BACKGROUND Helicobacter pylori(H.pylori)infection can cause extensive apoptosis of gastric epithelial cells,serving as a critical catalyst in the progression from chronic gastritis,gastrointestinal metaplasia,and atyp...BACKGROUND Helicobacter pylori(H.pylori)infection can cause extensive apoptosis of gastric epithelial cells,serving as a critical catalyst in the progression from chronic gastritis,gastrointestinal metaplasia,and atypical gastric hyperplasia to gastric carcinoma.Prompt eradication of H.pylori is paramount for ameliorating the pathophysiological conditions associated with chronic inflammation of the gastric mucosa and the primary prevention of gastric cancer.Acacetin,which has multifaceted pharmacological activities such as anti-cancer,anti-inflammatory,and antioxidative properties,has been extensively investigated across various domains.Nevertheless,the impact and underlying mechanisms of action of acacetin on H.pylori-infected gastric mucosal epithelial cells remain unclear.AIM To explore the defensive effects of acacetin on apoptosis in H.pylori-infected GES-1 cells and to investigate the underlying mechanisms.METHODS GES-1 cells were treated with H.pylori and acacetin in vitro.Cell viability was assessed using the CCK-8 assay,cell mortality rate via lactate dehydrogenase assay,alterations in cell migration and healing capacities through the wound healing assay,rates of apoptosis via flow cytometry and TUNEL staining,and expression levels of apoptosis-associated proteins through western blot analysis.RESULTS H.pylori infection led to decreased GES-1 cell viability,increased cell mortality,suppressed cell migration,increased rate of apoptosis,increased expressions of Bax and cle-caspase3,and decreased Bcl-2 expression.Conversely,acacetin treatment enhanced cell viability,mitigated apoptosis induced by H.pylori infection,and modulated the expression of apoptosis-regulatory proteins by upregulating Bcl-2 and downregulating Bax and cleaved caspase-3.CONCLUSION Acacetin significantly improved GES-1 cell viability and inhibited apoptosis in H.pylori-infected GES-1 cells,thereby exerting a protective effect on gastric mucosal epithelial cells.展开更多
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
AIM： To investigate whether activin regulates the cell proliferation of human gastric cancer cell line SNU-16 through the mRNA changes in activin receptors, Smads and p21^CIP1/WAF1. METHODS： The human gastric cancer...AIM： To investigate whether activin regulates the cell proliferation of human gastric cancer cell line SNU-16 through the mRNA changes in activin receptors, Smads and p21^CIP1/WAF1. METHODS： The human gastric cancer cell lines were cultured, RNAs were purified, and RT-PCRs were carried out with specifically designed primer for each gene. Among them, the two cell lines SNU-5 and SNU-16 were cultured with activin A for 24, 48 and 72 h. The cell proliferation was measured by MTT assay. For SNU-16, changes in ActRIA, ActRIB, ActRIIA, ActRIIB, Smad2, Smad4, Smad7, and p21^CIP1/WAF1 mRNAs were detected with RT-PCR after the cells were cultured with activin A for 24, 48 and 72 h. RESULTS： The proliferation of SNU-16 cells was down regulated by activin A whereas other cells showed no change. Basal level of inhibin/activin subunits, activin receptors, Smads, and p21^CIP1/WAF1 except for activin βB mRNAs was observed to have differential expression patterns in the human gastric cancer cell lines, AGS, KATO III, SNU-1, SNU-5, SNU-16, SNU-484, SNU-601, SNU-638, SNU-668, and SNU-719. Interestingly, significantly higher expressions of ActR IIA and IIB mRNAs were observed in SNU-16 cells when compared to other cells. After activin treatment, ActR IA, IB, and IIA mRNA levels were decreased whereas ActR IIB mRNA level increased in SNU-16 cells. Smad4 mRNA increased for up to 48 h whereas Smad7 mRNA increased sharply at 24 h and returned to the initial level at 48 h in SNU-16 cells. In addition, expression of the p21^CIP1/WAF1 the mitotic inhibitor, peaked at 72 h after activin treatment in SNU-16 cells. CONCLUSION： Our results suggest that inhibition of cell growth by activin is regulated by the negative feedback effect of Smad7 on the activin signaling pathway, and is mediated through p21^CIP1/WAF1 activation in SNU-16 cells.展开更多
基金Supported by the Doctoral Research Initiation Fund of Affiliated Hospital of Southwest Medical University,No.21037.
文摘BACKGROUND Helicobacter pylori(H.pylori)infection can cause extensive apoptosis of gastric epithelial cells,serving as a critical catalyst in the progression from chronic gastritis,gastrointestinal metaplasia,and atypical gastric hyperplasia to gastric carcinoma.Prompt eradication of H.pylori is paramount for ameliorating the pathophysiological conditions associated with chronic inflammation of the gastric mucosa and the primary prevention of gastric cancer.Acacetin,which has multifaceted pharmacological activities such as anti-cancer,anti-inflammatory,and antioxidative properties,has been extensively investigated across various domains.Nevertheless,the impact and underlying mechanisms of action of acacetin on H.pylori-infected gastric mucosal epithelial cells remain unclear.AIM To explore the defensive effects of acacetin on apoptosis in H.pylori-infected GES-1 cells and to investigate the underlying mechanisms.METHODS GES-1 cells were treated with H.pylori and acacetin in vitro.Cell viability was assessed using the CCK-8 assay,cell mortality rate via lactate dehydrogenase assay,alterations in cell migration and healing capacities through the wound healing assay,rates of apoptosis via flow cytometry and TUNEL staining,and expression levels of apoptosis-associated proteins through western blot analysis.RESULTS H.pylori infection led to decreased GES-1 cell viability,increased cell mortality,suppressed cell migration,increased rate of apoptosis,increased expressions of Bax and cle-caspase3,and decreased Bcl-2 expression.Conversely,acacetin treatment enhanced cell viability,mitigated apoptosis induced by H.pylori infection,and modulated the expression of apoptosis-regulatory proteins by upregulating Bcl-2 and downregulating Bax and cleaved caspase-3.CONCLUSION Acacetin significantly improved GES-1 cell viability and inhibited apoptosis in H.pylori-infected GES-1 cells,thereby exerting a protective effect on gastric mucosal epithelial cells.
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[目的]研究腹水草(Veronicastrum axillare,V.axillare)含药血清对乙醇损伤的人胃上皮细胞(gastric epithelial cells-1,GES-1)的保护作用及其对环腺苷酸依赖性激酶(protein kinase A,PKA)、环磷腺苷效应元件结合蛋白(c AMP-response element binding protein,CREB)、水通道蛋白1(aquaporin 1,AQP1)表达水平的调控作用。[方法]20只雄性SD大鼠随机分为5组(n=4),连续灌胃给药14d,制备正常组(生理盐水20 m L·kg-1)、雷尼替丁组(0.027g·kg-1)以及V.axillare低、中、高剂量组(0.7、1.4、2.8 g·kg-1)含药血清。MTT法检测体外培养的GES-1细胞的活性,研究V.axillare含药血清及PKA抑制剂H-89(25μmol·m L-1)预处理对5%乙醇诱导GES-1细胞活力的影响。荧光定量RT-PCR检测PKA、CREB及AQP1 m RNA的表达水平,Western blot检测AQP1蛋白表达水平。[结果]模型组和H-89组GES-1细胞活性低于正常组,差异有统计学意义(P<0.01);乙醇造模处理显著上调PKA、CREB及下调AQP1的表达水平,差异有统计学意义(P<0.01);H-89处理显著抑制PKA和CREB m RNA表达水平(P<0.01);加入各剂量V.axillare含药血清不能显著改善H-89对PKA、CREB和AQP1 m RNA表达水平的抑制作用。V.axillare中、高剂量含药血清细胞活性高于模型组,PKA、CREB m RNA表达水平低于模型组,差异有统计学意义(P<0.01),而V.axillare中、低剂量含药血清AQP1表达水平高于模型组,差异有统计学意义(P<0.01)。[结论]V.axillare含药血清显著减轻乙醇对GES-1细胞的损伤,对GES-1细胞具有保护作用,其保护机制与下调PKA、CREB及上调AQP1的表达有关。
基金Supported by the Research Fund 2003 from the Catholic University of Korea
文摘AIM： To investigate whether activin regulates the cell proliferation of human gastric cancer cell line SNU-16 through the mRNA changes in activin receptors, Smads and p21^CIP1/WAF1. METHODS： The human gastric cancer cell lines were cultured, RNAs were purified, and RT-PCRs were carried out with specifically designed primer for each gene. Among them, the two cell lines SNU-5 and SNU-16 were cultured with activin A for 24, 48 and 72 h. The cell proliferation was measured by MTT assay. For SNU-16, changes in ActRIA, ActRIB, ActRIIA, ActRIIB, Smad2, Smad4, Smad7, and p21^CIP1/WAF1 mRNAs were detected with RT-PCR after the cells were cultured with activin A for 24, 48 and 72 h. RESULTS： The proliferation of SNU-16 cells was down regulated by activin A whereas other cells showed no change. Basal level of inhibin/activin subunits, activin receptors, Smads, and p21^CIP1/WAF1 except for activin βB mRNAs was observed to have differential expression patterns in the human gastric cancer cell lines, AGS, KATO III, SNU-1, SNU-5, SNU-16, SNU-484, SNU-601, SNU-638, SNU-668, and SNU-719. Interestingly, significantly higher expressions of ActR IIA and IIB mRNAs were observed in SNU-16 cells when compared to other cells. After activin treatment, ActR IA, IB, and IIA mRNA levels were decreased whereas ActR IIB mRNA level increased in SNU-16 cells. Smad4 mRNA increased for up to 48 h whereas Smad7 mRNA increased sharply at 24 h and returned to the initial level at 48 h in SNU-16 cells. In addition, expression of the p21^CIP1/WAF1 the mitotic inhibitor, peaked at 72 h after activin treatment in SNU-16 cells. CONCLUSION： Our results suggest that inhibition of cell growth by activin is regulated by the negative feedback effect of Smad7 on the activin signaling pathway, and is mediated through p21^CIP1/WAF1 activation in SNU-16 cells.
