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: The first descriptions of apoptosis were made over 150 years ago, although the implications for tumor development were not appreciated until the 1970s. Natural cell death is a critical part of development of multicellular organisms, and also counter-balances the cell generating effects of mitosis. Disruptions in the highly regulated apoptotic pathway can lead to disease, such as tumors, due to the accumulation of excessive numbers of cells. Restoring normal apoptosis in cancer cells is one of the current challenges of cancer research. ... 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: 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: In addition to the immune system, apoptosis plays a role in the nervous system. An excessive number of cells are generated during embryogenesis and only neurons that make the correct connections at the right time survive. But then, these surviving neurons do not divide and they need to make it through the entire life of the organism and cannot be replaced once they are dead. The control over death and survival is therefore vitally important. ... Read more

Abstract: Apoptosis, or programmed cell death, plays a key role in the development, execution, and maintenance of immune functions. The dynamics of survival of subsets of T lymphocytes with the backdrop of human aging is discussed. ... Read more

Abstract: Authors believe that cancer is primarily a disorder of cell death rather than cell growth. There is a consequence when cells don't die an apoptotic death. Cells release a bunch of hazardous molecules when they die by necrosis. A new theory describes that necrotic death and chronic inflammation may foster the onset and growth of tumors. ... Read more

Antisense technology is based on a simple and beautiful concept: a short stretch of DNA, whose sequence is complementary to a specific mRNA of interest, binds to the target and induces its degradation or blocks its expression. Since the first application of antisense DNA on Rous sarcoma virus expression in 1978, numerous DNA oligos have undergone clinical trials. In over two decades of developing this technology, scientists have accumulated a lot of valuable information.

In order to avoid degradation, antisense DNA oligos have to be modified to increase their stability (see table on next page). However, structural modifications of ... Read more

On April 29, 2002, Genta Inc. of Berkeley Heights, New Jersey signed an agreement with pharmaceutical giant Aventis (Strasbourg, France) to co-develop and co-market Genasense, a Genta drug that is currently in 3 separate phase III clinical trials. The deal calls for Aventis to pay up to $480 million in cash, equity and convertible debt to Genta that hinges on key development and regulatory milestones. In return, Aventis and Genta will co-market Genasense in US, while Aventis will have the exclusive rights for marketing in the rest of the globe.

Genasense is an antisense drug that works by blocking the production ... Read more

Programmed cell death, or apoptosis, is just as important as cell growth and division in maintaining homeostasis. Apoptosis is essential in eliminating the superfluous or damaged cells, particularly with respect to developmental biology and immunology. An ill-conceived cell death program could derail many biological pathways and lead to abnormalities such as cancer, autoimmune diseases, and neurodegenerative diseases.

Apoptosis can be triggered by normal developmental signals, physiological stress signals, or cell damage resulting from exposure to toxins, oxygen and other free radicals, or injury. Once the program has run its course, the cell’s DNA is broken into fragments and the ... Read more