Several different types of cancer are observed at an increased frequency in acquired immune deficiency syndrome (AIDS) patients and in other immunosuppressed individuals. Most of these are virus-associated cancers.
Kaposi's sarcoma (KS) is the most common neoplasm that occurs in patients with AIDS (AIDS-KS). KS is believed to be caused by Kaposi's-sarcoma-associated herpesvirus/human herpesvirus 8 (KSHV/HHV-8), but the tumour microenvironment is an important aspect of KS progression.
AIDS-lymphoma is another significant cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected individuals. Over 50% of AIDS lymphomas are associated with Epstein–Barr virus (EBV) and/or KSHV infection. EBV activates B-cell precursors, leading to a transformed phenotype.
Human papillomavirus (HPV)-related cancers are another type of AIDS-related malignancy. There are likely to be two mechanisms by which papillomaviruses induce neoplasia — by altering the tumour microenvironment, and by directly disrupting cell differentiation, to induce cell proliferation.
Antiviral strategies might be used to prevent cancer in AIDS patients. For example, highly active antiretroviral therapy has been shown to prevent or stop the progression of KS in AIDS patients.
Cancer remains a significant burden for human immunodeficiency virus (HIV)-infected individuals. Most cancers that are associated with HIV infection are driven by oncogenic viruses, such as Epstein–Barr virus, Kaposi's sarcoma-associated herpesvirus and human papillomavirus. Gaining insight into the epidemiology and mechanisms that underlie AIDS-related cancers has provided us with a better understanding of cancer immunity and viral oncogenesis.
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Sondel, P. M., Rakhmilevich, A. L., de Jong, J. L. O. & Hank, J. A. in The Molecular Basis of Cancer (eds Mendelsohn, J., Howley, P. M., Israel, M. A. & Liotta, L. A.) 535–571 (W. B. Saunders Company, Philadelpia, 2001).
Burnet, F. M. Immunologic surveillance in neoplasia. Transplant. Rev. 7, 3 (1971).
Gross, L. Intradermal immunization of C3H mice against sarcoma that originated in an animal of the same line. Cancer Res. 3, 326 (1943).
Klein, G. & Klein, E. Genetic studies of the relationship of tumour-host cells. Nature 178, 1389 (1956).
Penn, I. Tumors arising in organ transplant recipients. Adv. Cancer Res. 28, 31–61 (1978).
Frisch, M., Biggar, R. J., Engels, E. A. & Goedert, J. J. Association of cancer with AIDS-related immunosuppression in adults. JAMA 285, 1736–1745 (2001).Analysis of the incidence of cancer among 302,834 adults with HIV/AIDS from 11 geographically diverse areas in the United States.
Stewart, T., Tsai, S. C., Grayson, H., Henderson, R. & Opelz, G. Incidence of de novo breast cancer in women chronically immunosuppressed after organ transplantation. Lancet 346, 796–798 (1995).
Gallagher, B., Wang, Z., Schymura, M. J., Kahn, A. & Fordyce, E. J. Cancer incidence in New York State acquired immunodeficiency syndrome patients. Am. J. Epidemiol. 154, 544–556 (2001).Population-based registry linkage analysis evaluating cancer risk in HIV/AIDS individuals in one of the areas of the United States most heavily afflicted by this disease.
Rickinson, A. B. et al. T cell recognition of Epstein–Barr virus associated lymphomas. Cancer Surv. 13, 53–80 (1992).
Parkin, D. M., Wabinga, H., Nambooze, S. & Wabwire-Mangen, F. AIDS-related cancers in Africa: maturation of the epidemic in Uganda. AIDS 13, 2563–2570 (1999).
Kaposi, M. Idiopathisches multiplespigmentsarcom der haut. Arch. Dermatologie Syphillis 4, 265–273 (1872).
Franceschi, S. & Serraino, D. Kaposi's sarcoma and KSHV. Lancet 346, 1360–1361 (1995).
Rothman, S. in Symposium on Kaposi's sarcoma (eds Ackerman, L. V. & Murray, J. F.) (Karger, Basel, 1962).
d'Oliveira, J. J. & Torres, F. O. Kaposi's sarcoma in the Bantu of Mozambique. Cancer 30, 553–561 (1972).
Olweny, C. L. Etiology of endemic Kaposi's sarcoma. IARC Sci. Publ. 63, 543–548 (1984).
Oettle, A. G. in Symposium on Kaposi's sarcoma (eds Ackerman, L. V. & Murray, J. F.) (Karger, Basel, 1962).
Harwood, A. R. et al. Kaposi's sarcoma in recipients of renal transplants. Am. J. Med. 67, 759–765 (1979).
Penn, I. Kaposi's sarcoma in transplant recipients. Transplantation 64, 669–673 (1997).
Qunibi, W. et al. Kaposi's sarcoma: the most common tumor after renal transplantation in Saudi Arabia. Am. J. Med. 84, 225–232 (1988).
Franceschi, S. & Geddes, M. Epidemiology of clasic Kaposi's sarcoma, with special reference to Mediterranean population. Tumori 81, 308–314 (1995).
Beral, V., Peterman, T. A., Berkelman, R. L. & Jaffe, H. W. Kaposi's sarcoma among persons with AIDS: a sexually transmitted infection? Lancet 335, 123–128 (1990).One of the first studies to indicate that an infectious agent other than HIV is involved in the pathogenesis of AIDS/KS.
Rabkin, C. S. & Yellin, F. Cancer incidence in a population with a high prevalence of infection with human immunodeficiency virus type 1. J. Natl Cancer Inst. 86, 1711–1716 (1994).Large study that examines the risk of cancer in gay men who are at risk of HIV/AIDS before the use of antiretroviral treatment.
Rabkin, C. S., Goedert, J. J., Biggar, R. J., Yellin, F. & Blattner, W. A. Kaposi's sarcoma in three HIV-1-infected cohorts. J. Acquir. Immune Defic. Syndr. 3 (Suppl. 1), S38–S43 (1990).
Chang, Y. et al. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science 266, 1865–1869 (1994).One of the most successful and important applications of Lisitsyn's representational difference analysis (RDA): the identification of KSHV sequences in AIDS/KS.
Kedes, D. H. et al. The seroepidemiology of human herpesvirus 8 (Kaposi's sarcoma-associated herpesvirus): distribution of infection in KS risk groups and evidence for sexual transmission. Nature Med. 2, 918–924 (1996).One of the first seroepidemiological studies that confirmed the link between KSHV and AIDS/KS.
Gao, S. J. et al. KSHV antibodies among Americans, Italians and Ugandans with and without Kaposi's sarcoma. Nature Med. 2, 925–928 (1996).
Liotta, L. A. & Kohn, E. C. The microenvironment of the tumour-host interface. Nature 411, 375–379 (2001).
Coussens, L. M. & Werb, Z. Inflammatory cells and cancer: think different! J. Exp. Med. 193, F23–F26 (2001).
Bissell, M. J. & Radisky, D. Putting tumours into context. Nature Rev. Cancer 1, 46–54 (2001).
Berd, D. & Prehn, R. T. Peritoneal macrophage response to leukemia L1210 in syngeneic mice. J. Natl Cancer Inst. 58, 1729–1734 (1977).
Ensoli, B., Salahuddin, S. Z. & Gallo, R. C. AIDS-associated Kaposi's sarcoma: a molecular model for its pathogenesis. Cancer Cells 1, 93–96 (1989).
Gallo, R. C. The enigmas of Kaposi's sarcoma. Science 282, 1837–1839 (1998).
Rabkin, C. S. et al. Monoclonal origin of multicentric Kaposi's sarcoma lesions. N. Engl. J. Med. 336, 988–993 (1997).
Gill, P. S. et al. Evidence for multiclonality in multicentric Kaposi's sarcoma. Proc. Natl Acad. Sci. USA 95, 8257–8261 (1998).
Roth, W. K., Brandstetter, H. & Sturzl, M. Cellular and molecular features of HIV-associated Kaposi's sarcoma. AIDS 6, 895–913 (1992).
Veikkola, T. et al. Signalling via vascular endothelial growth factor receptor-3 is sufficient for lymphangiogenesis in transgenic mice. EMBO J. 20, 1223–1231 (2001).
Jussila, L. et al. Lymphatic endothelium and Kaposi's sarcoma spindle cells detected by antibodies against the vascular endothelial growth factor receptor-3. Cancer Res. 58, 1599–1604 (1998).
Dupin, N. et al. Distribution of human herpesvirus-8 latently infected cells in Kaposi's sarcoma, multicentric Castleman's disease, and primary effusion lymphoma. Proc. Natl Acad. Sci. USA 96, 4546–4551 (1999).
Weninger, W. et al. Expression of vascular endothelial growth factor receptor-3 and podoplanin suggests a lymphatic endothelial cell origin of Kaposi's sarcoma tumor cells. Lab. Invest. 79, 243–251 (1999).
Salahuddin, S. Z. et al. Angiogenic properties of Kaposi's sarcoma-derived cells after long-term culture in vitro. Science 242, 430–433 (1988).
Miles, S. A. et al. AIDS Kaposi sarcoma-derived cells produce and respond to interleukin 6. Proc. Natl Acad. Sci. USA 87, 4068–4072 (1990).
Ensoli, B. et al. AIDS-Kaposi's sarcoma-derived cells express cytokines with autocrine and paracrine growth effects. Science 243, 223–226 (1989).
Fiorelli, V. et al. γ-Interferon produced by CD8+ T cells infiltrating Kaposi's sarcoma induces spindle cells with angiogenic phenotype and synergy with human immunodeficiency virus-1 Tat protein: an immune response to human herpesvirus-8 infection? Blood 91, 956–967 (1998).
Ensoli, B., Barillari, G. & Gallo, R. C. Cytokines and growth factors in the pathogenesis of AIDS-associated Kaposi's sarcoma. Immunol. Rev. 127, 147–155 (1992).
Albini, A., Barillari, G., Benelli, R., Gallo, R. C. & Ensoli, B. Angiogenic properties of human immunodeficiency virus type 1 Tat protein. Proc. Natl Acad. Sci. USA 92, 4838–4842 (1995).
Vogel, J., Hinrichs, S. H., Reynolds, R. K., Luciw, P. A. & Jay, G. The HIV tat gene induces dermal lesions resembling Kaposi's sarcoma in transgenic mice. Nature 335, 606–611 (1988).
Proceedings of the IARC Working Group on the evaluation of carcinogenic risks to humans. Epstein–Barr virus and Kaposi's sarcoma herpesvirus/human herpesvirus-8. Lyon, France, 17–24 June 1997. IARC Monogr Eval. Carcinog. Risks Hum. 70, 1–492 (1997).
Whitby, D. et al. Detection of Kaposi sarcoma associated herpesvirus in peripheral blood of HIV-infected individuals and progression to Kaposi's sarcoma. Lancet 346, 799–802 (1995).
Moore, P. S. et al. Kaposi's sarcoma-associated herpesvirus infection prior to onset of Kaposi's sarcoma. AIDS 10, 175–180 (1996).
Chatlynne, L. G. & Ablashi, D. V. Seroepidemiology of Kaposi's sarcoma-associated herpesvirus (KSHV). Semin. Cancer Biol. 9, 175–185 (1999).
Staskus, K. A. et al. Kaposi's sarcoma-associated herpesvirus gene expression in endothelial (spindle) tumor cells. J. Virol. 71, 715–719 (1997).
Sturzl, M. et al. Expression of HHV-8 latency-associated T0.7 RNA in spindle cells and endothelial cells of AIDS-associated, classical and African Kaposi's sarcoma. Int. J. Cancer 72, 68–71 (1997).
Radkov, S. A., Kellam, P. & Boshoff, C. The latent nuclear antigen of Kaposi sarcoma-associated herpesvirus targets the retinoblastoma–E2F pathway and with the oncogene Hras transforms primary rat cells. Nature Med. 6, 1121–1127 (2000).First study to show that KSHV, like other oncogenic viruses, encodes for a latent transforming protein that targets the retinoblastoma tumour-suppressor pathway.
An, J., Lichtenstein, A. K., Brent, G. & Rettig, M. B. The Kaposi sarcoma-associated herpesvirus (KSHV) induces cellular interleukin 6 expression: role of the KSHV latency-associated nuclear antigen and the AP1 response element. Blood 99, 649–654 (2002).
Judde, J. G. et al. Monoclonality or oligoclonality of human herpesvirus 8 terminal repeat sequences in Kaposi's sarcoma and other diseases. J. Natl Cancer Inst. 92, 729–736 (2000).
Ablashi, D. et al. Seroprevalence of human herpesvirus-8 (HHV-8) in countries of Southeast Asia compared to the USA, the Caribbean and Africa. Br. J. Cancer 81, 893–897 (1999).
Davidovici, B. et al. Seroepidemiology and molecular epidemiology of Kaposi's sarcoma-associated herpesvirus among Jewish population groups in Israel. J. Natl Cancer Inst. 93, 194–202 (2001).Definitive sero-epidemiological study showing that KSHV is transmitted among family members in a Western population.
Mayama, S. et al. Prevalence and transmission of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) in Ugandan children and adolescents. Int. J. Cancer 77, 817–820 (1998).
Sitas, F. et al. Antibodies against human herpesvirus 8 in black South African patients with cancer. N. Engl. J. Med. 340, 1863–1871 (1999).
Koelle, D. M. et al. Frequent detection of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) DNA in saliva of human immunodeficiency virus-infected men: clinical and immunologic correlates. J. Infect. Dis. 176, 94–102 (1997).
Pauk, J. et al. Mucosal shedding of human herpesvirus 8 in men. N. Engl. J. Med. 343, 1369–1377 (2000).
Olsen, S. J., Chang, Y., Moore, P. S., Biggar, R. J. & Melbye, M. Increasing Kaposi's sarcoma-associated herpesvirus seroprevalence with age in a highly Kaposi's sarcoma endemic region, Zambia in 1985. AIDS 12, 1921–1925 (1998).
Gessain, A. et al. Human herpesvirus 8 primary infection occurs during childhood in Cameroon, Central Africa. Int. J. Cancer 81, 189–192 (1999).
Plancoulaine, S. et al. Human herpesvirus 8 transmission from mother to child and between siblings in an endemic population. Lancet 356, 1062–1065 (2000).
Ariyoshi, K. et al. Kaposi's sarcoma in the Gambia, West Africa is less frequent in human immunodeficiency virus type 2 than in human immunodeficiency virus type 1 infection despite a high prevalence of human herpesvirus 8. J. Hum. Virol. 1, 193–199 (1998).
Goudsmit, J. et al. Human herpesvirus 8 infections in the Amsterdam Cohort Studies (1984–1997): analysis of seroconversions to ORF65 and ORF73. Proc. Natl Acad. Sci. USA 97, 4838–4843 (2000).
Ziegler, J. L. et al. Risk factors for Kaposi's sarcoma in HIV-positive subjects in Uganda. AIDS 11, 1619–1626 (1997).
Lunardi-Iskandar, Y. et al. Tumorigenesis and metastasis of neoplastic Kaposi's sarcoma cell line in immunodeficient mice blocked by a human pregnancy hormone. Nature 375, 64–68 (1995).
Thorley-Lawson, D. A. Epstein–Barr virus: exploiting the immune system. Nature Rev. Immunol. 1, 75–82 (2001).Important review arguing that Epstein–Barr virus exploits the normal maturation/differentiation of B lymphocytes for its own replication and survival.
Klein, G. Epstein–Barr virus strategy in normal and neoplastic B cells. Cell 77, 791–793 (1994).
Babcock, G. J. & Thorley-Lawson, D. A. Tonsillar memory B cells, latently infected with Epstein–Barr virus, express the restricted pattern of latent genes previously found only in Epstein–Barr virus-associated tumors. Proc. Natl Acad. Sci. USA 97, 12250–12255 (2000).
Kuppers, R., Klein, U., Hansmann, M. L. & Rajewsky, K. Cellular origin of human B-cell lymphomas. N. Engl. J. Med. 341, 1520–1529 (1999).
Gaidano, G. & Della-Favera, R. in The Molecular Basis of Cancer (eds Mendelsohn, J., Howley,P. M., Israel, M. A. & Liotta, L. A.) 189–237 (W. B. Saunders Company, Philadelphia, 2001).
Cesarman, E., Chang, Y., Moore, P. S., Said, J. W. & Knowles, D. M. Kaposi's sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas. N. Engl. J. Med. 332, 1186–1191 (1995).
Soulier, J. et al. Kaposi's sarcoma-associated herpesvirus-like DNA sequences in multicentric Castleman's disease. Blood 86, 1276–1280 (1995).
Shirai, A., Cosentino, M., Leitman-Klinman, S. F. & Klinman, D. M. Human immunodeficiency virus infection induces both polyclonal and virus-specific B cell activation. J. Clin. Invest. 89, 561–566 (1992).
Grulich, A. E. et al. B-cell stimulation and prolonged immune deficiency are risk factors for non-Hodgkin's lymphoma in people with AIDS. AIDS 14, 133–140 (2000).
Lane, H. C. et al. Abnormalities of B-cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome. N. Engl. J. Med. 309, 453–458 (1983).
Cunto-Amesty, G., Przybylski, G., Honczarenko, M., Monroe, J. G. & Silberstein, L. E. Evidence that immunoglobulin specificities of AIDS-related lymphoma are not directed to HIV-related antigens. Blood 95, 1393–1399 (2000).
Shope, R. E. Infectious papillomatosis. J. Exp. Med. 58, 607–624 (1933).
Rous, P. & Kidd, J. G. The carcinogenic effect of a virus upon tarred skin. Science 83, 468 (1936).
Zur Hausen, H. Human papillomaviruses and their possible role in squamous cell carcinomas. Curr. Top. Microbiol. Immunol. 78, 1 (1977).
Durst, M., Gissmann, L., Ikenberg, H. & zurHausen, H. A papillomavirus DNA from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions. Proc. Natl Acad. Sci. USA 80, 3812–3815 (1983).The identification of HPV sequences in cervical cancer and the first study to identify a human DNA tumour virus using only molecular techniques.
Lowry, W. S., Clark, D. A. & Hannemann, J. H. Skin cancer and immunosuppression. Lancet 1, 1290–1291 (1972).
Matas, A. J., Simmons, R. L. & Najarian, J. S. Chronic antigenic stimulation, herpesvirus infection, and cancer in transplant recipients. Lancet 1, 1277–1279 (1975).
Frazer, I. H., Medley, G., Crapper, R. M., Brown, T. C. & Mackay, I. R. Association between anorectal dysplasia, human papillomavirus, and human immunodeficiency virus infection in homosexual men. Lancet 2, 657–660 (1986).
Frisch, M., Biggar, R. J. & Goedert, J. J. Human papillomavirus-associated cancers in patients with human immunodeficiency virus infection and acquired immunodeficiency syndrome. J. Natl Cancer Inst. 92, 1500–1510 (2000).
Ateenyi-Agaba, C. Conjunctival squamous-cell carcinoma associated with HIV infection in Kampala, Uganda. Lancet 345, 695–696 (1995).
Gomousa-Michael, M., Gialama, E., Gomousas, N. & Gialama, G. Genital human papillomavirus infection and associated penile intraepithelial neoplasia in males infected with the human immunodeficiency virus. Acta Cytol. 44, 305–309 (2000).
Trottier, A. M. et al. Human immunodeficiency virus infection is a major risk factor for detection of human papillomavirus DNA in esophageal brushings. Clin. Infect. Dis. 24, 565–569 (1997).
Palefsky, J. M., Holly, E. A., Ralston, M. L. & Jay, N. Prevalence and risk factors for human papillomavirus infection of the anal canal in human immunodeficiency virus (HIV)-positive and HIV- negative homosexual men. J. Infect. Dis. 177, 361–367 (1998).
Palefsky, J. M. et al. Cervicovaginal human papillomavirus infection in human immunodeficiency virus-1 (HIV)-positive and high-risk HIV-negative women. J. Natl Cancer Inst. 91, 226–236 (1999).
Sun, X. W. et al. Human papillomavirus infection in women infected with the human immunodeficiency virus. N. Engl. J. Med. 337, 1343–1349 (1997).
Arany, I., Muldrow, M. & Tyring, S. K. Correlation between mRNA levels of IL-6 and TNF-α and progression rate in anal squamous epithelial lesions from HIV-positive men. Anticancer Res. 21, 425–428 (2001).
McMurray, H. R., Nguyen, D., Westbrook, T. F. & McCance, D. J. Biology of human papillomaviruses. Int. J. Exp. Pathol. 82, 15–33 (2001).
International Collaboration on HIV and Cancer. Highly active antiretroviral therapy and incidence of cancer in human immunodeficiency virus-infected adults. J. Natl Cancer Inst. 92, 1823–1830 (2000).Major international study that assesses the role of HAART in the incidence of AIDS-related malignancies.
Osmond, D. H. et al. Prevalence of Kaposi sarcoma-associated herpesvirus infection in homosexual men at beginning of and during the HIV epidemic. JAMA 287, 221–225 (2002).
Dupin, N. et al. The influence of highly active antiretroviral therapy on AIDS-associated Kaposi's sarcoma. Br. J. Dermatol. 140, 875–881 (1999).
Hoffmann, C. et al. Survival of AIDS patients with primary central nervous system lymphoma is dramatically improved by HAART-induced immune recovery. AIDS 15, 2119–2127 (2001).
Besson, C. et al. Changes in AIDS-related lymphoma since the era of highly active antiretroviral therapy. Blood 98, 2339–2344 (2001).
Kirk, O. et al. Non-Hodgkin lymphoma in HIV-infected patients in the era of highly active antiretroviral therapy. Blood 98, 3406–3412 (2001).
De Clercq, E. et al. Antiviral agents active against human herpesviruses HHV-6, HHV-7 and HHV-8. Rev. Med. Virol. 11, 381–395 (2001).
Spach, D. H. & Colven, R. Resolution of recalcitrant hand warts in an HIV-infected patient treated with potent antiretroviral therapy. J. Am. Acad. Dermatol. 40, 818–821 (1999).
Ellis, L. M. & Fidler, I. J. in The Molecular Basis of Cancer (eds Mendelsohn, J., Howley, P. M., Israel, M. A. & Liotta, L. A.) 173–189 (W. B. Saunders, Philadelphia, 2001).
Zabawski, E. J. Jr & Cockerell, C. J. Topical and intralesional cidofovir: a review of pharmacology and therapeutic effects. J. Am. Acad. Dermatol. 39, 741–745 (1998).
Faye, A., Van Den, A. T., Peuchmaur, M., Mathieu-Boue, A. & Vilmer, E. Anti-CD20 monoclonal antibody for post-transplant lymphoproliferative disorders. Lancet 352, 1285 (1998).
Corbellino, M. et al. Long-term remission of Kaposi sarcoma-associated herpesvirus-related multicentric Castleman disease with anti-CD20 monoclonal antibody therapy. Blood 98, 3473–3475 (2001).
Karkkainen, M. J., Makinen, T. & Alitalo, K. Lymphatic endothelium: a new frontier of metastasis research. Nature Cell Biol. 4, E2–E5 (2002).
Du, M. Q. et al. Kaposi sarcoma-associated herpesvirus infects monotypic (IgMλ) but polyclonal naive B cells in Castleman disease and associated lymphoproliferative disorders. Blood 97, 2130–2136 (2001).
Munger, K. The molecular biology of cervical cancer. J. Cell Biochem. 23 (Suppl.), 55–60 (1995).
Dyson, N., Howley, P. M., Munger, K. & Harlow, E. The human papilloma virus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product. Science 243, 934–937 (1989).First paper to show that a human oncogenic virus targets the retinoblastoma pathway.
Gage, J. R., Meyers, C. & Wetterstein, F. O. The E7 proteins of the nononcogenic human papillomavirus type 6b (HPV-6b) and the oncogenic HPV-16 differ in retinoblastoma protein binding and other properties. J. Virol. 64, 723–730 (1990).
Godden-Kent, D. et al. The cyclin encoded by Kaposi's sarcoma-associated herpesvirus stimulates CDK6 to phosphorylate the retinoblastoma protein and histone H1. J. Virol. 71, 4193–4198 (1997).
Ellis, M. et al. Degradation of p27(Kip) CDK inhibitor triggered by Kaposi's sarcoma virus cyclin–CDK6 complex. EMBO J. 18, 644–653 (1999).
Mann, D. J., Child, E. S., Swanton, C., Laman, H. & Jones, N. Modulation of p27(Kip1) levels by the cyclin encoded by Kaposi's sarcoma-associated herpesvirus. EMBO J. 18, 654–663 (1999).
Swanton, C. et al. Herpes viral cyclin–CDK6 complexes evade inhibition by CDK inhibitor proteins. Nature 390, 184–187 (1997).
Laman, H., Coverley, D., Krude, T., Laskey, R. & Jones, N. Viral cyclin-cyclin-dependent kinase 6 complexes initiate nuclear DNA replication. Mol. Cell. Biol. 21, 624–635 (2001).
Brander, C. et al. Impaired CTL recognition of cells latently infected with Kaposi's sarcoma-associated herpes virus. J. Immunol. 165, 2077–2083 (2000).
Wilkinson, J. et al. Identification of Kaposi's sarcoma-associated herpesvirus (KSHV)-specific cytotoxic T-lymphocyte epitopes and evaluation of reconstitution of KSHV-specific responses in human immunodeficiency virus type 1-infected patients receiving highly active antiretroviral therapy. J. Virol. 76, 2634–2640 (2002).
Liu, Z. et al. Epstein–Barr virus (EBV)-specific cytotoxic T lymphocytes for the prevention and treatment of EBV-associated post-transplant lymphomas. Recent Results Cancer Res. 159, 123–133 (2002).
Ensoli, B., Barillari, G., Salahuddin, S. Z., Gallo, R. C. & Wong-Staal, F. Tat protein of HIV-1 stimulates growth of cells derived from Kaposi's sarcoma lesions of AIDS patients. Nature 345, 84–86 (1990).
Ensoli, B. et al. Synergy between basic fibroblast growth factor and HIV-1 Tat protein in induction of Kaposi's sarcoma. Nature 371, 674–680 (1994).Classic paper on the interplay between HIV-1 Tat and bFGF to induce angiogenesis in an experimental model.
Tovo, P. A. Highly active antiretroviral therapy inhibits cytokine production in HIV-uninfected subjects. AIDS 14, 743–744 (2000).
Sgadari, C. et al. HIV protease inhibitors are potent anti-angiogenic molecules and promote regression of Kaposi's sarcoma. Nature Med. 8, 225–232 (2002).Provocative study on the future use of protease inhibitors to interfere with angiogenesis.
Bower, M. et al. Highly active anti-retroviral therapy (HAART) prolongs time to treatment failure in Kaposi's sarcoma. AIDS 13, 2105–2111 (1999).
Carmeliet, P. Developmental biology: one cell, two fates. Nature 408, 43–45 (2000).
Yamashita, J. et al. Flk1-positive cells derived from embryonic stem cells serve as vascular progenitors. Nature 408, 92–96 (2000).
Makinen, T. et al. Isolated lymphatic endothelial cells transduce growth, survival and migratory signals via the VEGF-C/D receptor VEGFR-3. EMBO J. 20, 4762–4773 (2001).
Witmer, A. N. et al. VEGFR-3 in adult angiogenesis. J. Pathol. 195, 490–497 (2001).
Breiteneder-Geleff, S. et al. Angiosarcomas express mixed endothelial phenotypes of blood and lymphatic capillaries: podoplanin as a specific marker for lymphatic endothelium. Am. J. Pathol. 154, 385–394 (1999).
Holzhausen, H. J., Stiller, D. & Sachs, M. [Morphological pathology of classic Kaposi's sarcoma. Ultrastructural studies and reflections on histogenesis]. Zentralbl. Allg. Pathol. 134, 435–447 (1988).
Akula, S. M., Pramod, N. P., Wang, F. Z. & Chandran, B. Integrin α3β1 (CD 49c/29) is a cellular receptor for Kaposi's sacroma-associated herpesvirus (KSHV/HHV-8) entry into the target cells. Cell 108, 407–419 (2002).
Rivas, C., Thlick, A. E., Parravicini, C., Moore, P. S. & Chang, Y. Kaposi's sarcoma-associated herpesvirus LANA2 is a B-cell-specific latent viral protein that inhibits p53. J. Virol. 75, 429–438 (2001).
We apologize to colleagues whose primary research papers are not cited, due to the restricted number of references. We would like to thank T. Sharp, H. Laman, A. Godfrey and S. Direkze for advice on the text and figures. The authors studies are supported by Cancer Research UK, the Medical Research Council UK, The Wellcome Trust, the Leukaemia Research Fund and GlaxoSmithKline.
(SEPTICAEMIA). A systemic infection that is caused by microbial organisms and their toxins in the blood (blood poisoning). Bacteraemia denotes the detecTable presence of bacteria in the bloodstream.
('Cells with feet'). Specialized epithelial cells that line the kidney glomerular capillaries. Their foot processes make an incomplete barrier for filtration of substances from the capillary.
A circular piece of DNA (such as a virus) that can replicate independently of the host chromosome (extrachromosomal), or integrate and replicate as part of the chromosome. The term was first used by Jacob and Wollman in 1958 in relation to genetic elements that can either exist independently in a cell or become integrated into the host chromosome.
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