简介：AbstractImmunotherapy has become the mainstay for lung cancer treatment, providing sustained therapeutic responses and improved prognosis compared with those obtained with surgery, chemotherapy, radiotherapy, and targeted therapy. It has the potential for anti-tumor treatment and killing tumor cells by activating human immunity and has moved the targets of anti-cancer therapy from malignant tumor cells to immune cell subsets. Two kinds of immune checkpoints, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1), are the main targets of current immunotherapy in lung cancer. Despite the successful outcomes achieved by immune checkpoint inhibitors, a small portion of lung cancer patients remain unresponsive to checkpoint immunotherapy or may ultimately become resistant to these agents as a result of the complex immune modulatory network in the tumor microenvironment. Therefore, it is imperative to exploit novel immunotherapy targets to further expand the proportion of patients benefiting from immunotherapy. This review summarizes the molecular features, biological function, and clinical significance of several novel checkpoints that have important roles in lung cancer immune responses beyond the CTLA-4 and PD-1/PD-L1 axes, including the markers of co-inhibitory and co-stimulatory T lymphocyte pathways and inhibitory markers of macrophages and natural killer cells.

简介：AbstractPancreatic cancer is one of the most aggressive malignancies. The poor prognosis of pancreatic cancer patients is mainly attributed to low diagnostic rate at the early stage, highly aggressive nature coupled with the inadequate efficacy of current chemotherapeutic regimens. Novel therapeutic strategies are urgently needed for pancreatic cancer. MicroRNAs (miRNAs) play an important regulatory role in key processes of cancer development. The aberrant expression of miRNAs is often involved in the initiation, progression, and metastasis of pancreatic cancer. The discovery of tumor suppressor miRNAs provides prospects for the development of a novel treatment strategy for pancreatic cancer. We reviewed recent progress on the understanding of the role of miRNAs in pancreatic cancer, highlighted the efficient application of miRNAs-based therapies for pancreatic cancer in animal models and clinical trials, and proposed future prospects. This review focuses on the promise of integrating miRNAs into the treatment of pancreatic cancer and provides guidance for the development of precision medicine for pancreatic cancer.

简介：Thefibroblastgrowthfactorreceptor(FGFR)familyplaysimportantrolesinregulatingcellgrowth,proliferation,survival,differentiationandangiogenesis.DeregulationoftheFGF/FGFRsignalingpathwayhasbeenassociatedwithmultipledevelopmentsyndromesandcancers,andthustherapeuticstrategiestargetingFGFsandFGFRinhumancancerarecurrentlybeingexplored.However,fewstudiesontheFGF/FGFRpathwayhavebeenconductedinsarcoma,whichhasapooroutcomewithtraditionaltreatmentssuchassurgery,chemotherapy,andradiotherapy.Hence,inthepresentreview,weprovideanoverviewoftheroleoftheFGF/FGFRpathwaysignalinsarcomaandFGFRinhibitors,whichmightbenewtargetsforthetreatmentofsarcomasaccordingtorecentresearch.

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简介：AbstractGlioblastoma is the most common form of primary brain tumor. Glioblastoma stem cells play an important role in tumor formation by activation of several signaling pathways. Wnt signaling pathway is one such important pathway which helps cellular differentiation to promote tumor formation in the brain. Glioblastoma remains to be a highly destructive type of tumor despite availability of treatment strategies like surgery, chemotherapy, and radiation. Advances in the field of cancer biology have revolutionized therapy by allowing targeting of tumor-specific molecular deregulation. In this review, we discuss about the significance of glioblastoma stem cells in cancer progression through Wnt signaling pathway and highlight the clinical targets being potentially considered for therapy in glioblastoma.

简介：INTRODUCTIONMolecularbiologyhasmadeatremendousimpactonthediagnosisandtreatmentofliverdiseases.Inparticular,advancesinmolecularbiologymadepossiblethediscovery

简介：Colorectalcancer(CRC)isthethirdmostcommoncancerinmenandthesecondmostcommoncancerinwomen,worldwide.Intheearlystagesofthedisease,biomarkerspredictingearlyrelapsewouldimprovesurvivalrates.Inmetastaticpatients,theuseofpredictivebiomarkerscouldpotentiallyresultinmorepersonalizedtreatmentsandbetteroutcomes.TheCXCfamilyofchemokines(CXCL1to17)aresmall(8to10kDa)secretedproteinsthatattractneutrophilsandlymphocytes.Thesechemokinessignalthroughchemokinereceptors(CXCR)1to8.Severalstudieshavereportedthatthesechemokinesandreceptorshavearoleineitherthepromotionorinhibitionofcancer,dependingontheircapacitytosuppressorstimulatetheactionoftheimmunesystem,respectively.Ingeneralterms,activationoftheCXCR1/CXCR2pathwayortheCXCR4/CXCR7pathwayisassociatedwithtumoraggressivenessandpoorprognosis;therefore,thespecificinhibitionofthesereceptorsisapossibletherapeuticstrategy.Ontheotherhand,thelesserknownCXCR3andCXCR5axesaregenerallyconsideredtobetumorsuppressorsignalingpathways,andtheirstimulationhasbeensuggestedasawaytofightcancer.Thesepathwayshavebeenstudiedintumortissues(usingimmunohistochemistryormeasuringmRNAlevels)orserum[usingenzyme-linkedimmunosorbentassay(ELISA)ormultiplexingtechniques],amongothersampletypes.CommonvariantsingenesencodingfortheCXCchemokineshavealsobeeninvestigatedaspossiblebiomarkersofthedisease.ThisreviewsummarizesthemostrecentfindingsontheroleofCXCchemokinesandtheirreceptorsinCRCanddiscussestheirpossiblevalueasprognosticorpredictivebiomarkersaswellasthepossibilityoftargetingthemasatherapeuticstrategy.

简介：在apoptotic小径以内的缺点在前列腺癌症(PCa)被含有tumorigenesis，变形前进和治疗抵抗。癌症的一个特点是出轨的能力由禁止apoptotic信号，减少apoptotic蛋白质的表达式或放大幸存的apoptosis通过antiapoptotic的增加的生产发信号分子。这评论描述在热吃惊蛋白质(HSP)和人的雄激素之间的协会受体(AR)，HSP的角色和在PCa开发的另外的导致压力的蛋白质和在指向这些保护的蛋白质对待PCa的新兴的策略。

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简介：Objective:Oxidativestressislinkedtoincreasedriskofgastriccancerandmatrixmetalloproteinases(MMPs)areimportantintheinvasionandmetastasisofgastriccancer.WeaimedtoanalyzetheeffectoftheaccumulationofoxidativestressinthegastriccancerMKN-45and23132/87cellsfollowinghydrogenperoxide(H2O2)exposureontheexpressionpatternsofMMP-1,MMP-3,MMP-7,MMP-9,MMP-10,MMP-11,MMP-12,MMP-14,MMP-15,MMP-17,MMP-23,MMP-28,andβ-cateningenes.Methods:ThemRNAtranscriptsinthecellsweredeterminedbyRT-PCR.FollowingH2O2exposure,oxidativestressintheviablecellswasanalyzedby2’,7’-dichlorofluoresceindiacetate(DCFH-DA).Caffeicacidphenethylester(CAPE)wasusedtoeliminateoxidativestressandtheconsequenceofH2O2exposureanditsremovalontheexpressionsofthegeneswereevaluatedbyquantitativereal-timePCR.Results:TheexpressionsofMMP-1,MMP-7,MMP-14,MMP-15,MMP-17andβ-catenininMKN-45cellsandonlytheexpressionofMMP-15in23132/87cellswereincreased.RemovaloftheoxidativestressresultedindecreaseintheexpressionsofMMPgenesofwhichtheexpressionswereincreasedafterH2O2exposure.β-catenin,atranscriptionfactorformanygenesincludingMMPs,alsodisplayeddecreasedlevelsofexpressioninbothofthecelllinesfollowingCAPEtreatment.Conclusions:OurdatasuggestthatthereisaremarkablelinkbetweentheaccumulationofoxidativestressandtheincreasedexpressionsofMMPgenesinthegastriccancercellsandMMPsshouldbeconsideredaspotentialtargetsoftherapyingastriccancersduetoitscontinuousexposuretooxidativestress.

简介：Chemokinesbelongtoalargefamilyofinflammatorycytokinesresponsibleformigrationandaccumulationofleukocytesatinflammatorysites.Overthepastdecade,accumulatingevidenceindicatedacrucialroleforchemokinesandchemokinereceptorsinthepathophysiologyofrheumatoidarthritis(RA).RAisachronicautoimmunediseaseinwhichthesynovialtissueisheavilyinfiltratedbyleukocytes.Chemokinesplayanimportantroleintheinfiltration,localization,retentionofinfiltratingleukocytesandgenerationofectopicgerminalcentersintheinflamedsynovium.RecentevidencealsosuggeststhatidentificationofinhibitorsdirectlytargetingchemokinesortheirreceptorsmayprovideanoveltherapeuticstrategyinRA.TraditionalChinesemedicinals(TCMs)havealonghistoryinthetreatmentofinflammatoryjointdisease.ThebasisfortheclinicalbenefitsofTCMremainslargelyunclear.Ourstudieshaveledtotheidentificationofnumerousnovelchemokine/chemokinereceptorinhibitorspresentinanti-inflammatoryTCMs.Alloftheseinhibitorswerepreviouslyreportedbyotherresearcherstohaveanti-arthriticeffect,whichmaybeattributable,atleastinpart,totheirinhibitoryeffectonchemokineand/orchemokinereceptor.Therefore,identificationofagentscapableoftargetingchemokine/chemokinereceptorinteractionshassuggestedamechanismofactionforseveralTCMcomponentsandprovidedameansofidentifyingadditionalanti-RATCM.Thus,thisapproachmayleadtothediscoveryofnewinhibitorsofchemokinesorchemokinereceptorsthatcanbeusedtotreatdiseasesassociatedwithinappropriatelyoveractivechemokinemediatedinflammatoryreactions.Cellular&MolecularImmunology.2004;1(5):336-342.

简介：AbstractThe present pandemic has posed a crisis to the economy of the world and the health sector. Therefore, the race to expand research to understand some good molecular targets for vaccine and therapeutic development for SARS-CoV-2 is inevitable. The newly discovered coronavirus 2019 (COVID-19) is a positive sense, single-stranded RNA, and enveloped virus, assigned to the beta CoV genus. The virus (SARS-CoV-2) is more infectious than the previously detected coronaviruses (MERS and SARS). Findings from many studies have revealed that S protein and RdRp are good targets for drug repositioning, novel therapeutic development (antibodies and small molecule drugs), and vaccine discovery. Therapeutics such as chloroquine, convalescent plasma, monoclonal antibodies, spike binding peptides, and small molecules could alter the ability of S protein to bind to the ACE-2 receptor, and drugs such as remdesivir (targeting SARS-CoV-2 RdRp), favipir, and emetine could prevent SASR-CoV-2 RNA synthesis. The novel vaccines such as mRNA1273 (Moderna), 3LNP-mRNAs (Pfizer/BioNTech), and ChAdOx1-S (University of Oxford/Astra Zeneca) targeting S protein have proven to be effective in combating the present pandemic. Further exploration of the potential of S protein and RdRp is crucial in fighting the present pandemic.

简介：Mitochondriaplayanimportantroleinneuronalapoptosiscausedbycerebralischemia,andtheroleismediatedbytheexpressionofmitochondrialproteins.Thisstudyinvestigatedtheinvolvementofmitochondrialproteinsinhippocampalcellapoptosisaftertransientcerebralischemia-reperfusioninjuryinagedratsusingacomparativeproteomicsstrategy.Ourexperimentalresultsshowthattheagedratbrainissensitivetoischemia-reperfusioninjuryandthattransientischemialedtocellapoptosisinthehippocampusandchangesinmemoryandcognitionofagedrats.Differentialproteomicsanalysissuggestedthatthisphenomenonmaybemediatedbymitochondrialproteinsassociatedwithenergymetabolismandapoptosisinagedrats.Thisstudyprovidespotentialdrugtargetsforthetreatmentoftransientcerebralischemia-reperfusioninjury.