Liposomal Sphingolipids to Target Breast Adenocarcinoma Apoptosis
Abstract
We have observed that certain sphingolipids (e.g., dimethyl-sphingosine: DMSP) induce apoptosis in vitro in tumor cells despite the over-expression of HER-2/neu and other resistance mechanisms relevant to breast cancer. In these studies, we translated formulation and toxicity studies of liposomal-DMSP (L-DMSP) to proof-of-principle efficacy studies in the nude mouse/human HER-2/neu over-expressing MDA-MD-361 breast adenocarcinoma model. In the first tier efficacy experiments, mice were treated with a multiple-dose MTD regimen of L-DMSP administered i.v. beginning either one-week after - tumor implantation or when tumors grew to 4-5 mm diameter. Early treatment caused a delay in or reduced subsequent tumor growth, but was rarely curative; the tumor growth curve was suggestive of stasis. Treatment initiated at the later timepoint was also efficacious, but less so; the response appeared to be primarily very brief stasis, with slight growth occurring through treatment, followed by a slower growth rate than for controls. In the second tier efficacy experiments using the later timepoint only, the effect of PEG in the liposomal formulation was evaluated, and the i.p. and i.v. routes of administration were compared. The PEG formulation appeared superior to the non-PEG, and the i.p. route did not prove efficacious.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2003
- Accession Number
- ADA418571
Entities
People
- Jim Klostergaard
Organizations
- The University of Texas MD Anderson Cancer Center