Anti-Cancer Agent May Have Simultaneous Regenerative Properties

MedicalResearch.com Interview with:

Lawrence Lum, Ph.D. Associate Professor Virginia Murchison Linthicum Scholar in Medical Research UT Southwestern Medical Center

Dr. Lum

Lawrence Lum, Ph.D.
Associate Professor
Virginia Murchison Linthicum Scholar in Medical Research
UT Southwestern Medical Center

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Scarring of the adult heart due to excessive fibrotic responses is common after a heart attack, or following radiation therapy for the treatment of certain cancers. We have identified an anti-cancer agent currently in clinical development called WNT-974 that decreases fibrotic responses and improves heart function following myocardial infarction in mice. This unexpected observation was the outcome of a study focused on identifying unwanted adult tissue toxicities associated with this class of chemicals.

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Two Polyomaviruses Linked To Dermatoses in Immunocompromised Patients

MedicalResearch.com Interview with:

Richard Wang, M.D., Ph.D. Assistant Professor UT Southwestern Medical Center

Dr. Wang

Richard Wang, M.D., Ph.D.
Assistant Professor
UT Southwestern Medical Center

MedicalResearch.com: What is the background for this study? What are the main findings?

Response:

Currently, there are 13 polyomaviruses known to infect humans. Several members of this family of double-stranded DNA viruses—including Merkel Cell Polyomavirus, Trichodysplasia Spinulosa Polyomavirus, Human Polyomavirus 6 (HPyV6), and Human Polyomavirus 7 (HPyV7)—can be shed from skin of healthy individuals. While most polyomavirus infections are common and subclinical, several polyomaviruses have been associated with debilitating diseases in immunocompromised individuals. Most recently, HPyV7 was discovered in a pruritic and dyskeratotic eruption in two immunosuppressed transplant patients. A closely related polyomavirus, Human Polyomavirus 6, has not yet been strongly linked to any infectious diseases. Using the previously described, characteristic histologic pattern, we identify 3 additional cases of skin eruptions associated with infections of HPyV6 and HPyV7. The association of the dermatoses with highly active infections were confirmed through electron microscopy, immunohistochemistry, quantitative PCR, and complete sequencing. HPyV7 infects keratinocytes and affects their normal differentiation. In addition, next generation sequencing revealed that HPyV6 could persist in a latent state in the skin of a previously infected patient.

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Intermittent Fasting Inhibits Cancer Cells in Childhood Leukemia ALL

MedicalResearch.com Interview with:

Chengcheng (Alec) Zhang, Ph.D. Associate Professor Hortense L. and Morton H. Sanger Professorship in Oncology Michael L. Rosenberg Scholar for Medical Research Department of Physiology  UT Southwestern Medical Center

Dr. Alec Zhang

Chengcheng (Alec) Zhang, Ph.D.
Associate Professor
Hortense L. and Morton H. Sanger Professorship in Oncology
Michael L. Rosenberg Scholar for Medical Research
Department of Physiology
UT Southwestern Medical Center

MedicalResearch.com: What is the background for this study?

Response: New therapeutic targets and approaches are needed to effectively treat leukemia. Acute myeloid leukemia (AML) is the most common form of adult acute leukemia whereas acute lymphoblastic leukemia (ALL) is the most common form of cancer in children; ALL also occurs in adults. Although treatment of pediatric ALL is highly effective, a sizeable number of patients are non-responders who succumb to this disease. The outcome of ALL in adults is significantly worse than for pediatric ALL. Additionally, some types of ALL have a much poorer prognosis than others.

Dietary restriction, including fasting, delays aging and has prolonged effects in a wide range of organisms and has been considered for cancer prevention. In certain types of solid tumor,_ENREF_1 dietary restriction regimens are able to promote T cell-mediated tumor cytotoxicity and enhance anticancer immunosurveillance, and coordinate with chemotherapy to promote the anti-cancer effects. However, the responsiveness of hematopoietic malignancies to dietary restriction, including fasting, remains unknown. Furthermore, whether dietary restriction alone can inhibit cancer development is not clear.

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Teledermatology Can Triage Many Post-Operative Skin Surgery Concerns

MedicalResearch.com Interview with:

Rajiv Nijhawan MD Department of Dermatology The University of Texas Southwestern Medical Center Dallas

Dr. Rajiv Nijhawan

Rajiv Nijhawan MD
Department of Dermatology
The University of Texas Southwestern Medical Center
Dallas

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: From a healthcare perspective, we are constantly working to improve access to patients, and telemedicine has proved to be an excellent platform for this goal especially in the field of dermatology. In regards to surgical dermatology, the role of telemedicine has been limited. The ubiquity of smartphones with photograph capability has provided an opportunity for patients to take self-acquired photographs (selfies) easily. Our experience has been that few patients who call with post-operative concerns have major issues (e.g. infection, bleeding, etc.) while the majority of concerns are minor in nature, and patients are often seeking reassurance.

Our study shows that the majority of concerns can easily be triaged and managed through patient-directed photography without burdening the patient to take time off work for another appointment, find transportation/travel (many of our patients travel hours for their visits), wait to see the provider, etc. This option of triaging a post-operative concern essentially immediately through the use of patient-directed photographs provides the opportunity for immediate feedback on the patient’s concerns and likely reduces anxiety while making the process as patient-centered as possible. In addition, it allows the physician to be as efficient as possible by not having to overbook his/her schedule to accommodate these often non-urgent concerns.

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Delayed Epinephrine Linked To Worse Survival From In-Patient Cardiac Arrest

MedicalResearch.com Interview with:
Rohan Khera, MD

Cardiology Fellow, T32 Clinical-Investigator Pathway
UT Southwestern Medical Center
Dallas, TX

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Nearly 200 thousand people have an in-hospital cardiac arrest in the US each year. Of these, the vast majority have a non-shockable initial rhythm – either pulseless electric activity (PEA) or asystole. The survival of this type of arrest remains poor at around 12-14%. Moreover, even after accounting for differences in case mix, there is a wide variation in survival across hospitals – and this serves as a potential avenue for targeting quality improvement strategies at poor performing hospitals.

Recent data suggest that a shorter time from the onset of cardiac arrest to the first dose of epinephrine is independently associated with higher survival. Against this background of wide hospital variation in cardiac arrest survival, and patient-level data suggesting an association between time to epinephrine and patient survival, we wanted to assess (A) if there were differences in time to epinephrine administration across hospitals, and (B) if a hospital’s rate of timely epinephrine use was associated with its cardiac arrest survival rate. Within Get With The Guidelines-Resuscitation, we identified nearly 104-thousand adult patients at 548 hospitals with an in-hospital cardiac arrest attributable to a non-shockable rhythms. delays to epinephrine,

We found that (a) proportion of cardiac arrests with delayed epinephrine markedly across hospitals, ranging from no arrests with delay (or 0%) to more than half of arrests at a hospital (54%).

There was an inverse correlation between a hospital’s rate of delayed epinephrine administration and its risk-standardized rate of survival to discharge and survival with functional recovery – compared to a low-performing hospitals, survival and recovery was 20% higher at hospitals that performed best on timely epinephrine use.

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Precise Structure of Cannabis Brain Receptor Defined

MedicalResearch.com Interview with:

(l-r) Dr. Zhenhua Shao and Dr. Daniel Rosenbaum

(l-r) Dr. Zhenhua Shao and Dr. Daniel Rosenbaum UT Southwestern

Dan Rosenbaum, Ph.D.
Principal Investigator
Department of Biophysics
The University of Texas Southwestern Medical Center
Dallas, Texas

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: This study focuses on the structure of the human CB1 cannabinoid receptor.

The CB1 protein is a membrane-embedded G protein-coupled receptor (GPCR) in the brain and peripheral tissues that responds to a variety of different compounds, including endogenous lipid messengers (‘endocannabinoids’), plant natural products (such as THC from the Cannabis sativa plant i.e. marijuana), and synthetic antagonists (such as the taranabant ligand used for this study). The CB1 receptor is involved in regulating neurotransmission in vertebrates, and is a potential therapeutic target for numerous conditions including obesity, pain, and epilepsy.

The main findings of this study entailed the solution of the high-resolution crystal structure of human CB1 receptor bound to the inhibitor taranabant. This structure revealed the precise shape of the inhibitor binding pocket, which is also responsible for binding THC and endocannabinoids. In addition to helping explain the mechanism of inhibitor and THC binding, our structure provides a framework for computational studies of binding to a large diversity of cannabinoid modulators of therapeutic importance.

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Increased Aortic Stiffness May Explain Elevated Hypertension Risk in African Americans

MedicalResearch.com Interview with:

Wanpen Vongpatanasin, M.D. Professor of Medicine Norman & Audrey Kaplan Chair in Hypertension Fredric L. Coe Professorship in Nephrolithiasis and Mineral Metabolism Research Director, Hypertension Section, Cardiology Division, UT Southwestern Medical Center Dallas, TX 75390-8586

Dr. Wanpen Vongpatanasin

Wanpen Vongpatanasin, M.D.
Professor of Medicine
Norman & Audrey Kaplan Chair in Hypertension
Fredric L. Coe Professorship in Nephrolithiasis and Mineral Metabolism Research
Director, Hypertension Section,
Cardiology Division,
UT Southwestern Medical Center
Dallas, TX 75390-8586

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Aortic stiffness is known to be associated with cardiovascular disease, including heart attack, stroke, and heart failure, possibly related to increase afterload to the left ventricle. Previous studies have not directly assessed proximal aortic function among ethnic minorities in the United States. We evaluated the multiethnic, population-based Dallas Heart Study participants (N=2544, 54.2% women, 49.7% Black) who underwent cardiovascular magnetic resonance imaging (CMR) at 1.5 Tesla. Aortic stiffness and characteristic impedance (Zc) were determined from aortic arch PWV and lumen area measurements. Linear regression was used to evaluate ethnic differences in proximal aortic wall stiffness using aortic arch PWV and Zc as dependent variables with and without adjustment for traditional cardiovascular risk factors.

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Little Change in PSA Use After Taskforce Recommendation

MedicalResearch.com Interview with:
Dr Ryan Hutchinson MD and
Yair Lotan MD

Department of Urology
University of Texas Southwestern Medical Center

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The United States Preventative Services Task Force recommendation against PSA screening generated significant controversy. Research since then has relied heavily on survey data to examine the impact of the recommendation on PSA screening practices. In a hotly charged issue such as this, such data can carry significant bias.

We examined a large, whole-institution data in the years before and after the USPSTF recommendations reflecting actual practice and found that the changes in PSA use at our institution, if any, were small. This is more consistent with behavior seen after the vast majority of practice recommendations.

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Genetic Ancestry using Mitochondrial DNA in patients with Triple-Negative Breast Cancer

MedicalResearch.com Interview with:

Roshni Rao, M.D Breast Surgery University of Texas Southwestern

Dr. Roshni Rao

Roshni Rao, M.D
Breast Surgery
University of Texas Southwestern

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Triple negative breast cancer (TNBC) is characterized by not having estrogen, progesterone, or Her2Neu receptors. Although a less common type, it is aggressive, and leads to a disproportionate number of deaths from breast cancer.

TNBC is more common in young, African American women, but can be found in other ethnic groups as well.

This study performed mitochondrial DNA (mtDNA) analysis, to evaluate for patient genetic ancestry, in 92 patients with TNBC. In regards to self-identified ethnicity, there were 31 African-Americans, 31 Whites, and 30 Hispanics. Utilizing mtDNA, 13% of patients had discordance between self identified ethnicity and mtDNA analysis. Discordance was highest in the Hispanic group. The Hispanic patients were also much younger at initial age of diagnosis, and less likely to have a family history of breast cancer. Ancestry from Nigeria, Cameroon, or Sierre Leone were most common in the African-Americans with triple negative breast cancer.

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High Phosphates in Processed Foods May Contribute To Increased Blood Pressure

MedicalResearch.com Interview with:

Dr-Wanpen-Vongpatanasin.jpg

Dr. Vongpatanasin

Wanpen Vongpatanasin, MD
Professor of Medicine
Norman & Audrey Kaplan Chair in Hypertension Research
Director, Hypertension Section
Cardiology Division
UT Southwestern Medical Center

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Inorganic phosphate has been added to our processed food at an enormous amount as food preservatives and flavor enhancer such that typical American diet contains twice as much as the recommended daily allowance. A high phosphate (Pi) diet was recently shown to trigger blood pressure (BP) elevation in otherwise normal rats but the mechanisms are still unknown.We found that rats treated with high phosphate diet that mimics the excess Pi consumed by the general American population developed high BP related to increased sympathetic nerve activity (SNA), resulting in excessive peripheral vasoconstriction. This exaggerated increase in SNA and BP is evident particularly during exercise. This study is conducted in collaboration with Drs. Masaki Mizuno and Scott Smith, the two leading experts in neural control of circulation at UT Southwestern in the Department of Health Care Sciences.

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Study Detects Mechanism That Keeps Insulin Receptors on Cell Surface

MedicalResearch.com Interview with:
Dr. Eunhee Choi
Research scientist in the Yu laboratory and lead author of the study
UT SouthWestern
Dr. Hongtao Yu, Professor of Pharmacology at UT Southwestern and
Investigator with the Howard Hughes Medical Institute (HHMI).

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Diabetes is a metabolic disease. High blood sugar is a common symptom of diabetes, and over time it can lead to serious damage to multiple organs. Insulin, a hormone made by the pancreas, regulates blood sugar. Diabetes can occur either when the pancreas does not produce enough insulin (type 1 diabetes) or when the cells in our body cannot efficiently respond to insulin (type 2 diabetes). Diabetes is now a major global epidemic. The World Health Organization (WHO) estimates that more than 400 million people worldwide have diabetes.

Insulin binds the insulin receptor (IR) at the cell surface. The insulin-bound IR can send signals inside the cell and instruct the cell to take up sugar from the blood, thus maintaining healthy blood sugar levels. After insulin has done its job, insulin-bound IR is packaged into small vesicles with a protein coat and dragged into the cell, thus terminating the signals. An adequate level of IR on the cell surface is crucial for insulin signaling and blood sugar metabolism. We have found a new mechanism that keeps IR at the cell surface. Without such a mechanism, IR is prematurely dragged inside the cell before it encounters insulin.

Our discovery is quite unexpected. A main interest of our lab is to study the molecular control of cell division. During each cell division, the duplicated sister chromosomes are evenly separated into two daughter cells. A cellular surveillance system called the spindle checkpoint ensures the accuracy of sister-chromosome separation. Three checkpoint proteins, p31comet, MAD2 and BUBR1, are critical for accurate chromosome segregation. In the process of studying this checkpoint, we have unexpectedly discovered that mice lacking p31comet in the liver develop diabetes. Liver cells lacking p31comet do not have IR on the cell surface, and thus cannot respond to insulin. We have further shown that MAD2 directly binds to IR, and along with BUBR1, helps to drag IR inside the cell. p31comet prevents BUBR1 from interacting with IR-bound MAD2, thus keeping IR at the cell surface. In cells lacking p31comet, MAD2 and BUBR1 gain the upper hand and remove IR from the cell surface. Thus, the dynamic tug-of-war between p31comet and MAD2-BUBR1 determines the status of IR at the cell surface.

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Potassium Compound In Fruits/Vegetables May Reduce Oxidative Stress

MedicalResearch.com Interview with:

Dr-Wanpen-Vongpatanasin.jpg

Dr. Vongpatanasin

Dr. Wanpen Vongpatanasin MD
The Norman and Audrey Kaplan Chair in Hypertension
UT Southwestern Medical Center

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Diet rich in fruits, vegetables, and dairy products, known as the DASH diet, is known to reduce blood pressure in hypertensive patients. More recently, the DASH diet was shown to reduce oxidative stress in people with and without high blood pressure . However, the main nutritional ingredient responsible for these beneficial effects of the DASH diet remain unknown. Because the DASH diet is rich in potassium (K), magnesium (Mg), and alkali, we performed a randomized, double-blinded, placebo-controlled study to compare effects of KMg Citrate (KMgCit), K Chloride (KCl), and K Citrate (KCit) to allow dissociation of the three in hypertensive and prehypertensive individuals. This study was conducted in collaboration with Drs. Charles Pak and Orson Moe at UT Southwestern, the two leading experts in the field of Mineral Metabolism. We found that oxidative stress was markedly reduced by KMgCit powder compared to placebo, K Chloride, and K Citrate. On the hand, KMgCit has no significant effects on blood pressure .

MedicalResearch.com Editor’s note:  DO NOT Take Potassium supplements unless under the direction of your health care provider.

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