Florida - December 2012 Archives

JACKSONVILLE, Fla. — Researchers at Mayo Clinic's campus in Florida have identified an enzyme specifically linked to aggressive prostate cancer, and have also developed a compound that inhibits the ability of this molecule to promote the metastatic spread of the cancer. Their study, published in the Dec. 18 online edition of Molecular Cancer Research, is the first to link the enzyme PRSS3 to prostate cancer. "This molecule is a protease, which means it digests other molecules. Our data suggests PRSS3 activity changes the environment around prostate cancer cells — perhaps by freeing them from surrounding tissue — to promote malignancy and invasiveness," says the study's senior investigator, Evette Radisky, Ph.D., a cancer biologist in the Mayo Clinic Cancer Center. "I don't think PRSS3 is the only factor involved in driving aggressive prostate cancer, but it may be significant for a certain subset of this cancer — the kind that is potentially lethal," she says. Dr. Radisky and five colleagues at Mayo Clinic in Florida made the discovery by investigating publicly available databases, derived from clinical studies, which contain data on molecules that are upregulated — irregularly switched on — in cancer. They had previously discovered a link between the protease and the earlier stages of breast cancer. The research team wanted to see if any other cancer abnormally expresses this protease, and at what stages so they mined multiple databases. "The link between PRSS3 activity and aggressive prostate cancer jumped out at us," Dr. Radisky says. "We found a definitive trend of increasing PRSS3 expression with cancer progression." Then, in mice models of prostate cancer, the researchers demonstrated that expression of the protease was critical for prostate cancer metastasis. Cancer did not spread in mice in which PRSS3 was silenced. The group had earlier crystallized the structure of the PRSS3 protease, and discovered a place on the enzyme where a small protein therapeutic could bind to plug up the "scissoring" action of the molecule. "The protease has an active site that breaks down other proteins, and our inhibiting agent sticks to the site, shutting it down," Dr. Radisky says. The researchers say their finding suggests several possible future clinical applications.

JACKSONVILLE, Fla. — A research team led by scientists at Mayo Clinic in Florida have decoded the entire pathway that regulates leakiness of blood vessels — a condition that promotes a wide number of disorders, such as heart disease, cancer growth and spread, inflammation and respiratory distress. They say their findings, published online Dec. 17 in the Journal of Cell Biology, suggest that several agents already being tested for other conditions might reverse vessel leakiness. "Now that we understand a lot more about the pathway that leads to leaky blood vessels, we can begin to try to target it in an efficient way, and that is very exciting," says the study's lead investigator, Panos Z. Anastasiadis, Ph.D., chair of the Department of Cancer Biology at Mayo Clinic in Florida. Physicians have attempted to regulate that pathway in cancer through use of VEGF inhibitors, such as Bevacizumab, but these drugs are not as effective as they might be if other parts of the pathway were also inhibited, Dr. Anastasiadis says. The research team, led by Dr. Anastasiadis and Arie Horowitz, Ph.D., at Cleveland Clinic Foundation, found that VEGF is one of two different molecules that affect a key downstream protein, Syx, to regulate the permeability of blood vessels. Blood vessels are made up of endothelial cells that have to fit tightly together to form a solid tubular structure that blood can flow through. The researchers discovered that VEGF turns off Syx, which normally ensures the junctions between endothelial cells are strong. Without Syx, adhesion between the cells is loose, and the blood vessels are leaky. When new blood vessels are needed — such as to feed a growing tumor — VEGF loosens up endothelial cells so new vessels can sprout. Then, after new vessels are formed, a second molecule, angiopoietin-1 (Ang1) works to glue the cells back together, Dr. Anastasiadis says. "These molecules have opposing, yin and yang effects. VEGF kicks Syx out of the junctions between cells, promoting leakiness, and Ang1 brings it back in to stabilize the vessel," he says. The issue in cancer, however, is that VEGF overwhelms the system. "There isn't enough Ang1 to glue the vessels back together, and this leakiness allows cancer cells to escape the tumor and travel to other parts of the body," Dr. Anastasiadis says. "In late stages of the cancer, it also promotes the leaking of liquids into organs, such as the lungs. This results in profound effects that are often lethal." Other disorders, such as inflammation and sepsis, a deadly bacterial infection that can result from excess liquid in lungs, are also induced by a leaky vascular system, he says.

JACKSONVILLE, Fla. — Florida Blue and Mayo Clinic jointly announce a new collaboration aimed at providing the utmost in quality care for knee replacement patients ...

JACKSONVILLE, Fla. — Mayo Clinic's hospital on its Florida campus is being recognized this week as one of the top hospitals in the nation by the Leapfrog Group, an independent, national nonprofit organization run by employers and other large purchasers of health benefits. Only 92 U.S. hospitals out of 1,200 were named to the 2012 Top Hospitals list. Of those 92, three from Mayo Clinic made the list: Mayo Clinic hospital, Florida Mayo Clinic Hospital, Arizona Saint Marys Hospital, Rochester Mayo Clinic is the only hospital in Northeast Florida and one of only two hospitals in the state to make the list of top hospitals. The selection is based on the results of the Leapfrog Group's annual hospital survey, which measures hospitals' performance on patient safety and quality by focusing on three critical areas of hospital care: how patients fare, resource use, and management structures in place to prevent errors. Survey results are posted online and are open to patients and families, the public, employers, and other purchasers of health care. "We strive every day to provide the highest quality of care to our patients," says William Rupp, M.D., chief executive officer of Mayo Clinic in Florida. "We commend the hard work of our employees for this outstanding recognition as we continue to achieve our quality goals of reducing mortality rates and health-care associated infections, and increasing patient satisfaction. Our mission is to deliver evidence-based medicine in a safe environment with compassion, integrity and respect for our patients." Patient safety Last week Leapfrog also recognized Mayo Clinic's hospitals in Florida, Arizona and Rochester and two Mayo Clinic Health System hospitals that earned an "A" for patient safety. Mayo Clinic hospitals that received an "A" grade are: Mayo Clinic hospital, Florida Mayo Clinic Hospital, Arizona Saint Marys Hospital, Rochester Rochester Methodist Hospital, Rochester Austin, Minn., Mayo Clinic Health System Fairmont, Minn., Mayo Clinic Health System The Hospital Safety Score uses 26 measures of publicly available hospital safety data to produce a single grade that is intended to reflect a hospital's overall capacity to keep patients safe from infections, injuries and errors.

JACKSONVILLE, Fla. — Researchers at Mayo Clinic in Florida have uncovered a toxic cellular process by which a protein that maintains the health of neurons becomes deficient and can lead to dementia. The findings shed new light on the link between culprits implicated in two devastating neurological diseases: frontotemporal dementia and amyotrophic lateral sclerosis, also known as Lou Gehrig's disease. The study is published Dec. 10 in the online issue of Proceedings of the National Academy of Sciences. There is no cure for frontotemporal dementia, a disorder that affects personality, behavior and language and is second only to Alzheimer's disease as the most common form of early-onset dementia. While much research is devoted to understanding the role of each defective protein in these diseases, the team at Mayo Clinic took a new approach to examine the interplay between TDP-43, a protein that regulates messenger ribonucleic acid (mRNA) — biological molecules that carry the information of genes and are used by cells to guide protein synthesis — and sortilin, which regulates the protein progranulin. "We sought to investigate how TDP-43 regulates the levels of the protein progranulin, given that extreme progranulin levels at either end of the spectrum, too low or too high, can respectively lead to neurodegeneration or cancer," says the study's lead investigator, Mercedes Prudencio, Ph.D., a neuroscientist at the Mayo Clinic campus in Florida. The neuroscientists found that a lack of the protein TDP-43, long implicated in frontotemporal dementia and amyotrophic lateral sclerosis, leads to elevated levels of defective sortilin mRNA. The research team is the first to identify significantly elevated levels of the defective sortilin mRNA in autopsied human brain tissue of frontotemporal dementia/TDP cases, the most common subtype of the disease. "We found a lack of TDP-43 disrupts the cellular process called mRNA splicing that precedes protein synthesis, resulting in the generation of a defective sortilin protein," Dr. Prudencio says. "More important, the defective sortilin binds to progranulin and as a result deprives neurons of progranulin's protective effects that stave off the cell death associated with disease."

SAN ANTONIO, Texas — Adding the drug trastuzumab to chemotherapy prevents cancer recurrence and improves survival in a large number of women with early stage HER2-positive breast cancer. But trastuzumab does not stop tumors from returning in about 25 percent of patients — and oncologists haven't been able to identify these women before treatment. This situation may soon change, according to a Mayo Clinic study being presented at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium. VIDEO ALERT: Video of Dr. Perez is available on the Mayo Clinic News Network. A team of U.S. researchers, led by oncologists at Mayo Clinic's campus in Florida, have discovered 27 genes that are significantly associated with a good outcome with concurrent use of trastuzumab and chemotherapy, as well as five other genes linked to a poor outcome using the same treatment regimen. Results of their study — believed to be the first to use gene expression profiling to predict outcome to trastuzumab as part of adjuvant breast cancer therapy — offer a number of future potential benefits, says Edith Perez, M.D., deputy director at large of the Mayo Clinic Comprehensive Cancer Center and director of the Breast Cancer Translational Genomics Program at Mayo Clinic. "These findings also are getting us closer to unraveling the biological factors that are relevant to patient outcome, which will help us improve clinical care," Dr. Perez says. For example, the discovery may help scientists devise a genetic test that can help oncologists select the best treatment for their HER2-positive patients, she says. Further analysis will illuminate the inner biological workings of individual HER2-positive tumors, which could provide clues for novel treatments, Dr. Perez adds. The researchers have already found that the genes linked to outcome can be grouped into different categories that affect tumor functioning, such as cell cycle, cell death, cell receptor signaling, and gene transcription. Dr. Perez and her team plan to validate their findings through collaborations with researchers in the United States and Europe who have led other trastuzumab clinical studies.