báo cáo hóa học:" Sodium arsenite and hyperthermia modulate cisplatin-DNA damage responses and enhance platinum accumulation in murine metastatic ovarian cancer xenograft after hyperthermic intraperitoneal chemotherapy (HIPEC)"

Tuyển tập các báo cáo nghiên cứu về hóa học được đăng trên tạp chí sinh học quốc tế đề tài : Sodium arsenite and hyperthermia modulate cisplatin-DNA damage responses and enhance platinum accumulation in murine metastatic ovarian cancer xenograft after hyperthermic intraperitoneal chemotherapy (HIPEC) | Muenyi et al. Journal of Ovarian Research 2011 4 9 http content 4 1 9 RESEARCH JOURNAL OF OVARIAN RESEARCH Open Access Sodium arsenite and hyperthermia modulate cisplatin-DNA damage responses and enhance platinum accumulation in murine metastatic ovarian cancer xenograft after hyperthermic intraperitoneal chemotherapy HIPEC I- r I r r c l li I M r Ì1 su s A c 4 4 Z r 1 I wx r A I I I_I K l r-t rr 1 I z rz r Ạ E ì 2 3 4 5 6 A ìllìnv í I_IS-. I rn 7 z l Clarisse S Muenyi Vanessa A States Joshua H Masters leresa W ran C William Helm ana J Christopher States1 4 5 6 Abstract Background Epithelial ovarian cancer EOC is the leading cause of gynecologic cancer death in the USA. Recurrence rates are high after front-line therapy and most patients eventually die from platinum Pt - resistant disease. Cisplatin resistance is associated with increased nucleotide excision repair NER decreased mismatch repair MMR and decreased platinum uptake. The objective of this study is to investigate how a novel combination of sodium arsenite NaAsO2 and hyperthermia 43 C affect mechanisms of cisplatin resistance in ovarian cancer. Methods We established a murine model of metastatic EOC by intraperitoneal injection of A2780 CP70 human ovarian cancer cells into nude mice. We developed a murine hyperthermic intraperitoneal chemotherapy model to treat the mice. Mice with peritoneal metastasis were perfused for 1 h with 3 mg kg cisplatin 26 mg kg NaAsO2 at 37 or 43 C. Tumors and tissues were collected at 0 and 24 h after treatment. Results Western blot analysis of p53 and key NER proteins ERCC1 XPC and XPA and MMR protein MSH2 suggested that cisplatin induced p53 XPC and XPA and suppressed MSH2 consistent with resistant phenotype. Hyperthermia suppressed cisplatin-induced XPC and prevented the induction of XPA by cisplatin but it had no effect on Pt uptake or retention in tumors. NaAsO2 prevented XPC induction by cisplatin it maintained higher levels of MSH2 in tumors and

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