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)

The over-expression of the proto-oncogene HER-2 (c-erbB-2/neu) in ovarian, endometrial and mammary carcinoma is an important indicator for poor prognosis. We have previously shown in 3 out of 4 ovarian carcinoma cell lines an interferon-gamma (IFN-gamma)-mediated reduction in HER-2 specific protein and RNA levels. The oncogene expression was lowered only in the ovarian carcinoma cell lines but not in 3 IFN-gamma-sensitive human breast cancer cell lines. We extended our observations also to IFN type I, alpha and omega. The expression of the oncogene was measured by both the p185HER-2 ELISA and in selected cases by a living cell radioimmunoassay using the monoclonal antibody (MAb) 4D5 against the extracellular domain. Both IFN types reduced the expression of HER-2 in the ovarian carcinoma cell lines OVCAR-3, HTB-77, 2774 and SKOV-6, and in the SKUT-2 endometrial carcinoma cells. In contrast, SKOV-8 human ovarian carcinoma cells were sensitive for both IFN types regarding proliferation, but only IFN-gamma reduced proto-oncogene expression. In the SKBR-3 human mammary carcinoma cells, neither IFN type had an effect on HER-2 expression. The antibodies 4D5, 7C2, 3E8, and 3H4 which bind to the extracellular domain of p185HER-2 protein specifically inhibited anchorage-independent growth of SKBR-3 and HTB-77 cells. Expression of the oncogene HER-2 is the leading prognostic factor in ovarian cancer. Its modulation might represent a mechanism by which IFNs inhibit cell proliferation.
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PMID:Effects of interferons on the expression of the proto-oncogene HER-2 in human ovarian carcinoma cells. 137 Feb 27

We previously reported that recombinant interferon-gamma (IFN-gamma) induces HLA-DR (human lymphocyte antigen) molecules of the major histocompatibility complex in human endometrial epithelial cells in vitro. We now report that IFN-gamma inhibits the proliferation of human endometrial epithelial cells and a human endometrial carcinoma cell line (EnCa101AE). Human endometrial epithelial cells expressed HLA-DR molecules and underwent morphological changes when exposed to IFN. Furthermore, the proliferation of these cells, as evidenced by nuclear labeling of bromodeoxyuridine (an analog of thymidine that is incorporated into cells in S phase), was markedly reduced, in a dose-dependent manner, by IFN-gamma. IFN-gamma induced HLA-DR expression, morphological changes, shedding from the substratum, and cell death in EnCa101AE cells. In addition, cell number and the numbers of bromodeoxyuridine-, Ki-67 (a nuclear marker of proliferation)-, and MPM-2 (a marker of mitotic cells)-positive cells were markedly lower in the EnCa101AE cultures treated with IFN-gamma than those in control cultures. The cytostatic and HLA-DR-inducing effects of IFN-gamma could be abrogated by neutralization with a polyclonal antibody, and IFN-gamma effects were reversible within days after its withdrawal. These findings indicate that IFN-gamma inhibits proliferation of human endometrial epithelial cells and suggest that this factor may locally regulate the proliferation of these epithelial cells in vivo.
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PMID:Antiproliferative effect of interferon-gamma in human endometrial epithelial cells in vitro: potential local growth modulatory role in endometrium. 245 43

With flow-cytometry we tested whether or not interferon can induce surface expression of HLA-ABC antigen on cell lines derived from various gynecologic cancers. The tumor cell lines used were Hela S3 derived from cervical cancer, OVK-18 derived from ovarian cancer, HHUA derived from endometrial cancer, SCH, JaR and BeWo derived from choriocarcinoma. 1000 IU/ml of interferon-gamma induced HLA-ABC antigen expression on Hela S3, OVK-18 and SCH but not on BeWo. HLA-ABC antigen was expressed on neither the surface of HHUA or JaR nor was its appearance induced by interferon. The clinical application of interferon may be effective in killing some tumors, taking advantage of the increased expression of HLA antigen.
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PMID:Enhanced expression of HLA antigens on gynecologic cancer cells by interferon-gamma. 309 Jan 75

The in vitro antiproliferative activity of human recombinant interferon-gamma (IFN-gamma) was tested against human tumor cells in vitro in combination with doxorubicin, cisplatin, or vinblastine. Using a human tumor clonogenic assay (HTCA), IFN-gamma alone showed dose-dependent inhibition of colony growth in six or seven human tumor cell lines as well as in each of nine fresh ovarian tumor specimens. The combination of IFN-gamma and either doxorubicin or cisplatin showed additive antiproliferative effects against all the cell lines with the exception of an IFN-gamma-resistant endometrial cancer cell line (HEC-1A). In combination with vinblastine, IFN-gamma rarely had an additive effect. Inclusion of macrophages from malignant effusions in the HTCA potentiated the antiproliferative effect of IFN-gamma alone as well as the combination of IFN-gamma and doxorubicin; however, the efficacy of the two agents was never more than additive. The results show that combinations of IFN-gamma with doxorubicin or cisplatin are additive and warrant further investigation. The antitumor effect of IFN-gamma alone or in combination with cytotoxic drugs may be significantly enhanced by tumor-associated macrophages.
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PMID:Interferon-gamma and cytotoxic agents studied in combination using a soft agarose human tumor clonogenic assay. 310 48

Malignant tumors may contribute to host response that involves both the adaptive and innate immune systems. Among other biochemical indicators of systemic immune and inflammatory activity, activation of macrophages by interferon-gamma induces a marked increase in the production of neopterin. Neopterin production by activated macrophages is also associated with tryptophan degradation. In addition to tumors of other primary locations, increased urinary and serum neopterin concentrations have been reported in patients with gynecological cancers, including epithelial ovarian carcinoma, cervical carcinoma, endometrial carcinoma, uterine sarcomas, and vulvar carcinoma, but not in women with benign neoplasms or precancerous disorders. Increased neopterin concentrations have been associated with poor prognosis. Elevated levels of neopterin have also been observed in the tumor microenvironment. Systemic (urinary or serum) or local (ascitic fluid) neopterin concentrations increased after therapeutic administration of cytokines. Elevated neopterin concentrations have been associated with anemia of chronic disease and increased urinary zinc loss in patients with gynecological malignancy. Elevated neopterin has also been connected with depressed function of peripheral blood lymphocytes and a decrease in CD4+ T-cell numbers.
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PMID:Neopterin as an indicator of immune activation and prognosis in patients with gynecological malignancies. 1644 39