詳細

賴　晋也 （ライ　シンヤ）

  • 医学科　医学部講師
Last Updated :2024/04/25

コミュニケーション情報 byコメンテータガイド

  • コメント

    骨髄腫や悪性リンパ腫などの造血器腫瘍に対する分子標的治療を専門とする。

  • 報道関連出演・掲載一覧

    ＜報道関連出演・掲載一覧＞ ●2019/12/20 　サンケイスポーツ 　びまん性大細胞B細胞リンパ腫について

研究者情報

学位

  • 医学博士（近畿大学）

ホームページURL

J-Global ID

現在の研究分野（キーワード）

    骨髄腫や悪性リンパ腫などの造血器腫瘍に対する分子標的治療を専門とする。

研究分野

  • ライフサイエンス / 血液、腫瘍内科学

経歴

  • 近畿大学医学部 血液・膠原病内科講師

学歴

  •         - 2005年03月   近畿大学   医学部

所属学協会

  • 日本リンパ網内系学会   日本移植学会   日本リウマチ学会   日本輸血・細胞治療学会   日本エイズ学会   日本造血細胞移植学会   日本血液学会   日本内科学会   

研究活動情報

論文

  • 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 Matsumura
    Journal 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.
  • Yuqin Song; Herve Tilly; Shinya Rai; Huilai Zhang; Jie Jin; Hideki Goto; Yasuhito Terui; Ho-Jin Shin; Won Seog S Kim; Junning Cao; Jifeng Feng; Hyeon-Seok Eom; Tae Min Kim; Xavier Cheng-Hong Tsai; Jyh-Pyng Gau; Hideo Koh; Liling Zhang; Yongping Song; Yu Yang; Wei Li; He Huang; Kiyoshi Ando; Jeff P Sharman; Laurie H Sehn; Lilian Bu; Xin Wang; Yanwen Jiang; Jamie Hirata; Calvin Lee; Jun Zhu; Koji Izutsu
    Blood 141 16 1971 - 1981 2023年01月 
    In the phase 3 POLARIX study (NCT03274492), polatuzumab vedotin combined with rituximab plus cyclophosphamide, doxorubicin and prednisone (Pola-R-CHP) significantly improved progression-free survival (PFS) compared with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) with similar safety in previously untreated diffuse large B-cell lymphoma. Patients were randomized 1:1 to 6 cycles of Pola-R-CHP or R-CHOP plus 2 cycles of rituximab alone. For registration of POLARIX in China, consistency of PFS in an Asia subpopulation (defined as ≥50% of the risk reduction in PFS expected in the global population) was evaluated. Overall, 281 patients were analyzed: 160 patients from Asia in the intent-to-treat (ITT) population of the global study and 121 from an ITT China extension cohort. Of these, 141 were randomized to Pola-R-CHP and 140 to R-CHOP. At data cut-off (June 28, 2021; median follow-up 24.2 months), PFS met the consistency definition with the global population and was superior with Pola-R-CHP versus R-CHOP (hazard ratio 0.64; 95% confidence interval [CI], 0.40-1.03). Two-year PFS was 74.2% (95% CI, 65.7-82.7) and 66.5% (95% CI, 57.3-75.6) with Pola-R-CHP and R-CHOP, respectively. Safety was comparable between Pola-R-CHP and R-CHOP, including rates of grade 3-4 adverse events (AEs; 72.9% vs 66.2%, respectively), serious AEs (32.9% vs 32.4%), grade 5 AEs (1.4% vs 0.7%), AEs leading to study treatment discontinuation (5.0% vs 7.2%), and any-grade peripheral neuropathy (44.3% vs 50.4%). These findings demonstrate consistent efficacy and safety of Pola-R-CHP versus R‑CHOP in the Asian and global populations in POLARIX.
  • Shinya Rai; Won Seog Kim; Kiyoshi Ando; Ilseung Choi; Koji Izutsu; Norifumi Tsukamoto; Masahiro Yokoyama; Kunihiro Tsukasaki; Junya Kuroda; Jun Ando; Michihiro Hidaka; Youngil Koh; Hirohiko Shibayama; Toshiki Uchida; Deok Hwan Yang; Kenji Ishitsuka; Kenichi Ishizawa; Jin Seok Kim; Hong Ghi Lee; Hironobu Minami; Hyeon Seok Eom; Mitsutoshi Kurosawa; Jae Hoon Lee; Jong Seok Lee; Won Sik Lee; Hirokazu Nagai; Takero Shindo; Dok Hyun Yoon; Shinichiro Yoshida; Mireille Gillings; Hiroshi Onogi; Kensei Tobinai
    Haematologica 108 3 811 - 821 2022年10月 
    Tucidinostat (formerly known as chidamide) is an orally available, novel benzamide class of histone deacetylase (HDAC) inhibitor that selectively blocks class I and class IIb HDACs. This multicenter phase IIb study aimed to investigate the efficacy and safety of tucidinostat, 40 mg twice per week (BIW), in patients with relapsed/refractory (R/R) peripheral T-cell lymphoma (PTCL). The primary endpoint was overall response rate (ORR) assessed by an independent overall efficacy review committee. Between March 2017 and March 2019, 55 patients were treated, and 46 and 55 were evaluated for efficacy and safety, respectively. Twenty-one of 46 patients achieved objective responses with an ORR of 46% (95% confidence interval [CI]: 30.9, 61.0), including five patients with complete response (CR). Responses were observed across various PTCL subtypes. In angioimmunoblastic T-cell lymphoma, there were 2 CRs and 5 partial responses (PR) among eight patients, achieving an ORR of 88%. The disease control rate (CR + PR + stable disease) was 72% (33/46). The median progression-free survival, duration of response, and overall survival were 5.6 months, 11.5 months, 22.8 months, respectively. The most common adverse events (AEs) (all grades) were thrombocytopenia, neutropenia, leukopenia, anemia, and diarrhea. The grade ≥ 3 AEs emerging in ≥20% of patients included thrombocytopenia (51%), neutropenia (36%), lymphopenia (22%), and leukopenia (20%). Importantly, most of the AEs were manageable by supportive care and dose modification. In conclusion, the favorable efficacy and safety profiles indicate that tucidinostat would be a new therapeutic option in patients with R/R PTCL. (ClinicalTrials.gov identifier: NCT02953652).
  • Shinya Rai; Yoshinori Tanizawa; Zhihong Cai; Yu-Jing Huang; Kaisa Taipale; Masaomi Tajimi
    Advances in therapy 39 10 4792 - 4807 2022年10月 
    INTRODUCTION: Treatment options in patients with mantle cell lymphoma (MCL) failing ibrutinib are limited, with no standard therapies defined. This study aimed to investigate real-world treatment patterns and outcomes for patients with MCL following ibrutinib. METHODS: This study utilized a de-identified hospital-based claims database (Medical Data Vision) in Japan. Eligible patients were adults who were diagnosed with MCL and had received antitumor drugs between December 2010 and July 2020. Patients were followed from the first antitumor drug treatment until the end of available data up to July 2021. Time-to-event analyses utilized the Kaplan-Meier method. Factors for receiving post-ibrutinib therapy were explored with logistic regression analysis. RESULTS: Of the 1386 patients who started antitumor drug therapy, 247 patients received and discontinued ibrutinib at any line of therapy. Among them, 137 patients (55.5%) received subsequent therapy. The median age at the end of ibrutinib therapy was 77 (range 42-95), and 44 patients had a dependent activity of daily living (ADL). Factors negatively associated with receiving post-ibrutinib therapy after discontinuation of ibrutinib were age ≥ 75 years (odds ratio [95% CI] 0.46 [0.26-0.80]) and emergency hospital admissions (0.37 [0.17-0.84]). Immediate post-ibrutinib therapy regimens were highly diverse, with BR (bendamustine, rituximab) only prescribed in more than 10% of patients. The median duration of post-ibrutinib therapy was 1.5 months (95% CI 1.07-2.07). The median overall survival from the end of ibrutinib therapy in patients regardless of the receipt of post-ibrutinib therapy (n = 247), in those who did not receive post-ibrutinib therapy (n = 110), and in those who received post-ibrutinib therapy (n = 137) was 5.6 months (95% CI 3.8-8.7), 2.3 months (95% CI 1.2-3.9), and 8.7 months (95% CI 5.6-13.8), respectively. The most common adverse event during post-ibrutinib therapy was infection, with the use of anti-infectives (17%). CONCLUSIONS: Patients with MCL previously treated with ibrutinib have poor ability to carry out ADL and experience very poor outcomes. New safe, effective therapies are needed.
  • Koji Izutsu; Shinichi Makita; Kisato Nosaka; Makoto Yoshimitsu; Atae Utsunomiya; Shigeru Kusumoto; Satoko Morishima; Kunihiro Tsukasaki; Toyotaka Kawamata; Takaaki Ono; Shinya Rai; Hiroo Katsuya; Jun Ishikawa; Hironori Yamada; Kazunobu Kato; Masaya Tachibana; Yasuyuki Kakurai; Nobuaki Adachi; Kensei Tobinai; Kentaro Yonekura; Kenji Ishitsuka
    Blood 141 10 1159 - 1168 2022年09月 [査読有り]
     
    Adult T-cell leukemia/lymphoma (ATL) is an aggressive non-Hodgkin lymphoma with poor prognosis and few treatment options for patients with relapsed, recurrent, or refractory disease. We evaluated the efficacy and safety of valemetostat, a potent EZH1 and EZH2 inhibitor, in treating relapsed/refractory (R/R) ATL. This multicenter phase 2 trial (NCT04102150; https://clinicaltrials.gov/ct2/show/NCT04102150; DS3201-A-J201) enrolled patients with R/R aggressive ATL (acute, lymphoma, unfavorable chronic type). Patients received valemetostat 200 mg/day until progressive disease or unacceptable toxicity. The primary endpoint was overall response rate (ORR) centrally assessed by an independent efficacy assessment committee (IEAC). Secondary endpoints included best response in disease compartments, duration of response (DOR), pharmacokinetics, and safety. Twenty-five patients (median age, 69.0) with a median of 3 prior lines of therapy were enrolled; 24 had prior mogamulizumab treatment. The primary endpoint was met with a centrally reviewed ORR of 48.0% (90% CI, 30.5% to 65.9%), including 5 complete and 7 partial remissions. Patients pretreated with mogamulizumab had an ORR of 45.8% (4 complete and 7 partial remissions). IEAC-assessed median DOR was not reached (NR; 95% CI, 1.87 months to NR). Treatment-emergent adverse events (TEAEs) were manageable. TEAEs that occurred in ≥20% of patients included thrombocytopenia, anemia, alopecia, dysgeusia, neutropenia, lymphopenia, leukopenia, decreased appetite, and pyrexia. Grade ≥3 TEAEs included thrombocytopenia, anemia, lymphopenia, leukopenia, and neutropenia. Valemetostat demonstrated promising efficacy and tolerability in heavily pretreated patients, warranting further investigation in treating R/R ATL.
  • 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 Matsumura
    Biochemical 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.
  • Naohiro Sekiguchi; Shinya Rai; Wataru Munakata; Kenshi Suzuki; Hiroshi Handa; Hirohiko Shibayama; Tomoyuki Endo; Yasuhito Terui; Noriko Iwaki; Noriko Fukuhara; Hiro Tatetsu; Shinsuke Iida; Takayuki Ishikawa; Daisuke Iguchi; Koji Izutsu
    Cancer science 113 6 2085 - 2096 2022年06月 
    The phase II study of tirabrutinib monotherapy at a daily dose of 480 mg under fasting conditions for treatment-naïve and relapsed/refractory Waldenström's macroglobulinemia (ONO-4059-05 study) demonstrated a promising efficacy and tolerable safety profile. We conducted an unplanned analysis with a median follow-up of 24.8 months to update the efficacy and safety results and to report patient-reported quality of life. Of 27 enrolled patients, 22 patients continued receiving the study drug. The major response assessed by an independent review committee was observed in 25 patients (93%), including one and five patients who newly achieved complete response and very good partial response, respectively, after the primary analysis. The progression-free and overall survival rates at 24 months were 92.6% and 100%, respectively. Serum IgM levels in all patients except one declined and were maintained at low levels, although transient increases occurred after temporal interruption of the study drug. The disease-related symptoms including recurrent fever and hyperviscosity mostly disappeared. Health-related quality of life, assessed by cancer-specific questionnaires, was mostly maintained. Grade 3-4 neutropenia, lymphopenia, and leukopenia were newly recognized in three, two, and one patient, respectively. Grade 3 treatment-related hypertriglyceridemia was also recognized. Nine patients experienced grade 1-2 bleeding events (33%), one patient experienced grade 2 treatment-related atrial fibrillation, and one patient experienced grade 1 treatment-related hypertension. Treatment-related skin adverse events were observed in 14 patients (52%). Taken together, tirabrutinib has durable efficacy with an acceptable safety profile for treatment-naïve and refractory/relapsed Waldenström's macroglobulinemia.
  • Katsuyoshi Takata; Lauren C Chong; Daisuke Ennishi; Tomohiro Aoki; Michael Yu Li; Avinash Thakur; Shannon Healy; Elena Viganò; Tao Dao; Daniel Kwon; Gerben Duns; Julie S Nielsen; Susana Ben-Neriah; Ethan Tse; Stacy S Hung; Merrill Boyle; Sung Soo Mun; Christopher M Bourne; Bruce Woolcock; Adèle Telenius; Makoto Kishida; Shinya Rai; Allen W Zhang; Ali Bashashati; Saeed Saberi; Gianluca D'Antonio; Brad H Nelson; Sohrab P Shah; Pamela A Hoodless; Ari M Melnick; Randy D Gascoyne; Joseph M Connors; David A Scheinberg; Wendy Béguelin; David W Scott; Christian Steidl
    The Journal of clinical investigation 132 10 2022年05月 
    PRAME is a prominent member of the cancer testis antigen family of proteins, which triggers autologous T cell-mediated immune responses. Integrative genomic analysis in diffuse large B cell lymphoma (DLBCL) uncovered recurrent and highly focal deletions of 22q11.22, including the PRAME gene, which were associated with poor outcome. PRAME-deleted tumors showed cytotoxic T cell immune escape and were associated with cold tumor microenvironments. In addition, PRAME downmodulation was strongly associated with somatic EZH2 Y641 mutations in DLBCL. In turn, PRC2-regulated genes were repressed in isogenic PRAME-KO lymphoma cell lines, and PRAME was found to directly interact with EZH2 as a negative regulator. EZH2 inhibition with EPZ-6438 abrogated these extrinsic and intrinsic effects, leading to PRAME expression and microenvironment restoration in vivo. Our data highlight multiple functions of PRAME during lymphomagenesis and provide a preclinical rationale for synergistic therapies combining epigenetic reprogramming with PRAME-targeted therapies.
  • Kayoko Murayama; Toru Kiguchi; Koji Izutsu; Yoshihiro Kameoka; Michihiro Hidaka; Harumi Kato; Shinya Rai; Junya Kuroda; Kenichi Ishizawa; Satoshi Ichikawa; Kiyoshi Ando; Michinori Ogura; Koji Fukushima; Yasuhito Terui
    Annals of hematology 101 5 979 - 989 2022年05月 
    This single-arm phase 3 study was conducted to confirm the results of our phase 2 study of bendamustine (B)-rituximab (R) in patients with relapsed/refractory diffuse large B cell lymphoma (rrDLBCL). The primary endpoint was overall response rate (ORR). Autologous stem cell transplantation-ineligible rrDLBCL patients with ≤ 2 prior chemotherapy regimens received R 375 mg/m2 IV on day 1 and B 120 mg/m2/day IV on days 2 and 3 every 21 days up to 6 cycles. Thirty-eight patients with a median age of 74 years (range, 43-86) received BR. The ORR and complete response rates were 76.3% and 47.4%, respectively. With a median follow-up of 19.5 months including long-term follow-up, median progression-free survival was 11.9 months. Median OS was 29.2 months. Discontinuation of treatment due to Gr3-5 TEAE was observed among 13 of 38 patients (34.2%). One patient with cytomegalovirus enterocolitis died during follow-up. This BR regimen was confirmed to be effective and tolerable in studied patients. ClinicalTrials.gov Identifier: NCT03372837 registered on 14 December 2017, NCT04354402 registered on 21 April, 2020.
  • Takahide Taniguchi; Shoko Nakayama; Hirokazu Tanaka; Shinya Rai; Chikara Hirase; Yasuyoshi Morita; Yoichi Tatsumi; Takashi Ashida; Mitsuhiro Matsuda; Shigeo Hashimoto; Itaru Matsumura
    British journal of haematology 198 2 360 - 372 2022年04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.
  • Takahiro Kumode; Hirokazu Tanaka; Jorge Luis Esipinoza; Shinya Rai; Yasuhiro Taniguchi; Ryosuke Fujiwara; Keigo Sano; Kentaro Serizawa; Yoshio Iwata; Yasuyoshi Morita; Itaru Matsumura
    International 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.
  • 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 Matsumura
    International 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.
  • 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 Matsumura
    Cancer 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).
  • Hervé Tilly; Franck Morschhauser; Laurie H Sehn; Jonathan W Friedberg; Marek Trněný; Jeff P Sharman; Charles Herbaux; John M Burke; Matthew Matasar; Shinya Rai; Koji Izutsu; Neha Mehta-Shah; Lucie Oberic; Adrien Chauchet; Wojciech Jurczak; Yuqin Song; Richard Greil; Larysa Mykhalska; Juan M Bergua-Burgués; Matthew C Cheung; Antonio Pinto; Ho-Jin Shin; Greg Hapgood; Eduardo Munhoz; Pau Abrisqueta; Jyh-Pyng Gau; Jamie Hirata; Yanwen Jiang; Mark Yan; Calvin Lee; Christopher R Flowers; Gilles Salles
    The New England journal of medicine 386 4 351 - 363 2022年01月 
    BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is typically treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). However, only 60% of patients are cured with R-CHOP. Polatuzumab vedotin is an antibody-drug conjugate targeting CD79b, which is ubiquitously expressed on the surface of malignant B cells. METHODS: We conducted a double-blind, placebo-controlled, international phase 3 trial to evaluate a modified regimen of R-CHOP (pola-R-CHP), in which vincristine was replaced with polatuzumab vedotin, as compared with standard R-CHOP, in patients with previously untreated intermediate-risk or high-risk DLBCL. Patients 18 to 80 years of age were randomly assigned in a 1:1 ratio to receive six cycles of either pola-R-CHP or R-CHOP, plus two cycles of rituximab alone. The primary end point was investigator-assessed progression-free survival. Secondary end points included overall survival and safety. RESULTS: Overall, 879 patients underwent randomization: 440 were assigned to the pola-R-CHP group and 439 to the R-CHOP group. After a median follow-up of 28.2 months, the percentage of patients surviving without progression was significantly higher in the pola-R-CHP group than in the R-CHOP group (76.7% [95% confidence interval (CI), 72.7 to 80.8] vs. 70.2% [95% CI, 65.8 to 74.6] at 2 years; stratified hazard ratio for progression, relapse, or death, 0.73 by Cox regression; 95% CI, 0.57 to 0.95; P = 0.02). Overall survival at 2 years did not differ significantly between the groups (88.7% [95% CI, 85.7 to 91.6] in the pola-R-CHP group and 88.6% [95% CI, 85.6 to 91.6] in the R-CHOP group; hazard ratio for death, 0.94; 95% CI, 0.65 to 1.37; P = 0.75). The safety profile was similar in the two groups. CONCLUSIONS: Among patients with previously untreated intermediate-risk or high-risk DLBCL, the risk of disease progression, relapse, or death was lower among those who received pola-R-CHP than among those who received R-CHOP. (Funded by F. Hoffmann-La Roche/Genentech; POLARIX ClinicalTrials.gov number, NCT03274492.).
  • Koji Izutsu; Kiyoshi Ando; Momoko Nishikori; Hirohiko Shibayama; Takanori Teshima; Junya Kuroda; Koji Kato; Yoshitaka Imaizumi; Kisato Nosaka; Rika Sakai; Seiichiro Hojo; Tadashi Nakanishi; Shinya Rai
    Cancer science 112 9 3627 - 3635 2021年09月 
    Tazemetostat is a selective, reversible, small-molecule inhibitor of the histone methyltransferase enzyme, enhancer of zest homolog 2 (EZH2). In this multicenter, open-label, phase II study, we assessed the efficacy and safety of tazemetostat in Japanese patients with relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma harboring the EZH2 mutation. Tazemetostat (800 mg twice daily) was given orally (28-day cycle) until disease progression or unacceptable toxicity. Among the 20 eligible patients, 17 were enrolled in cohort 1 (follicular lymphoma [FL]), and three were enrolled in cohort 2 (diffuse large B-cell lymphoma). At data cut-off, the objective response rate in cohort 1 was 76.5%, including six patients (35.3%) with complete response and seven patients (41.2%) with partial response (PR). All three patients in cohort 2 achieved PR. In cohort 1, median progression-free survival (PFS) was not reached at the median follow-up of 12.9 months. The estimated PFS rate at 12 and 15 months was 94.1% and 73.2%, respectively. The most common grade 3 treatment-emergent adverse event (TEAE) was lymphopenia (n = 2). Grade 4 TEAEs included hypertriglyceridemia and pneumonia aspiration (n = 1 each), which were not related to tazemetostat. Treatment-emergent adverse events leading to study drug discontinuation were reported in four of the 20 patients, indicating that the safety profile of tazemetostat was acceptable and manageable. Tazemetostat 800 mg twice daily showed encouraging efficacy in patients with R/R EZH2 mutation-positive FL with a manageable safety profile in the overall population. Thus, tazemetostat could be a potential treatment for R/R EZH2 mutation-positive FL.
  • 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 Matsumura
    International 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.
  • Yasuhito Terui; Shinya Rai; Koji Izutsu; Motoko Yamaguchi; Jun Takizawa; Junya Kuroda; Takayuki Ishikawa; Koji Kato; Youko Suehiro; Noriko Fukuhara; Ken Ohmine; Hideki Goto; Kazuhito Yamamoto; Nobuhiro Kanemura; Yasunori Ueda; Kenichi Ishizawa; Kyoya Kumagai; Atsuko Kawasaki; Tomohisa Saito; Misato Hashizume; Hirohiko Shibayama
    Cancer science 112 7 2845 - 2854 2021年07月 
    Polatuzumab vedotin (pola) is a CD79b-targeted antibody-drug conjugate delivering a potent antimitotic agent (monomethyl auristatin E) to B cells. This was an open-label, single-arm study of pola 1.8 mg/kg, bendamustine 90 mg/m2 , rituximab 375 mg/m2 (pola + BR) Q3W for up to six cycles in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who received ≥1 prior line of therapy and were ineligible for autologous stem cell transplantation (ASCT) or experienced treatment failure with prior ASCT. Primary endpoint was complete response rate (CRR) at the end of the treatment (EOT) by positron emission tomography-computed tomography (PET-CT) using modified Lugano Response Criteria. Secondary endpoints included efficacy, safety, and pharmacokinetics. Thirty-five patients (median age 71 [range 46-86] years) were enrolled. Twenty-three (66%) patients had refractory disease, and 23 (66%) had ≥2 prior lines of therapy. At a median follow-up of 5.4 (0.7-11.9) months, patients received a median of five treatment cycles. CRR was 34.3% (95% confidence interval [CI] 19.1-52.2) at EOT. Overall response rate was 42.9% at EOT, and median progression-free survival was 5.2 months (95% CI 3.6-not evaluable). Median overall survival was not reached. No fatal adverse events (AEs) were observed. Grade 3-4 AEs were mainly hematological: anemia (37%), neutropenia (31%), white blood cell count decreased (23%), thrombocytopenia/platelet count decreased/neutrophil count decreased (20% each), and febrile neutropenia (11%). Grade 1-2 peripheral neuropathy (PN; sensory and/or motor) was reported in 14% of patients; there were no ≥grade 3 PN events. This study (JapicCTI-184048) demonstrated the efficacy and safety of pola + BR in Japanese patients with R/R DLBCL who were ineligible for ASCT.
  • Akinori Okada; Yuji Nozaki; Shinya Rai; Koji Kinoshita; Masanori Funauchi; Itaru Matsumura
    Life (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.
  • 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 62 3 205 - 205 (一社)日本血液学会-東京事務局 2021年03月
  • Shinya Rai; Hirokazu Tanaka; J Luis Espinoza; Takahiro Kumode; Itaru Matsumura
    Leukemia 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.
  • Yoshitaka Imaizumi; Masako Iwanaga; Kisato Nosaka; Kenji Ishitsuka; Kenichi Ishizawa; Shigeki Ito; Masahiro Amano; Takashi Ishida; Naokuni Uike; Atae Utsunomiya; Koichi Ohshima; Junji Tanaka; Yoshiki Tokura; Kensei Tobinai; Toshiki Watanabe; Kaoru Uchimaru; Kunihiro Tsukasaki; Akifumi Takaori; Masakatsu Hishizawa; Akira Kitanaka; Akiyoshi Takami; Asahi Ito; Kentaro Yonekura; Atsuko Mugitani; Chiaki Kato; Daisuke Ogawa; Daisuke Tsuruta; Eiichi Ohtsuka; Yoshio Saburi; Eizaburo Sueoka; Fujii Kazuyasu; Makoto Yoshimitsu; Fujio Matsubara; Fumi Miyagawa; Fumihiko Nakamura; Makoto Sugaya; Hajime Kobayashi; Hideho Heizan; Hiroe Fuse; Hirohiko Shibayama; Hiroki Yamaguchi; Hiroshi Ishikawa; Shinichiro Yoshida; Hiroshi Iwasaki; Hiroshi Kawano; Hiroshi Kazama; Hiroshi Yamasaki; Hiroyuki Kuroda; Michiko Yamada; Hitoshi Suzushima; Ilseung Choi; Naokuni Uike; Kaname Miyashita; Katsuyasu Saigo; Kazuiku Ohshiro; Kazuki Tatsuno; Takaaki Ono; Keiji Sugimoto; Ken Ohmachi; Kenichiro Etoh; Monji Koga; Kensuke Narukawa; Ki Ryang Koh; Kimiharu Uozumi; Koichi Nagai; Koji Adachi; Toru Motokura; Koji Izutsu; Koji Kato; Koji Nagafuji; Masaaki Yuge; Masaharu Miyahara; Masakazu Higuchi; Masaki Hayashi; Masaki Iino; Masanori Makita; Masao Hagihara; Masaru Shibano; Masato Ito; Masato Saito; Michiaki Koike; Michihiro Hidaka; Mitsutoshi Kurosawa; Motoharu Fukazawa; Motohiro Shindo; Motoi Takenaka; Naoki Kobayashi; Nobuharu Kosugi; Nobuhiko Nakamura; Nobuhiko Tominaga; Noriko Fukuhara; Rika Sakai; Ryohei Nawata; Satoshi Iyama; Satoshi Yamasaki; Sawako Nakachi; Takeaki Tomoyose; Shigeru Chiba; Shinya Rai; Takahiro Okada
    Cancer Science 111 12 4567 - 4580 2020年12月 
    Adult T-cell leukemia/lymphoma (ATL) is a mature T-cell neoplasm and is classified into four subtypes (acute, lymphoma, chronic, and smoldering) according to the Shimoyama classification, established in 1991 through several nationwide surveys based on the clinical diversity of patients diagnosed in 1983-1987 in Japan. Thereafter, no such studies have been conducted. Recently, we conducted a nationwide hospital survey using the method of the 1980s studies, collected baseline data on 996 ATL patients diagnosed in 2010-2011 from 126 hospitals, and reported their unique epidemiological characteristics. Here, we report the follow-up results of registered ATL patients with the goal of evaluating current prognoses and treatment modalities as of 2016-2017. Of 770 evaluable patients, 391 (50.8%) had acute-type, 192 (24.9%) had lymphoma-type, 106 (13.8%) had chronic-type, and 81 (10.5%) had smoldering-type ATL. The initial therapy regimens used for acute/lymphoma-type ATL were vincristine, cyclophosphamide, doxorubicin and prednisone, followed by doxorubicin, ranimustine, and prednisone and then by vindesine, etoposide, carboplatin, and prednisone (VCAP-AMP-VECP)-like in 38.5/41.7% and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-like in 14.6/13.7% of patients. Allogeneic hematopoietic stem cell transplantation was used to treat 15.9/10.4% of acute/lymphoma-type ATL patients. The 4-year survival rates (the median survival time, days) for acute-, lymphoma-, unfavorable chronic-, favorable chronic-, and smoldering-type ATL were 16.8% (252), 19.6% (305), 26.6% (572), 62.1% (1937), and 59.8% (1851), respectively. The 4-year survival rates for acute- and lymphoma-type ATL improved compared with those reported in 1991, but those for chronic- and smoldering-type ATL were not. Further efforts are warranted to develop more efficient therapeutic strategies to improve the prognosis of ATL in Japan.
  • 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 Matsumura
    Internal medicine (Tokyo, Japan) 59 21 2745 - 2749 2020年11月 [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.
  • 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 Matsumura
    British journal of haematology 191 2 243 - 252 2020年10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.
  • Naohiro Sekiguchi; Shinya Rai; Wataru Munakata; Kenshi Suzuki; Hiroshi Handa; Hirohiko Shibayama; Tomoyuki Endo; Yasuhito Terui; Noriko Iwaki; Noriko Fukuhara; Hiro Tatetsu; Shinsuke Iida; Takayuki Ishikawa; Ryota Shiibashi; Koji Izutsu
    Cancer science 111 9 3327 - 3337 2020年09月 [査読有り]
     
    Tirabrutinib is a second-generation Bruton's tyrosine kinase inhibitor with greater selectivity than ibrutinib. Here, we conducted a multicenter, phase II study of tirabrutinib in patients with treatment-naïve (Cohort A) or with relapsed/refractory (Cohort B) Waldenström's macroglobulinemia (WM). Patients were treated with tirabrutinib 480 mg once daily. The primary endpoint was major response rate (MRR; ≥ partial response). Secondary endpoints included overall response rate (ORR; ≥ minor response), time to major response (TTMR), progression-free survival (PFS), overall survival (OS), and safety. In total, 27 patients (18 in Cohort A; 9 in Cohort B) were enrolled. The median age was 71 y, and the median serum immunoglobulin M level was 3600 mg/dL. Among the patients, 96.2% had the MYD88L265P mutation. MRR and ORR were 88.9% and 96.3%, respectively (Cohort A: MRR, 88.9%; ORR, 94.4%; Cohort B: MRR, 88.9%; ORR, 100%). Median TTMR was 1.87 mo. PFS and OS were not reached with a median follow-up of 6.5 and 8.3 mo for Cohorts A and B, respectively. The most common adverse events (AEs) were rash (44.4%), neutropenia (25.9%), and leukopenia (22.2%), with most AEs classified as grade 1 or 2. Grade ≥ 3 AEs included neutropenia (11.1%), lymphopenia (11.1%), and leukopenia (7.4%). No grade 5 AEs were noted. All bleeding events were grade 1; none were associated with drug-related atrial fibrillation or hypertension. Although the follow-up duration was relatively short, the study met the primary endpoint. Therefore, tirabrutinib monotherapy is considered to be highly effective for both untreated and relapsed/refractory WM with a manageable safety profile. (JapicCTI-173646).
  • Shinya Rai; Hirokazu Tanaka; Mai Suzuki; J Luis Espinoza; Takahiro Kumode; Akira Tanimura; Takafumi Yokota; Kenji Oritani; Toshio Watanabe; Yuzuru Kanakura; Itaru Matsumura
    Nature 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.
  • 棟方 理; 関口 直宏; 頼 晋也; 鈴木 憲史; 半田 寛; 柴山 浩彦; 遠藤 知之; 照井 康仁; 岩城 憲子; 福原 規子; 立津 央; 飯田 真介; 石川 隆之; 椎橋 竜太; 伊豆津 宏二
    日本リンパ網内系学会会誌 60 79 - 79 (一社)日本リンパ網内系学会 2020年07月
  • 中山 聖子; 森田 泰慶; 頼 晋也; 谷口 康博; 谷口 貴英; 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 60 83 - 83 (一社)日本リンパ網内系学会 2020年07月
  • Majid A Almadi; Takao Itoi; Jong Ho Moon; Mahesh K Goenka; Dong Wan Seo; Rungsun Rerknimitr; James Y Lau; Amit P Maydeo; Jong Kyun Lee; Nam Q Nguyen; Saad K Niaz; Randhir Sud; Tiing Leong Ang; Abdulrahman Aljebreen; Benedict M Devereaux; Rakesh Kochhar; Jörg Reichenberger; Ichiro Yasuda; Arthur J Kaffes; Masayuki Kitano; Joyce Peetermans; Pooja G Goswamy; Matthew J Rousseau; D Nageshwar Reddy; Sundeep Lakhtakia; Yun Nah Lee; Vijay Kumar Rai; Kentaro Kamada; Reina Tanaka; Ryosuke Tonozuka; Akihiko Tsuchida; Tae Jun Song; Mohan K Ramchandani
    Endoscopy 52 7 574 - 582 2020年07月 [査読有り]
     
    BACKGROUND:  Peroral cholangioscopy (POCS) of indeterminate biliary strictures aims to achieve a diagnosis through visual examination and/or by obtaining targeted biopsies under direct visualization. In this large, prospective, multinational, real-life experience of POCS-guided evaluation of indeterminate biliary strictures, we evaluated the performance of POCS in this difficult-to-manage patient population. METHODS:  This prospective registry enrolled patients, with indeterminate biliary strictures across 20 centers in Asia, the Middle East, and Africa. The primary end points were the ability to visualize the lesion, obtain histological sampling when intended, and an assessment of the diagnostic accuracy of POCS for malignant strictures. Patients were followed for 6 months after POCS or until a definitive malignant diagnosis was made, whichever occurred first. RESULTS:  289 patients underwent 290 POCS procedures with intent to biopsy in 182 cases. The stricture/filling defect was successfully visualized in 286/290 (98.6 %), providing a visual diagnostic impression in 253/290 (87.2 %) and obtaining adequate biopsies in 169/182 (92.9 %). Procedure-related adverse events occurred in 5/289 patients (1.7 %). POCS influenced patient management principally by elucidating filling defects or the causes of bile duct stricture or dilation. The visual impression of malignancy showed 86.7 % sensitivity, 71.2 % specificity, 65.8 % positive and 89.4 % negative predictive value, and 77.2 % overall accuracy compared with final diagnosis. Histological POCS-guided samples showed 75.3 % sensitivity, 100 % specificity, 100 % positive and 77.1 % negative predictive value, and 86.5 % overall accuracy. CONCLUSION:  In this large, real-life, prospective series, POCS was demonstrated to be an effective and safe intervention guiding the management of patients with indeterminate biliary strictures.
  • 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 Matsumura
    Viruses 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.
  • Shoko Nakayama; Yasuyoshi Morita; Jorge Luis Espinoza; Shinya Rai; Yasuhiro Taniguchi; Takahide Taniguchi; Yoshiaki Miyake; Hirokazu Tanaka; Takashi Ashida; Itaru Matsumura
    Annals of hematology 99 2 381 - 383 2020年02月 [査読有り]
  • Shinya Rai
    [Rinsho ketsueki] The Japanese journal of clinical hematology 61 9 1266 - 1274 2020年 
    The development of targeted therapies, such as rituximab-an anti-CD20 antibody targeting CD20, has undergone a paradigm shift from conventional chemotherapy for malignant lymphoma (ML). Although a subset of ML patients has been cured, the treatment of refractory and relapsed diseases remains challenging. Fortunately, growing insights on molecular biology for ML have led to the development of a number of innovative agents. Moreover, a plethora of targeted therapies, including novel antibodies targeting surface antigens, and small molecular inhibitors targeting oncogenic signaling pathways, tumor suppressors, and epigenetic regulation are currently under investigation for the improvement of dismal prognosis. In addition, immunotherapies, including immune checkpoint inhibitors, bispecific T-cell engager antibodies, and chimeric antigen receptor T-cells for ML have been rapidly developed to target tumor microenvironment. These promising mechanism-based targeted therapies could lead to a successful ML management.
  • Takahiro Kumode; Shinya Rai; Hirokazu Tanaka; J Luis Espinoza; Hiroaki Kakutani; Yosaku Watatani; Shuji Minamoto; Yasuhiro Taniguchi; Shoko Nakayama; Yasuyoshi Morita; Takashi Ashida; Itaru Matsumura
    Leukemia 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.
  • 賴 晋也
    血液内科 = Hematology 79 4 514 - 520 科学評論社 2019年10月 [査読有り]
  • Shoko Nakayama; Yasuyoshi Morita; Jorge Luis Espinoza; Shinya Rai; Yasuyo Oyama; Takahide Taniguchi; Yoshiaki Miyake; Hirokazu Tanaka; Itaru Matsumura
    Leukemia & lymphoma 62 2 1 - 3 2019年09月 [査読有り]
  • 【B細胞リンパ腫をめぐる最新トピックス CAR-T療法や新規治療薬による治療成績向上への期待】濾胞性リンパ腫に対する新規治療薬への期待 初発/再発・難治性例ともに治療選択肢が広がる
    頼 晋也
    Hematopaseo 5 9 - 14 凸版印刷(株) 2019年09月 [査読有り]
  • 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 [査読有り]
     
    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。
  • Anas Younes; Laurie H Sehn; Peter Johnson; Pier Luigi Zinzani; Xiaonan Hong; Jun Zhu; Caterina Patti; David Belada; Olga Samoilova; Cheolwon Suh; Sirpa Leppä; Shinya Rai; Mehmet Turgut; Wojciech Jurczak; Matthew C Cheung; Ronit Gurion; Su-Peng Yeh; Andres Lopez-Hernandez; Ulrich Dührsen; Catherine Thieblemont; Carlos Sergio Chiattone; Sriram Balasubramanian; Jodi Carey; Grace Liu; S Martin Shreeve; Steven Sun; Sen Hong Zhuang; Jessica Vermeulen; Louis M Staudt; Wyndham Wilson
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology 37 15 1285 - 1295 2019年05月 [査読有り]
     
    PURPOSE: Ibrutinib has shown activity in non-germinal center B-cell diffuse large B-cell lymphoma (DLBCL). This double-blind phase III study evaluated ibrutinib and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in untreated non-germinal center B-cell DLBCL. PATIENTS AND METHODS: Patients were randomly assigned at a one-to-one ratio to ibrutinib (560 mg per day orally) plus R-CHOP or placebo plus R-CHOP. The primary end point was event-free survival (EFS) in the intent-to-treat (ITT) population and the activated B-cell (ABC) DLBCL subgroup. Secondary end points included progression-free survival (PFS), overall survival (OS), and safety. RESULTS: A total of 838 patients were randomly assigned to ibrutinib plus R-CHOP (n = 419) or placebo plus R-CHOP (n = 419). Median age was 62.0 years; 75.9% of evaluable patients had ABC subtype disease, and baseline characteristics were balanced. Ibrutinib plus R-CHOP did not improve EFS in the ITT (hazard ratio [HR], 0.934) or ABC (HR, 0.949) population. A preplanned analysis showed a significant interaction between treatment and age. In patients age younger than 60 years, ibrutinib plus R-CHOP improved EFS (HR, 0.579), PFS (HR, 0.556), and OS (HR, 0.330) and slightly increased serious adverse events (35.7% v 28.6%), but the proportion of patients receiving at least six cycles of R-CHOP was similar between treatment arms (92.9% v 93.0%). In patients age 60 years or older, ibrutinib plus R-CHOP worsened EFS, PFS, and OS, increased serious adverse events (63.4% v 38.2%), and decreased the proportion of patients receiving at least six cycles of R-CHOP (73.7% v 88.8%). CONCLUSION: The study did not meet its primary end point in the ITT or ABC population. However, in patients age younger than 60 years, ibrutinib plus R-CHOP improved EFS, PFS, and OS with manageable safety. In patients age 60 years or older, ibrutinib plus R-CHOP was associated with increased toxicity, leading to compromised R-CHOP administration and worse outcomes. Further investigation is warranted.
  • 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 59 119 - 119 (一社)日本リンパ網内系学会 2019年05月
  • 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 59 126 - 126 (一社)日本リンパ網内系学会 2019年05月
  • 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 59 129 - 129 (一社)日本リンパ網内系学会 2019年05月
  • 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 59 129 - 129 (一社)日本リンパ網内系学会 2019年05月
  • 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 65 2 471 - 471 (一社)日本輸血・細胞治療学会 2019年04月
  • 賴 晋也
    血液内科 = Hematology 78 4 538 - 544 科学評論社 2019年04月 [査読有り]
  • Hirokazu Tanaka; J. Espinoza; Ryosuke Fujiwara; Shinya Rai; Yasuyoshi Morita; Takashi Ashida; Yuzuru Kanakura; Itaru Matsumura
    Cells 8 3 226 - 226 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.
  • 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 - 66 (一社)日本血液学会-東京事務局 2019年01月
  • Takahide Taniguchi; Shoko Nakayama; Yasuyoshi Morita; Shinya Rai; Jorge L Espinoza; Itaru Matsumura
    British journal of haematology 184 2 121 - 121 2019年01月 [査読有り]
  • Shoko Nakayama; Takahide Taniguchi; Hirokazu Tanaka; Jorge L Espinoza; Shinya Rai; Itaru Matsumura
    British journal of haematology 184 2 122 - 122 2019年01月 [査読有り]
  • 賴 晋也
    血液内科 = Hematology 77 6 718 - 723 科学評論社 2018年12月 [査読有り]
  • 末梢血幹細胞採取前のCD34細胞数測定の有用性
    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 37 Suppl. 131 - 131 (一社)日本アフェレシス学会 2018年10月
  • 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 Matsumura
    Cancers 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.
  • 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)
    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
    臨床血液 59 9 1486 - 1486 2018年09月
  • 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)
    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
    臨床血液 59 9 1572 - 1572 2018年09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)
    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
    臨床血液 59 9 1592 - 1592 2018年09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)
    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
  • 頼晋也; 松村到
    日本内科学会雑誌 107 7 1316‐1323  2018年07月
  • 【血液疾患を見逃さないために-プライマリ・ケアと専門医コンサルトのタイミング】血液疾患を疑う症候・病変の診かたと紹介のタイミング 甲状腺病変
    頼 晋也
    Medicina 55 8 1194 - 1197 (株)医学書院 2018年07月 
    ＜文献概要＞Point ◎甲状腺悪性リンパ腫の発症頻度は,甲状腺悪性腫瘍の1〜5%と非常に稀な疾患である.◎約90%に橋本病を合併しており,中高年女性に好発する.◎中悪性度のびまん性大細胞型B細胞性リンパ腫および低悪性度のMALTリンパ腫が主な組織型である.◎超音波検査では「著明な低エコー腫瘤像」が特徴的である.
  • 頼 晋也
    Medicina 55 8 1194 - 1197 (株)医学書院 2018年07月 [査読有り]
     
    ＜文献概要＞Point ◎甲状腺悪性リンパ腫の発症頻度は,甲状腺悪性腫瘍の1〜5%と非常に稀な疾患である.◎約90%に橋本病を合併しており,中高年女性に好発する.◎中悪性度のびまん性大細胞型B細胞性リンパ腫および低悪性度のMALTリンパ腫が主な組織型である.◎超音波検査では「著明な低エコー腫瘤像」が特徴的である.
  • 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 [査読有り]
  • 頼 晋也
    最新医学 別冊 悪性リンパ腫 187 - 193 (株)最新医学社 2018年04月 [査読有り]
     
    分子標的治療薬を始めとした新規薬剤の開発は、悪性リンパ腫の予後を大きく改善した。一方で、これらの薬剤は高額であり、治療法の開発・進歩が医療費高騰に及ぼす影響が懸念されている。本稿では医療経済学的な観点から、高額な新規薬剤の"積極的な使用"の意義を、諸外国での分析結果を交えながら検証してみたい。(著者抄録)
  • 【診断と治療のABC[133]悪性リンパ腫】 (第4章)管理・治療 費用対効果の観点から見た悪性リンパ腫の治療選択
    頼 晋也
    最新医学 別冊 悪性リンパ腫 187 - 193 (株)最新医学社 2018年04月 
    分子標的治療薬を始めとした新規薬剤の開発は、悪性リンパ腫の予後を大きく改善した。一方で、これらの薬剤は高額であり、治療法の開発・進歩が医療費高騰に及ぼす影響が懸念されている。本稿では医療経済学的な観点から、高額な新規薬剤の"積極的な使用"の意義を、諸外国での分析結果を交えながら検証してみたい。(著者抄録)
  • Shinya Rai; J Luis Espinoza; Yasuyoshi Morita; Hirokazu Tanaka; Itaru Matsumura
    Frontiers 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.
  • 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 Matsumura
    International 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/μl 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.
  • T. Kumode; H. Tanaka; R. Fujiwara; K. Sano; K. Serizawa; Y. Taniguchi; S. Rai; I. Matsumura
    HAEMATOLOGICA 102 452 - 453 2017年06月
  • 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
  • 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 [査読有り]
     
    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)
  • Shinya Rai; Hirokazu Tanaka; Toshio Watanabe; Yuzuru Kanakura; Itaru Matsumura
    EXPERIMENTAL HEMATOLOGY 43 9 S90 - S90 2015年09月 [査読有り]
  • Hirokazu Tanaka; Shinya Rai; Toshio Watazzabe; Yuzuru Kanakura; Itaru Matsumura
    EXPERIMENTAL HEMATOLOGY 43 9 S98 - S98 2015年09月 [査読有り]
  • 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 Watanabe
    FEBS 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.
  • 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 
    [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.
  • 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 Matsumura
    INTERNAL 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.
  • 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 Matsumura
    PLOS ONE 9 10 e109441  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.
  • Shinya Rai; Mitsuhiro Matsuda; Nozomi Yamairi; Go Eguchi; Takayuki Iwanaga; Yasuyoshi Morita; Hirokazu Tanaka; Yoichi Tatsumi; Takashi Ashida; Itaru Matsumura
    Internal medicine (Tokyo, Japan) 52 2 273 - 6 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.
  • 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
  • Naoki Oiso; Yoichi Tatsumi; Tokuzo Arao; Shinya Rai; Masatomo Kimura; Shigeo Nakamura; Tomoo Itoh; Kazuto Nishio; Itaru Matsumura; Akira Kawada
    EUROPEAN JOURNAL OF DERMATOLOGY 22 3 393 - 394 2012年05月 [査読有り]
  • 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 
    [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．
  • 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 Watanabe
    PLOS ONE 7 2 e31854  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.
  • Yasuyoshi Morita; Takahiro Shimada; Terufumi Yamaguchi; Shinya Rai; Chikara Hirase; Masakatsu Emoto; Kentaro Serizawa; Yasuhiro Taniguchi; Mayuko Ojima; Yoichi Tatsumi; Takashi Ashida; Itaru Matsumura
    INTERNATIONAL JOURNAL OF HEMATOLOGY 94 6 583 - 584 2011年12月 [査読有り]
  • Naoki Oiso; Yoichi Tatsumi; Shinya Rai; Itaru Matsumura; Akira Kawada
    EUROPEAN JOURNAL OF DERMATOLOGY 21 4 636 - 638 2011年07月 [査読有り]
  • Yasuyoshi Morita; Yuichi Ohyama; Shinya Rai; Masaya Kawauchi; Terufumi Yamaguchi; Takahiro Shimada; Yoichi Tatsumi; Takashi Ashida; Yasuhiro Maeda; Itaru Matsumura
    Internal medicine (Tokyo, Japan) 50 16 1737 - 40 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.
  • 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
  • 頼 晋也; 松田 光弘; 山入 望美; 數田 高生; 岩永 隆行; 青山 真人; 川村 正喜; 橋本 重夫; 板垣 信生
    臨床血液 51 4 281 - 285 「臨床血液」編集部 2010年04月 
    症例は51歳女性。慢性腎不全保存期で外来通院中であったが,2008年3月,汎血球減少が出現し,最重症型再生不良性貧血と診断された。抗ヒト胸腺細胞ウマ免疫グロブリン(ATG)療法を選択したが,効果は一時的であった。その後,維持腹膜透析(CAPD)導入となった。平成21年2月に抗ヒト胸腺細胞ウサギ免疫グロブリン(rATG)療法を施行したが,効果なく,種々の感染症により,徐々に全身状態の悪化を認めた。同胞がなく,平成21年8月にHLA半合致の長男をドナーとした母児間末梢血幹細胞移植を施行した。前処置は減量シクロフォスファミドとリン酸フルダラビンおよびrATGを,免疫抑制はFK506をそれぞれ使用し,Day10に生着を認めた。CAPD施行中の重症再生不良性貧血に対する造血幹細胞移植療法に関しては,これまでまとまった報告がなく,前処置を減量することにより,半合致ドナーからの移植でも生着を認めた貴重な症例と思われ,報告した。(著者抄録)
  • 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。
  • Yasuyoshi Morita; Mitsuhiro Matsuda; Terufumi Yamaguchi; Mika Sakaguchi; Shinya Rai; Yoshitaka Kanai; Chikara Hirase; Kazunobu Kawanishi; Junichi Miyatake; Takahiro Shimada; Yoichi Tatsumi; Takashi Ashida; Yasuhiro Maeda; Akihisa Kanamaru
    Internal medicine (Tokyo, Japan) 49 19 2163 - 6 2010年 [査読有り]
     
    We report a case of primary cardiac lymphoma (PCL) occurring in a 76-year-old man during maintenance hemodialysis. Chest computed tomography (CT) revealed a tumor with pericardial effusion in the left ventricular posterior wall. Cytological examination of the pericardial fluid revealed monotonous lymphoid cells positive for B-cell markers, and clonal immunoglobulin heavy chain gene rearrangement was detected, indicating B-cell lymphoma. Rituximab monotherapy was administered biweekly at the therapeutic level on hemodialysis. The follow-up chest CT showed tumor disappearance with pericardial fluid after two courses of therapy. Rituximab monotherapy was effective for an elderly hemodialysis patient with PCL.
  • Naoki Oiso; Shinya Rai; Shigeru Kawara; Yoichi Tatsumi; Akira Kawada
    Case Reports in Dermatology 2 1 18 - 21 2010年 [査読有り]
     
    Fournier's gangrene is a life-threatening disorder caused by aerobic and anaerobic bacterial infection. We report a case of genital infection as the initial warning sign of acute myeloid leukemia. We were able to prevent progression to Fournier's gangrene in our patient by immediate intensive therapy with incision, blood transfusions and intravenous administration of antibiotics. This case suggests that hematologists and dermatologists should keep in mind that genital infection can be a first sign of hematologic malignancy. Copyright © 2010 S. Karger AG, Basel.
  • MM Hudson; M Krasin; MP Link; SS Donaldson; C Billups; TE Merchant; L Kun; AL Billet; S Kaste; NJ Tarbell; S Howard; AM Friedmann; CA Hurwitz; JA Young; KC Marcus; S Rai; T Cowan; HJ Weinstein
    JOURNAL OF CLINICAL ONCOLOGY 22 22 4541 - 4550 2004年11月 [査読有り]
     
    Purpose To evaluate the efficacy of vinblastine, doxorubicin, methotrexate, and prednisone (VAMP) and cyclophosphamide, vincristine, and procarbazine (COP) chemotherapy and response-based, involved-field radiation, a combined-modality regimen that limits doses of alkylating agents, anthracyclines, and radiation, in children with advanced and unfavorable Hodgkin's disease. Patients and Methods From 1993 to 2000, 159 children and adolescents with unfavorable Hodgkin's disease received three alternating cycles (total of six cycles) of VAMP/COP chemotherapy followed by response-based, involved-field radiation therapy: 15 Gy was administered to patients achieving a complete response, and 25.5 Gy was administered to those achieving a partial response after the first two cycles of chemotherapy and to all sites of bulky lymphadenopathy. Unfavorable disease was defined as clinical stage I and II with bulky peripheral nodal disease greater than 6 cm, initial bulky mediastinal mass 33% or more of the intrathoracic diameter, and/or "B" symptoms and all stage III and IV. Results Study enrollment was closed after an interim analysis estimated a 5-year event-free survival (EFS) rate below a predefined level. Disease presentation was localized (stage I/II) in 77 patients (48.4%) and advanced (stage III/IV) in 82 patients (51.6%). At a median follow-up of 5.8 years (range, 1.3 to 10.0 years), 38 patients had events, including relapse/progression (n = 35), second malignancy (n = 2), and accidental death (n = 1); nine relapses (25.7%) occurred greater than 4 years from diagnosis. Five-year survival and EFS estimates are 92.7% +/- 2.5% and 75.6% +/- 4.1%, respectively. Conclusion Risk-adapted combined-modality therapy with VAMP/COP and response-based, involved-field radiation therapy results in an unsatisfactory outcome for pediatric patients with unfavorable presentations of Hodgkin's disease. (C) 2004 by American Society of Clinical Oncology.

講演・口頭発表等

  • 単一施設において同種造血幹細胞移植後に口腔固形腫瘍を発症した6例
    鳥畑さやか; 江原裕基; 助臺美帆; 下出孟史; 岩崎早苗; 李篤史; 川口美紅; 木下優子; 渡瀬遂生; 金澤仁美; 守屋実央; 安武夏海; 兵頭咲紀; 宮本あかね; 谷口康博; 頼晋也; 榎本明史; 濱田傑; 芦田隆司; 芦田隆司
    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
  • 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
  • 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
  • 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
  • 同種造血幹細胞移植前の口腔内病変に対する抜歯の有用性
    鳥畑さやか; 江原裕基; 助臺美帆; 下出孟史; 金澤仁美; 守屋実央; 安武夏海; 兵頭咲紀; 小森舞子; 源周治; 綿谷陽作; 井上宏昭; 口分田貴裕; 谷口康博; 頼晋也; 森田泰慶; 増田智丈; 榎本明史; 濱田傑; 芦田隆司; 芦田隆司
    日本造血細胞移植学会総会プログラム・抄録集 2020年
  • 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
  • 単一施設における初回同種造血幹細胞移植376例の経年的影響  [通常講演]
    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
  • 抗利尿ホルモン分泌異常症を呈したangioimmunoblastic T-cell lymphomaの1例  [通常講演]
    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 2019年01月
  • 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09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09月
  • 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
  • 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09月
  • 新規診断の輸血依存低リスク骨髄異形成症候群における鉄負荷に対するdeferasirox治療の実態と有用性  [通常講演]
    芦田 隆司; 谷口 康博; 頼 晋也; 森田 泰慶; 嶋田 高広; 田中 宏和; 辰巳 陽一; 地守 慶亮; 前田 朋子; 岩本 ちづる; 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; 椿本 祐子; 金光 靖; 前川 清; 松村 到
    第79回日本血液学会学術集会 2017年10月
  • Hodgkin variant of Richter syndromeに対してBR療法が著効した一例  [通常講演]
    藤本 昂; 頼 晋也; 齋藤 花往里; 口分田 貴裕; 井上 宏昭; 森田 泰慶; 田中 宏和; 嶋田 高広; 辰巳 陽一; 芦田 隆司; 松村 到
    第79回日本血液学会学術集会 2017年10月
  • 日本人DLBCL患者におけるオビヌツズマブの有効性及び安全性：GOYA試験部分集団解析  [通常講演]
    頼 晋也; 中前 博久; 内田 俊樹; 豊嶋 崇徳; 中世古 知昭; 伊豆津 宏二; 畠 清彦; 北野 俊行; 赤司 浩一; 鶴見 寿; 金倉 譲; 中島 秀明; 上田 恭典; 長藤 宏; 大嶺 謙; 飛内 賢正; 鈴宮 淳司; 石田 陽治; 張 高明; 田村 秀人; 石川 隆之; 上田 英典; 久力 洋; 辰巳 陽一
    第79回日本血液学会学術集会 2017年10月
  • 芦田隆司; 芦田隆司; 斎藤花往里; 藤本昴; 末田早苗; 角谷宏明; 大山泰世; 井上宏昭; 谷口康博; 頼晋也; 森田泰慶; 岩本ちづる; 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; 椿本祐子; 金光靖; 松村到
    日本造血細胞移植学会総会プログラム・抄録集 2017年02月
  • リツキシマブによる間質性肺炎をきたしたDLBCLの1例  [通常講演]
    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 2017年01月
  • 腹水貯留にて発症したprimary effusion lymphoma-like diffuse large B-cell lymphomaの1例  [通常講演]
    堀川 亮太; 頼 晋也; 齋藤 花往里; 森田 泰慶; 田中 宏和; 辰巳 陽一; 芦田 隆司; 松村 到
    臨床血液 2017年01月
  • 副腎不全を契機に診断した両側性副腎原発悪性リンパ腫の1例  [通常講演]
    波江野 高大; 頼 晋也; 藤本 昂; 森田 泰慶; 田中 宏和; 辰巳 陽一; 芦田 隆司; 松村 到
    臨床血液 2017年01月
  • CLEC-2 EXPRESSION IS A NEW MARKER FOR A SUBSET OF HEMATOPOIETIC STEM/PROGENITOR CELLS THAT CONTRIBUTES TO INFLAMMATION-INDUCED EMERGENT MEGAKARYOPOIESIS  [通常講演]
    T. Kumode; H. Tanaka; S. Rai; Y. Taniguchi; I. Matsumura
    HAEMATOLOGICA 2016年06月 FERRATA STORTI FOUNDATION
  • PROCOAGULANT MICROPARTICLE IS A NEW SURROGATE BIOMARKER FOR THROMBOTIC EVENTS IN PATIENTS WITH MYELOPROLIFERATIVE NEOPLASMS  [通常講演]
    Y. Taniguchi; H. Tanaka; T. Kumode; S. Rai; I. Matsumura
    HAEMATOLOGICA 2016年06月 FERRATA STORTI FOUNDATION
  • 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 2016年02月
  • 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 2016年02月
  • 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 2016年02月
  • 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 2015年06月
  • 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
    日本輸血細胞治療学会誌 2015年04月
  • 臍帯血移植における前処置の比較 全身放射線照射と抗胸腺グロブリン  [通常講演]
    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
    日本輸血細胞治療学会誌 2015年04月 (一社)日本輸血・細胞治療学会
  • 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 2015年02月
  • 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 2015年02月
  • 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 2015年02月
  • 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
    日本造血細胞移植学会総会プログラム・抄録集 2015年02月
  • Chlorpromazine, an Inhibitor of Intracellular Trafficking of FLT3-ITD and KIT D816V, Shows Prominent Anti-Leukemic Activities Against AML Cells and AML Stem Cells in Vitro and in Vivo.  [通常講演]
    Shinya Rai; Hirokazu Tanaka; Mai Suzuki; Akira Tanimura; Keiko Matsui; Toshio Watanabe; Yuzuru Kanakura; Itaru Matsumura
    BLOOD 2014年12月 AMER SOC HEMATOLOGY
  • Kanai Yoshitaka; Shimada Takahiro; Taniguchi Yasuhiro; Rai Shinya; Hirase Chikara; Hanamoto Hitoshi; Morita Yasuyoshi; Tanaka Hirokazu; Tatsumi Yoichi; Ashida Takashi; Matsumura Itaru
    ACTA MEDICA KINKI UNIVERSITY = The Kinki University Medical Association 2014年06月 Kinki University Medical Association
     
    [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.
  • LEUKEMOGENIC FLT3-ITD AND KIT D814V DEPEND MORE ON CALM FUNCTION THAN THEIR WILD TYPES TO TRANSMIT GROWTH/SURVIVAL SIGNALS: IDENTIFICATION OF CALM AS A NEW THERAPEUTIC TARGET  [通常講演]
    S. Rai; H. Tanaka; Y. Taniguchi; T. Shimada; M. Suzuki; A. Tanimura; K. Matsui; T. Watanabe; Y. Kanakura; I. Matsumura
    HAEMATOLOGICA 2014年06月 FERRATA STORTI FOUNDATION
  • CALM Plays a Critical Role in CYと杵Signaling by Regulating Cellilar Localization of RTKs院Hematopoietic Cells  [通常講演]
    賴 晋也
    2nd International Symposium of Training Pla for Oncology Professionals 2014年01月 2nd International Symposium of Training Pla for Oncology Professionals
  • Trib１and Trib2 block myeloid differentitation by sippressing AKT phosphorylation  [通常講演]
    金井 良高; 嶋田 高広; 谷口 康博; 賴 晋也; 平瀨 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
    第75回日本血液学会学術集会 2013年10月 札幌 第75回日本血液学会学術集会
  • CALM controls signaling RTKs by regulating their cellular localization in hematopoietic cells  [通常講演]
    賴 晋也; 田中 宏和; 松村 到; Mai Suzuki; Toshio Watanabe; 谷村 朗; 松井敬子; 金倉 譲
    第75回日本血液学会学術集会 2013年10月 札幌 第75回日本血液学会学術集会
  • Clinical outcome of radioimmunotherapy with ASCT(Z-LEED) for B-cell Lymphoma  [通常講演]
    辰巳 陽一; 賴 晋也; 金井 良高; 平瀨 主税; 山口 晃史; 森田 泰慶; 田中 宏和; 嶋田 高広; 宮武 淳一; 芦田 隆司
    第75回日本血液学会学術集会 2013年10月 札幌 第75回日本血液学会学術集会
  • Results of gemcitabine therapy for related of refractory Non-Hodgkin’slymphoma in one institute  [通常講演]
    芹澤 憲太郎; 森田 泰慶; 谷口 康博; 川内 超矢; 江口 剛; 江本 正克; 金井 良高; 賴 晋也; 平瀨 主税; 田中 宏和; 口分田 貴裕; 宮武 淳一; 辰巳 陽一; 芦田 隆司; 松村 到
    第75回日本血液学会学術集会 2013年10月 札幌 第75回日本血液学会学術集会
  • CALM links cytokine to hematopoietic cell growth and survival by regulating intracellulartrafficking of receptor tyrosune kinases  [通常講演]
    賴 晋也; 田中 宏和; 松村 到; Mai Suzuki; Toshio Watanabe; 谷村 朗; 松井敬子; 金倉 譲
    第18回 欧州血液学会 EHA 2013年06月 ストックホルム 第18回 欧州血液学会 EHA
  • 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 2013年02月
  • CLINICAL OUTCOME OF RADIOIMMUNOTHERAPY WITH ASCT (Z-LEED) FOR RELAPSED AND REFRACTORY B-CELL LYMPHOMA  [通常講演]
    Y. Tatsumi; S. Rai; Y. Kanai; C. Hirase; T. Yamaguchi; Y. Morita; H. Tanaka; T. Simada; K. Kawanishi; J. Miyaktake; T. Ashida; I. Matsumura
    ANNALS OF ONCOLOGY 2012年10月 OXFORD UNIV PRESS
  • Bioclonal acute myeloid leukemia with t(2;5;15)and ｔ（9;22)  [通常講演]
    芹澤 憲太郎; 綿谷 陽作; 大山 泰世; 江本 正克; 大山 雄一; 谷口 康博; 金井 良高; 頼 晋也; 平瀬 主税; 山口 晃史; 森田 泰慶; 田中 宏和; 嶋田 高広; 川西一信; 辰巳 陽一; 芦田 隆司; 松村 到
    第74回日本血液学会学術集会 2012年10月 京都 第74回日本血液学会学術集会
  • Clinical outcome of radioimmunotherapy with ASCT (Z-LEED)for relapsed and refractory B- cell lymphoma  [通常講演]
    辰巳 陽一; 賴 晋也; 金井 良高; 平瀨 主税; 山口 晃史; 森田 泰慶; 田中 宏和; 嶋田 高広; 川西 一信; 宮武 淳一; 芦田 隆司; 松村 到
    第10回日本臨床腫瘍学会学術集会 2012年07月 大阪 第10回日本臨床腫瘍学会学術集会
  • 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; 賴 晋也; 笹川淳; 平瀨 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
    第34回日本造血細胞移植学会総会 2012年02月 大阪 第34回日本造血細胞移植学会総会
  • Experience of indolent malignant lymphoma treated with Bendamustine in our institute  [通常講演]
    谷口 康博; 辰巳 陽一; 川内 超矢; 江本 正克; 頼 晋也; 金井 良高; 平瀬 主税; 森田 泰慶; 田中 宏和; 芹澤 憲太郎; 嶋田 高広; 川西一信; 宮武 淳一; 芦田 隆司; 松村 到
    第74回日本血液学会学術集会 2012年 京都 第74回日本血液学会学術集会
  • 鈴木麻衣; 田中宏和; 谷村朗; 田邊賢司; 大江夏子; 頼晋也; 昆俊亮; 福本学; 竹居孝二; 松村到; 金倉譲; 渡邊利雄
    日本分子生物学会年会プログラム・要旨集(Web) 2012年
  • Therapy-related myeliod/natural killer cell precursor acute leukemia  [通常講演]
    山入望美; 松田光弘; 岩永隆行; 板垣信生; 松村 到; 江口 剛; 賴 晋也
    第73回日本血液学会学術集会 2011年10月 名古屋 第73回日本血液学会学術集会
  • Clinical outcome of radioimmunotherapy with ASCT for relapsed mantle cell lymphoma  [通常講演]
    辰巳 陽一; 賴 晋也; 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
    第73回日本血液学会学術集会 2011年10月 名古屋 第73回日本血液学会学術集会
  • Analysis of iron overload in patients with transfusion-dependent hematological diseases  [通常講演]
    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; 大山 泰世; 尾嶋 真由子; 井上 宏昭; 口分田 貴裕; 芹澤 憲太郎; 江本 正克; 谷口 康博; 田中 宏和; 金井 良高; 賴 晋也; 笹川 淳; 平瀨 主税; 山口 晃史; 森田 泰慶; 嶋田 高広; 川西 一信; 辰巳 陽一; 松村 到
    第73回日本血液学会学術集会 2011年10月 名古屋 第73回日本血液学会学術集会
  • 同種末梢血幹細胞移植後早期再発の治療抵抗性非ホジキンリンパ腫に対し、ドナーリンパ球輸注を行うことで完全寛解し得た症例  [通常講演]
    山口 晃史; 頼 晋也; 川西一信; 芦田 隆司; 山田枝里佳; 井出大輔; 菅野知恵美; 伊藤志保; 峯 佳子; 藤田往子; 金光 靖; 松村 到; 金丸昭久
    第59回 日本輸血・細胞治療学会総会 2011年04月 東京 第59回 日本輸血・細胞治療学会総会
  • 山口晃史; 頼晋也; 川西一信; 芦田隆司; 山田枝里佳; 井手大輔; 菅野知恵美; 伊藤志保; 峯佳子; 藤田往子; 金光靖; 松村到; 金丸昭久
    日本輸血細胞治療学会誌 2011年03月
  • 同種末梢血幹細胞移植後早期再発の治療抵抗性ホジキンリンパ腫に対し、ドナーリンパ球輸注を行うことで完全寛解し得た症例  [通常講演]
    山口 晃史; 頼 晋也; 川西 一信; 芦田 隆司; 山田 枝里佳; 井手 大輔; 菅野 知恵美; 伊藤 志保; 峯 佳子; 藤田 往子; 金光 靖; 松村 到; 金丸 昭久
    日本輸血細胞治療学会誌 2011年03月 (一社)日本輸血・細胞治療学会
  • 頼晋也; 松田光弘; 口分田貴裕; 井上宏昭; 川内超矢; 江本正克; 芹澤憲太郎; 金井良高; 山口晃史; 森田泰慶; 嶋田高広; 宮武淳一; 辰巳陽一; 芦田隆司; 前田裕弘; 松村到
    日本造血細胞移植学会総会プログラム・抄録集 2011年
  • A young case diagnosed concomitantly as B-CLL and B-cell lymphoma  [通常講演]
    賴 晋也; 辰巳 陽一; 口分田 貴裕; 井上 宏昭; 川内 超矢; 江口 剛; 大山 雄一; 山口 晃史; 森田 泰慶; 嶋田 高広; 宮武 淳一; 芦田 隆司; 前田 裕弘; 松村 到; 松田 光弘
    第72回 日本血液学会学術集会 2010年09月 横浜 第72回 日本血液学会学術集会
  • 急性混合性白血病を発症し、同種骨髄移植にて寛解維持するも一年後骨腫瘤病変にて再発し再移植した症例  [通常講演]
    江口 剛; 山口 晃史; 口分田 貴裕; 井上 宏昭; 川内 超矢; 大山 雄一; 賴 晋也; 森田 泰慶; 嶋田 高広; 川西 一信; 宮武 淳一; 辰巳 陽一; 芦田 隆司; 前田 裕弘; 松村 到; 金丸 昭久; 佐野 徹明
    第20回 南近畿血液病フォーラム 2010年07月 大阪 第20回 南近畿血液病フォーラム
  • 辰巳陽一; 頼晋也; 金井吉高; 平瀬主悦; 山口晃史; 森田泰慶; 嶋田高弘; 川西一信; 宮武淳一; 芦田隆司; 前田裕弘; 金丸昭久
    日本リンパ網内系学会会誌 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 2010年05月
  • 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 2010年05月
  • 化学療法に抵抗性で急激な転帰をとったmyeloid/NK-cell precursor acute leukaemiaの一例  [通常講演]
    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 2010年05月 (一社)日本リンパ網内系学会
  • 辰巳陽一; 宮武淳一; 川西一信; 嶋田高広; 佐野徹明; 森田泰慶; 山口晃史; 川田修平; 頼晋也; 金井良高; 芦田隆司; 前田裕弘; 金丸昭久
    臨床血液 2009年09月
  • 造血幹細胞移植後の骨量に対する影響とビスフォスネート製剤介入の有効性の検討（造血幹細胞移植後骨粗鬆症に対する効果的な治療法に関する前方視的試験）  [通常講演]
    川西 一信; 金井 良高; 賴 晋也; 高井 俊輔; 平瀬 主税; 川田 修平; 森田 泰慶; 佐野 徹明; 宮武 淳一; 辰巳 陽一; 芦田 隆司; 前田 裕弘; 金丸 昭久; 池田 光正; 浜西 千秋
    第31回日本造血細胞移植学会総会 2009年02月 札幌 第31回日本造血細胞移植学会総会
     
    造血幹細胞移植患者において、骨粗鬆症の診療として利用される骨代謝マーカーを測定し、移植後の骨量に対する影響と骨量減少に対するビスフォスフォネート製剤介入の有効性の検討を前方視的に行った。
  • 川西一信; 金井良高; 頼晋也; 高井俊輔; 平瀬主税; 川田修平; 山口晃史; 森田泰慶; 佐野徹明; 宮武淳一; 辰巳陽一; 芦田隆司; 前田裕弘; 金丸昭久
    臨床血液 2008年09月
  • 頼晋也; 辰巳陽一; 平瀬主税; 高井俊輔; 川田修平; 森田泰慶; 佐野徹明; 宮武淳一; 川西一信; 芦田隆司; 前田裕弘; 金丸昭久
    臨床血液 2008年09月
  • 佐野徹明; 頼晋也; 高井俊介; 平瀬主税; 川田修平; 森田泰慶; 川西一信; 宮武淳一; 辰巳陽一; 芦田隆司; 前田裕弘; 金丸昭久
    臨床血液 2008年09月
  • 前田裕弘; 頼晋也; 金井良高; 平瀬主税; 高井俊輔; 川田修平; 山口晃史; 森田泰慶; 佐野徹明; 川西一信; 宮武淳一; 辰巳陽一; 芦田隆司; 金丸昭久; 浦瀬文明; 花本仁; 八木秀男; 椿和央
    臨床血液 2008年09月
  • 辰巳陽一; 頼晋也; 平瀬主税; 高井俊輔; 川田修平; 山口晃史; 森田康慶; 佐野徹明; 宮武淳一; 川西一信; 芦田隆司; 前田裕弘; 金丸昭久
    臨床血液 2008年09月
  • 中枢神経浸潤に対して手術・全脳照射後、非寛解期に児母間末梢血幹細胞移植を施行したAMLの一例  [通常講演]
    佐野 徹明; 頼 晋也; 高井 俊介; 平瀬 主税; 川田 修平; 森田 泰慶; 川西 一信; 宮武 淳一; 辰巳 陽一; 芦田 隆司; 前田 裕弘; 金丸 昭久
    臨床血液 2008年09月 (一社)日本血液学会-東京事務局
  • 骨髄破壊的同種骨髄移植後、T細胞混合キメラが持続した急性赤白血病の一例  [通常講演]
    川西 一信; 金井 良高; 頼 晋也; 高井 俊輔; 平瀬 主税; 川田 修平; 山口 晃史; 森田 泰慶; 佐野 徹明; 宮武 淳一; 辰巳 陽一; 芦田 隆司; 前田 裕弘; 金丸 昭久
    臨床血液 2008年09月 (一社)日本血液学会-東京事務局
  • 頼晋也; 辰巳陽一; 山口晃史; 川田修平; 森田泰慶; 佐野徹明; 川西一信; 宮武淳一; 芦田隆司; 前田裕弘; 金丸昭久
    日本リンパ網内系学会会誌 2008年05月
  • 同種骨髄移植後早期に血球貪食症候群を合併した二次性白血病症例  [通常講演]
    賴 晋也; 辰巳 陽一; 金井 良高; 山口 晃史; 川西 一信; 平瀨 主税; 高井 俊輔; 川田 修平; 森田 泰慶; 佐野 徹明; 宮武 淳一; 芦田 隆司; 前田 裕弘; 金丸 昭久
    第23回近畿細胞移植懇話会 2008年03月 大阪 第23回近畿細胞移植懇話会
  • 辰巳陽一; 頼晋也; 川田修平; 山口晃史; 森田泰慶; 佐野徹明; 川西一信; 宮武淳一; 前田裕弘; 金丸昭久
    日本内科学会雑誌 2008年02月
  • 中枢神経浸潤に対して手術・全脳照射後、非寛解期に児母間末梢血幹細胞移植を施行した一例  [通常講演]
    佐野 徹明; 山口 晃史; 賴 晋也; 川田 修平; 森田 泰慶; 川西 一信; 宮武 淳一; 辰巳 陽一; 芦田 隆司; 前田 裕弘; 金丸 昭久
    第四回 南大阪細胞移植療法研究会 2007年11月 大阪狭山 第四回 南大阪細胞移植療法研究会
  • 頼晋也; 辰巳陽一; 金井良高; 山口晃史; 森田泰慶; 佐野徹明; 川西一信; 宮武淳一; 芦田隆司; 前田裕弘; 金丸昭久
    臨床血液 2007年09月
  • 芦田隆司; 金井良高; 頼晋也; 川田修平; 渡辺克哉; 山口晃史; 森田泰憲; 土方康基; 佐野徹明; 川西一信; 宮武淳一; 辰巳陽一; 前田裕弘; 金丸昭久
    臨床血液 2007年09月
  • 川西一信; 金井良高; 頼晋也; 渡辺克哉; 川田修平; 山口晃史; 土方康基; 森田泰慶; 佐野徹明; 宮武淳一; 辰巳陽一; 芦田隆司; 前田裕弘; 金丸昭久
    臨床血液 2007年09月
  • 同種移植における目標血中濃度を400-450ng/mlに設定したシクロスポリンA持続投与法の有効性と安全性  [通常講演]
    芦田 隆司; 金井 良高; 頼 晋也; 川田 修平; 渡辺 克哉; 山口 晃史; 森田 泰慶; 土方 康基; 佐野 徹明; 川西 一信; 宮武 淳一; 辰巳 陽一; 前田 裕弘; 金丸 昭久
    臨床血液 2007年09月 (一社)日本血液学会-東京事務局
  • Patient benefit from trastuzumab plus a taxane regardless of estrogen receptor (ER) status or prior adjuvant therapy for HER2+metastatic breast cancer (MBC).  [通常講演]
    JC Reddy; S Rai; G Lieberman; P Klein
    JOURNAL OF CLINICAL ONCOLOGY 2004年07月 AMER SOC CLINICAL ONCOLOGY

MISC

  • 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
  • 腹水貯留にて発症したprimary effusion lymphoma-like diffuse large B-cell lymphomaの1例
    堀川 亮太; 頼 晋也; 齋藤 花往里; 森田 泰慶; 田中 宏和; 辰巳 陽一; 芦田 隆司; 松村 到 臨床血液 58 (1) 48 -48 2017年01月
  • 副腎不全を契機に診断した両側性副腎原発悪性リンパ腫の1例
    波江野 高大; 頼 晋也; 藤本 昂; 森田 泰慶; 田中 宏和; 辰巳 陽一; 芦田 隆司; 松村 到 臨床血液 58 (1) 53 -53 2017年01月
  • CLLの経過中に発症したHodgkin variant of Richter syndromeの1例
    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) 187 -187 2016年02月
  • 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
  • 臍帯血移植における前処置の比較 全身放射線照射と抗胸腺グロブリン
    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 日本輸血細胞治療学会誌 61 (2) 324 -324 2015年04月
  • 同種末梢血幹細胞移植後早期再発の治療抵抗性ホジキンリンパ腫に対し、ドナーリンパ球輸注を行うことで完全寛解し得た症例
    山口 晃史; 頼 晋也; 川西 一信; 芦田 隆司; 山田 枝里佳; 井手 大輔; 菅野 知恵美; 伊藤 志保; 峯 佳子; 藤田 往子; 金光 靖; 松村 到; 金丸 昭久 日本輸血細胞治療学会誌 57 (2) 332 -332 2011年03月
  • 再発・難治B細胞性リンパ腫に対する放射免疫療法選択における臨床背景の検討
    辰巳 陽一; 頼 晋也; 金井 吉高; 平瀬 主悦; 山口 晃史; 森田 泰慶; 嶋田 高弘; 川西 一信; 宮武 淳一; 芦田 隆司; 前田 裕弘; 金丸 昭久 日本リンパ網内系学会会誌 50 118 -118 2010年05月
  • 再発・治療抵抗性B細胞非ホジキンリンパ腫に対するゼバリン療法の臨床的検討
    辰巳 陽一; 宮武 淳一; 川西 一信; 嶋田 高広; 佐野 徹明; 森田 泰慶; 山口 晃史; 川田 修平; 頼 晋也; 金井 良高; 芦田 隆司; 前田 裕弘; 金丸 昭久 臨床血液 50 (9) 1020 -1020 2009年09月
  • 骨髄破壊的同種骨髄移植後、T細胞混合キメラが持続した急性赤白血病の一例
    川西 一信; 金井 良高; 頼 晋也; 高井 俊輔; 平瀬 主税; 川田 修平; 山口 晃史; 森田 泰慶; 佐野 徹明; 宮武 淳一; 辰巳 陽一; 芦田 隆司; 前田 裕弘; 金丸 昭久 臨床血液 49 (9) 1157 -1157 2008年09月
  • 中枢神経浸潤に対して手術・全脳照射後、非寛解期に児母間末梢血幹細胞移植を施行したAMLの一例
    佐野 徹明; 頼 晋也; 高井 俊介; 平瀬 主税; 川田 修平; 森田 泰慶; 川西 一信; 宮武 淳一; 辰巳 陽一; 芦田 隆司; 前田 裕弘; 金丸 昭久 臨床血液 49 (9) 1159 -1159 2008年09月
  • Relative Dose Intensity(RDI)から見た悪性リンパ腫臨床治療の現状
    辰巳 陽一; 頼 晋也; 平瀬 主税; 高井 俊輔; 川田 修平; 山口 晃史; 森田 康慶; 佐野 徹明; 宮武 淳一; 川西 一信; 芦田 隆司; 前田 裕弘; 金丸 昭久 臨床血液 49 (9) 1232 -1232 2008年09月
  • 慢性期CMLにおけるイマチニブ血中濃度測定の有用性
    前田 裕弘; 頼 晋也; 金井 良高; 平瀬 主税; 高井 俊輔; 川田 修平; 山口 晃史; 森田 泰慶; 佐野 徹明; 川西 一信; 宮武 淳一; 辰巳 陽一; 芦田 隆司; 金丸 昭久; 浦瀬 文明; 花本 仁; 八木 秀男; 椿 和央 臨床血液 49 (9) 1019 -1019 2008年09月
  • 非血縁者間骨髄移植後早期に発症した血球貪食症候群の一例
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  • 当科における再発/治療抵抗性悪性リンパ腫に対する化学療法と自家末梢血幹細胞移植の比較検討
    頼 晋也; 辰巳 陽一; 山口 晃史; 川田 修平; 森田 泰慶; 佐野 徹明; 川西 一信; 宮武 淳一; 芦田 隆司; 前田 裕弘; 金丸 昭久 日本リンパ網内系学会会誌 48 108 -108 2008年05月
  • 難治性造血器腫瘍における母児間免疫寛容理念に基づくHLA不一致血縁者間造血幹細胞移植の成績
    川西 一信; 金井 良高; 頼 晋也; 渡辺 克哉; 川田 修平; 山口 晃史; 土方 康基; 森田 泰慶; 佐野 徹明; 宮武 淳一; 辰巳 陽一; 芦田 隆司; 前田 裕弘; 金丸 昭久 臨床血液 48 (9) 1023 -1023 2007年09月
  • 同種移植における目標血中濃度を400-450ng/mlに設定したシクロスポリンA持続投与法の有効性と安全性
    芦田 隆司; 金井 良高; 頼 晋也; 川田 修平; 渡辺 克哉; 山口 晃史; 森田 泰慶; 土方 康基; 佐野 徹明; 川西 一信; 宮武 淳一; 辰巳 陽一; 前田 裕弘; 金丸 昭久 臨床血液 48 (9) 1024 -1024 2007年09月
  • 急速進行性糸球体腎炎を合併した血管免疫芽球性T細胞リンパ腫の一例
    頼 晋也; 辰巳 陽一; 金井 良高; 山口 晃史; 森田 泰慶; 佐野 徹明; 川西 一信; 宮武 淳一; 芦田 隆司; 前田 裕弘; 金丸 昭久 臨床血液 48 (9) 1087 -1087 2007年09月

産業財産権

共同研究・競争的資金等の研究課題

  • 日本学術振興会：科学研究費助成事業 基盤研究(C)
    研究期間 : 2020年04月 -2023年03月 
    代表者 : 田中 宏和; 松村 到; 頼 晋也; 森田 泰慶
     
    本研究では、多発性骨髄腫(MM)幹細胞を用いて、免疫チェックポイント分子の発現変化と発現調節機序を解析するとともに、同一患者由来の免疫担当細胞の特性を解析することで、MM患者の病態と抗腫瘍免疫との関連を包括的に明らかにすることを目的とする。昨年度はMM細胞集団CD38+138+45-19- (phenotypic MM cell, phMC）を幹細胞マーカーであるCD34の発現の有無によりCD34+, CD34- PhMCに分離し、それぞれにおける免疫チェックポイント分子の発現を網羅的に比較した。その結果CD274 (PDL1), CD155 (TIGIT), CD270 (TNFSFR14), GAL9等の抗腫瘍免疫の抑制分子の発現が、CD34-PhMCと比較してCD34+ PhMCにおいて有意に高いことを見出した。本年度は、これら分子が抗骨髄腫免疫に果たす機能について共培養系を用いて検討した。CD34+ phMC と同一症例から得た樹状細胞, pDC、細胞障害性T細胞, CTLとの共培養の系（Ref. Cancer Cell. 2009; 16: 309-23.）を用いた。各免疫チェックポイント分子の中和抗体を添加することによるCTL活性の変化を、CTLの増殖能、培養上清へのサイトカイン放出能等を評価することで、CTL 活性に及ぼす免疫チェックポイント分子の同定を試みた。その結果、症例ごとにMM 特異的 CD8+ CTL 活性を引き起こす中和抗体は異なり、症例ごとに免疫抑止に関わる分子は異なることが明らかになった。
  • 日本学術振興会：科学研究費助成事業 基盤研究(C)
    研究期間 : 2018年04月 -2021年03月 
    代表者 : 松村 到; 田中 宏和; 頼 晋也; 森田 泰慶
     
    本研究では、チロシンキナーゼ阻害薬（TKI）に抵抗性を示し、治療後も残存する慢性骨髄性白血病(CML)幹細胞の分子遺伝学的特性の全貌を明らかにすることを目的とする。本年度は、CML幹細胞の抗腫瘍免疫回避機構について解析を行った。 申請者らが見出したCD34+38-225+120a+で定義されるCML幹細胞において、免疫チェックポイント分子PDL1は、初発時18.8±14.2％に発現を認めたのに対し、TKI投与により細胞遺伝学的寛解(CyR)を得ている症例のCML幹細胞では47.6±22.5％と有意な発現上昇を認めた（n=17, p<0.01）。投与TKIによる差は認められず、PDL2の発現は初発、治療中いずれにおいても認められなかった。興味深いことにCD34+38-225+120a- CML細胞では、PDL1の発現上昇が軽度であったことから、CD120a/NF-κB経路がCML細胞におけるPDL1の発現調節に機能している可能性が示唆された。PDL1/L2以外の免疫チェックポイント分子であるCD80/CD86, B7ファミリー分子, CD112/CD155, CD226, Galectin 9, CD137 ligand, CD252 (OX40) ligandの発現に関しては、TKI治療前後での一定の傾向は認められなかった。次に、CyRを得ている患者骨髄よりPDL1＋、PDL1-CML幹細胞をsotingし、同一患者由来のCD8+細胞とサイトカイン非存在下で48時間共培養した際の培養上清中に産生される液性因子を定性的に評価した。その結果PDL1＋細胞との共培養では、PDL1-細胞との共培養と比較して、IFNγ, TNFα, IGFBP2の上清中の濃度が低く、IL10の濃度が高かったことから、PDL1＋細胞はCD8+細胞に対して抑制性に作用していると考えられた。
  • 日本学術振興会：科学研究費助成事業 基盤研究(C)
    研究期間 : 2016年04月 -2019年03月 
    代表者 : 田中 宏和; 松村 到; 頼 晋也; 森田 泰慶; 芹澤 憲太郎
     
    申請者らは、54例の多発性骨髄腫(MM)症例の骨髄サンプルを用いた解析を行い、CD38+ CD 138+ CD 19- CD 45-で定義されるMM細胞(PhMCs)からをMMの起源となる細胞を分離した。PhMCsには、CD34+のわずかな分画が存在し、in vitro および in vivoでのMM発症、抗腫瘍薬抵抗性に寄与した。骨髄中のCD34+ PhMCsの割合は、初発例よりも再発難治例で有意に高かった。遺伝子発現解析の結果、CD34- PhMCsでは一般的なMM細胞の遺伝子発現様式を示し、CD34+ PhMCsではより未分化な胚中心以前の発現様式を示した。
  • 日本学術振興会：科学研究費助成事業 若手研究(B)
    研究期間 : 2016年04月 -2017年03月 
    代表者 : 頼 晋也
     
    チロシンキナーゼ阻害剤(TKI)は、受容体チロシンキナーゼ(RTK)に変異を有する腫瘍の治療成績を劇的に改善した。しかしながらTKI単剤では、耐性獲得などにより再発する例が多く、新たな治療法の開発が求められている。 申請者らは、変異RTK を有する白血病細胞に対して、抗精神病薬chlorpromazine (CPZ)がRTKの細胞内局在を変化させることで、特異的な殺細胞効果をもたらすことを見出した。本研究では、この効果がTKI変異を有する様々な固形腫瘍において得られるかを検証するとともに、その分子機構を解析することで、様々な腫瘍におけるTKI耐性克服のための治療戦略基盤を確立することを目的とする。 平成28 年度は、CPZ の固形腫瘍における抗腫瘍効果の検証として、非小細胞肺癌細胞株HCC4006(EGFR活性化変異)、H1437(MET活性化変異)、H1993(MET増幅)、H3122(EML4-ALK)、胃癌細胞株MKN45(MET増幅)を用いて、各阻害剤Gefitinib、Tivantinib、Alectinibとの併用効果について解析した。CPZ を至適血中濃度の範囲0-10μM 添加し、5 日間培養を行った結果、いずれの細胞株もRTKの局在変化により濃度依存的なviabilityの低下を認めた。さらにCPZと各TKIとの併用効果を検討した結果、相乗的な殺細胞効果をもたらすことを見出した。同様の検討を、Gefitinib耐性株HCC827GR、PC-9ZDを用いて検討した結果、EGFRのゲートキーパー変異(T790M)を有するPC-9ZDにおいて、CPZ併用によりTKI感受性が回復し、耐性を克服できる可能性が示唆された。一方HCC827GRでは、過剰発現するMETの細胞内局在がCPZ処理によっても変化せず、Gefitinib耐性が保持されていると考えられた。

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