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

Uterine serous papillary cancer (USPC) represents a rare but highly aggressive variant of endometrial cancer, the most common gynecologic tumour in women. We used oligonucleotide microarrays that interrogate the expression of some 10 000 known genes to profile 10 highly purified primary USPC cultures and five normal endometrial cells (NEC). We report that unsupervised analysis of mRNA fingerprints readily distinguished USPC from normal endometrial epithelial cells and identified 139 and 390 genes that exhibited >5-fold upregulation and downregulation, respectively, in primary USPC when compared to NEC. Many of the genes upregulated in USPC were found to represent adhesion molecules, secreted proteins and oncogenes, such as L1 cell adhesion molecule, claudin-3 and claudin-4, kallikrein 6 (protease M) and kallikrein 10 (NES1), interleukin-6 and c-erbB2. Downregulated genes in USPC included SEMACAP3, ras homolog gene family, member I (ARHI), and differentially downregulated in ovarian carcinoma gene 1. Quantitative RT-PCR was used to validate differences in gene expression between USPC and NEC for several of these genes. Owing to its potential as a novel therapeutic marker, expression of the high-affinity epithelial receptor for Clostridium perfringens enterotoxin (CPE) claudin-4 was further validated through immunohistochemical analysis of formalin-fixed paraffin-embedded specimens from which the primary USPC cultures were obtained, as well as an independent set of archival USPC specimens. Finally, the sensitivity of primary USPC to the administration of scalar doses of CPE in vitro was also demonstrated. Our results highlight the novel molecular features of USPC and provide a foundation for the development of new type-specific therapies against this highly aggressive variant of endometrial cancer.
 ...
PMID:Gene expression fingerprint of uterine serous papillary carcinoma: identification of novel molecular markers for uterine serous cancer diagnosis and therapy. 1578 48

Molecular targeted therapies represent an interesting field of pharmacological research in endometrial cancer. The loss of PTEN (phosphatase and tensin homolog deleted on chromosome 10) function, with consequent activation of the PI3K (phosphatidylinositol-3-kinase)-AKT (serine/threonine-specific protein kinase)-mTOR (mammalian target of rapamycin) signaling pathway, occurs in 32-83% of endometrioid-type endometrial carcinomas, thus suggesting a role for mTOR inhibition in this malignancy. Some analogues of rapamycin (CCI-799, RAD-001, AP-23573) have been developed and tested in different tumors including endometrioid-type endometrial carcinoma. For example, AP-23573 achieved a clinical benefit response in 33% of 27 heavily pretreated patients, and CCI-799 obtained a 26% partial response rate and a 63% stable disease rate in 19 patients. Overexpression of ErbB-2 (epidermal growth factor type II receptor) has been detected in 18-80% of uterine papillary serous carcinomas (UPSCs), thus providing a biological rationale for the use of trastuzumab in these aggressive tumors. UPSC often overexpresses claudin-3 and claudin-4, which represent the epithelial receptors for Clostridium perfringens enterotoxin (CPE). CPE-mediated therapy might be a novel treatment modality for UPSC resistant to chemotherapy. A better understanding of the signaling transduction pathways that are dysregulated in endometrioid-type endometrial carcinoma and UPSC will allow the development of novel molecular targeted therapies.
 ...
PMID:Molecular target therapies in endometrial cancer: from the basic research to the clinic. 1856 27

The number of patients with uterine endometrial carcinoma, the cause of which involves sex hormones, has recently been growing rapidly because of increases in life expectancy and obesity. Tight junction proteins claudin-3 and -4 are receptors of Clostridium perfringens enterotoxin (CPE) and increase during endometrial carcinogenesis. In the present study of normal human endometrial epithelial (HEE) cells and the uterus cancer cell line Sawano, we investigate changes in the expression of tight junction proteins including claudin-3 and -4, the fence and barrier functions of the tight junction and the cytotoxic effects of CPE by sex hormones. In primary cultured HEE cells, treatment with progesterone (P4) but not estradiol (E2), induced claudin-1, -3, -4 and -7 and occludin, together with the downregulation of the barrier function but not the fence function. In Sawano cells, claudin-3 and -4 were upregulated by E2 but not by P4, together with a disruption of both the barrier and fence function. In primary cultured HEE cells, claudin-3 and -4 were localized at the apicalmost regions (tight junction areas) and no cytotoxicity of CPE was observed. In Sawano cells, claudin-3 and -4 were found not only in the apicalmost regions but also at the basolateral membrane and the cytotoxicity of CPE was enhanced by E2. Thus, tight junctions are physiological regulated by sex hormones in normal HEE cells during the menstrual cycle suggesting that safer and more effective therapeutic methods targeting claudins in uterine cancer can be developed.
...
PMID:Regulation of tight junctions by sex hormones in normal human endometrial epithelial cells and uterus cancer cell line Sawano. 2382 Jul 35