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Some uterine endometrial cancers conserve estrogen dependency in advancement. However, the concept of advancement in tumor is complicated, because it involves simple growth in primary tumor and secondary spreading. The expression manner of estrogen receptor alpha exon 5 splicing variant, ER beta, progesterone receptor-A (N-terminus deletion mutant) is associated with metastatic potential in uterine endometrial cancers. Increased estrogen-related receptor alpha expression is related to tumor advancement with the loss of estrogen dependency. Steroid receptor coactivator-3 contributes to tumor progression and can be used as a treatment target for advanced uterine endometrial cancers. Estrogen responsive oncogenes, c-jun and c-Ha-ras, are not modi-fied by progestin in uterine endometrial cancer cells and are considered to be an instinct phenotype as such cancers. By contrast, metastatic potential of estrogen-dependent uterine endometrial cancers can be partially controlled by progestin via metastasis-related genes, E-cadherin/catenins, plasminogen activator inhibitor-1, vascular endothelial growth factor. Thus, sex steroids related phenomena are impress-ive in the advancement of uterine endometrial cancers. [ABSTRACT FROM AUTHOR]

Objective: Angiogenesis is essential for the development, growth and advancement of solid tumors. Interferon-γ-inducible protein 10 (IP-10) regulates lymphocyte chemotaxis, mediates vascular pericyte proliferation and acts as an angiostatic agent, thus inhibiting tumor growth. This prompted us to study the clinical implications of IP-10 expression related to angiogenesis in uterine endometrial cancers. Method: Sixty patients underwent curative resection for uterine endometrial cancers. In the tissue of these cancers, the levels of IP-10, vascular endothelial growth factor, interleukin-8 and basic fibroblast growth factor (bFGF) were determined by enzyme immunoassay, and the localization of IP-10 and counts of microvessels were determined by immunohistochemistry. Result: IP-10 is diffusely localized in the cancer cells, but not in the stromal cells. There was a significant, reverse correlation between microvessel counts and IP-10 levels in uterine endometrial cancers. The IP-10 levels significantly decreased with more advanced disease and significantly reverse-correlated with bFGF levels in uterine endometrial cancers. Conclusions: IP-10 might affect the suppression of angiogenesis associated with bFGF in advanced cancer. Furthermore, IP-10 activation might be effective in the suppression of regrowth or recurrence after intensive treatment for advanced endometrial cancers. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Angiogenesis is essential for development, growth and advancement of solid tumors. Cyclooxygenase (COX)-2 is recognized as an angiogenic factor in various tumors. This prompted us to study the clinical implications of COX-2 expression related to angiogenesis in uterine cervical cancers. There was a significant correlation between microvessel counts and COX-2 levels in uterine cervical cancers. COX-2 localized in the cancer cells, but not in the stromal cells of uterine cervical cancer tissues. COX-2 levels increased with advancement, and the prognosis of the 30 patients with high COX-2 expression in uterine cervical cancers was poor (60%), while the 24-month survival rate of the other 30 patients with low COX-2 expression was 90%. Furthermore, COX-2 levels significantly correlated with VEGF levels in uterine cervical cancers. VEGF associated with COX-2 might work on angiogenesis in advancement. Therefore, long-term administration of COX-2 inhibitors might be effective on the suppression of regrowth or recurrence after intensive treatment for advanced uterine cervical cancers. [ABSTRACT FROM AUTHOR]

Angiogenesis is essential for the development, growth and advancement of solid tumors. Angiogenesis is induced by hypoxia with angiogenic transcription factor hypoxia inducible factors (HIF). This prompted us to study the clinical implications of HIF relative to angiogenesis in uterine cervical cancers. Although there was no significant difference in HIF-1α histoscores and mRNA levels according to histopathological type or lymph node metastasis, HIF-1α histoscores and mRNA levels increased significantly with advancing cancer stages. The prognosis of 30 patients with high HIF-1α in uterine cervical cancers was poor (73% survival), whereas the 24-month survival rate of the other 30 patients with low HIF-1α was 93%. HIF-1α histoscores and mRNA levels were correlated with the levels of the angiogenic factors thymidine phosphorylase and interleukin-8, and HIF-1α might be linked with these factors in cervical cancer tissue. HIF-1α is a candidate for prognostic indicator as an angiogenic mediator in uterine cervical cancer. ( Cancer Sci 2006; 97: 861–867) [ABSTRACT FROM AUTHOR]

Objective: Angiogenesis is essential for the development, growth and advancement of solid tumors. Angiogenesis is induced by hypoxia with the angiogenic transcription factor hypoxia-inducible factor (HIF). This prompted us to study the clinical implications of HIF relative to angiogenesis in uterine endometrial cancers. Methods: Sixty patients underwent curative resection for uterine endometrial cancers. In the tissue of 60 uterine endometrial cancers, HIF-1α, HIF-2α and HIF-1β mRNA levels, and the ratio of angiopoietin (Ang)-2 to Ang-1 (Ang-2/Ang-1) mRNA levels were determined by RT real-time PCR; histochemical scores and localization of HIF-1α were determined by immunohistochemistry. Levels of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), thymidine phosphorylase (TP) and interleukin-8 (IL-8) were determined by enzyme immunoassay. Results: In stage I uterine endometrial cancers, HIF-1α histochemical scores and mRNA levels significantly increased with myometrial invasion of uterine endometrial cancers. HIF-1α histochemical scores and mRNA levels correlated with the levels of Ang-2/Ang-1 and IL-8. Conclusion: The angiogenic mediator HIF-1α, linked to Angs and IL-8, might work on angiogenesis with myometrial invasion of cancer cells in uterine endometrial cancers. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: ETS-1 has been identified as a proto-oncogene and a transcription factor for tumor angiogenesis, which is essential for the growth, invasion and metastasis of solid tumors. The aim is to investigate the clinical implications of ETS-1 expression in peritoneal metastatic lesions of ovarian cancers. Methods: In primary tumors and peritoneal metastatic lesions from 30 patients with stage III ovarian cancers, ETS-1 histoscores and ets-1 mRNA levels were determined by immunohistochemistry and competitive RT-PCR-Southern blot analysis using recombinant RNA, respectively. Results: Immunohistochemical staining revealed that ETS-1 was expressed in the cancer cells and vascular endothelial cells. ETS-1 histoscores in the endothelial cells and ets-1 mRNA levels were significantly (p < 0.05) increased in 20 of 30 peritoneal metastatic lesions of ovarian cancers. There was a significant correlation between microvessel counts (MVCs) and ETS-1 histoscores in the endothelial cells (p < 0.001) and between MVCs and ets-1 mRNA levels in the primary tumor and the peritoneal metastatic lesion of ovarian cancers (p < 0.001). Furthermore, the 24-month survival rate of patients with significantly increased ets-1 mRNA level (2/20, 10%) was significantly (p < 0.01) lower than that of patients with no change in the level (6/10, 60%) from the primary tumor to the peritoneal metastatic lesion. Conclusions: ETS-1 might be associated with peritoneal metastasis dominantly as an angiogenic mediator and additionally as an oncogene product to activate tumor invasion in ovarian cancers. Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

ETS-1 has been identified as a transcription factor for angiogenesis, which is essential for the development and growth of the uterine endometrium. This characteristic prompted us to study whether ETS-1 functions as an angiogenic mediator in uterine endometrium. Immuno-histochemical staining revealed that the localization of ETS-1 was similar to that of vascular endothelial cells. There was a significant correlation between microvessel counts and both ETS-1 histoscores and ets-1 mRNA levels in uterine endometrium. The ETS-1 histoscores and ets-1 mRNA levels increased in the proliferative phase, reached a peak during peri-ovulation and decreased in the secretory phase. Furthermore, the ETS-1 histoscores and ets-1 mRNA levels correlated with vascular endothelial growth factor (VEGF) levels in the proliferative phase. This indicates that ETS-1 might be an angiogenic mediator in uterine endometrium linked to VEGF in the proliferative phase. [ABSTRACT FROM AUTHOR]