Crotum tiglium L is a shrub of the Euphorbiaciae family. The croton oil obtained from Croton tiglium L contains 12-O- tetradecanoylphorbol-13-acetate (TPA), an agent that has been widely studied as both a differentiation agent and a tumor promoter. The activity of TPA as a hematopoietic cell differentiating agent has been established by studies of human leukemia cell lines, primary myeloid leukemia cells, and normal hematopoietic stem cells. In addition to the induction of differentiation in these primary cells and cell lines, TPA has been demonstrated to modulate the growth, differentiation, survival, structure and metabolism of a variety of other primary cell and cell lines. As a consequence of it's biological activity as a differentiating agent, investigators in the People's Republic of China have recently reported on the use of TPA in patients with refractory myeloid malignancies. These studies demonstrated the feasibility and short term safety of administering TPA to humans. Some of the patients had a clinical response to regimens containing TPA and the toxicities were mild and reversible at most of the doses used. As a consequence of these studies, we have initiated a phase I trial of TPA in patients with refractory hematologic malignancies/bone marrow disorders. This """"""""Small Grant for Therapeutic Clinical Trials of Malignancies"""""""" is requesting support to undertake correlative studies in association with TPA administration. Specific objectives will include: (i) the development of physical and biological assays to detect TPA in human serum, (ii) the determination of biological correlates of TPA administration, and (iii) an assessment of TPA-induced morphologic and immunophenotypic changes in blood and marrow cells.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Research Grants (R03)
Project #
5R03CA085201-02
Application #
6350435
Study Section
Subcommittee G - Education (NCI)
Project Start
2000-02-01
Project End
2004-01-31
Budget Start
2001-02-01
Budget End
2004-01-31
Support Year
2
Fiscal Year
2001
Total Cost
$75,650
Indirect Cost
Name
University of Medicine & Dentistry of NJ
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
622146454
City
Piscataway
State
NJ
Country
United States
Zip Code
08854