The overall objectives of this application largely remain the same. Namely: 1) To conduct a comprehensive survey of key proliferative parameters of tumor cells in different types of human hematopoietic tumors, to correlate these with cell marker studies and clinical features, and to identify those factors which are associated with therapeutic success or failure; 2) To determine the effects of selected cytotoxic drugs on normal and neoplastic human hematopoietic cells in short-term cultures and in established cultures in order to develop leads for improved therapeutic programs; 3) To purify, isolate and characterize the clonogenic progenitor cells in normal huma blood and marrow and compare their proliferative kinetics with those of clonogenic progenitor cells in chronic myelogenous leukemia (CML) and other hematopoietic tumors; 4) To refine procedures for autologous transplantation for frozen and stored hematopoietic stem cells obtained from the marrow and/or blood of patients with poor prognosis lymphomas and other selected tumors prior to treatment to be used to rescue the patients following aggressive chemotherapy aimed at eradicating the tumor. We are also investigating improved methods for purging marrow of residual tumor cells, using cytotoxic drugs or monoclonal antibodies; 5) To develop improved flow microfluorometric procedures for kinetic analysis and improved mathematical models which more accurately and realistically define the kinetic behavior of normal and tumor cell populations and the interactions between them. It is anticipated that improved understanding of the kinetic behavior of the neoplastic cells in different hematopoietic tumors and of the kinetic perturbations caused by treatment will permit development of more individualized and effective treatment for each specific disease entity. This will require more complete knowledge of the cellular origins of the various tumors, more accurate classification and staging techniques, clearer definition of key prognostic factors, and better appreciation of variability in proliferative behavior and responsiveness to treatment within any given tumor category.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA019117-11
Application #
3165093
Study Section
Experimental Therapeutics Subcommittee 2 (ET)
Project Start
1976-06-30
Project End
1987-12-31
Budget Start
1986-05-01
Budget End
1987-12-31
Support Year
11
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Sloan-Kettering Institute for Cancer Research
Department
Type
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10065
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Gulati, S; Atzpodien, J; Lemoli, R M et al. (1990) Photoradiation methods for purging autologous bone marrow grafts. Prog Clin Biol Res 333:87-102
Wisniewski, D; Strife, A; Arlin, Z et al. (1989) Analysis of the individual and combined reactivities of monoclonal antibodies H25, H366, and MY9 with normal progenitor cells and blast cells from patients with acute myeloblastic leukemia. Leukemia 3:446-52
Atzpodien, J; Buhrer, C; Gulati, S C et al. (1989) Induction of nonspecific cell-mediated cytotoxicity: a multisignal event and its cellular regulation. Haematol Blood Transfus 32:273-80
Atzpodien, J; Gulati, S C; Shimazaki, C et al. (1988) Ewing's sarcoma: ex vivo sensitivity towards natural and lymphokine-activated killing. Oncology 45:437-43
Shimazaki, C; Wisniewski, D; Scheinberg, D A et al. (1988) Elimination of myeloma cells from bone marrow by using monoclonal antibodies and magnetic immunobeads. Blood 72:1248-54
Gulati, S C; Shank, B; Black, P et al. (1988) Autologous bone marrow transplantation for patients with poor-prognosis lymphoma. J Clin Oncol 6:1303-13
Strife, A; Lambek, C; Wisniewski, D et al. (1988) Discordant maturation as the primary biological defect in chronic myelogenous leukemia. Cancer Res 48:1035-41
Gulati, S C; Atzpodien, J; Langleben, A et al. (1988) Comparative regimens for the ex vivo chemopurification of B cell lymphoma-contaminated marrow. Acta Haematol 80:65-70
Atzpodien, J; Gulati, S C; Kwon, J H et al. (1988) Anti-tumor efficacy of interleukin-2-activated killer cells in human neuroblastoma ex vivo. Exp Cell Biol 56:236-44

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