SHIMOMATSUYA Takumi Fukui Medical University, University Hospital, Assistant, 医学部附属病院, 助手 (00187486)
MURAOKA Ryusuke Fukui Medical University, Faculty of Medicine, Professor, 医学部, 教授 (10026924)
|Budget Amount *help
¥4,200,000 (Direct Cost : ¥4,200,000)
Fiscal Year 1997 : ¥1,800,000 (Direct Cost : ¥1,800,000)
Fiscal Year 1996 : ¥2,400,000 (Direct Cost : ¥2,400,000)
Various type of chmosensitivity test assays have been developed to predict the human tumors to anticancer agents. Application of TIA (Tritium Incorporation Assay) has been developed to attain higher rates of evaluability and provide a rapid assessment of chmosensiytivities in our institute. However, even with such assays the chemotherapy to gastrointestinal cancers may not be always sufficient.
Angiogenesis is essential for growth of solid tumors. Intratumoral microvessel count, which represents a measure of tumor angiogenesis, has been associated with the overall survival of patients with gastric carcinomas (Cancer Res, 1996), coloniccarcinomas (Cancer Res, 1997), esophageal carcinomas (cancer, 1997) and hepatocellular carcinomas (Hepatology, 1997). Vascular endothelial growth factor (VEGF) expression plays a role in promotion of angiogenesis and has strong correlation between overall survival and development of hematogenous metastasis in human gastric carcinomas (J Clin Oncol, 1997). On the other hand, platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) is also one of the potent angiogenic factors. The expression of VEGF,which correlates intratumoral microvessel count and the expression of PD-ECGF/TP,is an independent prognostic factor in colorectal carcinomas (Cncer Letters, 1997).
PD-ECGF/TP is an enzyme that catalyzes the phosphorolysis of thymidine and converts 5' DFUR and tegafur to 5-FU.The tranfection of PD-ECGF gene to lung cancer cell line (PC-9) enhances the sensitivity to 5' DFUR,tegafur, and 5-FU.Besides this enhancement is promoted by non-contact type bystander effect (Br J Cancer, 1997).
The tranfection of PD-ECGF gene may be useful as a gene therapy strategy for cancer treatment, especially in cancerous peritonitis, by enhancemenet of drug sensitivity.