Drug-resistant genes downstream of Polycomb group genes in leukemia stem cells

• Project/Area Number: 20591128
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Hiroshima University
• Principal Investigator: MIHARA Keichiro Hiroshima University, 原爆放射線医科学研究所, 助教 (90363077)
• Co-Investigator(Kenkyū-buntansha): TAKIHARA Yoshihiro 広島大学, 原爆放射線医科学研究所, 教授 (60226967)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2009: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000); Fiscal Year 2008: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
• Keywords: BMI-1 / Survivin / MDR / survivin

Research Abstract

Lymphoma (ML) cells transduced with BMI-1 obtained resistance to anti-cancer drugs. Survivin was enhanced in cell lines overexpressing BMI-1. Intriguingly, survivin mRNA was not induced in transduced cell lines, leading to the post-translational regulation involved. The expression of BMI-1 and survivin was much higher in chemotherapy-resistant samples than that in chemotherapy-sensitive.

Research Products

• [Journal Article] Expression of CD38 with intracellular enzymatic activity : a possible explanation for the insulin release induced by intracellular cADPR. (2011)
  • Author(s): Ohta Y, Kitanaka A, Mihara K, Imataki O, Ohnishi H, Tanaka T, Taminato T, Kubota Y.
  • Journal Title: Mol Cell Biochem. in press
  • Peer Reviewed
• [Journal Article] The metastasis-associated microRNA miR-516a-3p is a novel therapeutic target for inhibiting peritoneal dissemination of human scirrhous gastric cancer. (2011)
  • Author(s): Takei Y, Takigahira M, Mihara K, Tarumi Y, Yanagihara K.
  • Journal Title: Cancer Res. 71(4) Pages: 1442-1453
  • Peer Reviewed
• [Journal Article] Expression of CD38 with intracellular enzymatic activity : a possible explanation for the insulin release induced by intracellular cADPR. (2011)
  • Author(s): Ohta Y, et al
  • Journal Title: Mol Cell Biochem. Volume: (In press)
  • Peer Reviewed
• [Journal Article] The metastasis-associated microRNA miR-516a-3p is a novel therapeutic target for inhibiting peritoneal dissemination of human scirrhous gastric cancer. (2011)
  • Author(s): Takei Y, et al
  • Journal Title: Cancer Res. Volume: 71 Pages: 1442-1453
  • Peer Reviewed
• [Journal Article] Synergistic and persistent effect of T-cell immunotherapy with anti-CD19 or anti-CD38 chimeric receptor in conjunction with rituximab on B-cell non-Hodgkin lymphoma. (2010)
  • Author(s): Mihara K, Yanagihara K, Takigahira M, Kitanaka A, Imai C, Bhattacharyya J, Kubo T, Takei Y, Yasunaga S, Takihara Y, Kimura A.
  • Journal Title: Br J Haematol. 151(1) Pages: 37-46
  • Peer Reviewed
• [Journal Article] Expansion of CD8+/perforin+ effector memory T cells in the bone marrow of patients with thymoma-associated pure red cell aplasia. (2010)
  • Author(s): Nitta H, Mihara K, Sakai A, Kimura A.
  • Journal Title: Br J Haematol. 150(6) Pages: 712-715
  • Peer Reviewed
• [Journal Article] Tec protein tyrosine kinase inhibits CD25 expression in human T-lymphocyte. (2010)
  • Author(s): Susaki K, Kitanaka A, Dobashi H, Kubota Y, Kittaka K, Kameda T, Yamaoka G, Mano H, Mihara K, Ishida T.
  • Journal Title: Immunol Lett. 4;127(2) Pages: 135-142
  • Peer Reviewed
• [Journal Article] An orthotopic implantation mouse model of human malignant pleural mesothelioma for in vivo photon counting analysis and evaluation of the effect of S-1 therapy. (2010)
  • Author(s): Yanagihara K, Tsumuraya M, Takigahira M, Mihara K, Kubo T, Ohuchi K, Seyama T.
  • Journal Title: Int J Cancer. 126(12) Pages: 2835-2846
  • Peer Reviewed
• [Journal Article] Synergistic and persistent effect of T-cell immunotherapy with anti-CD19 or anti-CD38 chimeric receptor on B-cell lymphoma in conjunction with rituximab (2010)
  • Author(s): Mihara K, e al
  • Journal Title: Br J Haematol. Volume: 151 Pages: 37-46
  • Peer Reviewed
• [Journal Article] Tec protein tyrosine kinase inhibits CD25 expression in human T-lymphocyte. (2010)
  • Author(s): Susaki K, et al
  • Journal Title: Immunol Lett. Volume: 127 Pages: 135-142
  • Peer Reviewed
• [Journal Article] An orthotopic implantation mouse model of human malignant pleural mesothelioma for in vivo photon counting analysis and evaluation of the effect of S-1 therapy. (2010)
  • Author(s): Yanagihara K, et al
  • Journal Title: Int J Cancer. Volume: 126 Pages: 2835-2846
  • Peer Reviewed
• [Journal Article] Activated T-cell-mediated immunotherapy with a chimeric receptor against CD38 in B-cell non-Hodgkin lymphoma. (2009)
  • Author(s): Mihara K, Yanagihara K, Takigahira M, Imai C, Kitanaka A, Takihara Y, Kimura A.
  • Journal Title: J Immunother. 32(7) Pages: 737-743
  • Peer Reviewed
• [Journal Article] BMI-1 expression is enhanced through transcriptional and posttranscriptional regulation during the progression of chronic myeloid leukemia. (2009)
  • Author(s): Bhattacharyya J, Mihara K, Yasunaga S, Tanaka H, Hoshi M, Takihara Y, Kimura A.
  • Journal Title: Ann Hematol. 88(4) Pages: 333-340
  • Peer Reviewed
• [Journal Article] BMI-1 expression is enhanced through transcriptional and posttranscriptional regulation during the progression of chronic myeloid leukemia. (2009)
  • Author(s): Bhattacharyya J
  • Journal Title: Annals of Hematology 88 Pages: 333-340
  • Peer Reviewed
• [Journal Article] Antitumor effect of SN-38-releasing polymeric micelles, NK012, on spontaneous peritoneal metastases from orthotopic gastric cancer in mice compared with irinotecan. (2008)
  • Author(s): Nakajima TE, Yanagihara K, Takigahira M, Yasunaga M, Kato K, Hamaguchi T, Yamada Y, Shimada Y, Mihara K, Ochiya T, Matsumura Y.
  • Journal Title: Cancer Res. 15;68(22) Pages: 9318-9322
  • Peer Reviewed
• [Journal Article] Antitumor effect of SN-38-releasing polymeric micelles, NK012, on spontaneous peritoneal metastases from orthotopic gastric cancer in mice compared with irinotecan. (2008)
  • Author(s): Nakajima TE
  • Journal Title: Cancer Research 68 Pages: 9318-9322
  • Peer Reviewed
• [Presentation] B-cell lymphoma cells overexpressing BMI-1 are correlated with drug resistance through enhanced expression of survivin and are effectively eliminated by T cells with anti-CD38 chimeric receptor. (2010)
  • Author(s): ジョイータ・バタチャリーヤ, 三原圭一朗, 大坪素秋, 安永晋一郎, 瀧原義宏, 星正治, 木村昭郎
  • Organizer: 52nd ASH Annual Meeting
  • Place of Presentation: Orlando, USA
  • Year and Date: 2010-12-06
• [Presentation] B-Cell Lymphoma Cells Overexpressing BMI-1 Are Correlated with Drug Resistance through Enhanced Expression of Survivin and Are Effectively Eliminated by T Cells with Anti-CD38 Chimeric Receptor (2010)
  • Author(s): Joyeeta Bhattacharyya, et al
  • Organizer: American Society of Hematology, Annual meeting
  • Place of Presentation: Orlando.FL.USA
  • Year and Date: 2010-12-06
• [Presentation] B細胞性リンパ腫におけるBMI-1の高発現はSurvivinの発現を促進し、抗癌剤耐性に関与する (2010)
  • Author(s): ジョイータ・バタチャリーヤ, 三原圭一朗, 大坪素秋, 安永晋一郎, 星正治, 瀧原義宏, 木村昭郎
  • Organizer: 第71回日本血液学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2010-09-25
• [Presentation] Overexpression of BMI-1 is correlated with drug resistance in B-cell lymphomas through enhanced expression of survivin (2010)
  • Author(s): Joyeeta Bhattacharyya, et al
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2010-09-25
• [Presentation] Overexpression of bmi-1 is correlated with drug resistance in b-cell lymphomas through enhanced expression of survivin. (2010)
  • Author(s): ジョイータ・バタチャリーヤ, 三原圭一朗, 大坪素秋, 安永晋一郎, 瀧原義宏, 星正治, 木村昭郎
  • Organizer: ISEH2010
  • Place of Presentation: Melbourne Australia
  • Year and Date: 2010-09-17
• [Presentation] OVEREXPRESSION OF BMI-1 IS CORRELATED WITH DRUG RESISTANCE IN B-CELL LYMPHOMAS THROUGH ENHANCED EXPRESSION OF SURVIVIN (2010)
  • Author(s): Joyeeta Bhattacharyya, et al
  • Organizer: ISEH
  • Place of Presentation: Melbourne, Australia
  • Year and Date: 2010-09-17
• [Presentation] 高発現BMI-1はB細胞性悪性リンパ腫の抗癌剤耐性に関与している (2010)
  • Author(s): Joyeeta Bhattacharyya
  • Organizer: 日本血液学会・地方会
  • Place of Presentation: 下関
  • Year and Date: 2010-03-06
• [Presentation] Synergistic and persistent effect of T-cell immunotherapy with anti-CD19 or anti-CD38 chimeric receptor on B-cell lymphoma in conjunction with rituximab (2008)
  • Author(s): Mihara K
  • Organizer: American Society of Hematology, Annual Meeting
  • Place of Presentation: San Francisco, CA, USA
  • Year and Date: 2008-12-07
• [Presentation] Synergistic effect of T-cell immunotherapy with anti-CD19 or anti-CD38 chimeric receptor on B-cell lymphoma in conjunction with rituximab (2008)
  • Author(s): Mihara K
  • Organizer: International Conference on Malignant Lymphoma
  • Place of Presentation: Lugano, Switzerland
  • Year and Date: 2008-06-05