Angiogenesis in female genital tract cancers and its inhibition

女性生殖道癌症的血管生成及其抑制

基本信息

批准号：
11671606
负责人：
FUJIMOTO Jiro
金额：
$ 2.3万
依托单位：
Gifu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671606/
关键词：
female genital tract cancers metastasis angiogenisis angiogenic factors transcription factors angiogenic inhibitors tumor dormancy therapy 血管新生阻害剤 basic FGF VEGF PD-ECGF

项目摘要

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 … More 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

在子宫颈癌中，胸苷磷酸化酶（TP）的表达与血小板源性内皮细胞生长因子（PD-ECGF）相关，尤其是从原发肿瘤到转移淋巴结的PD-ECGF水平升高。此外，血清 PD-ECGF 被认为是患者预后的更敏感指标，无论组织病理学如何，均可用作宫颈癌进展的新型肿瘤标志物。与子宫颈癌中的 PD-ECGF 和白细胞介素 ( IL )-8 相关的转录因子 ets-1 可以通过血管生成促进生长和继发性扩散。 5-氟尿嘧啶、PD-ECGF 底物和 ets-1 抑制剂可能对宫颈癌有效，尤其是对卵巢癌中的转移性淋巴结、血管癌的表达。内皮生长因子 (VEGF) 亚型 VEGFi … More 65 和 ets-1 与患者预后相关，但与组织病理学类型和临床分期无关，尤其是在转移性腹膜病变中，因为 VEGF 和 ets-1 可被认为促进生长和继发性扩散。通过血管生成，VEGF 受体酪氨酸激酶抑制剂、抗 VEGF 抗体和 ets-1 抑制剂可能对卵巢癌有效，尤其是转移性卵巢癌在子宫内膜癌的腹膜病变中，碱性成纤维细胞生长因子（bFGF）的表达与临床分期相关，PD-ECGF和VEGF的表达部分受到性类固醇的调节，它们可能在子宫内膜癌的早期生长。 IL-8 在子宫肌层浸润时被诱导并达到峰值水平，可能作为血管生成开关。 ets-1 在分化良好的子宫内膜中表达。子宫内膜癌中 ets-1 的表达与 VEGF 相关，低分化子宫内膜癌中 ets-1 的表达与 bFGF 相关，因此，必须攻击与临床分期和分化级别相关的靶血管生成因子，以抑制特异性血管生成。导致子宫内膜癌的高效治疗。