1 ALPHA-Hydroxyvitamin D5 as a Chemotherapeutic and Possibly Chemopreventive Agent
Abstract
We identified a novel vitamin D analog, 1 alpha-hydroxy-24 ethyl vitamin D5 (1 alpha(OH)D5) that showed potent growth inhibitory and cell-differentiating actions in breast cancer cells. Based on our findings in vitro and in vivo, we hypothesized that 1 alpha(OH)D5 (D5), when administered to women with breast cancer, will induce differentiation of dedifferentiated cells and thereby prevent progression of malignancy. In 1999-2000, we completed preclinical studies in rats, showing that D5 has no serious toxicity; high doses led to a hypercalcemic effect, which was reversible. In vitro studies showed that D5 has no effect on normal breast epithelial cells but induces apoptosis in breast cancer and showed apoptotic effect in fibroadenomas. In 2000-2001, under GMP, we completed preclinical toxicity studies in dogs and completed synthesis of 1 alpha(OH)D5. In vitro studies suggested that D5 has no effect on normal breast tissues. In 2001-2002, in vitro studies showed D5 to have no effect of cell proliferation , cell death, or differentiation markers (casein) in nonmalignant breast epithelial cells. In 2002-2003, in vitro studies suggested a differential effect of D5 on ER+ vs. ER- cells and that D5's action may be mediated, in part, by VDR. Clinical trial protocols were updated for both the UIC IRB and FDA. In 2003-2004, the clinical protocol was updated and approved by the UIC IRB, and Lutheran General Hospital was removed from the protocol. Currently, all of the preclinical toxicology and pharmacology studies have been completed and an ND application has been submitted to the FDA. The FDA has asked for some additional.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2004
- Accession Number
- ADA432552
Entities
People
- Tapas K. Das Gupta
Organizations
- University of Illinois at Chicago