資源描述：
《抗惡性腫瘤藥》由會員上傳分享，免費在線閱讀，更多相關(guān)內(nèi)容在行業(yè)資料-天天文庫。
1、高分飛抗惡性腫瘤藥AntineoplasticAgents概述惡性腫瘤(malignanttumor,malignantneoplasm)，又稱癌癥(cancer)。全世界每年死于惡性腫瘤的患者達數(shù)百萬之多，約占總死亡人數(shù)的1/4。目前人類第二大死因。WorldwideoverallannualcancerincidenceDeathratesforheartdiseaseandcanceramongpeopleyoungerandolderthanage85.癌癥特點不受機體約束的增殖與細胞增殖有關(guān)的基因被開啟或激活；與細
2、胞分化有關(guān)的基因被關(guān)閉或抑制；局部侵襲(localinvasiveness)轉(zhuǎn)移(metastasis)低分化(lessdifferentiated)保留原組織一些特征TheAimofCancerTreatmentsPalliation——緩解癥狀，姑息治療AlleviationofsymptomsIncreasedsurvivalandimprovedqualityoflifeRemission——臨床治愈allmacroscopicandmicroscopicfeaturesofthecancerdisappear,th
3、oughdiseaseisknowntopersistCure——治愈allthecellsoftheclonemustbedestroyed目前主要治療手段SixEstablishedTherapeuticModalitiesSurgery(外科手術(shù))：實體瘤Rediotherapy(放射治療)：鼻咽癌、早期聲帶癌Cytotoxicchemotherapy(化學(xué)治療,化療)Endocrinetherapy(內(nèi)分泌治療)Immunotherapy(免疫治療)Biological/targetedtherapy(生物治療)CT
4、Mtreatment(中醫(yī)治療)Multi-modalitytreatment腫瘤化療的障礙毒性反應(yīng)選擇性差“殺敵一千，自損五百”耐藥性不敏感從單一治療向綜合治療從單一藥物到聯(lián)合用藥從姑息治療向根治治療從細胞毒性藥物向針對機制多環(huán)節(jié)新型藥物抗惡性腫瘤藥的三大趨勢BiologicbasisofchemotherapyCellCycleandCancer細胞周期的調(diào)控1322001年生理學(xué)或醫(yī)學(xué)獎LelandH.Hartwell(1939-,USA)控制點(checkpoint)RTimothyHunt(1943-,UK)周期蛋
5、白依賴性激酶(cyclindependentkinase,Cdk)PaulM.Nurse(1949-,UK)細胞周期蛋白(cyclin)CellCycleMITOSISENTRY(G2/M)ReplicationCompleteGrowth/ProteinSynthesisadequateNoDNADamageS-PHASEENTRY(G1/S)MitosisComplete?signal-cyclindegradationGrowth/ProteinSynthesis(G1CYCLINS)NoDNADamageOTHERS
6、MITOSISEXIT:?couplingtoS-phaseSPHASE:couplingtomitosisalsoinresponsetoDNAdamageG1sequenceofeventssignalingfromcellsurface生長比率(Growthfraction,GF)GF大：早期。急性白血病、何杰金病、絨癌，對藥物敏感；GF?。和砥凇Ｂ园籽?、多數(shù)實體瘤，對藥物敏感↓GF=腫瘤增殖期細胞數(shù)總腫瘤細胞數(shù)靜止細胞群非增殖細胞群（G0期）對藥物不太敏感，是復(fù)發(fā)根源。Thegrowthfractionofatu
7、mordeclinesexponentiallyovertime.Thegrowthrateofatumorpeaksbeforeitisclinicallydetectable.Tumorsizeincreasesslowly,goesthroughanexponentialphase,andslowsagainasthetumorreachesthesizeatwhichlimitationofnutrientsorauto-orhostregulatoryinfluencescanoccur.Themaximumgro
8、wthrateoccursat1/e,thepointatwhichthetumorisabout37%ofitsmaximumsize.Tumorbecomesdetectableataburdenofabout109(1cm3)cellsandkillsthepatientatatum
