上海交通大学：《病理生理学》课程教学资源（PPT课件讲稿）第二章 肿瘤学

肿瘤学 Oncology)

肿瘤学 （Oncology)

肿蜜(umor) Carcinoma 癌症( cancei) Sarcoma 内瘤 Leukemia 血病

肿瘤(tumor) Carcinoma 癌 Sarcoma 肉瘤 Leukemia 白血病 癌症良性(cancer) 恶性

恶性肿瘤: 人类死亡的第一或第二元凶 现代医学面临的重要挑战之- 提高肿瘤防治水平和寻找 治疗肿瘤的新方法已成为 科学家和临床医学家所面 临的最大挑战

恶性肿瘤依然是现代医学面临的重要挑战之一。恶性肿瘤已经成为人类死亡的第一或第二元凶。 恶性肿瘤: 人类死亡的第一或第二元凶 现代医学面临的重要挑战之一 807 200 620 150 4000 450 0 1000 2000 3000 4000 年新发病数 年死亡数 年病例数 全球 儿童肿瘤发病率在逐渐升 中国 高。在5-10岁儿童中，恶 性肿瘤在造成死亡病种中 排名第一位。 提高肿瘤防治水平和寻找 治疗肿瘤的新方法已成为 科学家和临床医学家所面 临的最大挑战

initiation Promotion Cenversion Progression o Defects in Terminal Differentiation Defects in Growth Control Resistance to Cytotoxicity Defects in Programmed Cell Death Clonal Genetic 多因素、多步骤 CELL LESION TUMOA CANCER ETASTASIS s Activation of Proto-Oncogenes Inactivation of Tumor Suppressor Genes Inactivation of Antimetastasis genes Cancer Susceptibility Genes

多因素、多步骤

第一节 肿瘤病因学

第一节 肿瘤病因学

PotP(775童年时当过烟囱清扫工的男性患阴囊癌的比率增高 Folkman and Bell(1870s) 长期与石蜡油和焦油接触的工人易患皮肤瘟 Rehn(1880s 接触苯胺的工人类魔 cinogen Yamagiwa and Ichikawa(1915) 反复用煤焦油涂擦兔耳成功地诱发了皮肤癌 Cook James (1933) 证明多种化学致癌物( Benzopyrene) 与动物肿瘤的关系

Pott P(1775): Volkman and Bell (1870’s): Rehn (1880’s): Yamagiwa and Ichikawa (1915): Cook James (1933): Chemical carcinogen 童年时当过烟囱清扫工的男性患阴囊癌的比率增高 长期与石蜡油和焦油接触的工人易患皮肤癌 接触苯胺的工人发生泌尿道膀胱肿瘤 反复用煤焦油涂擦兔耳成功地诱发了皮肤癌 证明多种化学致癌物(Benzopyrene) 与动物肿瘤的关系

入机体后,无需代谢活化即有致癌作用的化学致癌物 独作用无致癌角,但对其致癌秘县有促进作 β-丙内酯、硫酸二甲酯、氮 芥溶肉瘤素、亚硝酸胺类、 Pott P(1775) (氯甲)醚等 苯巴比 direct Pro- Folkman and Bell(1870s) carcinogen Rehn(1880s) Chemical carcinogen Yamagiwa and Ichikawa(1915) Cook James (1933) indirect 进人体内后,必需经过体内代谢活化,寥曇豹癌傷思胺类 亚硝胺、黄曲雲素

Pott P(1775): Volkman and Bell (1870’s): Rehn (1880’s): Yamagiwa and Ichikawa (1915): Cook James (1933): Chemical carcinogen direct indirect Pro￾carcinogen β-丙内酯、硫酸二甲酯、氮 芥、溶肉瘤素、亚硝酸胺类、 二（氯甲）醚等 巴豆油、糖精、 苯巴比妥 多环芳香烃、芳香胺类、 亚硝胺、黄曲霉素 进入机体后，无需代谢活化即有致癌作用的化学致癌物 单独作用无致癌作用，但对其它致癌物具有促进作用 进人体内后，必需经过体内代谢活化，才具致癌作用

Indirect Carcinogen 前致癌物 precarcinogen 未经代谢活化的、不活泼的间接致癌物 Proximate carcinogen 近致癌物 经代谢转变为化学性质活泼 寿命极短的致癌物 Ultimate carcinogen 终致癌物 带正电荷的亲电子物质

Indirect Carcinogen precarcinigen Proximate carcinigen Ultimate carcinigen 前致癌物 未经代谢活化的、不活泼的间接致癌物 近致癌物 经代谢转变为化学性质活泼、 寿命极短的致癌物 终致癌物 带正电荷的亲电子物质

Indirect Carcinogen Cytochrome P-450(CYP): phase I precarcinogen enzymes Jact by adding atom onto the substrate inducible by polycyclic aromatic and chlorinated hydrocarbons Proximate carcinogen Largely responsible for the metabolic activation and detoxication Phase ii enzymes: act on oxidized substrates Ultimate carcinogen methyltransferases, acetyltransferases glutathione transferases, uridine 5 diphosphoglucuronosyl transferases sulfotransferases, nicotinamide-adenine dinucleotide(NAD)-and nicotinamide-adenine dinucleotide phosphate (NADP)-dependent alcohol, aldehyde and steroid dehydrogenases, quinone reductases NADPH diaphorase, azo reductases, aldoketoreductases transaminases, esterases, and hydrolases

Indirect Carcinogen precarcinigen Proximate carcinigen Ultimate carcinigen Cytochrome P-450 (CYP) : phase I enzymes ❑act by adding O atom onto the substrate ❑inducible by polycyclic aromatic and chlorinated hydrocarbons. ❑largely responsible for the metabolic activation and detoxication. Phase II enzymes: act on oxidized substrates methyltransferases, acetyltransferases, glutathione transferases, uridine 5'- diphosphoglucuronosyl transferases, sulfotransferases, nicotinamide-adenine dinucleotide (NAD)- and nicotinamide-adenine dinucleotide phosphate (NADP)-dependent alcohol, aldehyde and steroid dehydrogenases, quinone reductases, NADPH diaphorase, azo reductases, aldoketoreductases, transaminases, esterases, and hydrolases

Cytochrome P-450(CYP): phase I enzymes Jact by adding atom onto the substrate inducible by polycyclic aromatic and chlorinated hydrocarbons Largely responsible for the metabolic activation and detoxication Phase ii enzymes: act on oxidized substrates methyltransferases, acetyltransferases glutathione transferases, uridine 5 diphosphoglucuronosyl transferases de-adenine dinucleotide (Nad)-and eotide phosphate(NADP)-dependent dehydrogenases, quinone reductases uctases. aldoketoreductases hydrolases

Cytochrome P-450 (CYP) : phase I enzymes ❑act by adding O atom onto the substrate ❑inducible by polycyclic aromatic and chlorinated hydrocarbons. ❑largely responsible for the metabolic activation and detoxication. Phase II enzymes: act on oxidized substrates methyltransferases, acetyltransferases, glutathione transferases, uridine 5'- diphosphoglucuronosyl transferases, sulfotransferases, nicotinamide-adenine dinucleotide (NAD)- and nicotinamide-adenine dinucleotide phosphate (NADP)-dependent alcohol, aldehyde and steroid dehydrogenases, quinone reductases, NADPH diaphorase, azo reductases, aldoketoreductases, transaminases, esterases, and hydrolases