Molecular target study for Kaposi sarcoma-associated virus-associated diseases

• Project/Area Number: 20590068
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Keio University
• Principal Investigator: NOGUCHI Kohji Keio University, 薬学部, 准教授 (80291136)
• 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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: がんウイルス / 分子標的 / 遺伝子 / 抗ウイルス薬 / KSHV / ヘルペスウイルス / がん / 抗がん剤 / 感受性 / NF-kappaB / cyclin / NF-KappaB

Research Abstract

In this study, we examined the effects of KSHV-associated viral gene expressions on cellular chemosensitivity to various drugs. Our results showed that vFLIP expression apparently conferred bleomycin sensitivity in HEK293 cells. Moreover, knockdown experiment for Ikappa-Balpha showed similar results, suggesting that an activation of NF-kappaB pathway contributes to the belomycin chemosensitization induced by vFLIP.

Research Products

• [Journal Article] Functional availability of gamma-herpesvirus K-cyclin is regulated by cellular CDK6 and p16INK4a. (2010)
  • Author(s): Yoshioka H, Noguchi K, et al.
  • Journal Title: Biochem Biophys Res Commun. 394 Pages: 1000-1005
  • Peer Reviewed
• [Journal Article] Pharmacological interaction with sunitinib is abolished by a germ-line mutation (1291T>C) of BCRP/ABCG2 gene. (2010)
  • Author(s): Kawahara H, Noguchi K, Sugimoto Y, et al.
  • Journal Title: Cancer Sci. 101 Pages: 1493-1500
  • Peer Reviewed
• [Journal Article] In vivo expansion of MDR1-transduced cells accompanied by a post-transplantation chemotherapy regimen with mitomycin C and methotrexate. (2010)
  • Author(s): Mitsuhashi J, Noguchi K, Sugimoto Y, et al.
  • Journal Title: J Gene Med. 12 Pages: 596-603
  • Peer Reviewed
• [Journal Article] BCRP/ABCG2 confers anticancer drug resistance without covalent dimerization. Cancer Sci. (2010)
  • Author(s): Shigeta J, Noguchi K, Sugimoto Y, et al.
  • Journal Title: 101 1813-1821
  • Peer Reviewed
• [Journal Article] Functional availability of gamma-herpesvirus K-cyclin is regulated by cellular CDK6 and p16INK4a. (2010)
  • Author(s): Yoshioka H
  • Journal Title: Biochemical Biophysical Research Communications Volume: 394 Pages: 1000-1005
  • Peer Reviewed
• [Journal Article] Pharmacological interaction with sunitinib is abolished by a germ-line mutation (1291T>C) of BCRP/ABCG2 gene. (2010)
  • Author(s): Kawahara H
  • Journal Title: Cancer Science Volume: 101 Pages: 1493-1500
  • Peer Reviewed
• [Journal Article] BCRP/ABCG2 confers anticancer drug resistance without covalent dimerization. (2010)
  • Author(s): Shigeta J
  • Journal Title: Cancer Science Volume: 101 Pages: 1813-1821
  • Peer Reviewed
• [Journal Article] In vivo expansion of MDR1-transduced cells accompanied by a post-transplantation chemotherapy regimen with mitomycin C and methotrexate. (2010)
  • Author(s): Mitsuhashi J
  • Journal Title: Journal of Gene Medicine Volume: 12 Pages: 596-603
  • Peer Reviewed
• [Journal Article] Pharmacological Interplay between breast cancer resistance protein and gefitinib in epidermal growth factor receptor signaling. (2009)
  • Author(s): Katayama K, Noguchi K, Sugimoto Y, et al.
  • Journal Title: Anticancer Res 29 Pages: 1059-1065
  • Peer Reviewed
• [Journal Article] Substrate-dependent bidirectional modulation of P-glycoprotein-mediated drug resistance by erlotinib. (2009)
  • Author(s): Noguchi K, Sugimoto Y, et al.
  • Journal Title: Cancer Sci. 100 Pages: 1701-1707
  • Peer Reviewed
• [Journal Article] Identification of bisindolylmaleimides and indolocarbazoles as inhibitors of HCV replication by tube-capture-RT-PCR. (2009)
  • Author(s): Murakami Y, Noguchi K, et al.
  • Journal Title: Antiviral Res 83 Pages: 112-117
  • Peer Reviewed
• [Journal Article] Functions of the breast cancer resistance protein (BCRP/ABCG2) in chemotherapy. (2009)
  • Author(s): Noguchi K, Sugimoto Y, et al.
  • Journal Title: Adv Drug Deliv Rev. 61 Pages: 26-33
  • Peer Reviewed
• [Journal Article] Identification of bisindolylmaleimides and indolocarbazoles as inhibitors of HCV replication by tube-capture-RT-PCR (2009)
  • Author(s): Murakami Y
  • Journal Title: Antiviral Research 83 Pages: 112-117
  • Peer Reviewed
• [Journal Article] Substrate-dependent bidirectional modulation of P-glycoprotein-mediated drug resistance by erlotinib (2009)
  • Author(s): Noguchi K
  • Journal Title: Cancer Science 100 Pages: 1701-1707
  • Peer Reviewed
• [Journal Article] Pharmacological Interplay between breast cancer resistance protein and gefitinib in epidermal growth factor receptor signaling. (2009)
  • Author(s): Katayama K, 他
  • Journal Title: Anticancer Research 29(掲載決定)
  • Peer Reviewed
• [Journal Article] Functions of the breast cancer resistance protein (BCRP/ABCG2)in chemotherapy (2009)
  • Author(s): Noguchi K, 他
  • Journal Title: Advanced Drug Delivery Reviews 61 Pages: 26-33
  • Peer Reviewed
• [Presentation] EBNA1機能阻害剤による抗EBV作用 (2011)
  • Author(s): 野口耕司
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 静岡
  • Year and Date: 2011-03-31
• [Presentation] EBNA1蛋白質のDNA結合能を阻害する化合物の探索研究 (2010)
  • Author(s): 野口耕司
  • Organizer: 第58回日本ウイルス学会学術集会
  • Place of Presentation: 徳島
  • Year and Date: 2010-11-09
• [Presentation] ヒトiPS細胞におけるレトロウイルス挿入部位の同定と評価 (2010)
  • Author(s): 山原裕輔
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-23
• [Presentation] Epstein-Barr virus由来のEBNA1蛋白質に対する機能阻害剤の探索 (2010)
  • Author(s): 安田愛
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-22
• [Presentation] プロテアソーム阻害剤UO126によるP-糖タンパク質の発現低下を克服する (2010)
  • Author(s): 片山和浩
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-22
• [Presentation] Functional availability of KSHV cyclin is regulated by cellular CDK6 and p16INK4a. (2010)
  • Author(s): Noguchi K, Yoshioka H, Maeda A, Katayama K, Mitsuhashi J, Sugimoto Y.
  • Organizer: 13th International Workshop on Kaposi's Sarcoma Associated Herpesvirus (KSHV) and Related Agents.
  • Place of Presentation: Los Angeles, CA, USA
  • Year and Date: 2010-08-30
• [Presentation] Functional availability of KSHV cyclin is regulated by cellular CDK6 and p16INK4a. (2010)
  • Author(s): 野口耕司
  • Organizer: 13th International Workshop on Kaposi's Sarcoma Associated Herpesvirus (KSHV) and Related Agents
  • Place of Presentation: Los Angeles, CA, USA
  • Year and Date: 2010-08-30
• [Presentation] がんウイルスEpstein-Barr Virus由来のEBNA1蛋白質のDNA結合能を阻害する化合物の探索研究 (2010)
  • Author(s): 野口耕司,片山和浩,蓑島維文,板東俊和,杉山弘,杉本芳一
  • Organizer: 第14回日本がん分子標的治療学会
  • Place of Presentation: 東京
  • Year and Date: 2010-07-07
• [Presentation] Kaposi's sarcoma-associated herpesvirus (KSHV)由来k-cyclinの制御機構 (2010)
  • Author(s): 吉岡秀哲、片山和浩、三橋純子、杉本芳一,野口耕司
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
  • Year and Date: 2010-03-30
• [Presentation] Kaposi's sarcoma-associated herpesvirus(KSHV)由来k-cyclinの制御機構 (2010)
  • Author(s): 吉岡秀哲
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
  • Year and Date: 2010-03-30
• [Presentation] がんウイルスEpstein-Barr Virus由来のEBNA1を新規分子標的とする阻害薬の探索研究 (2010)
  • Author(s): 安田愛,片山和浩,三橋純子,蓑島維文,板東俊和,杉山弘,山越智,杉本芳一,野口耕司
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
  • Year and Date: 2010-03-28
• [Presentation] ヒトiPS細胞におけるレトロウイルス挿入部位の同定と評価(1) (2010)
  • Author(s): 岩崎佳奈
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
  • Year and Date: 2010-03-28
• [Presentation] ヒトiPS細胞におけるレトロウイルス挿入部位の同定と評価(2) (2010)
  • Author(s): 山原裕輔
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
  • Year and Date: 2010-03-28
• [Presentation] MAPK経路によるP-糖タンパク質の発現制御 (2010)
  • Author(s): 笹波瑛子
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
  • Year and Date: 2010-03-28
• [Presentation] U0126によるP-糖タンパク質の発現制御機構の解明 (2010)
  • Author(s): 片山和浩
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
  • Year and Date: 2010-03-28
• [Presentation] ヒトABCB5の機能解析 (2010)
  • Author(s): 佐藤麻恵
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
  • Year and Date: 2010-03-28
• [Presentation] がんウイルス Epstein-Barr Virus 由来のEBNA1を新規分子標的とする阻害薬の探索研究 (2010)
  • Author(s): 安田愛
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
  • Year and Date: 2010-03-28
• [Presentation] Chemosensitization to bleomycin conferred by a constitutive activation of IKK pathway in viral FLIP expressing cells. (2009)
  • Author(s): Kohji Noguchi, Yuri Masuda, Kazuhiro Katayama, Junko Mitsuhashi, Yoshikazu Sugimoto
  • Organizer: AACR-EORTC-NCI Molecular Targets and Cancer Therapeutics Conference 2009
  • Place of Presentation: Boston, MA, USA
  • Year and Date: 2009-11-17
• [Presentation] Chemosensitization to bleomycin conferred by a constitutive activation of IKK pathway in viral FLIP expressing cells (2009)
  • Author(s): 野口耕司
  • Organizer: 2009 AACR-EORTC-NCI Molecular Targets and Cancer Therapeutics Conference
  • Place of Presentation: 米国マサチューセッツ州ボストン
  • Year and Date: 2009-11-17
• [Presentation] ABCトランスポーターのP-gp/ABCB1、BCRP/ABCG2に対するsunitinibの効果の違い (2009)
  • Author(s): 河原はる香,野口耕司,片山和浩,三橋純子,杉本芳一
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 東京
  • Year and Date: 2009-10-26
• [Presentation] カポジ肉腫関連ウイルス由来vFLIPの発現とブレオマイシン感受性 (2009)
  • Author(s): 野口耕司,増田由梨,片山和浩,杉本芳一
  • Organizer: 第57 回日本ウイルス学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2009-10-26
• [Presentation] カポジ肉腫関連ウイルス由来vFLIPの発現とブレオマイシン感受性 (2009)
  • Author(s): 野口耕司
  • Organizer: 第57回日本ウイルス学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2009-10-26
• [Presentation] カポジ肉腫関連ヘルペスウイルス由来vFLIP発現細胞のBleomycin高感受性について (2009)
  • Author(s): 増田由梨、野口耕司、三橋純子、片山和浩、杉本芳一
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-01
• [Presentation] カポジ肉腫関連ヘルペスウイルス由来vFLIP発現細胞の Bleomycin 高感受性について (2009)
  • Author(s): 増田由梨
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-01
• [Presentation] ABCトランスポーターのP-gp/ABCB1、BCRP/ABCG2に対する sunitinib の効果の違い (2009)
  • Author(s): 河原はる香
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-01
• [Presentation] Retrovirus integration site analysis if human induced pluripotent stem(iPS)cells (2009)
  • Author(s): 杉本芳一
  • Organizer: 第15回日本遺伝子治療学会
  • Place of Presentation: 大阪
  • Year and Date: 2009-07-11
• [Presentation] カポジ肉腫関連ウイルス由来vFLIP発現と抗がん剤感受性 (2009)
  • Author(s): 野口耕司、片山和浩、杉本芳一
  • Organizer: 第13回日本がん分子標的治療学会学術集会
  • Place of Presentation: 徳島
  • Year and Date: 2009-06-26
• [Presentation] KSHV/HHV-8 viral genes expression modulates chemosensitivity of human 293 cells (2008)
  • Author(s): 野口耕司,片山和浩,杉本芳一
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-28
• [Presentation] カポシ肉腫関連ウイルスの遺伝子発現と抗がん剤感受性変化 (2008)
  • Author(s): 野口耕司,片山和浩,杉本芳一
  • Organizer: 第56 回日本ウイルス学会学術集会
  • Place of Presentation: 岡山
  • Year and Date: 2008-10-26
• [Presentation] カポシ肉腫関連ウイルスの遺伝子発現と抗がん剤感受性変化 (2008)
  • Author(s): 野口耕司, 他
  • Organizer: 第56回日本ウイルス学会学術集会
  • Place of Presentation: 岡山
  • Year and Date: 2008-10-26
• [Presentation] がん関連ウイルスの遺伝子発現による抗がん剤感受性への影響 (2008)
  • Author(s): 吉岡秀哲,片山和浩,野口耕司,杉本芳一
  • Organizer: 第52 回日本薬学会関東支部大会
  • Place of Presentation: 野田
  • Year and Date: 2008-10-04
• [Presentation] カポシ肉腫関連ウイルスの分子標的に関する研究 (2008)
  • Author(s): 野口耕司,片山和浩,杉本芳一
  • Organizer: 第12回がん分子標的治療研究会総会
  • Place of Presentation: 東京
  • Year and Date: 2008-06-26