Liposomal Sphingolipids to Target Breast Adenocarcinoma Apoptosis
Abstract
The purpose of these studies was: (1) to evaluate the interactions between Wortmannin-mediated inhibition of the Akt/PKB pathway and sphingolipid-induced apoptosis in a panel of human breast adenocarcinoma cell lines with basal or over-expression of HER-2/neu, and (2) to translate the formulation and toxicity studies conducted in the first year to initial proof-of-principle studies in nude mouse/human HER-2/neu over-expressing breast adenocarcinoma models. Investigations pertinent to Aims 1 (apoptosis) and 5 (efficacy studies) were the main focus. Progress in Aim 1 has been acceptable and studies are continuing in a model with low/basal expression and transfectants with high HER-2/neu expression. Our results indicate that inhibition of the Akt/PKB pathway enhances the apoptotic response to sphingolipids. Progress pertinent to Aim 5 has been stymied until very recently due to the lack of reproducible in vivo tumorigenic behavior of the MDA-361 HER-2/neu over-expressing human breast adenocarcinoma model. We believe that this can be linked to sub-optimal in vitro culture conditions which either select for variants or otherwise compromise subsequent tumorigenicity. With this obstacle apparently successfully overcome, we expect satisfactory progress on the remaining Tasks.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2001
- Accession Number
- ADA394257
Entities
People
- Jim Klostergaard
Organizations
- The University of Texas MD Anderson Cancer Center