| Project/Area Number |
10671543
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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 |
Obstetrics and gynecology
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| Research Institution | Shimane Medical University |
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Principal Investigator |
HATA Kohkichi Shimane Medical University, Department of Obstetrics and Gynecology, Assistant Professor, 医学部, 講師 (70180875)
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| Project Period (FY) |
1998 – 1999
|
| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | ovarian cancer / inhibition / angiogenesis / thymidine phosphorylase / Furtulon / RT-PCR / tumor dormacy therapy / gene / ovarian cancer |
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| Research Abstract |
Thymidine phosphorylase (TP) is associated with angiogenesis and the progression of solid tumors. High intracellular levels of this enzyme indicate increased chemosensitivity to pyrimidine antimetabolites. TP gene expression in 56 cases of epithelial ovarian cancer, (27 of serous, 10 mucinous, 12 endometrioid, 5 clear cell, and 2 undifferentiated) were analyzed by polymerase chain reaction of RNA after reverse transcription. These included 8 of low malignant potential. Twenty were stage I, 4 stage II, 27 stage III, and 5 stage IV. The level of TP gene expression was presented by the relative yield of the TP gene to the β2-microglobulin gene. TP gene expression ranged from 0.19 to 5.38 (median 0.93). The value of TP gene expression in stage III-IV was significantly higher than that of TP gene expression in stage I-II (P = 0.0005). Histological grade significantly associated with TP gene expression (P = 0.008), but histological subtype did not (P = 0.166). A follow-up study of 34 cases a
… More
fter complete resection of the primary tumors by surgical operation could be performed. TP gene expression of the cases with recurrence showed significantly higher levels compared to cases without recurrence (P = 0.049). Survival data were available for 47 of the 56 patients. The prognosis of the patients with high TP gene expression (equal to or grater than median) was to be significantly worse than that of those with low TP gene expression (less than median) (P = 0.021). The TP gene expression level may play one of the key roles in the biology of ovarian epithelial cancer and define a more aggressive tumor phenotype. A new therapeutic intervention mediated by TP protein activity is anticipated. TP converts thymidine to thymine and 2'-deoxyribose-1-phosphate and can also metabolize the prodrug 5'-deoxy-5-fluorouridine (Furtulon) to 5-fluorouracil and 5'-deoxy-D-ribose-1-phosphate. We have noted that the use of TP activity in combination with Furtulon might provide a potentially highly effect method by which to reduce the level of inherent to tumor-stimulated angiogenesis in pathological conditions, thereby limiting disease progression. Therefore, these results lead to tumor dormancy therepy in epithelial ovarian cancer. Less
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