Dallas, TX, United States
Dallas, TX, United States

Time filter

Source Type

News Article | May 9, 2017
Site: www.eurekalert.org

DALLAS - May 8, 2017 - UT Southwestern Medical Center researchers found in a recent phase one clinical trial that stereotactic partial breast radiation was as safe as traditional radiation but decreased treatment time from six weeks to just days. UT Southwestern's Harold C. Simmons Comprehensive Cancer Center is the only site in Texas and one of a few in the world to offer stereotactic partial breast radiation treatment to early-stage breast cancer patients. "Standard breast cancer treatments are delivered daily to the entire breast area over three to six weeks. We sought to deliver partial breast radiation in a noninvasive way, using precise image-guided stereotactic radiation," said Dr. Asal Rahimi, Assistant Professor of Radiation Oncology and first author of the study. "Our trial decreased treatment time to just five treatments delivered every other day." Seventy-five patients were studied from 2010-2016, in whom stereotactic partial breast radiation demonstrated both outstanding tumor control and excellent cosmetic results. Patients in the trial had been recently diagnosed with early-stage breast cancer. The study is published in the International Journal of Radiation Oncology, Biology and Physics and was funded by a grant from Accuray, producers of the Cyberknife used to deliver stereotactic partial breast radiation. One of the trial participants is Dr. Rahimi's patient Leslie LeBlanc, a dental hygienist and resident of Arlington, Texas. Mrs. LeBlanc was diagnosed with early-stage breast cancer four years ago at age 47. Her daughter had just started college and her son was in high school. "The same day that I got the diagnosis was mother's weekend for my daughter at college. I drove straight to Austin and told her the news," said Mrs. LeBlanc, who recalled the shock of being diagnosed. "It's like you're in the eye of a hurricane. Everything is buzzing around you, but you can't do anything but what they ask you to do, or tell you is the best option." While no genetic link has been established, her two sisters had previously been diagnosed with breast cancer, so the family had some experience with the disease. Mrs. LeBlanc was already in a risk assessment program at UT Southwestern and had mammograms and MRIs every six months, which helped catch her disease early. "It was overwhelming to consider doing several weeks of daily radiation while trying to work fulltime, be with my family, and do everything that I needed to do. This treatment option was so much better. I only missed a few days from work," said Mrs. LeBlanc, who is looking forward to reaching her 5-year mark as a survivor next year. "Mrs. LeBlanc is a working woman, a mom, and a wife. She's a great example of many women that will be impacted by this disease," said Dr. Rahimi. "We wanted to make this treatment more convenient for patients, because cancer is never convenient." The researchers plan continued studies of the partial breast radiation technique. "As technology improves, we will detect more early-stage breast cancers." said Dr. Robert Timmerman, Professor of Radiation Oncology and senior author on the study. "Patients with these early cancers might particularly benefit from a local therapy approach that both minimizes the normal tissue exposure while improving the convenience for patients who already lead hectic lives." According to the National Cancer Institute, 252,710 women will be diagnosed with breast cancer this year. When breast cancer is found early before it has spread, the patient has an improved chance of surviving five years after being diagnosed. For breast cancer I females, 61.8 percent are diagnosed at the local stage. The 5-year survival for localized breast cancer in women is 98.9 percent. Stereotactic partial breast radiation is delivered with the latest generation CyberKnife, one of several technologies in UT Southwestern's newly opened $66 million, 63,000-square-foot Radiation Oncology facility. The new facility houses a comprehensive mix of UT Southwestern's best cancer treatment technologies and medical expertise under one roof, and has dedicated areas for each major disease site such as brain, breast, and gastrointestinal cancer. Additional UT Southwestern researchers involved in the study include: Dr. Ann Spangler, Associate Professor of Radiation Oncology; Dr. Roshni Rao, Associate Professor of Surgery; Dr. Marilyn Leitch, Professor of Surgery; Dr. Rachel Wooldridge, Assistant Professor of Surgery; Dr. Aeisha Rivers, Assistant Professor of Surgery; Dr. Stephen Seiler, Assistant Professor of Radiology; Dr. Kevin Albuquerque, Associate Professor of Radiation Oncology; Dr. Sally Goudreau, Professor of Radiology; Dr. Barbara Haley, Professor of Internal Medicine; Dr. David Euhus, (former faculty); Dr. Chuxiong Ding, Associate Professor of Radiation Oncology; and Dr. Chul Ahn, Professor of Clinical Sciences. Dr. Timmerman holds the Effie Marie Cain Distinguished Chair in Cancer Therapy Research. Dr. Leitch holds the S.T. Harris Family Distinguished Chair in Breast Surgery, in Honor of A. Marilyn Leitch, M.D. Dr. Haley holds the Charles Cameron Sprague, M.D., Chair in Clinical Oncology. The Harold C. Simmons Comprehensive Cancer Center is the only NCI-designated Comprehensive Cancer Center in North Texas and one of just 47 NCI-designated Comprehensive Cancer Centers in the nation. Simmons Comprehensive Cancer Center includes 13 major cancer care programs. In addition, the Center's education and training programs support and develop the next generation of cancer researchers and clinicians. Simmons Comprehensive Cancer Center is among only 30 U.S. cancer research centers to be designated by the NCI as a National Clinical Trials Network Lead Academic Participating Site. UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution's faculty has received six Nobel Prizes, and includes 22 members of the National Academy of Sciences, 18 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The faculty of more than 2,700 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in about 80 specialties to more than 100,000 hospitalized patients, 600,000 emergency room cases, and oversee approximately 2.2 million outpatient visits a year.


News Article | May 9, 2017
Site: www.eurekalert.org

DALLAS - May 9, 2017 - UT Southwestern research investigating the blood glucose-regulatory actions of the hormone ghrelin may have implications for development of new treatments for diabetes. Blood glucose is tightly regulated by the opposing actions of the hormones insulin and glucagon. Earlier studies led by Dr. Roger Unger, Professor of Internal Medicine at UT Southwestern Medical Center, demonstrated that experimentally deleting or neutralizing receptors for glucagon can prevent or correct dangerously high blood glucose levels in different models of diabetes. "Dr. Unger's research suggested that high or unopposed glucagon action that results from insulin deficiency is the main culprit in the development of high blood glucose - known as hyperglycemia - in diabetes," said Dr. Jeffrey Zigman, Professor of Internal Medicine and Psychiatry at UT Southwestern and senior author of the study, published online today in the journal Diabetes. "He proposed that blocking or neutralizing glucagon action may serve as a new treatment for Type 1 and Type 2 diabetes. This idea formed the basis of our current study," Dr. Zigman added. Like glucagon and insulin, ghrelin also plays an important role in blood glucose control. But because the hormone was only discovered in the 1990s, ghrelin's actions on blood glucose haven't been studied as much as those of glucagon and insulin. The UTSW research team wanted to learn more about the role of ghrelin in diabetes. "We studied mice that lacks glucagon receptors. When we tried to make these animals diabetic by giving them an agent that destroys insulin-producing cells, the mice did not develop diabetes. Their blood sugar was normal. In addition to these results, we found that their ghrelin levels were high," said Dr. Zigman, who holds the Kent and Jodi Foster Distinguished Chair in Endocrinology, in Honor of Daniel Foster, M.D., the Mr. and Mrs. Bruce G. Brookshire Professorship in Medicine, and The Diana and Richard C. Strauss Professorship in Biomedical Research. In a related set of studies, when the researchers blocked the action of the elevated ghrelin, doing so caused the animals' blood sugar levels to drop below normal, he added. "These findings suggest that when glucagon activity is blocked, circulating levels of ghrelin rise, which helps to prevent dangerously low blood sugars from developing, a condition known as hypoglycemia," Dr. Zigman said. Pharmaceutical companies are now developing drugs targeting glucagon receptors to treat diabetes, including antibodies that will neutralize glucagon receptors or drugs that will block glucagon receptors, he added. "The body's normal ghrelin response should protect diabetic individuals being treated with agents that target glucagon receptors from experiencing hypoglycemia," Dr. Zigman said. Since the current study focused on a Type 1 diabetes model, researchers next plan to examine the coordinated actions of the ghrelin and glucagon systems in a Type 2 diabetes model. They also want to study the impact of ghrelin on hypoglycemia. "A potential side effect with any treatment that lowers blood sugar is that hypoglycemia may develop," Dr. Zigman said. "We would like to determine whether the administration of ghrelin or a compound that mimics the action of ghrelin could help correct that hypoglycemia." Lead author of the study is Dr. Bharath Mani, Instructor of Internal Medicine, and the co-senior authors include Dr. Unger, who holds the Touchstone/West Distinguished Chair in Diabetes Research, and Dr. Eric Berglund, Assistant Professor in the Advanced Imaging Research Center and of Pharmacology. Other contributing UTSW researchers are Dr. Aki Uchida, postdoctoral research fellow; Dr. Young Lee, Assistant Professor of Internal Medicine; and Sherri Osborne-Lawrence, senior research scientist. The study received support from the National Institutes of Health, the Novo Nordisk Foundation Center for Basic Metabolic Research, and the Hilda & Preston Davis Foundation. UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution's faculty has received six Nobel Prizes, and includes 22 members of the National Academy of Sciences, 18 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The faculty of more than 2,700 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in about 80 specialties to more than 100,000 hospitalized patients, 600,000 emergency room cases, and oversee approximately 2.2 million outpatient visits a year. This news release is available on our website at http://www. . To automatically receive news releases from UT Southwestern via email, subscribe at http://www. .


News Article | May 19, 2017
Site: www.eurekalert.org

DALLAS - May 19, 2017 - Otherwise healthy young people with high systolic blood pressure over 140 are at greater risk for future artery stiffening linked to an increased risk of stroke as well as possible damage to the kidneys and brain, new research shows. The condition, called isolated systolic hypertension (ISH), occurs in people 18 to 49 who exhibit systolic blood pressure of 140 or higher (versus the optimal of under 120), but a normal diastolic pressure of around 80. Systolic pressure is the top number in a blood pressure reading and diastolic is the bottom number. This study - the largest ever conducted in the U.S. looking at whether young, otherwise healthy ISH patients actually have a cardiovascular problem - suggests the common approach of ignoring higher systolic blood pressure levels in younger adults may be wrong, said study author Dr. Wanpen Vongpatanasin, Director of UT Southwestern Medical Center's Hypertension Program. "I think we should consider treating these patients sooner rather than later," said Dr. Vongpatanasin, Professor of Internal Medicine in the Division of Cardiology at UT Southwestern Medical Center. "I'm concerned that not treating these individuals now will lead to more brain and kidney damage in the future. This condition is not going to get better. It's going to get worse." Although the condition is commonly treated in elderly patients, some physicians have avoided treating it in younger patients, thinking the higher systolic reading was an anomaly related to youth that would self-correct, or perhaps even a sign of a stronger heart since it sometimes showed up in high school athletes, said Dr. Vongpatanasin, who holds the Norman and Audrey Kaplan Chair in Hypertension and the Fredric L. Coe Professorship in Nephrolithiasis in Mineral Metabolism at UT Southwestern. The findings are important because although young people rarely have heart attacks or strokes, the incidence of isolated systolic hypertension in Americans 18 to 39 more than doubled over the last two decades and is now estimated to be about 5 percent, Dr. Vongpatanasin said. Researchers suspect the growing numbers may be related to increasing rates of obesity. This new study, published in the journal Hypertension, found that the threat of aortic stiffness is not only real, but also visible. UT Southwestern researchers examined 2,001 participants in the Dallas Heart Study, a population-based study of more than 6,000 adults in Dallas County. The researchers took cardiovascular magnetic resonance (CMR) pictures of the participants' hearts to assess the condition of the aorta - the major artery that carries oxygenated blood from the heart to the body. A section of the aorta that leads directly from the heart, called the proximal aorta, was the part found to be stiffened in young individuals with high systolic blood pressure. The next step will be to scan kidneys, brains, and hearts of participants from the Dallas Heart Study to determine what effect the aortic stiffening has had. The Dallas Heart Study is the centerpiece of the Donald W. Reynolds Foundation Cardiovascular Clinical Research Center in Dallas, one of three such Centers in the nation, along with those at Harvard and Johns Hopkins. The Dallas Heart Study is a multiethnic population-based study of 6,101 adults from Dallas County designed to: Funding for the study came from the Reynolds Foundation, the National Institutes of Health, the American Heart Association Strategically Focused Research Networks, the Dedman Family Endowed Program for Scholars in Clinical Care, the UT Southwestern George M. O'Brien Kidney Research Core Center, and the Norman and Audrey Kaplan Chair in Hypertension Research. Other researchers involved in this study included Dr. Ian Neeland, Assistant Professor of Internal Medicine; Colby Ayers, Faculty Associate in Clinical Sciences; Dr. Ronald Peshock, Professor of Radiology and Internal Medicine; and Dr. Jarett Berry, Associate Professor of Internal Medicine and of Clinical Sciences, and Dedman Family Scholar in Clinical Care. The national study also included researchers from the University of Mississippi Medical Center, the Northwestern University Feinberg School of Medicine, and Cardiovascular Engineering, Inc., of Norwood, Mass. UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution's faculty has received six Nobel Prizes, and includes 22 members of the National Academy of Sciences, 18 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The faculty of more than 2,700 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in about 80 specialties to more than 100,000 hospitalized patients, 600,000 emergency room cases, and oversee approximately 2.2 million outpatient visits a year.


News Article | May 18, 2017
Site: www.eurekalert.org

DALLAS - May 17, 2017 - One in three patients hospitalized for medical problems experienced a drop in their red blood cell count due to the hospitalization - a concept called hospital-acquired anemia, new research showed. Moreover, the worse the hospital-acquired anemia - or the more blood lost - the higher the risk of death or readmission, even after adjusting for other important factors, UT Southwestern Medical Center researchers reported in a study involving 11,000 patients cared for in six hospitals. "This study shines a spotlight on a very common but underappreciated risk of hospitalization, hospital-acquired anemia, which has traditionally been viewed as an incidental change in the red blood count of no significance. However, our results showed that hospital-acquired anemia was associated with worse clinical outcomes after leaving the hospital so it needs to be taken more seriously," said senior author Dr. Ethan Halm, Director of UT Southwestern's Center for Patient-Centered Outcomes Research and Chief of the William T. and Gay F. Solomon Division of General Internal Medicine at UT Southwestern. Dr. Halm, Professor of Internal Medicine and Clinical Sciences, holds the Walter Family Distinguished Chair in Internal Medicine in Honor of Albert D. Roberts, M.D. Hospital-acquired anemia is defined as having a normal blood count on admission but developing anemia during the course of hospitalization. The most severe form of hospital-acquired anemia was independently associated with a 39 percent increase in the odds of being readmitted or dying within 30 days after hospital discharge compared with not developing hospital-acquired anemia. The most severe form was defined as a hematocrit of 27 percent or less at the time of discharge, occurring in 1.4 percent of all hospitalizations in the study, which appears in the Journal of Hospital Medicine. "This is the first study of post-discharge adverse outcomes of hospital-acquired anemia among a diverse group of patients who were hospitalized for different reasons," said lead author Dr. Anil Makam, Assistant Professor of Internal Medicine and Clinical Sciences and a member of the Center for Patient-Centered Outcomes Research. Other studies have examined post-discharge outcomes in patients hospitalized for heart attacks. While the study does not establish preventability, it points to several directly associated risk factors of developing hospital-acquired anemia. "Our findings suggest that reducing blood loss during major surgeries and reducing unnecessary testing during hospital stays may lower a patient's risk of developing severe hospital-acquired anemia, and potentially improve their recovery," said Dr. Makam. In the current study, researchers found that the two strongest potentially modifiable predictors of developing moderate or severe hospital-acquired anemia are length of hospital stay and patients undergoing major surgery. In the future, researchers hope to examine other patient-centered outcomes that may be related to hospital-acquired anemia, such as fatigue, functional impairment, and the trajectory of post-hospital recovery. Others involved in the study included Dr. Oanh Nguyen, Assistant Professor of Internal Medicine and Clinical Sciences, and analyst Christopher Clark in the Office of Research Administration at Parkland Health and Hospital System. The study was supported by UT Southwestern's Center for Patient-Centered Outcomes Research (PCOR) and the National Institute on Aging. PCOR helps facilitate studies designed to ensure delivery of high-quality, patient-centered, evidence-based, equitable care. The UT Southwestern PCOR Center is funded through a grant from the Agency for Healthcare Research and Quality (AHRQ), with a mission to produce evidence to make health care safer, higher quality, more accessible, equitable, and affordable, and to work with the U.S. Department of Health and Human Services and other partners to ensure that the evidence is understood and used. UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution's faculty includes many distinguished members, including six who have been awarded Nobel Prizes since 1985. The faculty of almost 2,800 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide medical care in about 80 specialties to more than 100,000 hospitalized patients and oversee approximately 2.2 million outpatient visits a year. This news release is available on our website at http://www. To automatically receive news releases from UT Southwestern via email, subscribe at http://www.


News Article | May 31, 2017
Site: www.eurekalert.org

DALLAS - May 31, 2017 - Scientists have identified more than 100 genes linked to memory, opening new avenues of research to better understand memory processing in the human brain. A study at the Peter O'Donnell Jr. Brain Institute includes the results of a new strategy to identify genes that underlie specific brain processes. This strategy may eventually help scientists develop treatments for patients with memory impairments. "Our results have provided a lot of new entry points into understanding human memory," said Dr. Genevieve Konopka, Assistant Professor of Neuroscience with the O'Donnell Brain Institute at UT Southwestern Medical Center. "Many of these genes were not previously linked to memory, but now any number of labs could study them and understand their basic function in the brain. Are they important for brain development; are they more important for aspects of behavior in adults?" The study published in Cerebral Cortex stems from previous research by Dr. Konopka that linked specific genes to resting-state brain behavior. She wanted to use that same assessment to evaluate brain activity during active information processing. To do so, she collaborated with Dr. Bradley Lega, a neurosurgeon with the O'Donnell Brain Institute conducting memory research on epilepsy patients while helping to locate the source of their seizures. Dr. Lega maps the brain waves of these patients to understand what patterns are critical for successful memory formation. Combining their techniques, the doctors found that a different group of genes is used in memory processing than the genes involved when the brain is in a resting state. A number of them had not previously been linked to any brain process, Dr. Konopka said. Dr. Lega is hopeful the findings can help scientists better understand and treat a range of conditions involving memory impairment, from epilepsy to Alzheimer's disease. He also hopes the study's success in combining genetics and cognitive neuroscience will encourage more scientists to reach beyond their areas of expertise to elevate their research. "This kind of collaboration is not possible unless high-quality neuroscience research and academically minded clinicians are in close physical and intellectual proximity. I don't think either of us working or thinking independently would've come up with this type of analysis. Ideally, the O'Donnell Brain Institute will be a natural incubator for these sorts of collaborations for a number of neuroscience fields," said Dr. Lega, Assistant Professor of Neurological Surgery, Neurology and Neurotherapeutics, and Psychiatry. The study was supported by UT Southwestern Jon Heighten Scholar in Autism Research, the National Institutes of Health, the James S. McDonnell Foundation 21st Century Science Initiative in Understanding Human Cognition Scholar Award, Friends of the Alzheimer's Disease Center at UT Southwestern, the David M. Crowley Foundation, and a UT BRAIN Initiative Seed Grant. UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution's faculty has received six Nobel Prizes, and includes 22 members of the National Academy of Sciences, 18 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The faculty of more than 2,700 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in about 80 specialties to more than 100,000 hospitalized patients, 600,000 emergency room cases, and oversee approximately 2.2 million outpatient visits a year. This news release is available on our website at http://www. . To automatically receive news releases from UT Southwestern via email, subscribe at http://www. .


News Article | February 16, 2017
Site: www.eurekalert.org

DALLAS - Feb. 16, 2017 - A component of an enzyme family linked to DNA repair, stress responses, and cancer also plays a role in enhancing or inhibiting major cellular activities under physiological conditions, new research shows. The UT Southwestern Medical Center research focused on PARP-1, a member of the PARP enzyme family. Short for poly (ADP-ribose) polymerase, PARP became the focus of attention in 2014 with approval of the first PARP inhibitor drug to treat advanced ovarian cancer associated with mutant BRCA DNA repair genes. The drug, Lynparza or olaparib, blocks nuclear PARP enzymes, inhibiting DNA repair even further and causing genome instability that kills the cancer cells. In two related studies published in Molecular Cell, UT Southwestern scientists describe how PARP-1 can act at a molecular level under physiological conditions to reduce the formation of fat cell precursors and to help maintain the unique ability of embryonic stem cells to self-renew and become any of a variety of different cell types. One of the studies is published online today; the earlier study posted Jan. 19. PARP-1's role in these cellular processes occurs during gene transcription, when DNA is copied into messenger RNA molecules, which can then be used as a template to produce new proteins. Researchers already knew about PARP's role in DNA damage-related diseases like cancer, said Dr. W. Lee Kraus, senior author of both UTSW studies and Professor of Obstetrics and Gynecology, and Pharmacology at UT Southwestern. Dr. Kraus also directs the Cecil H. and Ida Green Center for Reproductive Biology Sciences and holds the Cecil H. and Ida Green Distinguished Chair in Reproductive Biology Sciences. These findings take the field in a new direction, Dr. Kraus said. "Our research shows that PARP-1 also plays a role in normal physiological processes and normal cellular functions. It's an important component of the cellular machinery that senses and responds to the environment," he said. While studies in mouse models show PARP-1 is not essential for life, it becomes important when an organism needs to adapt to changing environmental or physiological cues, such as developmental processes or altered diet, Dr. Kraus said. Understanding how PARP-1 works could one day help researchers find ways to target the protein to treat metabolic disorders or obesity, he said. The two new UT Southwestern studies outline for the first time the exact molecular mechanisms of PARP-1's roles in inhibiting the formation of fat cell precursors and in maintaining stem cells. Here are the key findings: Dr. Ziying Liu, a former graduate student and current postdoctoral researcher, was lead author of the study released today. Co-first authors of the earlier study were Dr. Xin Luo, a former graduate student and current data scientist, and Keun Woo Ryu, a graduate student. Other authors contributing to one or both studies were Dr. Dae-Seok Kim, Dr. Rebecca Gupte, and Dr. Bryan Gibson, postdoctoral researchers; Tulip Nandu, computational biologist; Dr. Yonghao Yu, Assistant Professor of Biochemistry and a Virginia Murchison Linthicum Scholar in Medical Research; and Dr. Rana Gupta, Assistant Professor of Internal Medicine. Researchers from the Perelman School of Medicine at the University of Pennsylvania also contributed. The study was supported by funding from the National Institutes of Health's National Institute of Diabetes and Digestive and Kidney Diseases, the Department of Defense Breast Cancer Research Program, the American Heart Association, the Welch Foundation, and the Cecil H. and Ida Green Center for Reproductive Biology Sciences. UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution's faculty includes many distinguished members, including six who have been awarded Nobel Prizes since 1985. The faculty of almost 2,800 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide medical care in about 80 specialties to more than 100,000 hospitalized patients and oversee approximately 2.2 million outpatient visits a year. This news release is available on our website at http://www. To automatically receive news releases from UT&bsp;Southwestern via email, subscribe at http://www.


DALLAS - March 1, 2017 - A large national study suggests that treating pregnant women for mildly low thyroid function does not improve the IQs of their babies or reduce preterm births or other negative outcomes. The 10-year study, conducted at UT Southwestern Medical Center and 14 other universities and medical centers in the National Institutes of Health's (NIH) Maternal Fetal Medicine Units Network, found no benefit in treating the women during their pregnancies. The results are published today in The New England Journal of Medicine (NEJM). Full-blown hypothyroidism during pregnancy, especially when untreated, has long been associated with lower mental functioning in offspring, as well as low birth weight, stillbirth, and preterm labor. It is commonly treated by giving expectant mothers a synthetic substitute to boost their low thyroid hormone, thyroxine. In 1999, another NEJM study raised concerns that the same problems might occur in women with even mild, or subclinical, hormone abnormalities. As a result, several physician groups called for routine testing of all pregnant women in the U.S. -- about 4 million women a year -- and treatment for these marginal hormone problems. The American College of Obstetricians and Gynecologists has recommended against universal screening for thyroid disease in pregnant women. "Our study found that treatment did not benefit children born to these women," said Dr. Brian Casey, Professor of Obstetrics and Gynecology at UT Southwestern Medical Center and first author of the new study. "There's no evidence that treatment improves either pregnancy outcomes or the children's neurodevelopmental or behavioral outcomes through 5 years of age." Dr. Casey is Division Director of Maternal-Fetal Medicine at UT Southwestern and holds the Gillette Professorship of Obstetrics and Gynecology. He is also Chief of Obstetrics at Parkland Health & Hospital System. The NIH study grew out of research begun in 2000 at UT Southwestern, when Dr. Casey and his colleagues performed a study on thyroid disease during pregnancy in over 25,000 women at Parkland Memorial Hospital. That study culminated in his proposal of a multicenter treatment study to the NIH in 2005. Dr. Casey now is principal investigator of the NIH study and chair of the protocol subcommittee. Starting in October 2006, researchers screened more than 97,000 pregnant women for the study and enrolled 1,203 who had either subclinical hypothyroidism or isolated hypothyroxinemia. Subclinical hypothyroidism is characterized by high levels of a pituitary gland hormone, TSH, which stimulates the thyroid to produce thyroxine. In isolated hypothyroxinemia, the pituitary hormone level is normal, but thyroxine, or free T4, is abnormally low. Half the study participants were given levothyroxine, a synthetic substitute for their thyroid hormone; the other half received a placebo. Researchers then analyzed pregnancy outcomes of both groups and followed the neurocognitive development of the women's babies for five years. IQ levels and other test scores were not significantly different between the children of women given levothyroxine and children whose mothers received a placebo, Dr. Casey said. Children of the women treated for subclinical hypothyroidism scored an average of 97 on the IQ test, compared with 94 for those born to women in the placebo group. In the hypothyroxinemia part of the study, the children of those treated averaged 94, while offspring of those given placebos averaged 91. These scores are considered normal and the three-point differences are not viewed as significant, Dr. Casey said. The results suggest there is no benefit to widespread testing and treatment for subclinical thyroid problems during pregnancy, he said. "If treatment doesn't improve outcomes, then it calls into question whether we should be screening every pregnant woman for this mild degree of thyroid deficiency." A 2012 study published in The Journal of Clinical Endocrinology & Metabolism estimated a cost of $25 (in 2009 dollars) for the TSH test and $13 to test the free T4 thyroid hormone level, in addition to the cost of the physician visits and consultation. Pregnant women diagnosed with a thyroid problem would then need continued testing, as well as potential treatment with levothyroxine at an estimated cost of $170 (again, in 2009 dollars) for a year's supply. The current study's findings followed those of a large British study, published in NEJM in 2012, which screened more than 20,000 pregnant women. That study concluded treatment for reduced thyroid function in pregnant women did not improve cognitive function in their children at age 3. The newly published study was funded by the NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development, along with the National Institute of Neurological Disorders and Stroke. UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution's faculty includes many distinguished members, including six who have been awarded Nobel Prizes since 1985. The faculty of almost 2,800 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide medical care in about 80 specialties to more than 100,000 hospitalized patients and oversee approximately 2.2 million outpatient visits a year. This news release is available on our website at http://www. To automatically receive news releases from UT Southwestern via email, subscribe at http://www.


News Article | February 16, 2017
Site: www.eurekalert.org

DALLAS - Feb. 16, 2017 - Researchers at UT Southwestern Medical Center, working with a California biotech firm, have developed a potential drug to treat polycystic kidney disease - an incurable genetic disease that often leads to end-stage kidney failure. The drug, now called RGLS4326, is in preclinical animal testing at San Diego-based Regulus Therapeutics Inc. An investigational new drug filing to pave the way for human clinical trials is expected later this year, said Dr. Vishal Patel, Assistant Professor of Internal Medicine at UT Southwestern. Dr. Patel is senior author of a study describing research that led to the drug's development, published online today in Nature Communications. Affecting about 600,000 people in the U.S., autosomal dominant polycystic kidney disease (ADPKD) causes numerous fluid-filled cysts to form in the kidney. An affected kidney, normally the size of a human fist, sometimes grows as large as a football. As their numbers and sizes increase, these cysts eventually interfere with the kidney's ability to filter blood and remove bodily waste. The cysts can quietly grow for decades until symptoms appear such as blood in the urine, Dr. Patel said. About half of those affected with ADPKD suffer kidney failure by age 60, according to the National Kidney Foundation. "There isn't a single drug on the U.S. market right now to treat the disease," Dr. Patel said. "Once your kidneys fail, your only option for survival is to get a transplant or start dialysis." In 2009, Dr. Patel began searching for microRNAs that might underlie progression of ADPKD. MicroRNAs - or MiRs for short - are tiny RNA fragments that interfere with normal gene expression. Proof that such RNA fragments even existed came in the early 1990s; their presence in humans was first reported in 2000. Those discoveries led to a groundswell of interest in developing drugs to treat diseases caused by microRNAs, Dr. Patel said - in part because the process can be straightforward once the problem-causing fragment is identified. "Because miRs are so small, drugs can easily be designed against them. And since we know the nucleotide sequence of every known microRNA, all that is required is to prepare an anti-miR with a sequence that is exactly the opposite of the miR's," he said. In this study, researchers in Dr. Patel's lab focused on microRNA cluster 17~92 following identification of potential miR targets. A National Institutes of Health grant funded the UTSW research. In 2013, Dr. Patel and fellow researchers reported in Proceedings of the National Academy of Sciences that this microRNA cluster indeed appeared to promote kidney cyst growth. Using four mouse models, the researchers next studied whether inhibiting this microRNA could slow cyst growth and thus delay ADPKD progression. They found that genetically deleting microRNA-17~92 slowed cyst growth and more than doubled the life spans of some mice tested. Based on that finding, Dr. Patel's lab collaborated with Regulus Therapeutics to test an anti-microRNA-17 drug. The test drug slowed the growth of kidney cysts in two mouse models and in cell cultures of human kidney cysts, the study showed. In the Nature Communications study, UTSW researchers also reported how miR-17 causes cyst proliferation: the molecule essentially reprograms the metabolism of kidney cells so that cellular structures called mitochondria use less nutrients, freeing up resources to instead make cell parts that become cysts. MiR-17 accomplishes this by repressing a protein involved in making RNA called peroxisome proliferator-activated receptor alpha (PPARα), the researchers found. Other UT Southwestern researchers included lead author Dr. Sachin Hajarnis, a research scientist; Dr. Ronak Lakhia, Instructor in Internal Medicine; Matanel Yheskel and Andrea Flaten, research technicians; Darren Williams, former research associate; Dr. Shanrong Zhang, research engineer; Joshua Johnson, an M.D./Ph.D. student; Dr. William Holland and Dr. Christine Kusminski, Assistant Professors of Internal Medicine; and Dr. Philipp Scherer, Professor of Internal Medicine and Cell Biology, who holds the Gifford O. Touchstone, Jr. and Randolph G. Touchstone Distinguished Chair in Diabetes Research. Also contributing to the study were researchers from the University of Minnesota Medical School, the Mayo Clinic School of Medicine, the University of Montreal, the University of Kansas, and Regulus Therapeutics. Funding was provided by the National Institutes of Health (NIH) and the PKD Foundation. Research reported in this publication was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the NIH under Award Number R01DK102572. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. UT Southwestern and Regulus Therapeutics have applied for a patent for treatment of polycystic kidney disease with miR-17 inhibitors. In addition, Dr. Patel's laboratory has a sponsored research agreement with Regulus, and Dr. Patel serves as a consultant for Regulus. UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution's faculty includes many distinguished members, including six who have been awarded Nobel Prizes since 1985. The faculty of almost 2,800 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide medical care in about 80 specialties to more than 100,000 hospitalized patients and oversee approximately 2.2 million outpatient visits a year.


News Article | February 21, 2017
Site: www.eurekalert.org

DALLAS - Feb. 20, 2017 - How we think and fall in love are controlled by lightning-fast electrochemical signals across synapses, the dynamic spaces between nerve cells. Until now, nobody knew that cancer cells can repurpose tools of neuronal communication to fuel aggressive tumor growth and spread. UT Southwestern Medical Center researchers report those findings in two recent studies, one in the Proceedings of the National Academy of Sciences (PNAS) and the second in Developmental Cell "Many properties of aggressive cancer growth are driven by altered cell signaling," said Dr. Sandra Schmid, senior author of both papers and Chair of Cell Biology at UT Southwestern. "We found that cancer cells are taking a page from the neuron's signaling playbook to maintain certain beneficial signals and to squelch signals that would harm the cancer cells." The two studies find that dynamin1 (Dyn1) - a protein once thought to be present only in nerve cells of the brain and spinal cord - is also found in aggressive cancer cells. In nerve cells, or neurons, Dyn1 helps sustain neural transmission by causing rapid endocytosis - the uptake of signaling molecules and receptors into the cell - and their recycling back to the cell surface. These processes ensure that the neurons keep healthy supplies at the ready to refire in rapid succession and also help to amplify or suppress important nerve signals as necessary, Dr. Schmid explained. "This role is what the cancer cells have figured out. Aggressive cancer cells have usurped the mechanisms that neurons use for the rapid uptake and recycling of neural transmitters. Instead of neural transmitters, the cancer cells use Dyn1 for rapid uptake and recycling of EGF (epidermal growth factor) receptors. Mutations in EGF receptors are drivers of breast and lung cancers," she said of the Developmental Cell study. In order to thrive, cancer cells must multiply faster than nearby noncancerous cells. EGF receptors help them do that, she explained. Cancer cell survival is another factor in disease progression. In the PNAS study, the Schmid lab found that aggressive cancer cells appear to have adapted neuronal mechanisms to thwart a key cancer-killing pathway triggered by activating "death receptors" (DRs) on cancer cells. Specifically, aggressive cancer cells appear to have adapted ways to selectively activate Dyn1 to suppress DR signaling that usually leads to cancer cell death. "It is amazing that the aggressive cancers use a signaling pathway to increase the activity of EGF and also turn on Dyn1 pathways to suppress cancer death - so you have this vicious circle," said Dr. Schmid, who holds the Cecil H. Green Distinguished Chair in Cellular and Molecular Biology. She stressed that less aggressive cancers respond to forms of chemotherapy that repress EGF signaling and/or die in response to the TRAIL-DR pathway. However, aggressive lung and breast cancer cells have adapted ways to commandeer the neuronal mechanisms identified in these studies. The hope is that this research will someday lead to improved strategies to fight the most aggressive cancers, she said. Currently, her laboratory is conducting research to identify Dyn1 inhibitors as potential anticancer drugs using a 280,000-compound library in a shared facility at UT Southwestern. "Cancer is a disease of cell biology. To grow, spread, and survive, cancer cells modify normal cellular behavior to their advantage. They can't reinvent the underlying mechanisms, but can adapt them. In these studies, we find that some cancer cells repurpose tools that neurons use in order to get a competitive advantage over nearby normal cells," she said. Lead author of the PNAS study is Dr. Carlos Reis, a former postdoctoral researcher. Other UT Southwestern co-authors in Cell Biology are Dr. Nawal Bendris, a former postdoctoral researcher, and Dr. Ping-Hung Chen, a postdoctoral fellow. This research was supported by grants from the National Institutes of Health (NIH) and the Cancer Prevention and Research Institute of Texas (CPRIT). Dr. Chen is lead author of the Developmental Cell study. Other UT Southwestern co-authors include: Dr. Bendris, Dr. Reis, and Dr. Marcel Mettlen, Assistant Professor of Cell Biology. Researchers from Taiwan also participated. This study received support from the NIH and a National Science Council of Taiwan grant. Other assistance came from the National Cancer Institute-supported Harold C. Simmons Comprehensive Cancer Center and the Texas Institute for Brain Injury and Repair-supported Whole Brain Microscopy Facility, both of which are located at UT Southwestern. The Harold C. Simmons Comprehensive Cancer Center is the only NCI-designated comprehensive cancer center in North Texas and one of just 47 NCI-designated comprehensive cancer centers in the nation. Simmons Cancer Center includes 13 major cancer care programs. In addition, the Center's education and training programs support and develop the next generation of cancer researchers and clinicians. Simmons Cancer Center is among only 30 U.S. cancer research centers to be designated by the NCI as a National Clinical Trials Network Lead Academic Participating Site. UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution's faculty includes many distinguished members, including six who have been awarded Nobel Prizes since 1985. The faculty of almost 2,800 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide medical care in about 80 specialties to more than 100,000 hospitalized patients and oversee approximately 2.2 million outpatient visits a year. This news release is available on our website at http://www. To automatically receive news releases from UT Southwestern via email, subscribe at http://www.


News Article | February 27, 2017
Site: www.eurekalert.org

DALLAS - February 27, 2017 - Lack of exercise and excessive weight are strongly associated with a type of heart failure that has a particularly poor prognosis, UT Southwestern Medical Center researchers determined in an analysis of data from three large studies. Heart failure is a chronic condition in which the heart is unable to supply enough oxygenated blood to meet the demands of the body. Heart failure is approximately equally divided between two subtypes: heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). Ejection fraction refers to the percentage of the blood that exits the heart with each contraction. "Previous studies have consistently found an association between low levels of physical activity, high BMI, and overall risk of heart failure, but this study shows that the association is more pronounced for heart failure with preserved ejection fraction, the type of heart failure that is the most challenging to treat," said preventive cardiologist Dr. Jarett Berry, Associate Professor of Internal Medicine at UT Southwestern, and the study's senior author. The study appears in the Journal of the American College of Cardiology. In heart failure with preserved ejection fraction, the heart stiffens. Instead of being soft, it's rigid and it resists expansion. Cardiologists often explain the difference between the two types of heart failure by saying that in heart failure with preserved ejection fraction, the heart doesn't relax enough, while in heart failure with reduced ejection fraction the heart doesn't squeeze enough. Many treatments have been developed for treating the latter but there are no evidence-based treatments for the former. "The five-year survival rate among heart failure with preserved ejection fraction patients is around 30 to 40 percent. While heart failure with reduced ejection fraction survival has improved significantly over the years, heart failure with preserved ejection fraction prognosis is little changed," said Dr. Ambarish Pandey, a cardiology fellow in Internal Medicine at UT Southwestern Medical Center and first author of the study. The pooled analysis looked at data from 51,000 participants in three cohort studies, the Women's Health Initiative, the Multiethnic Study of Atherosclerosis (MESA), and the Cardiovascular Health Study. Among the 51,000 participants, there were 3,180 individuals who developed heart failure. Of these, 39 percent were heart failure with preserved ejection fraction, 29 percent were heart failure with reduced ejection fraction, and 32 percent had not been classified when the data was gathered. The incidence of heart failure with preserved ejection fraction was 19 percent lower for individuals who exercised at recommended levels. Similarly, body mass index (BMI) had an inverse relationship with heart failure with preserved ejection fraction. Higher BMI levels were more strongly associated with heart failure with preserved ejection fraction than with heart failure with reduced ejection fraction. Heart failure with preserved ejection fraction is a growing problem as the population ages, and is particularly a problem among elderly women. Medications such as ACE inhibitors, beta blockers, and aldosterone antagonists have been shown in large-scale randomized trials to reduce mortality in patients with heart failure with reduced ejection fraction. Clinical trials have not identified medications that reduce mortality in patients with heart failure with preserved ejection fraction. Heart transplant is the ultimate option for some patients with heart failure with reduced ejection fraction but is not an option for patients with heart failure with preserved ejection fraction, all of which means that prevention is crucial for heart failure with preserved ejection fraction. "These findings highlight the importance of lifestyle interventions such as increasing physical activity levels and reducing weight to combat the growing burden of this disease," said Dr. Berry, Dedman Family Scholar in Clinical Care. Other UT Southwestern researchers who contributed to this study are Colby Ayers, faculty associate, and Dr. James de Lemos, Professor of Internal Medicine and holder of the Sweetheart Ball?Kern Wildenthal, M.D., Ph.D. Distinguished Chair in Cardiology. Funding for this study was provided by the American Heart Association. UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution's faculty includes many distinguished members, including six who have been awarded Nobel Prizes since 1985. The faculty of almost 2,800 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide medical care in about 80 specialties to more than 100,000 hospitalized patients and oversee approximately 2.2 million outpatient visits a year. This news release is available on our website at http://www. . To automatically receive news releases from UT Southwestern via email, subscribe at http://www.

Loading Ut Southwestern Medical Center collaborators
Loading Ut Southwestern Medical Center collaborators