AIM:To elucidate high mobility group-box 3(HMGB3) protein expression in gastric adenocarcinoma,its potential prognostic relevance,and possible mechanism of action.METHODS:Ninety-two patients with gastric adenocarcinom...AIM:To elucidate high mobility group-box 3(HMGB3) protein expression in gastric adenocarcinoma,its potential prognostic relevance,and possible mechanism of action.METHODS:Ninety-two patients with gastric adenocarcinomas surgically removed entered the study.HMGB3 expression was determined by immunohistochemistry through a tissue microarray procedure.The clinicopathologic characteristics of all patients were recorded,and regular follow-up was made for all patients.The inter-relationship of HMGB3 expression with histological and clinical factors was analyzed using nonparametric tests.Survival analysis was carried out by Kaplan-Meier(log-rank) and multivariate Cox(Forward LR) analyses between the group with overexpression of HMGB3 and the group with low or no HMGB3 ex-pression to determine the prognosis value of HMGB3 expression on overall survival.Further,HMGB3 expression was knocked down by small hairpin RNAs(shRNAs) in the human gastric cancer cell line BGC823 to observe its influence on cell biological characteristics.The MTT method was utilized to detect gastric cancer cell proliferation changes,and cell cycle distribution was analyzed by flow cytometry.RESULTS:Among 92 patients with gastric adenocarcinomas surgically removed in this study,high HMGB3 protein expression was detected in the gastric adenocarcinoma tissues vs peritumoral tissues(P < 0.001).Further correlation analysis with patients' clinical and histology variables revealed that HMGB3 overexpression was obviously associated with extensive wall penetration(P = 0.005),a positive nodal status(P = 0.004),and advanced tumor-node-metastasis(TNM) stage(P = 0.001).But there was no correlation between HMGB3 overexpression and the age and gender of the patient,tumor localization or histologic grade.Statistical Kaplan-Meier survival analysis disclosed significant differences in overall survival between the HMGB3 overexpression group and the HMGB3 no or low expression group(P = 0.006).The expected overall survival time was 31.00 ± 3.773 mo(95%CI = 23.605-38.395) for patients with HMGB3 overexpression and 49.074 ± 3.648 mo(95%CI = 41.925-57.311) for patients with HMGB3 no and low-level expression.Additionally,older age(P = 0.040),extensive wall penetration(P = 0.008),positive lymph node metastasis(P = 0.005),and advanced TNM tumor stage(P = 0.007) showed negative correlation with overall survival.Multivariate Cox regression analysis indicated that HMGB3 overexpression was an independent variable with respect to age,gender,histologic grade,extent of wall penetration,lymph nodal metastasis,and TNM stage for patients with resectable gastric adenocarcinomas with poor prognosis(hazard ratio = 2.791,95%CI = 1.233-6.319,P = 0.019).In the gene function study,after HMGB3 was knocked down in the gastric cell line BGC823 by shRNA,the cell proliferation rate was reduced at 24 h,48 h and 72 h.Compared to BGC823 shRNA-negative control(NC) cells,the cell proliferation rate in cells that had HMGB3 shRNA transfected was significantly decreased(P < 0.01).Finally,cell cycle analysis by FACS showed that BGC823 cells that had HMGB3 knocked down were blocked in G1/G0 phase.The percentage of cells in G1/G0 phase in BGC823 cells with shRNA-NC and with shRNA-HMGB3 was 46.84% ± 1.7%,and 73.03% ± 3.51% respectively(P = 0.001),whereas G2/M cells percentage decreased from 26.51% ± 0.83% to 17.8% ± 2.26%.CONCLUSION:HMGB3 is likely to be a useful prognostic marker involved in gastric cancer disease onset and progression by regulating the cell cycle.展开更多
AIM:To determine the incidence of human epidermal growth factor receptor 2(HER2) over expression in oesophageal cancers.METHODS:A retrospective study,of one hundred consecutive cases of endoscopic histological samples...AIM:To determine the incidence of human epidermal growth factor receptor 2(HER2) over expression in oesophageal cancers.METHODS:A retrospective study,of one hundred consecutive cases of endoscopic histological samples of oesophageal cancers from a single British cancer network were included.Cancer cases were diagnosed between April 2007 and June 2010.HER2 over expression was assessed using immunohistochemistry,those that scored "0" and "+1" were considered "negative" for HER2;those that scored "+3" were considered "Positive".Cases that were scored "+2" on immunohistochemistry further went on to have HER2 gene analysis using the Ventana HER brightfield dual-colourin situ hybridisations(HER B DISH) assay and either came back to be positive or negative for HER2 over expression.Overall survival was measured from date of histological diagnosis until date of death.93% of the cases were followed up till five years or death,and all were followed up till two years.Cases of gastro-oesophageal junctional tumours were excluded.RESULTS:The median age of our sample was 66 years(range:38-91 years).Eighty one were male and 19 female.Ninety-one of the cases were adenocarcinoma of the oesophagus and the rest were cases of squamous cell carcinoma.The anatomical distribution of the tumours was;upper oesophagus 2,middle oesophagus 11,and 87 were in the lower oesophagus.Operative resection was completed in 15 cases;seven cases had attempted surgical resections,i.e.,open and close,33 patients received definitive chemo-radiation and 52 had palliative treatment.Twenty-five of the cancers showed evidence of HER2 over expression,all were adenocarcinomas.Of the 25 cases that showed evidence of HER2 over expression,21(84%) were located in the lower third of the oesophagus.On staging,24 out of the 25 HER2 positive cases were at stage 3 or more(13 at stage 3 and 11 at stage 4),For HER2 negative cases 37 were at stage 3 and 32 were staged as stage 4.Seventeen out of twenty five cases(68%) with HER2 over expression received palliative therapy,in comparison to thirty five out of seventy five(46.7%) in tumours not expressing HER2.No significant difference in overall survival was demonstrated between patients whose cancers showed evidence of HER2 over expression and those who did not;median overall survival for HER2 positive tumours was 15 mo(95%CI,11-19 mo) compared to 13 mo(95%CI,9-17 mo) for HER2 negative ones.Two years cumulative survival for cases with HER2 over expression was 33.7% compared to 31.6% in cases without HER2 over expression(P = 0.576).Only cancer's stage significantly affected overall survival on both univariant and multivariable analysis(P = 0.034 and P = 0.009 respectively).None of the patients included in this study received Trastuzumab.CONCLUSION:Twenty-seven point five percent of oesophageal adenocarcinomas showed evidence of HER2 over expression.Routine testing for human HER2 in oesophageal adenocarcinomas can have significant implication on treatments offered to patients that may potentially affect their prognosis.展开更多
To improve the efficiency of operating rooms, reduce the hospital' s costs and improve the level of service qualities, a scheduling method is presented based on a filtered-beam-search-based algo- rithm. Firstly, a sc...To improve the efficiency of operating rooms, reduce the hospital' s costs and improve the level of service qualities, a scheduling method is presented based on a filtered-beam-search-based algo- rithm. Firstly, a scheduling problem domain is described. Mathematical programming models are al- so set up with an objective function of minimizing related costs of the system. On the basis of the de= scriptions mentioned above, a solving policy of generating feasible scheduling solutions is estab- lished. Combining with the speeific constraints of operation theatres, a filtered-beam-search-based algorithm is put forward to solve scheduling problems. Finally, simulation experiments are designed. The performance of the proposed algorithm is evaluated and compared with that of other approaches through simulations. Results indicate that the proposed algorithm can reduce costs, and are of prac- ticality and effectiveness.展开更多
基金Supported by Zhenjiang Science and Technology Bureau,No. SH2010016
文摘AIM:To elucidate high mobility group-box 3(HMGB3) protein expression in gastric adenocarcinoma,its potential prognostic relevance,and possible mechanism of action.METHODS:Ninety-two patients with gastric adenocarcinomas surgically removed entered the study.HMGB3 expression was determined by immunohistochemistry through a tissue microarray procedure.The clinicopathologic characteristics of all patients were recorded,and regular follow-up was made for all patients.The inter-relationship of HMGB3 expression with histological and clinical factors was analyzed using nonparametric tests.Survival analysis was carried out by Kaplan-Meier(log-rank) and multivariate Cox(Forward LR) analyses between the group with overexpression of HMGB3 and the group with low or no HMGB3 ex-pression to determine the prognosis value of HMGB3 expression on overall survival.Further,HMGB3 expression was knocked down by small hairpin RNAs(shRNAs) in the human gastric cancer cell line BGC823 to observe its influence on cell biological characteristics.The MTT method was utilized to detect gastric cancer cell proliferation changes,and cell cycle distribution was analyzed by flow cytometry.RESULTS:Among 92 patients with gastric adenocarcinomas surgically removed in this study,high HMGB3 protein expression was detected in the gastric adenocarcinoma tissues vs peritumoral tissues(P < 0.001).Further correlation analysis with patients' clinical and histology variables revealed that HMGB3 overexpression was obviously associated with extensive wall penetration(P = 0.005),a positive nodal status(P = 0.004),and advanced tumor-node-metastasis(TNM) stage(P = 0.001).But there was no correlation between HMGB3 overexpression and the age and gender of the patient,tumor localization or histologic grade.Statistical Kaplan-Meier survival analysis disclosed significant differences in overall survival between the HMGB3 overexpression group and the HMGB3 no or low expression group(P = 0.006).The expected overall survival time was 31.00 ± 3.773 mo(95%CI = 23.605-38.395) for patients with HMGB3 overexpression and 49.074 ± 3.648 mo(95%CI = 41.925-57.311) for patients with HMGB3 no and low-level expression.Additionally,older age(P = 0.040),extensive wall penetration(P = 0.008),positive lymph node metastasis(P = 0.005),and advanced TNM tumor stage(P = 0.007) showed negative correlation with overall survival.Multivariate Cox regression analysis indicated that HMGB3 overexpression was an independent variable with respect to age,gender,histologic grade,extent of wall penetration,lymph nodal metastasis,and TNM stage for patients with resectable gastric adenocarcinomas with poor prognosis(hazard ratio = 2.791,95%CI = 1.233-6.319,P = 0.019).In the gene function study,after HMGB3 was knocked down in the gastric cell line BGC823 by shRNA,the cell proliferation rate was reduced at 24 h,48 h and 72 h.Compared to BGC823 shRNA-negative control(NC) cells,the cell proliferation rate in cells that had HMGB3 shRNA transfected was significantly decreased(P < 0.01).Finally,cell cycle analysis by FACS showed that BGC823 cells that had HMGB3 knocked down were blocked in G1/G0 phase.The percentage of cells in G1/G0 phase in BGC823 cells with shRNA-NC and with shRNA-HMGB3 was 46.84% ± 1.7%,and 73.03% ± 3.51% respectively(P = 0.001),whereas G2/M cells percentage decreased from 26.51% ± 0.83% to 17.8% ± 2.26%.CONCLUSION:HMGB3 is likely to be a useful prognostic marker involved in gastric cancer disease onset and progression by regulating the cell cycle.
文摘AIM:To determine the incidence of human epidermal growth factor receptor 2(HER2) over expression in oesophageal cancers.METHODS:A retrospective study,of one hundred consecutive cases of endoscopic histological samples of oesophageal cancers from a single British cancer network were included.Cancer cases were diagnosed between April 2007 and June 2010.HER2 over expression was assessed using immunohistochemistry,those that scored "0" and "+1" were considered "negative" for HER2;those that scored "+3" were considered "Positive".Cases that were scored "+2" on immunohistochemistry further went on to have HER2 gene analysis using the Ventana HER brightfield dual-colourin situ hybridisations(HER B DISH) assay and either came back to be positive or negative for HER2 over expression.Overall survival was measured from date of histological diagnosis until date of death.93% of the cases were followed up till five years or death,and all were followed up till two years.Cases of gastro-oesophageal junctional tumours were excluded.RESULTS:The median age of our sample was 66 years(range:38-91 years).Eighty one were male and 19 female.Ninety-one of the cases were adenocarcinoma of the oesophagus and the rest were cases of squamous cell carcinoma.The anatomical distribution of the tumours was;upper oesophagus 2,middle oesophagus 11,and 87 were in the lower oesophagus.Operative resection was completed in 15 cases;seven cases had attempted surgical resections,i.e.,open and close,33 patients received definitive chemo-radiation and 52 had palliative treatment.Twenty-five of the cancers showed evidence of HER2 over expression,all were adenocarcinomas.Of the 25 cases that showed evidence of HER2 over expression,21(84%) were located in the lower third of the oesophagus.On staging,24 out of the 25 HER2 positive cases were at stage 3 or more(13 at stage 3 and 11 at stage 4),For HER2 negative cases 37 were at stage 3 and 32 were staged as stage 4.Seventeen out of twenty five cases(68%) with HER2 over expression received palliative therapy,in comparison to thirty five out of seventy five(46.7%) in tumours not expressing HER2.No significant difference in overall survival was demonstrated between patients whose cancers showed evidence of HER2 over expression and those who did not;median overall survival for HER2 positive tumours was 15 mo(95%CI,11-19 mo) compared to 13 mo(95%CI,9-17 mo) for HER2 negative ones.Two years cumulative survival for cases with HER2 over expression was 33.7% compared to 31.6% in cases without HER2 over expression(P = 0.576).Only cancer's stage significantly affected overall survival on both univariant and multivariable analysis(P = 0.034 and P = 0.009 respectively).None of the patients included in this study received Trastuzumab.CONCLUSION:Twenty-seven point five percent of oesophageal adenocarcinomas showed evidence of HER2 over expression.Routine testing for human HER2 in oesophageal adenocarcinomas can have significant implication on treatments offered to patients that may potentially affect their prognosis.
基金Supported by the National Natural Science Foundation of China(No.61273035,71471135)
文摘To improve the efficiency of operating rooms, reduce the hospital' s costs and improve the level of service qualities, a scheduling method is presented based on a filtered-beam-search-based algo- rithm. Firstly, a scheduling problem domain is described. Mathematical programming models are al- so set up with an objective function of minimizing related costs of the system. On the basis of the de= scriptions mentioned above, a solving policy of generating feasible scheduling solutions is estab- lished. Combining with the speeific constraints of operation theatres, a filtered-beam-search-based algorithm is put forward to solve scheduling problems. Finally, simulation experiments are designed. The performance of the proposed algorithm is evaluated and compared with that of other approaches through simulations. Results indicate that the proposed algorithm can reduce costs, and are of prac- ticality and effectiveness.