1998 Fiscal Year Final Research Report Summary
p53 gene therapy for esophageal cancer
| Project/Area Number |
09671282
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | CHIBA UNIVERSITY SCHOOL OF MEDICINE |
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Principal Investigator |
OCHIAI Takenori Chiba University School of Medicine, Surgery, Professor, 医学部, 教授 (80114255)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUBARA Hisahiro Chiba University School of Medicine, Surgery, Assistsnt, 医学部附属病院, 助手 (20282486)
SHIMADA Hideaki Chiba University School of Medicine, Surgery, Assistsnt, 医学部附属病院, 助手 (20292691)
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| Project Period (FY) |
1997 – 1998
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| Keywords | p53 / gene-therapy / esophageal cancer |
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| Research Abstract |
Background ; Despite improvements in perioperative adjuvant therapy, survival ratio is still very low among many patients with advanced esophageal cancer. Alteration of the p53 gene function is a major factor in the development of esophageal cancer. We examined the efficacy of an adenovirus- mediated wild-type p53 gene transfer on the proliferation of human esophageal squamous cell carcinoma cells with and without p53 gene mutation in in vitro as well as in vivo to test the ability of clinical application. Methods ; Seven human esophageal cancer cell lines (EGGI-10, T.Tn, TE-1, TE-10, TE-1 1, TE-13) with p53 alteration and one cell lines (TE-2) without p53 alteration were used. p16 genetic alteration was evident in TE-10, TE-1 1, TE-13, EGGI-10. The transduction efficiency, p53 expression, and growth suppression were assessed in in vitro in these cell lines by infecting the recombinant p53 adenoviral vector or LacZ vector. The tumor growth suppression in vivo was assessed in nude mice bearing T.Tn tumors. Results ; The trasnduciton efficiency was 60% with 100 MOI infection. In vitro growth assays revealed significant growth suppression following 30 or more MOI of p53 adenoviral vector, In vivo studies in nude mice showed that tumor volume were reduced in mice that received intratumoral injection of p53 adenoviral vector. Conclusion ; These data suggest that p53 adenoviral vector may be a potential therapeutic agent for locally advanced esophageal cancer.
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