Abstract

We wish to continue our studies of the induction of thymic T-cell lymphomas in mice exposed to ionizing radiation or to chemical leukemogens. Specifically, we plan to investigate: 1. the contribution of lymphostromal and lymphoepithelial multicellular complexes to the thymus microenvironment essential for murine T-cell lymphomagenesis. 2. the role of natural killer (NK) cells and other mechanisms of immune surveillance in lymphomagenesis. 3. the hypothesis that viral envelope antigens induce autostimulatory blastogenesis leading to tumor development. 4. the evolution of autonomy of such lymphomas as related to phenotypic markers and chromosome numbers. 5. the hypothesis that radiation or chemicals activate an oncogenic replication-defective """"""""xenotropic-like"""""""" retroviral genome which then induces apparently virus-negative lymphomas. 6. the hypothesis that lymphomagenic, replication-competent retrovirus may later be generated when such lymphomas are infected by a sporadically expressed non-oncogenic ecotropic virus, leading to """"""""rescue' of the replication-defective """"""""xenotropic-like"""""""" oncogenic genome. 7. the """"""""promoter insertion"""""""" hypothesis and other possible molecular mechanisms of murine retroviral lymphomagenesis.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA003352-32
Application #
3163143
Study Section
Pathology B Study Section (PTHB)
Project Start
1979-04-01
Project End
1989-06-30
Budget Start
1988-03-01
Budget End
1989-06-30
Support Year
32
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Stanford University
Department
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305

  Publications

Sen-Majumdar, A; Guidos, C; Kina, T et al. (1994) Characterization of preneoplastic thymocytes and of their neoplastic progression in irradiated C57BL/Ka mice. J Immunol 153:1581-92
Sen-Majumdar, A; Weissman, I L; Hansteen, G et al. (1994) Radiation leukemia virus-induced thymic lymphomas express a restricted repertoire of T-cell receptor V beta gene products. J Virol 68:1165-72
Small, M; Majumdar, A S; Lieberman, M et al. (1994) Isolation of CD3-, CD4-, CD8-, IL-2R+ thymocyte precursors by panning. J Immunol Methods 167:103-7
Waller, E K; Ziemianska, M; Bangs, C D et al. (1993) Characterization of posttransplant lymphomas that express T-cell-associated markers: immunophenotypes, molecular genetics, cytogenetics, and heterotransplantation in severe combined immunodeficient mice. Blood 82:247-61
Sen-Majumdar, A; Lieberman, M; Alpert, S et al. (1992) Differentiation of CD3-4-8- thymocytes in short-term thymic stromal cell culture. J Exp Med 176:543-51
Waller, E K; Sen-Majumdar, A; Kamel, O W et al. (1992) Human T-cell development in SCID-hu mice: staphylococcal enterotoxins induce specific clonal deletions, proliferation, and anergy. Blood 80:3144-56
Lieberman, M; Hansteen, G A; Waller, E K et al. (1992) Unexpected effects of the severe combined immunodeficiency mutation on murine lymphomagenesis. J Exp Med 176:399-405
Waller, E K; Kamel, O W; Cleary, M L et al. (1991) Growth of primary T-cell non-Hodgkin's lymphomata in SCID-hu mice: requirement for a human lymphoid microenvironment. Blood 78:2650-65
Majumdar, A S; Guidos, C; Kaneshima, H et al. (1990) An immunodominant murine lymphoma cell surface heterodimer marks thymic progenitor subsets. J Immunol 144:111-21
McCune, J M; Kaneshima, H; Lieberman, M et al. (1989) The scid-hu mouse: current status and potential applications. Curr Top Microbiol Immunol 152:183-93

Showing the most recent 10 out of 17 publications