医科大学病理学英文课件Section 8.Etiology and pathogenesis of tumor

1、Section 8. Etiology and pathogenesis of tumor,8.1 Molecular basis of oncogenesis,8.1.1 Oncogene 1. Protooncogene , oncogene and products (1) Protooncogene: cellular genes that promote normal cell growth and differentiation, exist in normal cells, in the form of inactivity. (2) Oncogene: derived from

2、 protooncogene promote abnormal growth,3) Mode of protooncogenes activation Point mutation Chromosomal rearrangement Gene amplification promoter insertion,4) Products and functions of protooncogenes,Growth factors: PDGF,FGF, EGF Growth factor receptors Signal- transducing proteins: ras Nuclear regul

3、atory proteins: myc Cell cycle regulatory proteins: cyclins,8.1.2 Tumor suppressor gene,1.Concept: cellular genes that exist in normal cells inhibit normal growth and cause cells to malignant transform when they become inactive. 2. Examples: Rb , p53 , P16,TGF-, BRCA-1 , BRCA-2 3. mechanism: allele

4、mutation, deletion, methylation,8.1.3 Genes that regulate apoptosis and DNA repair,Genes that regulate apoptosis Bcl (B-cell lymphoma)family: Bcl-2: inhibit apoptosis Bax: induce apoptosis 2. Genes that regulate DNA repair,8.1.4 Telomeres, telomerase and cancer,1.Telomeres shorting is believed to be

5、 a clock that counts cell division, is a tumor-suppressive mechanism. 2.Telomerase: Sustain the function of telomeres Absent from most somatic cell Increased activity of it tumor,8.1.5 Molecular basis of multistep carcinogenesis,8.2 Environmental factors and their mechanism,8.2.1 Cheminal carcinogen

6、ic agents Indirect-acting agent Polycyclic hydrocarbons:in fossil fuel or combustion of tabacco in smoking ,relate to the development of skin, lung, stomach carcinoma (2) Aromatic amines and azo dyes: bladder, hepatocellular carcinoma (3) Aflatoxin: potent hepatocarcinogen (4)Nitrosamines:lung, gast

7、ric, esophagus,2. Direct-acting agents (1) Alkylatingand acylating agents: anticancer drugs cyclophosphamide (2) Others arsenicskin carcinoma chromiumlung carcinoma cadmiumprostate carcinoma nickellung carcinoma,8.2.2 Physical carcinogenic factors,1. Ionizing radiation: X-ray, -ray related to leukem

8、ia , carcinoma of skin, lung, breast,colon. 2. UV: skin carcinoma 3. Others: asbestos mesothelioma artificial mammary carcinoma,8.2.3 Biologic carcigenic agents,1. RNA virus: Transduction/ insertional mutagenesis HTLV-1 : human T cell leukemia/ lymphoma 2. DNA virus: (1) HPV:cervical squamous cell c

9、arcinoma (2) Epstein-Barr virus :nasopharyngeal carcinoma (3) HBV: hepatocyte carcinoma 3. Helicobacter pylori: chronic gastritis, B lymphoma of stomach,8.3 Internal factors and its mechanism,8.3.1 Inherited predisposition to carcinogens 1. Inherited cancer syndrome (Autosomal dominant) Familial ret

10、inoblastoma 2. Autosomal recessive syndromes: Bloom syndrome, fanconi anemia 3. Familial cancer: breast,ovary,colon,8.3.2 Tumor immunity,1.Tumor antigen: Tumor specific Ag :only in neoplastic Tumor associated Ag: CEA, AFP 2. Antitumor immunity: mainly cell immunity T cell: lymphotoxin NK cell, Macrophage :ADCC 3. Immunesurveilance: Immunodificient host/ immunosuppressed 4. Immunotherapy: stimulate the endogenous reaction, increase the function of antitumor,复习思考题 1.比较良、恶性肿瘤的区别？ 2.高分化鳞癌的结构特点？ 3.何谓实性癌？简述其病理特点？