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.
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