Liposomal Sphingolipids to Target Breast Adenocarcinoma Apoptosis

Abstract

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-2/neu 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 Akt/PKB 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-2/neu 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.

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Document Details

Document Type
Technical Report
Publication Date
Jun 01, 2000
Accession Number
ADA383846

Entities

People

  • Jim Klostergaard

Organizations

  • The University of Texas MD Anderson Cancer Center

Tags

DTIC Thesaurus Topics

  • Adenocarcinoma
  • Apoptosis
  • Biomedical Research
  • Body Weight
  • Breast Cancer
  • Cancer
  • Cell Line
  • Cell Membrane
  • Cells
  • Inhibition
  • Laboratory Animals
  • Lipids
  • Materials
  • Neoplasms
  • Sphingolipids
  • Synthetic Membranes
  • Toxicity

Fields of Study

  • Chemistry

Readers

  • Cellular and Molecular Pathways of Apoptosis.
  • Oncology (Cancer Research).