Gastric cancer is among the most frequently occurring cancers and a leading cause of cancer-related deaths globally.Because gastric cancer is highly heterogenous and comprised of different subtypes with distinct molec...Gastric cancer is among the most frequently occurring cancers and a leading cause of cancer-related deaths globally.Because gastric cancer is highly heterogenous and comprised of different subtypes with distinct molecular and clinical characteristics,the management of gastric cancer calls for better-defined,biomarker-guided,molecular-based treatment strategies.MET is a receptor tyrosine kinase mediating important physiologic processes,such as embryogenesis,tissue regeneration,and wound healing.However,mounting evidence suggests that aberrant MET pathway activation contributes to tumour proliferation and metastasis in multiple cancer types,including gastric cancer,and is associated with poor patient outcomes.As such,MET-targeting therapies are being actively developed and promising progress has been demonstrated,especially with MET tyrosine kinase inhibitors.This review aims to briefly introduce the role of MET alterations in gastric cancer and summarize in detail the current progress of MET tyrosine kinase inhibitors in this disease area with a focus on savolitinib,tepotinib,capmatinib,and crizotinib.Building on current knowledge,this review further discusses existing challenges in MET alterations testing,possible resistance mechanisms to MET inhibitors,and future directions of MET-targeting therapies.展开更多
BACKGROUND Cognitive reserve(CR)and the catechol-O-methyltransferase(COMT)Val/Met polymorphism are reportedly linked to negative symptoms in schizophrenia.However,the regulatory effect of the COMT genotype on the rela...BACKGROUND Cognitive reserve(CR)and the catechol-O-methyltransferase(COMT)Val/Met polymorphism are reportedly linked to negative symptoms in schizophrenia.However,the regulatory effect of the COMT genotype on the relationship between CR and negative symptoms is still unexamined.AIM To investigate whether the relationship between CR and negative symptoms could be regulated by the COMT Val/Met polymorphism.METHODS In a cross-sectional study,54 clinically stable patients with schizophrenia underwent assessments for the COMT genotype,CR,and negative symptoms.CR was estimated using scores in the information and similarities subtests of a short form of the Chinese version of the Wechsler Adult Intelligence Scale.RESULTS COMT Met-carriers exhibited fewer negative symptoms than Val homozygotes.In the total sample,significant negative correlations were found between negative symptoms and information,similarities.Associations between information,similarities and negative symptoms were observed in Val homozygotes only,with information and similarities showing interaction effects with the COMT genotype in relation to negative symptoms(information,β=-0.282,95%CI:-0.552 to-0.011,P=0.042;similarities,β=-0.250,95%CI:-0.495 to-0.004,P=0.046).CONCLUSION This study provides initial evidence that the association between negative symptoms and CR is under the regulation of the COMT genotype in schizophrenia.展开更多
文摘目的研究幽门螺杆菌(Hp)对肝癌HepG2细胞原癌基因C-Met表达的影响。方法将Hp与HepG2细胞共同培养,设置空白对照组、Hp组、C-Met抑制剂空白组和C-Met抑制剂Hp组,每组设副孔5个,采用CCK8试剂盒检测HepG2细胞增殖活性,采用Western blot和qPCR方法检测C-Met原癌基因蛋白和mRNA表达水平。结果相较于空白对照组,Hp处理组HepG2细胞增殖活性升高且与时间呈正相关,而C-Met抑制剂可以抑制HepG2细胞的增殖活性。同时,Hp组HepG2细胞C-Met基因蛋白和mRNA表达水平均上调,C-Met抑制剂组则显著下调。相较于Hp共培养12 h,共培养24 h C-Met蛋白和mRNA表达水平均上调。结论Hp促进HepG2细胞的增殖可能与其提高原癌基因C-Met的蛋白及其mRNA表达水平有关,为后续更深入研究肝癌发生发展的复杂机制提供了理论依据。
基金supported by the National Natural Science Foundation of China(Grant No.81602057)the Beijing Natural Science Foundation(Grant No.Z210015)。
文摘Gastric cancer is among the most frequently occurring cancers and a leading cause of cancer-related deaths globally.Because gastric cancer is highly heterogenous and comprised of different subtypes with distinct molecular and clinical characteristics,the management of gastric cancer calls for better-defined,biomarker-guided,molecular-based treatment strategies.MET is a receptor tyrosine kinase mediating important physiologic processes,such as embryogenesis,tissue regeneration,and wound healing.However,mounting evidence suggests that aberrant MET pathway activation contributes to tumour proliferation and metastasis in multiple cancer types,including gastric cancer,and is associated with poor patient outcomes.As such,MET-targeting therapies are being actively developed and promising progress has been demonstrated,especially with MET tyrosine kinase inhibitors.This review aims to briefly introduce the role of MET alterations in gastric cancer and summarize in detail the current progress of MET tyrosine kinase inhibitors in this disease area with a focus on savolitinib,tepotinib,capmatinib,and crizotinib.Building on current knowledge,this review further discusses existing challenges in MET alterations testing,possible resistance mechanisms to MET inhibitors,and future directions of MET-targeting therapies.
基金Supported by the National Natural Science Foundation of China,No.81971250 and No.82171501Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support,No.ZLRK202335Early Psychosis Cohort Program of Beijing Anding Hospital,No.ADDL-03.
文摘BACKGROUND Cognitive reserve(CR)and the catechol-O-methyltransferase(COMT)Val/Met polymorphism are reportedly linked to negative symptoms in schizophrenia.However,the regulatory effect of the COMT genotype on the relationship between CR and negative symptoms is still unexamined.AIM To investigate whether the relationship between CR and negative symptoms could be regulated by the COMT Val/Met polymorphism.METHODS In a cross-sectional study,54 clinically stable patients with schizophrenia underwent assessments for the COMT genotype,CR,and negative symptoms.CR was estimated using scores in the information and similarities subtests of a short form of the Chinese version of the Wechsler Adult Intelligence Scale.RESULTS COMT Met-carriers exhibited fewer negative symptoms than Val homozygotes.In the total sample,significant negative correlations were found between negative symptoms and information,similarities.Associations between information,similarities and negative symptoms were observed in Val homozygotes only,with information and similarities showing interaction effects with the COMT genotype in relation to negative symptoms(information,β=-0.282,95%CI:-0.552 to-0.011,P=0.042;similarities,β=-0.250,95%CI:-0.495 to-0.004,P=0.046).CONCLUSION This study provides initial evidence that the association between negative symptoms and CR is under the regulation of the COMT genotype in schizophrenia.
