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JACKSONVILLE, Fla. — June 20, 2012.  A molecule widely believed to fight many forms of cancer actually helps deadly thyroid tumors grow, and cancer therapies now being tested in humans might boost the activity of this newly revealed bad guy, researchers at Mayo Clinic in Florida say. Their findings are published online this month in the Journal of Cell Science. The study found that in anaplastic thyroid cancer, the Forkhead transcription factor, FOXO3a, is not the helpful tumor suppressor everyone thought it was, but, instead, is a lethal promoter of tumor growth. When FOXO3a was silenced in laboratory models of human anaplastic thyroid cancer, the cells grew slowly, but when it was added, they grew much faster. "This result is exactly the opposite of what we expected," says senior author John A. Copland, Ph.D., a Mayo cancer biologist. "We were more than surprised. We were concerned." FOXO3a is known as a suppressor of tumor growth because it responds to all forms of cell stress, including that produced in cancer, by turning on genes inside the nucleus that trigger the cell's death. Cancer, in turn, is known to shut down FOXO3a by sending it out of the nucleus and into the cell's cytoplasm, where it is degraded. The molecule that ships FOXO3a out of the nucleus is Akt, which tries to keep cancer cells alive. The research team used an Akt blocker — similar to the ones now being used in human cancer clinical trials — expecting to increase nuclear FOXO3a and suppress cancer growth in anaplastic thyroid cancer. They were trying to find a treatment for one of the deadliest known cancers, which accounts for just 2 percent of thyroid cancer cases in the U.S. but is responsible for about 40 percent of thyroid cancer deaths. "The issue we are grappling with is that there are no effective treatments for this cancer. These tumors are so aggressive because there are so many genetic abnormalities," says study co-author Robert Smallridge, M.D., a Mayo endocrinologist who treats thyroid cancer patients. "We are studying what drives this cancer and how it can be treated." The study showed that FOXO3a remained in the nucleus, with the use of an Akt inhibitor, and that instead of helping to kill cancer cells, FOXO3a was accelerating their growth. This raises concern about the use of Akt inhibitors since one of the mechanisms is to cause FOXO3a to remain active in the nucleus. "We discovered a biological switch that turns FOXO3a from a good guy into a bad actor, but we don't know what that is yet, or in which cancers that might happen," says lead researcher Laura Marlow, a Mayo biologist. "Cancer researchers, including those testing Akt inhibitors, should know that FOXO3a has pro-cancer activity as well as anti-cancer properties," Dr. Copland says. "Concern should be raised that an Akt inhibitor will enhance retention of FOXO3a in the nucleus, causing FOXO3a to remain active.

JACKSONVILLE, Fla. — June 6, 2012.  Using a new and powerful approach to understand the origins of neurodegenerative disorders such as Alzheimer's disease, researchers at Mayo Clinic in Florida are building the case that these diseases are primarily caused by genes that are too active or not active enough, rather than by harmful gene mutations. VIDEO ALERT: Video resources of Nilufer Ertekin-Taner, M.D., Ph.D., discussing the study are available here. In the June 7 online issue of PLoS Genetics, they report that several hundred genes within almost 800 brain samples of patients with Alzheimer's disease or other disorders had altered expression levels that did not result from neurodegeneration. Many of those variants were likely the cause. "We now understand that disease likely develops from gene variants that have modest effects on gene expression, and which are also found in healthy people. But some of the variants — elevating expression of some genes, reducing levels of others — combine to produce a perfect storm that leads to dysfunction," says lead investigator Nilufer Ertekin-Taner, M.D., Ph.D., a Mayo Clinic neurologist and neuroscientist. "If we can identify the genes linked to a disease that are too active or too dormant, we might be able to define new drug targets and therapies," she says. "That could be the case for both neurodegenerative disease as well as disease in general." Dr. Ertekin-Taner says no other lab has performed the extent of brain gene expression study conducted at Mayo Clinic's Florida campus. "The novelty, and the usefulness, of our study is the sheer number of brain samples that we looked at and the way in which we analyzed them. These results demonstrate the significant contribution of genetic factors that alter brain gene expression and increase risk of disease," she says. This form of data analysis measures gene expression levels by quantifying the amount of RNA produced in tissue and scans the genome of patients to identify genetic variants that associate with these levels. Mayo researchers measured the level of 24,526 transcripts (messenger RNA) for 18,401 genes using cerebellar autopsy tissue from 197 Alzheimer's disease patients and from 177 patients with other forms of neurodegeneration. The researchers then validated the results by examining the temporal cortex from 202 Alzheimer's disease patients and from 197 with other pathologies. The difference between these samples is that while the temporal cortex is affected by Alzheimer's disease, the cerebellum is relatively spared. From these analyses, the researchers identified more than 2,000 markers of altered expression in both groups of patients that were common between the cerebellum and temporal cortex. Some of these markers also influenced risk of human diseases, suggesting their contribution to development of neurodegenerative and other diseases regardless of their location in the brain. They identified novel expression "hits" for genetic risk markers of diseases that included progressive supranuclear palsy, Parkinson's disease, and Paget's disease, and confirmed other known associations for lupus, ulcerative colitis, and type 1 diabetes. "Altered expression of brain genes can be linked to a number of diseases that affect the entire body," Dr. Ertekin-Taner says.

JACKSONVILLE, Fla. — May 24, 2012.   The Jacksonville campus of Mayo Clinic will invest about $97 million in two new major construction projects scheduled to begin this summer. The projects include the addition of two floors and 90 beds to its hospital, and the construction of an off-site primary care center that will be built near the intersection of Interstate 295 East Beltway (formerly 9A) and Gate Parkway. The expansion projects will add about 400 new jobs at Mayo and 250 construction jobs, says William Rupp, M.D., chief executive officer of Mayo Clinic in Florida. Mayo Clinic currently has about 4,900 employees and generates $1.6 billion annually to the northeast Florida economy. "Our hospital has been operating at or near capacity almost since it first opened four years ago," Dr. Rupp says. "The additional beds and other improvements to the hospital will help us continue to offer the highest quality of care and meet the needs of our patients." This marks the first expansion of the Mayo Clinic hospital since it opened in April 2008. Currently, the hospital has 214 beds. After the $80 million expansion, the hospital will have 304 private rooms and eight floors. The two-story, 40,000-square-foot primary care center will be designed to support 20 physicians and providers and offer X-ray, mammography, ultrasound and laboratory services. The high-performance and environmentally friendly building design will allow Mayo to seek LEED (Leadership in Energy and Environmental Design) certification when construction is completed.

JACKSONVILLE, Fla. — May 18, 2012.  Recent studies have shown that palliative care interventions aimed at addressing patients' emotional, spiritual and social needs have a significant impact on cancer patients' quality of life and may even improve cancer patients' overall survival. Despite this, most cancer patients being cared for in their communities do not have access to these services. VIDEO ALERT: Additional audio and video resources, including comments by Dr. Colon-Otero, are available on YouTube. Most cancer patients also do not have advance directives addressed and are not aware of the benefits of hospice services. In order to address this issue, researchers at Mayo Clinic in Florida decided to test whether a nurse practitioner-driven consultation that used quality-of-life assessment tools and advance directives tools resulted in improvement in the cancer patients' quality of life. The researchers, who published their findings online in the Journal of Palliative Medicine, say their study suggests that a consultative visit between a nurse practitioner and a metastatic cancer patient goes a long way to improving that patient's emotional and mental well-being. The study results were strongly positive despite the fact that only 26 patients were enrolled. A total of 100 had been planned but accrual to the study was halted when other recently completed randomized studies had shown the benefit of similar nurse driven palliative interventions. Patients also frequently refused to enroll if they were randomized to the "control" arm, which did not include a discussion with an oncology advanced registered nurse practitioner about advance directives and how their symptoms could best be managed. The 12 patients who did receive intervention from a nurse had a significant improvement in their emotional health, compared to the 14 patients in the control arm. "The findings should be extremely helpful to oncologists in both community and academic medical practices concerned about how to incorporate palliative care, including discussions about advance directives in the outpatient management of their cancer patients," says the study's senior investigator, Gerardo Colon-Otero, M.D., an oncologist in the Division of Hematology/Oncology at Mayo Clinic in Florida. The study also demonstrates that oncology clinics are not doing enough to help improve their patients' quality of life because they are so focused on treating the cancer. As a result, there are missed opportunities to provide additional support and many patients end up enrolling in hospice care much too late and do not have advance directives completed in a timely fashion. "This study suggests that we shouldn't be afraid of these discussions, and that many of our patients actually welcome having advance directives and hearing about hospice services," Dr. Colon-Otero says. "This relatively simple strategy of having a nurse practitioner trained in palliative care and embedded within the oncology clinic to provide these consultation services is helpful, all the way around."

JACKSONVILLE, Fla. — May 17, 2012.  By simply shining a tiny light within the small intestine, close to that organ's junction with the pancreas, physicians at Mayo Clinic's campus in Florida have been able to detect pancreatic cancer 100 percent of the time in a small study. The light, attached to a probe, measures changes in cells and blood vessels in the small intestine produced by a growing cancer in the adjoining pancreas. VIDEO ALERT: Video of Dr. Michael Wallace discussing the study is available on the Mayo Clinic News Network, our new method for delivering embargoed media content. The network requires a username and password, which can be obtained at http://NewsNetwork.MayoClinic.org. Learn about this new network by watching this short video. This minimally invasive technique, called Polarization Gating Spectroscopy, will now be tested in a much larger international clinical trial led by the Mayo Clinic researchers. The preliminary study suggests it may be possible, one day, to use a less invasive endoscope to screen patients for early development of pancreatic cancer. The findings are being highlighted in a special address by Mayo Clinic gastroenterologist Michael Wallace, M.D., at the international Digestive Disease Week 2012, the world's largest gathering of physicians and researchers who treat, and study, disorders of the gastrointestinal tract. The pancreas is notoriously hard to reach and see due to its very deep location in the abdomen, surrounded by intestines. The study investigators theorized that there may be changes in the nearby "normal appearing" tissue of the small intestine which is much more accessible. "No one ever thought you could detect pancreatic cancer in an area that is somewhat remote from the pancreas, but this study suggests it may be possible," says Dr. Wallace, the chairman of the Division of Gastroenterology at Mayo Clinic in Florida. "Although results are still preliminary, the concept of detection field effects of nearby cancers holds great promise for possible early detection of pancreatic cancer." Pancreatic cancer is one of the most deadly of human tumors. It is only curable in 5 percent of cases, and even when it is surgically removed, 70 percent of patients have a recurrence that is fatal, Dr. Wallace says. There are no ways currently to detect the cancer early enough to cure a substantial number of patients, he says. Pancreatic cancer is now usually detected through an imaging scan, followed by an invasive biopsy. Tumors found in this way are usually at an advanced stage. In this study, the Mayo Clinic physicians tested a light probe developed by their long-time collaborators at Northwestern University.

JACKSONVILLE, Fla. — A single gene that promotes initial development of the most common form of lung cancer and its lethal metastases has been identified by researchers at Mayo Clinic in Florida. Their study suggests other forms of cancer may also be driven by this gene, matrix metalloproteinase-10 (MMP-10). The study, published in the journal PLoS ONE on April 24, shows that MMP-10 is a growth factor secreted and then used by cancer stem-like cells to keep themselves vital. These cells then drive lung cancer and its spread, and are notoriously immune to conventional treatment. The findings raise hope for a possible treatment for non-small cell lung cancer, the leading cause of U.S. cancer deaths. Researchers discovered that by shutting down MMP-10, lung cancer stem cells lose their ability to develop tumors. When the gene is given back to the cells, they can form tumors again. The power of this gene is extraordinary, says senior investigator Alan Fields, Ph.D., the Monica Flynn Jacoby Professor of Cancer Research within the Department of Cancer Biology at Mayo Clinic in Florida. "Our data provides evidence that MMP-10 plays a dual role in cancer. It stimulates the growth of cancer stem cells and stimulates their metastatic potential," he says. "This helps explain an observation that has been seen in cancer stem cells from many tumor types, namely that cancer stem cells appear to be not only the cells that initiate tumors, but also the cells that give rise to metastases." Dr. Fields says the findings were unexpected, for several reasons. The first is that the cancer stem cells express MMP-10 themselves, and use it for their own growth. Most of the known members of the matrix metalloproteinase genes are expressed in the tumor's microenvironment, the cells and tissue that surround a tumor, he says. The enzymes produced by these genes are involved in breaking down the microenvironment that keeps a tumor in place, allowing cancer cells to spread, which is why other genes in this family have been linked to cancer metastasis. "The fact that a gene like MMP-10, which codes for a matrix metalloproteinase that has been linked to metastasis, is actually required for the growth and maintenance of cancer stem cells is very surprising. One would not have predicted that such a gene would be involved in this process," Dr. Fields says.

JACKSONVILLE, Fla. — Mayo Clinic in Florida will be one of the first health care institutions in the United States to offer a newly approved device to treat gastroesophageal reflux disease (GERD). The condition, also known as acid reflux disease, can lead to serious health problems. VIDEO ALERT: Additional video resources, including excerpts from an interview with Dr. C. Daniel Smith describing the device and procedure, are available on the Mayo Clinic News Blog. The U.S. Food and Drug Administration (FDA) approved the device and treatment procedure on March 22 for patients with GERD who continue to have chronic reflux symptoms despite taking medication. Mayo Clinic in Florida expects to offer the new treatment immediately, says C. Daniel Smith, M.D., chair of the Surgery Department at Mayo Clinic in Florida, and an internationally recognized expert on the treatment of GERD. Dr. Smith is experienced in using the system because Mayo Clinic in Florida was one of only 14 centers nationally that participated in a clinical trial that led to the FDA's approval of the device. "Mayo has been a leader in the treatment of esophageal diseases, especially GERD, and we are pleased to be offering this new treatment to our patients immediately," he says. GERD is a condition in which liquid, or food, in the stomach flows back up into the esophagus due to the inability of a ring of muscle between the lower esophagus and the top of the stomach to close properly. If drugs aimed at neutralizing the acid in the stomach fails to prevent GERD, an operation designed to correct the mechanical defect is considered. But between 1.5 million and 2 million patients of those patients could benefit from treatment that is much less complex than current surgical options, Dr. Smith says. "The new system will offer a long-needed treatment option for a large group of underserved patients," he says. The results of the clinical study that led to approval of the device have not yet been published. But "the data presented to the FDA revealed striking results when compared to other GERD treatments that have been investigated over the past 20 years," Dr. Smith says. "The system offers effective control of GERD with limited side effects and thus far an excellent safety record." The implanted device is a ring of tiny magnetic titanium beads that is wrapped around the junction between the stomach and esophagus, serving as a mechanical augmentation of the lower esophageal sphincter (the ring of muscle). The magnetic attraction between the beads is strong enough to keep the sphincter closed to refluxing acid, but weak enough so that food can pass through it into the stomach, Dr. Smith says. The device can be implanted using minimally invasive surgery methods. Dr. Smith performs about 200 GERD-related surgeries a year and has been involved with many new treatments over the past several decades. "I expect this device to be a game changer for the treatment of GERD in select patients who have failed management with drugs," says Dr. Smith.

JACKSONVILLE, Fla. — April 10, 2012.   Mayo Clinic researchers have discovered a new class of molecular mutation in various forms of breast cancer, a finding that may shed new light on development and growth of different types of breast tumors. Called fusion transcripts, the mutated forms of RNA may also provide a way to identify tumor subtypes and offer new strategies to treat them, investigators say. Their study, published in the April 15 issue of Cancer Research, is the first to systematically search for fusion genes and fusion transcripts linked to different types of breast tumors. Oncologists currently recognize three basic types of breast tumors — estrogen-receptor (ER)-positive, HER2-positive, and triple negative. "But breast cancer is much more complex than indicated by these three subtypes, and one of the challenges of treating the disease is to identify gene markers that predict how a tumor will respond to a specific treatment," says senior investigator Edith Perez, M.D., deputy director of the Mayo Clinic Comprehensive Cancer Center in Florida and director of the Breast Cancer Translational Genomics Program, which involves researchers at all three Mayo Clinic campuses. "The discovery of subtype-specific fusion transcripts in breast cancer represents a step in this direction," she says. "Our findings indicate that fusion transcripts are much more common in breast cancer than had been realized. They represent a new class of mutation whose role in breast cancer is not understood at all." "Fusion transcripts have the power to produce proteins that are relevant to tumor development, growth, and sensitivity to treatment, so we may have a brand new set of genomic changes that may help us understand, and treat, breast cancer in a new way," says E. Aubrey Thompson, Ph.D., professor of Biology at Mayo Clinic's Comprehensive Cancer Center, and co-director of the Breast Cancer Translational Genomics Program. "This is a novel discovery that will now require additional investigation," he says. "We need to understand what these fusion transcripts and proteins are doing." Fusion transcripts are created when chromosomes break apart and recombine, an event that commonly occurs in cancer cells. During this process, fusion genes are created when two halves of normal genes become linked. Fusion genes (DNA) create fusion transcripts (RNA), which then produce fusion proteins. "Mistakes are made," Dr. Thompson says. "That is one of the salient properties of tumor cells, because they are defective in repairing damage to their genes." "These mutated proteins may have an entirely new, cancer-promoting function, or they may interfere with normal cellular functions." Fusion transcripts are common in blood cancers, such as leukemia and lymphoma. Before this discovery, however, few were found in solid cancers such as breast tumors. Because fusion genes, transcript, and protein are generally found only in tumors, they make ideal biomarkers to identify tumor cells, Dr. Perez says.

JACKSONVILLE, Fla. — Findings of an extensive investigation at Mayo Clinic, published in the April 3 issue of the Annals of Internal Medicine, serve as a warning to other health care institutions that drug diversion by a health care worker can spread hepatitis C, a potentially fatal viral infection, to patients. The report details the effort that Mayo Clinic in Florida undertook to find the source of a genetically related hepatitis C virus that appeared in three patients over a 2 to 3 year period of time. Investigators eventually traced the source to a radiology technician who was using a portion of narcotics contained within syringes intended for patients, and then replacing the missing fluid with saline. The process contaminated the syringes with hepatitis C. Mayo Clinic then identified 3,929 patients who were at risk for exposure to hepatitis C, and invited them to be screened. Of the 3,444 patients who were tested, two additional cases of genetically related hepatitis C infection attributed to the employee were identified. The report, written by infectious disease experts and epidemiologists at Mayo Clinic, the Florida Department of Health, and the U.S. Centers for Disease Control and Prevention, is the most thoroughly documented instance of hepatitis C transmission caused by drug diversion in an American hospital or clinic, according to the report's lead author, Walter Hellinger, M.D., a health care epidemiologist. Four other instances have been reported to date in the United States and, of these, only one in which narcotic diversion was suspected but not confirmed has been published in a peer-reviewed medical journal, he says. "We owe our patients the best care possible, which meant conducting a thorough, investigation," says Dr. Hellinger, who also serves as chair of Infection Control at the Mayo Clinic campus in Florida.

JACKSONVILLE, Fla. — Researchers have identified a gene that causes adult-onset primary cervical dystonia, an often-painful condition in which patients' necks twist involuntarily. The discovery by a team from the Jacksonville, Fla., campus of Mayo Clinic and the University of Tennessee Health Sciences Center sheds light on a movement disorder that physicians previously could seldom explain. Their research appears in the Annals of Neurology. In 1990, a man with a crooked neck came to see Ryan Uitti, M.D., a neurologist then at Mayo Clinic in Rochester, Minn. Dr. Uitti knew about adult-onset primary cervical dystonia, which results in involuntary twisting of the neck to the left or right, backward or forward. Most people who have it suffer from muscle pain and abnormalities in head position. Some don't think it is all that unusual and may not seek medical help, Dr. Uitti says. "They think they slept wrong at some point, or, because the twisting might straighten out with another maneuver, such as walking backwards, they might actually be accused of being a little crazy," Dr. Uitti says. Dr. Uitti had been taught that there is usually no explanation for the disorder, when it shows up in adulthood. But working with a team of neurologists who have found the genetic causes of other rare conditions, Dr. Uitti began to investigate.

JACKSONVILLE, Fla. — Satilla Health Services, Inc., parent company of Satilla Regional Medical Center, joins with the Jacksonville campus of Mayo Clinic effective March 1. Satilla will be renamed "Mayo Clinic Health System in Waycross." Satilla's integration with Mayo Clinic means health care consumers in Waycross will have access to all of the knowledge and expertise of Mayo Clinic available right in their own community. Satilla and Mayo Clinic have identified several areas in which they share common goals and philosophies, such as preserving and enhancing health care services available to patients in the greater Waycross region. Both organizations are committed to patients receiving the great majority of their health care services in Waycross. The boards of Mayo Clinic and Satilla, as well as the Georgia Attorney General, have approved the integration of the two organizations. At closing, Mayo Clinic will become the sole member, parent organization of Satilla. Kenneth T. Calamia, M.D., currently a physician at Mayo Clinic, has been appointed chief executive officer of Mayo Clinic Health System in Waycross. Robert Trimm, president and chief executive officer of Satilla, has been appointed chief administrative officer of Mayo Clinic Health System in Waycross. "This is a wonderful opportunity to work together with Mayo Clinic in an effort to bring the best health care possible to the people in our surrounding communities," Trimm says. "We're interested in expanding the availability of health care resources locally and ensuring the continuing presence of excellent, community health care for the future."

JACKSONVILLE, Fla. — A research team led by investigators at Mayo Clinic in Florida has found that a small device worn on a patient's brow can be useful in monitoring stroke patients in the hospital. The device measures blood oxygen, similar to a pulse oximeter, which is clipped onto a finger. VIDEO ALERT: Additional audio and video resources, including comments by Dr. Freeman about the new device, are available online. Their study, published in the Feb. 1 issue of Neurosurgical Focus, suggests this tool, known as frontal near-infrared spectroscopy (NIRS), could offer hospital physicians a safe and cost-effective way to monitor patients who are being treated for a stroke, in real time. "About one-third of stroke patients in the hospital suffer another stroke, and we have few options for constantly monitoring patients for such recurrences," says the study's senior investigator, neurocritical care specialist William Freeman, M.D., an associate professor of neurology at Mayo Clinic. "This was a small pilot study initiated at Mayo Clinic's campus in Florida, but we plan to study this device more extensively and hope that this bedside tool offers significant benefit to patients by helping physicians detect strokes earlier and manage recovery better," he says.