Abstract: The dynamic and multiple functions of p53, together with its involvement in the most common non-infectious diseases, underscore the need to elucidate the complexity of the p53 regulatory networks. Pathological conditions such as cancer, neurodegeneration, ischemia, cholestasis, and atherosclerosis are all strongly associated with deregulated levels of apoptosis in which p53 dysfunction has a prominent role. We will highlight recent developments of p53-induced apoptosis in human diseases, with a focus on modulation of liver cell apoptosis. In addition, we will discuss controversies arising from widespread p53 activation as a therapeutic approach to cancer. Recent studies have provided relevant and unprecedented information about mechanistic antiapoptotic functions of the endogenous bile acid, ursodeoxycholic acid (UDCA), suggesting that the finely tuned, complex control of p53 by Mdm-2 (mouse double minute-2, an oncoprotein) is a key step in UDCA modulation of p53-triggered apoptosis. We will also review recent therapeutic strategies and clinical applications of targeted agents, their safety, and efficacy, with particular emphasis on potential benefits of UDCA. ... Read more

Abstract: Glioblastoma multiforme is the most aggressive fatal brain tumor with a median survival of about a year after diagnosis. The current available treatment options only marginally improve patient outcome. The complexity and heterogeneity of the disease pose an extensive challenge to the development of novel therapeutic agents. Through molecular and genetic profiling, it has been possible to both identify mechanisms of disease progression and its therapeutic resistance. This paper highlights the significance of these advances. ... Read more

Abstract: With the human genome sequence at hand, it is now possible to sequence coding regions of cancer cell genomes to identify the mutated genes that drive tumor formation. The clinical importance of breast and colorectal cancer, together causing 14% of yearly cancer deaths, make these two tumor types suitable initial candidates for cancer genome sequencing. We recently surveyed more than half of the known human genes for somatic mutations in eleven breast and eleven colorectal cancers, and defined 122 and 69 genes, respectively, as candidate cancer genes in these two diseases. The study design provides a blueprint for future cancer genome sequencing efforts, validated by its ability to detect known and novel cancer genes. The findings shed light on heterogeneity between and within tumor types and provide novel research avenues for cancer biology. ... Read more

Abstract: Some chemicals have been known as carcinogens. Today, many more chemicals have been shown to be carcinogens with many of them being precarcinogens, which are bioactivated through enzymatic conversion into active carcinogens. Cellular pathways targeted by chemical carcinogens and the molecular specificities of these carcinogens are discussed. ... Read more