Grant Number:	5R01CA073475-02 Interpret this number
Primary Investigator:	Martinez-Maza, Otoniel
Organization:	Children'S Hospital-La
Project Title:	Molecular Epidemiology of AIDS-Associated Lymphoma
Fiscal Year:	1998

DESCRIPTION (adapted from the Abstract): Non-Hodgkin's B-cell lymphoma is seen in greatly-elevated frequency in the acquired immunodeficiency syndrome (AIDS) and in infection with the human immunodeficiency virus (HIV). In this application, the Principal Investigator proposes studies to elucidate the molecular epidemiology of AIDS-lymphoma. In preliminary work, the Principal Investigator found that elevated serum levels of sCD23, as well as elevated levels of other immune system molecules (IgE, sCD27), precede the appearance of AIDS-lymphoma. Also, the elevated levels of sCD23 seen to precede AIDS-lymphoma may be due to the production of this molecule by tumor cells. In the proposed studies, the Investigator and associates will test the hypotheses that the over-expression of sCD23 (and other molecules) that precedes AIDS-lymphoma reflects: (1) immune dysfunction leading to B-cell hyper-activation and enhanced Ig isotype switching, perhaps contributing to the c-myc:Ig gene chromosomal translocation commonly seen in this cancer, or alternatively, (2) the production of these substances (sCD23 and other molecules) by the lymphoma cells themselves, or (3) reactivation of EBV infection. Also, they will examine the predictive value of the expression of these molecules for AIDS-lymphoma, and the expression of these molecules in lymphoma not associated with HIV infection, including African endemic Burkitt's lymphoma. Their specific aims are to: (1) define the pattern of expression of sCD23 prior to the emergence of AIDS-lymphoma; (2) determine/confirm which immune system molecules, other than sCD23, are elevated in those who develop AIDS-lymphoma; (3) determine if the measurement of serum levels of molecules other than sCD23 provides additional information for predicting the appearance of AIDS-lymphoma; and (4) determine if sCD23 or other immune system molecules are elevated in non-Hodgkin's B-cell lymphoma not associated with HIV infection, or in AIDS-lymphoma in hemophiliacs. The accomplishment of these specific aims will add valuable new information to our understanding of the molecular epidemiology of AIDS-lymphoma, as well as the role of immune dysfunction in the generation and growth of this cancer.




B-cell stimulatory cytokines and markers of immune activation are elevated several years prior to the diagnosis of systemic AIDS-associated non-Hodgkin B-cell lymphoma.
Authors: Breen E.C. , Hussain S.K. , Magpantay L. , Jacobson L.P. , Detels R. , Rabkin C.S. , Kaslow R.A. , Variakojis D. , Bream J.H. , Rinaldo C.R. , et al. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2011 Jul; 20(7), p. 1303-14.
PMID: 21527584
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Effect of highly active antiretroviral therapy on biomarkers of B-lymphocyte activation and inflammation.
Authors: Regidor D.L. , Detels R. , Breen E.C. , Widney D.P. , Jacobson L.P. , Palella F. , Rinaldo C.R. , Bream J.H. , Martínez-Maza O. .
Source: Aids (london, England), 2011-01-28 00:00:00.0; 25(3), p. 303-14.
PMID: 21192231
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HIV-associated immune dysfunction and viral infection: role in the pathogenesis of AIDS-related lymphoma.
Authors: Epeldegui M. , Vendrame E. , Martínez-Maza O. .
Source: Immunologic Research, 2010 Dec; 48(1-3), p. 72-83.
PMID: 20717742
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Cytokine signaling pathway polymorphisms and AIDS-related non-Hodgkin lymphoma risk in the multicenter AIDS cohort study.
Authors: Wong H.L. , Breen E.C. , Pfeiffer R.M. , Aissani B. , Martinson J.J. , Margolick J.B. , Kaslow R.A. , Jacobson L.P. , Ambinder R.F. , Chanock S. , et al. .
Source: Aids (london, England), 2010-04-24 00:00:00.0; 24(7), p. 1025-33.
PMID: 20299965
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Expression and Function of the Chemokine, CXCL13, and Its Receptor, CXCR5, in Aids-Associated Non-Hodgkin's Lymphoma.
Authors: Widney D.P. , Gui D. , Popoviciu L.M. , Said J.W. , Breen E.C. , Huang X. , Kitchen C.M. , Alcantar J.M. , Smith J.B. , Detels R. , et al. .
Source: Aids Research And Treatment, 2010; 2010, p. 164586.
PMID: 21490903
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The major histocompatibility complex conserved extended haplotype 8.1 in AIDS-related non-Hodgkin lymphoma.
Authors: Aissani B. , Ogwaro K.M. , Shrestha S. , Tang J. , Breen E.C. , Wong H.L. , Jacobson L.P. , Rabkin C.S. , Ambinder R.F. , Martinez-Maza O. , et al. .
Source: Journal Of Acquired Immune Deficiency Syndromes (1999), 2009-10-01 00:00:00.0; 52(2), p. 170-9.
PMID: 19654554
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Elevated expression of activation induced cytidine deaminase in peripheral blood mononuclear cells precedes AIDS-NHL diagnosis.
Authors: Epeldegui M. , Breen E.C. , Hung Y.P. , Boscardin W.J. , Detels R. , Martínez-Maza O. .
Source: Aids (london, England), 2007-11-12 00:00:00.0; 21(17), p. 2265-70.
PMID: 18090274
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The effect of atopy, childhood crowding, and other immune-related factors on non-Hodgkin lymphoma risk.
Authors: Cozen W. , Cerhan J.R. , Martinez-Maza O. , Ward M.H. , Linet M. , Colt J.S. , Davis S. , Severson R.K. , Hartge P. , Bernstein L. .
Source: Cancer Causes & Control : Ccc, 2007 Oct; 18(8), p. 821-31.
PMID: 17588155
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Infection of human B cells with Epstein-Barr virus results in the expression of somatic hypermutation-inducing molecules and in the accrual of oncogene mutations.
Authors: Epeldegui M. , Hung Y.P. , McQuay A. , Ambinder R.F. , Martínez-Maza O. .
Source: Molecular Immunology, 2007 Feb; 44(5), p. 934-42.
PMID: 16730063
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Pathogenesis of AIDS lymphoma: role of oncogenic viruses and B cell activation-associated molecular lesions.
Authors: Epeldegui M. , Widney D.P. , Martínez-Maza O. .
Source: Current Opinion In Oncology, 2006 Sep; 18(5), p. 444-8.
PMID: 16894291
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Elevated serum soluble CD30 precedes the development of AIDS-associated non-Hodgkin's B cell lymphoma.
Authors: Breen E.C. , Fatahi S. , Epeldegui M. , Boscardin W.J. , Detels R. , Martínez-Maza O. .
Source: Tumour Biology : The Journal Of The International Society For Oncodevelopmental Biology And Medicine, 2006; 27(4), p. 187-94.
PMID: 16651853
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Serum levels of the homeostatic B cell chemokine, CXCL13, are elevated during HIV infection.
Authors: Widney D.P. , Breen E.C. , Boscardin W.J. , Kitchen S.G. , Alcantar J.M. , Smith J.B. , Zack J.A. , Detels R. , Martínez-Maza O. .
Source: Journal Of Interferon & Cytokine Research : The Official Journal Of The International Society For Interferon And Cytokine Research, 2005 Nov; 25(11), p. 702-6.
PMID: 16318584
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Elevated levels of soluble CD44 precede the development of AIDS-associated non-Hodgkin's B-cell lymphoma.
Authors: Breen E.C. , Epeldegui M. , Boscardin W.J. , Widney D.P. , Detels R. , Martínez-Maza O. .
Source: Aids (london, England), 2005-10-14 00:00:00.0; 19(15), p. 1711-2.
PMID: 16184051
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Expression and function of CD28 on Epstein-Barr virus-positive B cell lines and AIDS-associated non-Hodgkin's lymphoma cell lines.
Authors: Widney D. , Boscardin W.J. , Kasravi A. , Martínez-Maza O. .
Source: Tumour Biology : The Journal Of The International Society For Oncodevelopmental Biology And Medicine, 2003 Mar-Apr; 24(2), p. 82-93.
PMID: 12853703
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B-cell activation and lymphoma in patients with HIV.
Authors: Martínez-Maza O. , Breen E.C. .
Source: Current Opinion In Oncology, 2002 Sep; 14(5), p. 528-32.
PMID: 12192272
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Viral interleukin 6 stimulates human peripheral blood B cells that are unresponsive to human interleukin 6.
Authors: Breen E.C. , Gage J.R. , Guo B. , Magpantay L. , Narazaki M. , Kishimoto T. , Miles S. , Martínez-Maza O. .
Source: Cellular Immunology, 2001-09-15 00:00:00.0; 212(2), p. 118-25.
PMID: 11748928
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Aberrant expression of CD27 and soluble CD27 (sCD27) in HIV infection and in AIDS-associated lymphoma.
Authors: Widney D. , Gundapp G. , Said J.W. , van der Meijden M. , Bonavida B. , Demidem A. , Trevisan C. , Taylor J. , Detels R. , Martínez-Maza O. .
Source: Clinical Immunology (orlando, Fla.), 1999 Nov; 93(2), p. 114-23.
PMID: 10527687
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Human herpesvirus 8-encoded interleukin 6 activates HIV-1 in the U1 monocytic cell line.
Authors: Gage J.R. , Breen E.C. , Echeverri A. , Magpantay L. , Kishimoto T. , Miles S. , Martínez-Maza O. .
Source: Aids (london, England), 1999-10-01 00:00:00.0; 13(14), p. 1851-5.
PMID: 10513642
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The development of AIDS-associated Burkitt's/small noncleaved cell lymphoma is preceded by elevated serum levels of interleukin 6.
Authors: Breen E.C. , van der Meijden M. , Cumberland W. , Kishimoto T. , Detels R. , Martínez-Maza O. .
Source: Clinical Immunology (orlando, Fla.), 1999 Sep; 92(3), p. 293-9.
PMID: 10479534
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Immune dysfunction and the pathogenesis of AIDS-associated non-Hodgkin's lymphoma.
Authors: Martínez-Maza O. , Widney D. , van der Meijden M. , Knox R. , Echeverri A. , Breen E.C. , Magpantay L. , Miles S.A. .
Source: Memo¿rias Do Instituto Oswaldo Cruz, 1998 May-Jun; 93(3), p. 373-81.
PMID: 9698872
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