BACKGROUND Although treatment options for gastric cancer(GC)continue to advance,the overall prognosis for patients with GC remains poor.At present,the predictors of treatment efficacy remain controversial except for h...BACKGROUND Although treatment options for gastric cancer(GC)continue to advance,the overall prognosis for patients with GC remains poor.At present,the predictors of treatment efficacy remain controversial except for high microsatellite instability.AIM To develop methods to identify groups of patients with GC who would benefit the most from receiving the combination of a programmed cell death protein 1(PD-1)inhibitor and chemotherapy.METHODS We acquired data from 63 patients with human epidermal growth factor receptor 2(HER2)-negative GC with a histological diagnosis of GC at the Cancer Hospital,Chinese Academy of Medical Sciences between November 2020 and October 2022.All of the patients screened received a PD-1 inhibitor combined with chemotherapy as the first-line treatment.RESULTS As of July 1,2023,the objective response rate was 61.9%,and the disease control rate was 96.8%.The median progression-free survival(mPFS)for all patients was 6.3 months.The median overall survival was not achieved.Survival analysis showed that patients with a combined positive score(CPS)≥1 exhibited an extended trend in progression-free survival(PFS)when compared to patients with a CPS of 0 after receiving a PD-1 inhibitor combined with oxaliplatin and tegafur as the first-line treatment.PFS exhibited a trend for prolongation as the expression level of HER2 increased.Based on PFS,we divided patients into two groups:A treatment group with excellent efficacy and a treatment group with poor efficacy.The mPFS of the excellent efficacy group was 8 months,with a mPFS of 9.1 months after excluding a cohort of patients who received interrupted therapy due to surgery.The mPFS was 4.5 months in patients in the group with poor efficacy who did not receive surgery.Using good/poor efficacy as the endpoint of our study,univariate analysis revealed that both CPS score(P=0.004)and HER2 expression level(P=0.015)were both factors that exerted significant influence on the efficacy of treatment the combination of a PD-1 inhibitor and chemotherapy in patients with advanced GC(AGC).Finally,multivariate analysis confirmed that CPS score was a significant influencing factor.CONCLUSION CPS score and HER2 expression both impacted the efficacy of immunotherapy combined with chemotherapy in AGC patients who were non-positive for HER2.展开更多
Objective:To explore the influence of silencing Bcl-2 expression by small interfering RNA（siRNA） on Bcl-2 protein expression,cell apoptosis rale and radiosensilivity of gastric cancer BCC823 cells.Methods:siRNA segm...Objective:To explore the influence of silencing Bcl-2 expression by small interfering RNA（siRNA） on Bcl-2 protein expression,cell apoptosis rale and radiosensilivity of gastric cancer BCC823 cells.Methods:siRNA segment for Bcl-2 gene was designed and synthesized,then was induced into gastric cancer BGC 823 cells by liposome transfection.Bcl-2 protein expression was detected by Western Blotting.After X radiation,flow cytometry and clone forming assay were used to determine the effects of RNA interference on BGC823 cell apoptosis rate and radiosensitivity. Result:After the transfection of Bcl-2 siRNA,the positive expression rate of Bcl-2 protein in BGC823 cells was（35.45±2.35）%.Compared with the control group and negative siRNA transfection group,the rate was significantly decreased（P【0.01）.The apoptosis rate of BGC823-RNAi cell was（10.81±0.91）%,which was significantly higher than the control group and negative siRNA transfection group（P【0.01）.After 48h X radiation,the apoptosis rate of BGC823-RNAi was（28.91±1.40）%,which was significantly higher than the control group and the group without radiation （P【0.01）.During clone forming assay D<sub>0</sub>,D<sub>4</sub> and SF<sub>2</sub> values in Bcl-2 siRNA1 transfection group were all lower than those in the control group.The radiosensitivity ratio was 1.28（the ratio of D<sub>0</sub>） and 1.60（the ratio of D<sub>4</sub>）.Conclusions:Specific siRNA of Bcl-2 gene can effectively inhibit the expression of Bcl-2 gene,enhance the radiosensitivity and apoptosis of gastric cancer BGC823 cells,having good clinical application perspective.展开更多
AIM: To explore the inducing effect of human mutant p27 gene on the apoptosis of the human gastric cancer cell line MKN-45 and its associated mechanisms. METHODS: The recombinant adenovirus Ad-p27mt was constructed to...AIM: To explore the inducing effect of human mutant p27 gene on the apoptosis of the human gastric cancer cell line MKN-45 and its associated mechanisms. METHODS: The recombinant adenovirus Ad-p27mt was constructed to infect the human gastric cancer cell line MKN-45. Using flow cytometry, TUNEL assay and DNA fragment analysis, we measured the apoptotic effect of Ad-p27mt on the human gastric cancer cells. RESULTS: Ad-p27mt was successfully constructed and the infection efficiency reached 100%. After 18 h of infection, we observed an apoptotic hypodiploid peak on the flow cytometer before G1-S and apoptotic characteristic bands in the DNA electrophoresis. The apoptotic rate detected by TUNEL method was significantly higher in the Ad-p27mt group (89.4±3.12%)compared to the control group (3.12±0.13%, P ＜ 0.01).CONCLUSION: Human mutant p27 can induce apoptosis of the human gastric cancer cells in vitro.展开更多
Objective: Human induced pluripotent stem(i PS) cells exhibit great potential for generating functional human cells for medical therapies. In this paper, we report for use of human i PS cells labeled with fluorescent ...Objective: Human induced pluripotent stem(i PS) cells exhibit great potential for generating functional human cells for medical therapies. In this paper, we report for use of human i PS cells labeled with fluorescent magnetic nanoparticles(FMNPs) for targeted imaging and synergistic therapy of gastric cancer cells in vivo. Methods: Human i PS cells were prepared and cultured for 72 h. The culture medium was collected, and then was coincubated with MGC803 cells. Cell viability was analyzed by the MTT method. FMNP-labeled human i PS cells were prepared and injected into gastric cancer-bearing nude mice. The mouse model was observed using a small-animal imaging system. The nude mice were irradiated under an external alternating magnetic field and evaluated using an infrared thermal mapping instrument. Tumor sizes were measured weekly. Results: iP S cells and the collected culture medium inhibited the growth of MGC803 cells. FMNP-labeled human iP S cells targeted and imaged gastric cancer cells in vivo, as well as inhibited cancer growth in vivo through the external magnetic field. Conclusion: FMNP-labeled human i PS cells exhibit considerable potential in applications such as targeted dual-mode imaging and synergistic therapy for early gastric cancer.展开更多
AIM:To investigate telomerase activity and human telomerase reverse transcriptase(hTERT)expression in normal human gastric mucosal epithelial cells(nhGMECs)and fibroblasts(nhGMFs).METHODS:nhGMECs and nhGMFs were isola...AIM:To investigate telomerase activity and human telomerase reverse transcriptase(hTERT)expression in normal human gastric mucosal epithelial cells(nhGMECs)and fibroblasts(nhGMFs).METHODS:nhGMECs and nhGMFs were isolated and cultured from specimens obtained during routine surgery for bleeding peptic ulcer.Telomerase activity in nhGMFs,nhGMECs,and the tumor cell lines BGC-823,SGC-7901 and MKN-28 cells was analyzed using the telomeric repeat amplification protocol assay.hTERT protein was determined in nhGMECs,nhGMFs,BGC-823,SGC-7901 and MKN-28 cells by indirect immunofluorescence.served in nhGMECs,nhGMFs and BGC-823,SGC-7901,MKN-28 cell lines.Positive hTERT immunostaining was detected in nhGMECs,nhGMFs,BGC-823,SGC-7901and MKN-28 cell lines.CONCLUSION:The use of telomerase or hTERT as diagnostic markers for gastric cancer may require further studies.展开更多
AIM To investigate the expression of annexin II in gastric carcinoma and its role in the metastasis of gastric cancer.METHODS The expression of annexin II in 51 cases of gastric carcinoma and 24 cases of adjacent tiss...AIM To investigate the expression of annexin II in gastric carcinoma and its role in the metastasis of gastric cancer.METHODS The expression of annexin II in 51 cases of gastric carcinoma and 24 cases of adjacent tissues was detected by immunohistochemistry. The relationship between annexin II and clinical features of gastric cancer was analyzed. Annexin II specific si RNA was used to inhibit the expression of annexin II in gastric cancer HGC-27 cells, and the effects of annexin II on the migration and secretion of matrix metalloproteinases(MMPs) were observed.RESULTS The positive rate of annexin II protein was 82.4% in gastric cancer tissues and 37.5% in adjacent tissues. There was significant difference between the two groups(P < 0.01); and the positive expression of annexin II was not related to the sex and age of the patients(P > 0.05). The expression of annexin IIprotein was correlated with tumor size, histological differentiation, TNM stage, Lymph node metastasis and other clinical features were significantly correlated, the difference was statistically significant(P < 0.05). Inhibition of annexin II expression, gastric cancer HGC-27 cells migration and secretion of MMPs were significantly decreased, the difference was statistically significant(P < 0.05).CONCLUSION Annexin II is highly expressed in gastric cancer tissues, annexin II protein expression is related to tumor size, histological differentiation, TNM staging, lymph node metastasis and other clinical features were significantly correlated. Annexin II high expression can promote the invasion and metastasis of gastric cancer.展开更多
背景与目的：探讨丹参酮ⅡA（tanshinoneⅡA，TanⅡA）对人胃癌BGC-823细胞增殖及凋亡的影响。材料与方法：采用0～10μg／ml Tan ⅡA分别作用于BGC-823细胞48h及72h，MTT比色法观察药物对细胞生长的抑制效应；2、5、10μg／ml TanⅡA...背景与目的：探讨丹参酮ⅡA（tanshinoneⅡA，TanⅡA）对人胃癌BGC-823细胞增殖及凋亡的影响。材料与方法：采用0～10μg／ml Tan ⅡA分别作用于BGC-823细胞48h及72h，MTT比色法观察药物对细胞生长的抑制效应；2、5、10μg／ml TanⅡA分别作用于细胞72h，应用HE染色、DNA琼脂糖凝胶电泳、流式细胞术分析药物对细胞凋亡的影响。结果：TanⅡA明显抑制BGC-823细胞增殖、诱导细胞凋亡，镜下可见BGC-823细胞明显的凋亡特征性改变；5、10μg／ml Tan ⅡA处理组细胞DNA电泳可见典型的“梯状”条带；FCM结果显示5、10μg／ml TanⅡA处理组细胞，凋亡率分别为（20．60±1．84）％、（31．03±1．47）％，与对照组（5．23±0．39）％比较差异有统计学意义（P〈0．01）。结论：在一定条件下，TanⅡA可抑制人胃癌BGC-823细胞增殖，诱导其凋亡。展开更多
目的研究香加皮水提取物(CPE)诱导人胃癌细胞BGC-823凋亡及其作用机制。方法采用G iem sa染色观察细胞凋亡形态学变化;电子显微镜观察凋亡细胞的超微结构变化;流式细胞术和琼脂糖凝胶电泳方法检测BGC-823细胞凋亡率、细胞周期和细胞凋亡...目的研究香加皮水提取物(CPE)诱导人胃癌细胞BGC-823凋亡及其作用机制。方法采用G iem sa染色观察细胞凋亡形态学变化;电子显微镜观察凋亡细胞的超微结构变化;流式细胞术和琼脂糖凝胶电泳方法检测BGC-823细胞凋亡率、细胞周期和细胞凋亡的DNA水平变化;RT-PCR方法检测细胞凋亡相关基因bcl-2、bax和surv iv in mRNA表达水平变化;免疫细胞化学方法检测bcl-2、bax和surv iv in蛋白表达的变化。结果经CPE作用后,人胃癌细胞BGC-823出现明显的细胞凋亡形态学变化及超微结构改变,细胞DNA琼脂糖凝胶电泳呈现梯形图。经250μg/mL CPE处理48 h后,多数BGC-823细胞被阻滞在G2/M期,而且细胞发生明显的凋亡变化,BGC-823细胞凋亡率可达18.9%。CPE可抑制BGC-823细胞bcl和surv iv in mRNA及蛋白的表达,促进baxmRNA及蛋白的表达。CPE可明显延长S180荷瘤小鼠生存期,且具有剂量依赖性。结论CPE通过阻滞BGC-823细胞于G2/M期及诱导BGC-823细胞凋亡发挥抗肿瘤作用,其作用机制与抑制细胞的bcl-2和surv iv in基因mRNA及蛋白表达、促进bax基因和蛋白的表达有关。展开更多
基金Supported by Beijing CSCO Clinical Oncology Research Foundation,No.Y-HH202102-0314。
文摘BACKGROUND Although treatment options for gastric cancer(GC)continue to advance,the overall prognosis for patients with GC remains poor.At present,the predictors of treatment efficacy remain controversial except for high microsatellite instability.AIM To develop methods to identify groups of patients with GC who would benefit the most from receiving the combination of a programmed cell death protein 1(PD-1)inhibitor and chemotherapy.METHODS We acquired data from 63 patients with human epidermal growth factor receptor 2(HER2)-negative GC with a histological diagnosis of GC at the Cancer Hospital,Chinese Academy of Medical Sciences between November 2020 and October 2022.All of the patients screened received a PD-1 inhibitor combined with chemotherapy as the first-line treatment.RESULTS As of July 1,2023,the objective response rate was 61.9%,and the disease control rate was 96.8%.The median progression-free survival(mPFS)for all patients was 6.3 months.The median overall survival was not achieved.Survival analysis showed that patients with a combined positive score(CPS)≥1 exhibited an extended trend in progression-free survival(PFS)when compared to patients with a CPS of 0 after receiving a PD-1 inhibitor combined with oxaliplatin and tegafur as the first-line treatment.PFS exhibited a trend for prolongation as the expression level of HER2 increased.Based on PFS,we divided patients into two groups:A treatment group with excellent efficacy and a treatment group with poor efficacy.The mPFS of the excellent efficacy group was 8 months,with a mPFS of 9.1 months after excluding a cohort of patients who received interrupted therapy due to surgery.The mPFS was 4.5 months in patients in the group with poor efficacy who did not receive surgery.Using good/poor efficacy as the endpoint of our study,univariate analysis revealed that both CPS score(P=0.004)and HER2 expression level(P=0.015)were both factors that exerted significant influence on the efficacy of treatment the combination of a PD-1 inhibitor and chemotherapy in patients with advanced GC(AGC).Finally,multivariate analysis confirmed that CPS score was a significant influencing factor.CONCLUSION CPS score and HER2 expression both impacted the efficacy of immunotherapy combined with chemotherapy in AGC patients who were non-positive for HER2.
文摘Objective:To explore the influence of silencing Bcl-2 expression by small interfering RNA（siRNA） on Bcl-2 protein expression,cell apoptosis rale and radiosensilivity of gastric cancer BCC823 cells.Methods:siRNA segment for Bcl-2 gene was designed and synthesized,then was induced into gastric cancer BGC 823 cells by liposome transfection.Bcl-2 protein expression was detected by Western Blotting.After X radiation,flow cytometry and clone forming assay were used to determine the effects of RNA interference on BGC823 cell apoptosis rate and radiosensitivity. Result:After the transfection of Bcl-2 siRNA,the positive expression rate of Bcl-2 protein in BGC823 cells was（35.45±2.35）%.Compared with the control group and negative siRNA transfection group,the rate was significantly decreased（P【0.01）.The apoptosis rate of BGC823-RNAi cell was（10.81±0.91）%,which was significantly higher than the control group and negative siRNA transfection group（P【0.01）.After 48h X radiation,the apoptosis rate of BGC823-RNAi was（28.91±1.40）%,which was significantly higher than the control group and the group without radiation （P【0.01）.During clone forming assay D<sub>0</sub>,D<sub>4</sub> and SF<sub>2</sub> values in Bcl-2 siRNA1 transfection group were all lower than those in the control group.The radiosensitivity ratio was 1.28（the ratio of D<sub>0</sub>） and 1.60（the ratio of D<sub>4</sub>）.Conclusions:Specific siRNA of Bcl-2 gene can effectively inhibit the expression of Bcl-2 gene,enhance the radiosensitivity and apoptosis of gastric cancer BGC823 cells,having good clinical application perspective.
基金Supported by the Natural Science Foundation of Shanghai,No. 04ZB14072
文摘AIM: To explore the inducing effect of human mutant p27 gene on the apoptosis of the human gastric cancer cell line MKN-45 and its associated mechanisms. METHODS: The recombinant adenovirus Ad-p27mt was constructed to infect the human gastric cancer cell line MKN-45. Using flow cytometry, TUNEL assay and DNA fragment analysis, we measured the apoptotic effect of Ad-p27mt on the human gastric cancer cells. RESULTS: Ad-p27mt was successfully constructed and the infection efficiency reached 100%. After 18 h of infection, we observed an apoptotic hypodiploid peak on the flow cytometer before G1-S and apoptotic characteristic bands in the DNA electrophoresis. The apoptotic rate detected by TUNEL method was significantly higher in the Ad-p27mt group (89.4±3.12%)compared to the control group (3.12±0.13%, P ＜ 0.01).CONCLUSION: Human mutant p27 can induce apoptosis of the human gastric cancer cells in vitro.
基金supported by National Natural Science Foundation of China (Grant No. 81225010, 20803040, 81028009, and 31170961)National Key Basic Research Program of China (973 Program) (Grant No. 2010CB933902 and 2015CB931802)+1 种基金National Key Technology Research and Development Program (863 Program) (Grant No. 2012AA022703 and 2014AA020700)Shanghai Science and Technology Fund (Grant No.13NM1401500)
文摘Objective: Human induced pluripotent stem(i PS) cells exhibit great potential for generating functional human cells for medical therapies. In this paper, we report for use of human i PS cells labeled with fluorescent magnetic nanoparticles(FMNPs) for targeted imaging and synergistic therapy of gastric cancer cells in vivo. Methods: Human i PS cells were prepared and cultured for 72 h. The culture medium was collected, and then was coincubated with MGC803 cells. Cell viability was analyzed by the MTT method. FMNP-labeled human i PS cells were prepared and injected into gastric cancer-bearing nude mice. The mouse model was observed using a small-animal imaging system. The nude mice were irradiated under an external alternating magnetic field and evaluated using an infrared thermal mapping instrument. Tumor sizes were measured weekly. Results: iP S cells and the collected culture medium inhibited the growth of MGC803 cells. FMNP-labeled human iP S cells targeted and imaged gastric cancer cells in vivo, as well as inhibited cancer growth in vivo through the external magnetic field. Conclusion: FMNP-labeled human i PS cells exhibit considerable potential in applications such as targeted dual-mode imaging and synergistic therapy for early gastric cancer.
基金Supported by National Natural Science Foundation of China,No.30270609
文摘AIM:To investigate telomerase activity and human telomerase reverse transcriptase(hTERT)expression in normal human gastric mucosal epithelial cells(nhGMECs)and fibroblasts(nhGMFs).METHODS:nhGMECs and nhGMFs were isolated and cultured from specimens obtained during routine surgery for bleeding peptic ulcer.Telomerase activity in nhGMFs,nhGMECs,and the tumor cell lines BGC-823,SGC-7901 and MKN-28 cells was analyzed using the telomeric repeat amplification protocol assay.hTERT protein was determined in nhGMECs,nhGMFs,BGC-823,SGC-7901 and MKN-28 cells by indirect immunofluorescence.served in nhGMECs,nhGMFs and BGC-823,SGC-7901,MKN-28 cell lines.Positive hTERT immunostaining was detected in nhGMECs,nhGMFs,BGC-823,SGC-7901and MKN-28 cell lines.CONCLUSION:The use of telomerase or hTERT as diagnostic markers for gastric cancer may require further studies.
文摘AIM To investigate the expression of annexin II in gastric carcinoma and its role in the metastasis of gastric cancer.METHODS The expression of annexin II in 51 cases of gastric carcinoma and 24 cases of adjacent tissues was detected by immunohistochemistry. The relationship between annexin II and clinical features of gastric cancer was analyzed. Annexin II specific si RNA was used to inhibit the expression of annexin II in gastric cancer HGC-27 cells, and the effects of annexin II on the migration and secretion of matrix metalloproteinases(MMPs) were observed.RESULTS The positive rate of annexin II protein was 82.4% in gastric cancer tissues and 37.5% in adjacent tissues. There was significant difference between the two groups(P < 0.01); and the positive expression of annexin II was not related to the sex and age of the patients(P > 0.05). The expression of annexin IIprotein was correlated with tumor size, histological differentiation, TNM stage, Lymph node metastasis and other clinical features were significantly correlated, the difference was statistically significant(P < 0.05). Inhibition of annexin II expression, gastric cancer HGC-27 cells migration and secretion of MMPs were significantly decreased, the difference was statistically significant(P < 0.05).CONCLUSION Annexin II is highly expressed in gastric cancer tissues, annexin II protein expression is related to tumor size, histological differentiation, TNM staging, lymph node metastasis and other clinical features were significantly correlated. Annexin II high expression can promote the invasion and metastasis of gastric cancer.
文摘背景与目的：探讨丹参酮ⅡA（tanshinoneⅡA，TanⅡA）对人胃癌BGC-823细胞增殖及凋亡的影响。材料与方法：采用0～10μg／ml Tan ⅡA分别作用于BGC-823细胞48h及72h，MTT比色法观察药物对细胞生长的抑制效应；2、5、10μg／ml TanⅡA分别作用于细胞72h，应用HE染色、DNA琼脂糖凝胶电泳、流式细胞术分析药物对细胞凋亡的影响。结果：TanⅡA明显抑制BGC-823细胞增殖、诱导细胞凋亡，镜下可见BGC-823细胞明显的凋亡特征性改变；5、10μg／ml Tan ⅡA处理组细胞DNA电泳可见典型的“梯状”条带；FCM结果显示5、10μg／ml TanⅡA处理组细胞，凋亡率分别为（20．60±1．84）％、（31．03±1．47）％，与对照组（5．23±0．39）％比较差异有统计学意义（P〈0．01）。结论：在一定条件下，TanⅡA可抑制人胃癌BGC-823细胞增殖，诱导其凋亡。
文摘目的研究香加皮水提取物(CPE)诱导人胃癌细胞BGC-823凋亡及其作用机制。方法采用G iem sa染色观察细胞凋亡形态学变化;电子显微镜观察凋亡细胞的超微结构变化;流式细胞术和琼脂糖凝胶电泳方法检测BGC-823细胞凋亡率、细胞周期和细胞凋亡的DNA水平变化;RT-PCR方法检测细胞凋亡相关基因bcl-2、bax和surv iv in mRNA表达水平变化;免疫细胞化学方法检测bcl-2、bax和surv iv in蛋白表达的变化。结果经CPE作用后,人胃癌细胞BGC-823出现明显的细胞凋亡形态学变化及超微结构改变,细胞DNA琼脂糖凝胶电泳呈现梯形图。经250μg/mL CPE处理48 h后,多数BGC-823细胞被阻滞在G2/M期,而且细胞发生明显的凋亡变化,BGC-823细胞凋亡率可达18.9%。CPE可抑制BGC-823细胞bcl和surv iv in mRNA及蛋白的表达,促进baxmRNA及蛋白的表达。CPE可明显延长S180荷瘤小鼠生存期,且具有剂量依赖性。结论CPE通过阻滞BGC-823细胞于G2/M期及诱导BGC-823细胞凋亡发挥抗肿瘤作用,其作用机制与抑制细胞的bcl-2和surv iv in基因mRNA及蛋白表达、促进bax基因和蛋白的表达有关。
