Accession Number : ADA292515

Title :   A New Class of Membrane Active Drugs for the Treatment of Breast Cancer Cells Transplanted into Athymic Mice.

Descriptive Note : Final rept.,

Corporate Author : BAYLOR RESEARCH INST DALLAS TX

Personal Author(s) : Gulliya, Kirpal S.

PDF Url : ADA292515

Report Date : 07 DEC 1994

Pagination or Media Count : 51

Abstract : The main objective of this study was to determine the effect of preactivated merocyanine 540 (pM4C540) and merodantoin on the growth of established human MCF-7 breast cancer xenografts and study the toxicity, biodistribution and plasma clearance of merodantoin. Treatment of established tumors with pMC540 and merodantoin resulted in a 74% and 84% inhibition of tumor growth, respectively. Under the conditions of estradiol deprivation, this inhibition was reduced to 42% and 25%, respectively. Combined treatment with either pMC540 or merodantoin plus tamoxifen did not produce a significant enhancement of tumor growth inhibition. The LD50 and LD90 of merodantoin were determined to be 1042 mg/kg and 1250 mg/kg, respectively. The plasma half-life of merodantoin was 25 hours. Organ specific accumulation of medrodantoin was not observed and majority (>70%) of the drug was eliminated via urine and feces. Both pMC540 and merodantoin were found to mediate their cytotoxic effects via initial interaction with topoisomerase II. There is a correlation between DNA topoisomerase II activity and drug-sensitive (MCF-7) and -insensitive (MDA-MB-231) breast cancer cell lines. Breast cancer cells resistant to pMC540 and merodantoin were found to contain undetectable or very low levels of topoisomerase II.

Descriptors :   *TOXICITY, *DRUGS, *CANCER, CELLS, GROWTH(GENERAL), PLASMAS(PHYSICS), NEOPLASMS, DEOXYRIBONUCLEIC ACIDS, LOW LEVEL, MEMBRANES, CYTOTOXINS, ACCUMULATION, INHIBITION, FECES, URINE, ORGANS(ANATOMY), MAMMARY GLANDS, RESISTANCE(BIOLOGY), HALF LIFE, CHEMOTHERAPEUTIC AGENTS, BIOSTATISTICS.

Subject Categories : Medicine and Medical Research
      Toxicology
      Pharmacology

Distribution Statement : APPROVED FOR PUBLIC RELEASE