Gastric cancer(GC)is one of the most common malignancies and remains the second leading cause of cancer-related death worldwide.There is an increasing understanding of the roles that genetic and epigenetic alterations...Gastric cancer(GC)is one of the most common malignancies and remains the second leading cause of cancer-related death worldwide.There is an increasing understanding of the roles that genetic and epigenetic alterations play in GCs.Recent studies using nextgeneration sequencing(NGS)have revealed a number of potential cancer-driving genes in GC.Whole-exome sequencing of GC has identified recurrent somatic mutations in the chromatin remodeling gene ARID1A and alterations in the cell adhesion gene FAT4,a member of the cadherin gene family.Mutations in chromatin remodeling genes(ARID1A,MLL3 and MLL)have been found in 47%of GCs.Whole-genome sequencing and whole-transcriptome sequencing analyses have also discovered novel alterations in GC.Recent studies of cancer epigenetics have revealed widespread alterations in genes involved in the epigenetic machinery,such as DNA methylation,histone modifications,nucleosome positioning,noncoding RNAs and microRNAs.Recent advances in molecular research on GC have resulted in the introduction of new diagnostic and therapeutic strategies into clinical settings.The antihuman epidermal growth receptor 2(HER2)antibody trastuzumab has led to an era of personalized therapy in GC.In addition,ramucirumab,a monoclonal antibody targeting vascular endothelial growth factor receptor(VEGFR)-2,is the first biological treatment that showed survival benefits as a single-agent therapy in patients with advanced GC who progressed after firstline chemotherapy.Using NGS to systematically identify gene alterations in GC is a promising approach with remarkable potential for investigating the pathogenesis of GC and identifying novel therapeutic targets,as well as useful biomarkers.In this review,we will summarize the recent advances in the understanding of the molecular pathogenesis of GC,focusing on the potential use of these genetic and epigenetic alterations as diagnostic biomarkers and novel therapeutic targets.展开更多
The present paper reports the results of a detailed experimental study aimed at investigating the dynamics of a laminar separation bubble, from the origin of separation up to the breakdown to turbulence of the large s...The present paper reports the results of a detailed experimental study aimed at investigating the dynamics of a laminar separation bubble, from the origin of separation up to the breakdown to turbulence of the large scale co- herent structures generated as a consequence of the Kelvin-Helmholtz instability process. Measurements have been performed along a fiat plate installed within a double contoured test section, designed to produce an adverse pressure gradient typical of Ultra-High-Lift turbine blade profiles, which induces the formation of a laminar separation bubble at low Reynolds number condition. Measurements have been carried out by means of comple- mentary techniques： hot-wire （HW） anemometry, Laser Doppler Velocirnetry （LDV） and Particle Image Veloci- metry （PIV）. The high accuracy 2-dimensional LDV results allow investigating reverse flow magnitude and both Reynolds normal and shear stress distributions along the separated flow region, while the high frequency response of the HW anemometer allows analyzing the amplification process of flow oscillations induced by instability mechanisms. PIV results complement the flow field analysis providing information on the generation and evolu- tion of the large scale coherent structures shed as a consequence of the separated shear layer roll-up, through in- stantaneous velocity vector maps. The simultaneous analysis of the data obtained by means of the different meas- uring techniques allows an in depth view of the instability mechanisms involved in the transition/reattachrnent processes of the separated shear layer.展开更多
基金Supported by Grants-in-Aid for Scientific Research from the Ministry of Education,Culture,Sports,Science and Technology of Japan
文摘Gastric cancer(GC)is one of the most common malignancies and remains the second leading cause of cancer-related death worldwide.There is an increasing understanding of the roles that genetic and epigenetic alterations play in GCs.Recent studies using nextgeneration sequencing(NGS)have revealed a number of potential cancer-driving genes in GC.Whole-exome sequencing of GC has identified recurrent somatic mutations in the chromatin remodeling gene ARID1A and alterations in the cell adhesion gene FAT4,a member of the cadherin gene family.Mutations in chromatin remodeling genes(ARID1A,MLL3 and MLL)have been found in 47%of GCs.Whole-genome sequencing and whole-transcriptome sequencing analyses have also discovered novel alterations in GC.Recent studies of cancer epigenetics have revealed widespread alterations in genes involved in the epigenetic machinery,such as DNA methylation,histone modifications,nucleosome positioning,noncoding RNAs and microRNAs.Recent advances in molecular research on GC have resulted in the introduction of new diagnostic and therapeutic strategies into clinical settings.The antihuman epidermal growth receptor 2(HER2)antibody trastuzumab has led to an era of personalized therapy in GC.In addition,ramucirumab,a monoclonal antibody targeting vascular endothelial growth factor receptor(VEGFR)-2,is the first biological treatment that showed survival benefits as a single-agent therapy in patients with advanced GC who progressed after firstline chemotherapy.Using NGS to systematically identify gene alterations in GC is a promising approach with remarkable potential for investigating the pathogenesis of GC and identifying novel therapeutic targets,as well as useful biomarkers.In this review,we will summarize the recent advances in the understanding of the molecular pathogenesis of GC,focusing on the potential use of these genetic and epigenetic alterations as diagnostic biomarkers and novel therapeutic targets.
文摘The present paper reports the results of a detailed experimental study aimed at investigating the dynamics of a laminar separation bubble, from the origin of separation up to the breakdown to turbulence of the large scale co- herent structures generated as a consequence of the Kelvin-Helmholtz instability process. Measurements have been performed along a fiat plate installed within a double contoured test section, designed to produce an adverse pressure gradient typical of Ultra-High-Lift turbine blade profiles, which induces the formation of a laminar separation bubble at low Reynolds number condition. Measurements have been carried out by means of comple- mentary techniques： hot-wire （HW） anemometry, Laser Doppler Velocirnetry （LDV） and Particle Image Veloci- metry （PIV）. The high accuracy 2-dimensional LDV results allow investigating reverse flow magnitude and both Reynolds normal and shear stress distributions along the separated flow region, while the high frequency response of the HW anemometer allows analyzing the amplification process of flow oscillations induced by instability mechanisms. PIV results complement the flow field analysis providing information on the generation and evolu- tion of the large scale coherent structures shed as a consequence of the separated shear layer roll-up, through in- stantaneous velocity vector maps. The simultaneous analysis of the data obtained by means of the different meas- uring techniques allows an in depth view of the instability mechanisms involved in the transition/reattachrnent processes of the separated shear layer.
