肿瘤的生物学特性

1、4物质代谢及酶的变化 肿瘤细胞的分化肿瘤细胞的生长肿瘤细胞扩散的过程机制 肿瘤侵袭和转移相关基因物质代谢及酶的变化 核酸代谢核酸增多是肿瘤迅速生长的物质基础ADNA拓扑异构酶端粒酶物质代谢及酶的变化核酸代谢DNA拓扑异构酶存在于细胞核内的一类酶，他们能够催化DNA链的 断裂和结合，从而控制DNA的拓扑状态。DNA拓扑异构酶通过形成短暂的单链裂解-结合循环,催化盛复制的拓扑异构状态的变化7Type IBkDgCTop3cx. 112Topap 97Tc>p1lOOTopi nrt 70CTopZcx. 1 70 (X2)Top2p 1 80 (x2)P-Y ALk.B±1Topo

2、 ITopo IIIGy raseType IIA!：7 t-aK8 P-Y ALk9874,GyrA 97 (X2) GyrK 90 Cx2)S'士2士NFItT81Topi Topi mlEllipticineAzatoxln Quinolones Isoflavonesincino'；ARC-1 1 1Etopo%id<? Doxorubicin Quin older?%Tcp2<i TopZji Gy rase Topo ivC/CflvctcyeParC 84 <x2)5,Pi»rE 70 <x2)thItTqp1TCP141H(A)

3、 Classification of human DNA topoisomerases. Type IB are the only enzymes that form cleavage complexes (cc) with 30-phosphotyrosyl (30-P-Y) intermediates.(C) Noncovalent binding of type IB enzymes. (D) Scheme of the 30phosphotyrosine covalent bond in the Toplcc. The arrow indicates thereversible (re

4、ligation) reaction, which is favored under normal conditions. G)Scheme of the 50-phosphotyrosine covalent bond in the Top2cc. 6zpSer pSer pTtTopoismerase H a _134就Tyr-805pS er-1106 /.vV./二r t I i- i « ra i i a t i i a ' * '，卜J" J' .ir pSer pSer pSer pSer pSerx.-r*'J J J ,1-

5、/耐 pSer pSer pt XJ247 1337 1354 K1531.>er pScr pThr pSer p5c一 $77 1393 1470 1474 1525XDNA Binding/ DMA CleavageTopoismeraseFig, (1). Primary domain structure of the topoisomerase Ila and topoisomerase Up isozymes. The homologous N-tcnniiial ATPasc region and central catalytic core regions of the

6、two enzymes arc depicted by similarly filled boxes,whereas the non-homologus C-terminal regulatory domains are depicted by boxes with different stripes. NLS mdicatcs nuclear localization signal; pScr and pThr indicate phosphorylated serine and phosphorylated threonine amino acid rcsidue, respectivel

7、y. The amino acid numbers arc based on tlie topoisomerase Ila sequence -SwissProt accession Pl 1388 and topoisomerase lip sequence - SwissProt accession Q02880.物质代谢及酶的变化核酸代谢端粒酶It is thought that length or integrity of chromosome end is used as a mitotic counting mechanism in vitro一Each mammalian chr

8、omosome end has adistinctive DNA-protein structure, which preventsthe degradation and fusion of chromosome endsby helping distinguish chromosome ends from adouble strand break in the genomic DNA.核酸代谢端粒酶Mammalian have a stretch of a simple repeat sequenceunit (TTAGGG) and in , length is 15-20 kb.Fift

9、y to 200 bp of the telomeric DNA shortens at eachround of mitosis. When average DNA reaches acritically short length, about 4-7 kb, is arrestedIrreversibly.核酸代谢 ，蛋白质代谢 ，糖代谢二 /酶系统酶系统增殖相关和分化相关的酶转化相关和演进相关的酶转化相关细胞恶变的指标Q主要正常细胞发生转化，总可出现这类酶活性的 改变。演进相关的酶 酶活性于恶性程度呈平行关系的酶15肿瘤细胞的分化17分化的概念同一来源的（特定的生理功能 各种不同幼稚细胞

10、A类型细胞（分化细胞）特定的生化特征特定的形态结构细胞分化特点：稳定性全能性选择性条祸卷1 一 '未分化恶性肿瘤是由于起源组织中的干细胞 丧失了分化的能力。肿瘤细胞分化异常的机制遗传学改变信号转化异常微环境的影响诱导分化治疗肿瘤19肿瘤细胞的生长细胞增殖活性的原位检测方法及意义细胞增殖活性： 细胞增生快慢的能力含量测定确定增生细胞的比例Flow cytometry 法DNA ploidy and proliferative activity asrepresented by the S-phase fraction (SPF).A link exists between high SP

11、F values and increased risk of recurrence and death for patients with primary BC,22免疫组织化学方法Only papers published in English in peer reviewed journals before June 2004 that include at least 100 evaluable patients were selected. In addition, the prognostic and predictive role of the proliferative mark

12、ers had to be assessed through multivariate analyses. One hundred and thirty-two papers fulfilled these criteria and 159 516 patients analyzed.> Ki-67-Several monoclonal antibodies reacting with different proliferating cell nuclear antigens have been described, such as PCNA, Ki-67 and MIB 1, KiS1

13、 and others.The Ki-67/MIB 1 protein has a rognostivalue for many types of malignant tumors.免疫组织化学方法细胞周期蛋白The different cyclins: the concentration rise and fall at specific stages throughout the cell cycle, have a temporally distinct and highly regulated patterrifexpression, i.e. they are synthesized

14、 and degraded at specific stages of the cell cycle.Cyclin E is the limiting factor for G1 phaseprogression and S phase entryRecently, several splice variants of cyclin E1, which are not present in normal cells, have also been discovered； which stimulate cells to progress through the cell cycle much more efficiently than the full length cyclin E1肿瘤细胞的生长免疫组织化学方法细胞周期蛋白Cyclin E was prognostic in seven out of 10 studies.The overexpression of cyclin E was accompanied bythe appearance of low molecular weig