Strategies for Treatment of Bone Metastases from Breast Cancer

Abstract

The major goal of this project is to optimize the strategies for using radioactive strontium for palliation of bone pain due to breast cancer metastases. One approach is to determine ways of selectively increasing strontium uptake at the metastatic site. Bisphosphonates are useful in the treatment of osteoporosis and bone metastases. Bisphosphonates sequester calcium and strontium. Strontium was non toxic to human breast cancer cells. Bisphosphonates are charged molecules that do not easily cross hydrophobic cell membranes. The nature of the counter ion to the anionic phosphonate was found to have an effect on the cellular uptake of bisphosphonate such as etidronate. The cytotoxicty of zoledronic acid towards MCF-7 cells greater than pamidronate and etidronate. The presence of strontium chloride in the culture medium inhibited calcium uptake by MDA-MB 231 cells. Etidronic acid treatment perturbed cell cycle progression of MCF-7 cells, causing a G2/M block and decreased the proportion of cells in S-phase. This suggests that a bisphosphonate such as etidronate may be useful in combination with ionizing radiation for treatment of bone metastases.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2005
Accession Number
ADA469975

Entities

People

  • Rajagopalan Sridhar

Organizations

  • Howard University

Tags

DTIC Thesaurus Topics

  • Bone And Bones
  • Bone Diseases
  • Bone Fractures
  • Breast Cancer
  • Cell Line
  • Cell Membrane
  • Cell Physiological Processes
  • Cells
  • Chemistry
  • Growth Factors
  • Ionizing Radiation
  • Neoplasms
  • Osteoblasts
  • Osteogenesis
  • Osteoporosis
  • Programmed Cell Death
  • Tumor Cell Line

Readers

  • Analytical Chemistry
  • Immunology and Pathology
  • Molecular Biology and Genetics