BACKGROUND Although surgery remains the primary treatment for gastric cancer(GC),the identification of effective alternative treatments for individuals for whom surgery is unsuitable holds significance.HER2 overexpres...BACKGROUND Although surgery remains the primary treatment for gastric cancer(GC),the identification of effective alternative treatments for individuals for whom surgery is unsuitable holds significance.HER2 overexpression occurs in approximately 15%-20%of advanced GC cases,directly affecting treatment-related decisions.Spectral-computed tomography(sCT)enables the quantification of material compositions,and sCT iodine concentration parameters have been demonstrated to be useful for the diagnosis of GC and prediction of its invasion depth,angioge-nesis,and response to systemic chemotherapy.No existing report describes the prediction of GC HER2 status through histogram analysis based on sCT iodine maps(IMs).AIM To investigate whether whole-volume histogram analysis of sCT IMs enables the prediction of the GC HER2 status.METHODS This study was performed with data from 101 patients with pathologically confirmed GC who underwent preoperative sCT examinations.Nineteen parameters were extracted via sCT IM histogram analysis:The minimum,maximum,mean,standard deviation,variance,coefficient of variation,skewness,kurtosis,entropy,percentiles(1st,5th,10th,25th,50th,75th,90th,95th,and 99th),and lesion volume.Spearman correlations of the parameters with the HER2 status and clinicopathological parameters were assessed.Receiver operating characteristic curves were used to evaluate the parameters’diagnostic performance.RESULTS Values for the histogram parameters of the maximum,mean,standard deviation,variance,entropy,and percentiles were significantly lower in the HER2+group than in the HER2–group(all P<0.05).The GC differentiation and Lauren classification correlated significantly with the HER2 status of tumor tissue(P=0.001 and 0.023,respectively).The 99th percentile had the largest area under the curve for GC HER2 status identification(0.740),with 76.2%,sensitivity,65.0%specificity,and 67.3%accuracy.All sCT IM histogram parameters correlated positively with the GC HER2 status(r=0.237-0.337,P=0.001-0.017).CONCLUSION Whole-lesion histogram parameters derived from sCT IM analysis,and especially the 99th percentile,can serve as imaging biomarkers of HER2 overexpression in GC.展开更多
AIM:To investigate the effects of mitofusin-2(MFN2) on insulin sensitivity and its potential targets in the liver of rats fed with a high-fat diet(HFD).METHODS:Rats were fed with a control or HFD for 4 or 8 wk,and wer...AIM:To investigate the effects of mitofusin-2(MFN2) on insulin sensitivity and its potential targets in the liver of rats fed with a high-fat diet(HFD).METHODS:Rats were fed with a control or HFD for 4 or 8 wk,and were then infected with a control or an MFN2 expressing adenovirus once a week for 3wk starting from the 9th wk.Blood glucose(BG),plasma insulin and insulin sensitivity of rats were determined at end of the 4th and 8th wk,and after treatment with different amounts of MFN2 expressing adenovirus(108,109 or 1010 vp/kg body weight).BG levels were measured by Accu-chek Active Meter.Plasma insulin levels were analyzed by using a Rat insulin enzymelinked immunosorbent assay kit.Insulin resistance was evaluated by measuring the glucose infusion rate(GIR) using a hyperinsulinemic euglycemic clamp technique.The expression or phosphorylation levels of MFN2 and essential molecules in the insulin signaling pathway,such as insulin receptor(INSR),insulin receptor substrate 2(IRS2),phosphoinositide-3-kinase(PI3K),protein kinase beta(AKT2) and glucose transporter type 2(GLUT2) was assayed by quantitative real-time polymerase chain reaction and Western-blotting.RESULTS:After the end of 8wk,the body weight of rats receiving the normal control diet(ND) and the HFD was not significantly different(P>0.05).Compared with the ND group,GIR in the HFD group was significantly decreased(P<0.01),while the levels of BG,triglycerides(TG),total cholesterol(TC) and insulin in the HFD group were significantly higher than those in the ND group(P<0.05).Expression of MFN2 mRNA and protein in liver of rats was significantly downregulated in the HFD group(P<0.01) after 8 wk of HFD feeding.The expression of INSR,IRS2 and GLUT2 were down-regulated markedly(P<0.01).Although there were no changes in PI3K-P85 and AKT2 expression,their phosphorylation levels were decreased significantly(P<0.01).After intervention with MFN2 expressing adenovirus for 3wk,the expression of MFN2 mRNA and protein levels were up-regulated(P<0.01).There was no difference in body weight of rats between the groups.The levels of BG,TG,TC and insulin in rats were lower than those in the Ad group(P<0.05),but GIR in rats infected with Ad-MFN2 was significantly increased(P<0.01),compared with the Ad group.The expression of INSR,IRS2 and GLUT2 was increased,while phosphorylation levels of PI3K-P85 and AKT2 were increased(P<0.01),compared with the Ad group.CONCLUSION:HFDs induce insulin resistance,and this can be reversed by MFN2 over-expression targeting the insulin signaling pathway.展开更多
基金Supported by Science and Technology Program of Fujian Province,No.2021J01430Joint Funds for the Innovation of Science and Technology of Fujian Province,No.2021Y9229.
文摘BACKGROUND Although surgery remains the primary treatment for gastric cancer(GC),the identification of effective alternative treatments for individuals for whom surgery is unsuitable holds significance.HER2 overexpression occurs in approximately 15%-20%of advanced GC cases,directly affecting treatment-related decisions.Spectral-computed tomography(sCT)enables the quantification of material compositions,and sCT iodine concentration parameters have been demonstrated to be useful for the diagnosis of GC and prediction of its invasion depth,angioge-nesis,and response to systemic chemotherapy.No existing report describes the prediction of GC HER2 status through histogram analysis based on sCT iodine maps(IMs).AIM To investigate whether whole-volume histogram analysis of sCT IMs enables the prediction of the GC HER2 status.METHODS This study was performed with data from 101 patients with pathologically confirmed GC who underwent preoperative sCT examinations.Nineteen parameters were extracted via sCT IM histogram analysis:The minimum,maximum,mean,standard deviation,variance,coefficient of variation,skewness,kurtosis,entropy,percentiles(1st,5th,10th,25th,50th,75th,90th,95th,and 99th),and lesion volume.Spearman correlations of the parameters with the HER2 status and clinicopathological parameters were assessed.Receiver operating characteristic curves were used to evaluate the parameters’diagnostic performance.RESULTS Values for the histogram parameters of the maximum,mean,standard deviation,variance,entropy,and percentiles were significantly lower in the HER2+group than in the HER2–group(all P<0.05).The GC differentiation and Lauren classification correlated significantly with the HER2 status of tumor tissue(P=0.001 and 0.023,respectively).The 99th percentile had the largest area under the curve for GC HER2 status identification(0.740),with 76.2%,sensitivity,65.0%specificity,and 67.3%accuracy.All sCT IM histogram parameters correlated positively with the GC HER2 status(r=0.237-0.337,P=0.001-0.017).CONCLUSION Whole-lesion histogram parameters derived from sCT IM analysis,and especially the 99th percentile,can serve as imaging biomarkers of HER2 overexpression in GC.
文摘AIM:To investigate the effects of mitofusin-2(MFN2) on insulin sensitivity and its potential targets in the liver of rats fed with a high-fat diet(HFD).METHODS:Rats were fed with a control or HFD for 4 or 8 wk,and were then infected with a control or an MFN2 expressing adenovirus once a week for 3wk starting from the 9th wk.Blood glucose(BG),plasma insulin and insulin sensitivity of rats were determined at end of the 4th and 8th wk,and after treatment with different amounts of MFN2 expressing adenovirus(108,109 or 1010 vp/kg body weight).BG levels were measured by Accu-chek Active Meter.Plasma insulin levels were analyzed by using a Rat insulin enzymelinked immunosorbent assay kit.Insulin resistance was evaluated by measuring the glucose infusion rate(GIR) using a hyperinsulinemic euglycemic clamp technique.The expression or phosphorylation levels of MFN2 and essential molecules in the insulin signaling pathway,such as insulin receptor(INSR),insulin receptor substrate 2(IRS2),phosphoinositide-3-kinase(PI3K),protein kinase beta(AKT2) and glucose transporter type 2(GLUT2) was assayed by quantitative real-time polymerase chain reaction and Western-blotting.RESULTS:After the end of 8wk,the body weight of rats receiving the normal control diet(ND) and the HFD was not significantly different(P>0.05).Compared with the ND group,GIR in the HFD group was significantly decreased(P<0.01),while the levels of BG,triglycerides(TG),total cholesterol(TC) and insulin in the HFD group were significantly higher than those in the ND group(P<0.05).Expression of MFN2 mRNA and protein in liver of rats was significantly downregulated in the HFD group(P<0.01) after 8 wk of HFD feeding.The expression of INSR,IRS2 and GLUT2 were down-regulated markedly(P<0.01).Although there were no changes in PI3K-P85 and AKT2 expression,their phosphorylation levels were decreased significantly(P<0.01).After intervention with MFN2 expressing adenovirus for 3wk,the expression of MFN2 mRNA and protein levels were up-regulated(P<0.01).There was no difference in body weight of rats between the groups.The levels of BG,TG,TC and insulin in rats were lower than those in the Ad group(P<0.05),but GIR in rats infected with Ad-MFN2 was significantly increased(P<0.01),compared with the Ad group.The expression of INSR,IRS2 and GLUT2 was increased,while phosphorylation levels of PI3K-P85 and AKT2 were increased(P<0.01),compared with the Ad group.CONCLUSION:HFDs induce insulin resistance,and this can be reversed by MFN2 over-expression targeting the insulin signaling pathway.
