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

To know the potential of growth, invasion and metastasis of uterine endometrial cancer associated with neovascularization, the expressions of VEGF and its mRNA, especially their subtypes, in uterine endometrial cancers and normal uterine endometria as controls were determined by Western blot analyses with a sandwich enzyme immunoassay and RT-PCR-Southern blot analysis, respectively, and the relation between their expressions and histological grades, grades of myometrial invasion and clinical stages of uterine endometrial cancers was analyzed. The levels of VEGF (VEGF165 and VEGF121) protein and mRNA were in a wide range and higher in normal uterine endometria than in the malignant counterparts. The levels of VEGF protein were higher in order of histopathological differentiation (normal uterine endometrium > well-differentiated (G1) > moderately differentiated (G2) and poorly differentiated (G3)) and those of VEGF protein and VEGF121 mRNA were lower in order of the advance of clinical stages (normal uterine endometrium > stage I > stage II > stages III and IV). There was, however, no significant difference in their levels among uterine endometrial cancers classified according to grades of myometrial invasion. This suggests that VEGF is downregulated during uterine endometrial cancer progression with dedifferentiation. Namely, VEGF in some endometrial cancers might contribute to the early process of advancing of malignancy via angiogenic activity.
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PMID:Expressions of vascular endothelial growth factor (VEGF) and its mRNA in uterine endometrial cancers. 1038 Nov 25

Currently, at least five different mRNA species encoding vascular endothelial growth factor-A (VEGF-A) have been characterized. These variants result from alternative splicing of the VEGF-A transcript and encode human isoforms of VEGF protein of 121, 145, 165, 189, and 206 amino acids. In the rat, a similar profile of VEGF-A splice variants has been described, each encoding one fewer amino acid than the human species. Studies of mammalian tissues have shown that these mRNA isoforms vary in abundance. Whereas VEGF 188/189, 164/165, and 120/121 (rat/human, respectively) are the predominant forms expressed in most tissues and cells examined, VEGF 144/145 and 205/206 are rare variants. Previously, VEGF 144/145 had been detected only in placental and uterine tissues and endometrial carcinoma cell lines, whereas VEGF 205/206 was detected only in fetal liver and placenta. Using an RT-PCR technique, cDNA cloning, and sequencing, we have detected and confirmed the presence of mRNA encoding VEGF 144/145 and 205/206 in both adult rat lung and penis. Therefore, these low-abundance VEGF splice variants have a more diverse expression pattern than originally predicted.
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PMID:Expression of VEGF splice variants 144/145 and 205/206 in adult male tissues. 1063 69

This study assessed whether serum VEGF measurement in women presenting with endometrial cancer could predict advanced stage disease. Preoperative sera from 37 women undergoing laparotomy for suspected endometrial cancer were assayed for VEGF, CA125 and platelet count. Significant positive correlation was shown between VEGF and platelet levels (P = 0.003, r = 0.477). However, no correlation was demonstrated between VEGF and stage overall, and no significant difference was shown between those with early (stage 1A/1B, n = 20) compared to those with advanced (stage >1B, n = 13) or disseminated (stage >2, n = 7) disease. Serum VEGF measurement was not beneficial in the preoperative assessment of stage in patients with endometrial carcinoma. Strong correlation with platelet levels suggests that this is one of the sources of VEGF measured.
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PMID:Investigation of women with endometrial carcinoma using serum vascular endothelial growth factor (VEGF) measurement. 1132 16

Quercetin and other polyphenols have anti-carcinogenic and anti-tumorigenic activity in various organs, however, studies of this activity are lacking in endometrial cancer. We hypothesize that quercetin has anti-proliferative activity and the mechanisms of quercetin action may be through modulation of cell cycle and cell growth regulatory genes. To test this hypothesis, we treated endometrial cancer cells (Ishikawa cell line) with quercetin, and cell proliferation, expression of growth signal genes (EGF, VEGF, and TGF-alpha), cell cycle genes (p53, p21, p73, and cyclin D1), and apoptosis-related genes (bcl-2 and bax) were analyzed. Results of these experiments demonstrate that after a 7-day exposure to 1, 10 and 100 micro M of quercetin, growth of Ishikawa cells was inhibited by 3, 51 and 87%, respectively. The gene and protein expression data suggest that quercetin treatment (100 micro M) significantly decreased EGF and cyclin D1, whereas VEGF was up-regulated in Ishiwaka cell lines. Other genes such as TGF-alpha, p53, p21, p73, bcl-2 and bax were not significantly changed with quercetin treatment in Ishiwaka cell lines. The present study suggests that quercetin can suppress proliferation of Ishikawa cells through down-regulation of EGF and cyclin D1.
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PMID:Quercetin regulates growth of Ishikawa cells through the suppression of EGF and cyclin D1. 1246 99

Resveratrol and other polyphenols have anti-carcinogenic and anti-tumorigenic activities in various carcinomas. However, such studies are limited in endometrial cancer. We hypothesize that resveratrol suppresses cancer growth through modulation of cell cycle and cell growth regulatory genes. To test this hypothesis, we treated endometrial cancer cells (Ishikawa cell line) with resveratrol (1, 10, 50 and 100 micro M) for 1, 3, 5 and 7 days, and analyzed for growth signal genes (EGF and VEGF), cell cycle regulatory genes (p53 and p21), and apoptosis-related genes (bcl-2 and bax). Results of these experiments demonstrate that after resveratrol treatment, the growth of Ishikawa cells was inhibited in a dose dependent manner. The gene and protein expression data suggest that resveratrol treatment significantly decreased EGF, whereas VEGF was up-regulated in Ishiwaka cell lines. Interestingly, protein expressions of p21 and Bax were decreased, even though their mRNA expressions did not show significant changes. The present study suggests that resveratrol can suppress proliferation of Ishikawa cells through down-regulation of EGF.
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PMID:Resveratrol suppresses growth of Ishikawa cells through down-regulation of EGF. 1296

Endometrial cancer (EC) most commonly affects postmenopausal women. It is curable if treated early, but tumours with adverse histopathological features or at an advanced stage are associated with a high mortality rate. These cancers require a complex therapeutic approach, consisting of surgery, radiotherapy, chemotherapy and/or hormonal therapy. As one of the leading causes of death from malignancy in women, EC has been subject to intense clinical investigation. This article examines recent advances in the surgical treatment of the disease, such as sentinel lymph node sampling and total laparoscopic hysterectomy, as well as topics such as conservative treatment of EC for fertility preservation. Furthermore, new agents for EC treatment are presented, for example inhibitors of the mTOR pathway and the angiogenesis-inhibitor VEGF-trap.
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PMID:Advances in the treatment of endometrial cancer. 1581 58

Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is a newly identified angiogenic and permeability-enhancing factor, predominantly expressed in steroidogenic tissues. Recently, we found that EG-VEGF is also expressed in the normal peri-implantation endometrial samples from patients of reproductive ages (80%). Immunohistochemistry analysis showed that EG-VEGF is predominantly expressed in the glandular epithelial cells and its expression is dynamic during the menstrual cycle with a peak expression at the mid-luteal phase. We also found that EG-VEGF transcripts are up-regulated in all the peri-implantation endometrial samples from the patients after the ovulating dose of human chorionic gonadotropin in gonadotropin-stimulated cycles and patients receiving hormone replacement therapy. In in vitro endometrial cell culture, EG-VEGF mRNA was detected in endometrial cells only in the presence of steroids, suggesting that EG-VEGF expression is highly dependent on the steroid hormones. Subsequent expression analyses on the EG-VEGF receptors showed that hPK-R1 and hPK-R2 are differentially expressed in human endometrium, but show no significant correlation with the hormonal treatments. On the other hand, EG-VEGF transcript was rarely detected in the endometrial samples from the postmenopausal patients and patients with endometrial carcinoma. It may imply that EG-VEGF may only play a role in vascular function of peri-implantation endometrium, but is unlikely to be associated with the etiology of endometrial cancer development.
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PMID:Endocrine gland-derived vascular endothelial growth factor is expressed in human peri-implantation endometrium, but not in endometrial carcinoma. 1621 Mar 75

Molecular genetic evidence indicates that endometrial carcinoma likely develops as the result of a multistep process of oncogene activation and tumor suppressor gene inactivation. These molecular alterations appear to be specific for Type I (endometrioid) and Type II (non endometrioid) cancers. Type I cancers are characterized by mutation of PTEN, KRAS2, defects in DNA mismatch repair, as evidenced by the microsatellite instability phenotype, and a near diploid karyotype. Type II cancers often contain mutations of TP53 and Her-2/neu and are usually nondiploid. The clinical value of many of these molecular markers is now being tested and it may help to refine diagnosis and establish an accurate prognosis. Furthermore, some of these tumor biomarkers constitute the targets for emerging therapies. Transtuzumab against Her-2/neu and bevacizumab against VEGF overexpressing carcinomas are among the promising novel treatments. Additional translational research is needed to identify molecular and genetic alterations with potential for therapeutic interventions.
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PMID:Molecular alterations in the pathogenesis of endometrial adenocarcinoma. Therapeutic implications. 1664 98

Angiopoietin-1 (ANGPT1), Angiopoietin-4 (ANGPT4), VEGF, FGF2, FGF4, HGF, Ephrin, IL8 and CXCL12 (SFD1) are pro-angiogenic factors (angiogenic activators), while Angiopoietin-2 (ANGPT2), Angiostatin, Endostatin, Tumstatin, Canstatin, THBS1, THBS2, TNFSF15 (VEGI) and Vasohibin (VASH1) are anti-angiogenic factors (angiogenic inhibitors). ANGPT1 and ANGPT2 are ligands for TIE family receptor tyrosine kinases, TIE1 and TIE2 (TEK). Angiopoietin family consists of ANGPT1, ANGPT2, ANGPT4, ANGPTL1 (ANGPT3), ANGPTL2, ANGPTL3 (ANGPT5), ANGPTL4, ANGPTL5, ANGPTL6 and ANGPTL7. TCF/LEF binding sites within the promoter region of human Angiopoietin family members were searched for by using bioinformatics and human intelligence (Humint). Because four TCF/LEF-binding sites were identified within the human ANGPTL7 promoter, comparative genomics analyses on ANGPTL7 orthologs were further performed. ANGPTL7 gene at human chromosome 1p36.22 was located within intron 28 of FRAP1 gene encoding mTOR protein. Chimpanzee ANGPTL7 gene, consisting of five exons, was located within NW_101546.1 genome sequence. Chimpanzee ANGPTL7 showed 99.4% and 86.1% total-amino-acid identity with human ANGPTL7 and mouse Angptl7, respectively. Human ANGPTL7 mRNA was expressed in neural tissues, keratoconus cornea, trabecular meshwork, melanotic melanoma and uterus endometrial cancer, while mouse Angptl7 mRNA was expressed in four-cell embryo, synovial fibroblasts, thymus, uterus and testis. Four TCF/LEF-binding sites within human ANGPTL7 promoter were conserved in chimpanzee ANGPTL7 promoter; however, only an unrelated TCF/LEF-binding site occurred in mouse and rat Angptl7 promoters. Human ANGPTL7, characterized as potent target gene of WNT/ beta-catenin signaling pathway, is a pharmacogenomics target in the fields of oncology and regenerative medicine.
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PMID:Comparative integromics on Angiopoietin family members. 1668 28

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


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