AIM: To analyze the expression profiles of premalignant and/or preclinical lesions of gastric cancers.METHODS: We analyzed the expression profiles of normal gastric pit, tubular adenoma and carcinoma in situ using mic...AIM: To analyze the expression profiles of premalignant and/or preclinical lesions of gastric cancers.METHODS: We analyzed the expression profiles of normal gastric pit, tubular adenoma and carcinoma in situ using microdissected cells from routine gastric biopsies. For the DNA microarray analysis of formalin-fixed samples,we developed a simple and reproducible RNA extraction and linear amplification procedure applying two polymerasebinding sites. The amplification procedure took only 8 h and yielded comparable DNA microarray data between formalin-fixed tissues and unfixed controls.RESULTS: In comparison with normal pit, adenoma/carcinoma showed 504 up-regulated and 29 down-regulated genes at the expected false significance rate 0.15%. The differential expression between adenoma and carcinoma in situ was subtle: 50 and 22 genes were up-, and down-regulated in carcinomas at the expected false significance rate of 0.61%, respectively. Differentially expressed genes were grouped according to patterns of the sequential changes for the 'tendency analysis' in the gastric mucosaadenoma-carcinoma sequence.CONCLUSION: Groups of genes are shown to reflect the sequential expression changes in the early carcinogenic steps of stomach cancer. It is suggested that molecular carcinogenic pathways could be analyzed using routinely processed biopsies.展开更多
The biosynthesis of host lipids and/or lipid droplets(LDs)has been studied extensively as a putative therapeutic target in diverse viral infections.However,directly targeting the LD lipolytic catabolism in virus-infec...The biosynthesis of host lipids and/or lipid droplets(LDs)has been studied extensively as a putative therapeutic target in diverse viral infections.However,directly targeting the LD lipolytic catabolism in virus-infected cells has not been widely investigated.Here,we show the linkage of the LD-associated lipase activation to the breakdown of LDs for the generation of free fatty acids(FFAs)at the late stage of diverse RNA viral infections,which represents a broad-spectrum antiviral target.Dysfunction of membrane transporter systems due to virus-induced cell injury results in intracellular malnutrition at the late stage of infection,thereby making the virus more dependent on the FFAs generated from LD storage for viral morphogenesis and as a source of energy.The replication of SARS-CoV-2 and influenza A virus(IAV),which is suppressed by the treatment with LD-associated lipases inhibitors,is rescued by supplementation with FFAs.The administration of lipase inhibitors,either individually or in a combination with virus-targeting drugs,protects mice from lethal IAV infection and mitigates severe lung lesions in SARS-CoV-2-infected hamsters.Moreover,the lipase inhibitors significantly reduce proinflammatory cytokine levels in the lungs of SARS-CoV-2-and IAV-challenged animals,a cause of a cytokine storm important for the critical infection or mortality of COVID-19 and IAV patients.In conclusion,the results reveal that lipase-mediated intracellular LD lipolysis is commonly exploited to facilitate RNA virus replication and furthermore suggest that pharmacological inhibitors of LD-associated lipases could be used to curb current COVID-19-and future pandemic outbreaks of potentially troublesome RNA virus infection in humans.展开更多
基金Supported by a Korea Research Foundation Grant, KRF-2003-041-E00052
文摘AIM: To analyze the expression profiles of premalignant and/or preclinical lesions of gastric cancers.METHODS: We analyzed the expression profiles of normal gastric pit, tubular adenoma and carcinoma in situ using microdissected cells from routine gastric biopsies. For the DNA microarray analysis of formalin-fixed samples,we developed a simple and reproducible RNA extraction and linear amplification procedure applying two polymerasebinding sites. The amplification procedure took only 8 h and yielded comparable DNA microarray data between formalin-fixed tissues and unfixed controls.RESULTS: In comparison with normal pit, adenoma/carcinoma showed 504 up-regulated and 29 down-regulated genes at the expected false significance rate 0.15%. The differential expression between adenoma and carcinoma in situ was subtle: 50 and 22 genes were up-, and down-regulated in carcinomas at the expected false significance rate of 0.61%, respectively. Differentially expressed genes were grouped according to patterns of the sequential changes for the 'tendency analysis' in the gastric mucosaadenoma-carcinoma sequence.CONCLUSION: Groups of genes are shown to reflect the sequential expression changes in the early carcinogenic steps of stomach cancer. It is suggested that molecular carcinogenic pathways could be analyzed using routinely processed biopsies.
基金Basic Science Research Program(2020R1A2B03002517 and 2021R1A2C1094274)through the National Research Foundation of Korea and the KRIBB Research Initiative Program(KGM 5242221)which are funded by the Ministry of Science,ICT and Future Planning,Republic of Korea.
文摘The biosynthesis of host lipids and/or lipid droplets(LDs)has been studied extensively as a putative therapeutic target in diverse viral infections.However,directly targeting the LD lipolytic catabolism in virus-infected cells has not been widely investigated.Here,we show the linkage of the LD-associated lipase activation to the breakdown of LDs for the generation of free fatty acids(FFAs)at the late stage of diverse RNA viral infections,which represents a broad-spectrum antiviral target.Dysfunction of membrane transporter systems due to virus-induced cell injury results in intracellular malnutrition at the late stage of infection,thereby making the virus more dependent on the FFAs generated from LD storage for viral morphogenesis and as a source of energy.The replication of SARS-CoV-2 and influenza A virus(IAV),which is suppressed by the treatment with LD-associated lipases inhibitors,is rescued by supplementation with FFAs.The administration of lipase inhibitors,either individually or in a combination with virus-targeting drugs,protects mice from lethal IAV infection and mitigates severe lung lesions in SARS-CoV-2-infected hamsters.Moreover,the lipase inhibitors significantly reduce proinflammatory cytokine levels in the lungs of SARS-CoV-2-and IAV-challenged animals,a cause of a cytokine storm important for the critical infection or mortality of COVID-19 and IAV patients.In conclusion,the results reveal that lipase-mediated intracellular LD lipolysis is commonly exploited to facilitate RNA virus replication and furthermore suggest that pharmacological inhibitors of LD-associated lipases could be used to curb current COVID-19-and future pandemic outbreaks of potentially troublesome RNA virus infection in humans.
