Endotoxin/lipopolysaccharide (LPS) is the major mediator that triggers the cellular and humoral responses of the shock induced by Gram-negative bacteria. The toxic responses of LPS are mediated by various factors and mainly by tumor necrosis factor α (TNFα). To study the role of TNF and to iden ...
This chapter describes the methods for measuring the increase in vascular permeability induced by tumor necrosis factor α (TNFα), or other mediators, in vivo in animal models. Mouse liver or kidney are perfused through the portal vein or the renal artery, respectively, by intravascular inje ...
Tumor necrosis factor α (TNFα) is a crucial mediator involved in the communications between immune and nervous systems in physiological conditions, and its relevance is amplified during disease. Considered originally detrimental and a target for therapeutic intervention, rece ...
Tumor necrosis factor (TNF) is a pleiotropic cytokine that signals inflammation as well as cell death. We focus herein on the inflammatory pathway, giving particular emphasis to the in vitro methods used to study intracellular signaling mediators. The signal transduction cascade that T ...
We describe a semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) technique for the quantification of the messenger RNA of human and murine tumor necrosis factor α (TNFα) and related receptors. This protocol can be adapted for blood, peripheral blood lymphoc ...
Central to the tumor suppressor activity of certain proteins is the ability to interact physically with DNA. A well-studied example of this is the tumor suppressor p53 (1,2). The p53 protein has been implicated in several diverse growth-related pathways, including apoptosis and cell cycle a ...
The field of diagnostics has gathered the first crop of the genetic insurgency in the identification of the genetic basis of common and uncommon hereditary diseases. Discoveries of genes that predispose to cancer have led to the development of genetic tests. In turn, genetic tests can provide i ...
The classic paper by Schmitz and Galas (1) established the usefulness of footprinting analysis for identifying protein-bound sites on DNA. The basis of the footprinting technique is that DNA-bound proteins protect the phosphodiester backbone of DNA from modification or cleavage by ex ...
Gene expression is controlled at several steps. Transcription is one of the important steps at which regulation occurs. Tumor suppressors such as p53, which are basically transcription factors, carry out their function primarily by the transcriptional activation of the target genes. ...
There has never been a more exciting time than the present for discovering anti-cancer drugs. The past decade has witnessed the nearly complete sequencing of the human genome, major advances in the multidisciplinary application of new genomic technologies, and the integration of combin ...
The human body is composed of approximately 1014 cells, each of which is capable of committing suicide by apoptosis. Normally, the processes of cell division and cell death are tightly coupled, so that no net increase in cell numbers occurs. However, alterations in the expression or function of the g ...
Although chemotherapeutic agents are a cornerstone of therapy in medical oncology, hormonal and differentiating therapies play an increasingly important role. There is no clear-cut margin between chemotherapy, hormonal, and differentiating modalities. Although chemot ...
Tumor hypoxia originates from the inability of neovasculature to provide an adequate blood supply to accommodate the metabolic demands of the tissue. Hypoxia is operationally defined as a spectrum of reduced levels of oxygen that result in the impairment of tissue function. The upper end of t ...
It has long been appreciated that dysregulation of apoptosis, or programmed cell death, plays a critical role in the onset and progression of cancer (1). For the complexity of cell death pathways, this may result from deregulated overexpression of apoptosis inhibitors or loss/underrepre ...
The transcription factor nuclear factor-κB (NF-κB) has been demonstrated to control cellular proliferation and oncogenesis. Consistent with this, NF-κB activity is stimulated by various mitogenic stimuli and by the action of numerous oncoproteins. This role of NF-κB in controlling ...
A continuous supply of biochemical energy is required in order for cells to perform their physiologic functions as well as maintain their own homeostasis. Cellular energy is determined largely by the ratio of intracellular ATP to ADP. A high ratio of ATP/ADP is produced primarily by the oxidati ...
The development of anticancer drugs has relied primarily on two traditional approaches. Synthetic or natural compounds are routinely screened for anticancer activities using a cell-based assay. The National Cancer Institute (NCI) has relied on a panel of human tumor cell lines to search ...
The preceding chapters in these two volumes on tumor suppressor genes (TSG) are a comprehensive compilation of what is currently known about the structure, function, activation, and regulation of TSGs, along with the roles they play in the myriad biochemical pathways that network to result in ...
p53 is a key mediator of cell response to a variety of stresses, inducing growth arrest or apoptosis, thereby eliminating damaged and potentially dangerous cells from the organism (1,2). Once p53-dependent mechanisms are broken, conditions for rapid accumulation of genetic changes are e ...
Angiogenesis, the growth of new capillary blood vessels from preexisting vessels, is a fundamental process that is required for a wide variety of physiologic and pathophysiologic processes (1,2). Examples of physiologic processes that require angiogenesis include wound healing, ...