
Overview:
IRR or insulin receptor-related receptor is a tyrosine protein kinase that is required for the appearance of male gonads and thus for male sexual differentiation (1). The expression of IRR mRNA is restricted to a few tissue types and has been detected in neuronal tissues as well as in neuroblastomas. As a result of its occurrence in neuroblastomas, it has speculated that IRR may be involved in tumor genesis.RT-PCR and solution hybridization/RNAse protection assay have shown strong coupling of IRR mRNA in 18 tumor cell lines (2).
Gene Aliases:
INSRR
Genbank Number:
NM_014215
References:
1.Zhang, B. and Roth, R.A. The insulin receptor-related receptor. Tissue expression, ligand binding specificity, and signaling capabilities. J. Biol. Chem. 1992; 267 (26): 18320-8.2.Elmlinger,M.W. et al: Correlation of type I insulin-like growth factor receptor (IGF-I-R) and insulin receptor-related receptor (IRR) messenger RNA levels in tumor cell lines from pediatric tumors of neuronal origin. Regul. Pept., 1999;84 (1-3): 37-42.
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不加磷酸化抑制剂也可以做磷酸化蛋白WB,但是有可能会影响具体的实验结果,大部分时候不加磷酸化抑制剂也能得到结果的。
需要注意蛋白的磷酸化是一个非常迅速的反应,所以取样品的过程要迅速,样品要新鲜。
所以做磷酸化蛋白WB,提取蛋白时不加磷酸酶抑制剂会有影响
酶抑制剂新药发现的途径:一是来源于天然化合物,包括动植物和各种微生物等,二是化学合成物。在目前上市的药物中,以受体为作用靶点的药物占52%,以酶为靶点的药物占22%,以离子通道为靶点的药物占6%,以核酸为靶点的药物占3%。因此,酶抑制剂的开发是新药来源的一个主要途径。以酶为靶点开发新药存在巨大潜力,今后很长一段时间仍然是发现新药的重要着手点。
Author:Shih IeM, Wang TL.
Resource:Cancer Res. 2007 Mar 1;67(5):1879-82.
Impact Factor:8.0(2005)
Abstract:The Notch signaling pathway represents a critical component in the molecular circuits that control cell fate during development. Aberrant activation of this pathway contributes to tumorigenesis. The role of Notch in human cancer has been highlighted recently by the presence of activating mutations and amplification of Notch genes in human cancer and by the demonstration that genes in the Notch signaling pathway could be potential therapeutic targets. It has become clear that one of the major therapeutic targets in the Notch pathway are the Notch receptors, in which gamma-secretase inhibitors prevent the generation of the oncogenic (intracellular) domain of Notch molecules and suppress the Notch activity. This review article summarizes the biological roles of Notch molecules in cancer development with special emphasis on the promise and challenges in applying gamma-secretase inhibitors as a new line of targeted therapeutic agents.
PMID: 17332312
A9 B12 C17 D36
正确答案C
一次氧化的产物不是乙酰COA么,那么产生的ATP为什么不是十个
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Exercisedampensaromataseinhibitor–relatedjointpain
http://www.internalmedicinenews.com/specialty-focus/oncology-hematology/single-article-page/exercise-dampens-aromatase-inhibitor-related-joint-pain/33383ff19a0cd42399a7cf8590708ebf.html
SANANTONIO–Adoptingastandardexerciseprogramresultedinaclinicallymeaningful30%reductioninaromataseinhibitor-associatedjointpaininbreastcancerpatientswhoparticipatedinayear-longrandomizedtrial.
TheexerciseprescriptionutilizedintheHOPE(HormonesandPhysicalExercise)trialwaswhat’srecommendedinnationalguidelinesbothforcancersurvivorsandhealthyadults:150minutesperweekofatleastmoderate-intensityaerobicactivity,suchasbriskwalking,alongwithtwostrength-trainingsessionsperweek,MelindaL.Irwin,Ph.D.,explainedattheSanAntonioBreastCancerSymposium.
TheHOPEstudiesenrolled121postmenopausalwomenwhohadstage1-3,hormonereceptor–positivebreastcancersandwerephysicallyinactiveandoverweightyetphysicallyabletoexercise.Atenrollment,theywereexperiencingmoderatearomataseinhibitor(AI)–associatedjointpain,definedasascoreof5-7onthe0-10BriefPainInventory(BPI),afterabout18monthsonthemedication.Roughlytwo-thirdsofparticipantshadnohistoryofjointpainpriortostartingAItherapy;therestreportedtheAIexacerbatedtheirpreexistingjointpain.Subjectswererandomizedtotheexerciseprogramortousualcare,whichincludedwritteninformationabouttheimportanceofexercise.
Theprimarystudyendpointwasthe12-monthchangeinBPIworstpainscore,whichdroppedbyanaverageof30%amongtheexercisegroup.Thistranslatedtoanimprovementinpainlevelfrommoderateatbaselinetomildatfollow-up.Inaddition,BPIscoresratingpainseverityandpaininterferenceimprovedbyabout20%.Incontrast,patientsintheusualcarecontrolgroupexperiencedaslightincreaseinBPIscoresinallthreedomainsovertime,addedDr.Irwin,co-leaderofthecancerpreventionandcontrolresearchprogramatYaleUniversityCancerCenter,NewHaven,Conn.
TheHOPEresultsreceivedanenthusiasticaudiencereception.Physicianswereparticularlyimpressedwiththe70%exerciseadherencerateoverthecourseofayear.Theyaskedhowtheycankeeptheirpreviouslysedentarypatients’commitmenttoregularexercisefromwaningafteraninitialburstofenthusiasm,assooftenhappens.
Dr.Irwinrepliedthatadherencetolifestylechangeisalwaysachallenge.Socialsupportisquitehelpful.TheexercisegroupinHOPEreceivedapaidgymmembershipandmetinsmallgroupswithapersonaltrainertwiceweekly.
"Thewomenreallybondedwitheachother.Andtherearenowagrowingnumberoffreeprogramsthroughoutthecountry,whichgivecancersurvivorsastartonanexerciseprogramwithafreegymmembershipforseveralmonths.Forexample,theLivestrongFoundationhaspartneredwiththeYMCAtoofferfreeexerciseprogramsforcancersurvivorsatlocalYs,"shesaid.
TheHOPEtrialwasfundedbytheNationalCancerInstitute.Dr.Irwinreportedhavingnofinancialconflictsofinterest.
Thisdegreeofimprovementinjointpainisgreaterthanreportedinstudiesofglucosamine,acupuncture,orvitaminDsupplementation,shenoted.
Theimprovementinpainscoresintheexercisegroupwasgreaterat12monthsthanat3or6,suggestingthatayear-longexerciseprogramisprobablynecessarytoseesustainedreductioninjointpain.
At12monthsoffollow-up,womenintheexercisegroupaveraged159minutesofphysicalactivityperweek,110minutesmorethancontrols.Compliancewiththesupervisedexerciseprogramwasnotablygood,withwomenattendinganaverageof70%ofthetwice-weeklysmall-groupstrength-trainingsessions.
InadditiontotheimprovementinAI-relatedarthralgias,theexercisegroupexperiencedancillarybenefits:amean6.5%improvementinpeakoxygenconsumption,orVO2max,comparedwithbaseline,alongwitha3%reductioninbodyweight.
HOPEwasthefirstrandomizedtrialtoexaminetheeffectsofexerciseonAIsideeffectsinbreastcancerpatients.TheimpetusforthestudywastherecognitionthatarthralgiasarethemostcommonreasonforpooradherencetoanddiscontinuationofAItherapy.Upto20%ofbreastcancerpatientsdiscontinuetheirAIwithinthefirstyear.Andbothearlydiscontinuationandpooradherencehavebeenshowntobepredictiveofincreasedmortalityrisk.

