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丁香实验推荐阅读
The Temporal Sequence of Changes in Gene Expression by Drugs of Abuse

Addiction is a complex maladaptive behavior produced by repeated exposure to rewarding stimuli (1). There are two primary features of addiction to all forms of natural and pharmacological stimuli. First, the rewarding stimulus associated with the addiction is a compelling motivator of ...

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Transgenic Animal Models in Biomedical Research

Transgenic animals have become a key tool in functional genomics to generate models for human diseases and validate new drugs. Transgenesis includes the addition of foreign genetic information to animals and specific inhibition of endogenous gene expression. Recently, animal mod ...

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Keratin Transgenic and Knockout Mice: Functional Analysis and Validation of Disease-Causing Mutations

Summary The intermediate filament (IF) cytoskeleton of mammalian epithelia is generated from pairs of type I and type II keratins that are encoded by two large gene families, made up of 54 genes in humans and the mouse. These genes are expressed in a spatiotemporal and tissue-specific manner from the ...

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The HUVEC/Matrigel Assay: An In Vivo Assay of Human Angiogenesis Suitable for Drug Validation

The future ability to manipulate the growth of new blood vessels (angiogenesis) holds great promise for treating ischemic disease and cancer. Several models of human in vivo angiogenesis have been described, but they seem to depend on transgenic support and have not been validated in a therap ...

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A Murine Model for Studying Hematopoiesis and Immunity in Heart Failure

Recent epidemiological research indicates that a coexistent anemia among patients with heart failure might worsen their prognosis. However, whether the reduced synthesis of red blood cells is a contributing factor to the development and progression to overt heart failure, or wheth ...

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An Overview of the Immune System and Technical Advances in Tumor Antigen Discovery and Validation

The ability of the immune system to distinguish between self- and nonself antigens is controlled by mechanisms of central and peripheral tolerance. Although the induction and maintenance of tolerance is important for preventing autoimmunity, breaking self-tolerance is a crucial c ...

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Potential Target Antigens for Immunotherapy Identified by Serological Expression Cloning (SEREX)

Immunotherapy in cancer relies on the identification and characterization of potential target antigens that can be recognized by effector cells of the immune system. Several strategies have been developed to identify such antigens, which then can be used for immunization strategie ...

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Protein Arrays: A Versatile Toolbox for Target Identification and Monitoring of Patient Immune Responses

Functional proteomics is a promising technique for the rational identification of novel therapeutic targets and biological markers. The studies of protein-protein interactions have been gained from the development of high-throughput technologies such as the yeast two-hybr ...

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Identification of Tumor Antigens by Using Proteomics

The recent progress of proteomics has opened new avenues for tumor-associated antigen discovery. Here, I describe a two-dimensional (2D), gel-based Western blot approach for screening and identification of proteins eliciting a humoral response in cancer. Sera from patients are used in ...

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Main Approaches to Target Discovery and Validation

The identification and validation of disease-causing target genes is an essential first step in drug discovery and development. Genomics and proteomics technologies have already begun to uncover novel functional pathways and therapeutic targets in several human diseases such as ...

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Analysis of Gene Networks for Drug Target Discovery and Validation

Understanding responses of the cellular system for a dosing molecule is one of the most important problems in pharmacogenomics. In this chapter, we describe computational methods for identifying and validating drug target genes based on the gene networks estimated from microarray ge ...

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Bioinformatics Approaches to Cancer Gene Discovery

The Cancer Gene Anatomy Project (CGAP) database of the National Cancer Institute has thousands of known and novel expressed sequence tags (ESTs). These ESTs, derived from diverse normal and tumor cDNA libraries, offer an attractive starting point for cancer gene discovery. Data-mining t ...

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Target Discovery and Validation in Pancreatic Cancer

Pancreatic cancer is a lethal disease and rational strategies fo gene expression, and mass spectrometric analysis of proteins, have led to identification of cellular targets with considerable potential for clinical application and patient care. These studies underscore the imp ...

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Molecular Classification of Breast Tumors: Toward Improved Diagnostics and Treatments

Recent advances in gene expression profiling and other “omics” technologies have revolutionized cancer research and hold the potential of also revolutionizing clinical practice. These high-throughout approaches have radically changed our ability to study cells and tissues ...

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Discovery of Differentially Expressed Genes: Technical Considerations

Identification and characterization of differentially expressed genes may be an important first step toward the understanding of both normal physiology and disease. A multitude of techniques belonging to two main categories have been developed to identify the differences in gene ...

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Genome-Wide Screening by Using Small-Interfering RNA-Expression Libraries

RNA interference (RNAi) is an evolutionarily conserved phenomenon in which gene expression is silenced by double-stranded RNA (dsRNA) in a sequence-specific manner. This technology has the potential to affect all aspects of target discovery and validation. With the completion of the h ...

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Production of siRNA and cDNA-Transfected Cell Arrays on Noncoated Chambered Coverglass for High-Content Screening Microscopy in Living Cells

In this chapter, we provide a protocol for the production of transfected cell arrays in living mammalian cells on noncoated chambered coverglass for the systematic functional analyses of human genes by high-content screening microscopy. This method should facilitate drug target va ...

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Hammerhead Ribozyme-Based Target Discovery

With the accumulation of vast amounts of data as a result of the sequencing of the human genome, it is necessary to identify human genes that are involved in various cellular, developmental, and disease-related processes and to clarify their functions and potential utility as targets in the trea ...

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Suppression of Apoptosis in the Liver by Systemic and Local Delivery of Small-Interfering RNAs

RNA interference (RNAi) is a sequence-specific gene-silencing mechanism triggered by double-stranded RNA. RNAi was shown to allow transient or stable knockdown of gene expression in a broad range of species and has been used successfully for functional genomic screens in mammalian ce ...

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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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