Discovery of New Gene That Causes Sudden Death in Young Athletes

MedicalResearch.com Interview with:
Lia Crotti, MD, PhD

Department of Cardiovascular, Neural and Metabolic Sciences
San Luca Hospital
IRCCS Istituto Auxologico Italiano

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

Response: Sudden cardiac death in one of the major cause of death in Western Countries and among the causes of these deaths in young people under the age of 35, inherited forms of cardiomyopathy have a prominent role. Among these cardiomyopathies, Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) plays a major role. In ARVC, the heart tissue is replaced by fatty and fibrous tissue. This process encourages the development of life-threatening arrhythmias, such as ventricular fibrillation, that causes a cardiac arrest and sudden death in few minutes without a ready device to shock the heart. Intense physical activity favors the progression of the disease and arrhythmias are frequently triggered by adrenergic activation: those are the reason why young athletes with this disease are at high risk.

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70-Gene Signature Changes 50% of Breast Cancer Chemotherapy Advice

MedicalResearch.com Interview with:
Anne Kuijer, MD

Departments of Surgery and Radiology
University Medical Center Utrecht and
Thijs van Dalen, PhD
Department of Surgery
Netherlands Cancer Institute, Amsterdam

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

Response: In recent years it has become evident that clinicopathological factors fail to accurately determine prognosis in hormone receptor positive early stage breast cancer patients at intermediate risk of developing metastases. Gene-expression profiles, such as the 70-gene signature (MammaPrint) are therefore increasingly used for chemotherapy decision-making. In the current multicentre study we assessed the impact of 70-gene signature use on chemotherapy decisions in these patients. We demonstrated that, without the use of the 70-gene signature, half of patients was advised chemotherapy, which reflects the current controversy regarding chemotherapy benefit. Use of the 70-gene signature changed the chemotherapy advice in half of all patients and adherence to the 70-gene signature result was high.

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Effect of Moderate-Intensity Exercise Training on Peak Oxygen Consumption in Patients With Hypertrophic Cardiomyopathy

MedicalResearch.com Interview with:

Sara Saberi, MD Assistant Professor Inherited Cardiomyopathy Program Frankel Cardiovascular Center University of Michigan Hospital and Health Systems

Dr. Sara Saberi

Sara Saberi, MD
Assistant Professor
Inherited Cardiomyopathy Program
Frankel Cardiovascular Center
University of Michigan Hospital and Health Systems 

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

Response: Patients with hypertrophic cardiomyopathy are often told not to exercise or to significantly curb their exercise due to concern over the potential risk of increased ventricular arrhythmias and sudden cardiac death. There is no data regarding risks/benefits of exercise in HCM though. There is, however, data that shows that patients with HCM are less active and more obese than the general population AND a majority feel that exercise restrictions negatively impact their emotional well-being.

So, we devised a randomized clinical trial of a 16-week moderate-intensity aerobic exercise program versus usual activity with the primary outcome being change in peak VO2 (oxygen consumption). This exercise intervention resulted in a 1.27 mL/kg/min improvement in peak VO2 over the usual activity group, a statistically significant finding. There were no major adverse events (no death, aborted sudden cardiac death, appropriate ICD therapies, or sustained ventricular tachycardia). There was also a 10% improvement in quality of life as measured by the Physical Functioning scale of the SF-36v2.

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Racial Disparities in Genetic Testing of Women With Breast Cancer

MedicalResearch.com Interview with:

Cary P. Gross, MD Section of General Internal Medicine Yale University School of Medicine New Haven, CT

Dr. Cary Gross

Cary P. Gross, MD
Section of General Internal Medicine
Yale University School of Medicine
New Haven, CT

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

Response: Prior work has demonstrated racial and socioeconomic disparities in breast cancer diagnosis, treatment, and outcomes.  As the oncology field has progressed over the past decade, the use of genetic testing to guide treatment decisions is one of the most exciting new developments.

Our team was concerned that these new gene tests, which can offer important benefits, may have the potential to exacerbate disparities further.  That is, if there is unequal access to gene testing among patients for whom it is recommended, then our progress against cancer will not be equitably shared among people of all races and ethnicities.

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Genotypes Can Increase or Decrease Young Adult Financial Outcomes, Depending on Parental Income

MedicalResearch.com Interview with:

Emily Rauscher PhD Assistant Professor Department of Sociology University of Kansas

Dr. Rausher

Emily Rauscher PhD
Assistant Professor
Department of Sociology
University of Kansas  

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

Response: A lot of previous research has identified genotypes that increase sensitivity to context.  Much of this research, however, looks at particular aspects of health and is not able to address the methodological challenges of investigating gene-environment interactions.  To gain a better sense of the potential outcomes that may be susceptible to gene-environment interactions, I examine financial standing in young adulthood.  Testing this type of interaction is challenging because genotype and social environment are not randomly distributed throughout the population. Given this non-random distribution, unobserved confounders (such as parental behaviors, education, ethnicity, or social capital) could influence both parent and child financial standing.

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Democrats More Likely To Attribute Obesity to Genetics

MedicalResearch.com Interview with:

Professor Don Haider-Markel Chair, Department of Political Science University of Kansas Lawrence, KS 66045

Prof.  Haider-Markel

Professor Don Haider-Markel
Chair, Department of Political Science
University of Kansas
Lawrence, KS 66045

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

Response: We have studied causal attributions for conditions and problems in society for some time. We noticed that public debate over obesity had increased and new policy proposals were being proposed to address what was deemed as a growing public health problem. As the salience of the issue increased so too did partisan views on the topic.

Based on these observations, we wanted to explore individual beliefs about the causes, or attributions for, obesity. Existing research and theory suggested that Republicans following a conservative philosophy would be more likely to attribute obesity to personal choices, such as eating habits and lack of exercise—in short, putting the locus of control on individuals. Meanwhile liberal leaning Democrats, with a known predisposition to suggest conditions or problems are outside of the control of the individual, would be more likely to attribute obesity to either genetic or other biological factors, or the broader context of widely available low-cost high-fat food sources.

Additionally, we know that individuals tend to make attributions that are self-serving. In other words, people tend to make attributions that put themselves in a positive light. Thus, personal weight should factor into obesity attributions. Here we expected that overweight people would be more likely to make attributions that removed personal blame, such as pointing to a genetic cause. People closer to an ideal weight would, on the other hand, be more likely to attribute weight-level to personal choices.

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Gene “Decorations” Can Serve as Blood Biomarkers To Detect Cancer

MedicalResearch.com Interview with:

Kun Zhang, PhD Professor UCSD Department of Bioengineering La Jolla, CA 92093-0412

Dr. Kun Zhang

Kun Zhang, PhD
Professor
UCSD Department of Bioengineering
La Jolla, CA 92093-0412

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

Response: We have been interested in a type of chemical modification on the DNA, called CpG methylation, for years. This is like a decoration of DNA molecules that is specific to the cell type or tissue type. We were particularly interested in studying how such decoration spread along the DNA molecules. In this study, we did a very comprehensive search of the entire human genome for various human cell types and tissue types, and found close to 150,000 regions (called MHB in this study) in which adjacent CpG share the same decoration. We then went on to find out how many of such regions are unique to each normal cell/tissue type, and how many are specific to cancers. Then we took some of these highly informative regions as “biomarkers”, and showed that we can detect the absence or presence of cancer, and, in the latter case, where the tumor grow, in a patient’s blood.

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Genetic Variants Tied To Kidney Disease in African Americans

MedicalResearch.com Interview with:

Katalin Susztak MD, PhD Associate Professor of Medicine Perelman School of Medicine University of Pennsylvania Philadelphia, PA 19104

Dr. Susztak

Katalin Susztak MD, PhD
Associate Professor of Medicine
Perelman School of Medicine
University of Pennsylvania
Philadelphia, PA 19104

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

Response: Previous studies showed an association between genetic variants in the APOL1 gene and kidney disease development, but it has not been confidently shown that this genetic variant is actually causal for kidney disease. For this reason we developed a mouse model that recapitulates the human phenotype.

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Diabetes Drug Reverses Aging Medium That Promotes Melanoma

MedicalResearch.com Interview with:

Reeti Behera, Ph.D. Postdoctoral fellow in the Weeraratna lab The Wistar Institute Philadelphia PA

Dr. Behera

Reeti Behera, Ph.D.
Postdoctoral fellow in the Weeraratna lab
The Wistar Institute
Philadelphia PA

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

Response: Malignant melanoma is an aggressive disease and is the cause of the majority of skin cancer deaths. In particular, older individuals have a much poorer prognosis for melanoma and are more resistant to targeted therapy than compared to young individuals. A recently published study from our lab has shown that age-related changes in secreted factors in the microenvironment can drive melanoma progression and therapy resistance.

Klotho is a protein whose expression levels decreases with aging. In this study, we have shown that a decrease in klotho levels in the aged microenvironment drives melanoma aggression and therapy resistance by promoting the oncogenic signaling pathway Wnt5A. We also have shown that reconstituting klotho levels in the aged microenvironment by using rosiglitazone, an FDA-approved drug used to treat diabetes, can reduce tumor burden in aged mice. We also show that Klotho expression is decreased in therapy-resistant melanoma tumors. Reconstituting klotho levels in therapy-resistant melanoma cells by treating with rosiglitazone can inhibit Wnt5A levels and MAPK pathway. We also show that rosiglitazone can significantly decrease therapy-resistant tumor burden in the aged mice, but not in the young.

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Genetic Variant of p53 Gene May Explain Increased Breast Cancer Risk in African American Women

MedicalResearch.com Interview with:

Maureen E. Murphy, Ph.D. Professor and Program Leader, Molecular and Cellular Oncogenesis Program Associate Vice President for Faculty Affairs Associate Director for Education and Career Development The Wistar Institute Philadelphia, PA 19104

Dr. Murphy

Maureen E. Murphy, Ph.D.
Professor and Program Leader, Molecular and Cellular Oncogenesis Program
Associate Vice President for Faculty Affairs
Associate Director for Education and Career Development
The Wistar Institute
Philadelphia, PA 19104

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

Response: The Murphy group discovered a coding-region variant of the p53 tumor suppressor gene, called Pro47Ser, that exists in individuals of African descent. In previous studies this group reported that this amino acid change reduces the ability of p53 to function as a tumor suppressor.

In this study, African American women from two different large cohorts were assessed for the incidence of the Pro47Ser variant in pre-menopausal breast cancer. A modest but statistically significant association was found between Pro47Ser and pre-menopausal breast cancer.

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New Gene For Rare Type Of Muscular Dystrophy Identified

MedicalResearch.com Interview with:

Dr Chiara Manzini PhD Assistant Professor of Pharmacology and Physiology, and Integrative Systems Biology George Washington University

Dr Chiara Manzini

Dr Chiara Manzini PhD
Assistant Professor of Pharmacology and Physiology, and Integrative Systems Biology
George Washington University

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

Response: I have been working on finding genes that are mutated in rare forms of muscular dystrophy associated with brain and eye deficits for many years.

In the current study, which was a large collaborative effort, we found that mutations in the INPP5K gene cause a new type of muscular dystrophy with short stature, intellectual disability and cataracts. INPP5K is critical for processing a chemical called inositol phosphate which has multiple functions within the cell. We found that the mutations in the patients severely disrupt INPP5K function and when we removed the gene during zebrafish development, the fish showed the same findings observed in the patients: small size, disrupted muscle structure and eye deficits. We are very excited because this is a new disease gene for muscular dystrophy and a novel disease mechanisms, which can open up multiple new lines of investigation.

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Genetic Defect in DNA Repair Enzyme Linked to Prostate Cancer

MedicalResearch.com Interview with:
G. Andrés Cisneros, Ph.D.

Associate Professor
Department of Chemistry Center for Advanced Scientific Computing and Modeling, University of North Texas

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

Response: The accurate maintenance of DNA is crucial, if DNA damage is not addressed it can lead to various diseases including cancer. Therefore, the question arises about what happens if enzymes in charge of DNA repair are themselves mutated. We previously developed a method to perform targeted searches for cancer-related SNPs on genes of interest called HyDn-SNP-S. This method was applied to find prostate-cancer SNPs on DNA dealkylases in the ALKB family of enzymes.

Our results uncovered a particular mutation on ALKBH7, R191Q, that is significantly associated with prostate cancer. Subsequent computer simulations and experiments indicate that this cancer mutation results in a decreased ability of ALKBH7 to bind its co-factor, thus impeding its ability to perform its native function.

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