Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1140680 (ovarian cancer)
 28,141 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chemotherapy (CT) resistance in ovarian cancer is related to multiple factors, and assessment of these factors is necessary for the development of new drugs and therapeutic regimens. In an effort to identify such determinants, we evaluated the expression of approximately 21,000 genes using DNA microarray screening in paired tumor samples taken prior to and after CT treatment from 6 patients with predominantly advanced stage, high-grade epithelial ovarian cancer. A subset of differentially expressed genes was selected from all microarray data by initial filtering on confidence at p=0.05, followed by filtering on expression level (>or=2-fold). Using these selection criteria, we found 121 genes to be commonly up-regulated and 54 genes to be down-regulated in the post-CT tumors, compared to primary tumors. Up-regulated genes in post-CT tumors included substantial number of genes with previously known implication in mechanisms of chemoresistance (TOP2A, ETV4, ABCF2, PRDX2, COX2, COX7B, MUC1, MT3, MT2A), and tumorigenesis (SCGB2A2, S100A9, YWHAE, SFN, ATP6AP1, MGC5528, ASS, TACC3, ARHGAP4, SRA1; MGC35136, PSAP, SPTAN1, LGALS3BP, TUBA4, AMY2B, PPIA, COX1, GRB2, CTSL). Down-regulated genes in post-CT samples mostly included genes implicated in chemosensitivity (GRP, TRA1, ADPRTL1, TRF4-2), cell proliferation and cell cycle control (NGFRAP1, TPD52L1, TAX1BP1) and tumor suppression and apoptosis (SMOC2, TIMP3, AXIN1, CASP4, P53SCV). Additionally, gene clustering analysis revealed the existence of two distinct expression signatures of chemoresistant tumors, which was further confirmed by assessment of some genetic (p53 gene mutation status) and clinical parameters (CT regimens). Our data suggest that intrinsic and acquired chemoresistant phenotypes of post-CT tumors may be attributed to the combined action of different factors implicated in mechanisms of chemoresistance, tumor invasion/progression and control of cell proliferation. This type of molecular profiling could have important clinical implications in resolving chemoresistance and the development of novel treatment strategies designed to prevent its emergence.
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PMID:Gene expression profiling of paired ovarian tumors obtained prior to and following adjuvant chemotherapy: molecular signatures of chemoresistant tumors. 1677 80

Previously, we reported that ABCF2 protein expression is higher in clear cell than serous histotype of ovarian adenocarcinomas and that its expression correlates with chemoresponse in patients with clear cell ovarian cancer. In this study, we examined ABCF2 protein expression in mucinous, endometrioid, and poorly differentiated type of ovarian adenocarcinomas. In addition, ABCF2 expression was evaluated in clear cell adenocarcinomas derived from different organs. A total of 335 epithelial ovarian cancers, 23 clear cell adenocarcinomas of uterine corpus, and 34 clear cell adenocarcinomas of kidney were included in this study. ABCF2 protein expression was determined by immunohistochemistry. The results showed that cytoplasmic ABCF2 expression was significantly higher in clear cell-type ovarian cancer specimens compared with other types (P < .0001). There was a close relationship between nuclear ABCF2 expression levels and age of patients with clear cell ovarian cancer. Multivariate logistic regression model also demonstrated that cytoplasmic ABCF2 expression was associated with clear cell histology (odds ratio, 5.557; 95% confidence interval, 2.694-11.462; P < .0001). In addition, both clear cell adenocarcinomas of the ovary and the uterine corpus showed significantly higher levels of ABCF2 expression, compared with those of the clear cell adenocarcinoma of the kidney (P < .0001). These data suggest that ABCF2 protein may be a candidate marker for clear cell adenocarcinomas of the ovary and the uterine corpus and may be important for the pathogenesis of these diseases.
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PMID:Differential expression of ABCF2 protein among different histologic types of epithelial ovarian cancer and in clear cell adenocarcinomas of different organs. 1699 67

Previously, we have demonstrated that NRF2 plays a key role in mediating cisplatin resistance in ovarian cancer. To further explore the mechanism underlying NRF2-dependent cisplatin resistance, we stably overexpressed or knocked down NRF2 in parental and cisplatin-resistant human ovarian cancer cells, respectively. These two pairs of stable cell lines were then subjected to microarray analysis, where we identified 18 putative NRF2 target genes. Among these genes, ABCF2, a cytosolic member of the ABC superfamily of transporters, has previously been reported to contribute to chemoresistance in clear cell ovarian cancer. A detailed analysis on ABCF2 revealed a functional antioxidant response element (ARE) in its promoter region, establishing ABCF2 as an NRF2 target gene. Next, we investigated the contribution of ABCF2 in NRF2-mediated cisplatin resistance using our stable ovarian cancer cell lines. The NRF2-overexpressing cell line, containing high levels of ABCF2, was more resistant to cisplatin-induced apoptosis compared to its control cell line; whereas the NRF2 knockdown cell line with low levels of ABCF2, was more sensitive to cisplatin treatment than its control cell line. Furthermore, transient overexpression of ABCF2 in the parental cells decreased apoptosis and increased cell viability following cisplatin treatment. Conversely, knockdown of ABCF2 using specific siRNA notably increased apoptosis and decreased cell viability in cisplatin-resistant cells treated with cisplatin. This data indicate that the novel NRF2 target gene, ABCF2, plays a critical role in cisplatin resistance in ovarian cancer, and that targeting ABCF2 may be a new strategy to improve chemotherapeutic efficiency.
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PMID:ABCF2, an Nrf2 target gene, contributes to cisplatin resistance in ovarian cancer cells. 2811 39