Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0268140 (XPF)
 549 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously observed that the mRNA of selected genes involved in nucleotide excision repair appear to be coordinately expressed in human tissues from patients with ovarian cancer, testicular cancer, malignant brain tumors, and other malignancies. Such genes include ERCC1, XPA, XPB, XPD, XPF, and XPG. Coordinate mRNA expression appears to be most impressive in non-malignant tissues. We therefore began to explore possible reasons why such coordinate expression should occur. DNA sequences for the above noted genes were obtained from GeneBank. Two different software programs were applied to the DNA sequence, to the area 5' to the start of exon I of each gene. Analyses were performed by computer. The length of the 5' area assessed, was based on previous reports that determined what portion of the genomic sequence comprised the 5' UTR of the promoter of the respective gene. Based on this approach, potential DNA binding sites for no less than three dozen proteins, were identified in the 5'-flanking region of each of the NER genes studied. For each gene, potential binding sites for activator proteins and for repressor proteins were identified. The 5'-flanking regions for each gene noted above, had binding sites in common for 14 proteins with transcription modulatory activity. Eleven of these proteins are known for activator activity; two are reported to have repressor activity, and one has both repressor and activator function. These data suggest a possible molecular basis for the previously observed coordinate mRNA expression of selected NER genes in human tissue specimens.
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PMID:Computer based analyses of the 5'-flanking regions of selected genes involved in the nucleotide excision repair complex. 1089 49

Human renal cancer is extremely resistant to chemotherapy and radiation therapy. This clinical characteristic reduces the efficacy of chemotherapeutic agents in the treatment of recurrence or metastasis following surgical resection. Understanding the mechanism of chemotherapy resistance in renal cell carcinoma remains a significant challenge. In this study, we have shown that varied level of XPF expression was organ-tissue specific by comparing human renal cancer, bladder cancer, testicular cancer and their normal tissue counterparts, respectively. The expression of XPF was significantly higher in renal cancer than in bladder cancer and testicular cancer and correlated with the clinical characteristic of their chemotherapeutics sensitivity. These novel findings proposed that the intrinsic chemoresistance of human renal cell carcinomas might be derived from the high level of XPF expression. In a panel of five cancer cell lines, decreasing cisplatin sensitivity correlated with increasing levels of XPF expression. Knockdown of XPF expression not only increased sensitivity of renal carcinoma cells to cisplatin treatment by affecting the DNA damage response, including DNA repair, cell cycle regulation and apoptosis, but also increased senescence of renal cancer cell. Furthermore, experiment in vivo confirmed that silenced XPF significantly increased the sensitivity and survival following treatment with cisplatin in xenograft mice bearing renal cell tumor. These findings firstly uncover a partial mechanism of intrinsic chemoresistance in renal cancer and may provide a new approach to break through the obstacle of intrinsic chemoresistance by targeting the XPF protein with a potential new inhibitor.
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PMID:Higher expression of XPF is a critical factor in intrinsic chemotherapy resistance of human renal cell carcinoma. 2754 41