Butyrate Therapy for Poorly Differentiated Breast Cancer

Abstract

This project aims to devise a strategy for maintaining butyric acidemia in mice over a 24 hour period of time, so as to achieve a nearly complete inhibition of histone deacetylase activity. The basic approach is to use butyryiglycerides as a prodrug to butyrate and MCPA as an inhibitor of butyrate metabolism (MCPA). We monitor for both vital signs and blood chemistries to assure survival during the prolonged metabolic acidosis. Our hypothesis is that such a scheme will allow maintenance of butyrate blood levels between 1 and 5 mM, and that the mice will develop hyperacetylation of chromatin core histones sufficient to cause extensive cytolysis in xenografted tumors with known sensitivity to butyrate-induced apoptosis.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 1999
Accession Number
ADA382836

Entities

People

  • John Mcbain

Organizations

  • Dartmouth College

Tags

DTIC Thesaurus Topics

  • Acid-Base Imbalance
  • Apoptosis
  • Blood Chemistry
  • Breast Cancer
  • Butyric Acids
  • Cell Physiological Processes
  • Chemical Synthesis
  • Chemistry
  • Chromosome Structures
  • Inhibition
  • Inhibitors
  • Materials
  • Metabolic Diseases
  • Metabolism
  • Neoplasms
  • Physiological Monitoring
  • Vital Signs

Fields of Study

  • Biology

Readers

  • Analytical Chemistry
  • Cardiovascular Physiology
  • Molecular Biology and Genetics