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UT scientist studying new test to predict outcomes for lung cancer patients |
| By
Jim Winkler |
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Oct 2, 2008
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Scientists have been using polymerase chain reaction (PCR) for more than 20 years to analyze DNA, the famous twisted double strand of molecules that programs human cells and encodes genes.
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| Erin Crawford, biomedical research assistant, and Dr. James Willey, the George Isaac Professor for Cancer Research and professor of medicine, analyzed some research data. |
A technique that multiplies genetic material into usable amounts, PCR has revolutionized modern research, medicine and forensics and stands as the most important piece of technology to enter the biomedical laboratory in the 20th century.
Now a UT College of Medicine researcher has joined scientists from two biotechnology firms to test a new technology that holds the promise of making the analysis of genes simpler, cheaper and more effective.
With a $249,250 grant from the National Cancer Institute, Dr. James Willey, the George Isaac Professor for Cancer Research and a professor of medicine, and researchers from Biotrove Inc., a Woburn, Mass., nanofluidics company, and Gene Express Inc. of Wilmington, N.C., are testing the benefits of combining technology developed by Biotrove with technology developed by Willey and now licensed to Gene Express.
Biotrove has developed a highly innovative PCR device that uses nanolevel amounts of genetic, genomic, biochemical and cellular samples, permitting scientists to reduce by 1,000 times the cost and sample consumption required for PCR analysis.
The Gene Express technology, called StaRT-PCR, features a powerful set of quality-control standards for each gene that verifies the accuracy and reliability of PCR assay data.
Biotrove’s device is a wafer-sized metal chip that manipulates fluids through very tiny channels and reservoirs to reduce the quantity of a bodily fluid required for a test down to a miniscule amount. Tiny, laser-drilled holes in the chip allow fluid — whole blood, serum, tissue extracts, even cell culture medium with cells in it — to flow through channels that can be modified in numerous ways to accomplish various bioanalytical tasks.
The foundation for Gene Express, which was incorporated in 1992, came from Willey’s research at the former MCO and at the University of Rochester.
Willey said the time and expense required to produce large amounts of biological material, such as proteins or enzymes for drug screening, is a major reason for the interest in microfluidic PCR technology like Biotrove’s. By reducing the amount of material needed, companies can reduce the overhead costs of developing drugs and diagnostic tests, potentially gaining speed as well.
In addition to demonstrating the feasibility and advantages of merging the two technologies, the project is aimed at developing a test to help clinicians better determine the prognosis of patients with lung cancer and to eventually help provide targeted therapies for the hard-to-treat disease that is the world’s top cancer killer. About 175,000 new cases and 162,000 deaths from it annually occur in the United States.
The test would be highly sensitive and accurate, need only a small amount of DNA, cost far less than existing methods, and produce results that would be identical in different laboratories and in the hands of different scientists.
“The goal is not only to bring these two technologies together, but also to develop a diagnostic test for predicting outcomes of lung cancer,” explained Willey, whose research interest is lung cancer and who has been interested for some 25 years in determining the genetic characteristics that cause some people to be predisposed to cancer, why some cancers respond to a particular treatment and other cancers don’t, and why some cancers grow faster and metastasize earlier than others.
He began measuring gene expression in the 1990s by testing classes of genes involved in the development of cancer with the aim of trying to determine the difference between a healthy cell and one with cancer and what genes are turned off in the cancer cell, but turned on in the normal cell.
To conduct the research, Willey and his lab associate, Erin Crawford, will design and prepare the StaRT-PCR control materials for 16 genes that are predictive for lung tumors.
The combined Biotrove and Gene Express technology, which will require approximately 1,000 times less material, including DNA sample and PCR reaction materials, will then be compared for accuracy and reliability with the current, less sophisticated PCR technology. Gene expression profiles of seven lung tumor tissue samples will be performed at three different labs to see if the new technology reduces variable test results.
“Currently, the potential for using expression signatures for cancer prognosis and treatment is hampered by lack of readily deployable tests with the accuracy, low RNA requirement and inter-site concordance required for routine clinical use,” Willey said. “We are proposing an innovative solution based on two well-validated PCR techniques whose combination uniquely addresses the problem of diagnostic assay reproducibility.”
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