Invention of novel cancer drug for refractory solid tumor

• Project/Area Number: 25430165
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor therapeutics
• Research Institution: Kanagawa Cancer Center Research Institute
• Principal Investigator: YAMADA ROPPEI 地方独立行政法人神奈川県立病院機構神奈川県立がんセンター(臨床研究所), その他部局等, その他 (30404974)
• Co-Investigator(Kenkyū-buntansha): Miyagi Yohei 地方独立行政法人神奈川県立病院機構神奈川県立がんセンター臨床研究所, がん分子病態学部 (00254194)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 難治性固形腫瘍 / 活性酸素 / 卵巣明細胞腺癌 / 細胞死

Outline of Final Research Achievements

We discontinued the invention of PACMA31 as a PDI inhibitor, because our data did not show reproduction. But PACMA5, other PACMA derivative, had four novel findings. 1) It showed potency for not normal cells but cancer cells. 2) It induced non-apoptotic cell death via ROS generation. 3) It showed efficacy for ovarian peritoneal dissemination. 4)Its target protein is Protein 1 (tentative name) which is closely related to ROS generation. Thus we believed PACMA5 can be a new candidate of a novel cancer drug for refractory solid tumor.

Research Products

• [Journal Article] Lipid starvation and hypoxia synergistically activate ICAM1 and multiple genes in an Sp-1dependent manner to promote the growth of ovarian cancer (2015)
  • Author(s): Shiro Koizume, Shin Ito, Yoshiyasu Nakamura, Mitsuyo Yoshihara, Mitsuko Furuya, Roppei Yamada, Etsuko Miyagi, Fumiki Hirahara, Yasuo Takano, Yohei Miyagi
  • Journal Title: Molecular Cancer Volume: 14 Pages: 77-77
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Annexin A4 is involved in proliferation, chemoresistance and migration and invasion in ovarian clear cell adenocarcinoma cells. (2013)
  • Author(s): Mogami T, Yokota N, Asai-sato M, Yamada R, Koizume S, Sakuma Y, Yoshihara M, Nakamura Y, Takano Y, Hirahara F, Miyagi Y, and Miyagi E.
  • Journal Title: PLOS ONE Volume: 8 Issue: 11 Pages: 1-8
  • DOI: 10.1371/journal.pone.0080359
  • Peer Reviewed
• [Presentation] コムギ無細胞タンパクアレイ技術を用いた、化合物から標的タンパクを同定する技術の開発
  • Author(s): 高橋宏隆、山田六平、傳田美和子、森下 了、宮城洋平
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸