2003 Fiscal Year Final Research Report Summary
Gene Therapy for Esophageal Cancer
| Project/Area Number |
13470250
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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 |
Digestive surgery
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| Research Institution | Chiba University |
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Principal Investigator |
OCHIAI Takenori Chiba University, Graduate School of Medicine, Professor, 大学院・医学研究院, 教授 (80114255)
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| Co-Investigator(Kenkyū-buntansha) |
GUNJI Yoshio Chiba University, Graduate School of Medicine, Associate Professor, 大学院・医学研究院, 助教授 (60241957)
MATSUBARA Hisahiro Chiba University, Graduate School of Medicine, Lecturer, 大学院・医学研究院, 講師 (20282486)
SHIMADA Hideaki Chiba University, Graduate School of Medicine, Lecturer, 大学院・医学研究院, 講師 (20292691)
NABEYA Yoshihiro Chiba University, University Hospital, Assistant, 医学部附属病院, 助手 (40322028)
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| Project Period (FY) |
2001 – 2003
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| Keywords | esophageal squamous cell carcinoma / p53 gene therapy / clinical study / local efficacy / biological efficacy / biohazard / p16 / p33 |
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| Research Abstract |
Despite improvement of surgical treatment and application of multi-modality therapies to advanced esophageal cancer, the prognosis is extremely poor in patients with unresectable tumors. Based on the genetic background of esophageal cancer, we have developed various gene therapy strategies against human esophageal cancer. In this article, we reviewed molecular events of esophageal cancer and p53 gene therapy approaches for its treatment. First, we analyzed p53 genetic alterations and angiogenesis in esophageal cancer. Second, we tested a p53 recombinant adenoviral vector (Ad5CMV-p53). Significant growth suppression was observed following infection with Ad5CMV-p53 in human esophageal cancer cell lines. This observation suggests that Ad5CMV-p53 may be a potentially effective therapeutic agent for locally advanced esophageal cancer. Promising avenues for investigation include double gene therapy and adjuvant use of gene therapy with radiation therapy. Third, based on recent reports of clinical trials of p53 gene therapy for lung cancer and head and neck cancer, we developed a clinical protocol for p53 gene therapy for unresectable advanced esophageal cancer. This clinical trial was planned to evaluate vector tolerability and efficacy. Up to March 1, 2004, 9 patients were enrolled into this phase I/II trial. No serious adverse events related to Ad5CMV-p53 have occurred so far in these patients, and the trial has been safely conducted.
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[Publications] Shimada, H., Liu, Tian-Ling., Ochiai, T., Shimizu, T., Haupt, Y., Hamada, H., Abe, T., Oka, M., Takiguchi, M., Hiwasa, T.: "Facilitation of adenoviral wild-type p53-induced apoptotic cell death by overexpression of p33^<ING1> in T. Tn human esophageal carcinoma cells."Oncogene. 21. 1208-1216 (2002)
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「研究成果報告書概要(欧文)」より
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[Publications] Matsubara, H., Gunji, Y., Maeda, T., Tasaki, K., Koide, Y., Asano, T., Ochiai, T., Sakiyama, S, Tagawa, M.: "Electroporation-mediated Transfer of Cytokine Genes into Human Esophageal Tumors Produces Anti-tumor Effects in Mice."Anticancer Res. 21. 2501-2504 (2001)
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「研究成果報告書概要(欧文)」より
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[Publications] Shimada, H., Shimizu, T., Ochiai, T., Ting-Ling Liu, Sashiyama, H., Nakamura, A., Matsubara, H., Gunji, Y., Kobayashi, S., Tagawa, M., Sakiyama, S., Hiwasa, T.: "Preclinical Study of Adenoviral p53 Gene Therapy for Esophageal Cancer."Surg Today. 31. 597-604 (2001)
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「研究成果報告書概要(欧文)」より
