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Tissue Microarrays: Current Status By Anil Sehgal Ph.D. With the cost of drug discovery and development increasing, there is critical need for tools and technologies that can reduce the cost or time length from discovery to marketing of a product. In the past decade, a large number of gene targets have been identified, and it is estimated that there are over 30,000 genes that may encode for over 100,000 proteins. With such a huge number of potential gene and protein targets being identified, the pharmaceutical industry is faced with the daunting task of filtering targets to pick the right ones for further development. Target validation is a critical step in sifting through such targets, allowing for identification of lead compounds for serious development consideration. In the past, target validation was done with static assays such as Northern blot analysis, RT-PCR, macroarray, microarray, and gene chips. With these technologies, even though the differential expression of specific genes can be evaluated, only rudimentary clinical information is obtained. In the majority of molecular biology techniques, tissue is homogenized to isolate the RNA for expression analysis. Furthermore, the tissue obtained is not made up of only the disease cell population. Such a tissue homogenate can contain normal cells, tumor cells, blood cells, muscle cells, and other cell types that may dilute and/or result in misleading information. In the majority of drug discovery cases, target validation is done by analyzing expression of genes and proteins in tissue samples. In the past, most target validation was done one tissue at a time on single slide section. Such studies require large amount of precious human tissue samples. With the inception of tissue microarray technology, it is now
possible to study the expression of a single gene target in hundreds of human
tumor or normal tissue samples. One of the shortcomings of the tissue microarray
technology is that only a small portion of the tissue section is represented.
Tissue microarray vendors are now picking tissue samples from multiple different
areas to overcome this problem. With hundreds of tissue samples from discovery
and clinical studies, the amount of information generated from tissue
microarrays is increasing at a fast pace. To overcome this problem, several
companies have developed devices, scanners, automated scanners, and software.
Pathologists in major hospitals and research centers are now utilizing several
tissue microanalysis instruments and software. One of the major bottlenecks that
has been realized in the past few years is the quantitative, efficient, and
specific analysis of the data generated from tissue microarrays. Extensive
progress has now been made in the analysis of tissue microarrays by several
vendors listed below (Table 1). Tissue microarray analysis can now be done based
on staining intensity, shape, as well as mitotic figures. Additional software is
also being developed to analyze expression of particular antigens on the cell
membrane. As the evolution of tissue microarray analysis and application takes
place, it will continue to make fruitful contributions in speeding and reducing
the cost of drug discovery and development.
Source: D&MD. This update was written by Anil Sehgal Ph.D., Freelance Writer, Dublin, CA. He may be contacted via e-mail at cancersci@hotmail.com. To view and purchase D&MD reports click here! |
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