佐久間 圭一朗(サクマ ケイイチロウ)

農学部 食品栄養学科教授

Last Updated :2024/06/18

■教員コメント

コメント

がんができる仕組みや進行する仕組みを分子レベルで解明し、新しい治療法や予防法を開発することを目標に、研究をおこなっています。

■研究者基本情報

学位

  • 医学博士(京都大学大学院医学研究科)

科研費研究者番号

90402891

研究キーワード

  • がん   治療標的分子   

現在の研究分野(キーワード)

がんができる仕組みや進行する仕組みを分子レベルで解明し、新しい治療法や予防法を開発することを目標に、研究をおこなっています。

研究分野

  • ライフサイエンス / 腫瘍生物学

■経歴

経歴

  • 2022年04月 - 現在  近畿大学大学院農学研究科応用生命化学専攻近畿大学農学部食品栄養学科教授
  • 2018年04月 - 2022年03月  愛知県がんセンター研究所がん病態生理学分野分子病態ユニット長
  • 2017年04月 - 2018年03月  愛知県がんセンター研究所分子病態学部室長
  • 2007年04月 - 2017年03月  愛知県がんセンター研究所分子病態学部主任研究員
  • 2005年04月 - 2007年03月  京都大学医学部附属病院呼吸器内科医員
  • 2001年04月 - 2005年03月  京都大学大学院医学研究科呼吸器内科学専攻課程修了中退
  • 1999年06月 - 2001年03月  福井赤十字病院内科
  • 1998年05月 - 1999年05月  京都大学医学部附属病院内科研修医

学歴

  • 2001年04月 - 2005年03月   京都大学大学院医学研究科   呼吸器内科学専攻
  • 2001年10月 - 2003年09月   自然科学研究機構   生理学研究所   分子神経生理部門 受託大学院生
  • 1992年04月 - 1998年03月   京都大学   医学部

■研究活動情報

論文

  • Keiichiro Sakuma; Eiichi Sasaki; Waki Hosoda; Koji Komori; Yasuhiro Shimizu; Yasushi Yatabe; Masahiro Aoki
    Cancer science 112 9 3846 - 3855 2021年07月 [査読有り]
     
    HNRNPLL (heterogeneous nuclear ribonucleoprotein L-like) , a suppressor of colorectal cancer (CRC) metastasis, is transcriptionally downregulated when CRC cells undergo epithelial-mesenchymal transition (EMT). Here we show that decrease of MYB mediates the downregulation of HNRNPLL during EMT. The promoter activity was attributed to a region from -273 to -10 base pairs upstream of the transcription start site identified by 5'-RACE analysis, and the region contained potential binding sites for MYB and SP1. Luciferase reporter gene assays and knockdown or knockout experiments for genes encoding the MYB family proteins, MYB, MYBL1, and MYBL2, revealed that MYB was responsible for an approximately half of the promoter activity. On the other hand, treatment with mithramycin A, an inhibitor for SP1 and SP3, suppressed the promoter activity and their additive contribution was confirmed by knockout experiments. The expression level of MYB was decreased upon EMT while those of SP1 and SP3 were unchanged, suggesting that the downregulation of HNRNPLL during EMT was mediated by the decrease of MYB expression while SP1 and SP3 determine the basal transcription level of HNRNPLL. Histopathological analysis confirmed the accumulation of MYB-downregulated cancer cells at the invasion front of clinical CRC tissues. These results provide an insight into the molecular mechanism underlying CRC progression.
  • Keiichiro Sakuma; Reiji Kannagi
    Methods in Molecular Biology 2132 111 - 118 2020年 [査読有り]
     
    Cell–cell interactions mediated by selectins and their ligand glycans play pivotal roles in a variety of biological processes represented by leukocyte recruitment to inflammatory sites, lymphocyte homing, and extravasation of cancer cells. The interactions are enhanced at least partly through the upregulation of the selectin-ligand glycan expression, which is observed, for instance, during the activation of leukocytes or epithelial-mesenchymal transition of cancer cells. Selectin-binding assays such as cell adhesion assay or rolling assay have long been used to directly evaluate the activity of these cells in the selectin-mediated processes. In this chapter, we introduce a highly quantitative assay by flow cytometry using recombinant selectin-Ig(Fc) chimera proteins, showing our procedure and tips for E-selectin-binding assay of colon cancer cells undergoing epithelial-mesenchymal transition.
  • Hijioka S; Sakuma K; Aoki M; Mizuno N; Kuwahara T; Okuno N; Hara K; Yatabe Y
    Cancer chemotherapy and pharmacology 83 1 43 - 52 2018年10月 [査読有り]
     
    PURPOSE: This study aimed to determine the correlation between DNA repair enzyme O6-methylguanine DNA methyltransferase (MGMT) status and the response to streptozocin in advanced well-differentiated pancreatic neuroendocrine tumors (WD panNETs). METHODS: To test the hypothesis that MGMT deficiency was required for an alkylating drug response, we retrospectively reviewed the response of 13 patients with WD panNETs to alkylating agents in relation to MGMT status. We also studied MGMT expression in streptozocin resistance using panNET cell lines. RESULTS: The cohort included 54% of patients with and 46% without MGMT expression. Among these, 83.3% (5/6) of MGMT-negative cases showed a partial response to streptozocin. In contrast, only 14.2% (1/7) of MGMT-positive cases showed a partial response (P = 0.013). Induced expression of MGMT in BON1 cells (a panNET cell line with undetectable endogenous MGMT) produced streptozocin resistance. Knockdown of MGMT in QGP1 cells, which express MGMT endogenously, did not alter the response to streptozocin. CONCLUSIONS: We observed a relationship between MGMT status and streptozocin response in both patients and cell culture. Despite limited cases examined, high concordance of negative expression of MGMT and response to streptozocin treatment suggest that MGMT expression can be a potential biomarker for this treatment.
  • Sakuma K; Sasaki E; Kimura K; Komori K; Shimizu Y; Yatabe Y; Aoki M
    Cancer Science 109 8 2458 - 2468 2018年08月 [査読有り]
     
    Heterogeneous nuclear ribonucleoprotein L-like (HNRNPLL), an RNA-binding protein that regulates alternative splicing of pre-mRNA, has been shown to regulate differentiation of lymphocytes, as well as metastasis of colorectal cancer cells. Here, we show that HNRNPLL promotes cell cycle progression and, hence, proliferation of colorectal cancer cells. Functional annotation analysis of those genes whose expression levels were changed threefold or more in RNA sequencing analysis between SW480 cells overexpressing HNRNPLL and those knocked down for HNRNPLL revealed enrichment of DNA replication-related genes by HNRNPLL overexpression. Among 13 genes detected in the DNA replication pathway, PCNA, RFC3 and FEN1 showed reproducible upregulation by HNRNPLL overexpression both at mRNA and at protein levels in SW480 and HT29 cells. Importantly, knockdown of any of these genes alone suppressed the proliferation-promoting effect induced by HNRNPLL overexpression. RNA-immunoprecipitation assay presented a binding of FLAG-tagged HNRNPLL to mRNA of these genes, and HNRNPLL overexpression significantly suppressed the downregulation of these genes during 12 h of actinomycin D treatment, suggesting a role of HNRNPLL in mRNA stability. Finally, analysis of a public RNA sequencing dataset of clinical samples suggested a link between overexpression of HNRNPLL and that of PCNA, RFC3 and FEN1. This link was further supported by immunohistochemistry of colorectal cancer clinical samples, whereas expression of CDKN1A, which is known to inhibit the cooperative function of PCNA, RFC3 and FEN1, was negatively associated with HNRNPLL expression. These results indicate that HNRNPLL stabilizes mRNA encoding regulators of DNA replication and promotes colorectal cancer cell proliferation.
  • Keiichiro Sakuma; Eiichi Sasaki; Kenya Kimura; Koji Komori; Yasuhiro Shimizu; Yasushi Yatabe; Masahiro Aoki
    Gut 67 6 1103 - 1111 2018年06月 [査読有り]
     
    Objective: Despite the recent advances in treatment of colon cancer, the prognosis is unfavourable for patients with distant metastases. The aim of this study was to identify targets for prevention and/or therapy of colon cancer metastasis. Design: CMT93 cells, a murine rectal cancer cell line with poor metastasising activity, were transduced with lentiviral shRNA library and transplanted into the rectum of syngeneic C57BL/6 mice. Genomic DNA was collected from metastatic lesions, and the integrated shRNA were retrieved by PCR for sequencing, followed by identification of the candidate genes targeted by the shRNA. Results: The genome-wide shRNA library screen identified Hnrnpll (heterogeneous nuclear ribonucleoprotein L-like) encoding a pre-mRNA splicing factor as a candidate metastasis suppressor gene. Knockdown of Hnrnpll enhanced matrigel invasion activity of colon cancer cells in vitro, as well as their metastatic ability in vivo. An RNA-immunoprecipitation analysis showed Hnrnpll-binding to Cd44 pre-mRNAs, and the level of Cd44 variable exon 6 (Cd44v6), a poor prognosis marker of colorectal cancer, was increased by knocking down Hnrnpll. A neutralising Cd44v6 antibody suppressed the matrigel invasion ability induced by Hnrnpll knockdown. HNRNPLL expression was downregulated when colon cancer cells were induced to undergo epithelial-mesenchymal transition (EMT). Immunohistochemistry of clinical samples indicated that colorectal cancer cells with low E-cadherin expression at the invasion front exhibited decreased HNRNPLL expression. Conclusions: HNRNPLL is a novel metastasis suppressor of colorectal cancer, and modulates alternative splicing of CD44 during EMT.
  • Reiji Kannagi; Bi-He Cai; Hsiang-Chi Huang; Chia-Chun Chao; Keiichiro Sakuma
    Methods in Molecular Biology 1804 143 - 171 2018年 [査読有り]
     
    Tumor-associated gangliosides play important roles in regulation of signal transduction induced by growth-factor receptors including EGFR, FGFR, HGF and PDGFR in a specific microdomain called glycosynapse in the cancer cell membranes, and in interaction with glycan recognition molecules involved in cell adhesion and immune regulation including selectins and siglecs. As the genes involved in the synthesis and degradation of tumor-associated gangliosides were identified, biological functions became clearer from the experimental results employing forced overexpression and/or knockdown/knockout of the genes. Studies on the regulatory mechanisms for their expression also achieved great advancements. Epigenetic silencing of glycan-related genes is a dominant mechanism in glycan alteration at early stages of carcinogenesis. Development of hypoxia resistance involving activation of a transcription factor HIF, and acquisition of cancer stem cell-like characteristics through epithelial–mesenchymal transition are important mechanisms for glycan modulations in the later stages of cancer progression. In the initial stages of studies, the gangliosides which specifically appear in cancers attracted attention under the name of tumor-associated gangliosides. However, it became apparent that not only the cancer-associated gangliosides but also the normal gangliosides present in nonmalignant cells and tissues perform important biological functions, and some of them tend to disappear in cancer cells resulting in the loss of the physiological functions, and this sometimes facilitates progression of cancers.
  • Regulation of cell surface glycan expression in cancer stem cells
    Kannagi R; Cai BH; Huang HC; Sakuma K
    Cancer Metastasis and Cancer Stem Cell/Niche 24 - 60 2016年 [査読有り]
  • Tumor-associated glycans and their functional roles in the multistep process of human cancer progression
    Kannagi R; Sakuma K; Cai BH; Yu SY
    Sugar Chains 139 - 158 2015年 [査読有り]
  • Reiji Kannagi; Keiichiro Sakuma; Katsuyuki Ohmori
    Glycoscience: Biology and Medicine 617 - 625 2015年01月 [査読有り]
     
    Several sialyl sulfoglycans in human cells and tissues have recently been found to serve as specific ligands for carbohydrate-recognition molecules in the selectin and siglec families and are expected to play crucial roles in the regulation of immune cell functions in health and diseases. One such sialyl sulfoglycan, sialyl 6-sulfo Lewis X, can serve as a ligand for all members of the selectin family and siglec-7. This glycan was known to be expressed in skinhoming central helper memory T-cells which exhibited bidirectional homing behavior to the skin and peripheral lymph nodes, and was recently found to be involved in the pathophysiology of atopic dermatitis. The binding activity of this glycan to selectins and siglecs is regulated by cyclization of the terminal sialic acid residue, and examination of T-cell subsets expressing sialyl 6-sulfo Lewis X with normal and cyclic sialic acid residues in peripheral blood of the patients is proposed to be clinically useful in evaluating the risk of atopic dermatitis recurrence.
  • Michael L. Patnode; Shin-Yi Yu; Chu-Wen Cheng; Ming-Yi Ho; Lotten Tegesjoe; Keiichiro Sakuma; Kenji Uchimura; Kay-Hooi Khoo; Reiji Kannagi; Steven D. Rosen
    GLYCOBIOLOGY 23 3 381 - 394 2013年03月 [査読有り]
     
    The addition of sulfate to glycan structures can regulate their ability to serve as ligands for glycan-binding proteins. Although sulfate groups present on the monosaccharides glucosamine, uronate, N-acetylglucosamine and N-acetylgalactosamine are recognized by defined receptors that mediate important functions, the functional significance of galactose-6-O-sulfate (Gal6S) is not known. However, in vitro studies using synthetic glycans and sulfotransferase overexpression implicate Gal6S as a binding determinant for the lymphocyte homing receptor, L-selectin. Only two sulfotransferases have been shown to generate Gal6S, namely keratan sulfate galactose 6-O-sulfotransferase (KSGal6ST) and chondroitin 6-O-sulfotransferase-1 (C6ST-1). In the present study, we use mice deficient in KSGal6ST and C6ST-1 to test whether Gal6S contributes to ligand recognition by L-selectin in vivo. First, we establish that KSGal6ST is selectively expressed in high endothelial venules (HEVs) in lymph nodes and Peyer's patches. We also determine by mass spectrometry that KSGal6ST generates Gal6S on several classes of O-glycans in peripheral lymph nodes. Furthermore, KSGal6ST, but not C6ST-1, is required for the generation of the Gal6S-containing glycan, 6,6'-disulfo-3'sLN (Sia alpha 2 -> 3[6S]Gal beta 1 -> 4[6S]GlcNAc) or a closely related structure in lymph node HEVs. Nevertheless, L-selectin-dependent short-term homing of lymphocytes is normal in KSGal6ST-deficient mice, indicating that the Gal6S-containing structures we detected do not contribute to L-selectin ligand recognition in this setting. These results refine our understanding of the biological ligands for L-selectin and introduce a mouse model for investigating the functions of Gal6S in other contexts.
  • Keiichiro Sakuma; Takuya Furuhashi; Sachiko Kondo; Uichiro Yabe; Katsuyuki Ohmori; Hidemi Ito; Masahiro Aoki; Akimichi Morita; Reiji Kannagi
    JOURNAL OF DERMATOLOGICAL SCIENCE 68 3 187 - 193 2012年12月 [査読有り]
     
    Background: The molecular pathogenesis underlying recurrent exacerbations of atopic dermatitis (AD) is unclear. Some peripheral CCR4(+) and CCR7(+) helper memory T cells express the specific homing receptor, sialyl 6-sulfo Lewis X (G152 glycan). This glycan loses receptor activity via cyclization of its sialic acid moiety, thus becoming cyclic sialyl 6-sulfo Lewis X (G159 glycan). These findings suggest that the disordered expression of G152 and G159 glycans may be associated with recurrent exacerbations of AD. Objective: To assess the possible association of G152 and G159 glycans, which are expressed on peripheral helper T (Th) cells, with frequency of exacerbations. Methods: The percentage of glycan-expressing cells among peripheral blood CD4(+)CD45RO(+) lymphocytes was determined by flow cytometry. The association of glycans with the frequency of exacerbations determined by recurrence scores as well as with current disease activity was statistically tested. Results: Current disease activity was significantly associated with CCR4(+)CCR7(-) memory Th cells expressing CSLEX-1 glycan, the conventional skin-trafficking receptor without sialic-acid-cyclization activity. In contrast, the frequency of exacerbations was positively and negatively associated with CCR4+CCR7 memory Th cells expressing G152 and G159 glycans, respectively. Receiver operating characteristics analyses indicated that the ratio of the G152(+)/G159(+) cell percentages discriminated patients with highly recurrent AD with the best accuracy. Conclusion: Flow cytometric determination of G159 and G152 glycans on peripheral helper memory T cells may be clinically useful for identifying patients with highly recurrent AD. Disordered sialic acid cyclization of G152 glycan may underlie highly recurrent AD, which may provide a novel therapeutic approach. (C) 2012 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
  • Sakuma K; Chen GY; Aoki M; Kannagi R
    Biochimica et biophysica acta 1820 7 841 - 848 2012年07月 [査読有り]
  • Keiko Miyazaki; Keiichiro Sakuma; Yuki I. Kawamura; Mineko Izawa; Katsuyuki Ohmori; Motoaki Mitsuki; Toshiyuki Yamaji; Yasuhiro Hashimoto; Akemi Suzuki; Yukio Saito; Taeko Dohi; Reiji Kannagi
    JOURNAL OF IMMUNOLOGY 188 9 4690 - 4700 2012年05月 [査読有り]
     
    Immune cells are known to express specific recognition molecules for cell surface glycans. However, mechanisms involved in glycan-mediated cell cell interactions in mucosal immunity have largely been left unaccounted for. We found that several glycans preferentially expressed in nonmalignant colonic epithelial cells serve as ligands for sialic acid-binding Ig-like lectins (siglecs), the immunosuppressive carbohydrate-recognition receptors carried by immune cells. The siglec ligand glycans in normal colonic epithelial cells included disialyl Lewis(a), which was found to have binding activity to both siglec-7 and -9, and sialyl 6-sulfo Lewis(x), which exhibited significant binding to siglec-7. Expression of these siglec-7/-9 ligands was impaired upon carcinogenesis, and they were replaced by cancer-associated glycans sialyl Lewis(a) and sialyl Lewis(x), which have no siglec ligand activity. When we characterized immune cells expressing siglecs in colonic lamina propriae by flow cytometry and confocal microscopy, the majority of colonic stromal immune cells expressing siglec-7/-9 turned out to be resident macrophages characterized by low expression of CD14/CD89 and high expression of CD68/CD163. A minor subpopulation of CD8(+) T lymphocytes also expressed siglec-7/-9. Siglec-7/-9 ligation suppressed LPS-induced cyclooxygenase-2 expression and PGE(2) production by macrophages. These results suggest that normal glycans of epithelial cells exert a suppressive effect on cyclooxygenase-2 expression by resident macrophages, thus maintaining immunological homeostasis in colonic mucosal membranes. Our results also imply that loss of immunosuppressive glycans by impaired glycosylation during colonic carcinogenesis enhances inflammatory mediator production. The Journal of Immunology, 2012, 188: 4690-4700.
  • Keiichiro Sakuma; Masahiro Aoki; Reiji Kannagi
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 109 20 7776 - 7781 2012年05月 [査読有り]
     
    Sialyl Lewis x (sLe(x)) and sialyl Lewis a (sLe(a)) glycans are expressed on highly metastatic colon cancer cells. They promote extravasation of cancer cells and tumor angiogenesis via interacting with E-selectin on endothelial cells. Recently, epithelial-mesenchymal transition (EMT) has been noted as a critical phenotypic alteration in metastatic cancer cells. To address the association between sLe(x/a) expression and EMT, we assessed whether sLe(x/a) are highly expressed on colon cancer cells undergoing EMT. Treatment of HT29 and DLD-1 cells with EGF and/or basic FGF (bFGF) induced EMT and significantly increased sLe(x/a) expression resulting in enhanced E-selectin binding activity. The transcript levels of the glycosyltransferase genes ST3GAL1/3/4 and FUT3 were significantly elevated and that of FUT2 was significantly suppressed by the treatment. We provide evidence that ST3GAL1/3/4 and FUT3 are transcriptionally up-regulated by c-Myc with probable involvement of Ser62 phosphorylation, and that FUT2 is transcriptionally down-regulated through the attenuation of CDX2. The contribution of c-Myc and CDX2 to the sLe(x/a) induction was proved to be significant by knockdown or forced expression experiments. Interestingly, the cells undergoing EMT exhibited significantly increased VEGF secretion, which can promote tumor angiogenesis in cooperation with sLe(x/a). Finally, immunohistological study indicated high E-selectin ligand expression on cancer cells undergoing EMT in vivo, supporting their coexistence observed in vitro. These results suggest a significant link between sLe(x/a) expression and EMT in colon cancer cells and a pivotal role of c-Myc and CDX2 in regulating sLe(x/a) expression during EMT.
  • Reiji Kannagi; Katsuyuki Ohmori; Guo-Yun Chen; Keiko Miyazaki; Mineko Izawa; Keiichiro Sakuma
    Advances in Experimental Medicine and Biology 705 549 - 569 2011年 [査読有り]
     
    Selectin-mediated adhesion to endothelial cells is the first step of extravasation of leukocytes. Neutrophils constitutively express sialyl Lewis x, the selectin ligand, and are ready to adhere to endothelial cells once the latter cells express E- or P-selectin. This leads to rapid and massive extravasation of neutrophils into acute inflammatory lesions. © 2011 Springer Science+Business Media, LLC.
  • Kannagi R; Izawa M; Sakuma K
    Nihon rinsho. Japanese journal of clinical medicine 68 Suppl 7 720 - 725 2010年07月 [査読有り]
  • Reiji Kannagi; Keiichiro Sakuma; Keiko Miyazaki; Khe-Ti Lim; Akiko Yusa; Jun Yin; Mineko Izawa
    CANCER SCIENCE 101 3 586 - 593 2010年03月 [査読有り]
     
    The glycan molecules that preferentially appear in cancers are clinically utilized as serum tumor markers. The exact reason, however, why glycans are useful as tumor markers remain elusive. Here, we will summarize lessons learned from well-established cancer-associated glycans, and propose strategies to develop new cancer markers. Our recent results on cancer-associated glycans, sialyl Lewis A and sialyl Lewis X, indicated that the repressed transcription of some glycan genes by epigenetic silencing during early carcinogenesis, and the transcriptional induction of some other glycan genes by tumor hypoxia accompanying cancer progression at locally advanced stages, are two major factors determining cancer-associated glycan expression. Multiple genes are involved in glycan synthesis, and epigenetic silencing of a part of such genes leads to accumulation of glycans having truncated incomplete structures, which are readily detected by specific antibodies. Glycans are very unique and advantageous as marker molecules because they are capable of reflecting epigenetic silencing in their structures. Transcriptional induction of some glycan genes by tumor hypoxia at the later stages produces further glycan modifications, such as an unusual increase of the N-glycolyl sialic acid residues in the glycan molecules. The entire process of malignant transformation thus creates abnormal glycans, whose structures reveal the effects of both epigenetic silencing and tumor hypoxia. The second advantage of a glycan marker over a proteinous marker is that they can reflect the plurality of genetic anomalies in a singular molecule, as it is synthesized by the cooperative action of multiple genes. Glycans are sometimes covalently bound to well-known cancer-associated proteins, such as CD44v, and this eventually contributes to a high cancer specificity and functional relevancy in cancer progression. (Cancer Sci 2010; 101: 586-593)
  • Guo-Yun Chen; Keiichiro Sakuma; Reiji Kannagi
    JOURNAL OF BIOLOGICAL CHEMISTRY 283 50 34563 - 34570 2008年12月 [査読有り]
     
    Sulfated glycans play critical roles in various cell recognition events among leukocytes. The 6-sulfated lactosamine glycans in particular have been widely noted for their importance because they are involved in cell recognition events mediated by cell-adhesion molecules such as selectins and sialic acid-recognizing molecules such as siglecs and also in the activation of CD44 in binding to extracellular matrix hyaluronate. A pro-inflammatory cytokine, tumor necrosis factor-alpha, induces expression of 6-sulfated glycans on human leukocytes. Here we report that the transcription of the GlcNAc6ST-1 gene, the gene encoding a sulfotransferase for 6-sulfated glycan synthesis, is induced in human T-lymphoid cells through tandem NF-kappa B and GATA motifs in its 5'-regulatory region. Results of our reporter assays, immunoprecipitation, and chromatin immunoprecipitation analyses indicated that GATA-3 and/or GATA-2, but not GATA-1, associates with NF-kappa B in a transcription factor complex on the 5'-regulatory region of the gene and acts synergistically with NF-kappa B in triggering GlcNAc6ST-1 transcription. Recently, a skin-homing subset of helper memory T cells exhibiting the Th2 marker CCR4 was shown to specifically express 6-sulfated glycans. The transactivation mechanism described here suggested that GlcNAc6ST-1 transcription is coordinated with the NF-kappa B/GATA-3 axis, which is known to figure heavily in Th2 cell differentiation. In line with this, in vitro differentiation of human T cells to Th2 cells was found to significantly induce GlcNAc6ST-1 transcription and 6-sulfated glycan expression.
  • Katsuhiro Masago; Shiro Fujita; Yukimasa Hatachi; Akiko Fukuhara; Keiichiro Sakuma; Masataka Ichikawa; Yung Haku Kim; Tadashi Mio; Michiaki Mishima
    CANCER SCIENCE 99 11 2295 - 2301 2008年11月 [査読有り]
     
    Circulating amphiregulin and transforming growth factor-alpha (TGF-alpha) have been found to be correlated with an unfavorable response to gefitinib based on the identification of patients with a higher probability of resistance to the drug. However, the association between an epidermal growth factor receptor (EGFR) somatic mutation and the overexpression of its ligands has not been determined. To verify the clinical significance of the two serum markers and EGFR mutation status, we determined serum amphiregulin and TGF-alpha levels by enzyme-linked immunosorbent assay in 93 patients with advanced non-squamous, non-small cell lung cancer and EGFR somatic mutation status using the peptic nucleic acid-locked nucleic acid clamp method in 46 cases. The relationship between each independent clinicopathological variable and the response to gefitinib therapy was examined. We also evaluated the risk factors associated with prognosis. Fourteen (41.0%) of 34 progressive disease cases were positive for amphiregulin (P = 0.007). Eleven (32.4%) of 34 progressive disease cases were positive for TGF-alpha (P = 0.005). The median survival time of patients with the EGFR somatic mutation was significantly longer (P = 0.01). The same was true of amphiregulin- (P = 0.046) and TGF-alpha-negative patients (P < 0.01). In multivariate analysis, serum TGF-alpha positivity (hazard ratio, 2.558; P = 0.005) and the wild type EGFR gene (hazard ratio, 1.894; P = 0.003) were significant independent prognostic factors. Our study demonstrates that the status of the serum EGFR ligand, in addition to EGFR activating mutation, is a predictive factor for response to gefitinib therapy. (Cancer Sci 2008; 99: 2295-2301).
  • Katsuhiro Masago; Shiro Fujita; Tadashi Mio; Masataka Ichikawa; Keiichiro Sakuma; Young Hak Kim; Yukimasa Hatachi; Akiko Fukuhara; Kiyofumi Kamiyama; Makoto Sonobe; Ryo Miyahara; Hiroshi Date; Michiaki Mishima
    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY 13 5 442 - 446 2008年10月 [査読有り]
     
    Background. The importance of an epidermal growth factor receptor (EGFR) gene mutation has been recognized in patients with non-small cell lung cancer (NSCLC), and many reports have indicated that the presence of somatic mutations in the EGFR gene is a strong predictor of both clinical and in vitro sensitivity to EGFR tyrosine kinase inhibitors; thus necessitating the standardization of a mutation screening system based on the sources of tissue samples. Methods. In this study, we compared the results of EGFR mutation analyses in 19 small biopsy specimens with results obtained in surgical materials from the same patients with NSCLC. We used a laser microdissection method and a direct sequencing method, and we confirmed the accuracy of EGFR mutation analysis with small biopsy specimens. Results. The results obtained from the biopsy specimens were identical to those obtained from the surgical materials in 18 of the 19 patients analyzed. For the 1 patient in whom the results obtained from the two sets of materials were not identical, the number of cancer cells in one bronchoscopic specimen was insufficient to perform analyses of all three exons of interest (i.e., exons 18, 19, and 21), and so only exon 19 was sequenced, and no mutation was demonstrated. Conclusion. We conclude that satisfactory accuracy can be achieved by the genomic analysis of a small biopsy specimen from a patient with NSCLC and we note that it is possible to conduct prospective clinical trials that include patient assignment for treatment based on the results obtained.
  • Kannagi R; Chen GY; Sakuma K; Ohmori K
    Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme 53 12 Suppl 1525 - 1532 2008年09月 [査読有り]
  • Takahashi M; Hirami Y; Sakuma K; Mio T; Kawagoe N; Mandai M; Mishima M; Yoshimura N
    Nippon Ganka Gakkai zasshi 112 9 806 - 811 2008年09月 [査読有り]
  • Keiichiro Sakuma; Hajime Nakamura; Takayuki Nakamura; Yuma Hoshino; Shugo Ueda; Masataka Ichikawa; Chiharu Tabata; Shiro Fujita; Katsuhiro Masago; Junji Yodoi; Michiaki Mishima; Tadashi Mio
    INTERNAL MEDICINE 46 23 1905 - 1909 2007年12月 [査読有り]
     
    Objective Interstitial lung disease (ILD) is a severe adverse event of gefitinib therapy. However, the mechanism still remains unclear. The objective of this study was to examine whether or not oxidative stress, one of the common factors in drug-associated ILD, is involved in the pathogenesis of gefitinib-induced ILD. Patients and Methods Using an enzyme-linked immunosorbent assay (ELISA), we measured the concentration of serum thioredoxin (Trx), a redox-active protein with antioxidative effects, in 44 patients treated with gefitinib, including three patients who had ILD. Results In patients who had gefitinib-induced ILD, serum Trx levels were significantly elevated. They decreased after cessation of gefitinib therapy accompanying clinical improvement of ILD. Conclusion It was suggested that oxidative stress may be involved as a part of mechanisms causing or worsening gefitinib-induced ILD.
  • Akihiro Ishii; Takeshi Ikeda; Seiji Hitoshi; Ichiro Fujimoto; Tomohiro Torii; Keiichiro Sakuma; Shin-ichi Nakakita; Sumihiro Hase; Kazuhiro Ikenaka
    GLYCOBIOLOGY 17 3 261 - 276 2007年03月 [査読有り]
     
    Biosynthesis of N-glycans varies significantly among tissues and is strictly regulated spatially and temporally within the tissue. The strict molecular mechanisms that are responsible for control of N-glycan synthesis remain largely unknown. We developed complementary deoxyribonucleic acid (cDNA) macroarray system and analyzed gene expression levels of more than 140 glycosyltransferases and glycosidases in the cerebral cortex from developing and adult mice. We also analyzed the relative amounts of major N-glycans present in the cerebral cortex and examined how the synthesis of N-glycans might be regulated through the expression of these genes. We demonstrated that the content of N-linked oligosaccharides dramatically changed during the course of brain development. Some of these changes could not be explained by alterations in the expression of the corresponding genes. For example, the amount of core fucosylated sugar chains in the early embryonic brain and the expression level of fucosyltransferase VIII, the only gene known to be responsible for core fucosylation, did not change proportionately. This result suggests that post-transcriptional regulation of this gene plays an important role in regulating its enzymatic activity. On the other hand, the amount of beta 1,3-galactose residue-containing sugar chains increased postnatally following an increase in the level of beta 1,3-galactosyltransferase messenger ribonucleic acid (mRNA). Furthermore, the amount of sugar chains with an outer fucose residue, containing LewisX-BA-2, correlated well with the expression of fusocyltransferase IX mRNA. These findings add to our understanding of the molecular mechanisms responsible for the regulation of N-glycan biosynthesis in the cerebral cortex.
  • C Tabata; H Kubo; R Tabata; M Wada; K Sakuma; M Ichikawa; S Fujita; T Mio; M Mishima
    AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY 290 3 L597 - L606 2006年03月 [査読有り]
     
    Although high-dose thoracic radiotherapy is an effective strategy for some malignancies including lung cancers and malignant lymphomas, it often causes complications of radiation fibrosis. To study the mechanism initiating tissue fibrosis, we investigated irradiation-induced cytokine production from human lung fibroblastic cells and found that IL- 6 production was stimulated by irradiation. IL- 6 is an autocrine growth factor for human myeloma cells, and retinoic acid is reported to inhibit their growth. Thus we evaluated the effect of all-trans retinoic acid (ATRA) on cell proliferation of lung fibroblasts along with the cytokine/receptor system. Irradiation-dependent stimulation of IL- 6 production was correlated with increased NF-kappa B activity, and ATRA reduced this effect. Irradiation also increased the levels of mRNA for IL- 6R and gp130, which were blocked by coexisting ATRA. Furthermore, IL- 6 stimulated cell proliferation in dose-dependent manner but was overcome by pharmacological concentration of ATRA. These effects of ATRA were inhibited by rottlerin, which suggests ATRA abolished irradiation-induced stimulation through a PKC delta-dependent pathway. Finally, we demonstrated that IL- 6 transcripts in the lung were upregulated at 2 mo after irradiation, and the effect was inhibited by the intraperitoneal administration of ATRA. ATRA is expected to have an advantage for radiotherapy in its antitumor effects, as reported previously, and to prevent radiotherapy-induced pulmonary injury.
  • K Sakuma; Fujimoto, I; S Hitoshi; F Tanaka; T Ikeda; K Tanabe; S Toyokuni; H Wada; T Mio; M Mishima; K Ikenaka
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 340 3 829 - 835 2006年02月 [査読有り]
     
    N-Glycan structures on the surface of cancer cells have diverse structures and play significant roles in metastatic process. However, little is known about their roles in organ-selective metastasis. Our study revealed that an alpha 1,6-fucosylated biantennary N-glycan structure designated A2G2F is characteristic of lungs, with far more abundant expression in normal human and murine lungs than in other organs. In this study, we further examined the role of A2G2F in pulmonary metastasis. We stained metastatic cancers by of alpha 1,6-fucose-specific Lens culinaris agglutinin lectin and revealed that pulmonary metastatic nodules more abundantly expressed alpha 1,6-fucosylated N-glycans than hepatic metastatic nodules from common primary cancers. The most specific alpha 1,6-fucosylated N-glycan structure in pulmonary metastatic cancer was identified to be A2G2F. Using a B16 melanoma cell metastasis model, we showed that A2G2F-rich B16 cells formed more Pulmonary metastatic nodules than A2G2F-poor cells. Our results suggest that A2G2F plays a critical role in Pulmonary metastasis. (c) 2005 Elsevier Inc. All rights reserved.

MISC

  • 青木正博; 佐久間圭一朗 日本がん転移学会学術集会・総会プログラム抄録集 29th 2020年
  • 新規同定大腸癌転移抑制因子HNRNPLLは上皮間葉転換におけるCD44のmRNA前駆体の選択的スプライシングを制御する
    佐久間圭一朗; 青木正博 INTESTINE 23 (1) 91 -92 2019年
  • 佐久間圭一朗; 青木正博; 青木正博 日本癌学会学術総会抄録集(Web) 78th 2019年
  • Masahiro Aoki; Ryo Maeda; Yasushi Kojima; Keiichiro Sakuma CANCER SCIENCE 109 247 -247 2018年12月
  • HNRNPLLはDNA複製制御因子のmRNAを安定化することで大腸がん細胞の細胞周期を促進する(HNRNPLL promotes cell cycle progression in colon cancer cells by stabilizing mRNAs for regulators of DNA replication)
    佐久間 圭一朗; 青木 正博 日本癌学会総会記事 77回 62 -62 2018年09月
  • がんの転移における腫瘍微小環境の役割(The roles of tumor microenvironment in cancer metastasis)
    青木 正博; 前田 亮; 小島 康; 佐久間 圭一朗 日本癌学会総会記事 77回 272 -272 2018年09月
  • Masahiro Aoki; Eiichi Sasaki; Kenya Kimura; Koji Komori; Yasuhiro Shimizu; Yasushi Yatabe; Keiichiro Sakuma CANCER RESEARCH 78 (13) 2018年07月
  • 肱岡 範; 佐久間 圭一朗; 水野 伸匡; 青木 正博; 谷田部 恭; 原 和生 日本癌治療学会学術集会抄録集 55回 O27 -4 2017年10月
  • HNRNPLLは大腸がん細胞のEMTとMETにおける形質変化に関与する
    佐久間 圭一朗; 青木 正博 日本癌学会総会記事 76回 P -3143 2017年09月
  • 大腸がんの転移予測マーカーとしてのRNAスプライシング因子HNRPLLの有効性の検証
    佐久間 圭一朗 大和証券ヘルス財団研究業績集 (40) 83 -85 2017年03月
  • 青木正博; 佐久間圭一朗 日本がん転移学会学術集会・総会プログラム抄録集 26th 2017年
  • 新規大腸がん転移抑制因子HNRNPLLによってスプライシングを受ける遺伝子の同定
    佐久間 圭一朗; 青木 正博 日本癌学会総会記事 75回 J -2059 2016年10月
  • 大腸がん転移抑制因子候補HNRPLLは上皮間葉転換によって負の制御を受ける
    佐久間 圭一朗; 青木 正博 日本癌学会総会記事 74回 J -1275 2015年10月
  • shRNAライブラリーを用いた大腸がん転移抑制遺伝子のゲノムワイドスクリーニング(A genome-wide shRNA screen for colon cancer metastasis suppressor genes)
    佐久間 圭一朗; 青木 正博 日本癌学会総会記事 73回 J -2041 2014年09月
  • 大森 勝之; 佐久間 圭一朗; 神奈木 玲児 臨床免疫・アレルギー科 61 (1) 105 -111 2014年01月
  • 神奈木 玲児; 佐久間 圭一朗; 井澤 峯子 生体の科学 64 (3) 265 -272 2013年05月
  • c-MycとCDX2はEMTを起こした大腸がん細胞におけるE-セレクチンリガンド糖鎖の発現を媒介する(c-Myc and CDX2 mediate E-selectin ligand glycan expression in colon cancer cells undergoing EMT)
    佐久間 圭一朗; 神奈木 玲児; 青木 正博 日本癌学会総会記事 71回 88 -88 2012年08月
  • 【分子腫瘍マーカー-治療標的と経過指標として】治療標的としての腫瘍マーカー 新しい糖鎖分子を標的とした治療
    神奈木 玲児; 佐久間 圭一朗; 遊佐 亜希子; 井澤 峯子 カレントテラピー 29 (12) 1088 -1093 2011年12月
  • EGFとbFGFは大腸癌細胞にEMTとE-セレクチンリガンド糖鎖の発現を誘導する(EGF and bFGF induce EMT and E-selectin ligand glycan expression on colorectal cancer cells)
    佐久間 圭一朗; 青木 正博; 神奈木 玲児 日本癌学会総会記事 70回 79 -79 2011年09月
  • 増殖因子によるEMTは大腸癌細胞にE-セレクチンリガンド糖鎖の発現を誘導する(Growth factor-induced EMT enhances expression of E-selectin ligand glycans on colorectal cancer cells)
    佐久間 圭一朗; 神奈木 玲児 日本癌学会総会記事 69回 419 -419 2010年08月
  • 悪性リンパ腫細胞では内因性の硫酸化リガンドの欠失により活性化されたCD22が血管内皮との接着を促進する(Loss of endogenous sulfated ligands unmasks CD22 in malignant lymphoma and enhances cell adhesion to endothelial glycans)
    宮崎 敬子; 木村 尚子; 佐久間 圭一朗; 井澤 峯子; 神奈木 玲児 日本癌学会総会記事 68回 42 -42 2009年08月
  • 低酸素によって発現誘導される急性骨髄性白血病幹細胞の糖鎖構造(Hypoxia-induced glycans in acute myeloid leukemic stem cells)
    佐久間 圭一朗; 神奈木 玲児 日本癌学会総会記事 68回 279 -279 2009年08月
  • 悪性細胞における6-硫酸基転移酵素遺伝子の転写調節機構(Transcriptional regulation of 6-O-sulfotransferase genes in malignant cells)
    佐久間 圭一朗; 陳 国云; 木村 尚子; 神奈木 玲児 日本癌学会総会記事 67回 429 -429 2008年09月
  • 神奈木 玲児; 殷 軍; 宮崎 敬子; 佐久間 圭一朗 医学のあゆみ 225 (8) 643 -649 2008年05月
  • 病態生理に基づく臨床薬理学(翻訳)
    佐久間圭一朗 547 -562 2006年12月
  • 市川 昌孝; 三尾 直士; 手良向 聡; 中川 正嗣; 永田 靖; 藤田 史郎; 佐久間 圭一朗; 柳原 一広; 福島 雅典; 平岡 真寛; 三嶋 理晃 肺癌 46 (5) 564 -564 2006年11月
  • 肺癌症例における転移性脊椎腫瘍に対する手術療法の検討
    福原 晶子; 三嶋 理晃; 三尾 直士; 市川 昌孝; 藤田 史郎; 佐久間 圭一郎; 真砂 勝康; 旗智 幸政 肺癌 46 (5) 631 -631 2006年11月
  • ゲフィチニブによる間質性肺炎における血清チオレドキシン値の測定
    佐久間 圭一朗; 三尾 直士; 市川 昌孝; 田端 千春; 藤田 史郎; 真砂 勝泰; 三嶋 理晃 肺癌 46 (5) 572 -572 2006年11月
  • 当施設における進行肺癌心嚢水貯留例の臨床的検討
    旗智 幸政; 福原 晶子; 真砂 勝泰; 藤田 史郎; 佐久間 圭一朗; 市川 昌孝; 三尾 直士; 三嶋 理晃 肺癌 46 (5) 594 -594 2006年11月
  • 非小細胞肺癌生検検体における、EGFR遺伝子変異の検出精度
    藤田 史郎; 三尾 直士; 園部 誠; 神山 清文; 真砂 勝泰; 宮原 亮; 市川 昌孝; 佐久間 圭一朗; 和田 洋巳; 三嶋 理晃 肺癌 46 (5) 645 -645 2006年11月
  • ゲフィチニブによる間質性肺炎における血清チオレドキシン値の測定
    佐久間 圭一朗; 中村 肇; 上田 修吾; 市川 昌孝; 真砂 勝泰; 淀井 淳司; 三尾 直士 日本癌学会総会記事 65回 489 -489 2006年09月
  • 視力改善を認めたCARの1例
    佐久間 圭一朗; 真砂 勝泰; 三尾 直士; 三嶋 理晃 肺癌 46 (4) 383 -384 2006年08月
  • 当科における1995年から2004年における小細胞肺癌患者の治療に関する検討
    三尾 直士; 市川 昌孝; 佐久間 圭一朗; 田端 千春; 藤田 史郎; 三嶋 理晃 日本内科学会雑誌 94 (Suppl.) 203 -203 2005年02月
  • 佐久間圭一朗; 三尾直士; 三嶋理晃 日本内科学会雑誌 94 2005年
  • 市川 昌孝; 田端 千春; 佐久間 圭一朗; 三尾 直士; 三嶋 理晃 肺癌 44 (2) 139 -139 2004年04月
  • 森内隆幸; 竹村昌也; 田端千春; 佐久間圭一朗; 三尾直士; 三嶋理晃 肺癌 44 (2) 2004年
  • 石井章寛; 藤本一朗; 佐久間圭一郎; 出口章広; 池田武史; 池中一裕 生化学 75 (12) 2003年
  • 佐久間圭一朗; 藤本一朗; 池田武史; 田中文啓; 和田洋巳; 三嶋理晃; 池中一裕 生化学 75 (12) 2003年
  • 佐久間圭一朗 生化学 74 (8) 2002年

所属学協会

  • 日本癌学会   

共同研究・競争的資金等の研究課題

  • 大腸がん転移におけるp120-カテニンのアイソフォーム変換の意義の解明
    日本学術振興会:基盤研究C
    研究期間 : 2023年04月 -2026年03月
  • 新規同定大腸がん浸潤制御因子CTNND1アイソフォーム3Aの治療標的としての有効性の検証
    がん研究振興財団:がん研究助成金
    研究期間 : 2022年04月 -2023年03月
  • 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 : 佐久間 圭一朗
     
    前年度に引き続き、肺腺がん細胞における一次線毛発現制御分子KATNAL2の機能解明を試みた。方針としては、以下に示す2つの検討を並行しておこなった。 1. 細胞レベルの検討 前年度までの成果から、一次線毛陽性の肺腺がん細胞は高頻度に細胞周期の停止を認めることが既にわかっている。本年度は、この細胞周期停止のメカニズムを一次線毛との関連からアプローチして解明を試みると同時に、昨年度までに樹立したKATNAL2のノックアウト細胞を用いて、抗がん剤の感受性と一次線毛/KATNAL2の関係を検討した。結果、一次線毛陽性細胞は予想外のシグナル伝達経路を介して細胞周期の停止に至っていることが示唆された。このシグナル伝達系の活性化には、腫瘍細胞自体もしくは腫瘍微小環境の関与、いずれの可能性も考えられた。この点は今後臨床検体も用いて詳しく検討する必要がある。一方で、一次線毛/KATNAL2が一部の抗がん剤に対する感受性に大きな影響を与えていることが示唆された。抗がん剤耐性に一次線毛/KATNAL2が関与している可能性を示す結果であるが、一次線毛陽性細胞がいわゆるがん幹細胞と必ずしも一致するわけではないようである。この点も今後詳細な検証を要する。 2. 生体レベルの検討 国立長寿医療センター研究所との共同研究により、KATNAL2のコンディショナルノックアウトマウスの作出を試みている。昨年度は、マイクロインジェクション装置に故障が発生し、その更新に時間を要したため、目的のマウスを得るには至らなかった。
  • がん転移におけるCTNND1の機能の解明
    那古野医学振興会:研究奨励金
    研究期間 : 2020年04月 -2021年03月
  • 上皮間葉転換に伴い発現するCTNND1異常アイソフォームを標的とする大腸がん転移抑制薬の開発
    高松宮妃癌研究基金:研究助成金
    研究期間 : 2020年04月 -2021年03月
  • マウスモデルを用いた大腸がん転移の分子機序解明と予防・治療標的の同定
    日本学術振興会:基盤研究B
    研究期間 : 2018年 -2021年 
    代表者 : 青木正博
  • 大腸がんの転移におけるCTNND1の役割
    那古野医学振興会:研究奨励金
    研究期間 : 2018年04月 -2019年03月
  • がん転移における一次線毛の役割の解明
    日本学術振興会:基盤研究C
    研究期間 : 2016年 -2018年 
    代表者 : 佐久間圭一朗
  • 大腸がんの転移を予防・治療するための薬剤開発
    大幸財団:自然科学系学術研究助成
    研究期間 : 2018年 
    代表者 : 佐久間圭一朗
  • マウスモデルを用いた大腸がん転移機構の解明
    日本学術振興会:基盤研究B
    研究期間 : 2014年 -2017年 
    代表者 : 青木正博
  • 膵神経内分泌腫瘍におけるMGMT遺伝子のメチル化とストレプトゾシン耐性の関連についての細胞生物学的検証
    愛知県がん研究振興会:がんその他の悪性新生物研究助成金
    研究期間 : 2017年 
    代表者 : 佐久間圭一朗
  • 新規同定大腸がん転移抑制遺伝子の機能解明
    那古野医学振興会:研究奨励金
    研究期間 : 2017年 
    代表者 : 佐久間圭一朗
  • 一次線毛を標的とするがん転移抑制薬開発のための基盤研究
    持田記念医学薬学振興財団:研究助成金
    研究期間 : 2016年 
    代表者 : 佐久間圭一朗
  • 上皮間葉転換とシアリルルイス糖鎖を標的とした転移抑制薬開発のための基盤研究
    日本学術振興会:基盤研究C
    研究期間 : 2013年 -2015年 
    代表者 : 佐久間圭一朗
  • 大腸がんの転移予測マーカーとしてのRNAスプライシング因子HNRPLLの有効性の検証
    大和証券ヘルス財団:調査研究助成
    研究期間 : 2015年 
    代表者 : 佐久間圭一朗
  • 上皮間葉転換が選択的スプライシングの変化を介してがん細胞を悪性化させる機序の解明
    武田科学振興財団:医学系研究奨励(癌領域・基礎)
    研究期間 : 2015年 
    代表者 : 佐久間圭一朗
  • 大腸がん転移抑制遺伝子の同定およびその機能解析
    愛知県がんセンター:プロジェクト研究
    研究期間 : 2015年 
    代表者 : 佐久間圭一朗
  • 大腸がん転移抑制遺伝子の同定及び機能解明
    那古野医学振興会:研究奨励金
    研究期間 : 2015年 
    代表者 : 佐久間圭一朗
  • Pre-mRNAスプライシング異常を標的とする抗がん剤開発のための基盤研究
    がん研究振興財団:がん研究助成金
    研究期間 : 2015年 
    代表者 : 佐久間圭一朗
  • HNRPLLおよびその関連分子を標的とした転移抑制薬の開発
    鈴木謙三記念医科学応用研究財団:調査研究助成
    研究期間 : 2014年 
    代表者 : 佐久間圭一朗
  • マウス生体を用いたがん転移抑制因子スクリーニング系の確立
    日本学術振興会:挑戦的萌芽研究
    研究期間 : 2012年 -2013年 
    代表者 : 青木正博
  • 上皮成長因子と協調して大腸がん転移を促進する分子の同定
    テルモ科学技術振興財団:一般研究助成
    研究期間 : 2012年 
    代表者 : 佐久間圭一朗
  • 大腸がん細胞の上皮間葉転換と血管外脱出を標的とした転移抑制薬開発の基盤構築
    持田記念医学薬学振興財団:研究助成金
    研究期間 : 2012年 
    代表者 : 佐久間圭一朗
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    日本学術振興会:若手研究B
    研究期間 : 2010年 -2011年 
    代表者 : 佐久間圭一朗
  • 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 : 2009年 -2011年 
    代表者 : 神奈木 玲児; 佐久間 圭一朗; 後藤 嘉子
     
    低酸素によって同時に転写誘導される一連の細胞接着分子遺伝子の協同作用を解析した。またこれら以外に低酸素によって転写誘導されることがこれまで知られていなかった細胞接着分子があるかどうかについても検索した。その結果、低酸素によって糖脂質の糖部分と脂質部分に並行して変化が誘導され、糖蛋白質においても蛋白や糖側鎖に並行して変化が誘導され、これらの並行的変化が細胞の低酸素応答において互いに相乗的に機能することを示唆する成績が得られた。
  • 喘息の難治性評価におけるメモリーT細胞の糖鎖性ホーミング分子測定の意義
    日本学術振興会:若手研究B
    研究期間 : 2008年 -2009年 
    代表者 : 佐久間圭一朗
  • 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 : 2007年 -2008年 
    代表者 : 神奈木 玲児; 田口 修; 京ケ島 守; 佐久間 圭一朗; 後藤 嘉子; 安川 然太; 田口 修; 京ケ島 守; 佐久間 圭一朗; 後藤 嘉子; 安川 然太
     
    細胞接着に関与する遺伝子のうちに、低酸素誘導因子(HIF)により誘導されるものを検索し、多数の遺伝子を見いだした。これらの遺伝子のHIFによる誘導機構を解析し、一部の遺伝子群は調節領域に複数の低酸素反応エレメント(HRE, hypoxia-responsive-element)を持ち、HIF単独で有意な転写誘導が見られること、他の一群の遺伝子は単一のHREを持ち、HIF以外の転写因子と協同して転写を誘導することを明らかにした。後者については共役転写因子の同定を行った。

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