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Specific Gene Therapy for Pancreatic Cancer

Research Project

Project/Area Number 10470236
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionHOKKAIDO UNIVERSITY

Principal Investigator

KATOH Hiroyuki  Hokkaido Univ., Fac. Of Med., Pro., 医学部, 教授 (80002369)

Co-Investigator(Kenkyū-buntansha) KUZUMAKI Noboru  Hokkaido Univ., Fac. Of Med., Pro., 医学部, 教授 (80091445)
SUGIURA Hiroshi  Hokkaido Univ., Medical Hospital., Assis. Pro., 医学部・附属病院, 助手 (30292022)
KONDO Satoshi  Hokkaido Univ., Fac. Of Med., Asso. Pro., 医学部, 助教授 (30215454)
TAKIMOTO Masato  Hokkaido Univ., Fac. Of Med., Lec., 医学部, 講師 (30179585)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥12,600,000 (Direct Cost: ¥12,600,000)
Fiscal Year 1999: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 1998: ¥7,700,000 (Direct Cost: ¥7,700,000)
KeywordsCEA promoter / Pancreatic Cancer / Cancer Gene Therapy / N116Y / Vector
Research Abstract

In pancreatic cancer, the mutation of c-K-ras is a critical event of tumor growth and meastasis. We have previously demonstrated a dominant negative effect of N116Y on the growth of pancreatic cancer cells. To evaluate the potential of N116Y for suppressing the metastatic growth of pancreatic tumor cells, we made a replication-deficient recombinant N116Y adenovirus driven by the carcinoembryonic antigen (CEA) promoter (Ad CEA-N116Y). We demonstrated that the expression of N116Y, growth inhibition, and apoptotic death induction were all specific to pancreatic cancer cell lines (PCI-35 and PCI-43) that were promoter positive, whereas no growth retardation was observed in human embrynic pancreas-derived cell line 1C3D3 after Ad CEA-N116Y infection. We examined the effect of Ad CEA-N116Y on the metastatic growth of PCI-43 colonies in liver, which were generated by tumor injection into the spleen of nude mice. The results showed that Ad CEA-N116Y effectively reduced the number of metastatic colonies without any complication by injecting intrasplenically five days after tumor cell inoculation. Thus N116Y can selectively suppress the metastatic growth of pancreatic tumor cell by using the CEA promoter driven adenovirus vector indicating the N116Y gene therapy may be potentially useful for the treatment of pancreatic cancer patients with liver micrometastasis.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Katsunori Saito et al.: "INTERLEUKIN-6 PRODUCED BY PANCREATIC CARCINOMA CELLS ENHANCES HUMORAL IMMUNE RESPONSES AGEINST TUMOR CELLS : A POSSIBLE EVENTIN TUMOR REGRESSION"International Journal of Cancer. 75. 284-289 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Naoto Senmaru et al.: "SUPPRESSION OF Erk ACTIVATION AND IN VIVO GROWTH IN ESOPHAGEAL CANCER CELLS BY THE DOMINANT NEGATIVE Ras MUTANT, N116Y"International Journal of Cancer. 78. 366-371 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yomoyuki Yano et al.: "Hepatoid adenocarcinoma of the pancreas"Histopathology. 35. 90-02 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yasuhiro Hida et al.: "Clinical significance of hepatocyte growth factor and c-Met expression in extrahepatic biliary tract cancers"Oncology Report. 6. 1051-1056 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yasuhiro Hida et al.: "Vascular endothelial growth factor expression is an independent negative predictor in extrahepatic biliary tract carcinomas"Anticancer Research. 19. 2257-2260 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Islam HK et al.: "Immunohistochemical analysis of expression of molecular biologic factors in intraductal papillary-mucinous tumor of pancreas"Hepato-Gastroenterology. 46. 2599-2605 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 加藤紘之: "膵癌における癌転移の分析"医療ジャーナル. 351 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Katsunori Saito, Hiroshi Ishikura, Takashi Kishimoto, You Kawarada, Tomoyuki Yano, Toshiyuki Takahashi, Hiroyuki Katoh, Yakashi Yoshiki: "INTERLEUKlN-6 PRODUCED BY PANCREATIC CARCINOMA CELLS ENHANCES HUMORAL IMMUNE RESPONSES AGAINST TUMOR CELLS : A POSSIBLE EVENT IN TUMOR REGRESSION"Intemational Journal of Cancer. 75. 284-289 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Naoto Senmaru, Toshiaki Shichinohe, Motoya Takeuchi, Masaki Miyamoto, Ataru Sazawa, Yoshifumi Ogiso, Toshiyuki Takahashi, Syunichi Okushiba, Masato Takimoto, Hiroyuki Katoh, Noboru Kuzumaki: "SUPPRESSION OF Erk ACTIVATION AND IN VIVO GROWTH IN ESOPHAGEAL CANCER CELLS BY THE DOMINANT NEGATIER Ras MUTANT, N116Y."Intemational Journal of Cancer. 78. 366-371 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yano T, Ishikura H, Wada T, Klshimoto T, Kondo S, Katoh H, Yoshiki T.: "Hepatoid adenocarcinoma of the pancreas."Histopathology. 35. 90-92 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hida Y, Morita T, Fujita M, Miyasaka Y, Horita S, Fujioka Y, Nagashima K, Katoh H.: "Clinical significance of hepatocyte growth factor and c-Met expression in extrahepatic biliary tract cancers."Oncology Report. 6. 1051-1056 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hida Y, Morita T, Fujita M, Miyasaka Y, Horita S, Fujioka Y, Nagashima K, Katoh H.: "Vascular endothelial growth factor expression is an independent negative predictor in extrahepatic biliary tract carcinomas."Anticancer Research. 19. 2257-2260 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Islam HK, Fujioka Y, Tomidokoro T, Sugiura H, Takahashi T, Kondo S , Katoh H.: "Immunohistochemical analysis of expression of molecular biologic factors in intraductal papillary-mucinous tumor of pancreas."Hepato-Gastroenterology. 46. 25999-2605 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hiroyuki Katoh.: "Analysis of metastasis of pancreatic cancer."Medical Journal. 351 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tomoyuki Yano, et al.: "Hepatoid adenocarcinoma of the pancreas"Histopathology. 35. 90-92 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yasuhiro Hida, et al.: "Clinical significance of hepatocyte growth favtor and c-Met expression in extrahepatic biliary tract cancers"Oncology Report. 6. 1051-1056 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yasuhiro Hida, et al.: "Vascular endothelial growth factor expression is an independent negative predictor in extrahepatic biliary tract carcinomas"Anticancer Research. 19. 2257-2260 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Islam HK., et al.: "Immunohistochemical analysis of expression of molecular biologic factors in intraductal papillary-mucinous tumor of pancreas"Hepato-Gastroenterology. 46. 2599-2605 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Katsunori Saito,et al.: "INTERLEUKIN-6 PRODUCED BY PANCREATIC CARCINOMA CELLS ENHANCES HUMORAL IMMUNE RESPONSES AGAINST TUMOR CELLS:A POSSIBLE EVENT IN TUMOR REGRESSION." International Journal of Cancer. 75. 284-289 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Naoto Senmaru,et al.: "SUPPRESSION OF Erk ACTIVATION AND IN VIVO GROWTH IN ESOPHAGEAL CANCER CELLS BY THE DOMINANT NEGATIVE Ras MUTANT,N116Y." International Journal of Cancer. 78. 366-371 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 加藤紘之: "膵癌における癌転移の分析" 医療ジャーナル, 351 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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