New myeloma-obesity research reveals a way drugs could work arm-in-arm with body’s own defenses

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SAN ANTONIO (May 1, 2014) — Obesity increases the risk of myeloma, a cancer of plasma cells that accumulate inside the bones.

And with current obesity trends in the United States and especially in South Texas, that’s ominous.

“I’m predicting an increase in multiple myeloma,” said Edward Medina, M.D., Ph.D., “and with the obesity problems we see in the Hispanic population, there could be a serious health disparity on the horizon.”

Dr. Medina, a hematopathologist and assistant professor in the Department of Pathology at The University of Texas Health Science Center at San Antonio, is looking at exactly how obesity causes an increased risk for myeloma.

What he and his colleagues have discovered is a potential way to not only boost the effectiveness of current chemotherapy treatments for myeloma, but at the same time a way to help the body help itself.

In a paper published this week in the journal Leukemia, Dr. Medina and his team look at an important little protein called adiponectin.

Myeloma is often called multiple myeloma because it occurs at many sites within the bone marrow. Healthy plasma cells produce antibodies that fight infection in the body, but myeloma cells produce high levels of abnormal antibodies that, when the cancer cells accumulate, they crowd out production of other important blood cells, both red and white.

“They basically overtake the bone marrow,” Dr. Medina said.

The disease can lead to bone pain and fragility, confusion, excessive thirst and kidney failure. While survival rates for patients with myeloma have increased in recent years, many people do not live more than five years beyond diagnosis.

Adiponectin is a protective protein that plays several roles in keeping the body healthy, including killing cancer cells. While adiponectin is produced by fat cells, Medina said, obese people have less of it. The reason for this paradox is that in cases of obesity, fat cells function abnormally, including producing less adiponectin. What they produce more of, however, are fatty acids, and it is likely that myeloma cells can feed on these fatty acids.

“Synthesizing fatty acids is important for myeloma cells to build vital structures, including cell membranes, that enable them to keep on growing,” Medina said.

Focusing on adiponectin led Dr. Medina’s lab to protein kinase A or “PKA” — a protein that, when activated by adiponectin, suppresses the fatty acids that myeloma cells need, leading to their demise.

The idea is to use the understanding of the pathways that adiponectin uses to kill myeloma cells to create a drug that would do the same thing.

“If we could pharmacologically suppress these fatty acid levels in obese myeloma patients, we could boost the effects of the chemotherapy that targets PKA or fatty acid synthesis, and potentially decrease the chemotherapeutic dose,” Medina said. “Also, it would give your own body’s protective measures more of a chance to work against the cancer.”

Dr. Medina’s research was funded by the Multiple Myeloma Research Foundation and a KL2 award from the Health Science Center’s IIMS-Clinical and Translational Science Award from the National Institutes of Health’s National Center for Advancing Translational Sciences. Key contributors to this work include Kelli Oberheu, Srikanth Polusani, Ph.D., postdoctoral fellow in the Department of Biochemistry and Babatunde Oyajobi, M.D., Ph.D., associate professor of cellular and structural biology.

 

The Cancer Therapy & Research Center (CTRC) at The University of Texas Health Science Center at San Antonio is one of the elite academic cancer centers in the country to be named a National Cancer Institute (NCI) Designated Cancer Center, and is one of only four in Texas. A leader in developing new drugs to treat cancer, the CTRC Institute for Drug Development (IDD) conducts one of the largest oncology Phase I clinical drug programs in the world, and participates in development of cancer drugs approved by the U.S. Food & Drug Administration. For more information, visit www.ctrc.net.

In battle of wits, teams flex their axons and stretch their dendrites

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WHAT:

Brain Bowl 2014, a Jeopardy!-style quiz event sponsored by the Center for Biomedical Neuroscience at The University of Texas Health Science Center at San Antonio

WHEN:

7 p.m. Tuesday, April 29

WHERE:

UT Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78229

WHO:

Teams from The University of Texas at San Antonio, Texas A&M University and UT Arlington

WHY:

Training the next generation of neuroscientists studying schizophrenia, addiction, Parkinson’s disease and many other conditions

COLOR:

David Morilak, Ph.D., professor of pharmacology at the UT Health Science Center, is the emcee. The judges ring cowbells and blow horns, often comically. Dr. Morilak frequently inserts humor, such as this from last year’s Bowl: “The next category is drugs and the brain, which I caution you to know too much about — I remind you that your advisers are watching and maybe your parents, since we’re on live web feed!”

This is the 15th Brain Bowl at the Health Science Center.

 

The University of Texas Health Science Center at San Antonio, one of the country’s leading health sciences universities, ranks in the top 3 percent of all institutions worldwide receiving National Institutes of Health funding. The university’s schools of medicine, nursing, dentistry, health professions and graduate biomedical sciences have produced more than 29,000 graduates. The $765 million operating budget supports eight campuses in San Antonio, Laredo, Harlingen and Edinburg. For more information on the many ways “We make lives better®,” visit www.uthscsa.edu.

Chronic diseases start in the womb, guest lecturer will discuss

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Kent Thornburg, Ph.D.
Kent Thornburg, Ph.D., professor of medicine at the Knight Cardiovascular Institute of Oregon Health & Science University (OHSU)

SAN ANTONIO (April 24, 2014) — Kent Thornburg, Ph.D., professor of medicine at the Knight Cardiovascular Institute of Oregon Health & Science University (OHSU), will visit the UT Health Science Center at San Antonio on Monday to discuss evidence that chronic disease begins in the womb. His lecture starts at noon Monday, April 28, in lecture hall 3.104A at the Health Science Center’s Long Campus, 7703 Floyd Curl Drive (78229). The public is invited. Light refreshments will be provided.

Dr. Thornburg directs the Center for Developmental Health and the Bob and Charlee Moore Institute for Nutrition and Wellness at OHSU in Portland. His lecture is the first in a series sponsored by the Center of Excellence in Women’s Health at the UT Health Science Center.

Dr. Thornburg is internationally recognized for his pioneering work in the area of developmental origins of health and disease. His studies describe how life in utero during the nine months of pregnancy determines the risk of developing disease in childhood and adult life. Exposure to an adverse intrauterine environment resulting from, for example, life stresses, pollutants, poor nutrition and maternal medical conditions including diabetes and obesity, can program the offspring for disease.

This has special public health relevance to San Antonio and South Texas given the region’s high rates of diabetes and obesity and the desire to break the cycle of transmission of these diseases to successive generations.

The goal of the Center of Excellence in Women’s Health is to promote all aspects of women’s health in the community and be a leader in the promotion of women’s health clinical and research programs and translation of research findings into clinical practice to improve the health of the local community. The activities of the center of excellence include research, education, career development, community engagement, interaction with clinical services and philanthropy.

This lecture will be held in conjunction with a weeklong course, “Translational Science in Perinatal Biology,” presented by the Center for Pregnancy and Newborn Research in the Department of Obstetrics and Gynecology of the School of Medicine at the Health Science Center. The course is drawing 25 young investigators from around the world and will focus on pregnancy and developmental programming of health and disease. The course is intended to enhance translational research in obstetrics and neonatology.

 

The University of Texas Health Science Center at San Antonio, one of the country’s leading health sciences universities, ranks in the top 3 percent of all institutions worldwide receiving National Institutes of Health funding. The university’s schools of medicine, nursing, dentistry, health professions and graduate biomedical sciences have produced more than 29,000 graduates. The $765 million operating budget supports eight campuses in San Antonio, Laredo, Harlingen and Edinburg. For more information on the many ways “We make lives better®,” visit www.uthscsa.edu.

Study shows Hispanics, blacks substantially underrepresented in orthopaedic research

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SAN ANTONIO (April 24, 2014) – In San Antonio, orthopaedic surgeons commonly treat Hispanic and black patients for a vast array of orthopaedic diseases and injuries. When these doctors turned to their specialty’s most esteemed journals to learn more about treatments and breakthroughs, they noticed little to no reference to these minority groups.

Boris A. Zelle, M.D., assistant professor of orthopaedic trauma surgery at The University of Texas Health Science Center at San Antonio and an orthopaedic trauma surgeon with UT Medicine San Antonio, decided to investigate this underrepresentation of Hispanic and black patients in orthopaedic research. He called on his longtime friend and collaborator Mohit Bhandari, M.D., Ph.D., an orthopaedic surgeon and renowned researcher who is the research chair of muscoskeletal trauma and surgical outcomes at McMaster University in Canada.

An extensive and critical review of the most pertinent orthopaedic clinical studies over a four-year period recently resulted in Dr. Zelle’s publication, “Lack of Diversity in Orthopaedic Trials Conducted in the United States,” in The Journal of Bone and Joint Surgery, the premier orthopaedic journal.

“As an academic trauma surgeon, it is my responsibility to constantly review the most pertinent literature and to be up to date. When I started practicing in San Antonio three years ago, I began reviewing the literature with the particular focus to learn more about minority patients. I noticed that study after study made no reference to race or ethnicity,” he said.

“This is important to patients because our treatment algorithms are based on information found in the best available literature,” said Dr. Zelle. “As of now, this literature is poorly representing minority patients like our patient population in San Antonio. We know that Hispanic and black patients have different outcomes after treatment of orthopaedic injuries. We know that they have different associated medical problems as well as different perceptions toward their injury and their health care providers. We need to understand all of this so we can better treat these patients.”

With assistance from Jeremy S. Somerson, M.D., an orthopaedic surgery resident; Clayton Vaughan, M.D., a medical school graduate who was a student at the time, and Christopher S. Smith, M.Sc., from McMaster University, Dr. Zelle and Dr. Bhandari reviewed 158 randomized controlled trials from 2008 to 2011 that had been published in 32 different scientific journals.

“We found that minority patients were not appropriately represented in these clinical trials,” Dr. Zelle said. “In these studies, only 4.6 percent of participants were Hispanic and 6.2 percent were African-American. That is 3.5 times less than the actual Hispanic population, and two times less than the actual African-American population in the United States.”

This research determined that orthopaedic literature is failing to represent these minority populations, he said. “The entire body of orthopaedic literature needs to be challenged as the patients enrolled in clinical studies are not representative of the current U.S. population. Centers with diverse patient populations, such as the UT Health Science Center, must be part of future multicenter trials in order to allow for enrollment of minority patients. Inclusion of Hispanic and African-American patients in research must be a clear goal.”

Dr. Zelle said the UT Health Science Center’s solution to this disparity is developing study tools designed for these populations. For example, the development of outcome questionnaires in Spanish can greatly increase the amount of Hispanic patients who participate in such studies, he said.

“By developing these outcome tools and sharing them with other universities, we will be able to increase the number of Hispanics in future clinical trials. We hope to increase the number of minority patients in orthopaedic research studies across the country. Then we will have much better information to use when treating our patients.”

 

The University of Texas Health Science Center at San Antonio, one of the country’s leading health sciences universities, ranks in the top 3 percent of all institutions worldwide receiving National Institutes of Health funding. The university’s schools of medicine, nursing, dentistry, health professions and graduate biomedical sciences have produced more than 29,000 graduates. The $765 million operating budget supports eight campuses in San Antonio, Laredo, Harlingen and Edinburg. For more information on the many ways “We make lives better®,” visit www.uthscsa.edu.

Study comparing type 2 diabetes medications seeks volunteers

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UT Health Science Center, Texas Diabetes Institute among enrolling centers

SAN ANTONIO (April 17, 2014) — The first comprehensive, long-term study comparing different medications for type 2 diabetes is recruiting participants at The University of Texas Health Science Center at San Antonio and the University Health System’s Texas Diabetes Institute.

The Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) Study will compare the long-term benefits and risks of four widely used diabetes drugs in combination with metformin, the most common first-line medication for treating type 2 diabetes.

Ralph DeFronzo, M.D., principal investigator of the UT Health Science Center and Texas Diabetes Institute study site, said GRADE will compare the effects of four glucose-lowering medications — a sulfonylurea called glimepiride; a DPP-4 inhibitor, sitagliptin; a GLP-1 agonist, liraglutide; and a basal insulin, glargine — when each is added to metformin.

“All of these medications currently are approved for the treatment of type 2 diabetes, but it yet has not been established which antidiabetic medication provides the best glycemic control in diabetic patients who are suboptimally controlled on metformin,” Dr. DeFronzo said. He is division chief of diabetes in the School of Medicine of the Health Science Center and deputy director of the Texas Diabetes Institute.

Five-thousand patients will be enrolled in up to 50 academic and VA medical centers nationwide, including 150 in San Antonio. Patient outcomes will be followed for up to seven years. Participants will have their diabetes medications managed free of charge throughout the study, including at least four medical visits per year.

At enrollment, participants must be:

• At least 30 years of age with a diagnosis of type 2 diabetes
• Within 10 years of time of diagnosis
• Taking metformin only
• Willing to take a diabetes medication in addition to metformin

To inquire about study eligibility, please call 210-358-7200.

The GRADE Study is sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. It is coordinated by the Biostatistics Center, a research facility of George Washington University.

Anyone interested in learning more about the study can visit www.gradestudy.org.

The GRADE Study (ClinicalTrials.gov number: NCT01794143) is supported under NIH grant U01DK098246.

Type 2 Diabetes in the U.S., Texas and Bexar County

Type 2 diabetes is an epidemic that threatens to become the century’s major public health problem and poses enormous human and economic challenges worldwide. Nearly 26 million Americans are affected by diabetes and 79 million have prediabetes.

Diabetes is a chronic disease that, when left untreated or not properly managed, can result in serious complications, including kidney failure, blindness, limb amputation and death. In 2012, 11.4 percent of Bexar County adults reported being diagnosed with diabetes, a rate similar to the state of Texas. (Source: 2013 Bexar County Community Health Assessment, Page 168)

Bexar County was home to 1,785,787 people in 2012, according to the U.S. Census Bureau, and 11.4 percent of this figure totaled 203,579. Thousands more individuals in the area lived with undiagnosed diabetes.

 

UT Medicine San Antonio is the clinical practice of the School of Medicine at the UT Health Science Center San Antonio. With more than 700 doctors – all School of Medicine faculty – UT Medicine is the largest medical practice in Central and South Texas. Expertise is in more than 100 medical specialties and subspecialties. Primary care doctors and specialists see patients in private practice at UT Medicine’s flagship clinical home, the Medical Arts & Research Center (MARC), located at 8300 Floyd Curl Drive, San Antonio 78229. Most major health plans are accepted, and UT Medicine physicians also practice at several local and regional hospitals. Call (210) 450-9000 to schedule an appointment, or visit www.UTMedicine.org for a list of clinics and phone numbers.

Scientists unlock secrets of protein produced by disease-causing fungus

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SAN ANTONIO (April 16, 2014) — A team that includes scientists from the School of Medicine at The University of Texas Health Science Center at San Antonio, Johns Hopkins University and St. Mary’s University reported the structure of a protein that helps a common fungus to infect the body.

The fungal pathogen Candida albicans causes yeast infections, diaper rashes and oral thrush, and is the most common fungal pathogen to infect humans. It can also cause a life-threatening infection of the blood called disseminated candidiasis.

“In this study, we determined the three-dimensional structure of a never-before-seen cell wall protein called SOD5 that the organism uses as a defense against the human immune system,” said P. John Hart, Ph.D., the Ewing Halsell-President’s Council Distinguished Professor of biochemistry at the UT Health Science Center and Research Scientist in the South Texas Veterans Health Care System.

“SOD5 is a copper-only protein that exhibits significant structural differences from copper/zinc superoxide dismutases (SODs),” Dr. Hart said. “Because SOD5 molecules are widespread throughout fungi, including C. albicans, but are not found in humans, the structural differences can be exploited to develop compounds that specifically target SOD5 to treat a number of widespread fungal infections.”

Current conventional antifungal treatments such as fluconazole can be toxic to the liver in certain individuals, he noted.

“SOD5 is an unprecedented, very powerful antioxidant protein that enables C. albicans to ward off free radicals of the host immune response,” said study senior author Valeria Culotta, Ph.D., professor of biochemistry and molecular biology and environmental health sciences at the Johns Hopkins University Bloomberg School of Public Health. Free radicals are highly reactive molecules that can cause oxidative damage.

The finding was published April 7 online ahead of print by the journal Proceedings of the National Academy of Sciences of the United States of America.

Study collaborators included Drs. Hart and Culotta; Julie Gleason, Ph.D., and Ryan Peterson, Ph.D., also of the Bloomberg School of Public Health; Ahmad Galaleldeen, Ph.D., and Jessica Waninger-Saroni, B.S., of St. Mary’s University in San Antonio; Alexander Taylor, Ph.D., and Stephen Holloway, Ph.D., of the Department of Biochemistry at the UT Health Science Center at San Antonio; Brendan Cormack, Ph.D., of the Johns Hopkins University School of Medicine; and Diane Cabelli, Ph.D., of Brookhaven National Laboratories in Upton, N.Y.

 

The University of Texas Health Science Center at San Antonio, one of the country’s leading health sciences universities, ranks in the top 3 percent of all institutions worldwide receiving National Institutes of Health funding. The university’s schools of medicine, nursing, dentistry, health professions and graduate biomedical sciences have produced more than 29,000 graduates. The $765 million operating budget supports eight campuses in San Antonio, Laredo, Harlingen and Edinburg. For more information on the many ways “We make lives better®,” visit www.uthscsa.edu.