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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vascular endothelial growth factor (VEGF) is a potent angiogenic and prognostic factor for endometrial cancer. Estrogen and tamoxifen are considered to be associated with increasing risk of endometrial adenocarcinoma. To investigate the effects and mechanisms of estrogen and antiestrogens (tamoxifen and raloxifene) on the growth of endometrial carcinoma cells in vitro, we performed growth studies of estradiol and antiestrogens on estrogen receptor positive Ishikawa cells. The effects of estradiol and antiestrogens on the induction of VEGF and estrogen-responsive finger protein (Efp) were measured by QRT-PCR and ELISA or Western blotting. The siRNA method was used to investigate the action of Efp on Ishikawa cell growth and the induction of VEGF by estradiol and antiestrogens. Estradiol and tamoxifen induced Ishikawa cell proliferation and expression of Efp and VEGF on mRNA and protein levels, while raloxifene did not. The effects of estradiol were partly or almost completely inhibited by tamoxifen and raloxifene. When the Efp expression was suppressed by siRNA, the cell growth was decreased with estradiol treatment, and other actions of estradiol and tamoxifen such as induction of VEGF were decreased. These results demonstrate that estradiol and tamoxifen may regulate the growth of endometrial carcinoma cells by stimulating VEGF production through Efp, and the effects of estradiol could be amplified by Efp. This study suggest that tamoxifen acts as an agonist-antagonist, and raloxifene acts as an antagonist of estrogen in Ishikawa cells in vitro.
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PMID:Regulation of the vascular endothelial growth factor and growth by estrogen and antiestrogens through Efp in Ishikawa endometrial carcinoma cells. 1914 13

Vascular endothelial growth factor-A (VEGF-A) has several isoforms, which differ in their capacity to bind extracellular matrix proteins and also in their affinity for VEGF receptors. Although the relative contribution of the VEGF isoforms has been studied in tumor angiogenesis, little is known about the mechanisms that regulate the alternative splicing process. Here, we tested microenvironment cues that might regulate VEGF alternative splicing. To test this, we used endometrial cancer cells that produce all VEGF isoforms as a model, and exposed them to varying pH levels, hormones, glucose and CoCl(2) (to mimic hypoxia). Low pH had the most consistent effects in inducing variations in VEGF splicing pattern (VEGF121 increased significantly, p < 0.001, when compared to VEGF145, 165 or 189). This was accompanied by activation of the p38 stress pathway and SR proteins (splicing factors) expression and phosphorylation. SF2/ASF, SRp20 and SRp40 down-regulation by siRNA impaired the effects of pH stimulation, blocking the shift in VEGF isoforms production. Taken together, we show for the first time that acidosis (low pH) regulates VEGF-A alternative splicing, may be through p38 activation and suggest the possible SR proteins involved in this process.
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PMID:Microenvironment changes (in pH) affect VEGF alternative splicing. 1930 91

Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are two important angiogenic and prognostic factors for endometrial cancer. Estrogen is considered to be associated with increasing risk of endometrial adenocarcinoma. We investigated the expression of estrogen-responsive ring finger protein (Efp), VEGF and bFGF in endometrial cancer and correlated the results with clinicopathological features. We measured the expression of Efp, VEGF and bFGF in normal, hyperplastic and malignant endometrial tissues by quantitative RT-PCR, ELISA or Western blot analysis. The expression of Efp mRNA was significantly decreased in the groups of endometrial cancer (EC) in comparison with the groups of normal endometrium (NE) (P<0.05). Expression of VEGF mRNA in the groups of EC and atypical hyperplasia (AH) was significantly increased in comparison with the groups of NE (P<0.05). The expression of bFGF mRNA in groups of EC and AH was higher than that of NE groups (P<0.01 and P<0.05). There was positive relevance of bFGF expression and histologic grade and negative relevance of Efp expression and histologic grade. The expression of Efp, VEGF and bFGF protein was in agreement with the mRNA. The high expression of VEGF and bFGF indicate that both contribute in the angiogenesis of endometrial cancer. The regulation of Efp and bFGF expression during endometrial carcinogenesis suggests their potential utility as a prognostic biomarker.
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PMID:Expression of Efp, VEGF and bFGF in normal, hyperplastic and malignant endometrial tissue. 2012 22

Controlling lymph node metastasis is currently a key issue in cancer therapy. Lymph node metastasis is one of the most important prognostic factors in various types of cancers, including endometrial cancer. Vascular endothelial growth factor-C (VEGF-C) plays a crucial role in lymphangiogenesis, and is implicated to play an important role in lymph node metastasis. To evaluate the role of VEGF-C in lymph node metastasis, we developed an animal model by using an endometrial cancer cell line, HEC1A. This cell line is not invasive by nature and secretes moderate amounts of VEGF-C; intrauterine injection of HEC1A cells into Balb/c nude mice resulted in uterine cancer with lymph node metastasis after 8 weeks. To analyze the contribution of VEGF-C to lymph node metastasis, its corresponding gene was stably introduced into HEC1A cells (HEC1A/VEGF-C), which then produced more than 10 times the amount of VEGF-C. The number of lymph node metastases was significantly higher in HEC1A/VEGF-C cells than in HEC1A cells (3.2 vs 1.1 nodes/animal, respectively). Augmented lymphangiogenesis was observed within tumors when HEC1A/VEGF-C cells were inoculated. These results indicate that VEGF-C plays a critical role in lymph node metastasis, in addition to serving as a platform to test the efficacy of various therapeutic modalities against lymph node metastasis.
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PMID:Development of a mouse model for lymph node metastasis with endometrial cancer. 2191 Jul 84

Vascular endothelial growth factor [VEGF] pathway, which plays a key role in angiogenesis, may be blocked by either extracellular interference with VEGF itself (bevacizumab [BEV] or aflibercept), or intracytoplasmic inhibition of VEGF receptor (pazopanib, nintedanib, cediranid, sunitinib and sorafenib). An alternative approach is represented by trebananib, a fusion protein that prevents the interaction of angiopoietin [Ang]-1 and Ang-2 with Tie2 receptor on vascular endothelium. The combination of antiangiogenic agents, especially BEV, and chemotherapy is a rational therapeutic option for primary or recurrent ovarian carcinoma. However, it will be difficult to accept that it represents the new standard treatment, until biological characterization of ovarian carcinoma has not identified subsets of tumors with different responsiveness to BEV. Anti-angiogenesis is an interesting target also for recurrent cervical or endometrial cancer, but nowadays the use of anti-angiogenic agents in these malignancies should be reserved to patients enrolled in clinical trials.
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PMID:Antiangiogenic agents in gynecological cancer: State of art and perspectives of clinical research. 2612 94

Angiogenesis (the growth of new blood vessels) is essential in most of the body's physiological processes, such as in the normal functioning of the endometrium during and after the menstrual cycle. Vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP) are the mostly expressed angiogenic factors, especially, during the process of endometrial degeneration and remodeling. In carcinogenesis, tumor hypoxia-induced factors, through the process of "angiogenic switch", stimulate the production of angiogenic factors, particularly VEGF and MMP. Subsequently, these angiogenic factors are associated with degradation, differentiation, proliferation, and migration of vascular endothelial cells, enhancing the formation of new blood vessels to supply the tumor with oxygen and nutrients. This process is equally significant for tumor development and metastasis. Hence, like in other cancers, the overexpression of MMP and VEGF in endometrial cancer (EC) seems to play a significant role in its tumorigenesis and metastasis. This research will discuss the influence of MMP and VEGF on angiogenesis, metastasis, and the prognosis of EC as well as the clinical importance of the factors in the diagnosis of EC.
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PMID:The influence of vascular endothelial growth factor-A and matrix metalloproteinase-2 and -9 in angiogenesis, metastasis, and prognosis of endometrial cancer. 2903 80


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