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5-Fluorouracil (5-FU) is the most common chemotherapeutic agent used in the treatment of colorectal cancer, yet objective response rates are low. Recently, camptothecin (CPT) has emerged as an effective alternative therapy. Decisive means to determine treatment, based on the likelihood of response to each of these agents, could greatly enhance the(More)
The short-chain fatty acid butyrate, produced by microbial fermentation of dietary fiber in the large intestine, is a physiological regulator of major pathways of colonic epithelial cell maturation: cell cycle arrest, lineage-specific differentiation, and apoptosis. Microarray analysis of 8,063 sequences demonstrated a complex cascade of reprogramming of(More)
The platinum compound oxaliplatin has been shown to be an effective chemotherapeutic agent for the treatment of colorectal cancer. In this study, we investigate the molecular mechanisms of action of oxaliplatin to identify means of predicting response to this agent. Exposure of colon cancer cells to oxaliplatin resulted in G2/M arrest and apoptosis.(More)
Colonic epithelial cells undergo cell cycle arrest, lineage specific differentiation, and apoptosis, as they migrate along the crypt axis toward the lumenal surface. The Caco-2 colon carcinoma cell line models many of these phenotypic changes, in vitro. We used this model system and cDNA microarray analysis to characterize the genetic reprogramming that(More)
A defined rodent "new Western diet" (NWD), which recapitulates intake levels of nutrients that are major dietary risk factors for human colon cancer, induced colonic tumors when fed to wild-type C57Bl/6 mice for 1.5 to 2 years from age 6 weeks (two-thirds of their life span). Colonic tumors were prevented by elevating dietary calcium and vitamin D(3) to(More)
Human colonic cancer is associated with multiple genetic deletions, mutations, and alterations in gene expression; in contrast, gene amplification has not been recognized as a prominent characteristic of human colonic tumors. Although the c-myc gene is overexpressed in approximately 70% of human colonic cancers, previous studies have not detected frequent(More)
Colon carcinoma cells overexpress c-myc due to defective Wnt signaling, but only patients whose tumors have an amplified c-myc gene show improved disease-free and overall survival in response to 5-fluoruracil (5FU). Here we show that in two colon carcinoma cell lines that do not have an amplified c-myc gene but differ in their p53 status, high c-myc levels(More)
BACKGROUND & AIMS To define the genetic reprogramming that drives intestinal epithelial cell maturation along the crypt-villus axis, enterocytes were sequentially isolated from the villus tip to the crypts of mouse small intestine. METHODS Changes in gene expression were assessed using 27,405-element complementary DNA microarrays (14,685 unique genes) and(More)
Histone deacetylase inhibitors (HDACi) induce growth arrest and apoptosis in colon cancer cells and are being considered for colon cancer therapy. The underlying mechanism of action of these effects is poorly defined with both transcription-dependent and -independent mechanisms implicated. We screened a panel of 30 colon cancer cell lines for sensitivity to(More)
Aberrant crypt foci (ACF) are morphologically abnormal structures that can be identified in whole amounts of colonic tissue from rodents treated with colon carcinogens and from patients at risk for development of colon tumors. ACF are heterogeneous and exhibit properties, such as altered patterns of cell proliferation, the presence of dysplasia, and(More)