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

The aim of this study was to overtake the mechanism of the control system in endometrial cancer cell line in vitro. Ishikawa cell (IK cell) and HEC-1 cell (HEC cell) derived from endometrial cancers were cultured with serum free medium (SFM-101). IK cell possessed Estrogen receptor (ER), Progesterone receptor (PR), Epidermal growth factor (EGF) and its receptor (EGFR). HEC cell had PR, EGF, and EGFR, however HEC cell did not keep ER. EGF stimulated the growth of IK cell, but the growth of HEC cell was not stimulated by EGF. S phase cells were increased by EGF in IK cell, but were not increased by EGF in HEC cell. The growth of IK cell was stimulated significantly by EGF and Estradiol-17 beta (E2) +EGF than control. However, E2+EGF did not stimulate the growth of IK cell than EGF significantly. Danazol (D) and D+EGF inhibited the growth of IK cell significantly than control. S phase cells were decreased by the treatment of D and D+EGF. From our results, EGF stimulated the growth of ER positive endometrial cancer cell, but EGF did not stimulate ER negative endometrial cancer cell. E2+EGF and EGF stimulated the growth of IK cell as a same. However, D inhibited the growth of IK cell that was stimulated by EGF.
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PMID:[Cell cycle analysis of endometrial cancer cells in vitro treated with growth factor and steroid hormone]. 130

The monoclonal antibody (MAb) 1BE12 has recently been reported to react with several human normal and abnormal tissues. In human endometrium, it reacts more strongly with carcinomas than with normal tissue. To investigate the effectiveness of MAb 1BE12 in identifying cell proliferation in human endometrial cancers, 1BE12 immunocytochemical assays (ICAs) were performed on frozen (n = 47) and paraffin (n = 100) sections with subsequent computer-assisted microcytophotometric (SAMBA) evaluation of immunoprecipitate distribution. MAb 1BE12 immunoreactivity was not impaired by tissue fixation and paraffin embedding. It reacted with normal proliferative endometrium but not with normal secretory endometrium, and immunoreactivity increased with the degree of cell proliferation and malignancy, the amount of immunostaining being greater in invasive carcinomas than in normal proliferative endometrium and endometrial hyperplasia. ICAs showed no correlation between MAb 1BE12 immunoreactivity and estrogen and progesterone receptor antigenic sites. On the other hand, MAb 1BE12 staining in frozen sections increased with Ki67, EGFR, pHER-2/neu, and cathepsin immunostaining. These findings suggest that ICAs on frozen and paraffin-embedded biopsy specimens using MAb 1BE12 along with other markers can be useful for early detection and grading of endometrial carcinoma. The relevance of MAb 1BE12 to the selection of patients for laser ablation of the endometrium rather than hysterectomy is also discussed.
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PMID:Monoclonal antibody 1BE12 immunoreactivity with human endometrium. Correlations with hormone receptors and proliferation cell markers. 177 9

Radioreceptorial assessment of EGFR expression was prospectively performed on 60 primary human endometrial tumors. Of these, 26 were EGFR-positive while 13 expressed high EGFR levels. High EGFR levels correlated well with poor histopathological grading. No correlation with histopathological type, stage, myometrial invasion, lymph-node involvement or steroid hormone receptor status was observed. Disease-free survival rate was significantly shorter in the cases with high than in the cases with low EGFR levels. These results suggest a potential role of EGFR expression assessment in prognostic characterization of endometrial cancer patients.
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PMID:Significance of epidermal growth factor receptor expression in primary human endometrial cancer. 826 74

Epidermoid carcinoma (PSCC) of the endometrium is a rare form of endometrial cancer that constitutes about 0.1% of all malignant epithelial tumors of the uterus. The diagnosis of PSCC is based on strict criteria and is made in the absence of a glandular component of the tumor. Squamous cell carcinoma of the endometrium should enter the differential diagnosis in postmenopausal patients in the presence of atypical squamous cells in the uterine curettage, while the cervical biopsies are negative for malignancy. The presence of HPV should be investigated as well, so that its pathogenetic relation is clarified. While no significant relation was found to p-53, C-NEU and EGFR expression this investigation must be continued because. HPV may interact with tumor suppressor genes.
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PMID:Immunohistochemical investigation of p-53, C-NEU and EGFR expression in HPV-related epidermoid endometrial carcinoma. 1187 98

Estrogen and progestin combination in hormone replacement therapy (HRT) increases the incidence of breast cancer, but decreases the endometrial cancer risk of unopposed estrogen. Therefore, a SERM such as Tibolone, that delivers the beneficial, but not the adverse side effects, of steroid hormones would be clinically advantageous. However, data from the Million Women Study suggests that Tibolone increases the risk of both breast and endometrial cancer. Herein, we assessed the estrogenic and progestagenic actions of Tibolone using transvaginal sonography studies and an in vitro model of breast (ZR-75, MCF7) and endometrial cancer (Ishikawa). The known cancer associated proteins (ER, EGFR, STATS, tissue factor and Bcl-xL) were selected for study. Transvaginal sonography demonstrated that postmenopausal women treated with Tibolone displayed a thinner endometrium than in the late proliferative phase, but had a phenotype characteristic of the secretory phase, thus demonstrating the estrogenic and progestagenic actions of this SERM. In vitro, Tibolone acted as an estrogen in downregulating ER and upregulating Bcl-xL, yet as progesterone, increasing STAT5 and tissue factor in breast cancer cells. The increase in tissue factor by Tibolone correlated with its coagulative potential. Interestingly, EGFR was up-regulated by progesterone in the breast and by estrogen in endometrial cells, while Tibolone increased protein levels in both cell types. In conclusion, this study further demonstrates the estrogenic and progestagenic nature of Tibolone. The pattern of regulation of known oncogenes in cells of breast and endometrial origin dictates caution and vigilance in the prescription of Tibolone and subsequent patient monitoring.
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PMID:In vivo and in vitro estrogenic and progestagenic actions of Tibolone. 1623 3

To understand how type I and II endometrial tumors uniquely respond to tyrosine kinase inhibitor treatments, we evaluated the signaling pathways of epidermal growth factor (EGF) receptor (EGFR) under the effects of EGF and Iressa (ZD1839, gefitinib) using Ishikawa H and Hec50co cells that model type I and II endometrial carcinomas, respectively. The cells were assayed for the expression of EGFR and both cell lines express an average of 100,000 EGFR per cell; however, Ishikawa H cells express higher levels of HER-2/neu compared with Hec50co cells (1.38 x 10(5) compared with 2.04 x 10(4), respectively). Using the Kinetworks multi-immunoblotting approach, which profiles 31 signaling phosphoproteins, the most striking result was that Hec50co cells show a higher number of basal phosphorylated sites compared with Ishikawa H cells. Furthermore, we identified targets of Iressa treatment in both cell lines. Iressa, at a dose of 1 micromol/L, blocked the autophosphorylation of EGFR in Ishikawa H and Hec50co cells with some distinctive effects on downstream effectors. Nevertheless, in both cell lines, EGF stimulated and Iressa blocked the major EGFR target mitogen-activated protein kinases extracellular signal-regulated kinase 1 and 2 equally. The high basal phosphorylation of numerous signaling molecules in Hec50co cells that were not inhibited by Iressa indicates that other growth factor pathways are active in addition to EGFR. We conclude that endometrial cancer cells that model type I and II carcinomas have the capacity to respond to EGFR inhibition as a therapeutic strategy; however, the response of the more aggressive type II tumors may be limited by the constitutive activation of other signaling pathways.
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PMID:Regulation of signaling phosphoproteins by epidermal growth factor and Iressa (ZD1839) in human endometrial cancer cells that model type I and II tumors. 1637 4

The fact that the genetic alterations of PTEN are frequently found in hormone-dependent cancers, such as endometrial, breast, and prostate cancers, might suggest the involvement of PTEN in the hormone-dependent cell growth of such tumors. Estrogen promotes the cell growth of the tumors by inducing peptide growth factors in part. We analyzed the possible involvement of PTEN in peptide-growth factor-dependent cell growth in endometrial carcinoma cells. PTEN-null Ishikawa cells were efficiently infected with recombinant adenovirus at 20 MOI (multiplicity of infection) to express PTEN protein. In PTEN-IK cells, phospho-Akt/PKB was down-regulated regardless of the consistent expression of Akt/PKB. The cell growth of parental IK cells was significantly stimulated by EGF and IGF-I, and PTEN-IK cells were further sensitized to the EGF-or IGF-I-growth stimulation. EGFR antibody could completely compromise the stimulatory effects of EGF in both cell lines. Wortmannin, a PI3K inhibitor, or UO126, a MAPK inhibitor, partly suppressed EGF-mediated cell growth stimulation in both cell lines. EGF augmented the level of phospho-Akt/PKB of PTEN-IK cells more effectively than that of parental IK cells. These results imply that the dysfunction of PTEN leads cells into a less-sensitive phenotype to peptide growth factors by constitutive activation of the PI3K/Akt/PKB signaling pathway in endometrial carcinoma.
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PMID:PTEN sensitizes epidermal growth factor-mediated proliferation in endometrial carcinoma cells. 1652 71

This years ASCO-meeting reinforced the trend of the recent years to get off from empirical treatment concepts to tailored and individualized diagnostics and therapy. However, the basis for an individual therapy is a specific molecular diagnostic which can be reflected in the analysis of hormonal receptor, HER-1, HER-2 and topoisomerase IIalpha in breast cancer. All these markers are not only able to prognosticate the course of disease but they also can predict the success of specific treatment approaches. Trastuzumab is standard therapy in HER-2 positive breast cancer both in the adjuvant and palliative setting. But new therapeutic agents, as e. g. lapatinib, are promising in the treatment of HER-2 positive breast cancer even if trastuzumab is failing. Otherwise it might possibly be an alternative option but adequate clinical results have to be awaited. The targeted inactivation of EGFR-related signal transduction pathways by e. g. gefitinib did not show a substantial improvement neither as a single agent nor in combination with endocrine treatment. However, the appropriate subgroup which might benefit from this therapy has to be defined even if molecular data suggest that patients with ER positive and PR negative breast cancer might be such a group. The increasing knowledge in terms of the biology of bone metastasis led to the development of new treatment options as e. g. denosumab, a humanized monoclonal antibody for RANK ligand. Two adjuvant cytotoxic treatment trials revealed that taxanes improve the prognosis of node positive breast cancer and should be administered sequentially. The advantage of switching to an aromatase inhibitor after two to three years of tamoxifen in endocrine treatment of postmenopausal patients is proved by two clinical trials (IES, ARNO) which could demonstrate a survival benefit. In conclusion it seems to be evident that new targeted therapy options are effective and will set new standards for the treatment of breast cancer patients in the near future. The presentation for the ovarian cancer focused on the addition of a third cytotoxic agent to carboplatin and paclitaxel as the standard therapy for the primary treatment of ovarian cancer. New data of Bevacizumab in the treatment of primary and recurrent ovarian cancer were presented. However, this is not yet a standard treatment for all patients and needs further investigations within large, multicentre, randomised trials. The lymphonodectomy as part of the primary therapy of the endometrial cancer seems to be a benefit at least in patients with advanced disease or high risk stage I tumours. The adjuvant therapy of uterine sarcomas is still not yet very well investigated and clear. A trial which recruited 12 years demonstrated a benefit in overall survival which has to be interpreted with caution. In this year again there have been registered an increasing number of interesting contributions from Germany, which also received international attention.
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PMID:[Molecular diagnostic and targeted therapy--"Barking dogs are going to bite": presentations from the 42nd Annual Meeting of the American Society of Clinical Oncology, Atlanta 2006]. 1700 57

Endometrial cancer is associated with both EGFR and HER2 receptor activation. The EGFR and HER2 genes could be disease susceptibility candidate genes for this cancer. This study was conducted to investigate a possible association between EGFR and HER2 gene polymorphisms and endometrial cancer and the influence of these polymorphisms on the clinical outcome of endometrial cancer patients in a Japanese population. The authors compare the genotype distributions and allele frequencies of the EGFR +2073 A/T and HER2 +655 A/G polymorphisms in 116 endometrial cancer patients and 213 controls using polymerase chain reaction-restriction fragment length polymorphism (RFLP) analysis. RFLP results were confirmed by direct DNA sequencing. Of the 116 patients, 76 (65.5%) could be followed up. Disease-free survival estimates were computed using the Kaplan-Meier method, and differences between survival periods were assessed using the log-rank test. No significant differences were observed in either genotype distributions or allele frequencies in the EGFR +2073 A/T and HER2 +655 A/G polymorphisms between endometrial cancer patients and controls. The stratification by histological types and staging failed to identify significant differences between endometrial cancer patients and controls. No statistical differences were noted between these polymorphisms and disease-free survival (Kaplan-Meier log-rank test P = .55 and .66, for the EGFR +2073 A/T and HER2 +655 A/G, respectively). These results suggest that the EGFR +2073 A/T and HER2 +655 A/G polymorphisms are not associated with endometrial cancer in a Japanese population. These conclusions are based on relatively small numbers and will require verification from additional independent studies.
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PMID:Epidermal growth factor receptor and human epidermal growth factor receptor 2 gene polymorphisms in endometrial cancer in a Japanese population. 1764 7

Gene alterations and overexpression of various oncogenes and cell-cycle regulators are important in tumor development. In a population based series of 316 endometrial carcinomas with long and complete follow-up we investigated the distribution of HER-2/neu and EGFR expression and copy number alteration in endometrial cancers. HER-2/ neu, EGFR and Ki-67 expression in curettage and hysterectomy specimens were studied immunohistochemically for expression in relation to molecular markers and clinical phenotype. Fresh tumor samples (n=76) were studied by global characterization of genetic alterations by single nucleotide polymorphism (SNP) array for detection of high level amplification for HER-2/neu and EGFR. Pathological expression of HER-2/neu in curettage was detected in 23% which significantly correlated to high FIGO stage, non-endometrioid subtype, high grade and aneuploidy. In hysterectomy specimens, pathological HER-2/neu staining was seen in 13% which correlated significantly with high FIGO stage, non-endometrioid subtype, high proliferation and poor survival (p=0.009). Expression of EGFR was examined with three different antibodies, but none showed significant correlation with molecular markers or clinical phenotype. High level amplification of HER-2/neu or EGFR was seen in only one out of 76 samples, respectively. High proliferation estimated in tumors from hysterectomy specimens showed independent prognostic impact and was superior to estimation in curettage specimens as a prognostic marker. In conclusion, high level amplification of HER-2/neu or EGFR is infrequent in endometrial cancer. Pathological HER-2/neu staining identifies endometrial carcinomas with an aggressive phenotype, high proliferation and patients with poor survival in a population based setting. These results motivate further clinical trials with trastuzumab based on HER-2/neu status in endometrial carcinomas.
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PMID:HER-2/neu expression is associated with high tumor cell proliferation and aggressive phenotype in a population based patient series of endometrial carcinomas. 1820 52


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