1997 Fiscal Year Final Research Report Summary
Enhancement of drug sensitivity and a bystander effect in cancer cells transfected with a drug sensitivity gene (cancer gene therapy)
| Project/Area Number |
08671427
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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 | Fukui Medical University |
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Principal Investigator |
SHIMOMATSUYA Takumi Fukui Medical University, University Hospital, Assistant, 医学部附属病院, 助手 (00187486)
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| Co-Investigator(Kenkyū-buntansha) |
HORIUCHI Tetsuya Fukui Medical University, University Hospital, Assistant, 医学部附属病院, 助手 (20211550)
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| Project Period (FY) |
1996 – 1997
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| Keywords | 5-fluorouracil (5-FU) / cancer gene therapy / 'bystander effect' / angiogenesis / thymidine phosphorylase (TP) / VEGF / platelet-derived endothelial cell growth factor (PD-ECGF) |
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| Research Abstract |
A new strategy in cancer control is the introduction of a drug sensitivity gene which encodes an enzyme that intratumorally activated a prdrug. Doxifluridine and tegafur, prodrug of 5-fluorouracil (5-FU) are anticancer agents activated by thymidine phosphorylase (TP). In this study, we examined whether transfection of tumor cells with a human platelet-derived endothelial cell growth factor (PD-ECGF) cDNA expressing TP would sensitize the cells to the cytotoxic effects of pyrimdine antimetabolites in vitro. A cDNA encoding PD-ECGF was transfected into PC-9 cells (human lung adenocarcinoma). The transfected cells, DPE2, were more sensitive than parental PC-9 or D1 cells transfected with the pcDNA3 vector alone. In addition, we demonstrated that DPE2 cells were able to potentiate the cytotoxic effects of doxifluridine towards co-cultured parental PC-9 cells. This 'bystander effect' did not require cell-cell contact. These results suggest the transfection of PD-ECGF genes may be useful as a gene therapy strategy for cancer therapy.
In additon, we examined the association of TP expression with tumor angiogenesis, survival and vascular endothelial growth factor (VEGF) expression in human colorectal cancer specimens. The expression of TP correlated significantly with microvessel counts and VEGF expression. Moreover, we showed that TP and VEGF expression were independent prognostic factors. Angiogenic inhibitors may play important roles in future strategies for cancer therapy. Further investigations are considerd necessary to develop new treatment modalities which regulate the extent of tumor vascularity.
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[Publications] Tanigawa, N., Amaya, H., Matsumura, M., Simomatsuya, T., Horiuchi, T., Muraoka, R., ^<**>Iki, M.: "Extent of Tumor Vascularization Correlates with Prognosis and Hematogenous Metastasis in Gastric Carcinomas" Cancer Research. 56. 2671-2676 (1996)
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「研究成果報告書概要(欧文)」より
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[Publications] Tanigawa, N., Amaya, H., Matsumura, M., Katoh, Y., Kitaoka, A., Aotake, T., Shimomatsuya, T., ^<**>O.A.Rosenwasser, ^<**>Iki, M.: "Tumor angiogenesis and expression of thymidine phosphorylase/platelet derived endothelial cell growth factor in human gastric carcinoma" Cancer Letters. 108. 281-290 (1996)
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「研究成果報告書概要(欧文)」より
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[Publications] Tanigawa, N., Matsumura, M., Amaya, H., Kitaoka, A., Shimomatsuya, T., Lu, C., Muraoka, R., ^<**>Tanaka, T.: "Tumor Vascularity Correlates with the Prognosis of Patients with Esophageal Squamous Cell Carcinoma" Cancer. 79. 220-225 (1997)
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[Publications] Tanigawa, N., Amaya, H., Matsumura, M., Shimomatsuys, T.: "Correlation Between Expression of Vascular Endothelial Groeth Factor and tumor Vascularity, and Patient Outcome in Human Gastric Carcinoma. Journal of Clinical Oncology, 15 (2), 826-832,1997,2." Journal of Clinical Oncology. 15 (2). 826-832 (1997)
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[Publications] Tanigawa, N., Amaya, H., Matsumura, M., Lu, C., Kitaoka, A., Matsuyama, K., Muraoka, R.: "Tumor Angiogenesis and Mode of Metastasis in Patients with Colorectal Cancer" Cancer Research. 57. 1043-1046 (1997)
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「研究成果報告書概要(欧文)」より
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[Publications] Amaya, H., Tanigawa, N., Lu, C., Matsumura, M., Shimomatsuya, T., Horiuchi, T., Muraoka, R.: "Association of vascular endoth elial growth factor expression with tumor engiogenes is, survival and thymidine phosphorylose/platelet-derived endothelial cell growth factor expression in human colorectal cancer" Cancer Letters. 119. 227-235 (1997)
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「研究成果報告書概要(欧文)」より
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[Publications] Matumura, M., Chiba, Y., Lu, C., Amaya, H., Shimomatsuya, T., Horiuchi, T., Muraoka, R., Tanigawa, N.: "Platelet-derived endothelial cell growth factor/thymidine phosphorylase expression correlated with tumor angiogenesis and macrophage infiltration in colorectal cancer" Cancer Letters. (in press).
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「研究成果報告書概要(欧文)」より
