AIM: To investigate the role of DNA-PKcs subunits inradiosensitization by hyperthermia on hepatocellularcarcinoma HepG2 cell lines.METHODS: Hep G2 cells were exposed to hyperthermiaand irradiation. Hyperthermia was gi...AIM: To investigate the role of DNA-PKcs subunits inradiosensitization by hyperthermia on hepatocellularcarcinoma HepG2 cell lines.METHODS: Hep G2 cells were exposed to hyperthermiaand irradiation. Hyperthermia was given at 45.5 ℃Cellsurvival was determined by an in vitro clonogenic assay forthe cells treated with or without hyperthermia at varioustime points. DNA DSB rejoining was measured usingasymmetric field inversion gel electrophoresis (AFIGE). TheDNA-PKcs activities were measured using DNA-PKcs enzymeassay system.RESULTS: Hyperthermia can significantly enhanceirradiation-killing cells. Thermal enhancement ratio ascalculated at 10 % survival was 2.02. The difference inradiosensitivity between two treatment modes manifestedas a difference in the α components and the almost sameβ components, which α value was considerably higher inthe cells of combined radiation and hyperthermia ascompared with irradiating cells (1.07 Gy-1 versus 0.44 Gy1). Survival fraction showed 1 logarithm increase after an8-hour interval between heat and irradiation, whereas DNA-PKcs activity did not show any recovery. The cells wereexposed to heat 5 minutes only, DNA-PKcs activity wasinhibited at the nadir, even though the exposure time waslengthened. Whereas the ability of DNA DSB rejoining wasinhibited with the increase of the length of hyperthermictime. The repair kinetics of DNA DSB rejoining aftertreatment with Wortmannin is different from thehyperthermic group due to the striking high slow rejoiningcomponent.CONCLUSION: Determination with the cell extracts andthe peptide phosphorylation assay, DNA-PKcs activity wasinactivated by heat treatment at 45.5 C, and could notrestore. Cell survival is not associated with the DNA-PKcsinactivity after heat. DNA-PKcs is not a unique factor affectingthe DNA DSB repair. This suggests that DNA-PKcs do notplay a crucial role in the enhancement of cellularradiosensitivity by hyperthermia.展开更多
Several advances in diagnosis,treatment and palliation of cholangiocarcinoma(CC)have occurred in the last decades.A multidisciplinary approach to this disease is therefore recommended.CC is a relatively rare tumor and...Several advances in diagnosis,treatment and palliation of cholangiocarcinoma(CC)have occurred in the last decades.A multidisciplinary approach to this disease is therefore recommended.CC is a relatively rare tumor and the main risk factors are:chronic inflammation, genetic predisposition and congenital abnormalities of the biliary tree.While the incidence of intra-hepatic CC is increasing,the incidence of extra-hepatic CC is trending down.The only curative treatment for CC is surgical resection with negative margins.Liver transplantation has been proposed only for selected patients with hilar CC that cannot be resected who have no metastatic disease after a period of neoadjuvant chemo-radiation therapy.Magnetic resonance imaging/magnetic resonance cholangiopancreatography,positron emission tomography scan,endoscopic ultrasound and computed tomography scans are the most frequently used modalities for diagnosis and tumor staging.Adjuvant therapy,palliative chemotherapy and radiotherapy have been relatively ineffective for inoperable CC.For most of these patients biliary stenting provides effective palliation.Photodynamic therapy is an emerging palliative treatment that seems to provide pain relief,improve biliary patency and increase survival. The clinical utility of other emerging therapies such as transarterial chemoembolization,hepatic arterial chemoinfusion and high intensity intraductal ultrasound needs further study.展开更多
文摘AIM: To investigate the role of DNA-PKcs subunits inradiosensitization by hyperthermia on hepatocellularcarcinoma HepG2 cell lines.METHODS: Hep G2 cells were exposed to hyperthermiaand irradiation. Hyperthermia was given at 45.5 ℃Cellsurvival was determined by an in vitro clonogenic assay forthe cells treated with or without hyperthermia at varioustime points. DNA DSB rejoining was measured usingasymmetric field inversion gel electrophoresis (AFIGE). TheDNA-PKcs activities were measured using DNA-PKcs enzymeassay system.RESULTS: Hyperthermia can significantly enhanceirradiation-killing cells. Thermal enhancement ratio ascalculated at 10 % survival was 2.02. The difference inradiosensitivity between two treatment modes manifestedas a difference in the α components and the almost sameβ components, which α value was considerably higher inthe cells of combined radiation and hyperthermia ascompared with irradiating cells (1.07 Gy-1 versus 0.44 Gy1). Survival fraction showed 1 logarithm increase after an8-hour interval between heat and irradiation, whereas DNA-PKcs activity did not show any recovery. The cells wereexposed to heat 5 minutes only, DNA-PKcs activity wasinhibited at the nadir, even though the exposure time waslengthened. Whereas the ability of DNA DSB rejoining wasinhibited with the increase of the length of hyperthermictime. The repair kinetics of DNA DSB rejoining aftertreatment with Wortmannin is different from thehyperthermic group due to the striking high slow rejoiningcomponent.CONCLUSION: Determination with the cell extracts andthe peptide phosphorylation assay, DNA-PKcs activity wasinactivated by heat treatment at 45.5 C, and could notrestore. Cell survival is not associated with the DNA-PKcsinactivity after heat. DNA-PKcs is not a unique factor affectingthe DNA DSB repair. This suggests that DNA-PKcs do notplay a crucial role in the enhancement of cellularradiosensitivity by hyperthermia.
文摘Several advances in diagnosis,treatment and palliation of cholangiocarcinoma(CC)have occurred in the last decades.A multidisciplinary approach to this disease is therefore recommended.CC is a relatively rare tumor and the main risk factors are:chronic inflammation, genetic predisposition and congenital abnormalities of the biliary tree.While the incidence of intra-hepatic CC is increasing,the incidence of extra-hepatic CC is trending down.The only curative treatment for CC is surgical resection with negative margins.Liver transplantation has been proposed only for selected patients with hilar CC that cannot be resected who have no metastatic disease after a period of neoadjuvant chemo-radiation therapy.Magnetic resonance imaging/magnetic resonance cholangiopancreatography,positron emission tomography scan,endoscopic ultrasound and computed tomography scans are the most frequently used modalities for diagnosis and tumor staging.Adjuvant therapy,palliative chemotherapy and radiotherapy have been relatively ineffective for inoperable CC.For most of these patients biliary stenting provides effective palliation.Photodynamic therapy is an emerging palliative treatment that seems to provide pain relief,improve biliary patency and increase survival. The clinical utility of other emerging therapies such as transarterial chemoembolization,hepatic arterial chemoinfusion and high intensity intraductal ultrasound needs further study.
