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1、微生物与肿瘤,Infectious agents and cancer,与肿瘤相关的微生物,RNA病毒： 逆转录病毒 DNA病毒 疱疹病毒科的大多数成员如EBV、HCMV、HSV-2、HHV-8等 腺病毒科的腺病毒 乳多空病毒科的Simian Virus 40(SV40) Murine Polyoma Virus JC virus,BK virus 嗜肝病毒科的HBV 人乳头瘤病毒科的HPV 细菌：幽门螺杆菌,Viruses cause cancer 30-40% of cancers are known to have viral etiology But as more research
2、is done, this percentage is likely to be found to be higher,与肿瘤相关的微生物研究史,1908年 Ellerman和Bang用鸡白血病的无细胞滤液感染鸡，鸡可发生白血病 1911年 Rous用可过滤因子成功地诱发了鸡的肉瘤。1947年Claude等观察到病毒颗粒, 命名为Rous肉瘤病毒 1908年发现Avian leukemia virus. Ellermann V, Bang O. Experimentelle leukamie bei huhnern. Zentralbl Bakteriol Parasitenkd Infekt
3、ionskr Hyg1908;46:5957. 1911年发现Avian Rous sarcoma virus (RSV) 第一个被证实的肿瘤病毒. Rous P. A sarcoma of the fowl transmissible by an agent separable from the tumor cells. J Exp Med 1911;13:3979.,Cottontail rabbit papillomavirus(CRPV) Shope肉瘤病毒,1933年Shope将病毒所致的野兔乳头状瘤进行皮下移植试验，发生浸润性鳞癌，并证明兔粘液瘤、纤维瘤和乳头状瘤均由病毒引起，称为
4、Shope肉瘤病毒。 1933年发现Cottontail rabbit papillomavirus(CRPV) Shope RE, Hurst EW. Infectious papillomatosis of rabbits; with a note on the histopathology. J Exp Med1933;58:60724 1935年用CRPV 在家兔模型中诱发肿瘤,第一个被证实的DNA肿瘤病毒. Rous P, Beard JW. The progression to carcinoma of virus-induced rabbit papillomas (Shope)
5、. J Exp Med 1935;62:52348.,1936年发现Mouse mammary tumor virus 1951年发现Murine leukemia virus 1951年Gross分离出小鼠白血病病毒，并陆续报道了病毒引起的大鼠、豚鼠、猫、狗、猴白血病。 1953 年发现Mouse polyomavirus 1953-1954年发现Human adenovirus 1960年发现Simian virus 40 (SV40) Sweet BH, Hilleman MR. The vacuolating virus, SV40. Proc Soc Exp Biol Med 196
6、0;105:4207. 1962年SV40在仓鼠中诱发肿瘤 1962年发现人腺病毒在仓鼠中诱发肿瘤(第一个被证实有致瘤特性的人类病毒) Trentin JJ, Yabe Y, Taylor G. The quest for human cancer viruses. Science 1962;137:83541.,与肿瘤相关的微生物研究史,1962年Burkitt从流行病学调查和地理流行病学分析，认为东非儿童中高发的特殊类型的淋巴瘤可能与传染因子有关。 1964年Epstein和 Barr在淋巴瘤细胞培养液中发现病毒，命名为EB病毒。 Epstein, M. A., Barr, Y. M. 1
7、21:76170.,与肿瘤相关的微生物研究史,1967-1968 年发现Hepatitis B virus (HBV) Blumberg BS, Gerstley BJ, Hungerford DA, London WT, Sutnick AI. A serum antigen (Australia antigen) in Downs syndrome, leukemia, and hepatitis. Ann Intern Med 1967;66:92431. Okochi K, Murakami S. Observations on Australia antigen in Japanes
8、e. Vox Sang 1968;15:37485. Prince AM. An antigen detected in the blood during the incubation period of serum hepatitis. Proc Natl Acad Sci U S A 1968;60:81421.,与肿瘤相关的微生物研究史,1970年发现逆转录酶 Baltimore D. RNA-dependent DNA polymerase in virions of RNA tumour viruses. Nature 1970;226:120911. Temin HM, Mizut
9、ani S. RNA-dependent DNA polymerase in virions of Rous sarcoma virus. Nature 1970; 226:12113. 1976年发现细胞来源的逆转录病毒癌基因 Stehelin D, Varmus HE, Bishop JM, Vogt PK. DNA related to the transforming gene(s) of avian sarcoma viruses is present in normal avian DNA. Nature 1976;260:1703. 1975年发现HBV感染与原发性肝细胞癌之间的
10、联系 Blumberg BS, Larouze B, London WT, et al. The relation of infection with the hepatitis B agent to primary hepatic carcinoma. Am J Pathol 1975;81:66982. 1974-1984年发现HPV感染与宫颈癌之间的联系 zur Hausen H. Condylomata acuminata and human genital cancer. Cancer Res 1976;36:794. zur Hausen H, Meinhof W, Scheibe
11、r W, Bornkamm GW. Attempts to detect virus-specific DNA in human tumors. I. Nucleic acid hybridizations with complementary RNA of human wart virus. Int J Cancer 1974;13:6506. Boshart M, Gissmann L, Ikenberg H, Kleinheinz A, Scheurlen W, zur Hausen H. A new type of papillomavirus DNA, its presence in
12、 genital cancer biopsies and in cell lines derived from cervical cancer. EMBO J 1984;3:11517. Durst M, Gissmann L, Ikenberg H, zur Hausen H. A papillomavirus DNA from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions. Proc Natl Acad Sci U S A 1983;80:
13、38125. 1976年HBV疫苗研制成功并用于预防原发性肝细胞癌(第一个肿瘤疫苗) Buynak EB, Roehm RR, Tytell AA, Bertland AU II, Lampson GP, Hilleman MR. Vaccine against human hepatitis B. JAMA 1976;235:28324.,与肿瘤相关的微生物研究史,1979年发现p53肿瘤抑制基因 Lane DP, Crawford LV. T antigen is bound to a host protein in SV40-transformed cells. Nature 1979;
14、278:2613. Linzer DI, Levine AJ. Characterization of a 54K dalton cellular SV40 tumor antigen present in SV40-transformed cells and uninfected embryonal carcinoma cells.Cell 1979;17:4352. 1980年发现Human T-cell leukemia virus type I(HTLV-1) Poiesz BJ, Ruscetti FW, Gazdar AF, Bunn PA, Minna JD, Gallo RC.
15、 Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. Proc Natl Acad Sci U S A 1980;77:74159. 1981年发现HTLV-1感染与成人T细胞白血病之间的联系(在逆转录病毒科中发现的第一个人类肿瘤病毒) Hinuma Y, Nagata K, Hanaoka M, et al. Adult T-cell leukemia: antigen in
16、 an ATL cell line and detection of antibodies to the antigen in human sera. Proc Natl Acad Sci U S A 1981;78:647680. 1988年证实Rb肿瘤抑制基因产物与DNA肿瘤病毒致癌蛋白之间发生相互作用 DeCaprio JA, Ludlow JW, Figge J, et al. SV40 large tumor antigen forms a specific complex with the product of the retinoblastoma susceptibility gene. Cell 1988;54:27583. Whyte P, Buchkovich KJ, Horowitz JM, et al. Association between an oncogene and an anti-oncogene: the adeno
