Analysis of lenalidomide-resistance in multiple myeloma

• Project/Area Number: 19790673
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Hematology
• Research Institution: Sapporo Medical University
• Principal Investigator: YASUI Hiroshi Sapporo Medical University, 医学部, 研究員 (40448593)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,780,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥480,000); Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2007: ¥1,700,000 (Direct Cost: ¥1,700,000)
• Keywords: 血液内科学 / 多発性骨髄腫 / サリドマイド誘導体 / lenalidomide / 薬剤耐性 / アポトーシス / 遺伝子発現プロファイル / エピジェネティック / トランスレーショナルリサーチ

Research Abstract

多発性骨髄腫におけるレナリドマイド耐性の機序解析を行うため、レナリドマイド感受性骨髄腫細胞株から、レナリドマイド抵抗性の細胞株を樹立した。これら細胞株間の遺伝子発現の相違をDNAアレイにより解析し、レナリドマイドによる抗骨髄腫効果とレナリドマイド抵抗性の機序とを検討した。これらの機序解析は、レナリドマイド抵抗性を克服する新規併用療法を開発するにあたり、有用な情報となると考えられる。

Research Products

• [Journal Article] Genomic screening for genes silenced by DNA methylation revealed an association between RASD1 inactivation and dexamethasone resistance in multiple myeloma. (2009)
  • Author(s): Nojima M, Maruyama R, Yasui H, Suzuki H, Maruyama Y, Tarasawa I, Sasaki Y, Asaoku H, Sakai H, Hayashi T, Mori M, Imai K, Tokino T, Ishida T, Toyota M, Shinomura Y
  • Journal Title: Clin Cancer Res 15(13) Pages: 4356-64
  • Peer Reviewed
• [Journal Article] SNX-2112, a selective hsp90 inhibitor, potently inhibits tumor cell growth, angiogenesis, and osteoclastogenesis in multiple myeloma and other hematological tumors by abrogating signaling via Akt and ERK. (2009)
  • Author(s): Okawa Y, Hideshima T, Steed P, Vallet S, Hall S, Huang K, Rice J, Barabasz A, Foley B, Ikeda H, Raje N, Kiziltepe T, Yasui H, Enatsu S, Anderson KC
  • Journal Title: Blood 113(4 Pages: 846-55
  • Peer Reviewed
• [Journal Article] The monoclonal antibody nBT062 conjugated to cytotoxic maytansinoids has selective cytotoxicity against CD138-positive multiple myeloma cells in vitro and in vivo. (2009)
  • Author(s): Ikeda H, Hideshima T, Fulciniti M, Lutz RJ, Yasui H, Okawa Y, Kiziltepe T, Vallet S, Pozzi S, Santo L, Perrone G, Tai YT, Cirstea D, Raje NS, Uherek C, Dalken B, Aigner S, Osterroth F, Munshi N, Richardson P, Anderson KC
  • Journal Title: Clin Cancer Res 15(12) Pages: 4028-37
  • Peer Reviewed
• [Journal Article] SNX-2112, a selective hsp90 inhibitor, potently inhibits tumor cell growth, angiogenesis, and osteoclastogenesis in multiple myeloma and other hematological tumors by abrogating signaling via Akt and ERK (2009)
  • Author(s): Yutaka Okawa, et.al.
  • Journal Title: Blood 113 Pages: 846-55
  • Peer Reviewed
• [Journal Article] Genomic screening for genes silenced by DNA methylation revealed an association between RASD1 inactivation and dexamethasone resistance in multiple myeloma (2009)
  • Author(s): Masanori Nojima, et.al.
  • Journal Title: Clinical Cancer Research (in press)
  • Peer Reviewed
• [Journal Article] Novel molecular -targeted therapeutics for the treatment of cancer. (2008)
  • Author(s): Yasui H, Imai K
  • Journal Title: Anticancer Agents Med Chem 8(5) Pages: 470-80
  • Peer Reviewed
• [Journal Article] Fatty acid synthase is a novel therapeutic target in multiple myeloma. (2008)
  • Author(s): Okawa Y, Hideshima T, Ikeda H, Raje N, Vallet S, Kiziltepe T, Yasui H, Enatsu S, Pozzi S, Breitkreutz I, Cirstea D, Santo L, Richardson P, Anderson KC
  • Journal Title: Br J Haematol 141(5) Pages: 659-71
  • Peer Reviewed
• [Journal Article] Fatty acid synthase is a novel therapeutic target in multiple myeloma (2008)
  • Author(s): Yutaka Okawa, et.al.
  • Journal Title: British Journal of Haematology 141 Pages: 659-71
  • Peer Reviewed
• [Journal Article] Novel molecular-targeted therapeutics for the treatment of cancer (2008)
  • Author(s): Hiroshi Yasui, et al.
  • Journal Title: Anti-cancer Agents in Medicinal Chemistry 8 Pages: 470-80
  • Peer Reviewed
• [Journal Article] Up-regulation of c-Jun inhibits proliferation and induces apoptosis via caspase-triggered c-Abl cleavage in human multiple myeloma. (2007)
  • Author(s): Podar K, Raab MS, Tonon G, Sattler M, Barila D, Zhang J, Tai YT, Yasui H, Raje N, Depinho RA, Hideshima T, Chauhan D, Anderson KC
  • Journal Title: Cancer Res 67(4) Pages: 1680-1688
  • Peer Reviewed
• [Journal Article] JS-K, a GST-activated nitric oxide generator, induces DNA double strand breaks, activates DNA damage response pathways, and induces apoptosis in vitro and in vivo in human multiple myeloma cells. (2007)
  • Author(s): Kiziltepe T, Hideshima T, Ishitsuka K, Ocio EM, Raje N, Catley L, Li CQ, Trudel LJ, Yasui H, Vallet S, Kutok JL, Chauhan D, Mitsiades CS, Saavedra JE, Wogan GN, Keefer LK, Shami PJ, Anderson KC
  • Journal Title: Blood 110(2) Pages: 709-18
  • Peer Reviewed
• [Journal Article] KC, Carrasco DR. Targeting the {beta}-catenin/TCF transcriptional complex in the treatment of multiple myeloma. (2007)
  • Author(s): Sukhdeo K, Mani M, Zhang Y, Dutta J, Yasui H, Rooney MD, Carrasco DE, Zheng M, He H, Tai YT, Mitsiades C, Anderson KC, Carrasco DR
  • Journal Title: Proc Natl Acad Sci U S A 104(18) Pages: 7516-7521
  • Peer Reviewed
• [Journal Article] 5-Azacytidine, a DNA methyltransferase inhibitor, induces ATR-mediated DNA double-strand break responses, apoptosis, and synergistic cytotoxicity with doxorubicin and bortezomib against multiple myeloma cells. (2007)
  • Author(s): Kiziltepe T, Hideshima T, Catley L, Raje N, Yasui H, Shiraishi N, Okawa Y, Ikeda H, Vallet S, Pozzi S, Ishitsuka K, Ocio EM, Chauhan D, Anderson KC
  • Journal Title: Mol Cancer Ther 6(6) Pages: 1718-27
  • Peer Reviewed
• [Journal Article] MLN3897, a novel CCR1 inhibitor, impairs osteoclastogenesis and inhibits the interaction of multiple myeloma cells and osteoclasts. (2007)
  • Author(s): Vallet S, Raje N, Ishitsuka K, Hideshima T, Podar K, Chhetri S, Pozzi S, Breitkreutz I, Kiziltepe T, Yasui H, Ocio EM, Shiraishi N, Jin J, Okawa Y, Ikeda H, Mukherjee S, Vaghela N, Cirstea D, Ladetto M, Boccadoro M, Anderson KC
  • Journal Title: Blood 110(10) Pages: 3744-52
  • Peer Reviewed
• [Journal Article] Inhibition of Akt induces significant downregulation of survivin and cytotoxicity in human multiple myeloma cells. (2007)
  • Author(s): Hideshima T, Catley L, Raje N, Chauhan D, Podar K, Mitsiades C, Tai YT, Vallet S, Kiziltepe T, Ocio E, Ikeda H, Okawa Y, Hideshima H, Munshi NC, Yasui H, Richardson PG, Anderson KC
  • Journal Title: Br J Haematol 138(6) Pages: 783-91
  • Peer Reviewed
• [Journal Article] Biological pathways and in vivo antitumor activity induced by Atiprimod in myeloma. (2007)
  • Author(s): Neri P, Tassone P, Shammas M, Yasui H, Schipani E, Batchu RB, Blotta S, Prabhala R, Catley L, Hamasaki M, Hideshima T, Chauhan D, Jacob GS, Picker D, Venuta S, Anderson KC, Munshi NC
  • Journal Title: Leukemia 21(12) Pages: 2519-2526
  • Peer Reviewed
• [Journal Article] Inhibition of Akt induces significant downregulation of survivin and cytotoxicity in human multiple myeloma calls (2007)
  • Author(s): Teru Hideshima
  • Journal Title: British Joumal of Haematology 138 Pages: 783-791
  • Peer Reviewed
• [Journal Article] Targeting the {beta}-catenin/TCF transcriptional complex in treatment of multiple myeloma (2007)
  • Author(s): Kumat Sukhdeo
  • Journal Title: Teh Proceedings of the National Academy of Sciences 104 Pages: 7516-7521
  • Peer Reviewed
• [Journal Article] Biological pathways and in wivo antitumor activity induced by Atiprimod in myelona (2007)
  • Author(s): Paola Neri
  • Journal Title: Leukemia 21 Pages: 2519-2526
  • Peer Reviewed
• [Journal Article] JS-K,a GST-activated nitric oxide generator,induces DNA double strand breaks,activates DNA damage response pathways,and induces apoptosis in vitro and in vivo in human multiple myeloma cells (2007)
  • Author(s): Tanyel Kiziltepe
  • Journal Title: Blood 110 Pages: 709-718
  • Peer Reviewed
• [Journal Article] MLN3897,a novel CCR1 inhibitor,impairs osteoclastogenesis and inhibits the interaction of multiple myelona cells and osteoclasts (2007)
  • Author(s): Sonia Vallet
  • Journal Title: Blood 110 Pages: 3744-3752
  • Peer Reviewed
• [Journal Article] Up-regulation of c-Jun inhibits proliferation and induces apoptosis via caspase-triggered-triggered c-Abl cleavage in human multiple myeloma (2007)
  • Author(s): Klaus Podar
  • Journal Title: Cancer Research 67 Pages: 1680-168
  • Peer Reviewed
• [Journal Article] 5-Azacytidine, a DNA methyltransferase inhibitor, induces ATR-mediated DNA double-strand break responses, apoptosis, and synergistic cytotoxi city with doxorubicin and bortezomib against multiple myeloma cells (2007)
  • Author(s): Tanyel Kiziltepe
  • Journal Title: Molecular Cancer Therapy 6 Pages: 1718-1727
  • Peer Reviewed
• [Journal Article] がん会子標的治療の発展-抗体医薬を中心に- (2007)
  • Author(s): 安井 寛
  • Journal Title: Focus on Oncology 7 Pages: 14-15
• [Presentation] 多発性骨髄腫における新規メチル化標的遺伝子RASD1とデキサメサゾン感受性の検討 (2008)
  • Author(s): 安井寛, ら
  • Organizer: 第33回日本骨髄腫研究会総会
  • Place of Presentation: 広島市
  • Year and Date: 2008-11-15
• [Presentation] 多発性骨髄腫におけるDNA異常メチル化の網羅的解析と、新規メチル化標的遺伝子 (2008)
  • Author(s): 安井寛, ら
  • Organizer: 第70回日本血液学会総会
  • Place of Presentation: 京都市
  • Year and Date: 2008-10-11
• [Presentation] 多発性骨髄腫におけるDNA異常メチル化の網羅的解析と、新規メチル化標的遺伝子RASD1. (2008)
  • Author(s): 安井寛
  • Organizer: 第70回日本血液学会総会
  • Place of Presentation: 京都
  • Year and Date: 2008-10-10
• [Presentation] The monoclonal antibody nBT062 conjugated to cytotoxic maytansinoids has potent and selective cytotoxicity against CD138 positive multiple myeloma cells in vitro and in vivo (2008)
  • Author(s): Hiroshi Ikeda, et.al.
  • Organizer: 50th American Society of Hematology Annual Meeting
  • Place of Presentation: San Francisco, USA
• [Presentation] 多発性骨髄種における細胞死抵抗牲とDNAメチル化の役割 (2007)
  • Author(s): 安井 寛
  • Organizer: 第32回日本骨髄腫研究会絵会
  • Place of Presentation: 東京
  • Year and Date: 2007-11-11
• [Presentation] 多発性骨髄腫における細胞死抵抗性とDNAメチル化の役割 (2007)
  • Author(s): 安井寛
  • Organizer: 第32回日本骨髄腫研究会総会
  • Place of Presentation: 東京
  • Year and Date: 2007-11-10
• [Presentation] Genomic screening for genes silenced by DNA methylation in multiple myeloma. (2007)
  • Author(s): Yasui H.
  • Organizer: 35th Congress of the International Society for Oncodevelopmental Biology and Medicine
  • Place of Presentation: Czech Republic
  • Year and Date: 2007-09-15
• [Presentation] Genomic screening for genes silenced by DNA methylation in multiple myeloma (2007)
  • Author(s): Hiroshi Yasui
  • Organizer: 35th Congress of the International Society for Oncodev-elopmental Biology and Medicine
  • Place of Presentation: Prague, Czech Republic
  • Year and Date: 2007-09-15
• [Remarks]
  • URL: http://jglobal.jst.go.jp/detail.php?JGLOBAL_ID=200901022350771168&t=1&d=1&q=1000307656