Early screening is crucial for the prevention of intestinal-type gastric cancer.The current study aimed to ascertain the molecular evolution of intestinal-type gastric cancer based on the Correa cascade for precise ga...Early screening is crucial for the prevention of intestinal-type gastric cancer.The current study aimed to ascertain the molecular evolution of intestinal-type gastric cancer based on the Correa cascade for precise gastric cancer screening.We collected sequential lesions of the Correa cascade in the formalin-fixed and paraffin-embedded endoscopic submucosal dissection(ESD)-resected specimens from 14 Chinese patients by microdissection,and subsequently determined the profiles of somatic aberrations during gastric carcinogenesis using whole-exome sequencing,identifying multiple variants at different Correa stages.The results showed that TP53,PCLO,and PRKDC were the most frequently mutated genes in early gastric cancer(EGC).We found a high frequency of TP53 alterations in low-grade intraepithelial neoplasia(LGIN),which further increased in high-grade intraepithelial neoplasia(HGIN)and EGC.Intestinal metaplasia(IM)showed no significant correlation with EGC in terms of mutational spectra,whereas both LGIN and HGIN showed higher genomic similarities to EGC,compared with IM.Based on Jaccard similarity coefficients,we constructed three evolutionary models,with most patients showing linear progression from LGIN to HGIN,ultimately resulting in EGC.The extracellular matrix-receptor interaction pathway was revealed to be involved in the linear evolution.Additionally,the retrospective validation study of 39 patients diagnosed with LGIN indicated that PRKDC mutations,in addition to TP53 mutations,may drive LGIN progression to HGIN or EGC.In conclusion,the current study unveils the genomic evolution across the Correa cascade of intestinal-type gastric cancer,elucidates the underlying molecular mechanisms of gastric carcinogenesis,and provides evidence for potential personalized gastric cancer surveillance.展开更多
Objective:To evalueate hepatoprotective effects Feronia elephantum(F.elephantum)correa against thioacctamide(TA)induced liver necrosis in diabetic rats.Methods:Male wistar rats were made diabetic with alloxan(160 mg/k...Objective:To evalueate hepatoprotective effects Feronia elephantum(F.elephantum)correa against thioacctamide(TA)induced liver necrosis in diabetic rats.Methods:Male wistar rats were made diabetic with alloxan(160 mg/kg)on day 0 of the study.They were intoxicated with hepatotoxicant(thioacetamide,300 mg/kg,ip)on day 9 of study to produce liver necrosis.Effects of 7 day daily once administration(day 2 to day 9)of EF(400 and 800 mg/kg,po)were evaluated on necorosis of liver in terms of mortality,liver volume,liver weight,serum aspartate aminotransferase(AST)and serum alanine transaminase(ALT),and histopathology of liver sections(for signs of necorosis and inflammation)on day-9 of the study.Separate groups of rats with treated only with alloxan(DA control),thioacetamide(TA control)and both(TA+DA control)were maintained.Results:FE significantly lowered the mortality rate and showed improvement in liver function parameters in TA-induced diabetic rats without change in liver weight,volume and serum glucose levels.Conclusions:FE showed promising activity against TA-induced liver necorsis in diabetic rats and so might be useful for prevention of liver complications in DM.展开更多
Gastric cancer(GC)is both the fifth most common cancer worldwide and the fifth in mortality.Owing to a lack of symptoms in the early stages and unspecific cli-nical presentation in the later stages,GC is usually diagn...Gastric cancer(GC)is both the fifth most common cancer worldwide and the fifth in mortality.Owing to a lack of symptoms in the early stages and unspecific cli-nical presentation in the later stages,GC is usually diagnosed at advanced stages.This means that only approximately 60%of patients are eligible for curative treat-ment,and overall,GC patients have a 5-year survival rate of only 28.3%,under-scoring the importance of developing new treatment strategies.Drug repurposing involves identifying new therapeutic uses for approved drugs and is a promising strategy for cancer treatment because of its lower cost and faster development time.A variety of targetable pathways are involved in GC progression,including the mitogen-activated protein kinase,phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin,p53,Janus kinase 2/signal transducer and activator of transcription 3,hypoxia-inducible factor-1α,wingless-type mouse mammary tumor virus integration site family/beta-catenin(Wnt/β-catenin),nuclear factor kappa B,and Hippo pathways.Therefore,the repurposing of drugs targeting these pathways represents an interesting option in the search for new treatments for GC.In this review,we explore some relevant pathways involved in the development of GC and the possibilities of repurposing drugs that target them.展开更多
Over the last two decades there has been a broad paradigm shift in our understanding of gastric cancer(GC)and its premalignant states from gross histological models to increasingly precise molecular descriptions.In th...Over the last two decades there has been a broad paradigm shift in our understanding of gastric cancer(GC)and its premalignant states from gross histological models to increasingly precise molecular descriptions.In this review we reflect upon the historic approaches to describing premalignant lesions and GC,highlight the current molecular landscape and how this could inform future risk assessment prevention strategies.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.81871959,82373143,and 82003180).
文摘Early screening is crucial for the prevention of intestinal-type gastric cancer.The current study aimed to ascertain the molecular evolution of intestinal-type gastric cancer based on the Correa cascade for precise gastric cancer screening.We collected sequential lesions of the Correa cascade in the formalin-fixed and paraffin-embedded endoscopic submucosal dissection(ESD)-resected specimens from 14 Chinese patients by microdissection,and subsequently determined the profiles of somatic aberrations during gastric carcinogenesis using whole-exome sequencing,identifying multiple variants at different Correa stages.The results showed that TP53,PCLO,and PRKDC were the most frequently mutated genes in early gastric cancer(EGC).We found a high frequency of TP53 alterations in low-grade intraepithelial neoplasia(LGIN),which further increased in high-grade intraepithelial neoplasia(HGIN)and EGC.Intestinal metaplasia(IM)showed no significant correlation with EGC in terms of mutational spectra,whereas both LGIN and HGIN showed higher genomic similarities to EGC,compared with IM.Based on Jaccard similarity coefficients,we constructed three evolutionary models,with most patients showing linear progression from LGIN to HGIN,ultimately resulting in EGC.The extracellular matrix-receptor interaction pathway was revealed to be involved in the linear evolution.Additionally,the retrospective validation study of 39 patients diagnosed with LGIN indicated that PRKDC mutations,in addition to TP53 mutations,may drive LGIN progression to HGIN or EGC.In conclusion,the current study unveils the genomic evolution across the Correa cascade of intestinal-type gastric cancer,elucidates the underlying molecular mechanisms of gastric carcinogenesis,and provides evidence for potential personalized gastric cancer surveillance.
文摘Objective:To evalueate hepatoprotective effects Feronia elephantum(F.elephantum)correa against thioacctamide(TA)induced liver necrosis in diabetic rats.Methods:Male wistar rats were made diabetic with alloxan(160 mg/kg)on day 0 of the study.They were intoxicated with hepatotoxicant(thioacetamide,300 mg/kg,ip)on day 9 of study to produce liver necrosis.Effects of 7 day daily once administration(day 2 to day 9)of EF(400 and 800 mg/kg,po)were evaluated on necorosis of liver in terms of mortality,liver volume,liver weight,serum aspartate aminotransferase(AST)and serum alanine transaminase(ALT),and histopathology of liver sections(for signs of necorosis and inflammation)on day-9 of the study.Separate groups of rats with treated only with alloxan(DA control),thioacetamide(TA control)and both(TA+DA control)were maintained.Results:FE significantly lowered the mortality rate and showed improvement in liver function parameters in TA-induced diabetic rats without change in liver weight,volume and serum glucose levels.Conclusions:FE showed promising activity against TA-induced liver necorsis in diabetic rats and so might be useful for prevention of liver complications in DM.
基金Supported by the Instituto de Salud Carlos III,No.PI24/00784,No.PI24/00737,No.PI21/01181,No.PI21/00333 and No.INT22/00112Departamento de Universidad,Innovación y Transformación Digital Gobierno de Navarra,No.0011-1408-2024-000011,No.0011-1408-2022-000010.
文摘Gastric cancer(GC)is both the fifth most common cancer worldwide and the fifth in mortality.Owing to a lack of symptoms in the early stages and unspecific cli-nical presentation in the later stages,GC is usually diagnosed at advanced stages.This means that only approximately 60%of patients are eligible for curative treat-ment,and overall,GC patients have a 5-year survival rate of only 28.3%,under-scoring the importance of developing new treatment strategies.Drug repurposing involves identifying new therapeutic uses for approved drugs and is a promising strategy for cancer treatment because of its lower cost and faster development time.A variety of targetable pathways are involved in GC progression,including the mitogen-activated protein kinase,phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin,p53,Janus kinase 2/signal transducer and activator of transcription 3,hypoxia-inducible factor-1α,wingless-type mouse mammary tumor virus integration site family/beta-catenin(Wnt/β-catenin),nuclear factor kappa B,and Hippo pathways.Therefore,the repurposing of drugs targeting these pathways represents an interesting option in the search for new treatments for GC.In this review,we explore some relevant pathways involved in the development of GC and the possibilities of repurposing drugs that target them.
文摘Over the last two decades there has been a broad paradigm shift in our understanding of gastric cancer(GC)and its premalignant states from gross histological models to increasingly precise molecular descriptions.In this review we reflect upon the historic approaches to describing premalignant lesions and GC,highlight the current molecular landscape and how this could inform future risk assessment prevention strategies.
