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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）和血小板衍生内皮细胞生长因子（PD-ECGF）的表达与微血管密度和患者预后相关。特别是从原发肿瘤到转移淋巴结的PD-ECGF水平升高被认为是患者预后的更敏感指标。此外，血清PD-ECGF可作为一种新的肿瘤标志物，用于宫颈癌的进展，无论组织病理学类型。子宫颈癌中血管生成转录因子ets-1与PD-ECGF和白细胞介素（IL）-8相关由于PD-EGGF和ets-1可以被认为通过血管生成促进生长和继发性扩散，因此5-氟尿嘧啶的掩蔽化合物、PD-ECGF的底物和ets-1抑制剂可能对子宫颈癌有效，特别是对转移性淋巴结。在卵巢癌中，血管内皮生长因子（VEGF）亚型VEGFi的表达与卵巢癌的预后密切相关。 ...更多信息 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，尤其是在腹膜转移性病变中。由于VEGF和ets-1可以被认为通过血管生成促进生长和继发性扩散，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，特别是对转移性腹膜病变。在子宫内膜癌中，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的表达受性激素的部分调节，可能与子宫内膜癌的早期发生有关。IL-8在子宫肌层浸润过程中被诱导并达到高峰，可能起血管生成开关的作用。ets-1在高分化子宫内膜癌中的表达与VEGF的表达相关，在低分化子宫内膜癌中的表达与bFGF的表达相关。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，这可能导致子宫内膜癌的高效治疗。少