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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 r
3、egulatory 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: all
4、ele 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
5、to be 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 carci
6、nogenic 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,
7、 gastric, 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 l
8、eukemia , 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 c
9、ell carcinoma (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) Familia
10、l retinoblastoma 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,
11、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？ 4.异型性、分化程度及与肿瘤良恶性的关系？ 5.肿瘤性增生与炎症性增生的区别？ 6.恶性肿瘤对机体的影响？ 7.何谓癌前病变，请列举5种癌前病变或癌前疾病，并说明应如何正确对待癌前病变。 8.腺上皮可形成哪几种类型的恶性肿瘤，并简述各自的形态特点？ 9.试述转移瘤的形成过程及其形态特点？ 10.举例说明为什么说良恶性肿瘤的区别是相对的？,