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
Epidermal growth factor receptor(EGFR)signaling has become an importanttarget for drug development becauseEGFR signaling enhances tumor cell proliferation,migration,and invasion and inhibits apoptosis.However,theresul...Epidermal growth factor receptor(EGFR)signaling has become an importanttarget for drug development becauseEGFR signaling enhances tumor cell proliferation,migration,and invasion and inhibits apoptosis.However,theresults of clinical trials using EGFR inhibitors in patients with solid tumors have been disappointing.Here,wereport a protective effect of the EGFR inhibitors AG1478 and PD153035 against cell death induced by acute hy-poxia,which contrasts with their proapoptotic effects under normoxia.Under hypoxic conditions,both agents re-展开更多
AIM To demonstrate the relationship betweenH-ras oncogene and hepatocellular carcinoma(HCC) metastasis.METHODS Activated H-ras oncogene wastransfected into SMMC 7721, a cell line derivedfrom human HCC, by calcium phos...AIM To demonstrate the relationship betweenH-ras oncogene and hepatocellular carcinoma(HCC) metastasis.METHODS Activated H-ras oncogene wastransfected into SMMC 7721, a cell line derivedfrom human HCC, by calcium phosphatetransfection method. Some metastasis-relatedparameters were detected in vitro, includingadhesion assay, migration assay, expression ofcollagenase ⅣV (c ⅣV ase) and epidermal growthfactor receptor (EGFR).RESULTS The abilities of H-ras-transfected cellclones in adhesion to laminin (LN) or fibronectin(FN), migration, c Ⅳ ase secretion increasedmarkedly, and the expression of EGFR elevatedmoderately. More importantly, these alterationswere consistent positively with the expressionof p21, the protein product of H-ras oncogene.CONCLUSION H-ras oncogene could inducethe metastatic phenotype of HCC cell in vitro toraise its metastatic potential.展开更多
Objective:Circulating tumor cells(CTCs)play a critical role in cancer metastasis,but their prevalence and significance remain unclear.This study attempted to track the epithelial-mesenchymal transition(EMT)status of C...Objective:Circulating tumor cells(CTCs)play a critical role in cancer metastasis,but their prevalence and significance remain unclear.This study attempted to track the epithelial-mesenchymal transition(EMT)status of CTCs in breast cancer patients and investigate their clinical relevance.Methods:In this study,the established negFACS-IF:E/M platform was applied to isolate rare CTCs and characterize their EMT status in breast cancer.A total of 89 breast cancer patients were recruited,including stage 0–III(n=60)and late stage(n=29)cases.Results:Using the negFACS-IF:E/M platform,it was found that in human epidermal growth factor receptor 2(HER2)+patients,mesenchymal CTCs usually exhibited a high percentage of HER2+cells.Stage IV breast cancer patients had considerably more CTCs than stage 0–III patients.Among stage 0–III breast cancers,the HER2 subtype included a significantly higher percentage of mesenchymal and biphenotypic(epithelial and mesenchymal)CTCs than the luminal A or B subtypes.Among stage IV patients,CTCs were predominantly epithelial in cases with local recurrence and were more mesenchymal in cases with distant metastasis.By applying a support vector machine(SVM)algorithm,the EMT status of CTCs could distinguish between breast cancer cases with metastasis/local recurrence and those without recurrence.Conclusions:The negFACS-IF:E/M platform provides a flexible and generally acceptable method for the highly sensitive and specific detection of CTCs and their EMT traits in breast cancer.This study demonstrated that the EMT status of CTCs had high clinical relevance in breast cancer,especially in predicting the distant metastasis or local recurrence of breast cancer.展开更多
Objective:To investigate the expression levels and clinical prognosis of tyrosine protein kinase-7(PTK7),human epidermal growth factor receptor 2(HER-2)and minichromosome maintenance protein 5(Mcm5)in esophageal squam...Objective:To investigate the expression levels and clinical prognosis of tyrosine protein kinase-7(PTK7),human epidermal growth factor receptor 2(HER-2)and minichromosome maintenance protein 5(Mcm5)in esophageal squamous cell carcinoma(ESCC)value.Methods:180 patients with ESCC were enrolled as the study subjects.Tumor tissues were collected and 100 paracancerous tissues were randomly collected.The expression levels of PTK7,HER-2 and Mcm5 proteins were detected by immunohistochemical staining,and their clinical pathological features and prognosis.Relationship.Results:The positive rates of PTK7,HER-2 and Mcm5 in ESCC tissues were significantly higher than those in adjacent tissues(P<0.05).The positive rate of PTK7 in lymphatic metastasis was significantly higher than that in lymphatic metastasis(P<0.05).The tumor body diameter was greater than 2 cm,the TNM stage was stage III and IV,and the HER-2 positive rate of ESCC tissues with lymphatic metastasis was significantly increased(P<0.05).The positive rate of Mcm5 in stage III and IV and combined lymphatic metastasis ESCC was higher in TNM stage(P<0.05).The expression level of PTK7 in ESCC tissues was positively correlated with lymphatic metastasis(P<0.05).HER-2 was positively correlated with TNM stage and lymphatic metastasis(P<0.05).Mcm5 was positively correlated with tumor size,TNM stage and lymphatic metastasis(P<0.05).The tumor-free survival of PTK7,HER-2,and Mcm5-positive ESCC patients was significantly shorter than that of the negative group(P<0.05).Conclusion:The expression levels of PTK7,HER-2,and Mcm5 were significantly up-regulated in ESCC tissues,and high levels of HER-2 and Mcm5 predicted more severe pathological stage and lymphatic metastasis,and PTK7,HER-2,Mcm5 and worse.Prognosis is related.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Epidermal growth factor receptor(EGFR)signaling has become an importanttarget for drug development becauseEGFR signaling enhances tumor cell proliferation,migration,and invasion and inhibits apoptosis.However,theresults of clinical trials using EGFR inhibitors in patients with solid tumors have been disappointing.Here,wereport a protective effect of the EGFR inhibitors AG1478 and PD153035 against cell death induced by acute hy-poxia,which contrasts with their proapoptotic effects under normoxia.Under hypoxic conditions,both agents re-
文摘AIM To demonstrate the relationship betweenH-ras oncogene and hepatocellular carcinoma(HCC) metastasis.METHODS Activated H-ras oncogene wastransfected into SMMC 7721, a cell line derivedfrom human HCC, by calcium phosphatetransfection method. Some metastasis-relatedparameters were detected in vitro, includingadhesion assay, migration assay, expression ofcollagenase ⅣV (c ⅣV ase) and epidermal growthfactor receptor (EGFR).RESULTS The abilities of H-ras-transfected cellclones in adhesion to laminin (LN) or fibronectin(FN), migration, c Ⅳ ase secretion increasedmarkedly, and the expression of EGFR elevatedmoderately. More importantly, these alterationswere consistent positively with the expressionof p21, the protein product of H-ras oncogene.CONCLUSION H-ras oncogene could inducethe metastatic phenotype of HCC cell in vitro toraise its metastatic potential.
基金mostly supported through the funding provided by the National Natural Science Foundation of China(Grant No.81702866)the Key Program of the Natural Science Foundation of Zhejiang Province(Grant No.LZ16H160002)+2 种基金the Zhejiang Provincial Program for the Cultivation of HighLevel Innovative Health Talentsthe Foundation of the Education Department of Zhejiang Province(Grant No.Y201636451)partially supported through funding provided by the National Natural Science Foundation of China(Grant No.81472666)。
文摘Objective:Circulating tumor cells(CTCs)play a critical role in cancer metastasis,but their prevalence and significance remain unclear.This study attempted to track the epithelial-mesenchymal transition(EMT)status of CTCs in breast cancer patients and investigate their clinical relevance.Methods:In this study,the established negFACS-IF:E/M platform was applied to isolate rare CTCs and characterize their EMT status in breast cancer.A total of 89 breast cancer patients were recruited,including stage 0–III(n=60)and late stage(n=29)cases.Results:Using the negFACS-IF:E/M platform,it was found that in human epidermal growth factor receptor 2(HER2)+patients,mesenchymal CTCs usually exhibited a high percentage of HER2+cells.Stage IV breast cancer patients had considerably more CTCs than stage 0–III patients.Among stage 0–III breast cancers,the HER2 subtype included a significantly higher percentage of mesenchymal and biphenotypic(epithelial and mesenchymal)CTCs than the luminal A or B subtypes.Among stage IV patients,CTCs were predominantly epithelial in cases with local recurrence and were more mesenchymal in cases with distant metastasis.By applying a support vector machine(SVM)algorithm,the EMT status of CTCs could distinguish between breast cancer cases with metastasis/local recurrence and those without recurrence.Conclusions:The negFACS-IF:E/M platform provides a flexible and generally acceptable method for the highly sensitive and specific detection of CTCs and their EMT traits in breast cancer.This study demonstrated that the EMT status of CTCs had high clinical relevance in breast cancer,especially in predicting the distant metastasis or local recurrence of breast cancer.
基金Subject of Nanchong Science and Technology Bureau.Project No:18SXHZ0381.
文摘Objective:To investigate the expression levels and clinical prognosis of tyrosine protein kinase-7(PTK7),human epidermal growth factor receptor 2(HER-2)and minichromosome maintenance protein 5(Mcm5)in esophageal squamous cell carcinoma(ESCC)value.Methods:180 patients with ESCC were enrolled as the study subjects.Tumor tissues were collected and 100 paracancerous tissues were randomly collected.The expression levels of PTK7,HER-2 and Mcm5 proteins were detected by immunohistochemical staining,and their clinical pathological features and prognosis.Relationship.Results:The positive rates of PTK7,HER-2 and Mcm5 in ESCC tissues were significantly higher than those in adjacent tissues(P<0.05).The positive rate of PTK7 in lymphatic metastasis was significantly higher than that in lymphatic metastasis(P<0.05).The tumor body diameter was greater than 2 cm,the TNM stage was stage III and IV,and the HER-2 positive rate of ESCC tissues with lymphatic metastasis was significantly increased(P<0.05).The positive rate of Mcm5 in stage III and IV and combined lymphatic metastasis ESCC was higher in TNM stage(P<0.05).The expression level of PTK7 in ESCC tissues was positively correlated with lymphatic metastasis(P<0.05).HER-2 was positively correlated with TNM stage and lymphatic metastasis(P<0.05).Mcm5 was positively correlated with tumor size,TNM stage and lymphatic metastasis(P<0.05).The tumor-free survival of PTK7,HER-2,and Mcm5-positive ESCC patients was significantly shorter than that of the negative group(P<0.05).Conclusion:The expression levels of PTK7,HER-2,and Mcm5 were significantly up-regulated in ESCC tissues,and high levels of HER-2 and Mcm5 predicted more severe pathological stage and lymphatic metastasis,and PTK7,HER-2,Mcm5 and worse.Prognosis is related.
