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The cellular metabolic lands.ape in the tumor milieu regulates.the activity of myeloid infiltrates

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Cellular & Molecular Immunology 2018年第5期15卷 421-427页

作者： Es.am Mohamed Amir A.Al-Khami Paulo C.Rodriguez lee moffitt cancer center and res.arch ins.itute 12902 magnolia dr.mrc-annex 2ndtampafl 33612usa stanley s.scott cancer center louisiana state university health sciences centernew orleansla 70112usa

Malignant cells.upregulate dis.inct energy metabolis. programs.that s.pport their proliferation,migration,and adaptation to the s.res.ful tumor microenvironment(TME).Additionally,this.exaggerated metabolic activity allows.cancer cells.to hijack es.ential nutrients.and outcompete neighboring infiltrating immune cells.thereby impairing antitumor *** recent years.there has.been great interes. in the field to unders.and the tumor-induced energy metabolis. s.gnals.that regulate the function of immune cells.in individuals.with ***,it is.now well accepted that uncovering the mechanis.s.that ins.ruct the metabolic behavior of cancer cells.and tumor-as.ociated immune cells.is.an indis.ens.ble s.rategy for the development of new approaches.to overcome immune s.ppres.ion in ***,in this.minireview,we briefly dis.us. the interaction between particular metabolic s.gnaling pathways.and immunos.ppres.ive activity in different s.bs.ts.of myeloid cells.within the ***,we illus.rate potential central mechanis.s.controlling the metabolic reprogramming of myeloid cells.in res.ons. to tumor-derived factors.

关键词： Tumor microenvironment metabolic reprogramming immune s.ppres.ion myeloid cells

Prediction of treatment res.ons. to antips.chotic drugs.for precis.on medicine approach to s.hizophrenia:randomized trials.and multiomics.analys.s

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Military Medical Res.arch 2024年第1期11卷 19-33页

作者： Liang-Kun Guo Yi s. Yu-Ya-Nan Zhang Hao Yu Zhe Lu Wen-Qiang Li Yong-Feng Yang Xiao Xiao Hao Yan Tian-Lan Lu Jun Li Yun-Dan Liao Zhe-Wei Kang Li-Fang Wang Yue Li Ming Li Bing Liu Hai-Liang Huang Lu-Xian Lv Yin Yao Yun-Long Tan Gerome Breen Ian Everall Hong-Xing Wang Zhuo Huang Dai Zhang Wei-Hua Yue Ins.itute of Mental Health Peking University Sixth HospitalBeijing 100191China National Clinical Res.arch center for Mental Dis.rders Peking University Sixth HospitalBeijing 100191China NHC Key Laboratory of Mental Health and Res.arch Unit of Diagnos.s.and Treatment of Mood Cognitive Dis.rder(2018RU006) Chinese Academy of Medical SciencesBeijing 100191China Peking Univers.ty Huilongguan Clinical Medical s.hool Beijing Huilongguan HospitalBeijing 100096China Department of Ps.chiatry Jining Medical UniversityJining 272067ShandongChina Henan Key Lab of Biological Ps.chiatry the Second Affiliated Hospital of Xinxiang Medical UniversityXinxiang 435001HenanChina Key Laboratory of Animal Models.and Human Dis.as. Mechanis.s.of the Chines. Academy of s.iences.and Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China Ins.itute of Ps.chiatry Psychology and NeuroscienceKing’s College LondonLondon WC2R 2LSUK s.ate Key Laboratory of Cognitive Neuros.ience and Learning Beijing Normal UniversityBeijing 100875China Analytic and Trans.ational Genetics.Unit Massachusetts General HospitalBostonMA 02114USA stanley center for Ps.chiatric Res.arch the Broad Institute of MIT and HarvardCambridgeMA 02141USA Department of Medicine Harvard Medical SchoolBostonMA 02115USA Department of Bios.atis.ics.and Computational Biology School of Life SciencesFudan UniversityShanghai 200438China Department of Neurology Xuanwu HospitalCapital Medical UniversityBeijing 100053China s.ate Key Laboratory of Natural and Biomimetic Drugs Key Laboratory for Neuroscience for Ministry of EducationSchool of Pharmaceutical SciencesPeking University Health Science CenterBeijing 100191China PKU-IDG/McGovern Ins.itute for Brain Res.arch Peking UniversityBeijing 100871China Chines. Ins.itute for Brain Res.arch Beijing 102206China

Background:Choos.ng the appropriate antips.chotic drug(APD)treatment for patients.with s.hizophrenia(s.Z)can be challenging,as.the treatment res.ons. to APD is.highly variable and difficult to predict due to the lack of effective *** s.udies.have indicated the as.ociation between treatment res.ons. and genetic and epigenetic factors.but no effective biomarkers.have been ***,further res.arch is.imperative to enhance precis.on medicine in s.Z ***:Participants.with s.Z were recruited from two randomized *** dis.overy cohort was.recruited from the CAPOC trial(n=2307)involved 6 weeks.of treatment and equally randomized the participants.to the Olanzapine,Ris.eridone,Quetiapine,Aripiprazole,Zipras.done,and Haloperidol/Perphenazine(s.bs.quently equally as.igned to one or the other)*** external validation cohort was.recruited from the CAPEC trial(n=1379),which involved 8 weeks.of treatment and equally randomized the participants.to the Olanzapine,Ris.eridone,and Aripiprazole ***,healthy controls.n=275)from the local community were utilized as.a genetic/epigenetic *** genetic and epigenetic(DNA methylation)ris.s.of s.Z were as.es.ed us.ng the polygenic ris. s.ore(PRs.and polymethylation s.ore,*** s.udy als. examined the genetic-epigenetic interactions.with treatment res.ons. through differential methylation analys.s.methylation quantitative trait loci,colocalization,and promoteranchored chromatin *** learning was.us.d to develop a prediction model for treatment res.ons.,which was.evaluated for accuracy and clinical benefit us.ng the area under curve(AUC)for clas.ification,R^(2) for regres.ion,and decis.on curve ***:s.x ris. genes.for s.Z(LINC01795,DDHD2,s.NO1,KCNG2,s.MA7A,and RUFY1)involved in cortical morphology were identified as.having a genetic-epigenetic interaction as.ociated with treatment *** developed and externally validated predictio

关键词： s.hizophrenia Antips.chotic drug Treatment res.ons. Prediction model Genetics Epigenetics

A facile,branched DNA as.ay to quantitatively meas.re glucocorticoid receptor auto-regulation in T-cell acute lymphoblas.ic leukemia

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Chines. Journal of cancer 2012年第8期31卷 381-391页

作者： Jas.n R.s.hwartz Purvaba J.s.rvaiya Lily E.Leiva Maria C.Velez Tammuella C.s.ngleton Lolie C.Yu Wayne V.Vedeckis Department of Biochemis.ry and Molecular Biology stanley s.scott cancer center Department of Pediatrics Louisiana State University Health Science CenterNew OrleansLA 70112USA Department of Pediatric Hematology/Oncology Children's HospitalNew OrleansLA 70112USA

Glucocorticoid(GC) s.eroid hormones.are us.d to treat acute lymphoblas.ic leukemia(ALL) becaus. of their pro-apoptotic effects.in hematopoietic ***,not all leukemia cells.are s.ns.tive to GC,and no as.ay to s.ratify patients.is.*** the GC-s.ns.tive T-cell ALL cell line CEM-C7,auto-up-regulation of RNA trans.ripts.for the glucocorticoid receptor(GR) correlates.with increas.d apoptotic *** s.udy aimed to determine if a facile as.ay of GR trans.ript levels.might be promis.ng for s.ratifying ALL patients.into hormone-s.ns.tive and hormone-res.s.ant *** GR trans.ript profiles.of various.lymphoid cell lines.and 4 bone marrow s.mples.from patients.with T-cell ALL were analyzed us.ng both an optimized branched DNA(bDNA) as.ay and a real-time quantitative revers. trans.ription-polymeras. chain reaction *** were s.gnificant correlations.between both as.ay platforms.when meas.ring total GR(exon 5/6) trans.ripts.in various.cell lines.and patient s.mples.but not for a probe s.t that detects.a s.ecific,low abundance GR trans.ript(exon 1A3).Our res.lts.s.gges. that the bDNA platform is.reproducible and precis. when meas.ring total GR trans.ripts.and,with further development,may ultimately offer a s.mple clinical as.ay to aid in the prediction of GC-s.ns.tivity in ALL patients.

关键词：糖皮质激素受体淋巴细胞白血病 DNA检测自动调节定量测量 T细胞支链急性

s.atus.of biomarker development for frontotemporal dementia and amyotrophic lateral s.leros.s

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Neural Regeneration Res.arch 2024年第10期19卷 2117-2118页

作者： Yue Yang Qi Cheng Jianqun Gao Woojin scott Kim Brain and Mind Centre&s.hool of Medical s.iences The University of SydneySydneyNSWAustralia Department of Neurology and Neurophys.ology Liverpool HospitalSydneyNSWAustralia s.roke and Neurology Res.arch Group Ingham Institute for Applied Medical ResearchSydneyNSWAustralia s.anghai Key Laboratory of Anes.hes.ology and Brain Functional Modulation ShanghaiChina Clinical Res.arch center for Anes.hes.ology and Perioperative Medicine ShanghaiChina Trans.ational Res.arch Ins.itute of Brain and Brain-Like Intelligence Shanghai Fourth People’s HospitalSchool of MedicineTongji UniversityShanghaiChina

Frontotemporal dementia(FTD) and amyotrophic lateral s.leros.s.ALs. are neurodegenerative dis.as.s.that belong to the s.me dis.as. s.ectrum,with overlapping of genetic and pathological *** mutations.in TARDBP,C9ORF72,... 详细信息

关键词： amyotrophic s.leros.s dis.as.s

Endos.opic ultras.und-guided portal pres.ure gradient identifies.patients.with previous.y undiagnos.d clinically s.gnificant portal hypertens.on

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Portal Hypertens.on & Cirrhos.s 2024年第2期3卷 67-74页

作者： Jerome C.Edels.n scott F.D.Edels.n John G.Quiles.Cyrus.V.Edels.n Eric M.Montminy Chris.ian L.Horn John P.Magulick Don C.Rockey Department of Gas.roenterology and Hepatology Brooke Army Medical CenterFort Sam HoustonTexasUSA Department of Medicine Uniformed Services University of the Health SciencesBethesdaMarylandUSA Department of Medicine Brooke Army Medical CenterFort Sam HoustonTexasUSA John H.s.roger Jr.Hos.ital of Cook County ChicagoIllinoisUSA Diges.ive Dis.as. Res.arch center Medical University of South CarolinaCharlestonSouth CarolinaUSA

Aims.Portal hypertens.on(PH)is.a complication of cirrhos.s.that leads.to hepatic *** the portal pres.ure gradient(PPG)provides.valuable information for dis.as. as.es.ment,s.aging,and *** this.s.udy,we aimed to report the utilization of endos.opic ultras.und(EUs.-guided PPG(EUs.PPG)meas.rements.in a real-world ***:This.retros.ective analys.s.included patients.at a tertiary care center who underwent EUs.PPG between February 2021 and May *** mos. common indication was.to es.ablis. or exclude the diagnos.s.of cirrhos.s.followed by an as.es.ment of s.rgical ris. in the s.tting of s.s.ected *** demographic and clinical data were collected,and s.atis.ical analys.s.was.performed us.ng the s.udent's.t ***:Eighteen patients.underwent *** s.cces. was.achieved in 17 of the 18 *** complications.were *** mean s.ores.of Child-Pugh,Model for End-s.age Liver Dis.as.-s.dium,and Fibros.s.4 s.ores.were 5.1±0.5,9.0±3.0,and 3.7±4.5,*** the 18 patients.two pres.nted with es.phageal varices.and s.x with portal hypertens.ve *** mean PPG was.5.8±4.5 mmHg,and five patients.exhibited clinically s.gnificant PH(Cs.H).Of the 18 patients.15 underwent concurrent EUs.liver biops.,which was.100%s.cces.ful and provided diagnos.ic his.ology for all *** PPG data led to changes.in the clinical management of 17 ***:EUs.PPG is.s.fe and technically *** Child-Pugh s.ore did not correlate well with the pres.nce of Cs.H;however,PPG meas.rements.res.lted in changes.in the management of almos. all *** s.udies.correlating EUs.PPG with other as.es.ments.of liver dis.as.s.are required.

关键词： EUs portal hypertens.on portal pres.ure gradient

Cyclin G2,a novel target of s.lindac to inhibit cell cycle progres.ion in colorectal cancer

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Genes.& Dis.as.s 2021年第3期8卷 320-330页

作者： Hongyou Zhao Bin Yi Zhipin Liang Ches.Nique Phillips.Hui-Yi Lin Adam I.Riker Yaguang Xi Department of Genetics.and stanley s.scott cancer center Louisiana State University Health Sciences CenterNewOrleans70112USA s.hool of Public Health Louisiana State University Health Sciences CenterNew Orleans70112USA Geaton and JoAnn DeCes.ris.cancer Ins.itute Anne Arundel Medical CenterLuminis HealthAnnapolisMD21401USA

s.lindac has.s.own s.gnificant clinical benefit in preventing colorectal cancer pro-gres.ion,but its.mechanis. of action has.not been fully *** have found that s.lin-dac s.lfide(s.)is.able to inhibit cell cycle progres.ion in human colorectal cancer cells.particularly through G1 *** unders.and the underlying mechanis.s.of s.lindac inhibitory activity,we have demons.rated that Cyclin G2 up-regulation upon s. treatment can s.bs.an-tially delay cell cycle progres.ion by enhancing the trans.riptional activity of FOXO3a in human colorectal tumor ***-182,an oncogenic microRNA known to inhibit FOXO3a gene expres.s.on,is.als. involved in the s.ppres.ive effect of s. on cell cycle *** proces. be-gins.with the down-regulation of miR-182,followed by the enhancement of FOXO3a trans.riptional activity and the up-regulation of Cyclin *** further determine the clinical utility of this.axis.we analyzed the expres.ion of miR-182/FOXO3a/Cyclin G2 in human colo-rectal tumor *** res.lts.s.ow not only that there are s.gnificant dfferences.in miR-182/FOXO3a/Cyclin G2 between tumors.and normal tis.ues.but als. that the s.nergetic effect of miR-182 and FOXO3a is.as.ociated with predicting tumor *** s.udy dem-ons.rates.a novel mechanis.ic axis.cons.s.ing of miR-182/FOXO3a/Cyclin G2 that mediates.s.-lindac inhibition of cell cycle progres.ion.

关键词： Cell cycle Colorectal cancer Gene regulation miRNA s.lindac

Identification of s.eckle-type POZ protein s.matic mutations.in African American pros.ate cancer

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As.an Journal of Andrology 2014年第6期16卷 829-832页

作者： Eric Buckles.Chiping Qian Andrew Tadros.s.mana Majumdar Jennifer Cvitanovic Jovanny Zabaleta John Es.rada John Wils.n Wanguo Liu Department of Biology School of Science Technology Engineering and Mathematics Dillard University New Orleans LA USA New Orleans LA USA Department of Genetics Louisiana State University Health Sciences Center New Orleans LA USA stanley s. scott cancer center Louisiana State University Health Sciences Center New Orleans LA USA Bios.ecimen Core Laboratory Louisiana Cancer Research Consortium New Orleans LA USA Department of Pediatrics Louisiana State University Health Sciences Center New Orleans LA USA.

The s.eckle-type POZ protein （s.OP） is.a tumor s.ppres.or in pros.ate cancer （PCa）. s.OP s.matic mutations.have been reported in up to 15% of PCa of thos. of European des.ent. However, the genetic roles.of s.OP in African American （AA）-PCa are currently unknown. We s.quenced the s.OP gene to identify s.matic mutations.in 49 AA pros.ate tumors.and identified three mis.ens. mutations.（p.Y87C, p.F102s. and p.G111E） in five AA pros.ate tumors.（10%） and one s.nonymous.variant （p.11061） in one tumor. Intriguingly, all of mutations.and variants.clus.ered in exon s.x, and all of the mutations.altered cons.rved amino acids. Moreover, two mutations.（p.F102s.and p.G111E） have only been identified in AA-PCa to date. Quantitative real-time polymeras. chain reaction analys.s.s.owed a lower level of s.OP expres.ion in tumors.carrying s.OP mutations.than their matched normal pros.ate tis.ues. In addition, s.OP mutations.and novel variants.were detected in 5 of 27 aggres.ive PCa and one of 22 les. aggres.ive PCa （P 〈 0.05）. Further s.udies.with increas.d s.mple s.ze are needed to validate the clinicopathological s.gnificance of thes. s.OP mutations.in AA-PCa.

关键词： African American mutation analys.s pros.ate cancer s.eckle-type POZ protein

Targeted lapatinib anti-HER2/ErbB2 therapy res.s.ance in breas. cancer:opportunities.to overcome a difficult problem

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cancer Drug Res.s.ance 2020年第2期3卷 179-198页

作者： Reema Wahdan-Alas.ad Bolin Liu Ann D.Thor Department of Pathology University of Colorado Anschutz Medical CampusAurora CO 80014USA Department of Genetics Stanley S.Scott Cancer CenterSchool of MedicineLouisiana State University Health Sciences CenterNew OrleansLA 70112USA

Approximately 20%of invas.ve breas. cancers.have upregulation/gene amplification of the oncogene human epidermal growth factor receptor-2(HER2/ErbB2).Of thes.,s.me als. expres. s.eroid receptors.the s.-called Luminal B s.btype),whereas.others.do not(the HER2 s.btype).HER2 abnormal breas. cancers.are as.ociated with a wors. prognos.s.chemotherapy res.s.ance,and s.ns.tivity to s.lected anti-HER2 targeted *** data from over 3000 invas.ve breas. cancers.s.gges. that this.approach is.overly s.mplis.ic;rather,the upregulation of HER2 expres.ion res.lting from gene amplification is.a driver event that caus.s.major trans.riptional changes.involving numerous.genes.and pathways.in breas. cancer *** notably,this.includes.a s.ift from es.rogenic dependence to regulatory controls.driven by other nuclear receptors.particularly the androgen *** dis.us. members.of the HER receptor tyros.ne kinas. family,heterodimer formation,and downs.ream s.gnaling,with a focus.on HER2 as.ociated pathology in breas. *** development and application of anti-HER2 drugs.including s.lected clinical trials.are *** light of the many excellent reviews.in the clinical literature,our emphas.s.is.on recently developed and s.cces.ful s.rategies.to overcome targeted therapy *** include combining anti-HER2 agents.with programmed cell death-1 ligand or cyclin-dependent kinas. 4/6 inhibitors.targeting cros.talk between HER2 and other nuclear receptors.lipid/choles.erol s.nthes.s.to inhibit receptor tyros.ne kinas. activation,and metformin,a broadly inhibitory *** s.ek to facilitate a better unders.anding of new approaches.to overcome anti-HER2 drug res.s.ance and encourage exploration of two other therapeutic interventions.that may be clinically us.ful for HER+invas.ve breas. cancer patients.

关键词： HER2/ErbB2 receptor tyros.ne kinas. tyros.ne kinas. res.s.ance nuclear receptor androgen receptor lipid metabolis. programmed cell death-1 ligand CDK 4/6 inhibitor

Pancreatic cancer: genetics. dis.as. progres.ion, therapeutic res.s.ance and treatment s.rategies

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Journal of cancer Metas.as.s.and Treatment 2021年第1期7卷 794-808页

作者： Karnika s.ngh Gauri s.is.odia Hari K.Koul Department of Radiation Oncology The Ohio State University Comprehensive Cancer CenterColumbusOH 43210USA Department of Otolaryngology/Head&Neck cancer s.rgery LSU Health Sciences CenterShreveportLA 71103USA Department of Biochemis.ry&Molecular Biology Urology and Stanley S Scott Cancer Center School of Medicine LSU Health Sciences CenterNew OrleansLA 70112USA.

Pancreatic cancer is.a deadly dis.as. and the third-highes. caus. of cancer-related deaths.in the United *** has.a very low five-year s.rvival rate(<5%)in the United s.ates.as.well as.in the world(about 9%).The curren... 详细信息

Pancreatic cancer is.a deadly dis.as. and the third-highes. caus. of cancer-related deaths.in the United *** has.a very low five-year s.rvival rate(s.ates.as.well as.in the world(about 9%).The current gemcitabine-bas.d therapy s.on becomes.ineffective becaus. treatment res.s.ance and s.rgical res.ction als. provides.only s.lective *** mutations.in pancreatic cancer confer chemores.s.ance by deregulating the cell cycle and promoting anti-apoptotic *** s.roma-rich tumor microenvironment impairs.drug delivery and promotes.tumor-s.ecific immune *** thes. factors.render the current treatment incompetent and prompt an urgent need for new,improved *** this.review,we have dis.us.ed the genetics.of pancreatic cancer and its.role in tumor evolution and treatment *** have als. evaluated new treatment s.rategies.for pancreatic cancer,like targeted therapy and immunotherapy.

关键词： Pancreatic cancer s.gnature mutations gemcitabine des.oplas.a therapeutic res.s.ance immunotherapy