The biological response modifier and activator of protein kinase C - bryostatin is a natural product purified to homogeneity which has been demonstrated to stimulate normal hematopoiesis at the same concentrations which inhibit tumor cell growth. We plan experimental studies which will continue to dissect the mechanisms of action of bryostatin with simultaneous studies which will lead to a clinical trial with this agent.
Our specific aims i nclude determination of the functional response of primitive hematopoietic progenitor target populations to bryostatin. We will utilize murine and parallel human in vitro model systems to study the experimental therapeutic properties of bryostatin. The in vivo animal studies will be performed as a preclinical model in preparation for the clinical trial. We will also establish the utility of a transplantation model to study the effects in vivo on leukemic cell growth and determine if bryostatin can be used in purging bone marrow of minimal residual disease. Finally, we will attempt to determine the molecular biochemical mechanisms of action of bryostatin on both normal and malignant hematopoietic cells.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA047993-09
Application #
2007728
Study Section
Experimental Therapeutics Subcommittee 1 (ET)
Project Start
1988-07-01
Project End
1997-12-31
Budget Start
1997-01-01
Budget End
1997-12-31
Support Year
9
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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