The overall objective of this proposed Program Project is to elucidate the factors predisposing organ transplant recipients to develop cancer at a much higher frequency than that seen in the general population and to determine the host factors which contribute to the tumor regression seen in some cases upon reduction in immunosuppressive therapy. The University of Pittsburgh Medical and Health Care Division is a leading international center for organ transplantation, and a major complication of these procedures has been the frequent development (greater than 1%) of malignant disease, especially post-transplant lymphoproliferative disease (PTLD). The projects in this proposal are designed to understand better some of the pathogenetic and biological characteristics of this problem: Projects 1, 2 and 4 are designed primarily to prospectively evaluate the factors hat may contribute to the development of tumors which, although occurring at a high rate relative to the general population, affect only a small proportion of transplant recipients. Project 1 (Project leader: Dr. Monto Ho) is focused on the hypothesis that infection of the patients by Epstein-Barr virus (EBV), particularly as a primary infection in the immunosuppressed host, plays a strong role in the induction of PTLD. The possible contribution of other agents, particularly human B lymphotropic virus (HHV-6), will also be evaluated. Project 2 (Project Leader: Dr Theresa Whiteside) has been designed to evaluate the alterations in the immune system particularly in potential anti-tumor effector mechanisms, that are induced by organ transplantation and by administration of cyclosporine A (CsA) and other immunosuppressive treatments. In addition, by prospectively following the transplant recipients after the immunologic assessment, for possible development of malignant disease, it should be possible to determine a predictive profile of immunologic abnormalities. Project 3 (Project Leader: Dr. Theresa Whiteside) focuses on detailed studies of tumor infiltrating lymphocytes in liver tumors arising in patients transplanted for the treatment of primary hepatocellular carcinoma. Project 4 (Project Leader: Dr. Sandra Levy) is designed to examine psychosocial factors in transplant recipients which may contribute to disease development and progression.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA047445-02
Application #
3094238
Study Section
Special Emphasis Panel (SRC (I1))
Project Start
1989-09-01
Project End
1994-06-30
Budget Start
1990-07-01
Budget End
1991-06-30
Support Year
2
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Type
Schools of Medicine
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Craig, Fiona E; Johnson, Lawrence R; Harvey, Stephen A K et al. (2007) Gene expression profiling of Epstein-Barr virus-positive and -negative monomorphic B-cell posttransplant lymphoproliferative disorders. Diagn Mol Pathol 16:158-68
Shpilberg, O; Wilson, J; Whiteside, T L et al. (1999) Pre-transplant immunological profile and risk factor analysis of post-transplant lymphoproliferative disease development: the results of a nested matched case-control study. The University of Pittsburgh PTLD Study Group. Leuk Lymphoma 36:109-21
Nalesnik, M A; Zeevi, A; Randhawa, P S et al. (1999) Cytokine mRNA profiles in Epstein-Barr virus-associated post-transplant lymphoproliferative disorders. Clin Transplant 13:39-44
Wu, T T; Swerdlow, S H; Locker, J et al. (1996) Recurrent Epstein-Barr virus-associated lesions in organ transplant recipients. Hum Pathol 27:157-64
Vujanovic, N L; Polimeno, L; Azzarone, A et al. (1995) Changes of liver-resident NK cells during liver regeneration in rats. J Immunol 154:6324-38
Ho, M (1995) Risk factors and pathogenesis of posttransplant lymphoproliferative disorders. Transplant Proc 27:38-40
Lee, E S; Locker, J; Nalesnik, M et al. (1995) The association of Epstein-Barr virus with smooth-muscle tumors occurring after organ transplantation. N Engl J Med 332:19-25
Wu, T T; Swerdlow, S; Locker, J et al. (1995) Pathologic analysis of recurrent posttransplant lymphoproliferative disorders. Transplant Proc 27:1193-4
Appasamy, R; Bryant, J; Hassanein, T et al. (1994) Effects of therapy with interferon-alpha on peripheral blood lymphocyte subsets and NK activity in patients with chronic hepatitis C. Clin Immunol Immunopathol 73:350-7
Yasumura, S; Lin, W C; Hirabayashi, H et al. (1994) Immunotherapy of liver metastases of human gastric carcinoma with interleukin 2-activated natural killer cells. Cancer Res 54:3808-16

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