Liposomal Sphingolipids to Target Breast Adenocarcinoma Apoptosis
Annual rept. 15 May 1995-14 May 2000
M D ANDERSON CANCER CENTER HOUSTON TX
Pagination or Media Count:
The purpose of these studies was to develop key data for the approach to the proof-of-principle, efficacy studies in Aim 5 using orthotopic Her-2neu over-expressing human breast adenocarcinoma models. Investigations pertinent to Aims 1 apoptosis, 2 formulation and 4 toxicity were initiated and are still ongoing. In two models examined to date, one model demonstrated interactions which were additive or greater between Wortmannin-mediated inhibition of the AktPKB pathway and sphingolipid induced apoptosis. These studies were in related ovarian cell lines and are presently being extended to human breast adenocarcinoma lines, with basal or high Her-2neu expression. In formulation studies, we demonstrated that liposomes composed of 33 mole percent dimethyl-sphingosine DMSp and the balance of the lipids composed equivalently of dipalmitoyl-phosphatidyl choline and distearoyl-phosphatidyl choline, could be successfully formulated and that these were stable.
- Medicine and Medical Research