The Viral Epidemiology Branch (VEB) has used a variety of approaches to define the nature and magnitude of HIV-1 associated malignancies, including analyses of population- based data, prospective cohort studies, and laboratory investigations. Our current work has focused on Kaposis sarcoma and its associated herpesvirus, HHV-8. We have measured T-cell proliferative response to this infection and found evidence for cellular immunity; these responses were diminished in the presence of HIV infection, even with intact levels of CD4+ T-cells, which parallels the early increase in Kaposi?s sarcoma risk following HIV seroconversion. Using HHV- 8 serologic assays on banked blood specimens, VEB researchers identified pre-existing HHV-8 infection as a cause of transplant associated Kaposi?s sarcoma. In a collaborative work, we found that polymorphisms in HHV-8 latent nuclear antigen define a large repertoire of viral genotypes in the infected population, which may prove useful in defining the molecular epidemiology of this infection. We have used serologic assays to examine HHV-8 seroprevalence in various populations, and found low seroprevalence in Southeast Asia and the Caribbean, and high prevalence in African populations. In collaborative studies in Jamaica and Zambia, we determined that HHV-8 seroprevalence increases progressively with age. We also collaborated on a clinical trial which demonstrated potential efficacy of anti-angiogenic therapy in Kaposi?s sarcoma. - Human Subjects & Human Subjects: Minor under 18 Years Old & Human Subjects: Interview, Questionaires, or Surveys Only & Human Tissues, Fluids, Cells, etc.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CP005781-05
Application #
6289523
Study Section
Special Emphasis Panel (VEB)
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Division of Cancer Epidemiology and Genetics
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Rabkin, C S (2000) The need for investigations of prophylactic regimens to prevent AIDS-associated non-Hodgkin's lymphoma. Clin Infect Dis 30:762-3
Frisch, M; Biggar, R J; Goedert, J J (2000) Human papillomavirus-associated cancers in patients with human immunodeficiency virus infection and acquired immunodeficiency syndrome. J Natl Cancer Inst 92:1500-10
Biggar, RJ; Frisch, M (2000) Estimating the Risk of Cancer in Children With AIDS. JAMA 284:2593-2594
Biggar, R J; Frisch, M; Goedert, J J (2000) Risk of cancer in children with AIDS. AIDS-Cancer Match Registry Study Group. JAMA 284:205-9
Zhang, Y J; Deng, J H; Rabkin, C et al. (2000) Hot-spot variations of Kaposi's sarcoma-associated herpesvirus latent nuclear antigen and application in genotyping by PCR-RFLP. J Gen Virol 81:2049-58
Engels, E A; Frisch, M; Biggar, R J et al. (2000) AIDS-Related opportunistic illness and potent antiretroviral therapy. JAMA 283:2653-4
Rabkin, C S; Yang, Q; Goedert, J J et al. (1999) Chemokine and chemokine receptor gene variants and risk of non-Hodgkin's lymphoma in human immunodeficiency virus-1-infected individuals. Blood 93:1838-42
Zong, J C; Ciufo, D M; Alcendor, D J et al. (1999) High-level variability in the ORF-K1 membrane protein gene at the left end of the Kaposi's sarcoma-associated herpesvirus genome defines four major virus subtypes and multiple variants or clades in different human populations. J Virol 73:4156-70
Rabkin, C S (1999) Epidemiology of B-cell lymphomas. Curr Top Microbiol Immunol 246:235-9;discussion 240
Rabkin, C S; Sei, S (1999) Susceptibility genes for AIDS and AIDS-related lymphoma. Curr Top Microbiol Immunol 246:111-4;discussion 115

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