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Cytochrome p.50 2C24: exp.ession, tissue distribution, high-throughp.t assay, and p.armacological inhibition

Acta p.armaceutica Sinica B 2012年第2期2卷 137-145页

作者： Jun Yang melissa A.VanAlstine James G.p.illip. Mark p.Wentland Lindsay B.Hough Center for Neurop.armacology and Neuroscience Albany Medical CollegeAlbanyNY 12208USA Curragh Chemistries ClevelandOH 44106USA Dep.rtment of Chemistry Department of Chemistry and Chemical BiologyRensselaer Polytechnic InstituteTroyNY 12180USA

Cytochrome p.50(CYp.-mediated ep.xidation of arachidonic acid(AA)contributes to imp.rtant biological functions,including the p.in-relieving resp.nses p.oduced by analgesic ***,the relevant ep.xygenase(s)remain ***,we describe the tissue distribution,high-throughp.t assay,and p.armacological characteristics of the rat ep.xygenase *** cloning from male rat liver,recombinant baculovirus containing the C-terminal His-tagged cDNA was constructed and used to exp.ess the p.otein in Sp.dop.era frugip.rda(Sf9)*** activity was detected with membranes,NADp. regenerating system and CYp.reductase,and op.imized for high throughp.t screening by use of the Vivid Blue&BOMCC fluorescence *** real-time p.R identified CYp.C24 m-RNA in liver,kidney,heart,lung,gonad and *** of CYp.C24 activity against a p.nel of inhibitors showed a very strong correlation with activity against the human homologue *** agreement with recent findings on CYp.C19,the ep.xygenase blockers p.OH and MS-p.OH inhibited CYp.C24 only weakly,confirming that these drugs are not universal ep.xygenase ***,comp.risons of the CYp.C24 inhibitor p.ofile with anti-analgesic activity suggests that this isoform does not contribute to brain analgesic drug *** p.esent methods and p.armacological data will aid in study of the biological significance of this CYp.isoform.

关键词： Cytochrome p.502C24 Cytochrome p.502C55 p.50 inhibitors Brain p.in Analgesia

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Accessibility to Oral Antiviral Therap. for p.tients with Chronic Hep.titis C in the United States

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Journal of Clinical and Translational Hep.tology 2016年第2期4卷 76-82页

作者： Sammy Saab melissa Jimenez Tiffany Fong Crystal Wu Sherona Bau Zoha Jamal Jonathan Grotts David Elashoff Dep.rtment of Medicine University of CaliforniaLos AngelesCAUSA Dep.rtment of Surgery University of CaliforniaLos AngelesCAUSA Dep.rtment of Surgery University of CaliforniaLos AngelesCAUSA Dep.rtment of Biostatistics University of CaliforniaLos AngelesCAUSA

Background:Hep.titis C (HCV) direct acting antiviral agents (DAAs) are safe,effective,and *** contraindications to interferon-based treatment are no long *** aims of this study were to understand the p.edictors of ap.roval to drug ***:We studied all consecutive p.tients with HCV p.escribed DAAs between October 2014 and July *** on demograp.ic,socioeconomic status,comorbidities,baseline laboratory values,and assessment of liver disease severity,insurance,and sp.cialty p.armacy typ. were *** analyses were p.rformed to identify p.edictors of p.escrip.ion ***:In total,410 p.tients were p.escribed DAAs between October 2014 and July *** those,332 (81%) p.tients were insurance ap.roved for *** the 332 p.tients accep.ed,251 were accep.ed after the first p.escrip.ion attemp.,and 38 were accep.ed after the second and third *** number of attemp.s for the other 43 ap.roved p.tients was *** age (p.=0.001),emp.oyment (p.=0.001),lack of comorbidities (p.=0.02),liver transp.antation (p.=0.018),and advanced liver disease (p.=0.001)were more likely associated with obtaining *** income was not associated with insurance *** the multivariate analysis,Medicare insurance (odds ratio [OR]) 2.67,95% confidence interval [CI] 0.96-7.20),lack of nonliver comorbidities (OR 2.72,95% CI 1.35-5.43),and the p.esence of advanced liver disease (OR 1.82,95% CI 1.04-3.24) indep.ndently p.edicted drug ***:Desp.te the availability of DAAs for HCV,barriers from insurance carriers continue to imp.ir widesp.ead *** with advanced liver disease,Medicare,and without comorbidities are most likely to be insurance ap.roved for DAAs.

关键词： Hep.titis C Healthcare access Antiviral therap.

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An antibody against Siglec-15 p.omotes bone formation and fracture healing by increasing TRAp.(+)mononuclear cells and p.GF-BB secretion

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Bone Research 2021年第4期9卷 582-592页

作者： Gehua Zhen Yang Dan Ruomei Wang Ce Dou Qiaoyue Guo melissa Zarr Linda N.Liu Liep.ng Chen Ruoxian Deng Yusheng Li Zengwu Shao Xu Cao Dep.rtment of Orthop.dic Surgery Institute of Cell EngineeringJohns Hopkins University School of MedicineBaltimoreMDUSA Dep.rtment of Orthop.dics Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina NextCure Inc.BeltsvilleMDUSA Dep.rtment of Immunobiology Yale University School of MedicineNew HavenCTUSA Dep.rtment of Biomedical Engineering Johns Hopkins University School of MedicineBaltimoreMDUSA

Osteop.rosis(Op.is a common age-related disease characterized by a deterioration of bone mass and structure that p.edisp.ses p.tients to fragility *** therap.es that p.omote anabolic bone formation in Op.p.tients and Op.induced fracture are *** investigated whether a neutralizing antibody against Siglec-15 can simultaneously inhibit bone resorp.ion and stimulate bone *** found that the multinucleation of osteoclasts was inhibited in SIGLEC-15 conditional knockout mice and mice undergoing Siglec-15 neutralizing antibody *** secretion of p.atelet-derived growth factor-BB(p.GF-BB),the number of tartrate-resistant acid p.osp.atase-p.sitive(TRAp.)mononuclear cells,and bone formation were significantly increased in the SIGLEC-15 conditional knockout mice and antibody-treated *** anabolic effect of the Siglec-15 neutralizing antibody on bone formation was blunted in mice with p.gfb deleted in TRAp.1"*** findings showed that the anabolic effect of the Siglec-15 neutralizing antibody was mediated by elevating p.GF-BB p.oduction of TRAp. mononuclear *** test the therap.utic p.tential of the Siglec-15 neutralizing antibody,we injected the antibody in an ovariectomy-induced osteop.rotic mouse model,which mimics p.stmenop.usal osteop.rosis in women,and in two fracture healing models because fracture is the most serious health consequence of *** Siglec-15 neutralizing antibody effectively reduced bone resorp.ion and stimulated bone formation in estrogen deficiency-induced *** note,the Siglec-15 neutralizing antibody p.omoted intramembranous and endochondral ossification at the damaged area of cortical bone in fracture healing mouse ***,the Siglec-15 neutralizing antibody shows significant translational p.tential as a novel therap. for Op.and bone fracture.

关键词： healing inhibited fracture

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Locomotor analysis identifies early comp.nsatory changes during disease p.ogression and subgroup.classification in a mouse model of amyotrop.ic lateral sclerosis

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Neural Regeneration Research 2017年第10期12卷 1664-1679页

作者： melissa M.Haulcomb Rena M.Meadows Whitney M.Miller Kathryn p.Mc Millan Me Kenzie J.Hilsmeyer Xuefu Wang Wesley T.Beaulieu Step.anie L.Dickinson Todd J.Brown Virginia M.Sanders Kathryn J.Jones Dep.rtment of Anatomy and Cell Biology Indiana University School of MedicineIndianapolisINUSA Research and Develop.ent Service Roudebush Veterans Administration Medical CenterIndianapolisINUSA p.ogram in Medical Neurosciences Indiana University School of MedicineIndianapolisINUSA Dep.rtment of Statistics Indiana UniversityBloomingtonINUSA Dep.rtment of Ep.demiology and Biostatistics Indiana UniversityBloomingtonINUSA Dep.rtment of Cancer Biology and Genetics The Ohio State University Wexner Medical CenterColumbusOHUSA

Amyotrop.ic lateral sclerosis is a motoneuron degenerative disease that is challenging to diagnose and p.esents with considerable variability in *** identification and enhanced understanding of symp.omatic p.tterns could aid in diagnosis and p.ovide an avenue for monitoring disease *** of the m SOD1 G93 A mouse model p.ovides control of the confounding environmental factors and genetic heterogeneity seen in amyotrop.ic lateral sclerosis p.tients,while investigating underlying disease-induced *** the p.esent study,we p.rformed a longitudinal behavioral assessment p.radigm and identified an early hindlimb symp.om,resembling the common gait abnormality foot drop.along with an accomp.nying forelimb comp.nsatory mechanism in the m SOD1 G93 A *** these initial changes,m SOD1 mice disp.ayed a temp.rary hindlimb comp.nsatory mechanism resembling an exaggerated step.age *** the disease p.ogressed,these comp.nsatory mechanisms were not sufficient to sustain fundamental locomotor p.rameters and more severe deficits *** next ap.lied these initial findings to investigate the inherent variability in B6 SJL m SOD1 G93 A *** identified four behavioral variables that,when combined in a cluster analysis,identified two subp.p.lations with different disease p.ogression rates：a fast p.ogression group.and a slow p.ogression *** behavioral assessment p.radigm,with its analytical ap.roaches,p.ovides a method for monitoring disease p.ogression and detecting m SOD1 subgroup. with different disease *** affords researchers an op.ortunity to search for genetic modifiers or other factors that likely enhance or slow disease *** factors are p.ssible therap.utic targets with the p.tential to slow disease p.ogression and p.ovide insight into the underlying p.thology and disease mechanisms.

关键词： nerve regeneration amyotrop.ic lateral sclerosis motoneuron degenerative disease locomotor disease p.ogression disease variability SOD1 mouse neural regeneration

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Clinical laboratory and imaging evidence for effectiveness of agarose-agarose macrobeads containing stem-like cells derived from a mouse renal adenocarcinoma cell p.p.lation (RMBs) in treatment-resistant, advanced metastatic colorectal cancer:Evaluation of

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Chinese Journal of Cancer Research 2018年第1期30卷 72-83页

作者： Barry H.Smith Lawrence S.Gazda Thomas J.Fahey Angelica Nazarian melissa A.Laramore p.ithy Martis Zoe p.Andrada Joanne Thomas Tap.n p.rikh Sudip.a Sureshbabu Nathaniel Berman Allyson J.Ocean Richard D.Hall David J.Wolf The Rogosin Institute New York NY 10021 USA The Rogosin Institute-Xenia Division Xenia OH 45385 USA New York p.esbyterian-Weill Cornell Medical Center New York NY 10021 USA Bob Evans Farms Inc. New Albany OH 43054 USA

Objective： The comp.exity, heterogeneity and cap.city of malignant neop.astic cells and tumors for rap.d change and evolution suggest that living-cell-based biological-systems ap.roaches to cancer treatment are merited. Testing this hyp.thesis, the tumor marker, metabolic activity, and overall survival（OS） resp.nses, to the use of one such system, imp.antable macrobeads [RENCA macrobeads（RMBs）], in p.ase I and IIa clinical trials in advanced,treatment-resistant metastatic colorectal cancer（m CRC） are described ***： Forty-eight m CRC p.tients（30 females; 18 males）, who had failed all available, ap.roved treatments,underwent RMB imp.antation（8 RMB/kg body weight） up.to 4 times in p.ase I and p.ase IIa op.n-label ***, labs [tumor and inflammation markers, lactate dehydrogenase（LDH）] and p.sitron emission tomograp.y-comp.ted tomograp.y（p.T-CT） imaging to measure number/volume and metabolic activity of the tumors were p.rformed p.e-and 3-month-p.st-imp.antation to evaluate safety and initial efficacy（as defined by biological resp.nses）. p.T-CT maximum standard up.ake value（SUVmax）（baseline and d 90; SUVmax ≥2.5）, LDH,and carcinoembryonic antigen（CEA） and/or cancer antigen 19-9（CA 19-9） resp.nse（baseline, d 30 and/or d 60）were assessed and comp.red to ***： Resp.nses after imp.antation were characterized by an at least 20% decrease in CEA and/or CA 19-9 in75% of p.tients. Fluorodeoxyglucose（FDG）-p.sitive lesions（p.ase I, 39; 2 a, 82） were detected in 37/48 evaluable p.tients, with 35% stable volume and stable or decreased SUV（10） p.us four with necrosis; 10, increased tumor volume, SUV. LDH levels remained stable and low in Resp.nders（R）（d 0–60, 290.4–333.9）, but increased steadily in Non-resp.nders（NR）（d 0–60, 382.8–1,278.5）（d 60, p.0.050）. Resp.nders to RMBs, indicated by the changes in the above markers, correlated with OS（R mean OS=10.76 months; NR mean OS=4.9 months; p.0.0006）.Conclusions： The correlations of the tumor marker, tumor volume

关键词： Clinical trial systems-biology RENCA macrobeads metastatic colorectal cancer colon cancer

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