Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endometriosis has been shown to be associated with increased number and activity of peritoneal macrophages. The peritoneal macrophage-conditioned media from 33 women with or without endometriosis were studied for their effects on an endometrial carcinoma cell line, ECC-1. The media from six of six stage III/IV cases demonstrated a mitogenic effect, which was blocked by an antibody to epidermal growth factor receptor. However, the conditioned media from seven of nine stage I/II cases and 14 of 18 normal women did not show a mitogenic effect. The difference between stage III/IV and the other two groups was significant (p less than 0.01). The incorporation of tritium-thymidine was three times higher with the media from stage III/IV cases, as compared with that of controls. When purified cytokines were tested in the tritium-thymidine uptake assay, only epidermal growth factor-transforming growth factor-alpha was mitogenic on ECC-1, whereas tumor necrosis factor, interleukin-1, and platelet-derived growth factor had no effect. Thus peritoneal macrophages in patients with endometriosis may play an important role in the progression of endometriosis, and the noted effects could be mediated by epidermal growth factor or a related growth factor.
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PMID:Effects of peritoneal macrophages from patients with endometriosis on the proliferation of endometrial carcinoma cell line ECC-1. 175 Apr 84

Some endometrial cancers and endometrial adenocarcinoma cell lines show amplified expression of proto-oncogenes (fos, fms, myc, myb, neu, and erb-B) and augmented production of growth factors (colony-stimulating factor 1, epidermal growth factor, transforming growth factor-alpha, and transforming growth factor beta) and epidermal growth factor receptor. Oncogene expression, the presence of estrogen and progesterone receptors, and the fraction of cells in S phase are useful biochemical prognostic indicators of clinical outcome, and markers recognized by monoclonal antibodies are available for use in following the clinical course of the disease and responses to treatment. In vivo and in vitro studies on normal and neoplastic tissues are providing evidence of paracrine influences on epithelial cell proliferation. Long-term administration of tamoxifen as adjuvant therapy for breast cancer has recently been found to increase the risk for development of endometrial cancer.
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PMID:Endometrial cancer: biochemical and clinical correlates. 199 48

The biological significance of epidermal growth factor (EGF)-related proteins in the development and progression of endometrioid endometrial carcinoma was studied. Expression of EGF-related proteins including EGF, transforming growth factor-alpha (TGF-alpha), cripto (CR), amphiregulin (AR), and EGF receptor (EGFR) were immunohistochemically examined. Results were then correlated with clinicopathologic findings and steroid receptor status in 12 specimens with normal endometrium, 13 with endometrial hyperplasia, and 40 with endometrioid endometrial carcinoma. EGFR, EGF, TGF-alpha, and CR immunoreactivities were observed in 58.3%, 66.7%, 91.6%, and 66.7% of normal endometrial specimens; 100%, 15.4%, 100%, and 30.8% of endometrial hyperplasia specimens; and 67.5%, 32.5%, 65.0%, and 65.0% of endometrial carcinoma specimens, respectively. AR immunoreactivity was not observed in any of the normal, hyperplastic, or neoplastic endometrium. The presence or absence of EGFR or TGF-alpha in endometrial carcinoma correlated with surgical stage, depth of myometrial invasion, and findings from peritoneal washing cytology. EGF expression significantly correlated with the age of the patients and that of CR with surgical stage and peritoneal washing cytological findings. There was a significant correlation between EGFR and TGF-alpha expression, and between EGF and TGF-alpha. Co-expression of EGFR and TGF-alpha, EGFR and CR, and TGF-alpha and CR in carcinoma specimens significantly correlated with advanced surgical stage, deeper myometrial invasion, and positive peritoneal washing cytology. In normal as well as hyperplastic endometrium, endometrial glands immunohistochemically positive for TGF-alpha were generally positive for ER, but in poorly differentiated endometrial carcinoma, cells positive for TGF-alpha tended to be negative for ER. The results of the present study show that among EGF-related proteins, expression of TGF-alpha and CR seem to be associated with the progression of human endometrioid endometrial carcinoma. Additionally, expression of TGF-alpha became increasingly estrogen independent with increasing histological carcinoma grades.
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PMID:Expression of epidermal growth factor family proteins and epidermal growth factor receptor in human endometrium. 860 44

Transcription-modulating drugs achieve their therapeutic effects through the modulation of gene transcription. To understand how selectivity is achieved, four groups of such drugs - including immunosuppressants, estrogen analogs, the antidiabetic thiazolidinediones, and the anti-inflammatory salicylates - will be discussed. The immunosuppressants cyclosporin A and FK506, when complexed with immunophilins, inactivate the protein phosphatase calcineurin, resulting in the inhibition of interleukin-2 gene activation. Another immunosuppressant, rapamycin, binds to the same immunophilin as FK506 but inactivates a protein kinase p70(s6k). Estrogen analogs tamoxifen and rolaxifene antagonize one estrogen receptor transactivation function (AF-2) and agonize another (AF-1). They modulate expression of a wide variety of genes, including transforming growth factor-alpha, insulin-like growth factor-1, and transforming growth factor-beta3, which are important for breast and endometrial cancer proliferation and bone maintenance respectively. The antidiabetic drugs thiazolidinediones bind and activate peroxisome proliferator-activated receptor gamma and suppress insulin resistance mediated by tumor necrosis factor-alpha. Salicylates inhibit transcription factor NFkappaB, which is important for immune and inflammatory responses. Continuing understanding of molecular mechanisms of such drugs not only helps to identify better drugs for these targets but should also provide an insight into developing future transcription-modulating drugs with better selectivity and reduced toxicity.
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PMID:Transcription-modulating drugs: mechanism and selectivity. 893 43

We have developed an orthotopic model for human endometrial carcinoma in nude mice. The human serous papillary endometrial carcinoma cell line SPEC-2 was injected into the subcutis (ectopic site) or uterine wall (orthotopic site) of athymic mice. Tumors grew in both locations locally. However, only uterine wall tumors produced metastases in regional and distant lymph nodes and to the lungs and liver. Cell lines were established in culture from these uterine tumors and from lung and liver metastases, and then these cells were injected into the uteri of additional mice. The metastatic potential of the lines subsequently established from tumors growing in vivo was not significantly higher than the already highly metastatic parental culture cells. All SPEC-2 cell lines expressed high levels of both 72-kDa and 92-kDa collagenase type IV activity. mRNA for transforming growth factor-alpha, basic fibroblast growth factor, and epidermal growth factor-receptor was constant among the cell lines. These data support the concept that the orthotopic implantation of human endometrial carcinoma cells into the uteri of nude mice provides a valuable model for studying the biology of human endometrial adenocarcinoma.
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PMID:Development of a metastatic model for human endometrial carcinoma using orthotopic implantation in nude-mice. 2156 33