Accession Number : ADB268439


Title :   Xenograft Studies of Fatty Acid Synthesis Inhibition as Novel Therapy for Breast Cancer


Descriptive Note : Final rept. 1 Aug 1996-31 Aug 2000


Corporate Author : JOHNS HOPKINS UNIV BALTIMORE MD


Personal Author(s) : Kuhajda, Francis P


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/b268439.pdf


Report Date : Aug 2000


Pagination or Media Count : 49


Abstract : This grant proposed to study the effect of fatty acid synthesis inhibition in human breast cancer xenografts using C75, a novel inhibitor of fatty acid synthesis. We also proposed to study the mechanism of cell death by C75 and the effect of dietary fatty acids on this model. The purpose of this study is to demonstrate that the fatty acid synthesis is a novel pathway for breast cancer therapy development. We found that C75 inhibited fatty acid synthase (FAS) and had significant anti-tumor activity in both human breast cancer and human mesothelioma xenografts. In addition, we determined that malonyl-CoA is likely the trigger of apoptosis during FAS inhibition in cancer cells. During treatment of animals with C75, we noted significant reversible weight loss. Mechanistic studies of the weight loss showed that FAS inhibition leads to reduced neuropeptide-Y production in the hypothalamus. Thus, we have found that inhibition of FAS in mammals has a significant anti-tumor effect. In addition, FAS inhibition can cause weight reduction and correction of Type II diabetes in obese (ob/ob) mice.


Descriptors :   *SYNTHESIS(CHEMISTRY) , *FATTY ACIDS , *BREAST CANCER , CHEMICAL PROPERTIES , THERAPY , INHIBITION , CELLS(BIOLOGY) , DIET , WEIGHT REDUCTION , CONNECTIVE TISSUE , APOPTOSIS


Subject Categories : Biochemistry
      Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE