| Budget Amount *help |
¥3,670,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥270,000)
Fiscal Year 2007: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2006: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Research Abstract |
In attention to higher thymidine kinase activity of tumor cells, gene recombination of a replication-conditional herpes simplex virus 1 mutant was done to be able to multiply in principle it only in the whole tumor cells. A new vector (HSV1yCD) inserted a cytosine deaminase gene (yCD), which converted the prodrug 5-FC to the 5-FU in the tumor cells was developed. Experiment results were shown below.
1) In HSV1yCD-infected cells, the expression of yCD was found from postinfectious 12 hours, and the expression level was enlarged with time course. On the other hand, the yCD expression was not found in normal cells such as fibroblast, HUVEC, Hepatocyto.
2) When 5-FC was added in HSV1yCD-infected HT29 cells, a decrease of 5-FC level and an increase of 5-FU level were recognized.
3) In HSV1yCD-infected HT29 cells, the cell proliferation was significantly inhibited at 72 hours later, compared with control cells (49.1%). Furthermore, the cell proliferation was restrained remarkably when 5-FC was administered (23.2%).
4) For mouse subcutaneous tumor models, the tumor volume was 1/3 of a control in HSV1yCD treatment group. In addition, significant antitumor depression effect was shown in HSV1yCD+5-FC treatment group, and their tumors were cicatrized.
In this study, a development to future virus therapy establishment was suggested by combined treatment of HSV1yCD and 5-FC.
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