The objective of this study is to have the contractor examine a variety of potential biomarkers employing the MNU-induced rat mammary tumor model. The specific endpoints that are being employed include: A) Alterations of levels of cell cycle related endpoints e.g. PCNA, Ki 67 or S phase labeling with BuDR B) Alterations in apoptosis employing either DNA related assays (Fragmentation or Tunnel) and histopathologic determination of apoptosis C) Cellular necrosis as determined histopathologically. There are three sources of tissue at which the multiple biomarker assay are being examined to look for the effects of various chemopreventives: 1) """"""""Normal"""""""" tissue in tissues which have not been treated with carcinogen or in """"""""normal"""""""" tissues from rats which have been treated with carcinogen. 2) Small preinvasive lesions from defined specific lesions. 3) Late preinvasive lesions and early cancer. Substantial numbers of these lesions are made available at the end of these protocols. The primary objective of the present study is to expand on a prior contract which demonstrated modulation of biomarkers in palpable mammary lesions within 4-10 days following initiation of treatment with certain chemopreventives (tamoxifen, vorozole, ) . This study examines three compounds with striking chemopreventive efficacy as well as four compounds which are ineffective as chemopreventives in this specific tumor model.
| Shih, Shu-Ching; Robinson, Gregory S; Perruzzi, Carole A et al. (2002) Molecular profiling of angiogenesis markers. Am J Pathol 161:35-41 |
| Warso, M A; Maniotis, A J; Chen, X et al. (2001) Prognostic significance of periodic acid-Schiff-positive patterns in primary cutaneous melanoma. Clin Cancer Res 7:473-7 |
