Hepatocellular carcinoma(HCC)is the fifth most common cancer worldwide.Significant efforts have been devoted to identify new biomarkers for molecular imaging and targeted therapy of HCC.Copper is a nutritional metal r...Hepatocellular carcinoma(HCC)is the fifth most common cancer worldwide.Significant efforts have been devoted to identify new biomarkers for molecular imaging and targeted therapy of HCC.Copper is a nutritional metal required for the function of numerous enzymatic molecules in the metabolic pathways of human cells.Emerging evidence suggests that copper plays a role in cell proliferation and angiogenesis.Increased accumulation of copper ions was detected in tissue samples of HCC and many other cancers in humans.Altered copper metabolism is a new biomarker for molecular cancer imaging with position emission tomography(PET)using radioactive copper as a tracer.It has been reported that extrahepatic mouse hepatoma or HCC xenografts can be localized with PET using copper-64 chloride as a tracer,suggesting that copper metabolism is a new biomarker for the detection of HCC metastasis in areas of low physiological copper uptake.In addition to copper modulation therapy with copper chelators,short-interference RNA specific for human copper transporter 1(h Ctr1)may be used to suppress growth of HCC by blocking increased copper uptake mediated by h Ctr1.Furthermore,altered copper metabolism is a promising target for radionuclide therapy of HCC using therapeutic copper radionuclides.Copper metabolism has potential as a new theranostic biomarker for molecular imaging as well as targeted therapy of HCC.展开更多
We have developed a noninv asive imaging method to quantify in viwo drug delivery pharmaco-kinetics without the need for blood or tissue collection to determine drug concentration.By combining the techniques of hy per...We have developed a noninv asive imaging method to quantify in viwo drug delivery pharmaco-kinetics without the need for blood or tissue collection to determine drug concentration.By combining the techniques of hy perspectral imaging and a dorsal skinfold window chamber,this method enabled the real-time monitoring of vascular transport and tissue deposition of nano-particles labeled with near infrared(NIR)dye.Using this imaging method,we quantified the delivery pharmacokinetics of the native high-density lipoprotein(HDL)and epidermal growth factor receptor(EGFR)-targeted HDL nanoparticles and demonstrated these HDLs had long circulation time in blood stream(half-life>12h).These HDL nanoparticles could eficiently carry cargo DiR-BOA to extravasate from blood vesels,difuse through extr acellular matrix,and penetrate and be retained in the tumor site.The EGFR targeting specificity of EGFR-targeted HDL(EGFR-specific peptide conjugated HDL)was also visualized in vivo by competitive inhi bition with excess EGFR specifc peptide.In summary,this imaging technology may help point the way toward the development of novel imaging based pharmacokinetic assays for preclinical drugs and evaluation of drug delivery eficiency,providing a dynamic window into the devel opment and application of novel drug delivery systems.展开更多
In this investigation,sensitive and reproducible methods are described for quantitative determination of deflazacort in the presence of its degradation product.The method was based on high performance liquid chromatog...In this investigation,sensitive and reproducible methods are described for quantitative determination of deflazacort in the presence of its degradation product.The method was based on high performance liquid chromatography of the drug from its degradation product on reverse phase using Acquity UPLC BEH C18columns(1.7 urn,2.1 mm×150 mm)using acetonitrile and water(40:60 V/V)at a flow rate of 0.2 mL/minute in UPLC.UV detection was performed at 240.1 nm.Deflazacort was subjected to oxidative,acid,base,hydrolytic,thermal and photolytic degradation.The drug was found to be stable in water and thermal stress,as well as under neutral stress conditions.However,forced-degradation study performed on deflazacort showed that the drug degraded under alkaline,acid and photolytic stress.The degradation products were well resolved from the main peak,which proved the stability-indicating power of the method.The developed method was validated as per ICH guidelines with respect to accuracy,linearity,limit of detection,limit of quantification,accuracy,precision and robustness,selectivity and specificity.Apart from the aforementioned,the results of the present study also emphasize the importance of isolation characterization and identification of degradant.Hence,an attempt was made to identify the degradants in deflazacort.One of the degradation products of deflazacort was isolated and identified by the FTIR,NMR and LC-MS study.展开更多
The purpose of this study was to assess usefulness of local binary patterns (LBP) and related texture features, namely completed local binary patterns (CLBP) and local ternary patterns (LTP), for the classification of...The purpose of this study was to assess usefulness of local binary patterns (LBP) and related texture features, namely completed local binary patterns (CLBP) and local ternary patterns (LTP), for the classification of emphysema subtypes on low-dose CT images. Fifty patients (34 men and 16 women;age, 67.5 ± 10.1 years) who underwent low-dose CT (60 mAs) were included. They were comprised of 17 never smokers, 13 smokers without COPD, and 20 smokers with COPD. By consensus reading of low-dose CT images from these patients, two radiologists selected 3681 nonoverlapping regions of interest (ROIs) and annotated them as one of the following three classes: normal tissue, centrilobular emphysema, and paraseptal emphysema. From these ROIs, histogram of CT densities, LBP, CLBP, and LTP were calculated, and the 3 types of texture histograms were concatenated with the CT density histogram. These 3 types of histograms (referred to as combined LBP, combined CLBP, and combined LTP) were used to classify ROI using linear support vector machine. For each type of the combined histogram, the accuracy of classification was determined by patient-based 10-fold cross validation. The best accuracy of combined LBP, combined CLBP, and combined LTP were 81.36%, 82.99%, and 83.29%, respectively. Compared to the classification accuracies obtained with combined LBP, those with combined LTP or combined CLBP were consistently improved. In conclusion, the results of this study suggest that, on low-dose CT, LTP and CLBP were more useful for the classification of emphysema subtypes than LBP.展开更多
Extracellular vesicles(EVs)show potential for early diagnosis of Alzheimer’s disease(AD)and monitoring of its progression.However,EV-based AD diagnosis faces challenges due to the small size and low abundance of biom...Extracellular vesicles(EVs)show potential for early diagnosis of Alzheimer’s disease(AD)and monitoring of its progression.However,EV-based AD diagnosis faces challenges due to the small size and low abundance of biomarkers.Here,we report a fully integrated organic electrochemical transistor(OECT)sensor for ultrafast,accurate,and convenient point-of-care testing(POCT)of serum EVs from AD patients.By utilizing acoustoelectric enrichment,the EVs can be quickly propelled,significantly enriched,and specifically bound to the OECT detection area,achieving a gain of over 280 times response in 30 s.The integrated POCT sensor can detect serum EVs from AD patients with a limit of detection as low as 500 EV particles/mL and a reduced detection time of just two minutes.Furthermore,the integrated POCT sensors were used to monitor AD progression in an AD mouse model by testing the mouse AβEVs at different time courses(up to 18 months)and compared with the Aβaccumulation using high-resolution magnetic resonance imaging(MRI).This innovative technology has the potential for accurate and rapid diagnosis of Alzheimer’s and other neurodegenerative diseases,and monitoring of disease progression and treatment response.展开更多
基金Supported by(in part)A faculty research start-up fund to Peng F from the Carman and Ann Adams Foundation,Detroit,Michigan,United StatesHarold C Simmons Comprehensive Cancer Center,University of Texas Southwestern Medical Center,Dallas,Texas,United States.
文摘Hepatocellular carcinoma(HCC)is the fifth most common cancer worldwide.Significant efforts have been devoted to identify new biomarkers for molecular imaging and targeted therapy of HCC.Copper is a nutritional metal required for the function of numerous enzymatic molecules in the metabolic pathways of human cells.Emerging evidence suggests that copper plays a role in cell proliferation and angiogenesis.Increased accumulation of copper ions was detected in tissue samples of HCC and many other cancers in humans.Altered copper metabolism is a new biomarker for molecular cancer imaging with position emission tomography(PET)using radioactive copper as a tracer.It has been reported that extrahepatic mouse hepatoma or HCC xenografts can be localized with PET using copper-64 chloride as a tracer,suggesting that copper metabolism is a new biomarker for the detection of HCC metastasis in areas of low physiological copper uptake.In addition to copper modulation therapy with copper chelators,short-interference RNA specific for human copper transporter 1(h Ctr1)may be used to suppress growth of HCC by blocking increased copper uptake mediated by h Ctr1.Furthermore,altered copper metabolism is a promising target for radionuclide therapy of HCC using therapeutic copper radionuclides.Copper metabolism has potential as a new theranostic biomarker for molecular imaging as well as targeted therapy of HCC.
基金supported by a Department of Defense Breast Cancer Research Program Idea Award,the Susan G.Komen Foundation,Princess Margaret Hospital Foundation,Canadian Institute of Health Research,and Joey and Toby Tanen-baum/Brazilian Ball Chair in Prostate Cancer Research,University Health Network.
文摘We have developed a noninv asive imaging method to quantify in viwo drug delivery pharmaco-kinetics without the need for blood or tissue collection to determine drug concentration.By combining the techniques of hy perspectral imaging and a dorsal skinfold window chamber,this method enabled the real-time monitoring of vascular transport and tissue deposition of nano-particles labeled with near infrared(NIR)dye.Using this imaging method,we quantified the delivery pharmacokinetics of the native high-density lipoprotein(HDL)and epidermal growth factor receptor(EGFR)-targeted HDL nanoparticles and demonstrated these HDLs had long circulation time in blood stream(half-life>12h).These HDL nanoparticles could eficiently carry cargo DiR-BOA to extravasate from blood vesels,difuse through extr acellular matrix,and penetrate and be retained in the tumor site.The EGFR targeting specificity of EGFR-targeted HDL(EGFR-specific peptide conjugated HDL)was also visualized in vivo by competitive inhi bition with excess EGFR specifc peptide.In summary,this imaging technology may help point the way toward the development of novel imaging based pharmacokinetic assays for preclinical drugs and evaluation of drug delivery eficiency,providing a dynamic window into the devel opment and application of novel drug delivery systems.
文摘In this investigation,sensitive and reproducible methods are described for quantitative determination of deflazacort in the presence of its degradation product.The method was based on high performance liquid chromatography of the drug from its degradation product on reverse phase using Acquity UPLC BEH C18columns(1.7 urn,2.1 mm×150 mm)using acetonitrile and water(40:60 V/V)at a flow rate of 0.2 mL/minute in UPLC.UV detection was performed at 240.1 nm.Deflazacort was subjected to oxidative,acid,base,hydrolytic,thermal and photolytic degradation.The drug was found to be stable in water and thermal stress,as well as under neutral stress conditions.However,forced-degradation study performed on deflazacort showed that the drug degraded under alkaline,acid and photolytic stress.The degradation products were well resolved from the main peak,which proved the stability-indicating power of the method.The developed method was validated as per ICH guidelines with respect to accuracy,linearity,limit of detection,limit of quantification,accuracy,precision and robustness,selectivity and specificity.Apart from the aforementioned,the results of the present study also emphasize the importance of isolation characterization and identification of degradant.Hence,an attempt was made to identify the degradants in deflazacort.One of the degradation products of deflazacort was isolated and identified by the FTIR,NMR and LC-MS study.
文摘The purpose of this study was to assess usefulness of local binary patterns (LBP) and related texture features, namely completed local binary patterns (CLBP) and local ternary patterns (LTP), for the classification of emphysema subtypes on low-dose CT images. Fifty patients (34 men and 16 women;age, 67.5 ± 10.1 years) who underwent low-dose CT (60 mAs) were included. They were comprised of 17 never smokers, 13 smokers without COPD, and 20 smokers with COPD. By consensus reading of low-dose CT images from these patients, two radiologists selected 3681 nonoverlapping regions of interest (ROIs) and annotated them as one of the following three classes: normal tissue, centrilobular emphysema, and paraseptal emphysema. From these ROIs, histogram of CT densities, LBP, CLBP, and LTP were calculated, and the 3 types of texture histograms were concatenated with the CT density histogram. These 3 types of histograms (referred to as combined LBP, combined CLBP, and combined LTP) were used to classify ROI using linear support vector machine. For each type of the combined histogram, the accuracy of classification was determined by patient-based 10-fold cross validation. The best accuracy of combined LBP, combined CLBP, and combined LTP were 81.36%, 82.99%, and 83.29%, respectively. Compared to the classification accuracies obtained with combined LBP, those with combined LTP or combined CLBP were consistently improved. In conclusion, the results of this study suggest that, on low-dose CT, LTP and CLBP were more useful for the classification of emphysema subtypes than LBP.
基金F.G.acknowledges the National Institute of Health Awards(R01DK133864,DP2AI160242,and U01DA056242).
文摘Extracellular vesicles(EVs)show potential for early diagnosis of Alzheimer’s disease(AD)and monitoring of its progression.However,EV-based AD diagnosis faces challenges due to the small size and low abundance of biomarkers.Here,we report a fully integrated organic electrochemical transistor(OECT)sensor for ultrafast,accurate,and convenient point-of-care testing(POCT)of serum EVs from AD patients.By utilizing acoustoelectric enrichment,the EVs can be quickly propelled,significantly enriched,and specifically bound to the OECT detection area,achieving a gain of over 280 times response in 30 s.The integrated POCT sensor can detect serum EVs from AD patients with a limit of detection as low as 500 EV particles/mL and a reduced detection time of just two minutes.Furthermore,the integrated POCT sensors were used to monitor AD progression in an AD mouse model by testing the mouse AβEVs at different time courses(up to 18 months)and compared with the Aβaccumulation using high-resolution magnetic resonance imaging(MRI).This innovative technology has the potential for accurate and rapid diagnosis of Alzheimer’s and other neurodegenerative diseases,and monitoring of disease progression and treatment response.
