2005 Fiscal Year Final Research Report Summary
Tumor angiogenesis and molecular target therapy in refractory gynecological cancer
| Project/Area Number |
15591787
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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 | Osaka Medical College |
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Principal Investigator |
UEDA Masatsugu Osaka Medical College, Faculty of Medicine, Associate Professor, 医学部, 助教授 (50223467)
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| Project Period (FY) |
2003 – 2005
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| Keywords | refractory gynecological cancer / tumor angiogenesis / invasion and metastasis / apoptosis / molecular target therapy / genetic polymorphism |
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| Research Abstract |
1)The correlation between VEGF-C expression and invasive phenotype in 10 ovarian and 11 cervical cancer cell lines, was examined. Immunohistochemical expression of VEGF-C in 73 ovarian and 52 cervical cancer tissues was also correlated with clinicopathologic features and patient outcome. There was a statistical correlation between VEGF-C gene or protein expression and in vitro invasive activity, matrix metalloproteinase (MMP)-2 gene expression and its activity of tumor cells. VEGF-C expression in clinical tissue samples was well correlated with retroperitoneal lymphnode metastasis, MMP-2 expression and tumor vascularity. VEGF-C expression was also well associated with poorer prognosis. These results suggest that VEGF-C expression is closely related to invasive phenotype and affects the patient's survival in ovarian and cervical cancer.
2)Biological effects of paclitaxel (Taxol) on angiogenesis and invasive phenotype of ovarian cancer, were investigated. Taxol (1-10 nM) inhibited the pro
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liferation, migration and tube formation of bovine arterial endothelial cells and human umbilical vein endothelial cells induced by either VEGF or bFGF. Angiogenesis in Matrigel injected into mice subcutaneously was also inhibited by Taxol (100 nM). Moreover, weekly Taxol inhibited the growth of heterotransplanted tumor of Taxol-resistant ovarian cancer KF28TX cells. Thus, low dose of Taxol inhibited angiogenesis and invasive activity of ovarian cancer cells. Clinical application of a continuous low dose of this agent may be useful for tumor dormancy therapy of refractory ovarian cancer.
3)Single nucleotide polymorphism at -670 of Fas gene promoter (A/G) was examined in a total of 354 blood samples from normal healthy women and gynecological cancer patients. They consist of 95 normal, 83 cervical, 108 endometrial and 68 ovarian cancer cases. 83 patients with cervical cancer had statistically higher frequency of GG genotype and G allele than 95 controls (P=0.0353 and 0.0278, respectively). There was no significant difference in the genotype or allele prevalence between control subjects and endometrial or ovarian cancer patients. The Fas -670 GG genotype was associated with an increased risk for the development of cervical cancer (OR=2.56, 95% CI=1.08 to 6.10) compared with the AA genotype. The G allele also increased the risk of cervical cancer (OR=1.60, 95% CI=1.05 to 2.43) compared with the A allele. Germline polymorphism of Fas gene promoter -670 may be associated with the risk of cervical cancer in a Japanese population. Less
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