The applicant has found that certain high grade Herpes virus associated lymphomas are sensitive to anti-viral mediated apoptosis in vitro and in vivo. Epstein-Barr Virus positive Burkitt's lymphoma and Human Herpes Virus Type 8 related Primary Effusion Lymphomas undergo apoptosis when cultured in the presence of Azidothymidine (AZT) or AZT and Interferon Alpha (IFN Alpha). He has investigated the mechanisms by which this therapy causes apoptosis in these lymphoma subtypes. He has found that incubation of Burkitt's lymphoma cells with AZT results in upregulation of CD95 and apoptosis. Primary Effusion Lymphoma requires Interferon Alpha to potentiate AZT mediated apoptosis. He has also found that Interferon Alpha induces the death receptor ligands, TRAIL and Fas Ligand in B cell lymphomas. In contrast to Burkitt's lymphoma and Primary Effusion Lymphoma, EBV positive large cell immunoblastic lymphomas and Epstein-Barr virus negative lymphomas were resistant to AZT and Interferon Alpha. These initial findings indicate that some lymphomas might be selectively sensitive to anti-viral therapy. In susceptible lymphomas, AZT and Interferon Alpha mediated apoptosis does not occur solely through Fas/Fas-Ligand interaction and likely involves activation of additional mechanisms of apoptosis. The applicant will investigate the role of viral and cellular pro- and anti-apoptotic proteins in blocking or facilitating AZT and Interferon Alpha induction of apoptosis in primary lymphoma specimens and cell lines developed from these tumors. A mechanism of inducing apoptosis in aggressive lymphomas would benefit patients with these diseases.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA082274-03
Application #
6514053
Study Section
Special Emphasis Panel (ZRG1-ET-2 (05))
Program Officer
Bhatia, Kishor
Project Start
2000-04-01
Project End
2003-03-31
Budget Start
2002-04-01
Budget End
2003-03-31
Support Year
3
Fiscal Year
2002
Total Cost
$256,500
Indirect Cost
Name
University of Miami School of Medicine
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Miami
State
FL
Country
United States
Zip Code
33146
Gualco, Gabriela; Queiroga, Eduardo M; Weiss, Lawrence M et al. (2009) Frequent expression of multiple myeloma 1/interferon regulatory factor 4 in Burkitt lymphoma. Hum Pathol 40:565-71
Gualco, Gabriela; Chioato, Lucimara; Weiss, Lawrence M et al. (2009) Analysis of human T-cell lymphotropic virus in CD25+ anaplastic large cell lymphoma in children. Am J Clin Pathol 132:28-33
Xia, Tianli; O'Hara, Andrea; Araujo, Iguaracyra et al. (2008) EBV microRNAs in primary lymphomas and targeting of CXCL-11 by ebv-mir-BHRF1-3. Cancer Res 68:1436-42
Queiroga, Eduardo M; Gualco, Gabriela; Weiss, Lawrence M et al. (2008) Burkitt lymphoma in Brazil is characterized by geographically distinct clinicopathologic features. Am J Clin Pathol 130:946-56
Gualco, Gabriela; Weiss, Lawrence M; Bacchi, Carlos E (2008) Expression of p63 in anaplastic large cell lymphoma but not in classical Hodgkin's lymphoma. Hum Pathol 39:1505-10
Gualco, Gabriela; Bacchi, Carlos E (2008) B-cell and T-cell lymphomas of the breast: clinical--pathological features of 53 cases. Int J Surg Pathol 16:407-13
Queiroga, Eduardo M; Gualco, Gabriela; Chioato, Lucimara et al. (2008) Viral studies in burkitt lymphoma: association with Epstein-Barr virus but not HHV-8. Am J Clin Pathol 130:186-92
Gualco, Gabriela; van den Berg, Anke; Koopmans, Sicco et al. (2008) Autoimmune lymphoproliferative syndrome in a patient with a new minimal deletion in the death domain of the FAS gene. Hum Pathol 39:137-41
Minhas, Veenu; Crosby, Lynsey N; Crabtree, Kay L et al. (2008) Development of an immunofluorescence assay using recombinant proteins expressed in insect cells to screen and confirm presence of human herpesvirus 8-specific antibodies. Clin Vaccine Immunol 15:1259-64
Ramos, Juan Carlos; Ruiz Jr, Phillip; Ratner, Lee et al. (2007) IRF-4 and c-Rel expression in antiviral-resistant adult T-cell leukemia/lymphoma. Blood 109:3060-8

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