Abstract

) The AIDS epidemic was recognized in part because of the occurrence of unusual malignancies in gay men. Despite empiric advances in the treatment of AIDS malignancies, only a minority of affected patients are cured of their malignancies. The presence of HHV-8 in Kaposi's sarcoma, Epstein-Barr virus (EBV) in a large subset of AIDS-associated lymphomas, and both viruses in primary effusion lymphomas (PELs) provides an important handle for the investigation of the pathogenesis and ultimately the specific treatment of these neoplasms. The overall goal of this Program Project is to investigate herpesvirus genes relevant to tumorigenesis, prevention, and treatment. Project 1 (Gary S. Hayward) will focus on the candidate HHV-8 transporting genes ORK1 and ORF-K15. Project 2 (Paula Pitha-Rowe) will focus on HHV-8 genes homologous to the cellular proteins of interferon response factors (IRF). Project 3 (John Nicholas) will focus on the HHV-8 homologue of interleukin-6 (IL-6) which may play a role in supporting neoplastic proliferation. Project 4 (S. Diane Hayward) will focus on interactions between HHV-8 and EBV. Project 5 (Richard F. Ambinder) will focus on pharmacologic induction of HHV-8 and EBV encoded enzymes as a strategy to selectively kill virus infected tumor cells. The overall objective of this program project grant is to define the clinical role of radiolabeled, genetically engineered antibodies directed against anti- carcinoembryonic antigen (CEA).

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA081400-03
Application #
6513555
Study Section
Subcommittee G - Education (NCI)
Program Officer
Wong, May
Project Start
2000-09-30
Project End
2004-06-30
Budget Start
2002-07-10
Budget End
2003-06-30
Support Year
3
Fiscal Year
2002
Total Cost
$807,762
Indirect Cost

  Institution

Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218

  Publications

Beachler, Daniel C; Gellert, Lan L; Jacobson, Lisa P et al. (2011) Kaposi sarcoma-associated herpesvirus serum DNA and antibodies not associated with subsequent non-Hodgkin lymphoma risk. J Acquir Immune Defic Syndr 56:188-92
Lechowicz, Maryjo; Dittmer, Dirk P; Lee, Jeannette Y et al. (2009) Molecular and clinical assessment in the treatment of AIDS Kaposi sarcoma with valproic Acid. Clin Infect Dis 49:1946-9
Fu, De-Xue; Tanhehco, Yvette; Chen, Jianmeng et al. (2008) Bortezomib-induced enzyme-targeted radiation therapy in herpesvirus-associated tumors. Nat Med 14:1118-22
Hayward, G S; Zong, J C (2007) Modern evolutionary history of the human KSHV genome. Curr Top Microbiol Immunol 312:1-42
Zong, Jian-Chao; Arav-Boger, Ravit; Alcendor, Donald J et al. (2007) Reflections on the interpretation of heterogeneity and strain differences based on very limited PCR sequence data from Kaposi's sarcoma-associated herpesvirus genomes. J Clin Virol 40:1-8
Zong, Jian-Chao; Kajumbula, Henry; Boto, William et al. (2007) Evaluation of global clustering patterns and strain variation over an extended ORF26 gene locus from Kaposi's sarcoma herpesvirus. J Clin Virol 40:19-25
Yu, Yanxing; Wang, Shizhen Emily; Hayward, Gary S (2005) The KSHV immediate-early transcription factor RTA encodes ubiquitin E3 ligase activity that targets IRF7 for proteosome-mediated degradation. Immunity 22:59-70
Lubyova, Barbora; Kellum, Merrill J; Frisancho, Augusto J et al. (2004) Kaposi's sarcoma-associated herpesvirus-encoded vIRF-3 stimulates the transcriptional activity of cellular IRF-3 and IRF-7. J Biol Chem 279:7643-54
Wang, Shizhen Emily; Wu, Frederick Y; Chen, Honglin et al. (2004) Early activation of the Kaposi's sarcoma-associated herpesvirus RTA, RAP, and MTA promoters by the tetradecanoyl phorbol acetate-induced AP1 pathway. J Virol 78:4248-67
Guo, Hong-Guang; Sadowska, Mariola; Reid, William et al. (2003) Kaposi's sarcoma-like tumors in a human herpesvirus 8 ORF74 transgenic mouse. J Virol 77:2631-9

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