VITAMIN D ANALOGS AS ADJUVANTS IN CHEMOTHERAPY

Project Details

Description

Therapeutic drugs are increasingly effective in the treatment of lymphatic
leukemias, but drug induced remissions of myeloid and myelomonocytic forms
of this disease are followed by relapses and death. We propose to
investigate in a model system the potential of differentiating agents,
vitamin D3 and its analogs, as adjuncts to the cytotoxic treatment with
arabinocytosine (Ara C). This study will be conducted in tissue culture on
cells freshly isolated from leukemic patients, and from normal volunteers.
The mechanisms responsible for the potentiation of drug cytotoxicity by
vitamin D will be studied in leukemic cells susceptible to this regimen.
First we will determine if vitamin D3 increases drug retention. If, as we
anticipate, this mode of action does not fully account for the observed
effects, we shall initiate a systematic study of molecular changes affecting
the synthesis, repair and expression of DNA in leukemic cells subjected to
sequential treatment with Ara C and vitamin D3 analogs. These processes
will be studied both in intact cells and in subcellular systems, and
oncogene expression will be explored in order to relate inhibition of cell
proliferation, terminal differentiation and cytotoxicity to the altered
expression of these genes. This knowledge will be utilized to propose new
therapeutic strategies for improved treatment of leukemia.
StatusFinished
Effective start/end date12/31/896/30/20

Funding

  • National Cancer Institute: $222,013.00
  • National Cancer Institute: $216,873.00
  • National Cancer Institute: $46,319.00
  • National Cancer Institute: $191,385.00
  • National Cancer Institute
  • National Cancer Institute
  • National Cancer Institute
  • National Cancer Institute: $194,805.00
  • National Cancer Institute: $203,601.00
  • National Cancer Institute
  • National Cancer Institute
  • National Cancer Institute: $47,522.00
  • National Cancer Institute: $190,441.00
  • National Cancer Institute: $45,151.00

ASJC

  • Medicine(all)
  • Genetics
  • Molecular Biology
  • Oncology
  • Cancer Research
  • Cell Biology

Fingerprint

Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.