“Pancreatic cancer is an aggressive malignancy with a characteristic metastatic course of disease and resistance to conventional radiotherapy. As a result, the continual development of novel therapeutic agents is required to improve the current situation. In the present study, the effect of the hedgehog pathway inhibitor, cyclopamine, on cellular radiosensitivity was determined in K-RAS(wt) Colo-357 and K-RAS(mt) SW-1990 human pancreatic cancer cell lines using the clonogenic survival assay. Apoptosis
and cell cycle distribution were detected using flow cytometry assay. Following irradiation (30 mins), residual double-strand breaks were quantified by identification of gamma-H2AX foci of micronuclei and radiation-induced gamma-H2AX, p-ATM, DNA-PKcs and Ku70 expression was analyzed using western blot analysis. The selleck epidermal growth factor (EGF) and EGF receptor (EGFR) inhibitor, gefitinib, were utilized to determine the related mechanisms. The results revealed that cyclopamine treatment significantly reduced cell clonogenic survival but failed to induce apoptosis and radiation-induced G2 arrest. Flow cytometry revealed that cyclopamine treatment enhanced gamma-H2AX foci in Colo-357 and SW-1990 cells exposed to irradiation. In addition, radiation-induced p-ATM,
DNA-PKcs and Ku70 were all inhibited. EGF also rescued pancreatic cancer cells from cyclopamine-induced H2AX phosphorylation following irradiation. Thus, cyclopamine enhanced the radiosensitivity learn more AZD7762 of human pancreatic cancer cells, in part, through an EGFR-dependent pathway, indicating
a rational approach in combination with radiotherapy.”
“Background: Radiofrequency ablation (RFA) is a thermal energy delivery system used for coagulative cellular destruction of small tumors through percutaneous or intraoperative application of its needle electrode to the target area, and for assisting partial resection of liver and kidney. We tried to evaluate the regional oxidative and pre-inflammatory stress of RFA-assisted wedge lung resection, by measuring the MDA and tumor Necrosis Factor Alpha (TNF-alpha) concentration in the resected lung tissue of a swine model.\n\nMethod: Fourteen white male swines, divided in two groups, the RFA-group and the control group (C-group) underwent a small left thoracotomy and wedge lung resection of the lingula. The wedge resection in the RFA-group was performed using the RFA technique whereas in C-group the simple “cut and sew” method was performed. We measured the malondialdehyde (MDA) and TNF-alpha concentration in the resected lung tissue of both groups.\n\nResults: In C-group the MDA mean deviation rate was 113 +/- 42.6 whereas in RFA-group the MDA mean deviation rate was significantly higher 353 +/- 184 (p = 0.006).