The cytochrome P4503A(CYP3A)gene family’s role in early progression of gastric cancer was comprehensively investigated.Its potential as a therapeutic target was evaluated.Upon literature review,aberrant expression of...The cytochrome P4503A(CYP3A)gene family’s role in early progression of gastric cancer was comprehensively investigated.Its potential as a therapeutic target was evaluated.Upon literature review,aberrant expression of the CYP3A gene family has a strong correlation with gastric cancer onset,although the precise underlying mechanisms remain unclear.To assess its potential as a biomarker for early diagnosis and a therapeutic target,we have provided a comprehensive review of the regulatory mechanisms governing CYP3A gene family expression in gastric cancer,as well as its relation with early tumor progression and the tumor microenvironment.The CYP3A gene family is crucial in the proliferation,migration,and invasion of gastric cancer cells and promotes cancer progression by modulating inflammatory responses and oxidative stress within the tumor microenvironment.Furthermore,genetic polymorphisms in CYP3A enzymes highlight its potential value in personalized medicine.Based on these findings,this paper explores the feasibility of developing inhibitors and activators targeting CYP3A enzymes and discusses potential applications in gene therapy.This research provides crucial theoretical support for the CYP3A gene family as an early diagnostic marker and therapeutic target for gastric cancer.In the future,multi-omics studies and large-scale clinical trials will be essential to advance clinical translation of these findings.展开更多
BACKGROUND Kidney transplantation is an effective renal replacement therapy for improving survival and quality of life in chronic kidney disease patients.Kidney transplant recipients need lifelong immunosuppression to...BACKGROUND Kidney transplantation is an effective renal replacement therapy for improving survival and quality of life in chronic kidney disease patients.Kidney transplant recipients need lifelong immunosuppression to prevent rejection and allograft dysfunction.Tacrolimus,a calcineurin inhibitor,is metabolized differently based on cytochrome P4503A(CYP3A)5 genetic variations and this impacts the graft outcome.AIM To examine the clinical outcomes in kidney transplant recipients affected by the variable metabolism of tacrolimus due to the CYP3A5 genetic variation,emphasizing personalized immunosuppression strategies to optimize efficacy,minimize toxicity,and enhance long-term graft survival.METHODS A retrospective study was conducted at a tertiary care center in Central India on 95 kidney transplant recipients.Patient demographics,medical history,CYP3A5 polymorphism,post-transplant investigations,graft biopsy results,preexisting comorbidities,history of post–kidney transplant infections,and new onset diabetes after transplantation(NODAT)was collected.Tacrolimus was initiated at 0.1 mg/kg/day for CYP3A5 expressors and 0.05 mg/kg/day for non-expressors,with dose adjustments to maintain target C0 levels of 7-10 ng/mL for first 6 months and 5-7 ng/mL from 6 months to 12 months posttransplant.Patients were followed regularly for one year for glomerular filtration rate(GFR),creatinine,and the tacrolimus trough concentration(ng/mL)/daily tacrolimus dose(mg/kg/day)ratio(C/D).A P value≤0.05 was considered statistically significant.RESULTS Kidney transplant recipients were classified as expressors(CYP3A51 carriers,n=35)and non-expressors(CYP3A5*3*3,n=60).Both groups were comparable for age,sex,and donor characteristics.Tacrolimus dose was comparable post-transplant except at 6 months and 12 months,where expressors required higher doses.Kidney function(creatinine and estimated GFR),NODAT,hypomagnesemia,and infections showed no significant differences between the two groups over 12 months of follow-up.Biopsy-proven acute rejection(BPAR)was found to be more in expressors(22.9%vs 13.3%,P=0.2340)though it was not found to be statistically significant.Nonexpressors had a significantly higher tacrolimus levels and C/D ratio at multiple follow-ups.CONCLUSION CYP3A5 expressors require higher tacrolimus doses to maintain therapeutic levels as compared to non-expressors.BPAR was higher in expressors but the difference was not significant.Graft function,infection rate,and NODAT were comparable irrespective of CYP3A5 expression status,emphasizing the importance of pretransplant CYP3A5 genotyping and therapeutic drug monitoring to guide tacrolimus dosing for individualized immunosuppressive management.展开更多
文摘The cytochrome P4503A(CYP3A)gene family’s role in early progression of gastric cancer was comprehensively investigated.Its potential as a therapeutic target was evaluated.Upon literature review,aberrant expression of the CYP3A gene family has a strong correlation with gastric cancer onset,although the precise underlying mechanisms remain unclear.To assess its potential as a biomarker for early diagnosis and a therapeutic target,we have provided a comprehensive review of the regulatory mechanisms governing CYP3A gene family expression in gastric cancer,as well as its relation with early tumor progression and the tumor microenvironment.The CYP3A gene family is crucial in the proliferation,migration,and invasion of gastric cancer cells and promotes cancer progression by modulating inflammatory responses and oxidative stress within the tumor microenvironment.Furthermore,genetic polymorphisms in CYP3A enzymes highlight its potential value in personalized medicine.Based on these findings,this paper explores the feasibility of developing inhibitors and activators targeting CYP3A enzymes and discusses potential applications in gene therapy.This research provides crucial theoretical support for the CYP3A gene family as an early diagnostic marker and therapeutic target for gastric cancer.In the future,multi-omics studies and large-scale clinical trials will be essential to advance clinical translation of these findings.
文摘BACKGROUND Kidney transplantation is an effective renal replacement therapy for improving survival and quality of life in chronic kidney disease patients.Kidney transplant recipients need lifelong immunosuppression to prevent rejection and allograft dysfunction.Tacrolimus,a calcineurin inhibitor,is metabolized differently based on cytochrome P4503A(CYP3A)5 genetic variations and this impacts the graft outcome.AIM To examine the clinical outcomes in kidney transplant recipients affected by the variable metabolism of tacrolimus due to the CYP3A5 genetic variation,emphasizing personalized immunosuppression strategies to optimize efficacy,minimize toxicity,and enhance long-term graft survival.METHODS A retrospective study was conducted at a tertiary care center in Central India on 95 kidney transplant recipients.Patient demographics,medical history,CYP3A5 polymorphism,post-transplant investigations,graft biopsy results,preexisting comorbidities,history of post–kidney transplant infections,and new onset diabetes after transplantation(NODAT)was collected.Tacrolimus was initiated at 0.1 mg/kg/day for CYP3A5 expressors and 0.05 mg/kg/day for non-expressors,with dose adjustments to maintain target C0 levels of 7-10 ng/mL for first 6 months and 5-7 ng/mL from 6 months to 12 months posttransplant.Patients were followed regularly for one year for glomerular filtration rate(GFR),creatinine,and the tacrolimus trough concentration(ng/mL)/daily tacrolimus dose(mg/kg/day)ratio(C/D).A P value≤0.05 was considered statistically significant.RESULTS Kidney transplant recipients were classified as expressors(CYP3A51 carriers,n=35)and non-expressors(CYP3A5*3*3,n=60).Both groups were comparable for age,sex,and donor characteristics.Tacrolimus dose was comparable post-transplant except at 6 months and 12 months,where expressors required higher doses.Kidney function(creatinine and estimated GFR),NODAT,hypomagnesemia,and infections showed no significant differences between the two groups over 12 months of follow-up.Biopsy-proven acute rejection(BPAR)was found to be more in expressors(22.9%vs 13.3%,P=0.2340)though it was not found to be statistically significant.Nonexpressors had a significantly higher tacrolimus levels and C/D ratio at multiple follow-ups.CONCLUSION CYP3A5 expressors require higher tacrolimus doses to maintain therapeutic levels as compared to non-expressors.BPAR was higher in expressors but the difference was not significant.Graft function,infection rate,and NODAT were comparable irrespective of CYP3A5 expression status,emphasizing the importance of pretransplant CYP3A5 genotyping and therapeutic drug monitoring to guide tacrolimus dosing for individualized immunosuppressive management.
