BACKGROUND L-type calcium channels are the only protein channels sensitive to calcium channel blockers,and are expressed in various cancer types.The Cancer Genome Atlas database shows that the mRNA levels of multiple ...BACKGROUND L-type calcium channels are the only protein channels sensitive to calcium channel blockers,and are expressed in various cancer types.The Cancer Genome Atlas database shows that the mRNA levels of multiple L-type calcium channel subunits in esophageal squamous cell carcinoma tumor tissue are significantly higher than those in normal esophageal epithelial tissue.Therefore,we hypothesized that amlodipine,a long-acting dihydropyridine L-type calcium channel blocker,may inhibit the occurrence and development of esophageal cancer(EC).AIM To investigate the inhibitory effects of amlodipine on EC through endoplasmic reticulum(ER)stress.METHODS Cav1.3 protein expression levels in 50 pairs of EC tissues and corresponding paracancerous tissues were examined.Subsequently,the inhibitory effects of amlodipine on proliferation and migration of EC cells in vitro were detected using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide and Transwell assays.In vivo experiments were performed using murine xenograft model.To elucidate the underlying mechanisms,in vitro cell studies were performed to confirm that ER stress plays a role in inhibition proliferation and migration of EC cells treated with amlodipine.RESULTS The expression level of Cav1.3 in esophageal carcinoma was 1.6 times higher than that in paracancerous tissues.Amlodipine treatment decreased the viability of esophageal carcinoma cells in a dose-and time-dependent manner.In vivo animal experiments also clearly indicated that amlodipine inhibited the growth of EC tumors in mice.Additionally,amlodipine reduces the migration of tumor cells by inhibiting epithelial-mesenchymal transition(EMT).Mechanistic studies have demonstrated that amlodipine induces ER stress-mediated apoptosis and suppresses EMT.Moreover,amlodipine-induced autophagy was characterized by an increase in autophagy lysosomes and the accumulation of light chain 3B protein.The combination of amlodipine with the ER stress inhibitor 4-phenylbutyric acid further confirmed the role of the ER stress response in amlodipine-induced apoptosis,EMT,and autophagy.Furthermore,blocking autophagy increases the ratio of apoptosis and migration.CONCLUSION Collectively,we demonstrate for the first time that amlodipine promotes apoptosis,induces autophagy,and inhibits migration through ER stress,thereby exerting anti-tumor effects in EC.展开更多
Objective:To evaluate the efficacy of combination perindopril/amlodipine tablets in patients with high-altitude hypertension who were previously unable to control their blood pressure with monotherapy.Methods:A total ...Objective:To evaluate the efficacy of combination perindopril/amlodipine tablets in patients with high-altitude hypertension who were previously unable to control their blood pressure with monotherapy.Methods:A total of 151 patients with high-altitude hypertension whose blood pressure remained inadequately controlled with previous monotherapy were enrolled in this study.All patients received an 8-week treatment with a combination of perindopril/amlodipine tablets,consisting of perindopril 10 mg/day and amlodipine 5 mg/day.Blood pressure measurements,including both diastolic and systolic pressures,were taken at baseline,and after 2,4,6,and 8 weeks of treatment.Results:After 8 weeks of treatment,there was a significant reduction in both average systolic and diastolic blood pressure compared to baseline(P<0.0001).Specifically,the average systolic blood pressure decreased by 24.45±13.75 mmHg,and the average diastolic blood pressure decreased by 13.37±8.40 mmHg.The overall heart rate showed no significant changes during the treatment period.Conclusion:A combination of perindopril/amlodipine tablets significantly improved blood pressure control in patients with high-altitude hypertension after 8 weeks of treatment.These results support the efficacy of combination perindopril/amlodipine as a viable treatment option for high-altitude hypertension.展开更多
背景众多证据表明免疫逃逸在肿瘤形成过程中扮演重要角色,慢性萎缩性胃炎(chronic atrophic gastritis,CAG)是胃癌的癌前疾病.安胃汤被发现可改善CAG临床症状及病理表现,实现CAG的逆转,该作用是否与免疫逃逸机制相关有待进一步研究.目...背景众多证据表明免疫逃逸在肿瘤形成过程中扮演重要角色,慢性萎缩性胃炎(chronic atrophic gastritis,CAG)是胃癌的癌前疾病.安胃汤被发现可改善CAG临床症状及病理表现,实现CAG的逆转,该作用是否与免疫逃逸机制相关有待进一步研究.目的从细胞免疫逃逸角度,探讨程序性死亡受体-1(programmed cell death protein 1,PD-1)/程序性死亡受体配体-1(programmed cell death ligand 1,PD-L1)信号轴与安胃汤对CAG模型大鼠疗效之间的关系.方法采用1-甲基-3-硝基-1-亚硝基胍(1-Methyl-3-nitro-1-nitrosoguanidine,MNNG)慢性萎缩性胃炎大鼠模型,应用不同剂量安胃汤及维酶素片进行干预;HE染色观察安胃汤对CAG模型大鼠胃黏膜炎症细胞浸润及组织形态改变的影响;免疫组化检测CAG模型大鼠胃黏膜组织PD-1、PD-L1蛋白表达;ELISA检测血清CD4^(+)、CD8^(+)水平变化;qPCR检测CAG模型大鼠胃黏膜PD-1mRNA、PD-L1mRNA表达;Western-blot检测CAG模型大鼠胃黏膜组织PD-1、PD-L1蛋白表达.结果免疫组化结果示:与模型组和维酶素组比较,安胃汤高、低剂量组PD-L1表达均较低(P<0.01,P<0.05).ELISA实验结果示:与模型组比较,安胃汤高剂量组CD4^(+)表达及CD4^(+)/CD8^(+)比值升高(P<0.01,P<0.05),安胃汤各组和维酶素组CD8^(+)表达降低(P<0.01);与维酶素组比较,安胃汤高剂量组CD8^(+)表达降低(P<0.05).qPCR实验结果显示:与模型组比较,安胃汤高剂量组和维酶素组PD-1mRNA表达下降(P<0.01),安胃汤高、中剂量组PD-L1mRNA表达下降(P<0.01,P<0.05).Western-blot实验结果显示:与模型组比较,安胃汤高、中剂量组PD-1/Actin,PD-L1/Actin表达下降(P<0.01,P<0.05).结论安胃汤抗CAG作用可能与抑制PD-1/PD-L1信号通路诱导的细胞免疫逃逸有关.展开更多
目的探讨肉瘤样肾细胞癌组织中PD-L1的表达及肿瘤内微血管密度情况,为肉瘤样肾细胞癌免疫治疗及靶向治疗方案的选择提供理论依据。方法通过免疫组化法检测PD-L1、CD31及CD34在16例肉瘤样肾细胞癌(癌成分均为透明细胞肾细胞癌)中的表达,...目的探讨肉瘤样肾细胞癌组织中PD-L1的表达及肿瘤内微血管密度情况,为肉瘤样肾细胞癌免疫治疗及靶向治疗方案的选择提供理论依据。方法通过免疫组化法检测PD-L1、CD31及CD34在16例肉瘤样肾细胞癌(癌成分均为透明细胞肾细胞癌)中的表达,并评估肿瘤微血管密度。结果16例肿瘤中CD31和CD34免疫组化染色显示,肉瘤样肾细胞癌区域微血管密度明显高于不伴肉瘤样分化的区域,微血管密度计数分别为68.6±25.8 vs 38.7±16.0(t=3.931,P=0.0005)和69.5±28.1 vs 40.1±18.4(t=3.506,P=0.0015),差异有统计学意义。肉瘤样区域PD-L1表达水平高于非肉瘤样区域,CPS分别为34.7±26.9和25.9±27.6,但差异无统计学意义。结论在肉瘤样肾细胞癌中,肉瘤样区域微血管密度和PD-L1表达水平明显高于非肉瘤样区域,提示靶向治疗联合免疫治疗可能为此类肿瘤提供一种有效的治疗方法。展开更多
基金Supported by the Key Medical Scientific and Technological Project of Henan Province,No.SBGJ202102188Henan Provincial Medical Science and Technology Project,No.LHGJ20221012the Key Project of Science and Technology of Xinxiang,No.GG2020027.
文摘BACKGROUND L-type calcium channels are the only protein channels sensitive to calcium channel blockers,and are expressed in various cancer types.The Cancer Genome Atlas database shows that the mRNA levels of multiple L-type calcium channel subunits in esophageal squamous cell carcinoma tumor tissue are significantly higher than those in normal esophageal epithelial tissue.Therefore,we hypothesized that amlodipine,a long-acting dihydropyridine L-type calcium channel blocker,may inhibit the occurrence and development of esophageal cancer(EC).AIM To investigate the inhibitory effects of amlodipine on EC through endoplasmic reticulum(ER)stress.METHODS Cav1.3 protein expression levels in 50 pairs of EC tissues and corresponding paracancerous tissues were examined.Subsequently,the inhibitory effects of amlodipine on proliferation and migration of EC cells in vitro were detected using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide and Transwell assays.In vivo experiments were performed using murine xenograft model.To elucidate the underlying mechanisms,in vitro cell studies were performed to confirm that ER stress plays a role in inhibition proliferation and migration of EC cells treated with amlodipine.RESULTS The expression level of Cav1.3 in esophageal carcinoma was 1.6 times higher than that in paracancerous tissues.Amlodipine treatment decreased the viability of esophageal carcinoma cells in a dose-and time-dependent manner.In vivo animal experiments also clearly indicated that amlodipine inhibited the growth of EC tumors in mice.Additionally,amlodipine reduces the migration of tumor cells by inhibiting epithelial-mesenchymal transition(EMT).Mechanistic studies have demonstrated that amlodipine induces ER stress-mediated apoptosis and suppresses EMT.Moreover,amlodipine-induced autophagy was characterized by an increase in autophagy lysosomes and the accumulation of light chain 3B protein.The combination of amlodipine with the ER stress inhibitor 4-phenylbutyric acid further confirmed the role of the ER stress response in amlodipine-induced apoptosis,EMT,and autophagy.Furthermore,blocking autophagy increases the ratio of apoptosis and migration.CONCLUSION Collectively,we demonstrate for the first time that amlodipine promotes apoptosis,induces autophagy,and inhibits migration through ER stress,thereby exerting anti-tumor effects in EC.
文摘Objective:To evaluate the efficacy of combination perindopril/amlodipine tablets in patients with high-altitude hypertension who were previously unable to control their blood pressure with monotherapy.Methods:A total of 151 patients with high-altitude hypertension whose blood pressure remained inadequately controlled with previous monotherapy were enrolled in this study.All patients received an 8-week treatment with a combination of perindopril/amlodipine tablets,consisting of perindopril 10 mg/day and amlodipine 5 mg/day.Blood pressure measurements,including both diastolic and systolic pressures,were taken at baseline,and after 2,4,6,and 8 weeks of treatment.Results:After 8 weeks of treatment,there was a significant reduction in both average systolic and diastolic blood pressure compared to baseline(P<0.0001).Specifically,the average systolic blood pressure decreased by 24.45±13.75 mmHg,and the average diastolic blood pressure decreased by 13.37±8.40 mmHg.The overall heart rate showed no significant changes during the treatment period.Conclusion:A combination of perindopril/amlodipine tablets significantly improved blood pressure control in patients with high-altitude hypertension after 8 weeks of treatment.These results support the efficacy of combination perindopril/amlodipine as a viable treatment option for high-altitude hypertension.
文摘背景众多证据表明免疫逃逸在肿瘤形成过程中扮演重要角色,慢性萎缩性胃炎(chronic atrophic gastritis,CAG)是胃癌的癌前疾病.安胃汤被发现可改善CAG临床症状及病理表现,实现CAG的逆转,该作用是否与免疫逃逸机制相关有待进一步研究.目的从细胞免疫逃逸角度,探讨程序性死亡受体-1(programmed cell death protein 1,PD-1)/程序性死亡受体配体-1(programmed cell death ligand 1,PD-L1)信号轴与安胃汤对CAG模型大鼠疗效之间的关系.方法采用1-甲基-3-硝基-1-亚硝基胍(1-Methyl-3-nitro-1-nitrosoguanidine,MNNG)慢性萎缩性胃炎大鼠模型,应用不同剂量安胃汤及维酶素片进行干预;HE染色观察安胃汤对CAG模型大鼠胃黏膜炎症细胞浸润及组织形态改变的影响;免疫组化检测CAG模型大鼠胃黏膜组织PD-1、PD-L1蛋白表达;ELISA检测血清CD4^(+)、CD8^(+)水平变化;qPCR检测CAG模型大鼠胃黏膜PD-1mRNA、PD-L1mRNA表达;Western-blot检测CAG模型大鼠胃黏膜组织PD-1、PD-L1蛋白表达.结果免疫组化结果示:与模型组和维酶素组比较,安胃汤高、低剂量组PD-L1表达均较低(P<0.01,P<0.05).ELISA实验结果示:与模型组比较,安胃汤高剂量组CD4^(+)表达及CD4^(+)/CD8^(+)比值升高(P<0.01,P<0.05),安胃汤各组和维酶素组CD8^(+)表达降低(P<0.01);与维酶素组比较,安胃汤高剂量组CD8^(+)表达降低(P<0.05).qPCR实验结果显示:与模型组比较,安胃汤高剂量组和维酶素组PD-1mRNA表达下降(P<0.01),安胃汤高、中剂量组PD-L1mRNA表达下降(P<0.01,P<0.05).Western-blot实验结果显示:与模型组比较,安胃汤高、中剂量组PD-1/Actin,PD-L1/Actin表达下降(P<0.01,P<0.05).结论安胃汤抗CAG作用可能与抑制PD-1/PD-L1信号通路诱导的细胞免疫逃逸有关.
文摘目的探讨肉瘤样肾细胞癌组织中PD-L1的表达及肿瘤内微血管密度情况,为肉瘤样肾细胞癌免疫治疗及靶向治疗方案的选择提供理论依据。方法通过免疫组化法检测PD-L1、CD31及CD34在16例肉瘤样肾细胞癌(癌成分均为透明细胞肾细胞癌)中的表达,并评估肿瘤微血管密度。结果16例肿瘤中CD31和CD34免疫组化染色显示,肉瘤样肾细胞癌区域微血管密度明显高于不伴肉瘤样分化的区域,微血管密度计数分别为68.6±25.8 vs 38.7±16.0(t=3.931,P=0.0005)和69.5±28.1 vs 40.1±18.4(t=3.506,P=0.0015),差异有统计学意义。肉瘤样区域PD-L1表达水平高于非肉瘤样区域,CPS分别为34.7±26.9和25.9±27.6,但差异无统计学意义。结论在肉瘤样肾细胞癌中,肉瘤样区域微血管密度和PD-L1表达水平明显高于非肉瘤样区域,提示靶向治疗联合免疫治疗可能为此类肿瘤提供一种有效的治疗方法。
