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)

Endometrial carcinoma is considered a tumor which does not respond well to chemotherapeutic treatment. Among the various mechanisms of resistance to chemotherapy which are under investigation, two of them (multidrug resistance, mediated by P-glycoprotein, and glutathione-S-transferase-pi [GST-pi] overexpression) are of great interest for gynecologic oncologists, because they involve several drugs commonly used in practice, among which Adriamycin and cisplatin are probably the most important ones. We have studied 23 human endometrial carcinomas of different histological varieties and 3 normal endometrial samples for the overexpression of both P-glycoprotein and GST-pi by means of immunohistochemistry. Both resistance markers were detectable in all tumor samples, and in normal endometrial tissue as well. The concomitant intrinsic overexpression of these two resistance mechanisms may in part explain why these tumors tend to be extremely resistant to chemotherapy.
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PMID:Intrinsic overexpression of two different mechanisms of resistance to chemotherapy (P-glycoprotein and GST-pi) in human endometrial carcinoma. 791 81

The overexpression of P-glycoprotein was studied in 10 normal endometrial controls (five from the proliferative and five from the secretory phase of the menstrual cycle) and in 23 endometrial carcinomas of different histological varieties, using the C219 and JSB-1 monoclonal antibodies. Three of the tumours had been previously treated with combination chemotherapy containing doxorubicin. All endometrial carcinomas, whether treated or untreated, as well as the normal endometrial controls from both the proliferative and the secretory phase of the menstrual cycle, overexpressed P-glycoprotein. This puts endometrial carcinoma into the same category as other tumours arising in organs which normally overexpress P-glycoprotein, all of which tend to be intrinsically resistant to chemotherapy.
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PMID:High rate of expression of multidrug resistance-associated P-glycoprotein in human endometrial carcinoma and normal endometrial tissue. 809 23

The objective of the present study was to determine the MDR1 gene expression in endometrial cancer. Twenty-six newly diagnosed patients with endometrial carcinoma were included in this study. Patients were treated with surgery followed by adjuvant radiotherapy. Four- to six-micrometer sections of the archival paraffin-embedded blocks were cut, deparaffinized, and stained by immunohistochemical technique using P-glycoprotein dye. Endothelial cell staining was used as the positive control of the dye. Immunostaining was categorized from 0% to 100% based on the percentage of cells stained by examining 3-4 high-power fields. The mean P-glycoprotein immunoreactivity for the whole study group was 17 +/- 25% (0-90). Tauhe mean P-glycoprotein immunoreactivity was 21 +/- 26% (0-90) for the endometrioid histology and 6 +/- 13% (0-30) for the clear cell histology. P-glycoprotein immunoreactivity was not detected in a case of mucinous histologic subtype. There was a significant negative correlation between age and P-glycoprotein immunoreactivity (r = -0.530, P = 0.005). The P-glycoprotein immunoreactivity was found to be 30% positive in only one case of clear cell histologic type out of five. However, P-glycoprotein immunoreactivity was not significantly lower in clear cell histologic subtype compared with endometrioid subtype of endometrial cancer (P = 0.116). P-glycoprotein immunoreactivity was found to be 0% in grade 1 (n = 2), 22 +/- 28% in grade 2 (n = 17), and 8 +/- 14% in grade 3 (n = 7) patients (P = 0.273). Premenopausal patients were found to have a significantly higher P-glycoprotein expression (40 +/- 33)% vs. 11 +/- 20%, P = 0.04). P-glycoprotein immunoreactivity was found to be less with advanced age in endometrial carcinoma. However, premenopausal patients were found to have a significantly higher P-glycoprotein expression.
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PMID:MDR1 gene expression in endometrial carcinoma. 1467 53

Indole-3-carbinol (I3C) is produced by members of the family Cruciferae, and particularly members of the genus Brassica (e.g., cabbage, radishes, cauliflower, broccoli, Brussels sprouts, and daikon). Under acidic conditions, 13C is converted to a series of oligomeric products (among which 3,3'-diindolylmethane is a major component) thought to be responsible for its biological effects in vivo. In vitro, 13C has been shown to suppress the proliferation of various tumor cells including breast cancer, prostate cancer, endometrial cancer, colon cancer, and leukemic cells; induce G1/S arrest of the cell cycle, and induce apoptosis. The cell cycle arrest involves downregulation of cyclin D1, cyclin E, cyclin- dependent kinase (CDK)2, CDK4, and CDK6 and upregulation of p15, p21, and p27. Apoptosis by I3C involves downregulation antiapoptotic gene products, including Bcl-2, Bcl-xL, survivin, inhibitor-of-apoptosis protein (IAP), X chromosome-linked IAP (XIAP), and Fas-associated death domain protein-like interleukin-1-beta-converting enzyme inhibitory protein (FLIP); upregulation of proapoptotic protein Bax; release of micochondrial cytochrome C; and activation of caspase-9 and caspase-3. This agent inhibits the activation of various transcription factors including nuclear factor-kappaB, SP1, estrogen receptor, androgen receptor and nuclear factor-E2-related factor 2 (Nrf2). This indole potentiates the effects of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) through induction of death receptors and synergises with chemotherapeutic agents through downregulation of P-glycoprotein (P-gp). In vivo, I3C was found to be a potent chemopreventive agent for hormonal-dependent cancers such as breast and cervical cancer. These effects are mediated through its ability to induce apoptosis, inhibit DNA-carcinogen adduct formation, and suppress free-radical production, stimulate 2-hydroxylation of estradiol, inhibit invasion and angiogenesis. Numerous studies have indicated that I3C also has a strong hepatoprotective activity against various carcinogens. Initial clinical trials in women have shown that I3C is a promising agent against breast and cervical cancers.
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PMID:Molecular targets and anticancer potential of indole-3-carbinol and its derivatives. 1608 11

The P-glycoprotein (P-gp) plays an important role in carcinogen distribution and is connected with cell differentiation and apoptotic processes leading to carcinogenesis. Interindividual differences in P-gp activity could modulate susceptibility to cancer development. The MDR1 gene, coding for P-gp, is highly polymorphic and some mutations modulate P-gp activity. Recently, association between the MDR1 C3435T polymorphism and the cancer susceptibility was shown. We have hypothesized that MDR1 polymorphism could influence endometrial cancer susceptibility. We have matched 198 women with endometrial cancer and 198 controls. An additional group of 488 healthy volunteers was investigated. The MDR1 C3435T polymorphism was tested by LightCycler assay. The distribution of MDR1 3435 genotypes was significantly different between cases and controls (P = 0.006). Genotypes containing at least one 3435T allele were statistically significant more frequent in the endometrial cancer group (86.8% vs 75.2%, OR 2.18, P = 0.004). Our observation suggests that MDR1 C3435T polymorphism is correlated with endometrial cancer susceptibility.
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PMID:The significance of C3435T point mutation of the MDR1 gene in endometrial cancer. 1730 Jun 81