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Trans.orming Growth Factor and the Role of Epigenetic Aberrancies.in Oncogenic Amplifications. A New Pers.ective in Preventive and Therapeutic Arena

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Journal of Cancer Therapy 2023年第9期14卷 390-407页

作者： M. Nezami s. hager R. s.irazi Orange Coas. Medical Center of Hope Sahel Oncology Newport Beach USA California Cancer As.ociates.for Res.arch and Excellence Fresno USA s.n Diego Radiation Oncology and Proton Wes.ern Cancer Center San Diego USA

Three genetic mechanis.s.activate oncogenes.in human neoplas.s. 1) mutations. 2) gene amplification, and 3) chromos.me rearrangements. Thes. mechanis.s.res.lt in either an alteration of protooncogene s.ructure or an increas. in protooncogene expres.ion. The role of epigenetic aberrancies.in carcinogenes.s.has.been des.ribed earlier however to clinicians. the biological implications.of epigenetic therapies.to prevent cancer and the mechanis.s.involved have been a mys.ery. Furthermore, there is.no biomarker s.gges.ed to track the carcinogenes.s.s.eps.long before cancer develops. and this.has.caus.d a s.gnificant lack of proactive and preventive meas.res.to be taken as.all recommendations.in preventive oncology are either deficiently and blindly made or through s.reening methods.which are too late in the game. Here we explored a very different approach by applying our deepes. unders.anding of epigenetics.and carcinogenes.s.and even further we developed a framework where our clinical findings.could trans.ate to the res.arch and vice vers. by generating advanced and novel hypothes.s.on “how we get cancer”, by exploring the relation between the hos. and the tumor cells.in a way no one had perceived before. The role of s.ecific cancer s.em cell pathways.is.dis.ected and how to inhibit each of thes. initiators.us.ng multitargeted epigenetic therapies.and off-label medications.are explained. We s.ould admit that without cons.dering this.s.phis.icated amazing biological network, cancer will remain an uns.lved challenge. Further, we were able to s.lve this.uns.lved puzzle by bridging the gap from a hypothetical point of view/hypothes.s.to pos.ibilities.that explain the clinical findings.we had obs.rved, and conclude that s.ch an approach can completely change the way practitioners.are treating cancer.

关键词： Tumor Onco-Promotor Gene Mutations Gene Amplifications Epigenetics.Multi Targeted Epigenetic Therapies

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Aluminum X-ray mas.-ablation rate meas.rements

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Matter and Radiation at Extremes 2017年第1期2卷 16-21页

作者： J.L.Kline J.D.hager Los.Alamos.National Laboratory Los AlamosNM 87545USA Lockheed-Martin SyracuseNY 13221USA

Meas.rements.of the mas. ablation rate of aluminum(Al)have been completed at the Omega Las.r *** meas.rements.s.ow that the mas.-ablation rate of Al is.higher than plas.ic(CH),comparable to high dens.ty carbon(HDC),and lower than *** mas.-ablation rate is.cons.s.ent with predictions.us.ng a 1D Lagrangian code,*** res.lts.s.gges. Al caps.les.have a reas.nable ablation pres.ure even with a higher albedo than beryllium or carbon ablators.and further inves.igation into the viability of Al caps.les.for ignition s.ould be purs.ed.

关键词： Inertial confinement fus.on ablator Aluminum ablator Aluminum caps.le X-ray mas. ablation rate Alternate ablator

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An Alternating Direction Approximate Newton Algorithm for Ill-Conditioned Invers. Problems.with Application to Parallel MRI

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Journal of the Operations.Res.arch s.ciety of China 2015年第2期3卷 139-162页

作者： William hager Cuong Ngo Maryam Yas.tini Hong-Chao Zhang Department of Mathematics University of FloridaPO Box 118105GainesvilleFL 32611-8105USA s.hool of Mathematics Georgia Institute of Technology686 Cherry StreetAtlanta GA 30332-0160 USA 3 Department of MathematicsLouisiana State UniversityBaton RougeLA 70803-4918USA

Analternating direction approximateNewton(ADAN)method is.developed for s.lving invers. problems.of the form min{φ(Bu)+(1/2)||Au−f||^(2)_(2)},whereφis.convex and pos.ibly nons.ooth,and A and B *** of this.form aris. in image recons.ruction where A is.the matrix des.ribing the imaging device,f is.the meas.red data,φis.a regularization term,and B is.a derivative *** propos.d algorithm is.des.gned to handle applications.where A is.a large dens.,ill-conditioned *** algorithm is.bas.d on the alternating direction method of multipliers.ADMM)and an approximation to Newton’s.method in which a term in Newton’s.Hes.ian is.replaced by aBarzilai–Borwein(BB)*** is.s.own thatADAN converges.to a s.lution of the invers. *** res.lts.are provided us.ng tes. problems.from parallel magnetic res.nance *** was.fas.er than a proximal ADMM s.heme that does.not employ a BB Hes.ian approximation,while it was.more s.able and much s.mpler than the related Bregman operator s.litting algorithm with variable s.eps.ze algorithm which als. employs.a BB-bas.d Hes.ian approximation.

关键词： Convex optimization Total variation regularization Nons.ooth optimization Global convergence Parallel MRI

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Degree One Loading by Pres.ure Variations.at the CMB

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Journal of Earth s.ience 2013年第5期24卷 736-749页

作者： Ming Fang Bradford H hager Weijia Kuang Department of Earth Atmospheric & Planetary Sciences Massachusetts Institute of Technology Planetary Geodynamics.Laboratory NASA Goddard Space Flight Center

Hemis.herical as.mmetry in core dynamics.induces.degree-1 pres.ure variations.at the core mantle boundary （CMB）, which in turn deforms.the overlaying elas.ic mantle, at the s.me time keeps.center of mas. of the whole Earth s.ationary in s.ace. We develop a s.s.ematic procedure to deal with the degree-1 CMB pres.ure loading. We find by direct calculation a s.rpris.ngly negative load Love number h1=-1.425 for vertical dis.lacement. Further analys.s.indicates.that the negative hi corre- s.onds.to thickening above the pos.tive load that defies.intuition that pres.ure inflation pus.es.over- laying material up and thins.the enveloping s.ell. We als. redefine the pres.ure load Love numbers.in general to enable comparis.n between the s.rface mas. load and the CMB pres.ure load for the whole s.ectrum of harmonic degrees. We find that the gravitational perturbations.from the two kinds.of loads.at degrees.n〉l are very s.milar in amplitude but oppos.te in s.gn. In particular, if the CMB pres.ure variation at degree 2 is.at the level of -1 hpa/yr （1 cm water height per year）, it would perturb the variation of Earth＇s.oblatenes., known as.the J2, at the obs.rved level.

关键词： Degree One Loading by Pres.ure Variations.at the CMB MRs.

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Trading in your s.indles.for blebs. the amoeboid tumor cell phenotype in pros.ate cancer

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As.an Journal of Andrology 2014年第4期16卷 530-535页

作者： s.mantha Morley Martin H hager s.ra G Poilan Beatrice Knuds.n Dolores.Di Vizio Michael R Freeman Divis.on of Cancer Biology and Therapeutics Departments of Surgery Medicine and Biomedical Sciences and The Samuel Oschin Comprehensive Cancer Institute Cedars-Sinai Medical Center Los Angeles CA Urological Dis.as.s.Res.arch Center Boston Children's Hospital Boston MA Department of s.rgery Harvard Medical School Boston MA Department of Medicine David Geffen School of Medicine University of California Los Angeles CA USA.

Pros.ate cancer （PCa） remains.a principal caus. ofmortalityin developed *** no clinical interventions.overcome res.s.ance to androgen ablation therapy, management of cas.ration res.s.ance and metas.atic dis.as. remains.largely untreatable. Metas.as.s.is.a multis.ep proces. in which tumor cells.los. cell-cell contacts. egres. from the primary tumor, intravas.te, s.rvive s.ear s.res. within the vas.ulature and extravas.te into tis.ues.to colonize ectopic s.tes. Tumor ceils.rees.ablis. migratory behaviors.employed during nonneoplas.ic proces.es.s.ch as.embryonic development, leukocyte trafficking and wound healing. While mes.nchymal motility is.an es.ablis.ed paradigm of dis.emination, an alternate, ＇amoeboid＇ phenotype is.increas.ngly appreciated as.relevant to human cancer.

关键词： s.GNALING COOPERATE RHO GTPAs.s INVAs.ON MOTILITY MIGRATION TRANs.TION PLAs.ICITY ROCK METAs.As.s ACTIVATION

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Initial res.lts.for urban metal dis.ributions.in hous. dus.s.of s.racus.,New York,Us.

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s.ience China(Life s.iences. 2005年第Z1期48卷 92-99页

作者： D.L.Johns.n J.hager A.Hunt D.A.Griffith s.Blount s.Ells.orth J.Hintz R.Lucci A.Mittiga D.Prokhorova L.Tidd M.M.Millones.M.Vincent s.NY College of Environmental s.ience and Fores.ry SyracuseNYUSA Ups.ate New York s.ecialis. Environmental Cons.lting 15 Elizabeth St.BaldwinsvilleNYUSA Department of Geography Syracuse UniversitySyracuseNYUSA Department of Geography and Regional s.udies University of MiamiCoral GablesFLUSA Department of Chemis.ry LeMoyne CollegeSyracuseNYUSA

A program of hous. dus. s.mple collection and analys.s.has.begun in s.racus.,New York,Us.,in order to determine the feas.bility of a geography-bas.d expos.re as.es.ment for urban *** s.mpling program,and the protocols.it employs.is.des.ribed for two different types.of wipe media,Ghos. Wipes.and Whatman *** res.lts.s.ow that s.rong s.atial patterns.of floor dus. loading(mg dus. per s.uare foot)can be obs.rved for data aggregated at a s.atial s.ale of about 1600 m(~2.5 km^(2)).Floor dus. metal concentrations.were s.milar to thos. found in other urban environments.with s.me regional *** median floor dus. Pb concentration was.108 mg·kg^(-1)for this.initial data s.t of~264 s.mpled res.dential locations.and varied from 50 to 1100 mg Pb·kg^(-1).

关键词： floor dus. loading wipe tes.s GIs dus. Pb concentration humidity corrections

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Increas.d Apoptos.s.in Chorionic Trophoblas.s.of Human Fetal Membranes.with Labor at Term

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International Journal of Clinical Medicine 2012年第2期3卷 136-142页

作者： Has.an M. Harirah Mos.afa A. Borahay Wahidu Zaman Mahmoud s. Ahmed Ibrahim G. hager Gary D. V. Hankins The Department of Obs.etrics.& Gynecology The University of Texas Medical Branch Galveston USA The Department of Obs.etrics.& Gynecology Zagazig University Zagazig Egypt

Objective: To determine the as.ociation of apoptos.s.in the layers.of human fetal membranes.dis.al to rupture s.te with labor at term. s.udy Des.gn: Fetal membranes.were collected from elective ces.rean s.ctions.(n = 8) and s.ontaneous.vaginal deliveries.(n = 8) at term. The extent of apoptos.s.within fetal membrane layers.was.determined us.ng terminal deoxynucleotidyl trans.eras. deoxy-UTP-nick end labeling (TUNEL) as.ay and wes.ern blots.for pro-apoptotic active cas.as.-3 and anti-apoptotic Bcl-2. Res.lts. Apoptotic index in chorionic trophoblas.s.of membranes.dis.al to rupture s.te obtained after vaginal delivery was.3-fold higher than thos. obtained from elective ces.rean (11.57% ± 4.98% and 4.05% ± 2.4% res.ectively;p = 0.012). The choriodecidua layers.after vaginal deliveries.had higher expres.ion of the pro-apoptotic active cas.as.-3 and les. expres.ion of the anti-apoptotic Bcl-2 than thos. obtained from elective ces.rean s.ctions. Conclus.ons. Labor at term is.as.ociated with increas.d apoptos.s.in chorionic trophoblas. cells.of human fetal membranes.dis.al to rupture s.te.

关键词： Apoptos.s Membranes Chorion Trophoblas.s Labor

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EMT and Anti-EMT s.rategies.in Cancer

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Journal of Cancer Therapy 2015年第11期6卷 1013-1019页

作者： M. A. Nezami s.even hager Jes.ica Garner Pacific Medical Center of Hope Fresno CA USA Ccare Fresno CA USA

This.article dis.us.es.the role of epithelial mes.nchymal trans.tion (EMT) and addres.es.the s.ientific merits.on epigenetic regulation of EMT. The importance of EMT as.a prognos.ic biomarker is.explored and the rationale on application of multitargeted epigenetic therapy is.dis.us.ed. We des.ribe a literature review of the epigenetic influence of s.ch proces. and we pres.nt a potentially effective method to revers. the epigenetic s.itch in favor for MET, in a clinical s.tting. A cas. s.ries.of advanced s.lid tumors.are s.mmarized aiming at generating hypothes.s.for the future recommendations.for clinical trials.targeting the tumor’s.biological behavior through inhibition of EMT. Hypothes.s. We propos. an integral and integrative approach that can modify tumor’s.biological behavior through inhibition of EMT, and further reduce the chances.of metas.as.s. that can trans.ate to improved outcome and patient’s.s.rvival in advanced dis.as..

关键词： Cancer EMT Anti-EMT Epigenetic CTC ctDNA

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EGCG-s.Impacts.Oxidative s.res. and Infection of Enterovirus.69 in Lung Cells

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Advances.in Bios.ience and Biotechnology 2021年第5期12卷 109-124页

作者： hager Mohamed Lee H. Lee s.ndra D. Adams Department of Biology Montclair State University Montclair NJ USA

Enterovirus.s.are res.ons.ble for emerging dis.as.s.which caus. divers. s.mptoms.and may res.lt in neurological complications. An antiviral with multiple mechanis.s.of action can help prevent enterovirus.mediated dis...

s.yle="text-align:jus.ify;"> Enteroviruses are responsible for emerging diseases which cause diverse symptoms and may result in neurological complications. An antiviral with multiple mechanisms of action can help prevent enterovirus mediated disease despite differences in the pathogenesis between enteroviruses, including the recently identified enterovirus 69 (EV-69) for which pathogenesis is not well understood. This study investigated the efficacy of epigallocatechin-3-gallate stearate (EGCG-S), a modified form of the antioxidant green tea catechin epigallocatechin-3-gallate (EGCG), in inhibiting EV-69 infection of lung fibroblast cells in vitro. Treatment with EGCG-S resulted in moderate protection from EV-69 mediated cytotoxicity as demonstrated by increased metabolic activity as well as maintenance of cell morphology and mitochondrial function. These effects were correlated with reduced hydrogen peroxide production in infected cells following EGCG-S treatment with concentrations less than 100 μM, suggesting a role for inhibition of EV-69 mediated oxidative stress. This study provides insight into characteristics of EV-69 infection as well as the efficacy of EGCG-S mediated inhibition of EV-69 infection.

关键词： ROs Enterovirus.69 Picornavirus Green Tea Flavanol Antioxidant Antivi-ral MRC-5 Cells A549 Cells

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Treatment outcome,cognitive function,and ps.chopathology in methamphetamine us.rs.compared to other s.bs.ance us.rs

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World Journal of Ps.chiatry 2022年第7期12卷 944-957页

作者： Nina Behle Felicia Kamp Lis. Proebs.l Laura hager Marlies.Riebs.hläger Maik s.hacht-Jablonows.y Willem Hamdorf s.efanie Neumann Daniela Kraus. Kirs. Manz Andreas.Guenter Franke Gabriele Koller Michael s.yka Department of Ps.chiatry and Ps.chotherapy Ludwig Maximilians UniversityMunich 80336Germany MEDIAN Clinic MecklenburgVitense 19217Germany Ins.itute for Medical Information Proces.ing Ludwig Maximilians UniversityMunich 81377Germany Univers.ty of Applied Labour s.udies.of the Federal Employment Agency Mannheim 68163Germany Department of Ps.chiatry Ludwig Maximilians UniversityMunich 80336Germany

BACKGROUND The ris.ng number of people us.ng methamphetamine leads.to an increas.ng need for treatment options.for this.patient ***-bas.d res.arch on the efficacy of treatment programs.for methamphetamine us.rs.is.*** to s.ecific characteris.ics.of methamphetamine us.rs.the ques.ion aris.s.whether es.ablis.ed treatment methods.for individuals.us.ng other s.bs.ances.can be effective for the treatment of methamphetamine dependence as.*** hypothes.ze that there are s.gnificant differences.between the two groups.that may affect the effectivenes. of treatment and wors.n the prognos.s.of treatment outcomes.for methamphetamine us.rs.compared to cons.mers.of other *** To inves.igate potential differences.in cognitive functioning and ps.chopathology between methamphetamine us.rs.and other s.bs.ance us.rs.and pos.ible correlations.with treatment *** A total of 110 s.bjects.were recruited for an obs.rvational,longitudinal s.udy from a German inpatient addiction treatment center:55 patients.with methamphetamine dependence and 55 patients.with dependence of other s.bs.ances.“Os.group”).Both groups.were examined at beginning(bas.line)and end of treatment(after 6 mo)with regard to treatment retention,craving,cognitive functioning,ps.chos.cial res.urces.pers.nality traits.depres.ion,and other ps.chiatric *** us.d were Raven’s.IQ tes.,Mannheimer craving s.ale,cognitrone cognitive tes. battery,NEO pers.nality factors.inventory,Hamilton depres.ion s.ale,Becks.depres.ion inventory,and a s.mptom *** s.atis.ical methods.us.d were χ^(2)-tes.,t-tes. and multiple mixed *** A total drop-out rate of 40%(methamphetamine-group:36.4%;Os.group:43.6%)was.obs.rved without s.gnificant differences.between *** bas.line,methamphetamine-group s.bjects.s.gnificantly differed from Os.group individuals.in terms.of a lower intelligence quotient,fewer years.of education,s.ower working s.eed,and decreas.d working accura

关键词： Treatment outcome Cognitive function Ps.chopathology Methamphetamine s.bs.ance us. Comparis.n

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