| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Research Abstract |
In uterine cervical cancers, the expression of thymidine phosphorylase ( TP ) identified with platelefrderived endothelial cell growth factor ( PD-ECGF ) correlated with microvessel density and patient prognosis. Especially, the increased level of PD-ECGF from the primary tumor to metastatic lymph nodes was recognized as a more sensitive indicator for patient prognosis. Furthermore, serum PD-ECGF can be used a novel tumor marker for advancement of uterine cervical cancers regardless of histopathological types. The transcription factor ets-1 for angiogenesis linked to PD-ECGF and interleukin ( IL )-8 in uterine cervical cancers. As PD-EGGF and ets-1 can be considered to promote growth and secondary spreading via angiogenesis, masked compounds of 5-fluorouracil, substrates of PD-ECGF, and ets-1 inhibitors might be effective on uterine cervical cancers, especially on the metastatic lymph nodes. In ovarian cancers, the expression of vascular endothelial growth factor ( VEGF ) isoform VEGFi
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65 and ets-1 correlated with patient prognosis, but not with histopathological types and clinical stages, especially in metastatic peritoneal lesions. As VEGF and ets-1 can be considered to promote growth and secondary spreading via angiogenesis, VEGF receptor tyrosine kinase inhibitors, anti-VEGF antibodies and ets-1 inhibitors might be effective on ovarian cancers, especially on metastatic peritoneal lesions. In uterine endometrial cancers, the expression of basic fibroblast growth factor ( bFGF ) correlated with clinical stages. The expression of PD-ECGF and VEGF was partially regulated by sex steroids, and they might grow the early stage of uterine endometrial cancers. IL-8 was induced and reached to the peak level in myometrial invasion, and might work as an angiogenic switch. The expression of ets-1 in well-differentiated uterine endometrial cancers correlated with that of VEGF, and the expression of ets-1 in poorly differentiated uterine endometrial cancers correlated with that of bFGF. Therefore, the target angiogenic factors associated with clinical stages and differentiated grades must be attacked to suppress the specific angiogenesis, which might lead to highly effective treatment with uterine endometrial cancers. Less
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