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

Although paclitaxel is one of the most effective chemotherapeutic agents, its usefulness is still limited in advanced and recurrent endometrial cancer. Amifostine protection of normal tissues against the side effects of chemotherapeutic agents has been clinically proven in cancer patients; however, its application in endometrial cancer has not been fully evaluated. We have investigated the use of paclitaxel and amifostine in controlling the growth of poorly differentiated endometrial cancer cells, Hec50co, in vitro and in vivo. Our studies show that amifostine had direct anticancer effects on endometrial cancer cells in vitro by arresting the cell cycle at the G1 phase and inducing apoptosis. Amifostine also inhibited s.c. tumor growth in athymic mice. Paclitaxel IC50 value was reduced from 14 to 2 nmol/L with pretreatment of a single dose of 178 micromol/L of amifostine for 72 hours. Amifostine also synergized with paclitaxel in the arrest of the cell cycle at the G2-M phase and in the induction of apoptosis. This two-drug regimen inhibited s.c. tumor growth as well as improved mouse survival significantly more than paclitaxel alone. Amifostine also significantly improved paclitaxel-induced cytotoxic effects on peripheral blood profiles. Our studies show that amifostine has direct anticancer effects on endometrial cancer. Our data have also shown a potential anticancer synergy between amifostine and paclitaxel in vitro and in vivo, whereas amifostine maintained a protective role in peripheral blood profiles. The dual specificity of amifostine action should be further investigated.
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PMID:A potential synergistic anticancer effect of paclitaxel and amifostine on endometrial cancer. 1623 Apr 17

Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis in estrogen responsive tissues. Estrogen receptors alpha and beta regulate production of VEGF in both breast and endometrial cancer cells. Alternative splicing of ER-alpha mRNA generates a mixture of transcripts with various exon deletions in normal breast and breast cancer cells and some of these variants are overexpressed in breast cancer. We analyzed the role of exon-deleted variants of ER-alpha in regulation of VEGF production by simultaneous transient transfection of CHO and MDA-MB-231 cells with a VEGF promoter luciferase construct. Estrogen (10 nM) treatment resulted in a 6-fold increase in luciferase activity in cells transfected with the exon 3 deleted variant (ERDelta3) compared to a 2-fold activity induction in cells transfected with wild type ER-alpha. Exon 5 and exon 7 deleted variants were unable to induce activation of the VEGF promoter. Using specific deletion constructs of the VEGF promoter linked to luciferase, we showed that the majority of activation by ERDelta3 was restricted to the -70 to -88 bp fragment that contains two Sp1 sites. Site-directed mutagenesis of both Sp1 sites indicated that ERDelta3 activates the VEGF promoter through interaction with Sp1 proteins. ERDelta3, a variant frequently overexpressed in breast cancer, may significantly contribute to the production of VEGF thus resulting in enhanced tumor growth in vivo.
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PMID:Activation of vascular endothelial growth factor (VEGF) by the ER-alpha variant, ERDelta3. 1626 16

Cyclooxygenase-2 (COX-2) plays a critical role not only in maintenance of the endometrium during the menstrual cycle, but also in the progression of endometrial cancer. The role of COX-2 in tumor growth and development is complex and multifaceted. This review presents evidence for the expression of COX-2 being linked to angiogenesis, tumor cell apoptosis, tumor cell growth, metastasis and local immunosuppression in cancer progression. It also outlines the clinicopathological and prognostic significance of COX-2 in endometrial cancer.
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PMID:Multiple roles of cyclooxygenase-2 in endometrial cancer. 1630 26

Angiogenesis is essential for tumor growth, invasion, and metastatic spread. Whereas microvessel density (MVD) has been widely used as a measure of tumor-associated angiogenesis, we now wanted to examine the significance of other angiogenic markers, especially vascular proliferation (by Ki-67/factor VIII staining) and the degree of pericyte coverage [by alpha-smooth muscle actin (alpha-SMA)/factor VIII staining], in a large and population-based series of endometrial carcinoma with complete follow-up. Due to limited information on the role of lymphangiogenesis in these tumors, lymphatic vessel density (LVD) by LYVE-1 staining was also determined, as well as selected angiogenic factors [vascular endothelial growth factor (VEGF)-A, VEGF-C, VEGF-D and basic fibroblast growth factor (bFGF)], which could possibly be related to vascular proliferation and lymphangiogenesis. The information on angiogenic phenotype was related to clinicopathologic features and disease progress. Median vascular proliferation, as estimated by vascular proliferation index (VPI), was 3.9% and high VPI was associated with features of aggressive tumors and decreased survival. The prognostic effect of VPI was superior to that of MVD. Presence of pericyte coverage, as estimated by the alpha-SMA index (SMAI), was 35% and low SMAI was significantly associated with vascular invasion by tumor cells and impaired prognosis. Peritumoral lymphatic vessels (LVD-pt) were found in 39.5% of the cases and high LVD-pt was significantly associated with aggressive tumor features and decreased survival. In multivariate survival analysis, only the extent of vascular proliferation had independent prognostic effect, in addition to well-known clinicopathologic factors, whereas MVD did not have significant prognostic value. In conclusion, our study indicates that vascular proliferation is a meaningful variable in assessing the angiogenic phenotype of endometrial carcinoma.
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PMID:Vascular proliferation is important for clinical progress of endometrial cancer. 1654 Jun 84

All the surgical procedures, which may be required to treat a gynecologic cancer, can be performed endoscopically. However prospective randomized studies required to confirm the oncologic efficacy of the technique are still lacking in gynecology, whereas such studies are available in digestive surgery. Animal studies suggested that the risk of tumor dissemination in non traumatized peritoneum is higher after a pneumoperitoneum than after a laparotomy. Experimental studies also emphasized two points: the surgeon and the surgical technique are essential, all the parameters of the pneumoperitoneum may influence the postoperative dissemination. Changing these parameters we may, in the future, be able to create a peritoneal environment adapted to oncologic patients in order to prevent or to decrease the risks of peritoneal dissemination and/or of postoperative tumor growth. Until the results of prospective randomized studies become available, the preoperative selection of the patients and the surgical technique should be very strict. In patients with endometrial cancer, the laparoscopic approach should be reserved to clinical stage I disease, if the vaginal extraction is anticipated to be easy accounting for the volume of the uterus and the local conditions. In cervical cancer, the laparoscopic approach should be reserved to patients with favorable prognostic factors: stage IB of less than 2 cm in diameter. Laparoscopy is the gold standard for the surgical diagnosis of adnexal masses. But the puncture should be avoided whenever possible. The surgical treatment of invasive ovarian cancer should be performed by laparotomy whatever the stage. In contrast restaging of an early ovarian cancer initially managed as a benign mass, is a good indication of the laparoscopic approach. The laparoscopic management of low malignant potential tumors should include a complete staging of the peritoneum. Knowledge of the principles of endoscopy and of oncologic surgery is required. Teaching and diffusion of endoscopic oncological techniques are among the major challenges of gynecologic surgery within the next few years.
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PMID:[Laparoscopy and gynecologic cancer in 2005]. 1657 58

The inducible enzyme cyclooxygenase-2 (COX-2) is an important mediator of angiogenesis and tumor growth. Several reports have indicated that vascular endothelial growth factor (VEGF)-positive tumors are associated with an increased amount of COX-2 protein. This study evaluated the significance of COX-2 in 34 patients with endometrial carcinoma and its relationship to angiogenesis. Immunohistochemical expression of COX-2 and VEGF was analyzed on paraffin-embedded tissue sections. Microvessel density (MVD) of endometrial carcinoma was also determined with anti-CD(34) as the label. COX-2 messenger RNA (mRNA) was analyzed by reverse transcription-polymerase chain reaction. The expression rate of COX-2 in 34 cases was 64.7% but not in control endometrium. COX-2 mRNA was higher in tumor specimens than in normal tissues. The level of COX-2 expression was higher in grade 2 tumors than in grade 3 tumors (P < 0.05). MVD was higher in COX-2-positive and VEGF-positive cases than in COX-2-negative and VEGF-negative cases (P < 0.05). The expression of COX-2 was positively correlated with the expression of VEGF and MVD (P < 0.05 and P < 0.01, respectively). The present findings suggest that overexpression of COX-2 may induce the expression of VEGF, increase angiogenesis, and enhance tumor growth.
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PMID:Overexpression of cyclooxygenase-2 correlates with tumor angiogenesis in endometrial carcinoma. 1688 83

Matrix metalloproteinase (MMPs) expression has been linked to gynecological tumor aggressiveness. The objective of this study was to determine MMP-2, MMP-7, and MMP-9 and tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2 expression in endometrial malignancies and their relation to clinical and histologic parameters. Formalin-fixed, paraffin-embedded tumor samples from 50 patients with endometrial carcinoma treated between 1999 and 2004 were stained with specific monoclonal antibodies. The tumors were grouped according to the FIGO classification. The staining results were compared to histologic and clinical data. Semiquantitative analysis of MMP and TIMP expression showed a significant difference in TIMP-2 expression according to the histologic subtype (P = 0.03) and also a trend towards a difference in MMP-9 expression (P = 0.05). MMP-2 expression increased and TIMP-2 expression fell as the histologic grade increased (P = 0.0007, P < 0.0001, respectively). MMP-2 expression correlated with lymph node metastasis (P = 0.04), while TIMP-2 expression correlated with the depth of myometrial invasion (P = 0.01), vasculolymphatic space involvement (P = 0.02), and lymph node metastasis (P = 0.0003). These results support the involvement of MMPs and TIMPs in endometrial tumor growth and progression. High MMP-2 and low TIMP-2 expression were the most potent markers of endometrial tumors with a high risk of local and distant spread.
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PMID:Endometrial tumor invasiveness is related to metalloproteinase 2 and tissue inhibitor of metalloproteinase 2 expressions. 1700 91

The objective of this study was to investigate the antitumor effect of antisense telomerase oligodeoxynucleotides to endometrial cancer cells in vitro and in vivo. Antisense oligodeoxynucleotides (ODNs) against the human telomerase transcripatse (hTERT) synthesized to serve as telomerase inhibitors. Reverse transcription-polymerase chain reaction and 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide (MTT) assay were used to test the expression of hTERT messengerRNA (mRNA) and inhibition of cell proliferation in vitro. In vivo, antitumor effects of ODNs or combined with cisplatin were evaluated in endometrial cancer xenograft. Telomerase activity was tested by telomeric repeat amplification protocol. Antisense ODNs could inhibit proliferation of human endometrial cancer cells (HEC-1-A) in vitro, and downregulate the expression hTRET mRNA in a dose- and period-dependent manner. The tumor growth inhibitory rate of low- and high-dose ODNs were 34.20% and 89.21%, and combined group was 75.30%. Telomerase activity was downregulated to 87.32% compared to the control in the ODNs-treated xenograft tumors. Antisense oligonucleotides of hTERT effectively inhibit the growth of endometrial cancer cell line. Telomerase inhibitor might be a new strategy for chemotherapy or chemoprevention in endometrial cancer.
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PMID:Telomerase antisense inhibition for the proliferation of endometrial cancer in vitro and in vivo. 1717 36

In the endometrium, angiogenesis plays important roles not only in tumor growth but also in the menstrual cycle. The purpose of the present paper was to investigate immunohistochemically the correlation between angiogenic factor expression and angiogenic score in normal and neoplastic endometrium. Immunohistochemical staining for vascular endothelial growth factor (VEGF), angiopoietin (Ang)-1, Ang2, Tie2, CD34 and CD105 was performed on formalin-fixed and paraffin-embedded tissues from 31 normal endometrium and 85 endometrial adenocarcinoma. VEGF, Ang1, Ang2 and Tie2 expression was localized in the cytoplasm of glandular and tumor cells. The levels of each angiogenic factor were different in the phases of the menstrual cycle and each layer of normal endometrium. In general, VEGF and Tie2 expression was higher in adenocarcinoma than in normal epithelial cells. Conversely, Ang1 and Ang2 expression was higher in normal epithelium than in adenocarcinoma. The angiogenic score (CD105/CD34) tended to be higher in the adenocarcinoma than in the normal epithelium. It is suggested that the angiogenic pathway and the role of these factors seem to differ between normal tissue and carcinoma of the endometrium.
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PMID:Angiogenic factors in normal endometrium and endometrial adenocarcinoma. 1729 46

Recent studies suggested that Ob (Ob) and its receptor (ObR) could be involved in the pathogenesis of various human malignancies, among others in endometrial cancer. Moreover, hypoxia, which is associated with solid tumors, might stimulate, through hypoxia-inducible factor 1alpha (HIF-1alpha), expression of Ob and ObR. In this article, we analyzed by immunohistochemistry the expression of Ob, ObR, and HIF-1alpha in 60 cases of human endometrial cancer tissues as well as in 25 cases of normal endometria. Additionally, we assessed correlations among studied proteins as well as relationships with selected clinicopathological features of endometrial cancer. Immunoreactivity for Ob, ObR, and HIF-1alpha protein was observed in 56.7%, 30.0%, and 78.3% of endometrial cancers, respectively. The expression of HIF-1alpha showed a significant positive correlation with Ob (P < 0.0001, r = 0.573) and ObR (P = 0.020, r = 0.299). Moreover, we noted positive correlation between Ob and ObR (P = 0.001, r = 0.429). No statistically significant relationship was revealed between Ob, ObR, and HIF-1alpha protein in regard to patient's age, histological grade, and extent of tumor growth (pT). In conclusion, HIF-1alpha, which is related to tissue hypoxia in endometrial cancer, seems to be associated with overexpression of Ob and ObR. Ob could exert autocrine effect to stimulate endometrial cancer progression. Thus the autocrine Ob loop should be taken into consideration as a novel potential target in endometrial cancer prevention and treatment.
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PMID:Expression of leptin, leptin receptor, and hypoxia-inducible factor 1 alpha in human endometrial cancer. 1740 22


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