目的探讨Ku70蛋白表达与前列腺癌Gleason评分及前列腺特异抗原(prostate specific antigen,PSA)的关系。方法采用HE染色观察组织学形态,免疫组化SP法检测前列腺癌组织中Ku70蛋白表达,按前列腺癌Gleason评分和血清PSA值分组,比较各组间K...目的探讨Ku70蛋白表达与前列腺癌Gleason评分及前列腺特异抗原(prostate specific antigen,PSA)的关系。方法采用HE染色观察组织学形态,免疫组化SP法检测前列腺癌组织中Ku70蛋白表达,按前列腺癌Gleason评分和血清PSA值分组,比较各组间Ku70蛋白表达水平。结果 58例前列腺癌标本中Ku70蛋白均呈阳性表达,其表达强度与前列腺癌Gleason评分和血清PSA呈明显负相关。结论 Ku70蛋白表达水平能帮助判断前列腺癌预后及评价治疗效果,可用于临床指导个体化治疗。展开更多
BACKGROUND： Recent studies have shown that the selective inhibitor of c-Jun N-terminal kinases （JNKs） signaling pathway, SP600125, exhibits neuronal protective effects in a rat model of brain ischemia/reperfusion. ...BACKGROUND： Recent studies have shown that the selective inhibitor of c-Jun N-terminal kinases （JNKs） signaling pathway, SP600125, exhibits neuronal protective effects in a rat model of brain ischemia/reperfusion. OBJECTIVE： To determine the mechanisms of neuroprotective effects of SP600125 in a rat model of brain ischemia/reperfusion, and determine the role of the JNK signaling pathway in SP600125-induced effects. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Animal Experiment Center, Medical School of Xi＇an Jiaotong University from June 2007 to September 2008. MATERIALS： SP600125 was provided by Biosource, USA; rabbit anti-phospho-JNK （Thr183/Tyr185） polyclonal antibody from Cell Signaling Technology, USA; rabbit anti-X-ray repair cross-complementing protein 1 （XRCC1） and anti-Ku70 polyclonal antibodies from Santa Cruz Biotechnology, USA; and TUNEL kit from Beijing Huamei Biology, China. METHODS： A total of 108 male, 4-month-old, Sprague Dawley rats were randomly assigned to three groups, with 36 rats per group. The sham operation group and ischemia/reperfusion group （I/R group） were intracerebroventricularly injected with 10 μL 1% DMSO. The SP600125-treated group （pre-SP group） was given 10 μL SP600125 （3 μg/μL）. Thirty minutes later, brain ischemia was induced in the I/R and pre-SP groups using the four-vessel occlusion method. Specifically, whole brain ischemia was induced for 6 minutes, and the clips were released to restore carotid artery blood flow. Rats from each group were observed at 2, 6, 12, 24, 48, and 72 hours, with 6 rats for each time point. The sham operation group was treated with the same surgical exposure procedures, with exception of occlusion of the carotid artery. MAIN OUTCOME MEASURES： Hematoxylin-eosin staining was used to observe neuronal survival in the hippocampal CA1 region, TUNEL was used to detect apoptosis in the hippocampal CA1 region, and immunohistochemistry was used to detect expression of phospho-JNK, XRCC1, and Ku70. RESULTS： Following brain ischemia/reperfusion, neuronal survival significantly decreased, and the number of apoptotic cells significantly increased （P 〈 0.01）. Compared with the I/R group, neuronal survival significantly increased in the pre-SP group, and the number of apoptotic cells significantly decreased （P 〈 0.01）. Expression of phospho-JNK increased, and XRCC1 and Ku70 significantly decreased （P 〈 0.05） following ischemia/reperfusion. Compared with the I/R group, expression of phospho-JNK decreased, and XRCC1 and Ku70 significantly increased in the pre-SP group （P 〈 0.05）. Correlation analysis revealed an inverse correlation between phospho-JNK gray value and XRCC1 and Ku70 gray values in the hippocampal CA1 region （r = -0.983, -0.953, P 〈 0.01）. CONCLUSION： SP600125 treatment decreased apoptosis induced by global brain ischemia/reperfusion in the rat hippocampal CA1 region. Results suggested that the neuroprotective effects were due to inhibited phosphorylation of JNK and reduced down-regulation of XRCC1 and Ku70.展开更多
AIM:To determine the expression of the catalytic subunit of DNA-dependent protein kinase(DNA-PKcs)and the Ku70/Ku80 heterodimer(Ku 70/80)in gastric carcinoma.METHODS:Gastric biopsies were obtained from 146gastric carc...AIM:To determine the expression of the catalytic subunit of DNA-dependent protein kinase(DNA-PKcs)and the Ku70/Ku80 heterodimer(Ku 70/80)in gastric carcinoma.METHODS:Gastric biopsies were obtained from 146gastric carcinoma patients[Helicobacter pylori(H.pylori)-negative:89 and H.pylori-positive:57]and 34from normal subjects(H.pylori-negative:16 and H.pylori-positive:18)via surgery and endoscopic detection from April 2011 to August 2012 at the First Affiliated Hospital of Nanchang University.Pathological diagnosis and classification were made according to the criteria of the World Health Organization and the updated Sydney system.An‘‘in-house’’rapid urease test and modified Giemsa staining were employed to detect H.pylori infection.The expression of DNA-PKcs and the Ku 70/80protein was detected by immunohistochemistry.RESULTS:Overall,the positive rates of both DNA-PKcs and Ku 70/80 were significantly increased in gastric cancer(χ2=133.04,P<0.001 for DNA-PKcs andχ2=13.06,P<0.01 for Ku)compared with normal gastric mucosa.There was hardly any detectable expression of DNA-PKcs in normal gastric mucosa,and the positive rate of DNA-PKcs protein expression in patients with a normal gastric mucosa was 0%(0/34),whereas the rate in gastric cancer(GC)was 93.8%(137/146).The difference between the two groups was statistically significant.Additionally,the positive rate of Ku 70/80 was79.4%(27/34)in normal gastric mucosa and 96.6%(141/146)in gastric cancer.The DNA-PKcs protein level was significantly increased in gastric cancer(MannWhitney U=39.00,P<0.001),compared with normal gastric mucosa.In addition,there was a significant difference in the expression of Ku 70/80(Mann-Whitney U=1117.00,P<0.001)between gastric cancer and normal gastric mucosa.There was also a significant difference in Ku70/80 protein expression between GC patients with and without H.pylori infection(P<0.05).Spearman analysis showed a negative correlation between tumor differentiation and DNA-PKcs expression(r=-0.447,P<0.05).Moreover,Ku70/80 expression was negatively correlated with both clinical stage(r=-0.189,P<0.05)and H.pylori colonization(r=-0.168,P<0.05).CONCLUSION:Overall,this research demonstrated that enhanced DNA-PKcs and Ku 70/80 expression may be closely associated with gastric carcinoma.展开更多
文摘目的探讨Ku70蛋白表达与前列腺癌Gleason评分及前列腺特异抗原(prostate specific antigen,PSA)的关系。方法采用HE染色观察组织学形态,免疫组化SP法检测前列腺癌组织中Ku70蛋白表达,按前列腺癌Gleason评分和血清PSA值分组,比较各组间Ku70蛋白表达水平。结果 58例前列腺癌标本中Ku70蛋白均呈阳性表达,其表达强度与前列腺癌Gleason评分和血清PSA呈明显负相关。结论 Ku70蛋白表达水平能帮助判断前列腺癌预后及评价治疗效果,可用于临床指导个体化治疗。
基金Supported by: the National Natural Science Foundation of China, No. 30571790
文摘BACKGROUND： Recent studies have shown that the selective inhibitor of c-Jun N-terminal kinases （JNKs） signaling pathway, SP600125, exhibits neuronal protective effects in a rat model of brain ischemia/reperfusion. OBJECTIVE： To determine the mechanisms of neuroprotective effects of SP600125 in a rat model of brain ischemia/reperfusion, and determine the role of the JNK signaling pathway in SP600125-induced effects. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Animal Experiment Center, Medical School of Xi＇an Jiaotong University from June 2007 to September 2008. MATERIALS： SP600125 was provided by Biosource, USA; rabbit anti-phospho-JNK （Thr183/Tyr185） polyclonal antibody from Cell Signaling Technology, USA; rabbit anti-X-ray repair cross-complementing protein 1 （XRCC1） and anti-Ku70 polyclonal antibodies from Santa Cruz Biotechnology, USA; and TUNEL kit from Beijing Huamei Biology, China. METHODS： A total of 108 male, 4-month-old, Sprague Dawley rats were randomly assigned to three groups, with 36 rats per group. The sham operation group and ischemia/reperfusion group （I/R group） were intracerebroventricularly injected with 10 μL 1% DMSO. The SP600125-treated group （pre-SP group） was given 10 μL SP600125 （3 μg/μL）. Thirty minutes later, brain ischemia was induced in the I/R and pre-SP groups using the four-vessel occlusion method. Specifically, whole brain ischemia was induced for 6 minutes, and the clips were released to restore carotid artery blood flow. Rats from each group were observed at 2, 6, 12, 24, 48, and 72 hours, with 6 rats for each time point. The sham operation group was treated with the same surgical exposure procedures, with exception of occlusion of the carotid artery. MAIN OUTCOME MEASURES： Hematoxylin-eosin staining was used to observe neuronal survival in the hippocampal CA1 region, TUNEL was used to detect apoptosis in the hippocampal CA1 region, and immunohistochemistry was used to detect expression of phospho-JNK, XRCC1, and Ku70. RESULTS： Following brain ischemia/reperfusion, neuronal survival significantly decreased, and the number of apoptotic cells significantly increased （P 〈 0.01）. Compared with the I/R group, neuronal survival significantly increased in the pre-SP group, and the number of apoptotic cells significantly decreased （P 〈 0.01）. Expression of phospho-JNK increased, and XRCC1 and Ku70 significantly decreased （P 〈 0.05） following ischemia/reperfusion. Compared with the I/R group, expression of phospho-JNK decreased, and XRCC1 and Ku70 significantly increased in the pre-SP group （P 〈 0.05）. Correlation analysis revealed an inverse correlation between phospho-JNK gray value and XRCC1 and Ku70 gray values in the hippocampal CA1 region （r = -0.983, -0.953, P 〈 0.01）. CONCLUSION： SP600125 treatment decreased apoptosis induced by global brain ischemia/reperfusion in the rat hippocampal CA1 region. Results suggested that the neuroprotective effects were due to inhibited phosphorylation of JNK and reduced down-regulation of XRCC1 and Ku70.
基金Supported by The National natural science foundation of China,No.81270479
文摘AIM:To determine the expression of the catalytic subunit of DNA-dependent protein kinase(DNA-PKcs)and the Ku70/Ku80 heterodimer(Ku 70/80)in gastric carcinoma.METHODS:Gastric biopsies were obtained from 146gastric carcinoma patients[Helicobacter pylori(H.pylori)-negative:89 and H.pylori-positive:57]and 34from normal subjects(H.pylori-negative:16 and H.pylori-positive:18)via surgery and endoscopic detection from April 2011 to August 2012 at the First Affiliated Hospital of Nanchang University.Pathological diagnosis and classification were made according to the criteria of the World Health Organization and the updated Sydney system.An‘‘in-house’’rapid urease test and modified Giemsa staining were employed to detect H.pylori infection.The expression of DNA-PKcs and the Ku 70/80protein was detected by immunohistochemistry.RESULTS:Overall,the positive rates of both DNA-PKcs and Ku 70/80 were significantly increased in gastric cancer(χ2=133.04,P<0.001 for DNA-PKcs andχ2=13.06,P<0.01 for Ku)compared with normal gastric mucosa.There was hardly any detectable expression of DNA-PKcs in normal gastric mucosa,and the positive rate of DNA-PKcs protein expression in patients with a normal gastric mucosa was 0%(0/34),whereas the rate in gastric cancer(GC)was 93.8%(137/146).The difference between the two groups was statistically significant.Additionally,the positive rate of Ku 70/80 was79.4%(27/34)in normal gastric mucosa and 96.6%(141/146)in gastric cancer.The DNA-PKcs protein level was significantly increased in gastric cancer(MannWhitney U=39.00,P<0.001),compared with normal gastric mucosa.In addition,there was a significant difference in the expression of Ku 70/80(Mann-Whitney U=1117.00,P<0.001)between gastric cancer and normal gastric mucosa.There was also a significant difference in Ku70/80 protein expression between GC patients with and without H.pylori infection(P<0.05).Spearman analysis showed a negative correlation between tumor differentiation and DNA-PKcs expression(r=-0.447,P<0.05).Moreover,Ku70/80 expression was negatively correlated with both clinical stage(r=-0.189,P<0.05)and H.pylori colonization(r=-0.168,P<0.05).CONCLUSION:Overall,this research demonstrated that enhanced DNA-PKcs and Ku 70/80 expression may be closely associated with gastric carcinoma.
