Accession Number:

ADA371367

Title:

Development of Ligand-Transformed Alpha-Fetoprotein for Use Against Breast Cancer in Humans

Descriptive Note:

Final rept. 1 Jul 94-31 MAr 99

Corporate Author:

ALBANY MEDICAL COLL NY

Personal Author(s):

Report Date:

1999-04-01

Pagination or Media Count:

34.0

Abstract:

The purpose of this study was to produce large quantities of the active form of alpha-fetoprotein AFP and assess its effectiveness in the control of estrogen-stimulated growth of experimental human breast cancers. Both recombinant and natural AFP were produced for this purpose. AFP stopped the estrogen-stimulated growth of MCF-7 and T47 human breast cancers and the MCF-10A human benign breast tumor grown as xenografts in immune-deficient mice. AFP did not interfere with the estrogen-independent growth of MDA-MB-231 and BT20 human breast cancer xenografts. Positivity for sex steroid hormone receptors was a marker of tumor sensitivity to the growth-inhibitory effects of AFP. Elevations in serum FSH and E2 were intermediate markers of AFPs biological activity. The histomorphometric profile of growth-inhibited tumors was one of cytostasis, not cytotoxicity, with cells accumulating in the G0G1 phase of the cell cycle. There was no evidence of toxicity associated with chronic treatment with AFP. The active site of this protein is an 8-amino-acid peptide located near the C-terminal part of the molecule. This peptide was synthesized in quantity and retained full biological activity. The peptide requires further study, since it is more clinically translatable as a pharmaceutical for the treatment of breast cancer than the full-length protein.

Subject Categories:

  • Biochemistry
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE