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第十七章抗肿瘤药课件

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第十七 肿瘤 课件
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Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial ANTINEOPLASTIC AGENTS 抗肿瘤药 1 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial SECTION 1 Introduction 概述 SECTION 2 Agents directly acting on DNA 作用于DNA的药物 SECTION 3 Agents interfering with DNA synthesis 干扰DNA合成的药物 SECTION 4 Antimitotic agents 抗有丝分裂的药物 SECTION 5 New targets for antineoplastic agents 抗肿瘤药物的新靶点 2 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial SECTON 1 Introduction neoplasm 肿瘤 The medical term for cancer or tumor is neoplasm 肿瘤 which means a relatively autonomous growth of tissue Tumor is a general term indicating any abnormal mass or growth of tissue not necessarily life threatening A cancerous tumor is a malignant neoplasm with potential danger 3 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial sarcoma In the early embryo of a multicellular organism before organs begin to form cells arrange themselves in three layers ectodermal mesodermal and endodermal Mesodermal cells form bone muscle cartilage and related tissues A cancer that arises from mesodermal tissue is called sarcoma 4 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial carcinoma Ectodermal cells form skin its appendages and nerve tissue Endodermal cells form the intestinal system and its associated organs A cancer arises from ecto or endodermal cells is called a carcinoma 5 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Blastoma The suffix blastomais used to indicate certain types of tumors that have primitive appearance resembling embryonic structures Cancers of blood A cancer of the blood involving abnormal increase of leukocytes is called leukemia 6 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Cell growth cycles In a cell s nucleus DNA replication occurs during only one specific part of the cell cycle called S for synthesis Between division and S is a period called G1 in which cells grow but do not make DNA In G1 many molecules such as enzymes are synthesized Another period called G2 occurs between S and the period called M during which the two DNA copies separate 7 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Although each of these four main periods of the cell cycle G1 S G2 M is unique all in proper order are necessary for new cell production Normal and cancer cells behave differently Normal cell G1 G0 G1 Cancer cell G1 S G2 M G0 die 8 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial 9 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial SECTON 2 Agents directly acting on DNA 作用于DNA的药物 I Alkylating agents 烷化剂 II Platinum Complex 金属铂配合物 III Bleomycin 博来霉素类 IV 作用于DNA拓扑异构酶 topoismerase 的药物 10 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial I Alkylating agents Alkylating agents are reactive compounds that act on DNA RNA and certain enzymes 1 Nitrogen mustards 2 Aziridines 3 Methanesulfonate esters and multiple alcohols 4 Nitrosoureas 5 Triazemylimidazole 6 Hydrazine derivatives 11 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial I Alkylating agents 烷化剂 1 Nitrogen mustards 氮芥类 载体部分 烷基化部分 12 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Mechanism of nitrogen mustards 13 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial 14 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Many derivatives of the nitrogen mustards have been synthesized with various improvements These agents are thought to react with 7 position of guanine in each of the double strands of DNA causing cross linking which interferes with separation of the strands and prevents mitosis 15 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial The principle use of mechlorethamine is in combination chemotherapy of Hodgkin s disease and the non Hodgkin s lymphomas It has wide activity but more recent agents are safer and easier to use A major disadvantage ultimately carcinogenic effect on bone marrow stem cells culminating in a form of acute myelogenous leukemia Mechlorethamine Hydrochloride 盐酸氮芥 Mechlorethaminoxide Hydrochloride 盐酸氧氮芥 16 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Chlorambucil Chlorambucil is used chiefly in chronic lymphocytic leukemia usually orally because of its favorable aqueous solubility as the sodium salt and rapid conversion to the free drug Side effects are anorexia厌食 nausea and vomiting 17 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Melphalan It is effective in multiple myeloma 骨髓瘤 and has had a role in the treatment of breast and ovarian cancers Formylmerphalan N Formyl 4 bis b chloroethyl amino phenylalanine 国产 降低毒性 18 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Synthetic route of nitrogen mustards 19 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Cyclophosphamide 环磷酰胺 N N Bis 2 chloroethyl tetrahydro 2H 1 3 2 oxazaphosphorin 2 amine 2 oxide monohydrate 20 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Ifosfamide 异环磷酰胺 Trofosfamide 曲磷胺 21 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial 2 Aziridines 乙撑亚胺类 Tretamine Hexamethylmelamine Triethylenemelamine HMM 六甲蜜胺 TEM 三曲他胺 三乙蜜胺 p472 22 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Tepa Thiotepa 替哌 塞替哌 23 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Mitomycin C 丝裂霉素C Mitomycin C contains three groups that can damage cells the quinone that can participate in free radical reactions generating superoxides and aziridinyl and urethane 乌拉坦 氨基甲酸乙酯 24 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Reaction scheme for bioreductive activation of mitomycin C and the subsequent interstrand cross linking of DNA 25 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial 3 Methanesulfonate esters and multiple alcohols 甲磺酸酯及多元醇类 Busulfan 白消安 马利兰 双功能的烷化剂 临床对于慢性粒细胞白血病的疗效显 著 26 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Dibromomannitol Dibromodulcilol 二溴甘露醇 DBD 二溴卫矛醇 Dianhydrogalactitol DAG 脱水卫矛醇 R H Diacetyl dianhydrogalactitol DADAG 脱水卫矛醇双乙酰化物 R COCH3 27 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Carmustine BCNU 卡莫司汀 卡氮芥 N N Bis 2 chloroethyl N nitrosourea 4 Nitrosoureas 亚硝基脲类 28 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Synthetic route of Carmustine BCNU 卡莫司汀 卡氮芥 29 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Lomustine CCNU 洛莫司汀 R Semustine Me CCNU 司莫司汀 R Nimustine ACNU 盐酸尼莫司汀 R Ranimustine 雷莫司汀 R 30 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Decomposition of chloroethylnitrosoureas 氨甲酰化 31 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Streptozotocin 链左托星 R CH3 Chlorozotocin DCNU 氯脲霉素 R CH2CH2Cl 32 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial 5 Triazemylimidazole 三氮烯咪唑类 Dacarbazine DTIC 达卡巴嗪 5 3 3 dimethyl 1 triazemyl imidazole 4 carboxamide 临床用于黑色素病 何杰金氏病的治疗 33 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Bioactivation of dacarbazine 34 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial 6 Hydrazine derivatives 肼类 Procarbazine Hydrochloride 丙卡巴肼 甲基苄肼 N isopropyl 2 methyl hydrazino p toluamide hydrochloride 35 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Bioactivation of Procarbazine hydrochloride in vivo p479 36 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial II Platinum Complex 金属铂配合物 Cisplatin 顺铂 Cisplatin is the most active single agent against nonseminomatous 非精原细胞瘤的 testicular cancer and combinated with vinblastine and bleomycin it is usually curative It is also the most active single agent against ovarian cancer Other application include treatment of squamous and transitional cell carcinomas and treatment of small cell lung cancer 37 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial III Bleomycin 博来霉素类 Bleomycin is a group of glycopeptides with antitumor activity isolated from Streptomyces verticillus 放线菌 The clinical prepration is a mixture of bleomycin A2 A2I B1 4 etc with A2 the predominant component Bleomycin causes strand scission and fragment of DNA It acts in the form of a cupric complex inhibiting DNA ligase Bleomycin hs been used in basal cell carcinoma and pericardial sclerotherapy as well as in combination therapies especially because it lacks bone marrow toxicity and immune suppression It has modest activity in a variety of squamous cell cancer 38 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Bleomycin A2 X Bleomycin B2 X Bleomycin A5 X p482 39 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Antitumor mechanism of Bleomycin p484 40 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial 2 Agents acting on TopoII 作用于Topo II 的抗肿瘤药物 嵌入型抗肿瘤药物 L 苏氨酸 D 缬氨酸 L 脯氨酸 N 甲基甘氨酸 L N 甲基缬氨酸 放线菌素D p485 Actinomycin D Dactinomycin 吩噁嗪环 41 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Actinomycin is the most active of a series of cyclic pentapeptides isolated from Streptomyces parvulus The chemical structure of the antibiotics is composed of a tricyclic phenoxazin 3 one chromophore and two identical pentapeptide lactones group a and b attached to the chromophore Actinomycin binds with DNA by intercalation insertion between base pairs as in a sandwich and perpendicular to the main axis of the helix as are the base pairs Because of its flat rigid aromatic structure the oxazine 噁嗪 portion of actinomycin can bind nonconvalently between two successive bases in DNA elongating the DNA 42 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial p486 43 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Doxorubicin Adriamycin 多柔比星 阿 霉素 44 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Daunorubicin Epirubicin Daunomycin 柔红霉素 表柔比星 表阿霉素 45 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Anthracyclines 蒽环类抗肿瘤抗生素 represents a major class of antineoplastic drugs Doxorubicin is probably the most important anticancer drug available because of its relatively broad spectrum of activity and daunorubicin is an important agent in the treatment of acute lymphocytic and myelocytic leukemia Doxorubicin has a significant role in the treatment of solid tumors such as carcinoma of the breast lung thyroid and ovary as well as soft tissue sarcomas 46 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Zorubicin Aclacinomycin A 佐柔比星 阿柔比星 阿克拉霉素 47 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Mitoxantrone Novantrone 米托蒽醌 1 4 dihydro 5 8 bis 2 2 hydroxyethyl amino ethyl amino 9 10 anthracenedinone Bisantrene 比生群 Two anthracene derivatives showed low toxicity and especially low cardiac toxicity 48 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial SECTION 3 Agents interfering with DNA synthesis I Pyrimidine antagonists II Purines antagonists III Folic Acid Antagonists 49 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial I Pyrimidine antagonists 嘧啶拮抗物 1 Uracil derivatives 尿嘧啶衍生物 Fluorouracil 5 FU 氟脲嘧啶 5 氟尿嘧啶 5 fluoro 2 4 1H 3H pyrimidinedione 50 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Fluorouracil must be phosphorylated to the nucleotide to be active and as such inhibits thymidylate 胸苷酸 synthetase a key enzyme in the biosynthesis of DNA It has at least two biochemical actions that may account for its cytotoxicity It is converted first to the monophosphates 5 FUMP and 5 FdMP the latter binds tightly to thymidylate synthetase and inhibits the eventual synthesis of DNA On the other hand 5 FUMP after conversion to 5 FUTP is incorporated into RNA and
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