Development of anti-TRAIL receptor antibod y in combination with chemotherapeutic therapy against advanced genitourinary cancers : expansion of animal model

2010 Fiscal Year Final Research Report

• Project/Area Number: 20591858
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Urology
• Research Institution: Kagawa University
• Principal Investigator: WU Xiu-Xian Kagawa University, 医学部, 助教 (10346645)
• Co-Investigator(Kenkyū-buntansha): TSUNEMORI Hiroyuki 香川大学, 医学部附属病院, 助教 (20380173) ; SUGIMOTO Mikio 香川大学, 医学部附属病院, 准教授 (10243768) ; INUI MASASHI 香川大学, 医学部附属病院, 講師 (40314918) ; KAKEHI Yoshiyuki 香川大学, 医学部, 教授 (20214273)
• Project Period (FY): 2008 – 2010
• Keywords: TRAIL-R2 / laxatumumab / アドリアマイシン / 腎癌細胞 / カスパーゼ / アポトーシス

Research Abstract

Development of anti-TRAIL receptor antibody in combination with chemotherapeutic therapy against advanced genitourinary cancers was performed. We found : (1) anti-TRAIL death receptor 2 antibody lexatumumab in combination with clinically achievable concentrations of adriamycin, cisplastin, epirubicin, or pirarubicin had a synergistic cytotoxic effect ; (2) the synergistic cytotoxicity was significantly inhibited by caspase inhibitors demonstrating caspase cascade, especially caspase-8 plays an important role in the synergy ; (3)PCR array analysis identified 26 genes related with apoptosis.

Research Products

• [Journal Article] Effect of a phytotherapeutic agent, Eviprostat^<【○!R】>R, on prostatic and urinary cytokines/chemokines in a rat model of nonbacterial prostatitis. (2011)
  • Author(s): Sugimoto M, Oka M, Tsunemori H, Yamashita M, Kakehi Y
  • Journal Title: Prostate 71 Pages: 438-444
  • Peer Reviewed
• [Journal Article] View and present status of personnel involved in clinical trials : a survey of participants from the First Symposium of the Shikoku Collaborative Group for Promotion of Clinical Trials. (2011)
  • Author(s): Yanagawa H, Irahara M, Houchi H, Kakehi Y, Moritoyo T, Nomoto M, Miyamura M, Shuin T.
  • Journal Title: J Med Invest 58 Pages: 81-85
  • Peer Reviewed
• [Journal Article] Bladder Cancer Working Group report. (2010)
  • Author(s): Kakehi Y, Hirao Y, Kim WJ, Ozono S, Masumori N, Miyanaga N, Nasu Y, Yokomizo A.
  • Journal Title: Jpn J Clin Oncol 40 Pages: 157-164
  • Peer Reviewed
• [Journal Article] Positron emission tomography with 18F-fluorodeoxyglucose is a useful tool for the diagnosis of pheochromocytomas without distant metastasis, where malignancy is suspected on the basis of histopathologic analysis. (2010)
  • Author(s): Kikuchi F, Imachi H, Murao K, Ohyama T, Miyai Y, Kushida Y, Haba R, Kakehi Y, Ishida T.
  • Journal Title: Am J Med Sci 340 Pages: 160-163
  • Peer Reviewed
• [Journal Article] 転移性腎細胞癌に対する薬物療法の新たな展開 (2010)
  • Author(s): 筧善行
  • Journal Title: 臨床腫瘍プラクティス 6 Pages: 342-352
• [Journal Article] II.膀胱癌基礎研究総論膀胱癌基礎研究の歴史と現状-将来展望も含めて-.腎・泌尿器癌-基礎・臨床研究のアップデート- (2010)
  • Author(s): 筧善行, 呉秀賢
  • Journal Title: 日本臨床 68 Pages: 197-202
• [Journal Article] Induction of Apoptosis in Human Renal Cell Carcinoma Cells by Vitamin E Succinate in A Caspase-Independent Manner. (2009)
  • Author(s): Wu X-X, Kakehi Y, Jin X-H, Inui M, Sugimoto M.
  • Journal Title: Urology 73 Pages: 193-199
  • Peer Reviewed
• [Journal Article] A low molecular weight polysaccharide isolated from Agaricus blazei suppresses tumor growth and angiogenesis in vivo. (2009)
  • Author(s): Niu YC, Liu JC, Zhao XM, Wu X-X
  • Journal Title: Oncol Rep 21 Pages: 145-152
  • Peer Reviewed
• [Journal Article] Thymidylate synthase was associated with patient prognosis and the response to adjuvant therapy in bladder cancer. (2009)
  • Author(s): Li Y, Li X, Dai H, Sun X, Li J, Yang F, Gu H, Yong Y, Jin Z, Chu Y, Jin X, Kakehi Y, Wu X-X
  • Journal Title: BJU International 103 Pages: 547-552
  • Peer Reviewed
• [Journal Article] Effect of verapamil on the expression of EGFR and nm23 in lung cancer cells. (2009)
  • Author(s): Zhang C, Lv F, Zhou L, Li X, Wu XX, Hoffman RM.
  • Journal Title: Anticancer Research 29 Pages: 27-32
  • Peer Reviewed
• [Journal Article] Enhancement of Lexatumumab-induced Apoptosis in Human Solid Cancer Cells by Cisplatin. (2009)
  • Author(s): 呉秀賢, 筧善行
  • Journal Title: Clin Cancer Res 15 Pages: 2039-2047
  • Peer Reviewed
• [Journal Article] Expression of lysophospholipase D (autotaxin) and acylglycerol kinase enzymes in prostate cancer with relevance to clinicopathological parameters. (2009)
  • Author(s): Nouh MA, Wu X-X, Okazoe H, Tsunemori H, Ahmed MA, Abou-Zeid AM, Inui M, Sugimoto M, Kakehi Y
  • Journal Title: Cancer Sci 100 Pages: 1631-1638
  • Peer Reviewed
• [Journal Article] 分子標的薬を用いた腎細胞がん著効例 (2009)
  • Author(s): 杉元幹史
  • Journal Title: 臨床腫瘍プラクティス 5 Pages: 414-417
• [Journal Article] Agonistic antibodies to tumor necrosis factor related apoptosis-inducing ligand death receptors and cancer therapy. (2009)
  • Author(s): 呉秀賢, 筧善行
  • Journal Title: 中華外科雑誌 47(2)
  • Peer Reviewed
• [Journal Article] 【抗体を用いたがん治療の現状と問題点】腎癌(Bevacizumab) (2009)
  • Author(s): 筧善行, 呉秀賢
  • Journal Title: 腫瘍内科 3 Pages: 56-61
• [Journal Article] 腎臓がんの分子標的治療-現状と問題点- (2009)
  • Author(s): 筧善行
  • Journal Title: 腫瘍内科 4 Pages: 155-161
• [Presentation] Synergistic induction of apoptosis in human solid cancer cells by Lexatumumab and cisplatin in a caspase-dependent manner. (2010)
  • Author(s): 呉秀賢, 乾政志, 杉元幹史, 筧善行
  • Organizer: The 101th Annual Meeting for AACR.
  • Place of Presentation: Washington, USA
  • Year and Date: 20100417-20100421
• [Presentation] ラット非細菌性前立腺炎モデルにおける前立腺および尿中サイトカイン・ケモカイン濃度の解析-エビプロスタット^<【○!R】>R投与の影響- (2010)
  • Author(s): 常森寛行, 杉元幹史, 末永武寛, 矢野敏史, 加藤琢磨, 平間裕美, 山下資樹, 乾政志, 筧善行
  • Organizer: 第3回排尿障害モデル動物研究会
  • Place of Presentation: 静岡市
  • Year and Date: 2010-11-26
• [Presentation] 早期前立腺がんに対するPSA監視療法:患者選択と経過観察方法の標準化を目指して (2010)
  • Author(s): 杉元幹史, 常森寛行, 筧善行
  • Organizer: 第48回日本癌治療学会
  • Place of Presentation: 京都市
  • Year and Date: 2010-10-30
• [Presentation] StageT1c前立腺癌に対するPSA監視療法 厚生省研究班(11-10)における全摘症例の検討 (2010)
  • Author(s): 杉元幹史, 常森寛行, 神波大己, 賀本敏行, 白石泰三, 小川修, 筧善行
  • Organizer: 第48回日本癌治療学会
  • Place of Presentation: 京都市
  • Year and Date: 2010-10-29
• [Presentation] Synergistic apoptosis of lexatumumab and cisplatin against human renal cell carcinoma cells in a caspase-dependent manner. (2010)
  • Author(s): Wu X-X, Kato T, Hirama H, Tsunemori H, Zhang X, Yamashita M, Inui M, Sugimoto M, Kakehi Y
  • Organizer: 4^<st> Chinese-Japanese Urological Association Meeting.
  • Place of Presentation: Xian, China
  • Year and Date: 2010-10-20
• [Presentation] ヒト固形癌細胞におけるシスプラチンによるCaspase依存症のLexatumumab誘導アポトーシスの増強 (2010)
  • Author(s): 呉秀賢, 常森寛行, 乾政志, 杉元幹史, 筧善行
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪市
  • Year and Date: 2010-09-24
• [Presentation] ヒト固形癌細胞におけるシスプラチンによるカスパーゼ依存性のLexatumumab誘導アポトーシスの増強 (2010)
  • Author(s): 呉秀賢, 常森寛行, 植月祐次, 山下資樹, 平間裕美, 乾政志, 杉元幹史, 筧善行
  • Organizer: 第19回泌尿器科分子・細胞研究会
  • Place of Presentation: 神戸市
  • Year and Date: 2010-02-13
• [Presentation] Expression of Lysophospholipase D (Autotaxin) and Acylglycerol kinase enzymes in Prostate Cancer cells with relevance to Clinicopathological parameters American Urological (2009)
  • Author(s): Nouh MA, Wu X-X, Okazoe H, Tsunemori H, Abou-Zeid AM, Saleem MD, Inui M, Sugimoto M, Junken Aoki, Kakehi Y
  • Organizer: Association 2009 Annual Meeting.
  • Place of Presentation: Chicago, USA
  • Year and Date: 20090425-20090430
• [Presentation] 腎細胞癌に対する分子標的治療・現状と課題 (2009)
  • Author(s): 筧善行
  • Organizer: 第59回日本泌尿器科学会中部総会
  • Place of Presentation: 金沢市
  • Year and Date: 2009-10-31
• [Presentation] 腎癌の新規分子マーカーとしてのU7メッセンジャーRNA (2009)
  • Author(s): 呉秀賢, アハメドハメド, 常森寛行, 乾政志, 杉元幹史, 影山進, 吉貴達寛, 筧善行
  • Organizer: 第97回日本泌尿器科学会総会
  • Place of Presentation: 岡山市
  • Year and Date: 2009-04-17
• [Presentation] 固形癌細胞に対する低濃度アドリアマイシンと抗DR5モノクロナル抗体Lexatumumabによるアポトーシス増強効果 (2009)
  • Author(s): 呉秀賢, 常森寛行, 植月祐次, 山下資樹, 上田修史, 乾政志, 杉元幹史, 筧善行
  • Organizer: 第18回泌尿器科分子・細胞研究会
  • Place of Presentation: 鹿児島市
  • Year and Date: 2009-02-13
• [Presentation] Expression of Lysophospholipase D (Autotaxin) and Acylglycerol kinase enzymes in Prostate Cancer cells with relevance to Clinicopathological parameters. (2009)
  • Author(s): Nouh MA, Wu X-X, Okazoe H, Tsunemori H, Abou-Zeid AM, Saleem MD, Inui M, Sugimoto M, Aoki J, Kakehi Y
  • Organizer: 第18回泌尿器科分子・細胞研究会
  • Place of Presentation: 鹿児島市
  • Year and Date: 2009-02-13
• [Remarks] ホームページ等
  • URL: http://www.kms.ac.jp/~uro/links.html