Background:No clear evidence exists regarding the relationship between the systemic immune-inflammation index(SII)and the efficacy of first-line chemotherapy combined with immunotherapy in patients with advanced non-s...Background:No clear evidence exists regarding the relationship between the systemic immune-inflammation index(SII)and the efficacy of first-line chemotherapy combined with immunotherapy in patients with advanced non-small cell lung cancer(NSCLC).This study aimed to establish the relationship between the SII and survival of patients with advanced NSCLC.Methods:This study included 123 patients with advanced NSCLC.The cutoff value of the SII was determined to be 1172 using ROC curve analysis.We evaluated the relationship between the SII and progression-free survival(PFS)and overall survival(OS)using the Cox regression model and Kaplan-Meier(KM)curve analysis.We stratified patients into multiple subgroups based on covariates such as age,sex,and smoking history.Subgroup analysis was used to evaluate the relationship between high SII,disease progression,and mortality risk.Results:Univariate analysis indicated that no significant difference existed between SII and PFS,but univariate analysis showed a significant association between SII and OS(hazard ratio[HR]=1.93,95% confidence interval[CI]=1.14-3.29,p=0.015).The fully adjusted Cox regression analysis also showed a significant correlation between the SII and OS after adjustment for covariables(HR=1.76,95%CI=1.02-3.02,p=0.041).In some subgroups,a high SII positively correlated with the risk of disease progression,and the relationship between a high SII and the risk of mortality was consistent in almost all subgroups.Conclusions:These results indicate that pretreatment SII may be an independent predictivemarker for patients with advanced NSCLC undergoing first-line chemotherapy combined with immunotherapy.However,large-scale prospective studies are required to confirm our results.展开更多
Objective This study investigated the role of the STAT3/survivin signaling pathway in the EML4-ALK- positive lung adenocarcinoma cell line H2228 before and after crizotinib-induced resistance. The mecha- nism of resis...Objective This study investigated the role of the STAT3/survivin signaling pathway in the EML4-ALK- positive lung adenocarcinoma cell line H2228 before and after crizotinib-induced resistance. The mecha- nism of resistance was studied. Methods Cell viability was determined using the MTT assay. Crizotinib-induced apoptosis in H2228 and H2228 crizotinib-resistant cells treated with the indicated doses of crizotinib was measured at different times （24 h, 48 h, 72 h） using flow cytometry. The levels of p-ALK, ALK, p-STAT3, STAT3, and survivin after treatment of cells with 0, 0.3, and 1 pM crizotinib for 72 h were determined using Western blot analysis. DNA sequencing was used to identify mutations in H2228 crizotinib-resistant cells. Results The crizotinib IC50 values in H2228 and H2228 crizotinib-resistant cells at 72 h were 334.5 nM and 3418 nM, respectively. The resistance index of 1-12228 crizotinib-resistant cells was 10.20. Crizotinib induced apoptosis in H2228 cells and reduced the levels of p-ALK, p-STAT3, and survivin. In contrast, no changes in the levels of p-ALK, p-STAT3, and survivin were observed in H2228 crizotinib-resistant cells. The mutations 2067G--,A and 2182G--,C in EML4-ALK were present in the H2228 crizotinib-resistant cells. Conclusion Crizotinib decreased the viability of H2228 cells in a dose- and time-dependent manner. In the STAT3/survivin pathway, downregulation of p-ALK, p-STAT3, and survivin might contribute to crizo- tinib-induced apoptosis in H2228 ceils. However, the STAT3/survivin pathway in H2228 crizotinib-resistant cells was unaffected by crizotinib treatment. Acquired resistance in H2228 cells might be related to ALK mutations.展开更多
Objective This study aimed to study the role of the HGF/c-Met signaling pathway in crizotinib-induced apoptosis of various lung adenocarcinoma cell lines and xenograft tumor models.Methods In vitro, H2228, H1993, and ...Objective This study aimed to study the role of the HGF/c-Met signaling pathway in crizotinib-induced apoptosis of various lung adenocarcinoma cell lines and xenograft tumor models.Methods In vitro, H2228, H1993, and A549 cells were treated with crizotinib. The inhibition of proliferation was quantitated by a 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide(MTT) assay. Apoptosis was quantified by flow cytometry. Expression of key proteins of the HGF/c-Met signaling pathway was examined by western blotting. In vivo, H1993 and A549 tumor cell xenograft models were established. Immunohistochemical analysis was used to determine protein expression of HGF and c-MET and the amount of phospho-c-MET(p-c-Met). Real-time quantitative polymerase chain reaction(PCR) was applied to examine the messenger RNA(m RNA) expression of c-MET and serine/threonine protein kinase(AKT). The expression and activation of the key proteins were evaluated by western blotting.Results In vitro, the growth of H1993, H2228, and A549 cells was inhibited after crizotinib treatment for 72 h. Apoptotic rates of H1993 and H2228 cells increased with the crizotinib concentration and exposure time. In vivo, the growth-inhibitory rate of crizotinib for H1993 xenografts was 72.3%. Positive expression rates of HGF and c-MET in H1993 xenografts were higher than those in A549 xenografts; the p-c-MET amount was the largest in H1993 xenograft control but the lowest in the H1993 xenograft with crizotinib treatment. The m RNA expression levels of c-MET and AKT in H1993 xenografts were higher than those of A549 xenografts. The protein levels of c-MET, AKT, and extracellular regulated protein kinases(ERK) in H1993 xenografts were higher than those in A549 xenografts; the p-AKT amount was higher in H1993 xenograft control than in A549 xenografts; the largest amount of p-c-MET was detected in H1993 xenograft control; the amount of p-ERK was the lowest in the H1993 xenograft with crizotinib treatment.Conclusion The HGF/c-Met signaling pathway may mediate crizotinib-induced apoptosis and inhibition of proliferation of lung adenocarcinoma cells.展开更多
基金supported by grants from the“Joint Project on Regional High-Incidence Diseases Research of Guangxi Natural Science Foundation”under Grant No.2023JJA141341the“Guangxi Medical and Health Key Discipline Construction Project.”。
文摘Background:No clear evidence exists regarding the relationship between the systemic immune-inflammation index(SII)and the efficacy of first-line chemotherapy combined with immunotherapy in patients with advanced non-small cell lung cancer(NSCLC).This study aimed to establish the relationship between the SII and survival of patients with advanced NSCLC.Methods:This study included 123 patients with advanced NSCLC.The cutoff value of the SII was determined to be 1172 using ROC curve analysis.We evaluated the relationship between the SII and progression-free survival(PFS)and overall survival(OS)using the Cox regression model and Kaplan-Meier(KM)curve analysis.We stratified patients into multiple subgroups based on covariates such as age,sex,and smoking history.Subgroup analysis was used to evaluate the relationship between high SII,disease progression,and mortality risk.Results:Univariate analysis indicated that no significant difference existed between SII and PFS,but univariate analysis showed a significant association between SII and OS(hazard ratio[HR]=1.93,95% confidence interval[CI]=1.14-3.29,p=0.015).The fully adjusted Cox regression analysis also showed a significant correlation between the SII and OS after adjustment for covariables(HR=1.76,95%CI=1.02-3.02,p=0.041).In some subgroups,a high SII positively correlated with the risk of disease progression,and the relationship between a high SII and the risk of mortality was consistent in almost all subgroups.Conclusions:These results indicate that pretreatment SII may be an independent predictivemarker for patients with advanced NSCLC undergoing first-line chemotherapy combined with immunotherapy.However,large-scale prospective studies are required to confirm our results.
基金Supported by grants from the Bureau of Science and Technology,Guangxi Zhuang Autonomous Zone,China(No.201017)National Natural Science Foundation of China(No.81060188 and 81260357)
文摘Objective This study investigated the role of the STAT3/survivin signaling pathway in the EML4-ALK- positive lung adenocarcinoma cell line H2228 before and after crizotinib-induced resistance. The mecha- nism of resistance was studied. Methods Cell viability was determined using the MTT assay. Crizotinib-induced apoptosis in H2228 and H2228 crizotinib-resistant cells treated with the indicated doses of crizotinib was measured at different times （24 h, 48 h, 72 h） using flow cytometry. The levels of p-ALK, ALK, p-STAT3, STAT3, and survivin after treatment of cells with 0, 0.3, and 1 pM crizotinib for 72 h were determined using Western blot analysis. DNA sequencing was used to identify mutations in H2228 crizotinib-resistant cells. Results The crizotinib IC50 values in H2228 and H2228 crizotinib-resistant cells at 72 h were 334.5 nM and 3418 nM, respectively. The resistance index of 1-12228 crizotinib-resistant cells was 10.20. Crizotinib induced apoptosis in H2228 cells and reduced the levels of p-ALK, p-STAT3, and survivin. In contrast, no changes in the levels of p-ALK, p-STAT3, and survivin were observed in H2228 crizotinib-resistant cells. The mutations 2067G--,A and 2182G--,C in EML4-ALK were present in the H2228 crizotinib-resistant cells. Conclusion Crizotinib decreased the viability of H2228 cells in a dose- and time-dependent manner. In the STAT3/survivin pathway, downregulation of p-ALK, p-STAT3, and survivin might contribute to crizo- tinib-induced apoptosis in H2228 ceils. However, the STAT3/survivin pathway in H2228 crizotinib-resistant cells was unaffected by crizotinib treatment. Acquired resistance in H2228 cells might be related to ALK mutations.
基金Supported by grants from the National Natural Sciences Foundation of China(No.81060188 and No.81260351)Guangxi Sciense&Technology Development Funds(No.2015139 and No.201017)
文摘Objective This study aimed to study the role of the HGF/c-Met signaling pathway in crizotinib-induced apoptosis of various lung adenocarcinoma cell lines and xenograft tumor models.Methods In vitro, H2228, H1993, and A549 cells were treated with crizotinib. The inhibition of proliferation was quantitated by a 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide(MTT) assay. Apoptosis was quantified by flow cytometry. Expression of key proteins of the HGF/c-Met signaling pathway was examined by western blotting. In vivo, H1993 and A549 tumor cell xenograft models were established. Immunohistochemical analysis was used to determine protein expression of HGF and c-MET and the amount of phospho-c-MET(p-c-Met). Real-time quantitative polymerase chain reaction(PCR) was applied to examine the messenger RNA(m RNA) expression of c-MET and serine/threonine protein kinase(AKT). The expression and activation of the key proteins were evaluated by western blotting.Results In vitro, the growth of H1993, H2228, and A549 cells was inhibited after crizotinib treatment for 72 h. Apoptotic rates of H1993 and H2228 cells increased with the crizotinib concentration and exposure time. In vivo, the growth-inhibitory rate of crizotinib for H1993 xenografts was 72.3%. Positive expression rates of HGF and c-MET in H1993 xenografts were higher than those in A549 xenografts; the p-c-MET amount was the largest in H1993 xenograft control but the lowest in the H1993 xenograft with crizotinib treatment. The m RNA expression levels of c-MET and AKT in H1993 xenografts were higher than those of A549 xenografts. The protein levels of c-MET, AKT, and extracellular regulated protein kinases(ERK) in H1993 xenografts were higher than those in A549 xenografts; the p-AKT amount was higher in H1993 xenograft control than in A549 xenografts; the largest amount of p-c-MET was detected in H1993 xenograft control; the amount of p-ERK was the lowest in the H1993 xenograft with crizotinib treatment.Conclusion The HGF/c-Met signaling pathway may mediate crizotinib-induced apoptosis and inhibition of proliferation of lung adenocarcinoma cells.
