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 is the most common and most lethal primary brain tumor. While small progress has been made in treating this cancer in recent years, glioblastoma remains largely resistant to all existing therapies. It has been hoped that dissection of the genetics of this cancer would lead to more targeted and effective treatments, and new advances may finally be bringing this closer to fruition. Within the last few years, high-throughput efforts such as The Cancer Genome Atlas and a massive sequencing project have yielded novel insights and classifications of this dreaded cancer. The likely impact on care delivery in the clinic may only be a few years away. The rapid and exciting pace of advances in glioblastoma genetics has prompted this up-to-date review. ... Read more

Abstract: Increasing evidence suggests an important role for programmed cell death (PCD) pathways in aging phenotypes across species. PCD is critical to the homeostasis of tissues maintained by cell division, for example, the blood and the lining of the gut. During aging, accumulated cellular damage and non-optimal systemic signaling can cause too little cell death (hyperproliferation and cancer), or too much cell death (tissue atrophy and ectopic cell death), thereby limiting tissue function and life span. For these reasons PCD pathways are promising targets for interventions in aging and aging-related diseases: reactivation of PCD may be beneficial in clearing cancerous and senescent cells, whereas inhibiting PCD may help prevent muscle atrophy and nervous system degeneration. ... Read more

Abstract: Early detection of colorectal tumors through the identification of mutant DNA in serum or plasma could have a substantial impact on morbidity and mortality. Somatic mutations are specific biomarkers for neoplastic cells, but their detection requires sensitive assays, as the number of circulating mutant molecules is small compared to the number of normal DNA molecules. A newly developed method can provide this sensitivity and at the same time precisely quantify the fraction of mutant molecules present in the clinical sample. Using this technology, it has been found that more than half of patients with early stage disease contain mutant DNA in their circulation. ... Read more

Abstract: As with many other molecular agents that are involved in multiple aspects of cellular processes, E2F1 plays a dual role of cellular proliferation and apoptosis. How to take advantage of the apoptosis induction and sensitization properties of E2F1 for therapeutic purposes while minimizing its other properties has a significant bearing on how to turn a functionally complex molecule such as E2F1 into a drug target. ... Read more

Abstract: Apoptosis is a ubiquitous, highly coordinated process of self-destruction. Conventional cancer therapeutic agents can cause, to a certain degree, apoptosis of cancer cells. However, they do so in an indiscriminate manner leading to unacceptable side effects. Strategies of selectively activating apoptosis of cancer cells are described. ... Read more

Abstract: Stress influences the neuroendocrine dynamics and increases the release of glucocorticoids and catecholamines (such as norepinephrine and epinephrine). These hormones suppress the immune system. Stress doesn't by itself cause cancer. However it can alter the cancer cell growth dynamics in cancer's favor. ... 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

Abstract: HMGB1, the high mobility group box 1 protein, is a busy molecule. In the nucleus, it bends DNA and regulates various biochemical transactions. Outside cells, it is a potent signal of inflammation that sets the innate immune system on a fast-track response to injury and inflammation. ... Read more

Abstract: Colorectal cancer causes 492,000 deaths worldwide each year. The long transformation and asymptomatic period makes it amenable to early screening and preventive measures. Cells in the stools shed by intestinal mucosa are the ideal source of DNA for genetic screening of cancer genes and cancer stages. ... Read more