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Mayo Clinic Medical Science Blog – an eclectic collection of research- and research education-related stories: feature stories, mini news bites, learning opportunities, profiles and more from Mayo Clinic.


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Tue, Oct 23 6:00am · Predicting a Woman's Risk for Breast Cancer Following a Biopsy

Each year, more than one million women have biopsies that show non-cancerous changes in the breast, known as benign breast disease (BBD). Even though the changes may not require treatment, studies over the years at Mayo Clinic and elsewhere have found that not all cases of BBD are the same, and some will go on to develop breast cancer.

“The real challenge has been determining women’s individual risk for developing breast cancer in order to provide them with the best possible intervention,” says Mark Sherman, M.D., an epidemiologist and laboratory medicine and pathology researcher on Mayo Clinic’s campus in Florida.

Building on several decades of breast cancer research at Mayo Clinic, an interdisciplinary team aims to predict which women with BBD are at risk for breast cancer. The team, led by breast surgeon Amy Degnim, M.D., in Rochester, and Dr. Sherman, recently received a $3.1 million grant from the National Cancer Institute, a division of the National Institutes of Health to develop a breast cancer risk prediction model to help guide clinical care. The model will take into account demographic factors, as well as recent research about features of breast tissue that may heighten the risk for cancer.

Researchers at Mayo Clinic published the first report on a cohort of 9,000 women just over two decades ago, supporting previous studies that had stratified patients with BBD into high, medium and low risk categories. In the last 15 years, screening techniques have become more highly targeted, with the use of mammograms, magnetic resonance imaging (MRI), and radiologically-guided needle biopsies. They’re now catching more details in the breast changes. Just as significantly, new information has emerged about how characteristics of breast tissue, such as density, are relevant to risk. And recent studies have suggested when breast lobules, the ducts that make milk, don’t shrink as a woman ages, the risk for cancer increases.

Using information from more than 7,000 patients at Mayo Clinic in Rochester, the next-generation risk model will incorporate a wide range of risk factors, including demographics, samples from radiologically-guided needle biopsies, information about breast density, molecular biomarkers, and breast lobules. Partnering with a team from Karmanos Cancer Institute that has an established cohort of nearly 4,000 African American women, the study will also provide an understanding of ethnoracial breast cancer risk factors. The model will rely on big data and sophisticated machine learning techniques to generate risk predictions following a BBD diagnosis.

Ultimately, the model may provide women with highly individualized options. Those at high risk may consider preventive treatment, while those at low risk may avoid unnecessary tests.

“Even though we’ve been able to generalize predictions for patients, we know not everyone has the same degree of risk,” Dr. Sherman says. “Our goal is to achieve individualized risk prediction for a better targeted approach to care.”


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Tue, Jul 10 6:00am · Using biological particles from milk to target liver cancer

Extracellular vesicles from cow’s milk may be a potential delivery vehicle for medical treatments for liver cancer.

Among cancers, liver tumors have been particularly hard for doctors to treat. The cancer cells tend to be hardy from the beginning and even undergo changes that make them more resistant to chemotherapies. What’s clear is that an effective treatment needs to reach the cancer cells, and not affect or damage the normal liver.

The trick, however, is getting drugs to the tumor. Researchers have been pinning hopes on getting drugs to cancer sites using the body’s own messaging system—extracellular vesicles, or EVs—tiny pouches released by cells that typically carry molecular messages from one cell to another.

In his lab, Tushar Patel, M.B., Ch.B., dean for research at Mayo Clinic’s Florida campus, investigates using these EVs as a way to deliver drugs and treatments into cancer cells. “EVs are released by many types of cells, and can even be found in most if not all bodily fluids,” he explains. “But in order to use them for cancer treatment, large quantities of EVs need to be available.”

Tushar Patel, M.B., Ch.B., discusses their lab’s work with some of his associates.

In a recent paper in Laboratory Investigation, Dr. Patel’s team showed that EVs could be obtained from milk, and then used to deliver treatments to the cells of hepatocellular carcinoma, a primary liver tumor that can be caused by cirrhosis. Cow’s milk—like human milk—has been known to contain EVs. Using EVs from milk has been an intriguing area of study, says Dr. Patel, and they can be easily isolated in large quantity.

Dr. Patel’s lab developed a process to isolate the EVs from casein protein in skim milk and use them for drug delivery. In laboratory tests, the team found that milk-derived EVs could be used to deliver chemotherapy as well as a new type of treatment based on using RNA molecules, known as an antisense nucleotide, into liver cancer cells, causing the cells to die. Researchers also found the treatment shrank tumors in mice. “The study suggested that the use of milk-derived nanovesicles may be a promising approach for delivering drugs to liver tumors,” he says.

“These results are very preliminary,” Dr. Patel says, adding that his lab is also investigating any potential harmful effects of using these milk-derived nanovesicles. “We want to know whether we can manipulate the proteins on the vesicles so that they will more directly recognize the tumor cells, even for a particular tumor type. Ultimately, we also want to know whether we can deliver this type of treatment orally and have the same kind of effect.” Future studies will aim to refine the use of milk-derived EVs for drug delivery with the eventual goal of taking these into clinical trials.

The research was funded in part through the Office of the Director, National Institutes of Health and the National Center for Advancing Translational Sciences, as well as through the Mayo Clinic Center for Regenerative Medicine.

Other researchers are Joseph George, Ph.D., currently of the Kanazawa Medical University, Japan, and Irene K. Yan of Mayo Clinic.


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Nov 28, 2017 · Mayo Clinic Neurologist Receives Award for Stroke Research

Neurologist Thomas Brott, M.D., vividly remembers when he first saw his research making a difference for patients. It was 1987, and for years, he’d been devastated to see patients suffering the immediate effects of a stroke: facial drooping, loss of language, and paralysis. A physician at the University of Cincinnati, he’d learned of a new clot-dissolving drug—tissue plasminogen activator, or t-PA—that seemed capable of restoring blood flow in a blocked carotid artery. When the National Institutes of Health requested research proposals, he organized investigators at several medical centers to test t-PA in patients with acute strokes.

He was on call at a participating hospital in Cincinnati when a patient suffering stroke paralysis received t-PA. The patient slowly regained motion as the drug took effect. “It was breathtaking,” he recalls.

Dr. Brott, who came to Mayo Clinic’s Jacksonville, Florida, campus as a clinician-researcher in 1998, has devoted his career to studying numerous methods of treating and preventing dangerous clots and brain bleeds. He’s led complex, multi-institutional clinical studies involving thousands of patients and has helped define some of the best treatment options for patients.

This year, Dr. Brott, the Eugene and Marcia Applebaum Professor of Neurosciences, was selected as the recipient of the 2017 Research Achievement Award from the American Heart Association. He received the honor during the AHA Scientific Sessions in Anaheim, California, “for his pivotal role in the development of life-saving interventions that have revolutionized treatment of acute ischemic stroke, with enormous consequent benefits dramatically reducing stroke death and disability in the world’s population,” the AHA reports. He’s the fifth Mayo Clinic researcher to receive the honor since its inception in 1953.

But research hasn’t always been a smooth ride, he acknowledges, and succeeding has involved perseverance and luck. In the early 1980s he became interested in complication rates of carotid endarterectomy, a surgical method of preventing stroke by removing plaque from a carotid artery. With no funding, he examined more than 500 patient charts at 12 area hospitals and found complications of the procedure alarmingly high.

Though he would eventually serve for eight years as the Director of Research on Mayo’s campus in Florida, at the time, he could not get his first paper published. He finagled an invitation to present his study at a meeting of the American Academy of Neurology. In a twist of fate, a producer from ABC News attending the meeting became interested in his findings and developed a feature on 20/20 and Nightline. Suddenly endarterectomy was in the news. Surgeons—including pre-eminent neurosurgeon Thoralf Sundt, M.D., at Mayo Clinic’s campus in Rochester—were interested in discussing the study with Dr. Brott. Ultimately, the study helped lead to randomized clinical trials defining the risks and benefits of carotid surgery.

Dr. Brott forged ahead, researching intracerebral hemorrhage and defining the dynamic changes in some patients’ brains immediately after a hemorrhagic stroke. Collaborating with other researchers, he investigated a drug for stroke. “It didn’t work, but I learned all the ins and outs of conducting a clinical trial,” he says. When the NIH requested a method to measure the severity of a patient’s stroke disability, Dr. Brott worked with a team to develop the National Institute of Health Stroke Scale (NIHSS), which became the standard examination scale for stroke patients worldwide.

Around the same time, he noticed a Science paper describing the use of t-PA to unblock coronary arteries and prevent heart attacks.  He and others at an NIH meeting suggested a study using the drug to dissolve blood clots in arteries in the brain. NIH funded the study, and Dr. Brott’s team in Cincinnati enrolled most of the study’s patients. The introduction of the drug, now part of the standard of care for patients with small clots, was a key moment, says AHA President John Warner, M.D., “This triggered a major reorganization of stroke care delivery systems and the development of new tools to more reliably recognize its severity.”

During the last two decades at Mayo Clinic, Dr. Brott has focused on stroke prevention. He compared stenting—the insertion of wire mesh to widen a narrowed carotid artery—with endarterectomy in a randomized clinical trial involving more than 100 medical centers. Known as the Carotid Revascularization Endarterectomy vs. Stenting Trial, or CREST, the study he led evaluated more than 2,500 patients for ten years and found the two procedures to be equally safe and effective.

Dr. Brott is now the principal investigator for CREST II, for which he and neurologist James Meschia, M.D., received a National Institute of Neurological Disorders and Stroke grant of $39 million, one of the largest grants at Mayo Clinic. CREST II, a seven-year trial, is evaluating whether treatment with medicine (such as blood pressure drugs and statins) is as safe and effective as surgery or stenting in preventing a stroke. “Clinical research depends on good ideas, and I’ve learned it requires you to persevere, to be a bulldog. But you can’t do it without having great collaborators,” he says. “You have to be a bulldog who works with bulldogs.”


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Oct 10, 2017 · Researchers Link Alzheimer’s Gene to Type III Diabetes

Researchers have known for several years that being overweight and having Type II diabetes can increase the risk of developing Alzheimer’s disease. But they’re now beginning to talk about another form of diabetes—Type III diabetes—that’s also associated with the neurodegenerative disease. This newly defined diabetes occurs when the neurons in the brain become unable to respond to insulin, essential for basic tasks including memory and learning. In fact, some researchers believe insulin deficiency is central to the cognitive decline of Alzheimer’s disease. Mayo Clinic’s campuses in Rochester and Jacksonville recently participated in a multi-institution clinical study, testing whether a new, insulin nasal spray can improve Alzheimer’s symptoms. The results of that study are still forthcoming.

But is all of this tied to the Alzheimer’s gene APOE? A new study from the lab of neuroscientist Guojun Bu, Ph.D., Mary Lowell Leary Professor of Medicine, on Mayo Clinic’s campus in Florida, found that the culprit is the variant of the Alzheimer’s gene known as APOE4. Publishing in Neuron, the team found APOE4, present in approximately 20 percent of the general population and over 50 percent of Alzheimer’s cases, is responsible for interrupting how insulin gets processed in the brain. Mice with the APOE4 gene showed insulin impairment, particularly in old age. What’s more, a high-fat diet could accelerate the process in middle-aged mice with the gene. “The gene and the peripheral insulin resistance, caused by the high-fat diet, together induced insulin resistance in the brain,” Dr. Bu says.

The team went on to describe how it all works in the neurons. They found that the APOE4 protein, produced by the gene, is able to bind more aggressively to insulin receptors on the surfaces of neurons than its normal counterpart, APOE3. As if playing a game of musical chairs, the APOE4 protein out-competes the normal protein and blocks the receptor. APOE4 goes on to do lasting damage to brain cells. After blocking the receptor, the sticky APOE4 protein begins to clump and become toxic. Further, once the protein enters the interior of the neuron, the clumps get trapped within the cell’s machinery, making the receptors themselves unable to get back to the surface of the neuron to do their work. The insulin signal processing gets increasingly more impaired, resulting in brain cells that are effectively starved.

“This study has furthered our understanding of the gene that’s the strongest genetic risk factor known for Alzheimer’s disease,” says Dr. Bu, who adds that ultimately, the finding may help personalize treatment for individual patients. “For instance, an insulin nasal spray or a similar treatment may be significantly more helpful for patients who don’t have the APOE4 gene. Patients who have the gene may need additional medications to help prevent cognitive decline.”

Na Zhao, M.D., Ph.D., and Chia-Chen Lieu, Ph.D., of the Department of Neuroscience on Mayo Clinic’s campus in Florida, are co-first authors of this study.

In addition, other researchers on the team are:

  • Alexandra J. Van Ingelgom, Mayo Clinic
  • Yuka A. Martens, Ph.D., Mayo Clinic
  • Cynthia Linares, Mayo Clinic
  • Joshua A. Knight, Mayo Clinic
  • Patrick M. Sullivan, Ph.D., Duke University School of Medicine
  • Meghan M. Painter, Mayo Clinic


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