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Free radicals are ubiquitous in our body and are generated by normal physiological processes, including aerobic metabolism and inflammatory responses, to eliminate invading pathogenic microorganisms. Because free radicals can also inflict cellular damage, several defences have evolved both to protect our cells from radicals--such as antioxidant scavengers(More)
p53-mediated apoptosis may involve the induction of redox-controlling genes, resulting in the production of reactive oxygen species. Microarray expression analysis of doxorubicin exposed, related human lymphoblasts, p53 wild-type (WT) Tk6, and p53 mutant WTK1 identified the p53-dependent up-regulation of manganese superoxide dismutase (MnSOD) and(More)
Resveratrol (trans-3,5,4'-trihydroxystilbene), a polyphenolic compound found in plant products, including red grapes, exhibits anticancer, antioxidant, and anti-inflammatory properties. Using an animal model of multiple sclerosis (MS), we investigated the use of resveratrol for the treatment of autoimmune diseases. We observed that resveratrol treatment(More)
Primary hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. However, the viral-chemical etiology as well as molecular mechanisms of HCC pathogenesis remains largely unknown. Recent studies in our laboratory have identified several potential factors that may contribute to the pathogenesis of HCC. Oxidative stress and chronic(More)
The relative effects of postmenopausal hormone replacement therapy (HRT) with estrogen alone vs. estrogen+progestin on breast cell proliferation and on breast cancer risk are controversial. A cross-sectional observational study was carried out to examine the proliferative effects of HRT with estrogen or estrogen plus the progestin, medroxyprogesterone(More)
Nitric oxide (NO) is a key molecule involved in many physiological functions. However, evidence is accumulating that sustained high levels of NO over extended periods of time contribute to carcinogenesis. This article reviews recent data and outlines a dual role of NO in animal carcinogenesis. Following an inhibition of NO production, some studies find a(More)
NO produced in tumors can either positively or negatively regulate growth. To examine this dichotomy, effects of NO concentration and duration on the posttranslational regulation of several key proteins were examined in human breast MCF7 cells under aerobic conditions. We found that different concentration thresholds of NO appear to elicit a discrete set of(More)
Patients with chronic inflammatory bowel disease have a high risk of colon cancer. The molecules that initiate and promote colon cancer and the cancer pathways altered remain undefined. Here, using in vitro models and a mouse model of colitis, we show that nitric oxide (NO) species induce retinoblastoma protein (pRb) hyperphosphorylation and inactivation,(More)
The role of NF-κB activation in tumor initiation has not been thoroughly investigated. We generated Ikkβ(EE)(IEC) transgenic mice expressing constitutively active IκB kinase β (IKKβ) in intestinal epithelial cells (IECs). Despite absence of destructive colonic inflammation, Ikkβ(EE)(IEC) mice developed intestinal tumors after a long latency. However, when(More)
The p53 tumor suppressor gene is mutated in about half of all human cancer cases. The p53 protein modulates multiple cellular functions, such as gene transcription, DNA synthesis and repair, cell cycle arrest, senescence, and apoptosis. Mutations in the p53 gene can abrogate these functions and may lead to genetic instability and progress to cancer. The(More)