoshima; Hideo Yagi; Satoshi Yoshihara; Kensuke Ohta; Chihiro Shimazaki; Masayuki Hino; Akifumi Takaori-Kondo; Junya Kuroda; Itaru Matsumura; Yuzuru Kanakura; Shosaku NomuraBONE MARROW TRANSPLANTATION 2020年12月 SPRINGERNATURE
- 1日の勉強時間は科目試験よりも総合試験の成績に関係する [通常講演]池田 行宏; 三井 良之; 梶 博史; 磯貝 典孝; 赤木 將男; 松村 到医学教育 2020年07月 (一社)日本医学教育学会
- 3学年臨床各論運動器コース記述式試験における態度評価の試み [通常講演]赤木 將男; 柿木 良介; 宮本 裕史; 西村 俊司; 三井 良之; 梶 博史; 池田 行宏; 松村 到; 伊木 雅之医学教育 2020年07月 (一社)日本医学教育学会
- 臨床実習ログブック電子化の試み(第2報) [通常講演]三井 良之; 池田 行宏; 梶 博史; 赤木 將男; 松村 到医学教育 2020年07月 (一社)日本医学教育学会
- 木下 浩二; 船内 正憲; 松村 到臨床リウマチ 2020年06月 (一社)日本臨床リウマチ学会
症例は38歳男性。幼少期より気管支喘息と診断されステロイド薬による治療を受けていた。5年前に両側大腿骨頭壊死の既往あり。1年前から多関節痛あり関節リウマチ疑いにて当科受診。当初はリウマチとして抗リウマチ薬による治療を開始し、一時症状の改善を認めたが、その後痛みが再燃したためMRI検査を施行したところ多数の関節に骨壊死を認めたため、喘息治療で使用されていたステロイド薬による多発骨壊死と診断した。その後ステロイド薬を漸減、中止し、骨壊死に対し保存的治療を行った。(著者抄録) - 非寛解期,特に化学療法抵抗性の造血器腫瘍患者に対する同種造血幹細胞移植成績の検討谷口康博; 芦田隆司; 森田泰慶; 平瀬主税; 頼晋也; 中山聖子; 芹澤憲太郎; 口分田貴裕; 井上宏昭; 岩田吉男; 谷口貴英; 源周治; 角谷宏明; 藤本昂; 小森舞子; 波江野高大; 三宅義昭; 辰巳陽一; 田中宏和; 松村到日本造血細胞移植学会総会プログラム・抄録集 2020年
- 谷口貴英; 中山聖子; 森田泰慶; 頼晋也; 大山泰世; 三宅義昭; 田中宏和; 辰巳陽一; 芦田隆司; 松村到第80回日本血液学会学術集会 2019年10月
- 白血病Up to Date 慢性骨髄性白血病治療の進歩 [通常講演]松村 到日本癌治療学会学術集会抄録集 2019年10月 (一社)日本癌治療学会
- 臨床実習ログブック電子化の試み [通常講演]三井 良之; 池田 行宏; 梶 博史; 赤木 將男; 松村 到医学教育 2019年07月 (一社)日本医学教育学会
- Webを用いた学習環境調査は回答率、有効回答数の確保に有効である [通常講演]池田 行宏; 三井 良之; 梶 博史; 赤木 將男; 松村 到医学教育 2019年07月 (一社)日本医学教育学会
- 芦田 千聖; 志賀 俊彦; 野崎 祐史; 木下 浩二; 船内 正憲; 松村 到日本腎臓学会誌 2019年05月
- Interleukin-17産生のEvans症候群合併のangioimmunoblastic T-cell lymphomaの一例 [通常講演]谷口 貴英; 中山 聖子; 森田 泰慶; 頼 晋也; 平瀬 主税; 谷口 康博; 井上 宏昭; 大山 泰世; 三宅 義昭; Espinoza J Luis; 田中 宏和; 辰巳 陽一; 芦田 隆司; 松村 到日本リンパ網内系学会会誌 2019年05月
- 治療抵抗性TAFRO症候群に合併したAILTの1例 [通常講演]三宅 義昭; 頼 晋也; 井上 宏昭; 口分田 貴裕; 谷口 康博; 中山 聖子; 森田 泰慶; Espinoza J.L; 田中 宏和; 辰巳 陽一; 芦田 隆司; 松村 到日本リンパ網内系学会会誌 2019年05月
- ヘモグロビン値と血小板数に基づくびまん性大細胞型B細胞リンパ腫、非特異型の新たな予後指標の提唱 [通常講演]中山 聖子; 松田 光弘; 森田 泰慶; 頼 晋也; 谷口 康博; 井上 宏昭; 大山 泰世; 谷口 貴英; 三宅 義昭; 足立 達哉; 末田 早苗; Espinoza J. Luis; 田中 宏和; 辰巳 陽一; 芦田 隆司; 松村 到日本リンパ網内系学会会誌 2019年05月
- 十二指腸原発濾胞性リンパ腫における抗腫瘍免疫の寄与 [通常講演]井上 宏昭; 頼 晋也; 口分田 貴裕; 芹澤 憲太郎; 谷口 康博; 中山 聖子; 森田 泰慶; Luis Espinoza J; 田中 宏和; 辰巳 陽一; 芦田 隆司; 松村 到日本リンパ網内系学会会誌 2019年05月
- 芦田隆司; 芦田隆司; 小森舞子; 源周治; 大山泰世; 井上宏昭; 口分田貴裕; 谷口康博; 頼晋也; 森田泰慶; 地守慶亮; 前田朋子; 中野勝彦; 福島靖幸; 川野亜美; 井手大輔; 前田岳宏; 椿本祐子; 藤田往子; 金光靖; 松村到日本輸血細胞治療学会誌 2019年04月
- チロシンキナーゼ阻害薬の進歩 [通常講演]松村 到日本医学会総会会誌 2019年04月 日本医学会
- 脊椎関節炎-1 脊椎関節症におけるMASEI(MAdrid Sonographic Enthesitis Index)評価の乾癬性関節炎鑑別での有用性について [通常講演]赤澤 宗輝; 芦田 千聖; 野崎 祐史; 石村 香織; 池田 房代; 山本 敦弘; 岡田 晃典; 冨田 大介; 伊丹 哲; 酒井 健史; 井上 明日圭; 李 進海; 志賀 俊彦; 岸本 和也; 樋野 尚一; 廣岡 靖章; 木下 浩二; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 2019年03月 (一社)日本リウマチ学会
- 血管炎(大型血管炎)-3 大型血管炎に対するトシリズマブの継続率・治療効果に対する検討 [通常講演]山本 敦弘; 石村 香織; 赤澤 宗輝; 芦田 千聖; 池田 房代; 岡田 晃典; 冨田 大介; 伊丹 哲; 酒井 健史; 李 進海; 井上 明日圭; 志賀 俊彦; 岸本 和也; 廣岡 靖章; 野崎 祐史; 木下 浩二; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 2019年03月 (一社)日本リウマチ学会
- 顕微鏡的多発血管炎(MPA)の寛解導入療法におけるアザチオプリンの有効性と安全性 [通常講演]芦田 千聖; 志賀 俊彦; 野崎 祐史; 伊丹 哲; 石村 香織; 赤澤 宗輝; 池田 房代; 山本 敦弘; 酒井 健史; 井上 明日圭; 李 進海; 岸本 和也; 木下 浩二; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 2019年03月
- 無症候性右内頸動脈閉塞を伴う大型血管炎を合併したCrohn病の一例 [通常講演]石村 香織; 野崎 祐史; 赤澤 宗輝; 芦田 千聖; 池田 房代; 山本 敦弘; 伊丹 哲; 酒井 健史; 井上 明日圭; 李 進海; 志賀 俊彦; 岸本 和也; 木下 浩二; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 2019年03月
- 膠原病に伴う肺高血圧症における強皮症群と非強皮症群の比較検討 [通常講演]酒井 健史; 石村 香織; 赤澤 宗輝; 芦田 千聖; 池田 房代; 山本 敦弘; 伊丹 哲; 井上 明日圭; 李 進海; 志賀 俊彦; 岸本 和也; 野崎 祐史; 木下 浩二; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 2019年03月
- 関節リウマチ治療における第一選択抗リウマチ薬としてのイグラチモド治療効果について [通常講演]野崎 祐史; 井上 明日圭; 木下 浩二; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 2019年03月
- 生物学的製剤を使用している関節リウマチ患者に対するデノスマブの骨破壊抑制効果の検討 [通常講演]伊丹 哲; 岸本 和也; 野崎 祐史; 木下 浩二; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 2019年03月
- メトトレキサート関連リンパ増殖性疾患14例の臨床像の検討 [通常講演]池田 房代; 伊丹 哲; 石村 香織; 赤澤 宗輝; 芦田 千聖; 山本 敦弘; 酒井 健史; 李 進海; 井上 明日圭; 志賀 俊彦; 岸本 和也; 野崎 祐史; 木下 浩二; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 2019年03月
- NP-SLEの経過中にPrimacy Central Nervous System Lymphoma(PCNSL)を併発した全身性エリテマトーデスの一例 [通常講演]杉山 昌史; 岡田 晃典; 湯本 妙子; 井上 明日圭; 廣岡 靖章; 野崎 祐史; 木下 浩二; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 2019年03月
- インフリキシマブ治療におけるRemicheckQ測定意義と治療応用についての検討 [通常講演]野崎 祐史; 廣岡 靖章; 芦田 千聖; 冨田 大介; 岡田 晃典; 井上 明日圭; 木下 浩二; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 2019年03月
- 関節リウマチの治療(csDMARDs・bDMARDs) 生物学的製剤に効果不十分な関節リウマチ患者に対するイグラチモド併用効果の検討 [通常講演]冨田 大介; 伊丹 哲; 堤 聡; 奥田 康介; 野崎 祐史; 船内 正憲; 松村 到; 松原 司日本リウマチ学会総会・学術集会プログラム・抄録集 2019年03月
- リウマチ性疾患の合併症-2 リウマチ膠原病疾患におけるGerdQ問診票を用いたGERD症状評価の有用性について [通常講演]岸本 和也; 野崎 祐史; 伊丹 哲; 酒井 健史; 李 進海; 井上 明日圭; 志賀 俊彦; 木下 浩二; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 2019年03月
- 多彩な膠原病-3 成人Still病の診断における血清IL-18測定の有用性の検討 [通常講演]志賀 俊彦; 岸本 和也; 野崎 祐史; 木下 浩二; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 2019年03月
- 中山聖子; 松田光弘; 足立達哉; 末田早苗; 岩永隆行; 小川巌; 橋本重夫; 松村到日本内科学会雑誌 2019年02月
- びまん性大細胞型B細胞リンパ腫、非特異型におけるヘモグロビン値と血小板数に基づく新たな予後指標 [通常講演]中山 聖子; 松田 光弘; 足立 達哉; 末田 早苗; 岩永 隆行; 小川 巌; 橋本 重夫; 松村 到日本内科学会雑誌 2019年02月 (一社)日本内科学会
- 波江野高大; 口分田貴裕; 森田泰慶; 芦田隆司; 松村到; 高島康利; 木村雅友臨床血液 2019年01月
- 脊椎関節症におけるMASEI(MAdrid Sonographic Enthesitis Index)評価の乾癬性関節炎鑑別での有用性について赤澤宗輝; 芦田千聖; 野崎祐史; 石村香織; 池田房代; 山本敦弘; 岡田晃典; 冨田大介; 伊丹哲; 酒井健史; 井上明日圭; 李進海; 志賀俊彦; 岸本和也; 樋野尚一; 廣岡靖章; 木下浩二; 船内正憲; 松村到日本リウマチ学会総会・学術集会プログラム・抄録集 2019年
- 関節リウマチにおけるセルトリズマブペゴルのメトトレキサート用量別の治療効果・安全性について李進海; 野崎祐史; 赤澤宗輝; 芦田千聖; 池田房代; 山本敦弘; 伊丹哲; 酒井健史; 井上明日圭; 志賀俊彦; 岸本和也; 木下浩二; 船内正憲; 松村到日本リウマチ学会総会・学術集会プログラム・抄録集 2019年
- 当院におけるサリルマブの使用経験岸本和也; 野崎祐史; 赤澤宗輝; 芦田千聖; 岡田晃典; 志賀俊彦; 樋野尚一; 木下浩二; 船内正憲; 松村到日本臨床リウマチ学会プログラム・抄録集 2019年
- 25-(OH)D3-1α-hydroxylases産生のびまん性大細胞型B細胞リンパ腫の一例(25-Hydroxyvitamin D3-1α-hydroxylase- and multiple cytokine-producing diffuse large B-cell lymphoma) [通常講演]中山 聖子; 松田 光弘; 足立 達哉; 末田 早苗; 大橋 由香; 淡路 有恵; 橋本 重夫; 松村 到第80回日本血液学会学術集会 2018年10月
- 脳静脈洞血栓症を合併し、開頭減圧術・術後エクリズマブ投与が有効であったPNHの一例(Post-operative treatment with eculizumab for PNH presenting as cerebral venous sinus thrombosis) [通常講演]岩田 吉生; 森田 泰慶; 辻 潔; 頼 晋也; 田崎 貴之; 井上 宏昭; 谷口 康博; 藤本 昂; 田中 宏和; 芦田 隆司; 加藤 天美; 松村 到第80回日本血液学会学術集会 2018年10月
- KMFに登録されたボルテゾミブとIMiDs両剤に抵抗性の再発骨髄腫の予後解析(Clinical outcomes of relapsed myeloma, dual refractory to bortezomib and IMiDs in KMF registry) [通常講演]藤原 亮介; 田中 宏和; 芹澤 憲太郎; 金子 仁臣; 志村 勇司; 太田 健介; 淵田 真一; 中谷 綾; 諫田 淳也; 八木 秀男; 和田 勝也; 小杉 智; 魚嶋 伸彦; 柴山 浩彦; 小原 尚恵; 中谷 英仁; 内山 人二; 足立 陽子; 飯田 正人; 濱田 常義; 松田 光弘; 高折 晃史; 野村 昌作; 島崎 千尋; 日野 雅之; 黒田 純也; 谷脇 雅史; 今田 和典; 金倉 譲; 松村 到第80回日本血液学会学術集会 2018年10月
- Cytotoxic T-lymphocyte-associated antigen 4陽性の成人T細胞性白血病・リンパ腫の一例(Cytotoxic T-lymphocyte-associated antigen 4-positive aggressive adult T cell leukemia/lymphoma) [通常講演]末田 早苗; 中山 聖子; 足立 達哉; 大橋 由香; 淡路 有恵; 橋本 重夫; 松村 到; 松田 光弘第80回日本血液学会学術集会 2018年10月
- 骨髄異形成症候群に合併したSweet病に対するアザシチジンの免疫学的効果(Immunological effects of azacitidin on Sweet's disease associated with myelodysplastic syndromes) [通常講演]谷口 貴英; 芹澤 憲太郎; 田中 宏和; 森田 泰慶; 谷口 康博; 辰巳 陽一; 芦田 隆司; 松村 到第80回日本血液学会学術集会 2018年10月
- 形質細胞腫の後方視的多施設共同研究(関西骨髄腫フォーラム)(Retrospective multi-centers study of plasmacytoma) [通常講演]中谷 綾; 田中 宏和; 八木 秀男; 太田 健介; 柴山 浩彦; 諫田 淳也; 新堂 真紀; 志村 勇司; 小杉 智; 木田 亨; 金子 仁臣; 今田 和典; 烏野 隆博; 松田 光弘; 飯田 正人; 足立 陽子; 淵田 真一; 魚嶋 伸彦; 内山 人二; 高橋 良一; 松井 利充; 和田 勝也; 清田 実希; 島崎 千尋; 日野 雅之; 黒田 純也; 金倉 譲; 高折 晃史; 野村 昌作; 松村 到第80回日本血液学会学術集会 2018年10月
- 後天性赤芽球癆における予後不良因子とPRCA2016前向きコホート研究第2回中間解析の報告(Adverse risk factors for survival in acquired PRCA: the second interim analysis of PRCA2016 study) [通常講演]廣川 誠; 澤田 賢一; 藤島 直仁; 寺村 正尚; 別所 正美; 檀 和夫; 鶴見 寿; 中尾 眞二; 浦部 晶夫; 藤澤 信; 米村 雄士; 河野 文夫; 押味 和夫; 杉本 耕一; 松田 晃; 唐沢 正光; 新井 文子; 小松 則夫; 張替 秀郎; 通山 薫; 齋藤 明子; 松村 到; 小峰 光博; 小澤 敬也; 黒川 峰夫; 荒井 俊也; 三谷 絹子第80回日本血液学会学術集会 2018年10月
- KEYNOTE185 未治療多発性骨髄腫を対象としたLen/dex±pembrolizumab第3相試験(日本人解析含む)(KEYNOTE185: Randomized phase 3 study of Len/dex±pembrolizumab in untreated MM: including JPN subset) [通常講演]小杉 浩史; 竹迫 直樹; 松本 守生; 飯田 真介; 石川 隆之; 近藤 恭夫; 安藤 潔; 張 高明; 三木 浩和; 松村 到; 角南 一貴; 豊嶋 崇徳; 岩崎 浩己; 大西 康; 木崎 昌弘; 伊豆津 宏二; 丸山 大; 飛内 賢正; 鈴木 憲史第80回日本血液学会学術集会 2018年10月
- CD34陽性ヒト骨髄腫幹細胞の同定と特性解析(Identification and characterization of CD34+ myeloma cell population as myeloma-initiating cells) [通常講演]芹澤 憲太郎; 田中 宏和; 福井 彩乃; 藤原 亮介; 佐野 圭吾; 口分田 貴裕; 谷口 康博; 森田 泰慶; ルイス・エスピノザ; 辰巳 陽一; 芦田 隆司; 松村 到第80回日本血液学会学術集会 2018年10月
- 十二指腸型濾胞性リンパ腫は、抗腫瘍免疫により良好な予後を示す(Duodenal-type follicular lymphoma exhibits good prognosis through the increased anti-tumor immunity) [通常講演]井上 宏昭; 頼 晋也; 口分田 貴裕; 芹澤 憲太郎; 谷口 康博; 中山 聖子; 森田 泰慶; ルイス・エスピノザ; 田中 宏和; 辰巳 陽一; 芦田 隆司; 松村 到第80回日本血液学会学術集会 2018年10月
- 発熱性好中球減少症遷延に対する従来型経験的治療とD-indexによる早期治療の無作為割付比較試験(Classical empiric therapy vs. D-index-guided early therapy for persistent FN: First analysis of RCT) [通常講演]飯野 昌樹; 神田 善伸; 木村 俊一; 福田 隆浩; 堺田 惠美子; 小宅 達郎; 山口 博樹; 藤原 慎一郎; 城 有美; 岡本 晃直; 藤田 浩之; 高松 泰; 佐分利 能生; 松村 到; 山之内 純; 白鳥 聡一; 後藤 守孝; 中村 信元; 田村 和夫第80回日本血液学会学術集会 2018年10月
- 成人B細胞性急性リンパ性白血病のゲノム学的・臨床的な特徴(Genomic and clinical characterization of adult B-cell acute lymphoblastic leukemia) [通常講演]安田 貴彦; 西島 大; 小島 進也; 河津 正人; 上野 敏秀; 都築 忍; 清井 仁; 松村 到; 宮崎 泰司; 堀部 敬三; 間野 博行; 直江 知樹; 眞田 昌; 早川 文彦第80回日本血液学会学術集会 2018年10月
- BCR-ABL陰性骨髄増殖性腫瘍においてTET2変異は生存に対する予後不良因子である(TET2 mutation is a poor prognostic factor for survival in BCR-ABL-negative MPN patients) [通常講演]谷口 康博; 田中 宏和; 藤原 亮介; 森田 泰慶; 花本 仁; 辰巳 陽一; 芦田 隆司; 松村 到第80回日本血液学会学術集会 2018年10月
- RRMM患者に対するKRD療法およびKD療法の後方視的解析(関西骨髄腫フォーラム)(KRD and KD treatment for relapsed/refractory multiple myeloma in Kansai Myeloma Forum study) [通常講演]恩田 佳幸; 諫田 淳也; 金子 仁臣; 柴山 浩彦; 志村 勇司; 太田 健介; 田中 宏和; 淵田 真一; 中谷 綾; 魚嶋 伸彦; 小杉 智; 松田 光弘; 足立 陽子; 八木 秀男; 内山 人二; 新堂 真紀; 今田 和典; 日野 雅之; 野村 昌作; 島崎 千尋; 黒田 純也; 金倉 譲; 高折 晃史; 松村 到第80回日本血液学会学術集会 2018年10月
- 症候性骨髄腫1414例の後方視的解析 関西骨髄腫フォーラムからの最新報告(Retrospective analyses of 1,414 symptomatic multiple myeloma cases: update from Kansai Myeloma Forum) [通常講演]田中 宏和; 芹澤 憲太郎; 中谷 綾; 金子 仁臣; 太田 健介; 小杉 智; 八木 秀男; 花本 仁; 淵田 真一; 志村 勇司; 柴山 浩彦; 小原 尚恵; 中谷 英仁; 諫田 淳也; 魚嶋 伸彦; 和田 勝也; 烏野 隆博; 松井 利充; 内山 人二; 松田 光弘; 足立 陽子; 高折 晃史; 黒田 純也; 谷脇 雅史; 島崎 千尋; 日野 雅之; 今田 和典; 野村 昌作; 金倉 譲; 松村 到第80回日本血液学会学術集会 2018年10月
- 異常なRTKの細胞内輸送阻害は急性骨髄性白血病における有望な治療標的である(Intracellular trafficking of mutated RTKs shows promising therapeutic target against AML) [通常講演]頼 晋也; 田中 宏和; 鈴木 麻衣; Espinoza Luis; 谷村 朗; 森田 泰慶; 辰巳 陽一; 横田 貴史; 織谷 健司; 渡邊 俊雄; 金倉 譲; 松村 到第80回日本血液学会学術集会 2018年10月
- 造血器腫瘍における治療標的としてのチロシンキナーゼ(Tyrosine kinase as a therapeutic target in hematologic malignancies) [通常講演]松村 到第80回日本血液学会学術集会 2018年10月
- サリドマイド単剤治療を施行した症候性骨髄腫230例の後方視的解析(関西骨髄腫フォーラム) [通常講演]金子仁臣; 柴山浩彦; 八木秀男; 諫田淳也; 中谷 綾; 小杉 智; 木田 亨; 田中宏和; 志村勇司; 淵田真一; 足立陽子; 和田勝也; 清田実希; 魚嶋伸彦; 太田健介; 小原尚恵; 濱田常義; 小林正行; 内山人二; 烏野隆博; 黒田純也; 今田和典; 高折晃史; 島崎千尋; 金倉 譲; 日野雅之; 野村昌作; 松村 到第80回日本血液学会学術集会 2018年10月
- RRMM患者に対するKRD療法およびKD療法の後方視的解析(関西骨髄腫フォーラム) [通常講演]恩田佳幸; 諫田淳也; 金子仁臣; 柴山浩彦; 志村勇司; 太田健介; 田中宏和; 淵田真一; 中谷 綾; 魚嶋伸彦; 小杉 智; 松田光弘; 足立陽子; 八木秀男; 内山人二; 新堂真紀; 今田和典; 日野雅之; 野村昌作; 島崎千尋; 黒田純也; 金倉 譲; 高折晃史; 松村 到第80回日本血液学会学術集会 2018年10月
- 症候性骨髄腫1414例の後方視的解析:関西骨髄腫フォーラムからの最新報告 [通常講演]田中宏和; 芹澤憲太郎; 中谷 綾; 金子仁臣; 太田健介; 小杉 智; 八木秀男; 花本 仁; 淵田真一; 志村勇司; 柴山浩彦; 小原尚恵; 中谷英仁; 諫田淳也; 魚嶋伸彦; 和田勝也; 烏野隆博; 松井利充; 内山人二; 松田光弘; 足立陽子; 高折晃史; 黒田純也; 谷脇雅史; 島崎千尋; 日野雅之; 今田和典; 野村昌作; 金倉 譲; 松村 到第80回日本血液学会学術集会 2018年10月
- 形質細胞腫の後方視的多施設共同研究(関西骨髄腫フォーラム) [通常講演]中谷 綾; 田中宏和; 八木秀男; 太田健介; 柴山浩彦; 諫田淳也; 新堂真紀; 志村勇司; 小杉 智; 木田 亨; 金子仁臣; 今田和典; 烏野隆博; 松田光弘; 飯田正人; 足立陽子; 淵田真一; 魚嶋伸彦; 内山人二; 高橋良一; 松井利充; 和田勝也; 清田実希; 島崎 千尋; 日野雅之; 黒田純也; 金倉 譲; 高折晃史; 野村昌作; 松村到第80回日本血液学会学術集会 2018年10月
- KMFに登録されたボルテゾミブとIMiDs両剤に抵抗性の再発骨髄腫の予後解析 [通常講演]藤原亮介; 田中宏和; 芹澤憲太郎; 金子仁臣; 志村勇司; 太田健介; 淵田真一; 中谷 綾; 諫田淳也; 八木秀男; 和田勝也; 小杉智; 魚嶋伸彦; 柴山浩彦; 小原尚恵; 中谷英仁; 内山人二; 足立陽子; 飯田正人; 濱田常義; 松田光弘; 高折晃史; 野村昌作; 島崎千尋; 日野雅之; 黒田純也; 谷脇雅史; 今田和典; 金倉譲; 松村到第80回日本血液学会学術集会 2018年10月
- 異常なRTKの細胞内輸送阻害は急性骨髄性白血病における有望な治療標的である [通常講演]頼 晋也; 田中宏和; 鈴木麻衣; Luis Espinoza; 谷村 朗; 森田泰慶; 辰巳陽一; 横田貴史; 織谷健司; 渡邊俊雄; 金倉 譲; 松村 到第80回日本血液学会学術集会 2018年10月
- 脳静脈洞血栓症を合併し、開頭減圧術・術後エクリズマブ投与が有効であったPNHの一例(Post-operative treatment with eculizumab for PNH presenting as cerebral venous sinus thrombosis) [通常講演]岩田 吉生; 森田 泰慶; 辻 潔; 頼 晋也; 田崎 貴之; 井上 宏昭; 谷口 康博; 藤本 昂; 田中 宏和; 芦田 隆司; 加藤 天美; 松村 到臨床血液 2018年09月 (一社)日本血液学会-東京事務局
- KMFに登録されたボルテゾミブとIMiDs両剤に抵抗性の再発骨髄腫の予後解析(Clinical outcomes of relapsed myeloma, dual refractory to bortezomib and IMiDs in KMF registry) [通常講演]藤原 亮介; 田中 宏和; 芹澤 憲太郎; 金子 仁臣; 志村 勇司; 太田 健介; 淵田 真一; 中谷 綾; 諫田 淳也; 八木 秀男; 和田 勝也; 小杉 智; 魚嶋 伸彦; 柴山 浩彦; 小原 尚恵; 中谷 英仁; 内山 人二; 足立 陽子; 飯田 正人; 濱田 常義; 松田 光弘; 高折 晃史; 野村 昌作; 島崎 千尋; 日野 雅之; 黒田 純也; 谷脇 雅史; 今田 和典; 金倉 譲; 松村 到臨床血液 2018年09月 (一社)日本血液学会-東京事務局
- 症候性骨髄腫1414例の後方視的解析 関西骨髄腫フォーラムからの最新報告(Retrospective analyses of 1,414 symptomatic multiple myeloma cases: update from Kansai Myeloma Forum) [通常講演]田中 宏和; 芹澤 憲太郎; 中谷 綾; 金子 仁臣; 太田 健介; 小杉 智; 八木 秀男; 花本 仁; 淵田 真一; 志村 勇司; 柴山 浩彦; 小原 尚恵; 中谷 英仁; 諫田 淳也; 魚嶋 伸彦; 和田 勝也; 烏野 隆博; 松井 利充; 内山 人二; 松田 光弘; 足立 陽子; 高折 晃史; 黒田 純也; 谷脇 雅史; 島崎 千尋; 日野 雅之; 今田 和典; 野村 昌作; 金倉 譲; 松村 到臨床血液 2018年09月 (一社)日本血液学会-東京事務局
- The evaluation of consolidation and maintenance therapies after HDT/ASCT for symptomatic MM [通常講演]Aya Nakaya; Eiji Nakatani; Hitomi Kaneko; Hirohiko Shibayama; Yuji Shimura; Junya Kanda; Maki Shindo; Kensuke Ohta; Satoru Kosugi; Shin-Ichi Fuchida; Hideo Yagi; Hirokazu Tanaka; Yuri Kamitsuji; Takahiro Karasuno; Nobuhiko Uoshima; Eri Kawata; Yoko Adachi; Hitoji Uchiyama; Toshimitsu Matsui; Mitsuhiro Matsuda; Jun Ishikawa; Tsuneyoshi Hamada; Ryoichi Takahashi; Kazunori Imada; Chihiro Shimazaki; Masayuki Hino; Junya Kuroda; Yuzuru Kanakura; Akifumi Takaori-Kondo; Shosaku Nomura; Itaru MatsumuraBONE MARROW TRANSPLANTATION 2018年09月 NATURE PUBLISHING GROUP
- CLEC-2の発現は巨核球にバイアスした長期骨髄再建能を有する造血幹細胞集団を規定する(CLEC-2 identifies a functionally distinct subpopulation of megakaryocyte-biased HSCs) [通常講演]口分田 貴裕; 田中 宏和; Espinoza J. Luis; 岩田 吉生; 佐野 圭吾; 芹澤 憲太郎; 谷口 康博; 頼 晋也; 森田 泰慶; 辰巳 陽一; 芦田 隆司; 松村 到第80回日本血液学会学術集会 2018年09月
- 酒井健史; 野崎祐史; 李進海; 岸本和也; 永禮靖章; 船内正憲; 松村到日本腎臓学会誌 2018年04月
- 酒井健史; 赤澤宗輝; 芦田千聖; 池田房代; 山本敦弘; 岡田晃典; 冨田大介; 井上明日圭; 田崎知江美; 李進海; 志賀俊彦; 岸本和也; 永禮靖章; 野崎祐史; 船内正憲; 松村到日本リウマチ学会総会・学術集会プログラム・抄録集 2018年03月
- 山本敦弘; 井上明日圭; 岡田晃典; 芦田千聖; 冨田大介; 酒井健史; 李進海; 志賀俊彦; 岸本和也; 永禮靖章; 野崎祐史; 船内正憲; 松村到日本リウマチ学会総会・学術集会プログラム・抄録集 2018年03月
- 野崎祐史; 志賀俊彦; 岸本和也; 永禮靖章; 木下浩二; 船内正憲; 松村到日本リウマチ学会総会・学術集会プログラム・抄録集 2018年03月
- 永禮靖章; 赤澤宗輝; 芦田千聖; 池田房代; 山本敦弘; 岡田晃典; 冨田大介; 酒井健史; 井上明日圭; 李進海; 志賀俊彦; 岸本和也; 野崎祐史; 船内正憲; 松村到日本リウマチ学会総会・学術集会プログラム・抄録集 2018年03月
- 井上明日圭; 野崎祐史; 赤澤宗輝; 芦田千聖; 池田房代; 山本敦弘; 岡田晃典; 冨田大介; 酒井健史; 李進海; 志賀俊彦; 岸本和也; 永禮靖章; 船内正憲; 松村到日本リウマチ学会総会・学術集会プログラム・抄録集 2018年03月
- 芦田千聖; 野崎祐史; 樋野尚一; 赤澤宗輝; 池田房代; 山本敦弘; 岡田晃典; 冨田大介; 酒井健史; 李進海; 井上明日圭; 志賀俊彦; 岸本和也; 永禮靖章; 船内正憲; 松村到日本リウマチ学会総会・学術集会プログラム・抄録集 2018年03月
- 李進海; 野崎祐史; 赤澤宗輝; 芦田千聖; 池田房代; 山本敦弘; 岡田晃典; 冨田大介; 酒井健史; 井上明日圭; 志賀俊彦; 岸本和也; 永禮靖章; 船内正憲; 松村到日本リウマチ学会総会・学術集会プログラム・抄録集 2018年03月
- 岡田晃典; 志賀俊彦; 田崎知江美; 冨田大介; 伊丹哲; 酒井健史; 井上明日圭; 李進海; 岸本和也; 永禮靖章; 野崎祐史; 船内正憲; 松村到日本リウマチ学会総会・学術集会プログラム・抄録集 2018年03月
- 視神経脊髄炎に関節リウマチを合併した一例 [通常講演]池田房代; 岡田晃典; 岸本和也; 赤澤宗輝; 芦田千聖; 山本敦弘; 冨田大介; 酒井健史; 李進海; 井上明日香; 志賀俊彦; 永禮靖章; 野崎祐史; 船内正憲; 松村到日本リウマチ学会総会・学術集会プログラム・抄録集 2018年03月
- 赤澤宗輝; 志賀俊彦; 芦田千聖; 池田房代; 山本敦弘; 岡田晃典; 冨田大介; 酒井健史; 井上明日圭; 田崎知江美; 李進海; 岸本和也; 永禮靖章; 野崎祐史; 船内正憲; 松村到日本リウマチ学会総会・学術集会プログラム・抄録集 2018年03月
- 野崎祐史; 富田大介; 岡田晃典; 井上明日圭; 木下浩二; 船内正憲; 松村到日本リウマチ学会総会・学術集会プログラム・抄録集 2018年03月
- 難治多発性骨髄腫に移植前再寛解導入療法としてKRd療法を用いた1例 [通常講演]大山泰世; 芹澤憲太郎; 森田泰慶; 角谷 宏明; 藤本昂; 谷口貴英; 田中宏和; 辰巳陽一; 芦田隆司; 松村 到第219回 日本内科学会近畿地方会 2018年03月
- 関節超音波検査(US)を用いた非TNF阻害薬(アバタセプト;ABT、トシリズマブ;TCZ)有効性の比較検討 [通常講演]李 進海; 野崎 祐史; 赤澤 宗輝; 芦田 千聖; 池田 房代; 山本 敦弘; 岡田 晃典; 冨田 大介; 酒井 健史; 井上 明日圭; 志賀 俊彦; 岸本 和也; 永禮 靖章; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 2018年03月 (一社)日本リウマチ学会
- 骨粗鬆症と骨代謝/変形性関節症・軟骨2 治療抵抗性ステロイド性骨粗鬆症におけるデノスマブとテリパラチドの治療効果について [通常講演]永禮 靖章; 赤澤 宗輝; 芦田 千聖; 池田 房代; 山本 敦弘; 岡田 晃典; 冨田 大介; 酒井 健史; 井上 明日圭; 李 進海; 志賀 俊彦; 岸本 和也; 野崎 祐史; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 2018年03月
- 関節リウマチの治療8:用法・用量・スイッチ1 インフリキシマブ増量・減量プロトコルによる臨床効果及び骨破壊進行抑制効果について [通常講演]野崎 祐史; 富田 大介; 岡田 晃典; 井上 明日圭; 木下 浩二; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 2018年03月
- 強皮症・MCTD・重複症候群1 全身性強皮症におけるcapillary microscopeでの爪床部毛細血管所見の検討 [通常講演]酒井 健史; 赤澤 宗輝; 芦田 千聖; 池田 房代; 山本 敦弘; 岡田 晃典; 冨田 大介; 井上 明日圭; 田崎 知江美; 李 進海; 志賀 俊彦; 岸本 和也; 永禮 靖章; 野崎 祐史; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 2018年03月
- 多発性筋炎・皮膚筋炎3 当院における抗MDA5(melanoma differentiation-accociated gene5)陽性患者18例の予後不良因子解析 [通常講演]芦田 千聖; 野崎 祐史; 樋野 尚一; 赤澤 宗輝; 池田 房代; 山本 敦弘; 岡田 晃典; 冨田 大介; 酒井 健史; 李 進海; 井上 明日圭; 志賀 俊彦; 岸本 和也; 永禮 靖章; 船内 正憲; 松村 到日本リウマチ学会総会・学術集会プログラム・抄録集 2018年03月
- 複数の免疫異常を合併した脾辺縁帯リンパ腫の1例 [通常講演]三宅 義昭; 口分田 貴裕; 波江野 高大; 森田 泰慶; 嶋田 高広; 田中 宏和; 辰巳 陽一; 芦田 隆司; 松村 到臨床血液 2018年02月
- 難治性血栓症を伴うI型クリオグロブリン血症を合併したリンパ形質細胞性リンパ腫の1例 [通常講演]國田 裕貴; 口分田 貴裕; 波江野 高大; 森田 泰慶; 嶋田 高広; 田中 宏和; 辰巳 陽一; 芦田 隆司; 松村 到臨床血液 2018年02月
- 当院における抗MDA5(melanoma differentiation-accociated gene5)陽性患者18例の予後不良因子解析芦田千聖; 野崎祐史; 樋野尚一; 赤澤宗輝; 池田房代; 山本敦弘; 岡田晃典; 冨田大介; 酒井健史; 李進海; 井上明日圭; 志賀俊彦; 岸本和也; 永禮靖章; 船内正憲; 松村到日本リウマチ学会総会・学術集会プログラム・抄録集 2018年
- 末梢血幹細胞採取前のCD34細胞数測定の有用性 [通常講演]山田枝里佳; 斉藤花往里; 藤本昂; 角谷宏明; 岩田吉生; 谷口貴英; 源周治; 大山泰世; 口分田貴裕; 井上宏昭; 芹澤憲太郎; 谷口康博; 頼晋也; 平瀬主税; 森田泰慶; 田中宏和; 岡野意浩; 坂田尚己; 芦田隆司; 松村到日本アフェレシス学会雑誌 2018年
- 山本敦弘; 石村香織; 赤澤宗輝; 芦田千聖; 池田房代; 伊丹哲; 酒井建史; 李進海; 井上明日圭; 田崎知恵実; 志賀俊彦; 岸本和也; 永禮靖章; 野崎祐史; 木下浩二; 船内正憲; 松村到日本臨床リウマチ学会プログラム・抄録集 2018年