2000 Fiscal Year Final Research Report Summary
Development of cancer specific gene therapy for esophageal carcinoma and improvement of approach for human gene therapy
| Project/Area Number |
11470235
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
OKUSHIBA Shun-ichi Hokkaido Univ.Grad.School of Med., Asso.Prof., 大学院・医学研究科, 助教授 (70185536)
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| Co-Investigator(Kenkyū-buntansha) |
TAKIMOTO Masato Hokkaido Univ.Institute for Gene.Med., Lec., 遺伝子病制御研究所, 講師 (30179585)
KUZUMAKI Noboru Hokkaido Univ.Institute for Gene.Med., Prof., 遺伝子病制御研究所, 教授 (80091445)
KATOH Hiroyuki Hokkaido Univ.Grad.School of Med., Prof., 大学院・医学研究科, 教授 (80002369)
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| Project Period (FY) |
1999 – 2000
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| Keywords | Esophageal cancer / Cancer gene therapy / N116Y / Cancer specific promoter / Adenovirus vector |
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| Research Abstract |
Our previous studies demonstrated that introduction of a dominant negative H-ras mutant, N116Y, inhibits the growth of various types of cancer cells in vitro. We tested the efficacy of N116Y in blocking the growth of esophageal cancer cells using an adenoviral vector. The shuttle plasmid containing N116Y, pCA14-N116Y and pJM17 plasmid were co-transfected into 293 transformed human embryonic kidney cells to generate the Ad-N116Y.In Ad-N116Y infected esophageal cancer cells, 78% of cells were in G0-G1 phase and progression into S phase was blocked. Adenovirus-mediated N116Y gene transfer can suppress the growth of human esophageal cancers in vivo.
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 and growth inhibition were all specific to cancer cell lines that were CEA positive, whereas no growth retardation was observed in human normal cell lines after Ad CEA-N116Y infection.
We are making new adenoviruses driven by the squamous cell carcinoma antigen (SCCA) promoter (Ad SCCA-N116Y) and receptor-binding cancer antigen expressed on SiSo cells (RCAS1) promoter (Ad RCAS1-N116Y).
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