News Article | May 24, 2017
Patients with non-small cell lung cancer (NSCLC) often respond to standard chemotherapy, only to develop drug resistance later, and with fatal consequences. But what if doctors could identify those at greatest risk of relapse and provide a therapy to overcome or avoid it? Researchers at UT Southwestern Medical Center believe they have an answer: a 35-gene signature that identifies tumor cells most likely to develop resistance to treatment. The study, published today in Cell Reports, points to a new pharmacologic approach to target chemo-resistant lung cancer and even prevent development of such resistance in the first place. "Cancer relapse after chemotherapy poses a major obstacle to treating lung cancer, and resistance to chemotherapy is a big cause of that treatment failure," said study co-author Dr. John Minna, a Professor and Director of in the Hamon Center for Therapeutic Oncology Research at UT Southwestern. "These findings provide new insights into why resistance develops and how to overcome it." Dr. Minna, with additional appointments in Pharmacology and Internal Medicine, also holds the Sarah M. and Charles E. Seay Distinguished Chair in Cancer Research and the Max L. Thomas Distinguished Chair in Molecular Pulmonary Oncology. Investigators studied mouse and cellular models of NSCLC, a type of lung cancer that the American Cancer Society estimates accounts for 85 percent of all lung cancer cases in the United States. "Previous studies have shown that up to 70 percent of those cancers develop resistance to standard therapy, such as the platinum-taxane two-drug combo that is often given," said study senior author Dr. Elisabeth D. Martinez, Assistant Professor of Pharmacology and in the Hamon Center. Both she and Dr. Minna are also members of UTSW's Harold C. Simmons Comprehensive Cancer Center. Using long-term on/off drug cycles, lead author and former postdoctoral researcher Dr. Maithili Dalvi developed a series of cellular models of progressive tumor resistance to standard chemotherapy that ranged from very sensitive to highly insensitive. Next, the researchers identified genes commonly altered during the development of resistance across multiple cell line and mouse models and identified a 35-gene signature that indicated a higher genetic likelihood of chemotherapy resistance. "It's like a fingerprint for resistance," Dr. Martinez said, adding that it was predictive in both cells and mouse models. Next they compared this resistance biomarker using genetic profiles from human tumors in their National Cancer Institute (NCI) lung cancer Specialized Programs of Research Excellence (SPORE) database at UT MD Anderson Cancer Center in Houston. The database contained information on patient outcomes and those who had been treated with the two-drug chemotherapy. The genetic fingerprint for resistance correlated with cancer relapse in NSCLC patients in the database, she said. Researchers discovered that as cancer cells developed greater resistance to chemotherapy, they progressively made higher amounts of enzymes called JumonjiC lysine demethylases. Dr. Martinez said these enzymes facilitate resistance by changing the expression of - or turning on and off - genes. "Cancer cells use these enzymes to change, or reprogram, gene expression in order to survive the toxic stress of the chemotherapy. By changing the expression of genes, the tumor cells can adapt and survive the toxins," she said. Investigators then tested two potential drugs, both JumonjiC inhibitors. One of them, JIB-04, was found by UT Southwestern researchers in the Martinez lab during a small-molecule screen conducted at the National Center for Advancing Translational Sciences' Chemical Genomics Center in Bethesda, Maryland. "I believe this is the first report of NSCLC tumors taking advantage of multiple JumonjiC enzymes to reprogram gene expression in order to survive chemotoxic stress. In addition, and this is the most fascinating part: Dr. Dalvi found that greater chemotherapy resistance defines a new susceptibility to the JumonjiC inhibitors," she said. "The cancer cells develop a new Achilles' heel that we can hit." Because the chemo-resistant cancer cells are dependent on JumonjiC enzymes for survival, inhibiting those enzymes returns cancer cells to mortality and vulnerability to cell death, she explained. "We think these JumonjiC inhibitors have the potential to be used either to treat tumors once they become resistant to standard therapies, or to prevent resistance altogether," she said. "In our experiments these inhibitors appear to be much more potent in killing cancer cells than normal cells." Later, researchers tested whether the Jumonji inhibitors JIB-04 or GSK-J4 prevented chemotherapy resistance. This strategy succeeded in cell cultures and partially prevented resistance in animal models, Dr. Martinez said.
News Article | May 25, 2017
A new DNA vaccine when delivered to the skin prompts an immune response that produces antibodies to protect against toxic proteins associated with Alzheimer's disease -- without triggering severe brain swelling that earlier antibody treatments caused in some patients. Two studies from the Peter O'Donnell Jr. Brain Institute demonstrate in animals how a vaccine containing DNA of the toxic beta-amyloid protein elicits a different immune response that may be safe for humans. The vaccine, which will likely be tested further by the U.S. Food and Drug Administration, is on a shortlist of promising antibody treatments that may eventually help settle a high-stakes debate of whether amyloid is a vital target for preventing or curing Alzheimer's. "If you look at the hard reality, the odds are against us because so many therapies have failed through the years. But this has potential," said Dr. Roger Rosenberg, co-author of the studies and Director of the Alzheimer's Disease Center at UT Southwestern Medical Center. Dr. Rosenberg notes that earlier research established that antibodies significantly reduce amyloid buildup in the brain, but he needed to find a safe way to introduce these into the body. A vaccine developed elsewhere showed promise in the early 2000s, but when tested in humans it caused brain swelling in some patients. Dr. Rosenberg's idea was to start with DNA coding for amyloid and inject it into the skin rather than the muscle. The injected skin cells make the amyloid protein, and the body responds by producing new antibodies that inhibit the buildup of amyloid, which some scientists blame for destroying neurons. Although the DNA vaccine has not yet been tested in humans, it produces a different kind of immune response in the tested animals that significantly lessens the chance of an adverse response in the brain, according to the studies published in the Journal of Alzheimer's Disease and Alzheimer's Research & Therapy. The research is notable because it shows a DNA vaccine can be effective and safe in two large mammals. Most other vaccines only produced an immune response in mice but not large mammals. "We believe this kind of immune response has a high probability of being safe in humans and also being effective to make high levels of antibody," said Dr. Rosenberg, Professor of Physiology, Neurology and Neurotherapeutics. Alzheimer's disease is characterized by progressive deterioration of the brain as neurons are destroyed. More than 5 million Americans have the fatal disease, with the number expected to nearly triple by 2050, according to the Centers for Disease Control and Prevention. No known cure exists, though an array of antibody and other treatments are being researched to target amyloid plaques. One strategy involves preforming the antibodies in the laboratory and inserting them into the body -- a technique that is still being tested for clinical benefits. Dr. Rosenberg said there would be distinct advantages to allowing the body to produce its own antibodies through active immunization, if it can be done safely. Among them, the vaccine would be more accessible and less expensive. It also produces a wider variety of antibody types than the preformed antibodies, he said. "All the vaccines we received as kids and adults have been active vaccinations; we made the antibodies in the body," Dr. Rosenberg said. "It's safer, more effective, and it's sustained longer." Dr. Rosenberg's research is the latest contribution to decades of study across the globe focusing on clearing amyloid plaques in hopes of curing or slowing the progression of Alzheimer's. A lack of results over the years has prompted some scientists to question whether they are properly targeting the disease. A British study from 2008 showed that removing amyloid after it accumulates in the brain does not improve brain cognition. The findings highlight a couple of lingering questions that have crucial implications for the future of Alzheimer's research: Is amyloid merely a symptom, not the cause of the disease? And if there is causation, can earlier treatments make a difference? Dr. Rosenberg acknowledges that preventing amyloid buildup by itself may not be an adequate treatment for Alzheimer's, but it could be a major part of the solution. He and other researchers at UT Southwestern are also studying the potential benefits of preventing and removing tangles of toxic tau proteins from the brain, another hallmark of the disease. "Some in the scientific community believe the reason amyloid therapies have failed so far is because too little of the therapy was given, and too late," Dr. Rosenberg said. "The jury is still out." Dr. Rosenberg's latest studies show the potential of a DNA vaccine to prevent the buildup of amyloid in otherwise healthy people. The vaccine was administered to healthy animals, inducing an anti-inflammatory immune response of up to 40 times more anti-amyloid antibodies than an earlier vaccine Dr. Rosenberg tested a decade ago. Dr. Rosenberg expects the FDA will want further tests of the vaccine in its own labs before planning a potential clinical trial on people. If proven effective, the vaccine could be given to people who are at risk of developing Alzheimer's but have not yet started forming amyloid plaques. Dr. Rosenberg keeps his expectations in check, noting the billions of dollars and multitude of studies that have so far yielded little advancement in treating Alzheimer's disease. "Finding answers to this disease will knock you down fast," said Dr. Rosenberg, who has worked at UT Southwestern for 44 years and holds the Abe (Brunky), Morris and William Zale Distinguished Chair in Neurology. "I've made a commitment to this place and to this research. I'm trying, and I'll keep going."
News Article | May 25, 2017
The number of motor vehicle fatalities involving children under age 15 varies widely by state, but occurrences are more common in the South, and are most often associated with improperly or unused restraints and crashes on rural roads, a new review of child-related auto fatalities shows. The study, conducted jointly by researchers at Harvard and UT Southwestern Medical Center, is the first to look at state-level trends in child fatalities involving motor vehicle crashes, and to account for differences in geography and state laws and regulations. Overall, about 16 percent of children involved in fatal wrecks died -- 2,885 children total over the four-year review period from 2010 to 2014. The South proved deadliest: 1,550 children died in fatal wrecks; a mortality rate of 1.34 per 100,000 children per year. Safest was the Northeast, with 189 child fatalities and a mortality rate of 0.38 per 100,000 children per year. The Midwest had 585 child fatalities, a mortality rate of .89 per 100,000 children per year. The West had 561 child fatalities, a mortality rate of 0.76 per 100,000 children per year. The 2,885 child fatalities represented a mortality rate of 0.94 per 100,000 children per year. "Broadly what we found is that state laws and regulations, as well as consistent enforcement, were crucial factors in preventing childhood motor vehicles fatalities -- evidenced by the wide variation in child fatalities by state," said Dr. Faisal Qureshi, Associate Professor of Surgery at UT Southwestern and a pediatric surgeon at Children's Health℠. "Our analysis also demonstrated that revising weak regulations and improving enforcement could have a substantial impact on saving lives. Improving proper use of restraints showed the most potential to prevent these deaths." Notably, analysis showed that a 10 percent increase in proper use of restraints such as seat belts and car seats would lower deaths by more than 230 children annually or more than 1,100 over five years -- equal to nearly 40 percent of the deaths observed from 2010-2014. Researchers reviewed child fatalities for those 15 and under involved in 18,116 fatal crashes from 2010-2014 using the Fatality Analysis Reporting System. More than 18,000 children were involved in fatality accidents during the four-year period, and about 16 percent of those (2,885 children) died. The research appears in the Journal of Pediatrics. States with the most child fatalities (over 100) were Texas (346); California (200); Florida (144); North Carolina (132); Georgia (130); and Alabama (125). States with the highest percentages of child deaths were Nebraska (30 percent); Iowa (27 percent); South Dakota and Wyoming (24 percent); Indiana and Alabama (23 percent); Mississippi and Idaho (22 percent); Virginia and Minnesota (21 percent); and New York, Kansas, North Dakota, and West Virginia (20 percent). States with the highest child mortality rates per 100,000 per year were Mississippi (3.23); Wyoming (3.06); Alabama (2.71); Montana (2.23); West Virginia (2.16); Oklahoma (2.02). States with the fewest deaths were Rhode Island (3); Alaska (4); Delaware, New Hampshire, and Vermont (5); Maine (7); and Hawaii (9). States with the lowest percentages of child deaths were New Hampshire (8 percent); New Jersey and Alaska (11 percent); Florida, Pennsylvania, Wisconsin, and Ohio (12 percent). States with the lowest child mortality rate per 100,000 per year were Massachusetts (0.25); New York (0.29); New Jersey (0.32); Washington and Rhode Island (0.33); Connecticut (0.34); New Hampshire (0.48); and Alaska (0.50).
News Article | May 26, 2017
In a new study, scientists at The University of Texas at Dallas have found that some types of cancers have more of a sweet tooth than others. "It has been suspected that many cancer cells are heavily dependent on sugar as their energy supply, but it turns out that one specific type -- squamous cell carcinoma -- is remarkably more dependent," said Dr. Jung-whan "Jay" Kim, assistant professor of biological sciences and senior author of the study published May 26 in the online journal Nature Communications. Kim and his collaborators initially set out to investigate differences in metabolism between two major subtypes of non-small cell lung cancer -- adenocarcinoma (ADC) and squamous cell carcinoma (SqCC). About one quarter of all lung cancers are SqCC, which has been difficult to treat with targeted therapies, Kim said. The research team, which included a Dallas high school student who interned in Kim's lab, first tapped into a large government database called The Cancer Genome Atlas, which maps information about 33 types of cancer gathered from more than 11,000 patients. Based on that data, they found that a protein responsible for transporting glucose -- a kind of sugar -- into cells was present in significantly higher levels in lung SqCC than in lung ADC. The protein, called glucose transporter 1, or GLUT1, takes up glucose into cells, where the sugar provides a fundamental energy source and fuels cell metabolism. GLUT1 is also necessary for normal cell function, such as building cell membranes. "Prior to this study, it was thought that the metabolic signatures of these two types of lung cancers would be similar, but we realized that they are very different," Kim said. "These findings lend credence to the idea that cancer is not just one disease, but many diseases that have very different characteristics." With elevated GLUT1 implicated in SqCC's appetite for sugar, the researchers looked for additional evidence by examining human lung tissue and isolated lung cancer cells, as well as animal models of the disease. "We looked at this from several different experimental angles, and consistently, GLUT1 was highly active in the squamous subtype of cancer. Adenocarcinoma is much less dependent on sugar," Kim said. "Our study is the first to show systematically that the metabolism of these two subtypes are indeed distinct and unique." The researchers also investigated the effect of a GLUT1 inhibitor in isolated lung cancer cells and mice with both types of non-small cell lung cancer. "When we gave GLUT1 inhibitors to mice with lung cancer, the squamous cancer diminished, but not the adenocarcinoma," Kim said. "There was not a complete eradication, but tumor growth slowed. "Taken in total, our findings indicate that GLUT1 could be a potential target for new lines of drug therapy, especially for the squamous subtype of cancer." In addition to squamous cell lung cancer, the team found that GLUT1 levels were much higher in four other types of squamous cell cancer: head and neck, esophageal and cervical. "These are very different organs and tissues in the body, but somehow squamous cell cancers have a very similar commonality in terms of glucose uptake," Kim said. "This type of cancer clearly consumes a lot of sugar. One of our next steps is to look at why this is the case." An upcoming study by Kim's group will examine the effect of a sugar-restricted diet on the progression of lung cancer in an animal model of the disease. The U.S. Department of Agriculture estimates that in 2015, on average, each American consumed more than 75 pounds of refined sugar, high fructose corn syrup and other sweeteners combined. "As a culture, we are very addicted to sugar," Kim said. "Excessive sugar consumption is not only a problem that can lead to complications like diabetes, but also, based on our studies and others, the evidence is mounting that some cancers are also highly dependent on sugar. We'd like to know from a scientific standpoint whether we might be able to affect cancer progression with dietary changes." The research was supported by the National Institutes of Health, the American Lung Association, the Japan Agency for Medical Research and Development, the Takeda Science Foundation, the Welch Foundation, and the Cancer Prevention and Research Institute of Texas. Other UT Dallas researchers involved with the work are co-lead authors and biological sciences graduate students Justin Goodwin and Michael Neugent; undergraduate students Maddox Robinson and Dana Jenkins; former Kim lab members Dr. Shin Yup Lee, Dr. Hyunsung Choi, Robin Ruthenborg and high school student intern Joshua Choe; Dr. Zhenyu Xuan and Dr. Hyuntae Yoo, assistant professors of biological sciences; Dr. Min Chen, associate professor of mathematical sciences; and Dr. Jung-Mo Ahn, associate professor of chemistry and biochemistry. Paper authors also include researchers from UT Southwestern Medical Center, the University of South Carolina, University of Nebraska Medical Center, the University of California, Los Angeles, Kyungpook National University in South Korea, the University of Tokyo and the Osaka Medical Center for Cancer and Cardiovascular Diseases.
News Article | May 11, 2017
DALLAS--(BUSINESS WIRE)--UT Southwestern Medical Center (UTSW) has entered into a strategic license agreement with Pieces Technologies, Inc. (Pieces Tech) to scale a novel program to improve outcomes of adult patients requiring long-term parenteral antibiotic therapy. The program was developed by a multidisciplinary team led by Dr. Kavita Bhavan, Associate Professor of Internal Medicine at UT Southwestern, and will be distributed nationally on the Pieces DS software platform. The self-administered outpatient parenteral antibiotic therapy program, “S-OPAT” as it is known, has been tested extensively at Parkland Health & Hospital System in Dallas. The program has demonstrated upwards of $7.6 million in annual direct savings and a 47 percent reduction in 30-day readmission rate for patients engaged in self-care versus standard forms of OPAT. The cornerstone of the program focuses on training patients and families to safely self-administer parenteral antibiotics at home. Pieces Technologies estimates that health systems could realize 40 percent in direct savings through the use of this program. “Licensing materials developed at UT Southwestern allows us to effectively scale this program to interested hospitals across the country,” says Dr. Bhavan. “Pieces DS will serve as the data backbone of the program in a health system,” says Anand Shah, MD, Chief Clinical Officer at Pieces Technologies. “Working with Dr. Bhavan and UT Southwestern Medical Center, we’ll be able to ensure consistent implementation across diverse healthcare systems. The Pieces DS Platform, and the analytics behind it, will allow for continuous learning and benchmarking in this area.” About Pieces Tech: Pieces Technologies, Inc. is a Dallas-based health information technology company on a mission to advance health at every decision. Pieces™ DS is a cloud-based software platform that improves quality and cost of care by applying key algorithms throughout a patient’s journey, in real-time. Pieces™ DS is fully integrated with the electronic medical record and leverages class-leading risk modeling, natural language processing, machine learning, and artificial intelligence directly at the point of care. For more information about deploying the S-OPAT program at your health system, please email email@example.com.
News Article | May 9, 2017
"Since my Rezūm procedure, I've been free from having to know where the bathroom is right away," said patient James Huber. "It worked beautifully and there have been no side effects. I don't have to take pills, and don't have to pay for them. The end result is freedom, and when you're 75, that becomes a really important issue. It gives you the freedom you never thought you would have again." "Based on the conservation of sexual function and efficacy in treating LUTS/BPH, Rezūm could be offered as first-line treatment in lieu of drugs for patients with moderate to severe LUTS," said Dr. Kevin McVary, professor and chair, Division of Urology, Southern Illinois University School of Medicine in Springfield, Ill. BPH is one of the top 10 most common and costly diseases in the U.S., affecting more than 12 million American men aged 50 or older, with nearly 800,000 new diagnoses each year. BPH causes significant quality of life issues including waking up multiple times during the night to urinate, frequency, urgency, irregular and weak urinary flow, anxiety, challenges with sexual function and limitation in daily activities. The Rezūm System uses radiofrequency current to create thermal energy that is convectively delivered to obstructive prostate tissue through targeted, precise treatments. The treated tissue is then resorbed by the body's immune system which alleviates the symptoms of BPH and improves patients' quality of life and ability to urinate, while preserving sexual function. Urology experts will present five abstracts reporting the data from clinical studies they conducted on the Rezūm System to treat BPH during the 2017 American Urological Association (AUA) annual meeting in Boston May 13 - 15, 2017. These presentations will include Dr. Claus Roehrborn, chair of UT Southwestern Urology Department, presenting the two-year outcomes from the company's randomized controlled, level one pivotal study of the Rezūm System to relieve LUTS caused by BPH. Dr. Nikhil Gupta of Southern Illinois University will present clinical data demonstrating the effectiveness of the Rezūm System to treat BPH in (i) obese men, while preserving erectile and ejaculatory function (which received the "Best Abstract Award" from the AUA), (ii) men who are in retention as a result of their BPH, and (iii) men compared to the outcomes data from the National Institute of Health sponsored "Medical Therapy of Prostatic Symptoms" (MTOPS) study. In addition, Dr. Tobias Köhler, most recently of Southern Illinois University and now of The Mayo Clinic, will present the Rezūm procedure as part of the Plenary Prime Time BPH Surgical Techniques session. For more information about the Rezūm System, visit www.Rezūm.com. NxThera pioneered its convective radiofrequency thermotherapy platform technology to treat a variety of endourological conditions, beginning with BPH. NxThera's FDA-cleared Rezūm System is a next-generation transurethral needle ablation system using radiofrequency to create thermal energy that is convectively delivered to obstructive prostate tissue in targeted, precise thermotherapy treatments, with minimal discomfort, to improve the symptoms of BPH and quality of life. Founded in 2008, NxThera is located in Maple Grove, Minn. For more information, visit www.Rezūm.com. To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/nxthera-reaches-milestone-of-10000-patients-effectively-treated-for-enlarged-prostate-with-minimally-invasive-rezm-system-300454131.html
News Article | May 8, 2017
May 5, 2017 - UT Southwestern Medical Center researchers have identified the cells that directly give rise to hair as well as the mechanism that causes hair to turn gray - findings that could one day help identify possible treatments for balding and hair graying. "Although this project was started in an effort to understand how certain kinds of tumors form, we ended up learning why hair turns gray and discovering the identity of the cell that directly gives rise to hair," said Dr. Lu Le, Associate Professor of Dermatology with the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. "With this knowledge, we hope in the future to create a topical compound or to safely deliver the necessary gene to hair follicles to correct these cosmetic problems." The researchers found that a protein called KROX20, more commonly associated with nerve development, in this case turns on in skin cells that become the hair shaft. These hair precursor, or progenitor, cells then produce a protein called stem cell factor (SCF) that the researchers showed is essential for hair pigmentation. When they deleted the SCF gene in the hair progenitor cells in mouse models, the animal's hair turned white. When they deleted the KROX20-producing cells, no hair grew and the mice became bald, according to the study. The findings are published online in Genes & Development. Dr. Le, who holds the Thomas L. Shields, M.D. Professorship in Dermatology, said he and his researchers serendipitously uncovered this explanation for balding and hair graying while studying a disorder called Neurofibromatosis Type 1, a rare genetic disease that causes tumors to grow on nerves. Scientists already knew that stem cells contained in a bulge area of hair follicles are involved in making hair and that SCF is important for pigmented cells, said Dr. Le, a member of the Hamon Center for Regenerative Science and Medicine. What they did not know in detail is what happens after those stem cells move down to the base, or bulb, of hair follicles and which cells in the hair follicles produce SCF - or that cells involved in hair shaft creation make the KROX20 protein, he said. If cells with functioning KROX20 and SCF are present, they move up from the bulb, interact with pigment-producing melanocyte cells, and grow into pigmented hairs. But without SCF, the hair in mouse models was gray, and then turned white with age, according to the study. Without KROX20-producing cells, no hair grew, the study said. UT Southwestern researchers will now try to find out if the KROX20 in cells and the SCF gene stop working properly as people age, leading to the graying and hair thinning seen in older people - as well as in male pattern baldness, Dr. Le said. The research also could provide answers about why we age in general as hair graying and hair loss are among the first signs of aging. Other researchers include first author Dr. Chung-Ping Liao, Assistant Instructor; Dr. Sean Morrison, Professor and Director of the Children's Medical Center Research Institute at UT Southwestern and of Pediatrics, and Howard Hughes Medical Institute Investigator, who holds the Kathryne and Gene Bishop Distinguished Chair in Pediatric Research at Children's Research Institute at UT Southwestern and the Mary McDermott Cook Chair in Pediatric Genetics; and Reid Booker, a former UT Southwestern researcher. The research was supported by the National Cancer Institute, Specialized Programs of Research Excellence (SPORE) grant, National Institutes of Health, the Dermatology Foundation, the Children's Tumor Foundation, and the Burroughs Wellcome Fund. 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
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
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. .
Matsui M.,UT Southwestern |
Corey D.R.,UT Southwestern
Nature Reviews Drug Discovery | Year: 2017
Most of the human genome encodes RNAs that do not code for proteins. These non-coding RNAs (ncRNAs) may affect normal gene expression and disease progression, making them a new class of targets for drug discovery. Because their mechanisms of action are often novel, developing drugs to target ncRNAs will involve equally novel challenges. However, many potential problems may already have been solved during the development of technologies to target mRNA. Here, we discuss the growing field of ncRNA-including microRNA, intronic RNA, repetitive RNA and long non-coding RNA-and assess the potential and challenges in their therapeutic exploitation.