AIM:To investigate human epidermal growth factor receptor 2(HER2) gene amplification and protein expression in Chinese patients with resectable gastric cancer and the association with clinicopathological characteristi...AIM:To investigate human epidermal growth factor receptor 2(HER2) gene amplification and protein expression in Chinese patients with resectable gastric cancer and the association with clinicopathological characteristics and survival.METHODS:One hundred and ninety-seven gastric cancer patients who underwent curative surgery procedures were enrolled into this study.HER2 gene amplification and protein expression were examined using fluorescence in-situ hybridization(FISH) and immunohistochemistry(IHC) analysis on formalin-fixed paraffinembedded gastric cancer samples from all patients.For scoring,Hofmann's HER2 gastric cancer scoring system was adopted.All cases showing IHC3+ or FISH positiv-ity were defined as HER2 positive.Patient clinicopathological data and survival information were collected.Finally,χ 2 statistical analysis was performed to analyze the HER2 positivity rate amongst the subgroups with different clinicopathological characteristics including;gender,age,tumor location,Lauren classification,differentiation,TNM staging,depth of invasion,lymph node metastases and distant metastasis.The probability of survival for different subgroups with different clinicopathological characteristics was calculated using the Kaplan-Meier method and survival curves plotted using log rank inspection.RESULTS:According to Hofmann's HER2 gastric cancer scoring criteria,31 cases(15.74%) were identified as HER2 gene amplified and 19 cases(9.64%) were scored as strongly positive for HER2 membrane staining(3+),25 cases(12.69%) were moderately positive(2+) and 153 cases(77.66%) were HER2 negative(0/1+).The concordance rate between IHC and FISH analyses was 88.83%(175/197).Thirty-six cases were defined as positive for HER2 gene amplification and/or protein expression,with 24 of these cases being eligible for Herceptin treatment according to United States recommendations,and 29 of these cases eligible according to EU recommendations.Highly consistent results were detected between IHC3+,IHC0/1 and FISH(73.68% and 95.42%),but low consistency was observed between IHC2+ and FISH(40.00%).The positivity rates in intestinal type and well-differentiated gastric cancer were higher than those in diffuse/mixed type and poorly-differentiated gastric cancer respectively(28.57% vs 13.43%,P = 0.0103;37.25% vs 11.64%,P < 0.0001),but were not correlated with gender,age,tumor location or TNM stage,depth of invasion,lymph node metastases and distant metastasis.In poorly-differentiated gastric cancer patients,those without lymph node metastasis showed a higher HER2 positivity rate than those with lymph node metastasis(26.47% vs 7.14%,P = 0.0021).This association was not present in thosepatients with well-differentiated gastric cancer(28.57% vs 43.33%,P = 0.2832).Within our patient cohort,26 cases were lost to follow-up.The median survival time for the remaining 171 patients was 18 mo.The median survival times of the HER2 positive and negative groups were 17 and 18.5 mo respectively.Overall survival was not significantly different between HER2-positive and negative groups(χ 2 = 0.9157,P = 0.3386),but in patients presenting well-differentiated tumors,the overall survival of the HER2-positive group was significantly worse than that of the HER2-negative group(P = 0.0123).In contrast,patients with poorly differentiated and diffuse/mixed subtype gastric cancers showed no significant differences in overall survival associated with HER2.Furthermore,the median survival time of the HER2 positive group did not show any statistically significant differences when compared to the subgroups of gender,age,tumor location,TNM classification,lymph node metastases and distant metastasis.CONCLUSION:Patients with intestinal type gastric cancer(GC),well-differentiated GC and poorly-differentiated GC without lymph node metastasis,may all represent suitable candidates for targeted therapy using Herceptin.展开更多
目的探究达格列净联合常规治疗对2型糖尿病伴心力衰竭患者的心血管保护作用及对血清炎症因子和可溶性生长刺激表达基因2(sST2)水平的影响。方法前瞻性选取2020年9月至2022年8月江苏省昆山市第一人民医院收治的86例2型糖尿病伴心力衰竭...目的探究达格列净联合常规治疗对2型糖尿病伴心力衰竭患者的心血管保护作用及对血清炎症因子和可溶性生长刺激表达基因2(sST2)水平的影响。方法前瞻性选取2020年9月至2022年8月江苏省昆山市第一人民医院收治的86例2型糖尿病伴心力衰竭患者为研究对象,按随机数字表法分为对照组和观察组,各43例。对照组予以常规治疗降糖及抗心力衰竭治疗,观察组在对照组基础上增加达格列净治疗。比较两组治疗前、治疗6个月后的血糖[糖化血红蛋白(HbA1c)、空腹血糖、餐后2 h血糖(2 h PG)]、血脂[总胆固醇、甘油三酯、低密度脂蛋白胆固醇(LDL-C)]、心功能[左心室射血分数(LVEF)、血浆N端脑钠肽前体(NT-proBNP)、6 min步行试验(6MWT)]、血清指标[白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、sST2]水平及心血管事件及不良反应发生率。结果治疗6个月后,观察组的HbA1c、空腹血糖、2 h PG、总胆固醇、甘油三酯、LDL-C水平分别为(6.65±0.73)%、(6.25±1.54)mmol/L、(7.88±1.35)mmol/L、(3.87±0.85)mmol/L、(1.52±0.46)mmol/L、(2.41±0.63)mmol/L,均明显低于对照组[(7.07±0.85)%、(7.16±1.49)mmol/L、(8.82±1.48)mmol/L、(4.24±0.82)mmol/L、(1.73±0.51)mmol/L、(2.69±0.61)mmol/L],差异均有统计学意义(P<0.05)。治疗6个月后,观察组的LVEF、6MWT水平分别为(52.28±3.43)%、(424.87±72.58)m,均明显高于对照组[(50.79±3.25)%、(367.52±74.43)m],血浆NT-proBNP水平为(1778.65±224.37)pg/mL,低于对照组[(2943.41±256.22)pg/mL],差异均有统计学意义(P<0.05)。治疗6个月后,观察组的血清IL-1β、TNF-α、sST2水平分别为(6.60±1.14)pg/mL、(22.15±4.30)ng/L、(0.42±0.13)g/L,均明显低于对照组[(7.19±1.39)pg/mL、(29.68±5.24)ng/L、(0.50±0.16)g/L],差异均有统计学意义(P<0.05)。观察组心血管事件总发生率为9.30%,低于对照组(25.58%),差异有统计学意义(P<0.05)。两组均无严重不良反应发生。结论在使用常规降糖、抗心力衰竭治疗2型糖尿病伴心力衰竭患者基础上增加达格列净可有效降低其血糖、血脂及血清IL-1β、TNF-α、sST2水平,减少心血管事件的发生,具有一定心血管保护作用。展开更多
文摘AIM:To investigate human epidermal growth factor receptor 2(HER2) gene amplification and protein expression in Chinese patients with resectable gastric cancer and the association with clinicopathological characteristics and survival.METHODS:One hundred and ninety-seven gastric cancer patients who underwent curative surgery procedures were enrolled into this study.HER2 gene amplification and protein expression were examined using fluorescence in-situ hybridization(FISH) and immunohistochemistry(IHC) analysis on formalin-fixed paraffinembedded gastric cancer samples from all patients.For scoring,Hofmann's HER2 gastric cancer scoring system was adopted.All cases showing IHC3+ or FISH positiv-ity were defined as HER2 positive.Patient clinicopathological data and survival information were collected.Finally,χ 2 statistical analysis was performed to analyze the HER2 positivity rate amongst the subgroups with different clinicopathological characteristics including;gender,age,tumor location,Lauren classification,differentiation,TNM staging,depth of invasion,lymph node metastases and distant metastasis.The probability of survival for different subgroups with different clinicopathological characteristics was calculated using the Kaplan-Meier method and survival curves plotted using log rank inspection.RESULTS:According to Hofmann's HER2 gastric cancer scoring criteria,31 cases(15.74%) were identified as HER2 gene amplified and 19 cases(9.64%) were scored as strongly positive for HER2 membrane staining(3+),25 cases(12.69%) were moderately positive(2+) and 153 cases(77.66%) were HER2 negative(0/1+).The concordance rate between IHC and FISH analyses was 88.83%(175/197).Thirty-six cases were defined as positive for HER2 gene amplification and/or protein expression,with 24 of these cases being eligible for Herceptin treatment according to United States recommendations,and 29 of these cases eligible according to EU recommendations.Highly consistent results were detected between IHC3+,IHC0/1 and FISH(73.68% and 95.42%),but low consistency was observed between IHC2+ and FISH(40.00%).The positivity rates in intestinal type and well-differentiated gastric cancer were higher than those in diffuse/mixed type and poorly-differentiated gastric cancer respectively(28.57% vs 13.43%,P = 0.0103;37.25% vs 11.64%,P < 0.0001),but were not correlated with gender,age,tumor location or TNM stage,depth of invasion,lymph node metastases and distant metastasis.In poorly-differentiated gastric cancer patients,those without lymph node metastasis showed a higher HER2 positivity rate than those with lymph node metastasis(26.47% vs 7.14%,P = 0.0021).This association was not present in thosepatients with well-differentiated gastric cancer(28.57% vs 43.33%,P = 0.2832).Within our patient cohort,26 cases were lost to follow-up.The median survival time for the remaining 171 patients was 18 mo.The median survival times of the HER2 positive and negative groups were 17 and 18.5 mo respectively.Overall survival was not significantly different between HER2-positive and negative groups(χ 2 = 0.9157,P = 0.3386),but in patients presenting well-differentiated tumors,the overall survival of the HER2-positive group was significantly worse than that of the HER2-negative group(P = 0.0123).In contrast,patients with poorly differentiated and diffuse/mixed subtype gastric cancers showed no significant differences in overall survival associated with HER2.Furthermore,the median survival time of the HER2 positive group did not show any statistically significant differences when compared to the subgroups of gender,age,tumor location,TNM classification,lymph node metastases and distant metastasis.CONCLUSION:Patients with intestinal type gastric cancer(GC),well-differentiated GC and poorly-differentiated GC without lymph node metastasis,may all represent suitable candidates for targeted therapy using Herceptin.
文摘目的探究达格列净联合常规治疗对2型糖尿病伴心力衰竭患者的心血管保护作用及对血清炎症因子和可溶性生长刺激表达基因2(sST2)水平的影响。方法前瞻性选取2020年9月至2022年8月江苏省昆山市第一人民医院收治的86例2型糖尿病伴心力衰竭患者为研究对象,按随机数字表法分为对照组和观察组,各43例。对照组予以常规治疗降糖及抗心力衰竭治疗,观察组在对照组基础上增加达格列净治疗。比较两组治疗前、治疗6个月后的血糖[糖化血红蛋白(HbA1c)、空腹血糖、餐后2 h血糖(2 h PG)]、血脂[总胆固醇、甘油三酯、低密度脂蛋白胆固醇(LDL-C)]、心功能[左心室射血分数(LVEF)、血浆N端脑钠肽前体(NT-proBNP)、6 min步行试验(6MWT)]、血清指标[白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、sST2]水平及心血管事件及不良反应发生率。结果治疗6个月后,观察组的HbA1c、空腹血糖、2 h PG、总胆固醇、甘油三酯、LDL-C水平分别为(6.65±0.73)%、(6.25±1.54)mmol/L、(7.88±1.35)mmol/L、(3.87±0.85)mmol/L、(1.52±0.46)mmol/L、(2.41±0.63)mmol/L,均明显低于对照组[(7.07±0.85)%、(7.16±1.49)mmol/L、(8.82±1.48)mmol/L、(4.24±0.82)mmol/L、(1.73±0.51)mmol/L、(2.69±0.61)mmol/L],差异均有统计学意义(P<0.05)。治疗6个月后,观察组的LVEF、6MWT水平分别为(52.28±3.43)%、(424.87±72.58)m,均明显高于对照组[(50.79±3.25)%、(367.52±74.43)m],血浆NT-proBNP水平为(1778.65±224.37)pg/mL,低于对照组[(2943.41±256.22)pg/mL],差异均有统计学意义(P<0.05)。治疗6个月后,观察组的血清IL-1β、TNF-α、sST2水平分别为(6.60±1.14)pg/mL、(22.15±4.30)ng/L、(0.42±0.13)g/L,均明显低于对照组[(7.19±1.39)pg/mL、(29.68±5.24)ng/L、(0.50±0.16)g/L],差异均有统计学意义(P<0.05)。观察组心血管事件总发生率为9.30%,低于对照组(25.58%),差异有统计学意义(P<0.05)。两组均无严重不良反应发生。结论在使用常规降糖、抗心力衰竭治疗2型糖尿病伴心力衰竭患者基础上增加达格列净可有效降低其血糖、血脂及血清IL-1β、TNF-α、sST2水平,减少心血管事件的发生,具有一定心血管保护作用。
