Accession Number:

ADA454294

Title:

Use of Mitochondria-Specific Dye MKT-077 as a Radiosensitizer to Preoperatively Treat Locally Advanced Breast Cancer

Descriptive Note:

Annual summary rept. 15 Mar 2005-14 Mar 2006

Corporate Author:

WAYNE STATE UNIV DETROIT MI

Personal Author(s):

Report Date:

2006-04-01

Pagination or Media Count:

13.0

Abstract:

The major goal of this project is to determine if the rhodacyanine analog dye, MKT-077, can be used to inhibit breast cancer cell oxygen metabolism and raise tumor oxygen levels, thereby radiosensitizing the tumor. In the first year, we have performed in vitro experiments to determine drug uptake and subsequent MKT-077-induced metabolic inhibition in human MDA-MB 231 cells, as outlined in Tasks 1 and 2. We originally proposed to do this work in our multicellular layer MCL model of tumor parenchyma, but we had difficulty growing MCLs from this cell line consistently. Therefore, we have begun determining MKT-077 drug uptake and metabolic inhibition using MDA-MB 231 monolayers and cell suspensions. This approach has been successful, and we have been able to show that the cells rapidly take up the drug, which inhibits cellular oxygen metabolism by 22 at a dose of 4 gml. We are currently completing the drug uptake studies and determining the inhibition caused by other doses. In addition, we have begun the in vivo work in nude rats. We have determined that the rats can tolerate a dose of 10 mgkg MKT-077 infused at 1.25 mgkgmin. Soon we will begin measuring MKT-077-induced oxygen changes in orthotopic xenografts in vivo.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE