1999 Fiscal Year Final Research Report Summary
Specific Gene Therapy for Pancreatic Cancer
Project/Area Number |
10470236
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
General surgery
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Research Institution | HOKKAIDO UNIVERSITY |
Principal Investigator |
KATOH Hiroyuki Hokkaido Univ., Fac. Of Med., Pro., 医学部, 教授 (80002369)
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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)
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Project Period (FY) |
1998 – 1999
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Keywords | CEA 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.
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Research Products
(14 results)
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[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
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