腫瘤病因_發(fā)病機(jī)理ppt課件

1、.,1,腫 瘤 學(xué),王彩蓮,.,2,腫瘤的基本概念,腫瘤 機(jī)體在致瘤因子作用下，細(xì)胞遺傳物質(zhì)改變導(dǎo)致基因表達(dá)異常，細(xì)胞異常增殖而形成的新生物,.,3,腫瘤的基本概念,Cancer (medical term: malignant neoplasm) is a large, heterogeneous class of diseases in which a group of cells display uncontrolled growth, invasion that intrudes upon and destroys adjacent tissues, and often metasta

2、sizes, wherein the tumor cells spread to other locations in the body via the lymphatic system or through the bloodstream,.,4,腫瘤的基本概念,These three malignant properties of cancer differentiate malignant tumors from benign tumors, which do not grow uncontrollably, directly invade locally, or metastasize

3、 to regional lymph nodes or distant body sites like brain, bone, liver, or other organs,.,5,.,6,腫瘤發(fā)生原因,1、腫瘤發(fā)生的環(huán)境因素 化學(xué)致癌 化學(xué)致癌物 物理致癌 輻射致癌 生物致癌 病毒致癌 2、遺傳因素 3、腫瘤發(fā)生的學(xué)說,.,7,化學(xué)致癌,.,8,物理、生物致癌,.,9,遺傳性腫瘤與遺傳性腫瘤綜合征,.,10,遺傳性腫瘤與遺傳性腫瘤綜合征,.,11,遺傳性腫瘤與遺傳性腫瘤綜合征,.,12,腫瘤發(fā)生學(xué)說,三階段學(xué)說 兩次突變學(xué)說（克隆起源學(xué)說） 生殖細(xì)胞突變 體細(xì)胞突變 多階段學(xué)說 干細(xì)胞起源

4、學(xué)說,.,13,腫瘤發(fā)生學(xué)說,變異細(xì)胞,癌前病變,惡性腫瘤,三階段學(xué)說,啟動階段,促進(jìn)階段,發(fā)展階段,.,14,癌基因,Ras H-ras，K-ras, N-ras 編碼產(chǎn)物：鳥苷酸結(jié)合蛋白，具有GTP酶活性， 定位于細(xì)胞膜的內(nèi)側(cè)面，為細(xì)胞的第二信使 K-ras突變：50%結(jié)腸癌、70%-90%胰腺癌、30%肺腺癌,.,15,癌基因,myc 編碼產(chǎn)物：P62蛋白，使細(xì)胞從G0期進(jìn)入G1期，細(xì)胞分裂效應(yīng)蛋白 myc 擴(kuò)增：30%-40%小細(xì)胞肺癌、神經(jīng)母細(xì)胞瘤、膠質(zhì)細(xì)胞瘤,.,16,癌基因,1、HER-2 過表達(dá)：乳腺癌、卵巢癌、胃癌，Prognostic Marker 2、C-met 基因擴(kuò)增

5、、重排、過量表達(dá) 3、Bcl-2 基因：NHL 中有易位活化的該基因的表達(dá)，與凋亡相關(guān) 4、細(xì)胞周期蛋白：cyclin蛋白，淋巴瘤、乳腺癌、胃癌、食管癌有蛋白的過度表達(dá) 5、端粒酶：染色體末端由端粒DNA和端粒蛋白質(zhì)構(gòu)成,.,17,H-Ras structure PDB 121p, ribbon showing strands in purple, helices in aqua, loops in gray. Also shown are the bound GTP analog and magnesium ion.,.,18,抑癌基因,Rb P53 INK4基因家族 CIP-KIP基因家族

6、 PTEN FHIT BRCA APC DCC WT-1,.,19,抑癌基因,Rb： 視網(wǎng)膜母細(xì)胞瘤基因 基因缺失或突變 骨肉瘤 肺癌 軟組織肉瘤,.,20,抑癌基因,p53： 基因缺失或基因突變 抑制細(xì)胞生長，誘導(dǎo)細(xì)胞凋亡 結(jié)腸癌、胃癌、乳腺癌、膀胱癌、 肺癌、肝癌,.,21,抑癌基因,INK4基因家族： inhibitors of cyclin-dendent kinases-4 p15,p15,p18,p19 抑制細(xì)胞周期蛋白依賴性激酶（CDKs）的活性,.,22,抑癌基因,CIP-KIP基因家族： p21, p27, p57 抑制細(xì)胞周期蛋白依賴性激酶（CDKs） 的活性 參與細(xì)胞分化

7、、細(xì)胞周期及調(diào)控,.,23,抑癌基因,PTEN,Phosphatase and tensin homolog (PTEN) is a protein that, in humans, is encoded by the PTEN gene. Mutations of this gene are a step in the development of many cancers,Stucture of human PTEN,.,24,抑癌基因,PTEN acts as a tumor suppressor gene through the action of its phosphatase pr

8、otein product. This phosphatase is involved in the regulation of the cell cycle, preventing cells from growing and dividing too rapidly. It is one of the targets of an oncomiR, MIRN21.,.,25,抑癌基因,This gene was identified as a tumor suppressor that is mutated in a large number of cancers at high frequ

9、ency. The protein encoded by this gene is a phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase,.,26,抑癌基因,It negatively regulates intracellular levels of phosphatidylinositol-3,4,5-trisphosphate in cells and functions as a tumor suppressor by negatively regulating Akt/PKB signaling pathway,.,27,抑

10、癌基因,PTEN is one of the most commonly lost tumor suppressors in human cancer Frequent genetic inactivation of PTEN occurs in glioblastoma, endometrial cancer, and prostate cancer reduced expression is found in many other tumor types such as lung and breast cancer,.,28,抑癌基因,BRCA,Both BRCA genes are tu

11、mor suppressor genes that produce proteins that are used by the cell in an enzymatic pathway that makes very precise, perfectly matched repairs to DNA molecules that have double-stranded breaks. The pathway requires proteins produced by several other genes, including CHEK2, FANCD2 and ATM,Harmful mu

12、tations in any of these genes disable the gene or the protein that it produces,.,29,抑癌基因,The cancer risk caused by BRCA1 and BRCA2 mutations are inherited in an dominant fashion A mutated BRCA gene can be inherited from either parent. Because they are inherited from the parents, they are classified as hereditary or germline mutations rather than acquired or somatic mutations Cancer caused by a mutated gene is a hereditary cancer rather than a sporadic cancer,.,30,抑癌基因,Mutations have been associated with increased risk of developing any kind of invasive cancer stomach cancer pancreatic