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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.

JACKSONVILLE, Fla. — A novel test that measures proteins from nerve damage that are deposited in blood and spinal fluid reveals the rate of progression of amyotrophic lateral sclerosis (ALS) in patients, according to researchers from Mayo Clinic's campus in Florida, Emory University and the University of Florida. Their study, which appears online in the Journal of Neurology, Neurosurgery & Psychiatry, suggests this test, if perfected, could help physicians and researchers identify those patients at most risk for rapid progression. These patients could then be offered new therapies now being developed or tested. ALS — also known as Lou Gehrig's disease — is a progressive neurodegenerative disease caused by deterioration of motor neurons (nerve cells) that control voluntary muscle movement. The rate of progression varies widely among patients, and survival from the date of diagnosis can be months to 10 years or more, says Kevin Boylan, M.D., medical director of the ALS Clinic at Mayo Clinic in Florida. "In the care of our ALS patients there is a need for more reliable ways to determine how fast the disease is progressing," says Dr. Boylan, who is the study's lead investigator. "Many ALS researchers have been trying to develop a molecular biomarker test for nerve damage like this, and we are encouraged that this test shows such promise. Because blood samples are more readily collected than spinal fluid, we are especially interested in further evaluating this test in peripheral blood in comparison to spinal fluid." There are no curative or even significantly beneficial therapies in clinics now for ALS treatment, but many are in development, Dr. Boylan says. A test like this could help identify those patients who are at risk for faster progression of weakness. With experimental treatments that primarily slow progression of ALS, detecting a treatment response in patients with faster progression may be easier to detect, says Dr. Boylan. Now, patients with varying rates of progression participate together in clinical studies, which can make analysis of a drug's benefit difficult, he says. "If there were a way to identify people who are likely to have relatively faster progression, it should be possible to conduct therapeutic trials with smaller numbers of patients in less time than is required presently," Dr. Boylan says. A longer-range goal is to develop tests of this kind to gauge how well a patient is responding to experimental therapies, he adds. The test measures neurofilament heavy form in blood and spinal fluid. These are proteins that provide structure to motor neurons, and when these nerves are damaged by the disease, the proteins break down and float free in blood serum and in the spinal fluid. Earlier research in this area was conducted by Gerry Shaw, Ph.D., a neuroscientist at the University of Florida, who is the study's senior investigator and the developer of the neurofilament assay used in the study.

JACKSONVILLE, Fla. — A gene so powerful it nearly triples the risk of Alzheimer's disease has been discovered by an international team including researchers from Mayo Clinic. It is the most potent genetic risk factor for Alzheimer's identified in the past 20 years. The findings were reported Wednesday in the online edition of the New England Journal of Medicine. The team included researchers from 44 institutions around the world, including 10 from Mayo Clinic's campuses in Florida and Minnesota. The study was led by John Hardy, Ph.D., a researcher at the Institute of Neurology at University College London and a former professor at Mayo Clinic in Florida. The researchers used new sequencing techniques to home in on the TREM2 gene. Additional TREM2 sequencing was then performed, in part, by scientist Aleksandra Wojtas in the Mayo Clinic in Florida laboratory of Rosa Rademakers, Ph.D. These studies led to identification of a set of rare variants in TREM2 that occurred more often in 1,092 Alzheimer's disease patients than in a control group of 1,107 healthy people. The most common variant, R47H, was then evaluated in follow-up studies of a large number of Alzheimer's disease patients and controls. Minerva Carrasquillo, Ph.D., a scientist in the Mayo Clinic in Florida laboratory of Steven Younkin, M.D., Ph.D., spearheaded the direct genotyping and analysis of R47H in DNA samples from 1,994 Alzheimer's disease patients and 4,062 "control" participants — individuals verified not to have Alzheimer's. The patients and control participants were evaluated by Mayo Clinic physicians, led by co-authors Dennis Dickson, M.D., Neill Graff-Radford, M.D., and Ronald Petersen, M.D., Ph.D. These follow-up studies showed unequivocally that the R47H variant of TREM2 substantially increases the risk of Alzheimer's disease. "The TREM2 variant may be rare, but it is potent," Dr. Carrasquillo says. "In our series, it was present in 1.9 percent of the Alzheimer's patients and in only 0.37 percent of the controls. This strong effect rivals that of the well-established genetic variant known as APOE 4, and it was observed both in our study and in the independent study led by deCODE that was published with ours. R47H isn't fully penetrant — meaning that not all people who have the variant will develop Alzheimer's and in those who do, other genes and environmental factors will also play a role — but like APOE 4 it does substantially increase risk." Dr. Younkin comments: "R47H is the first goldilocks variant to show strong association with Alzheimer's disease." Now being identified using the new sequencing technologies, goldilocks variants are an important type of rare variant so named because they are just right, not too rare and strong enough to show highly significant association in well-powered follow-up genotypic studies like the one performed at Mayo. "There is a broad consensus that prevention will be the best way to manage Alzheimer's disease," Dr. Younkin says. "In my view, common variants like APOE 4 and goldilocks variants like TREM2 R47H are important because they could be used, in principal, to identify many healthy people at high risk of Alzheimer's disease who would be suitable for prevention trials. Patients whose Alzheimer's disease is driven by high risk genetic variants will frequently transmit these variants to their children. We now know that it takes a long time for the pathology of Alzheimer's disease to produce symptoms, so prevention in children who receive these variants would ideally begin when their elderly parents are diagnosed."

JACKSONVILLE, Fla. — September 24, 2012.  Men who undergo surgical removal of prostate cancer can experience significant levels of anxiety one year after surgery, and higher levels of anxiety appear to be linked to poor sexual satisfaction and depression, say researchers at Mayo Clinic's campus in Florida. Their recent study, published in the online edition of Psycho-Oncology, suggests that men who experience high levels of "cancer-specific anxiety" following surgery for prostate cancer could likely benefit from counseling designed to address their worries and improve their quality of life. "The 10-year survival for a man undergoing surgery to remove localized prostate cancer is greater than 95 percent. Given that the majority of men who undergo prostatectomy for prostate cancer will not die from their disease, we are concerned about what life will be like for these patients decades after diagnosis and treatment," says the study's senior investigator, Alexander Parker, Ph.D., an associate professor of epidemiology and urology. While prostate cancer can be a life threatening disease, most men diagnosed with prostate cancer do not die from it. According to the American Cancer Society, more than 2.5 million men in the United States who have been diagnosed with prostate cancer are still alive. "The odds of surviving for long periods of time following surgery for prostate cancer are very high," says surgeon and co-author Gregory Broderick, M.D., a professor of urology. "That means a lot of men are living as prostate cancer survivors and we at Mayo Clinic are committed to understanding factors that affect their quality of life, not just their quantity of life." Dr. Broderick presented these results at the joint meeting of the Sexual Medicine Society of North America and the International Society for Sexual Medicine this summer in Chicago. Data from studies in patients with other cancer types have shown that anxiety can significantly affect an individual's quality of life. "Our study is the first to specifically show that those men with higher cancer-specific anxiety one year after surgery for prostate cancer are more likely to report lower levels of satisfaction with their sex life and higher levels of depressive symptoms," Dr. Parker says. In their study, the Mayo Clinic researchers examined findings on 365 men who, one year after undergoing surgery for prostate cancer, completed a questionnaire designed to measure anxiety levels about the fact they have been diagnosed and treated for prostate cancer. The men also completed additional questionnaires to measure levels of erectile function, sexual satisfaction and depression.

JACKSONVILLE, Fla. — September 20, 2012.  To help Mayo Clinic design the most effective treatment possible for brain cancer patients, the JLG Brain Cancer Foundation is pledging to raise $250,000 to assist in the development of a brain tissue bank at Mayo Clinic's campus in Florida. It has already raised $145,000 toward that goal. The brain cancer tissue bank will include brain tumor tissues for all stages and types of brain cancers. "This vast tissue library will enable Mayo Clinic researchers to accurately identify the key molecular culprits in brain cancers — not just genes or proteins that influence cancer development, but the ones that make cancers more aggressive or resistant to therapies. Once found, these malignant forces can be stopped," says Jill Geehr, the daughter of Jacquie Lorraine Goldman, for whom the Foundation is named. Mrs. Goldman was diagnosed with glioblastoma multiforme, the most virulent form of brain cancer, in 2008. She participated in several experimental drug trials over the course of treatment at Mayo Clinic, but lost her struggle 1.5 years after diagnosis — well above the normal survival, says Ms. Geehr. "We want to see that people diagnosed with brain cancer have options for treatment that are effective," she says. "Right now, most people who receive this diagnosis have an outcome that is pretty bleak." "Mayo Clinic is pursuing a transformative vision for brain cancer care. We can help," says Ms. Geehr. The Foundation's annual fundraising events are being held later this month. The second annual TASTE food and wine event is Thursday, Sept. 27 at TPC Sawgrass, and the Unlock the Cure JLG 5K Fun Run is slated for Saturday, Sept. 29, in Jacksonville Beach at The Beach Restaurant. Brain tissue samples that are now starting to be collected at Mayo Clinic "will be instrumental in developing a new understanding of the biology and treatment of brain malignancies like that of Mrs. Goldman's," says Kurt Jaeckle, M.D., the Mayo Clinic neuro-oncologist who treated Mrs. Goldman. "This Brain Cancer Tissue Bank never would have been possible without the kind donation and pledge of the JLG Brain Cancer Foundation," he says. "It is our hope that every person who has fought or continues to fight brain cancer will lead us closer to unlocking a cure," says Ms. Geehr.

JACKSONVILLE, Fla. — September 17, 2012.  An enzyme that could represent a powerful new tool for combating Alzheimer's disease has been discovered by researchers at Mayo Clinic in Florida. The enzyme — known as BACE2 — destroys beta-amyloid, a toxic protein fragment that litters the brains of patients who have the disease. The findings were published online Sept. 17 in the science journal Molecular Neurodegeneration. MULTIMEDIA ALERT: Video resources, including an interview with Dr. Leissring, are available for journalists at the Mayo Clinic News Network. Alzheimer's disease is the most common memory disorder. It affects more that 5.5 million people in the United States. Despite the disorder's enormous financial and personal toll, effective treatments have not yet been found. The Mayo research team, led by Malcolm A. Leissring, Ph.D., a neuroscientist at Mayo Clinic in Florida, made the discovery by testing hundreds of enzymes for the ability to lower beta-amyloid levels. BACE2 was found to lower beta-amyloid more effectively than all other enzymes tested. The discovery is interesting because BACE2 is closely related to another enzyme, known as BACE1, involved in producing beta-amyloid. "Despite their close similarity, the two enzymes have completely opposite effects on beta-amyloid — BACE1 giveth, while BACE2 taketh away," Dr. Leissring says. Beta-amyloid is a fragment of a larger protein, known as APP, and is produced by enzymes that cut APP at two places. BACE1 is the enzyme responsible for making the first cut that generates beta-amyloid. The research showed that BACE2 cuts beta-amyloid into smaller pieces, thereby destroying it, instead. Although other enzymes are known to break down beta-amyloid, BACE2 is particularly efficient at this function, the study found. Previous work had shown that BACE2 can also lower beta-amyloid levels by a second mechanism: by cutting APP at a different spot from BACE1. BACE2 cuts in the middle of the beta-amyloid portion, which prevents beta-amyloid production. "The fact that BACE2 can lower beta-amyloid by two distinct mechanisms makes this enzyme an especially attractive candidate for gene therapy to treat Alzheimer's disease," says first author Samer Abdul-Hay, Ph.D., a neuroscientist at Mayo Clinic in Florida. The discovery suggests that impairments in BACE2 might increase the risk of Alzheimer's disease. This is important because certain drugs in clinical use — for example, antiviral drugs used to treat human immunodeficiency virus (HIV) — work by inhibiting enzymes similar to BACE2.

JACKSONVILLE, Fla. — September 12, 2012.  Today's researchers have a new set of tools to help uncover the roots of human disease and personalize prevention and treatment efforts. To take advantage of the emergence of faster, more affordable DNA sequencing technology, Mayo Clinic is establishing a biobank at its campus in Jacksonville. The Mayo Clinic Biobank is an extension of an effort that started at Mayo in Rochester, Minn. in 2007. Mayo Clinic in Florida has already begun enrolling volunteers in the Biobank, and expects to add at least 5,000 in the next five years, says Alexander Parker, Ph.D., an epidemiologist and Florida-based associate director of the Mayo Clinic Center for Individualized Medicine. "Our mission at Mayo is to improve understanding of human disease and translate this knowledge into better prevention and care for all populations," Dr. Parker says. "We are grateful to our participants in the Mayo Clinic Biobank for their willingness to provide the DNA samples and information that will support the next generation of scientific inquiry, and drive us closer to more individualized medical care for everyone." Participants who enroll in the Mayo Clinic Biobank are asked to grant access to their medical records, complete a 12-page lifestyle questionnaire and donate a blood sample, from which DNA is extracted and stored for future use. Participation in the Biobank is currently limited to people already receiving routine care at Mayo Clinic. It likely will eventually be opened to non-Mayo patients. More than 40 research projects are using genetic and health information housed in the Mayo Clinic Biobank to explore questions related to a range of human diseases, including heart disease, hypertension, hypothyroidism and cancers such as myeloma and leukemia, and cancers of the colon, breast, brain, lung, liver and kidney. Dr. Parker, a kidney specialist, says one study is looking at how frequently a genetic mutation found in kidney cancer patients occurs in healthy individuals. The Biobank makes it easier for researchers to perform studies because samples and information from many different people will be available in one place. Researchers can use the Biobank like a library. When they want to study a health issue they can use Biobank samples instead of finding new samples. "One of my goals is to understand how genetics interacts with the environment to affect a person's risk of developing kidney cancer," he says. "Now, through a simple query of the Mayo Biobank, we are able to rapidly identify control individuals who have no history of kidney cancer and gain access to their DNA and lifestyle data. This essentially reduces the time needed to do the work from years to months, which moves the process along at a faster pace." Other benefits of opening the Mayo Biobank in Florida include access to more diverse populations outside the Midwest and allowing for better design of studies aimed at disorders that have a higher prevalence in Southern states, such as skin cancer and kidney stones.