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Folic acid (M r = 441, Fig. 1) is a vitamin essential for de novo nucleotide synthesis and one-carbon metabolism. The ability to acquire folate, therefore, is important to the viability of proliferating cells.

Selective cytotoxicity is an important goal of specific drug targeting. Toward this end, toxins isolated primarily from higher plants and bacteria have been coupled to monoclonal antibodies (MAbs) and evaluated for their clinical efficacy in cancer, AIDS, and immunological diseas ...

Specific targeting of radioisotopes or toxic drugs to tumors for cancer detection and treatment is an enticing but elusive goal. It has proved difficult to achieve adequate concentration ratios between tumor and normal tissues to improve on standard diagnostic and therapeutic metho ...

The huge molecular radius of immunoglobulins would seem to be a major drawback for the targeting of solid tumors, because of slow extravasation into tumor interstitium and along plasma half-life. The permeability of normal continuous capillary endothelia to intravascular solutes of ...

Research into the treatment of cancer has often been driven by the idea that a common biochemical pathway might exist in all tumors, providing an ideal target for therapy. However, it is now clear that a great variety of genetic changes contributes to the development of individual cancers, and that no t ...

Recombinant toxins are cytotoxic proteins that are encoded by DNA sequences that can be expressed in prokaryotic or eukaryotic cells. The proteins contain both a ligand, for binding to cells, and a toxin, for killing the cells. In recombinant toxins the connection between the toxin and ligand is e ...

This chapter will describe methods that may be used to deliver agents to HIV-infected cells. These materials may be used for therapeutic or experimental purposes. There are several general approaches to delivering compounds to human immunodeficiency cells (HIV)-infected cells. All c ...

Targeting pharmaceuticals to the infarcted myocardium has two primary objectives: the diagnostic imaging of the infarcted myocardium and the delivery of therapeutic agents to compromised myocardial areas. Various diagnostic and therapeutic agents (such as radiolabeled co ...

Hydrogen peroxide formed in the lung tissue in ischemia/reperfusion or released from activated leukocytes causes oxidative injury of the vascular endothelial cells (1–3). H2O2-degrading enzyme, catalase, has been extensively explored in order to protect cells and tissues again ...

Malaria is a serious public health problem that affects about 300-500 million people and claims 1.5-2.7 million deaths every year. One-third of all humans live in zones where they risk catching it (1). The situation is aggravated because the malarial parasites are rapidly developing resistan ...

The overall goal of gene therapy is to cure or stabilize a disease process that results from the production of a mutant protein (for example, the chloride channel protein important in cystic fibrosis) or overproduction of a normal protein (such as the products of certain oncogenes). We can achieve t ...

There is a need for new biomarkers to enable faster detection of adverse events due to drugs and disease processes. One would prefer biomarkers that are useful in multiple species (i.e., translational or bridging biomarkers) so that it would be possible to directly link responses between speci ...

Public consortia provide a forum for addressing questions requiring more resources than one organization alone could bring to bear and engaging many sectors of the scientific community. They are particular well suited for tackling some of the questions encountered in the field of toxic ...

The field of toxicogenomics has been advancing during the past decade or so since its origin. Most pharmaceutical companies are using it in one or more ways to improve their productivity and supplement their classic toxicology studies. Acceptance of toxicogenomics will continue to grow as r ...

Genomics-based tools, such as microarrays, do appear to offer promise in evaluating the relevance of one species to another in terms of molecular and cellular response to a given treatment. However, to fulfill this promise the individual end points (i.e., the genes, proteins, or mRNAs) measured in ...

Autosomal recessive juvenile parkinsonism (AR-JP) is a familial levodoparesponsive parkinsonism resulting from Lewy body negative degeneration of nigral neurons in the zona compacta of the substantia nigra (1–4). The first proposal for a distinct clinical entity with recessiv ...

Parkinson’s disease (PD) is the most common neurodegenerative movement disorder (1). Neuropathologically, it is defined by nerve cell loss in the substantia nigra and the presence of Lewy bodies and Lewy neurites (2,3). In many cases, Lewy bodies are also found in the dorsal motor nucleus of the vag ...

Human α-synuclein was originally identified as the precursor of a peptide named non-Aβ component of Alzheimer’s disease (NAC) that was tightly associated to purified Alzheimer’s disease amyloid (1). Senile amyloid plaques consist predominantly of the 39-42 amino acid residue peptide ...

In the preceding chapter we described three paradigms by which we have studied programmed cell death in the substantia nigra (SN) of living animals: natural cell death and death induced either by developmental injury to the target striatum or by dopamine terminal destruction with the neurot ...

Apoptosis is a form of cell death in which genetically regulated programs intrinsic to the cell bring about its own demise. In recent years, there has been a tremendous growth of interest in apoptosis as a mechanism of disease in a wide range of human disorders including the neurodegenerative disea ...