Detecting the undetectable in prostate cancer screeningOctober 20, 2009New technology 300 times more sensitive than commercial tests, defines new PSA 'zero' A team of Northwestern University researchers, using an extremely sensitive tool based on nanotechnology, has detected previously undetectable levels of prostate-specific antigen (PSA) in patients who have undergone radical prostatectomy. The researchers found measureable PSA levels in each post-operative patient in its study, thanks to the power of the nanoparticle-based bio-barcode assay developed at Northwestern. The technology is 300 times more sensitive than commercially available PSA tests. After the removal of the prostate gland, patients typically have PSA levels that are undetectable when measured using conventional diagnostic tools. This ability to easily and quickly detect very low levels of PSA may enable doctors to diagnose men with prostate cancer recurrence years earlier than is currently possible. Prostate cancer is the second leading cause of cancer death for men in the United States. (Only lung cancer is more deadly.) "We have defined a new zero for PSA," said Chad A. Mirkin, George B. Rathmann Professor of Chemistry in the Weinberg College of Arts and Sciences, professor of medicine and professor of materials science and engineering. "This level of sensitivity in detecting low concentrations of PSA will take the blinders off the medical community, especially when it comes to tracking residual disease." The study will be published online during the week of Oct. 19 by the Proceedings of the National Academy of Sciences (PNAS). Mirkin and C. Shad Thaxton, M.D., assistant professor of urology in Northwestern's Feinberg School of Medicine, led the study. (Both are members of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.) "This new PSA assay may alter the management of patients who have been treated with surgery for prostate cancer," said William J. Catalona, M.D., professor of urology at the Feinberg School and director of the Clinical Prostate Cancer Program at the Lurie Cancer Center. He was the first to demonstrate that the PSA test, a simple blood test, could be used as a screening tool for prostate cancer. "Studies have shown that postoperative radiation therapy given early to patients with adverse pathology, called adjuvant radiation, reduces the recurrence rate and improves survival," Catalona said. "Because the 'nano-PSA assay' is more sensitive than the current commercially available PSA tests, it may allow physicians to target adjuvant radiation for patients destined to have a life-threatening tumor recurrence." The study is an early indicator of how nanotechnology can be used to improve medical diagnostics and early cancer detection. In the case of prostate cancer recurrence following primary surgical treatment, patients with detectable but non-rising PSA levels could be reassured that their cancer will not recur. This reassurance potentially could be delivered much earlier than with conventional diagnostic tools. For patients with increasing levels of PSA, detected before conventional tools are able, doctors could diagnose a recurrence and intervene accordingly. Furthermore, the effectiveness of post-operative treatment could be assessed by monitoring a patient's PSA levels. Tracking PSA levels early, before conventional tools are able, may allow doctors to validate treatments for recurrent cancer, such as radiation, hormone therapies and chemotherapies. The most effective will be able to keep down PSA levels. "The first route to a new therapeutic is a good diagnostic tool, and that's what we have here," said Mirkin, director of Northwestern's International Institute for Nanotechnology. "This bio-barcode assay, or a variant of it, could be a commercial tool in as little as 18 months. The technology is there. Now it's a business decision." PSA is a protein produced by the cells of the prostate gland and found in the bloodstream. This pilot study looked at serum samples from 18 post-prostatectomy patients collected over the course of a number of years. The researchers were able to reliably and accurately quantify PSA values at less than 0.1 nanograms per milliliter, the clinical limit of detection for commercial assays. The lower limit of detection for PSA using the bio-barcode assay is approximately 300 times lower than the lower limit of detection for commercial tests. The PSA measurements were used to classify the patients as either having no evidence of disease or having a relapse of disease. The Northwestern team is now conducting a similar retrospective study of 260 patients and eventually plans to do a large prospective study. The ultra-sensitive technology is based on gold nanoparticle probes, decorated with DNA and antibodies that can recognize and bind to PSA when present at extremely low levels in a blood sample. A magnetic microparticle, outfitted with a second antibody for PSA, also is used in the assay. When in solution, the antibody-functionalized particles "recognize" and bind to PSA, sandwiching the protein between the two particles. The key is that attached to each tiny gold nanoparticle (just 30 nanometers in diameter) are hundreds of identical strands of DNA. Mirkin calls this "bar-code DNA" because they have designed it as a label specific to the PSA target. After the "particle-protein-particle" sandwich is removed magnetically from solution, the DNA is removed from the sandwich and read using a Verigene® ID system, a nanotechnology platform designed to detect and quantify DNA. The amount of PSA present is calculated based on the amount of bar-code DNA. For each molecule of captured PSA, hundreds of DNA strands are released, which is one of the ways the PSA signal is amplified. The title of the PNAS paper is "The Nanoparticle-Based Bio-Barcode Assay Re-Defines 'Undetectable' PSA and Biochemical Recurrence Following Radical Prostatectomy." In addition to Mirkin and Thaxton, other authors of the paper are Robert Elghanian, Audrey D. Thomas, Savka I. Stoeva, Jae-Seung Lee, Norm D. Smith and Anthony J. Schaeffer of Northwestern, and Helmut Klocker, Wolfgang Horninger and Georg Bartsch of Innsbruck Medical University in Austria. Northwestern University |
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| Related Prostate Cancer Current Events and Prostate Cancer News Articles Common pain relief medication may encourage cancer growth Although morphine has been the gold-standard treatment for postoperative and chronic cancer pain for two centuries, a growing body of evidence is showing that opiate-based painkillers can stimulate the growth and spread of cancer cells. Young athletes need dual screening tests for heart defects, study suggests To best detect early signs of life-threatening heart defects in young athletes, screening programs should include both popular diagnostic tests, not just one of them, according to new research from heart experts at Johns Hopkins. Routine evaluation of prostate size not as effective in cancer screening, Mayo study finds New Mayo Clinic research studied the association between prostate-specific antigen (PSA) levels and prostate size and found that routine annual evaluation of prostate growth is not necessarily a predictor for the development of prostate cancer. Carnegie Mellon researchers link health-care debate to risk of dying in US and Europe The current health care debate in the United States is complicated. Trade-offs between heath care expenditures, lifestyle choices and life expectancy have been suggested but seldom clearly demonstrated. New finding suggests prostate biopsy is not always necessary Researchers at Wake Forest University School of Medicine and the University of Wisconsin-Madison have discovered that some elevated prostate-specific antigen (PSA) levels in men may be caused by a hormone normally occurring in the body, and are not necessarily a predictor of the need for a prostate biopsy. Does prostate-specific antigen velocity help in early detection prostate cancer? The November issue of European Urology, the official journal of the European Association of Urology, features an article focussing on prostate specific antigen (PSA) velocity and early cancer detection. It has been suggested that changes in PSA over time aid prostate cancer detection. New Synthetic Molecules Trigger Immune Response to HIV and Prostate Cancer Researchers at Yale University have developed synthetic molecules capable of enhancing the body's immune response to HIV and HIV-infected cells, as well as to prostate cancer cells. Their findings, published online in the Journal of the American Chemical Society, could lead to novel therapeutic approaches for these diseases. Chemo-radiation before prostate removal may prevent cancer recurrence Researchers in the Oregon Health & Science University Knight Cancer Institute and the Portland Veterans Affairs Medical Center have found a combination of radiation therapy and chemotherapy given before prostate removal is safe and may have the potential to reduce cancer recurrence and improve patient survival. Blood vessels might predict prostate cancer behavior A diagnosis of prostate cancer raises the question for patients and their physicians as to how the tumor will behave. Will it grow quickly and aggressively and require continuous treatment, or slowly, allowing therapy and its risks to be safely delayed? Short-term hormone therapy and intermediate dose radiation increases survivial for early stage prostate cancer Short-term hormone therapy given prior to and during intermediate dose radiation treatment for men with early stage prostate cancer increases their chance of living longer, compared to those who receive the same radiation alone. More Prostate Cancer Current Events and Prostate Cancer News Articles |
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