124 research outputs found
Resistance to ursodeoxycholic acid-induced growth arrest can also result in resistance to deoxycholic acid-induced apoptosis and increased tumorgenicity
BACKGROUND: There is a large body of evidence which suggests that bile acids increase the risk of colon cancer and act as tumor promoters, however, the mechanism(s) of bile acids mediated tumorigenesis is not clear. Previously we showed that deoxycholic acid (DCA), a tumorogenic bile acid, and ursodeoxycholic acid (UDCA), a putative chemopreventive agent, exhibited distinct biological effects, yet appeared to act on some of the same signaling molecules. The present study was carried out to determine whether there is overlap in signaling pathways activated by tumorogenic bile acid DCA and chemopreventive bile acid UDCA. METHODS: To determine whether there was an overlap in activation of signaling pathways by DCA and UDCA, we mutagenized HCT116 cells and then isolated cell lines resistant to UDCA induced growth arrest. These lines were then tested for their response to DCA induced apoptosis. RESULTS: We found that a majority of the cell lines resistant to UDCA-induced growth arrest were also resistant to DCA-induced apoptosis, implying an overlap in DCA and UDCA mediated signaling. Moreover, the cell lines which were the most resistant to DCA-induced apoptosis also exhibited a greater capacity for anchorage independent growth. CONCLUSION: We conclude that UDCA and DCA have overlapping signaling activities and that disregulation of these pathways can lead to a more advanced neoplastic phenotype
Analyzing the regulation of metabolic pathways in human breast cancer
<p>Abstract</p> <p>Background</p> <p>Tumor therapy mainly attacks the metabolism to interfere the tumor's anabolism and signaling of proliferative second messengers. However, the metabolic demands of different cancers are very heterogeneous and depend on their origin of tissue, age, gender and other clinical parameters. We investigated tumor specific regulation in the metabolism of breast cancer.</p> <p>Methods</p> <p>For this, we mapped gene expression data from microarrays onto the corresponding enzymes and their metabolic reaction network. We used Haar Wavelet transforms on optimally arranged grid representations of metabolic pathways as a pattern recognition method to detect orchestrated regulation of neighboring enzymes in the network. Significant combined expression patterns were used to select metabolic pathways showing shifted regulation of the aggressive tumors.</p> <p>Results</p> <p>Besides up-regulation for energy production and nucleotide anabolism, we found an interesting cellular switch in the interplay of biosynthesis of steroids and bile acids. The biosynthesis of steroids was up-regulated for estrogen synthesis which is needed for proliferative signaling in breast cancer. In turn, the decomposition of steroid precursors was blocked by down-regulation of the bile acid pathway.</p> <p>Conclusion</p> <p>We applied an intelligent pattern recognition method for analyzing the regulation of metabolism and elucidated substantial regulation of human breast cancer at the interplay of cholesterol biosynthesis and bile acid metabolism pointing to specific breast cancer treatment.</p
Aberrant crypt foci in colorectal carcinogenesis. Cell and crypt dynamics
Aberrant crypt foci (ACF) have been identified on the colonic mucosal surface of rodents treated with colon carcinogens and of humans after methylene-blue staining and observation under a light microscope. Several lines of evidence strongly suggest that ACF with certain morphological, histological, cell kinetics, and genetic features are precursor lesions of colon cancer both in rodents and in humans. Thus, ACF represent the earliest step in colorectal carcinogenesis. This paper has the main purpose of reviewing the evidence supporting this view, with particular emphasis on cell and crypt dynamics in ACF. ACF have been used as intermediate biomarkers of cancer development in animal studies aimed at the identification of colon carcinogens and chemopreventive agents. Recently, evidence has also shown that ACF can be effectively employed in chemopreventive studies also in humans
Understanding renal posttransplantation anemia in the pediatric population
Advances in renal transplantation management have proven to be beneficial in improving graft and patient survival. One of the properties of a well-functioning renal allograft is the secretion of adequate amounts of the hormone erythropoietin to stimulate erythropoiesis. Posttransplantation anemia (PTA) may occur at any point in time following transplantation, and the cause is multifactoral. Much of our understanding of PTA is based on studies of adult transplant recipients. The limited number of studies that have been reported on pediatric renal transplant patients appear to indicate that PTA is prevalent in this patient population. Erythropoietin deficiency or resistance is commonly associated with iron deficiency. An understanding of the risk factors, pathophysiology and management of PTA in the pediatric renal transplant population may provide guidelines for clinicians and researchers in the pursuit of larger prospective randomized control studies aimed at improving our limited knowledge of PTA. Recognition of PTA through regular screening and evaluation of the multiple factors that may contribute to its development are recommended after transplantation
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Retinoids and carotenoids in the prevention of oral cancer: a critical appraisal.
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Retinoids and carotenoids in the prevention of oral cancer: a critical appraisal.
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Retinoids as potential chemopreventive agents in squamous cell carcinoma of the head and neck.
Although newer combined modality approaches, including neoadjuvant cytotoxic chemotherapy, for patients with squamous cell carcinoma (SCCA) of the head and neck have produced high initial complete response rates, they have not improved overall survival for patients with advanced disease. Vitamin A plays an essential role in the normal differentiation of epithelial tissues. Retinoids, analogs of vitamin A, are active in certain premalignant and malignant disorders including SCCA. Six studies, including one recently reported placebo-controlled randomized trial, have demonstrated the efficacy of retinoids in oral leukoplakia. Two studies (totalling 48 patients) have shown significant retinoid activity (67% overall complete response rate) in patients with aggressive, recurrent laryngeal papillomatosis. Two trials (including a randomized phase II trial) of isotretinoin in advanced, refractory SCCA of the head and neck have produced an objective response rate of 16%, which is comparable to that reported in single-agent studies with cytotoxic drugs. There is a need for further study of retinoids in head and neck cancer. The high initial response rates with current therapy and the high subsequent risks of local recurrence and of developing second primary tumors in head and neck cancer patients offer an excellent opportunity to investigate the use of retinoids as adjuvant therapy for this malignancy
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Retinoids as potential chemopreventive agents in squamous cell carcinoma of the head and neck.
Although newer combined modality approaches, including neoadjuvant cytotoxic chemotherapy, for patients with squamous cell carcinoma (SCCA) of the head and neck have produced high initial complete response rates, they have not improved overall survival for patients with advanced disease. Vitamin A plays an essential role in the normal differentiation of epithelial tissues. Retinoids, analogs of vitamin A, are active in certain premalignant and malignant disorders including SCCA. Six studies, including one recently reported placebo-controlled randomized trial, have demonstrated the efficacy of retinoids in oral leukoplakia. Two studies (totalling 48 patients) have shown significant retinoid activity (67% overall complete response rate) in patients with aggressive, recurrent laryngeal papillomatosis. Two trials (including a randomized phase II trial) of isotretinoin in advanced, refractory SCCA of the head and neck have produced an objective response rate of 16%, which is comparable to that reported in single-agent studies with cytotoxic drugs. There is a need for further study of retinoids in head and neck cancer. The high initial response rates with current therapy and the high subsequent risks of local recurrence and of developing second primary tumors in head and neck cancer patients offer an excellent opportunity to investigate the use of retinoids as adjuvant therapy for this malignancy
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