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Target Validation Using RNA Interference in Solid Tumors

Reverse genetics is one strategy that is currently used to establish a link between a target gene and a disease phenotype. In this process, the function of a gene is inhibited and the consequence of its loss on a desired biological function, such as tumor growth and metastasis, is monitored. RNA interfe ...

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Validation of Telomerase and Survivin as Anticancer Therapeutic Targets Using Ribozymes and Small-Interfering RNAs

In recent years expanding knowledge about basic biology and a detailed understanding of the molecular pathways involved in tumor cell growth and progression have allowed the identification of numerous genes as potential therapeutic targets. Studies in which the expression of these ...

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Collagen-Induced Arthritis in Mice: A Major Role for Tumor Necrosis Factor-

Collagen-induced arthritis is the most widely used animal model for the evaluation of novel therapeutic strategies for rheumatoid arthritis. The disease is induced by immunization of genetically susceptible strains of mice or rats with type II collagen in adjuvant. Susceptibility ...

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Novel Opportunities for Therapeutic Targeting in Systemic Autoimmune Diseases

Systemic autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis, continue to cause significant morbidity in affected persons. In the past few years, significant progress was made in understanding their pathogenesis and the underlying molecular me ...

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Regulatory RNAs: Future Perspectives in Diagnosis, Prognosis, and Individualized Therapy

With potentially up to 1000 microRNAs (miRNAs) present in the human genome, altogether regulating the expression of thousands of genes, one can anticipate that miRNAs will play a significant role in health and disease. Deregulated protein expression induced by a dysfunctional miRNA-b ...

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Considerations for Target Validation and Industrial Approaches

Target validation in health and disease integrates the modulation of a certain molecular target with an expected biological/biochemical/physiological or pathophysiological response or effect. The current state-of-the-art in target validation requires the interface of m ...

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Druggable Signaling Proteins

In normal cells, signaling pathways are tightly regulated. However, when they are aberrantly activated, certain pathways are capable of causing diseases. In many tumors, the aberrantly activated signaling proteins include members of the epidermal growth factor receptor family, t ...

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Treatment Options and Individualized Medicine

Although several drug targets are identified, current strategies in therapy do not take into account that patients vary in their response to drugs, both with respect to efficacy and toxic side effects. Whereas both clinical and histopathologic predictors of prognosis are established in ...

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DNA Methylation and Histone Modifications in Patients With Cancer: Potential Prognostic and Therapeutic Targets

Epigenetics, a combination of DNA modifications, chromatin organization, and variations in its associated proteins, configure a new entity that regulates gene expression throughout methylation, acetylation, and chromatin remodeling. In addition to silencing as a result of mu ...

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Adult Neural Stem/Progenitor Cells in the Forebrain: Implications for Psychostimulant Dependence and Medication

The question as to what exactly a stem cell is has remained contentious even after nearly three decades of debate. The prevailing view is that stem cells are cells with the capacity for unlimited or prolonged self-renewal that can produce at least one type of highly differentiated descendant. Usu ...

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Neuroprotective Effect of Naloxone in Inflammation-Mediated Dopaminergic Neurodegeneration: Dissociation from the Involvement of Opioid Receptors

Historically, the nociceptive/analgesic effect of naturally occurring opiates such as morphine has long been recognized by humans. Advances in research in the last several decades have revealed the existence of the so-called endogenous opioid peptides, can be divided into three cla ...

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Neuropharmacology and Neurotoxicity of 3,4-Methylenedioxymethamphetamine

With the continuing and increasing popularity of the amphetamine analog 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) as a drug of abuse, concern also has increased regarding the long-term psychological and neurochemical effects of this drug. The acute psychological ef ...

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Learning and Memory Mechanisms Involved in Compulsive Drug Use and Relapse

Chronic drug abuse is a complex behavioral and social phenomenon, that stems from a diverse set of underlying neural mechanisms. However, two defining features of drug addiction make it especially difficult to treat. First, addiction is compulsive—individuals often continue or resume ...

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From Drugs of Abuse to Parkinsonism: The MPTP Mouse Model of Parkinsons Disease

It began with a single case of drug abuse in Maryland (1), followed by four reported cases in California (2) in which young heroin addicts self-injected homemade “synthetic heroin” analogs contaminated with an impure chemical byproduct, 1-methyl-4-phenyl-1,2,3,6-tetrahydroperidi ...

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Analysis of mRNA Expression Using Double In Situ Hybridization Labeling with Isotopic and Nonisotopic Probes

A large number of in vivo studies in the last decade have confirmed that abused drugs are able to up-regulate gene expression in striatal neurons. For example, acute or chronic exposures to psychostimulants, cocaine and amphetamine, increased basal levels of mRNA and protein products of imme ...

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Quantification of mRNA in Neuronal Tissue by Northern Analysis

RNA is transcribed in the cell nucleus from a DNA template with ribonucleotides as the building blocks. As RNA is transported out of the nucleus, it is spliced; that is, predetermined sequences (introns) are cut out of the transcript. If certain introns serve as either exons or introns, “alternative ...

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Analysis of Gene Expression in Striatal Tissue by Multiprobe RNase Protection Assay

Studies of RNA expression within the central nervous system (CNS) have contributed significantly to increased understanding of both the acute and long-term neurological effects of drugs of abuse. Before beginning such an investigation, however, one must first determine the method of ...

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Semiquantitative Real-Time PCR for Analysis of mRNA Levels

The reverse transcription-polymerase chain reaction (RT-PCR) has become a standard tool in gene expression analysis studies (1,2). Starting with a very small amount of material (usually total RNA), the investigator is able to copy the RNA by reverse transcription (RT) to produce single-st ...

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Analysis of mRNA Expression in Striatal Tissue by Differential Display Polymerase Chain Reaction

Differential display polymerase chain reaction (DDPCR) is a technique that allows comparisons between the expressed mRNA population in two or more tissues, or in the same tissue under two or more different conditions. For example, it has been used to discover striatal genes whose expression ...

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Application of TaqMan RT-PCR for Real-Time Semiquantitative Analysis of Gene Expression in the Striatum

TaqMan reverse transcription-polymerase chain reaction (TaqMan RT-PCR) is a recently developed technique (1) that has been used to study gene expression in tissues of the central nervous system (CNS) including the striatum. For example, TaqMan has been used to profile mRNA distribution ...

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