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Author Interviews, Cancer Research, Colon Cancer, Genetic Research / 14.05.2016

MedicalResearch.com Interview with: Dr. Geoffrey Liu, MD MSC Princess Margaret Hospital/Ontario Cancer Institute University of Toronto Toronto, Ontario Canada MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Liu: Cetuximab is a monoclonal antibody therapy used in metastatic colorectal cancer patients when other chemotherapy options have been exhausted. Currently, the only useful biomarker to determine whether metastatic colorectal cancer patients will benefit from the drug, cetuximab, is whether patients carry a RAS mutation in their tumours. We evaluated additional biomarkers using samples from a Phase III clinical trial led by the Canadian Cancer Trials Group and the Australasian Gastrointestinal Trials Group. Our study identified a germline, heritable biomarker, a FCGR2A polymorphism, that further identifies an additional subgroup of patients who would benefit most from receiving cetuximab. This is important because the drug does have toxicity and is expensive to use; patients who are found not to likely benefit from this drug can go on quickly to try other agents, including participation in clinical trials. (more…)
Author Interviews, Brain Cancer - Brain Tumors, Genetic Research, PLoS / 13.05.2016

MedicalResearch.com Interview with: Katarina Truvé PhD Swedish University of Agricultural Sciences and Kerstin Lindblad-Toh Uppsala University MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Truvé: Gliomas are malignant brain tumors that are rarely curable. These tumors occur with similar frequencies in both dogs and humans. Gliomas in dogs are strikingly similar at the biological and imaging level to human tumor counterparts. Some dog breeds such as Boxer and Bulldog are at considerably higher risk of developing glioma. Since these breeds at high risk are recently related, they are most likely carrying shared genetic risk factors. Our goal was therefore to use the dog genome to locate genes that may be involved in the development of glioma in both dogs and humans. We found a strongly associated locus and identified three candidate genes, DENR, P2RX7 and CAMKK2 in the genomic region. We have shown that CAMKK2 is lower expressed in glioma tumors than normal tissue in both dogs and human, and it has been reported that the associated canine mutation in P2RX7 results in a decrease in receptor function. (more…)
Author Interviews, Education, Genetic Research, Nature / 13.05.2016

MedicalResearch.com Interview with: Dr. Daniel J. Benjamin PhD Associate Professor (Research), USC, 2015-present Associate Professor (with tenure), Cornell, 2013-2015 Assistant Professor, Cornell University, 2007-2013 Research Associate, NBER, 2013-present Faculty Research Fellow, NBER, 2009-2013  MedicalResearch.com: What is the background for this study? Dr. Benjamin: Educational attainment is primarily determined by environmental factors, but decades of twin and family studies have found that genetic factors also play a role, accounting for at least 20% of variation in educational attainment across individuals. This finding implies that there are genetic variants associated statistically with more educational attainment (people who carry these variants will tend on average to complete more formal education) and genetic variants associated statistically with less educational attainment (people who carry these variants will tend on average to complete less formal education). But none of these genetic variants had been identified until our 2013 paper on educational attainment. That paper, which studied a sample of roughly 100,000 individuals, identified 3 genetic variants associated with educational attainment, each of which has a very small effect. In the current paper, we expanded our sample to roughly 300,000 individuals, with the goal of learning much more about the genetic factors correlated with educational attainment. (more…)
Author Interviews, Biomarkers, Cancer Research, Genetic Research, MD Anderson / 11.05.2016

MedicalResearch.com Interview with: Dr. Han Liang PhD Associate Professor and Deputy Department Chair, Department of Bioinformatics and Computational Biology The University of Texas MD Anderson Cancer Center Faculty Member, Baylor College of Medicine Houston, TX MedicalResearch: What is the background for this study? What are the main findings? Dr. Liang: An individual’s sex has been long recognized as a key factor affecting the risk of cancer development and management. However, previous studies on the sex effect have been limited to individual genes, single molecular data types, and single cancer lineages. We performed a comprehensive analysis of molecular differences between male and female patients in a diversity of cancer types and revealed two sex-effect groups. One group contains a small number of sex-affected genes, whereas the other shows much more extensive sex-biased molecular signatures. More than half of clinically actionable genes (e.g., therapeutic targets or biomarkers) show sex-biased signatures. (more…)
Author Interviews, Genetic Research, Nature / 10.05.2016

MedicalResearch.com Interview with: Serena Nik-Zainal MD PhD Wellcome Beit Fellow & Honorary Consultant in Clinical Genetics CDF Group Leader Wellcome Trust Sanger Institute United Kingdom  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Nik-Zainal: We have used the massive improvement in speed of "sequencing" (reading the human genetic material) in order to obtain comprehensive whole genome maps of 560 human breast cancer patients. This is the largest whole genome sequencing study of a single cancer type in the world. We wanted to forensically search these cancers, find all the important genes that drive breast cancer, find all the important mutation patterns that tell us something about why breast cells turn into cancer cells and then to pull it altogether for each patient. We wanted to be able to "profile" each cancer patient, to see if we could further our understanding of personal cancer genomes. In all, we had 556 female and four male patients, and they were sought from all over the world – USA, Europe and Asia. (more…)
Author Interviews, BMJ, Diabetes, Genetic Research / 08.05.2016

MedicalResearch.com Interview with: Wenpeng You, PhD student Biological Anthropology and Comparative Anatomy Research Unit University of Adelaide | School of Medicine Adelaide, Australia  Maciej Henneberg, PhD, DSc, FAIBiol Wood Jones Professor of Anthropological and Comparative Anatomy University of Adelaide School of Medicine; Institute for Evolutionary Medicine, University of Zurich Editor in Chief, Journal of Comparative Human Biology HOMO MedicalResearch.com: What is the background for this study? What are the main findings? Response: Type 1 diabetes disease has very strong genetic background. Prevalence of type 1 diabetes has been increasing globally. Previous studies focusing on regional genetics and environmental factors cannot fully explain this phenomenon. Due to insufficient medical knowledge up until early 20th century, people with type 1 diabetes disease would most commonly die during their teens or early 20s. Therefore, they did not have the opportunity to pass on their genes providing background for the development of type 1 diabetes to their next generations. Since discovery and introduction of insulin to modern medicine in early 1920s, more and more type 1 diabetes patients have been able to survive their reproduction cycle (up until and past 50 years of age). This has made more and more genes related to type 1 diabetes to accumulate in human populations. We applied the Biological State Index which measures a probability to pass genes on to the next generation at population level.  We found that the rapid increase in type 1 diabetes over the last few decades was correlated with increases of the Biological State Index and its proxy, human life expectancy, especially in more developed world in which natural selection has been relaxed most. This correlation was found after statistically excluding differences in countries income, levels of urbanization, sugar consumption and obesity prevalence. (more…)
Author Interviews, Genetic Research, MD Anderson, Pain Research / 05.05.2016

MedicalResearch.com Interview with: Hui-Lin Pan, MD, PhD Helen T. Hawkins Distinguished Professor and Deputy Division Head for Research Division of Anesthesiology and Critical Care, Unit 110 The University of Texas MD Anderson Cancer Center Houston, TX MedicalResearch.com: What is the background for this study? Dr. Hui-Lin Pan: Chronic nerve pain caused by damage to the peripheral nerve is a debilitating health problem and remains very difficult to treat. Sensory neurons in the spinal cord are normally inhibited by inhibitory neurotransmitters (GABA and glycine) to regulate transmission of painful information. A major feature of nerve injury-induced chronic pain is reduced spinal cord inhibition, resulting from diminished activity of a chloride transporter called KCC2. In this study, we investigated whether increasing KCC2 expression at the spinal level using a lentiviral vector can restore KCC2 activity, thereby reducing chronic nerve pain. (more…)
Author Interviews, Genetic Research, Science / 04.05.2016

MedicalResearch.com Interview with: Lluís Ribas de Pouplana, Ph.D IRB Barcelona Barcelona 08028 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Ever since the discovery of the genetic code it became obvious that the system had not grown to its full theoretical potential of making proteins with 63 different amino acids. Francis Crick called the code 'a frozen accident', but it was unclear what had actually froze it. In this article we offer an explanation to that, and we validate it experimentally. What we find is that the central pieces of the genetic code, the transfer RNAs, are unable to incorporate enough specific elements for the system to be able to use 63 of them without confusion. Since you need a new tRNA for each new amino acid, once the tRNA identification limit is reached you also reach the maximum number of usable amino acids. This limit happened to be reached at 20, and that's where it has stayed for 3 billion years. (more…)
Addiction, Author Interviews, Genetic Research, PNAS / 29.04.2016

MedicalResearch.com Interview with: Shelly B. Flagel, PhD Molecular and Behavioral Neuroscience Institute Department of Psychiatry University of Michigan, Ann Arbor, MI 48109 MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Flagel: We used a unique genetic animal model to examine individual differences in addiction liability. This model of selectively bred rat lines allowed us to examine the brains of “addiction-prone” and “addiction-resilient” rats before and after they were exposed to cocaine. I mportantly, even though all rats were exposed to the same amount of drug, only a certain subset exhibited addiction-like behavior. We focused our neurobiological analyses on two molecules that have been previously implicated in response to drugs of abuse – the dopamine D2 receptor and fibroblast growth factor (FGF2). We examined gene expression and the epigenetic regulation of these molecules and found that low levels of FGF2 in the core of the nucleus accumbens, a brain region known for regulating motivated behavior, may protect individuals from becoming addicted; whereas low levels of D2 in this brain region may predispose individuals to addiction. Further, this is the first study to show that epigenetic modulation of these molecules may be a predisposing factor and that, the epigenetic regulation of D2 may be especially important in susceptibility to relapse. (more…)
Author Interviews, Breast Cancer, Compliance, Genetic Research, Mammograms / 27.04.2016

MedicalResearch.com Interview with: Stamatia Destounis, MD, FSBI, FACR Elizabeth Wende Breast Care, LLC, Clinical Professor of Imaging Sciences University of Rochester School of Medicine and Dentistry  Rochester NY 14620  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Destounis: Identification of women who have an increased risk of breast cancer is important, as they are often eligible for additional screening methods, such as breast MRI. One criterion for eligibility for screening breast MRI is >20% lifetime risk of breast cancer, as determined by risk assessment models through genetic counseling. At my facility, we have incorporated a genetics program. Through the program we are flagging and identifying a large volume of patients who are potentially eligible for additional services. This study was conducted to determine the value of screening MRI in the patient subgroup who have undergone genetic counseling at my facility. In this group we found 50% of patients who were referred for counseling were also recommended to have screening MRI. However, only 21.3% of those recommended actually pursued the exam. Of those patients who did have a screening MRI, 4 were diagnosed with breast cancer, all of which were invasive and node negative. We ultimately had a 10% biopsy rate and 50% cancer detection rate in this subgroup. (more…)
Author Interviews, Genetic Research, PLoS, Vitamin D / 27.04.2016

MedicalResearch.com Interview with: Haidong Zhu, MD, PhD Associate Professor of Pediatrics Georgia Prevention Institute Medical College of Georgia Augusta University MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Zhu: Vitamin D plays an important role in a wide range of body functions beyond bone health. Vitamin D deficiency is associated with increased risk of cancer and cardiovascular disease. Vitamin D deficiency is common among darker skin individuals, particularly African-Americans, which could contribute to health disparity. We want to understand underlying molecular mechanism (i.e. global DNA methylation) for how vitamin D deficiency causes cancer, cardiovascular disease and impaired immune function. DNA methylation, a chemical modification to our genome, is one of the ways that our body adapts to the environment. Low rate of global DNA methylation is a common event in cancer, which may lead to disturbances in the genome, make the genome more vulnerable to environmental damage and increase disease risk. Our study shows that majority of black teens are vitamin D deficient and have a lower rate of global DNA methylation than white teens. We further demonstrate that vitamin D3 supplementation for 16 weeks increases global DNA methylation in black teens and young adults. Our study provides an important piece of evidence that vitamin D plays a role in epigenetic regulation in humans, which could be an underlying mechanism for vitamin D-deficiency related disease risk and health disparity. (more…)
AACR, Author Interviews, Cancer Research, Genetic Research, MD Anderson, Weight Research / 20.04.2016

MedicalResearch.com Interview with: Dr. Xifeng Wu, MD PhD Department Chair, Department of Epidemiology, Division of OVP, Cancer Prevention and Population Sciences Director, Center for Translational and Public Health Genomics Professor, Department of Epidemiology Division of Cancer Prevention and Population Sciences The University of Texas MD Anderson Cancer Center, Houston, Texas Medical Research: What is the background for this study? What are the main findings? Dr. Wu: Obesity is a well-established risk factor for renal cell carcinoma (RCC), the most common form of kidney cancer. It has been estimated that more than 40% of RCC incident cases in the US may be attributed to excessive body weight. Growing body of evidence suggests that obesity may also influence clinical outcome of RCC; however, the findings are sometimes conflicting. So far, the molecular mechanism linking obesity to RCC risk or prognosis is not well understood. In this study, we evaluated the promoter CpG site methylation of 20 candidate obesity-related genes and their association with RCC risk and recurrence in a two-phase study of 240 newly diagnosed, previously untreated RCC patients. Pyrosequencing was conducted on paired RCC tumor and normal adjacent tissues to measure promoter methylation. Among the 20 markers, we found NPY, LEP and LEPR showed significant differential methylation levels between tumors and normal adjacent tissues, and methylation was significantly higher in tumors in both discovery and validation groups. Consistent with our findings, we also found lower expression of LEPR in tumor tissues compared to normal adjacent tissues in data obtained from The Cancer Genome Atlas. Additionally, high LEPR methylation in tumors was associated with more advanced tumor features, such as high pathologic stage, high grade and clear cell RCC histology, and increased risk of recurrence compared to the low methylation group. These results suggest that tissue changes in promoter methylation in obesity-related genes may provide some biological basis for the association between obesity and RCC outcome, and that LEPR may be an independent prognostic indicator of recurrence in RCC patients. Further research in larger study population and functional studies are warranted to validate our findings and to elucidate the underlying causal mechanisms. (more…)
Author Interviews, Exercise - Fitness, Genetic Research / 20.04.2016

MedicalResearch.com Interview with: Nicholas Jones BSc (Hons) MSc ISAK CSCS ASCC DNA Sports Performance Ltd Director MedicalResearch.com: What is the background for this study? Response: Coaches and trainers all know that individuals can respond differently to the same stimulus. One person may be a super responder to X training method, another may be a none-responder to the very same training method. The reasons for this have never been fully explained, however genetics have been discussed and thought to play a role for some time. MedicalResearch.com: What are the main findings? Response: At the beginning of the eight weeks of training, the participants were set two fitness tests to measure their power and endurance. Power was measured by a countermovement jump (CMJ) and endurance by an aerobic three minute cycle test (known as Aero3). After eight weeks, those whose training had been matched to their genes improved their CMJ power test of 7.4% compared to just a 2.6% increase in the mismatched group. In the cycle endurance test, those who trained to their genetic strengths saw an average 6.2% improvement compared to 2.3% for the mismatched group. (more…)
Author Interviews, Genetic Research, Heart Disease, JAMA, UCSD / 01.04.2016

MedicalResearch.com Interview with: H Kirk Hammond, MD Professor of Medicine (Cardiology) University of California San Diego Veterans Affairs San Diego Healthcare System San Diego, CA 92161  MedicalResearch.com: What is the background for this study? Dr. Hammond: Heart failure affects >28 million patients worldwide and is the only cardiovascular disease that is increasing in prevalence. Despite steady improvement in drug therapy for heart failure, recent hospitalization rates and mortality have changed little. New therapies are needed. Adenylyl cyclase type 6 (AC6), is a protein that catalyzes the conversion of ATP to cAMP and is an important determinant of heart function. The amount and function of AC6 are reduced in failing hearts, and preclinical studies have shown benefits of increased cardiac AC6 content on the heart. The aim of the trial was to determine safety and heart function gene transfer of AC6, achieved by intracoronary delivery of an inactivated virus carrying the gene for AC6 (Ad5hAC6) in patients with symptomatic heart failure and reduced ejection fraction. Our hypothesis was that AC6 gene transfer would safely increase function of the failing hearts of patients with heart failure. (more…)
Author Interviews, Genetic Research, JAMA, Schizophrenia / 26.03.2016

MedicalResearch.com Interview with: S. Hong Lee, PhD Queensland Brain Institute, The University of Queensland, Brisbane School of Environmental and Rural Science, University of New England, Armidale Australia  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Previous studies reported increased risk of schizophrenia (SCZ) in offspring associated with both early and delayed parental age. However, it remains unclear if the risk to the child is due to psychosocial factors associated with parental age or if those at higher risk for schizophrenia tend to have children at an earlier or later age. We found evidence for a significant overlap between genetic factors associated with risk of schizophrenia and genetic factors associated with Age at First Birth (AFB). We observed a U-shaped relationship between schizophrenia risk and maternal AFB, consistent with the previously reported relationship between schizophrenia risk in offspring and maternal age when not adjusted for age of the father. (more…)
Allergies, Author Interviews, Genetic Research / 26.03.2016

MedicalResearch.com Interview with: Dr Gabrielle A. Lockett PhD Postdoctoral Research Fellow Asthma Genetics Laboratory, Faculty of Medicine, University of Southampton MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Lockett: Season of birth has been known for decades to influence a huge range of traits, such as height and lifespan, as well as the risks of diseases such as allergy and schizophrenia. But until now the mechanism for season of birth effects was unknown. This study discovered that epigenetic marks (specifically DNA methylation) on the genome are associated with season of birth in 18-year-olds, suggesting that this could be a mechanism for such long-lasting birth season effects. Epigenetic marks on the genome are known to both influence gene expression and to change in association with environmental exposures. This study is the first to identify DNA methylation associated with season of birth. This discovery therefore extends our knowledge of environmental exposures that are able to affect the epigenome. The study also went on to further examine the genes identified to contain birth season-associated DNA methylation. Groups of these genes have functions related to development, cell death and the cell cycle, suggesting that season of birth alters the epigenetic regulation of these processes in particular. There was also suggestive evidence that season-associated DNA methylation could be on the functional pathway to allergic disease outcomes. (more…)
Alcohol, Author Interviews, Breast Cancer, Genetic Research, PLoS / 18.03.2016

MedicalResearch.com Interview with: Chin-Yo Lin, Ph.D. University of Houston Center for Nuclear Receptors and Cell Signaling Department of Biology and Biochemistry Science and Engineering Research Center (SERC) Houston, TX 77204-5056  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Lin: Many studies have established that alcohol consumption is a risk factor for breast cancer. Breast cancers associated with drinking tend to be hormone receptor-positive, the type is commonly treated with the drug tamoxifen which blocks the actions of estrogen in driving tumor growth in pre-menopausal women. Alcohol consumption has also been shown to increase the risk of disease recurrence in patients. Our study shows that alcohol can enhance the effects of estrogen by increasing cancer cell division and also reduce the efficacy of tamoxifen. The key mechanistic insight from the study is that alcohol treatment of breast cancer cells increased the expression of BRAF, a cancer-causing gene that is commonly mutated and activated in other types of cancers. (more…)
Author Interviews, Genetic Research, Heart Disease / 18.03.2016

MedicalResearch.com Interview with: Jonathan P. Davis , Ph.D. Associate ProfessorThe Ohio State University Medical Center Department of Physiology & Cell Biology. Columbus, OH 43210 MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Davis: Myocardial infarction (MI) is a leading cause of heart failure and death in the US. Since the infarcted heart does not contract as well, therapeutics have been designed (i.e. positive inotropes) to help the heart contract better. While current positive inotropes help the patients in the short-term, they have detrimental long-term effects (“feel better but die sooner”). There is a dire need to be able to increase cardiac contraction without the deleterious side effects. We have achieved this goal by engineering the Ca2+-dependent switch in the heart, troponin C, to be able to better bind Ca2+. Combining gene therapy with our smartly formulated TnC, we demonstrated that our novel strategy not only protected the mouse from the negative consequences of an MI, but was also therapeutic when given after the MI. (more…)
AHA Journals, Author Interviews, Genetic Research, Heart Disease, Lipids / 18.03.2016

MedicalResearch.com Interview with: Dr. Sarah de Ferranti MD MPH Boston Children’s Hospital Director, Preventive Cardiology Program Assistant Professor of Pediatrics Harvard Medical School MedicalResearch.com:  What are the main findings? Dr. de Ferranti: Familial hypercholesterolemia, or FH, is a genetic condition that causes severely elevated cholesterol levels from birth and is a leading cause of early heart attack. It is generally slowly progressive without symptoms until there is serious heart disease in the 3rd and 4th decade of life, making it important to look for it at a young age. Prior to this analysis it was thought that FH affected about 1 in 500 adults. The current study used data from 36,949 adults who took part in the 1999-2012 National Health and Nutrition Examination Survey (NHANES) and extrapolated to the 210 million U.S. adults aged 20 years and older. We identified cases of probably or definite Familial hypercholesterolemia in our analysis by using a combination of high levels of low-density-lipoprotein cholesterol (considered “bad” because it contributes to plaque buildup in arteries) and early heart disease in a person or close relative. (more…)
Author Interviews, Brain Injury, Genetic Research / 09.03.2016

MedicalResearch.com Interview with: Dr. Jane McDevitt Temple University in Philadelphia MedicalResearch.com: What is the background for this study? Dr. McDevitt: During a head impact there is a mechanical load that causes acceleration and deceleration forces on the brain within the cranium. The acceleration and deceleration causes stress to the neurons and initiates a neurometabolic cascade, where excitatory neurotransmitters such as glutamate are released and depolarize the cell.  This triggers protein channels to open and allow ions into and out of the cell.  Increases in calcium persist longer and have greater magnitude of imbalance than any other ionic disturbance. One channel responsible for allowing calcium into the cell is r-type voltage-gated calcium channel.  One of the main proteins within this voltage-gated calcium channel is the CACNA1E protein produced by the CACNA1E gene. This protein forms the external pore and contains a pair of glutamate residues that are required for calcium selectivity.   It is also responsible for modulating neuronal firing patterns. A variation within this gene (i.e,CACNA1E ) that regulates expression levels of CACNA1E could be associated with how an athlete recovers following a concussion injury. Upwards of 20% of the concussed population fall into the prolonged recovery category, which puts these athletes at risk for returning to play quicker than they should. Variation in recovery depends on extrinsic factors like magnitude of impact, and sport, or intrinsic factors like age or sex. One intrinsic factor that has not been definitively parsed out is genetic variation. Recovery is likely to be influenced by genetics because genes determine the structure and function of proteins involved in the cell’s resistance and response to mechanical stress. Due to CACNA1E’s relationship to calcium influx regulation, a single nucleotide polymorphism (SNP) could modify the expression level of the protein responsible for regulating calcium. Altered protein levels could lead to athlete’s responding to concussive injuries differently. The main objective of this study was to examine the association between CACNA1E SNPs with concussion recovery in athletes. (more…)
Author Interviews, Biomarkers, Cleveland Clinic, Genetic Research, Personalized Medicine, Prostate, Prostate Cancer, Urology / 07.03.2016

MedicalResearch.com Interview with: Eric A. Klein, MD Chairman, Glickman Urological and Kidney Institute Cleveland Clinic MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Klein: Prostate cancer is an enigma. While this tumor is the second leading cause of cancer death among American men, most newly diagnosed disease detected by PSA screening is biologically indolent and does not require immediate therapy. Currently, the main clinical challenge in these men is to distinguish between those who can be managed by active surveillance from those who require curative intervention. Current clinical and pathological tools used for risk stratification are limited in accuracy for distinguishing between these scenarios. An abundance of research in the last decade has provided evidence that genomics can offer meaningful and clinically actionable biological information to help inform decision making, and current National Comprehensive Cancer Network (NCCN) guidelines on prostate cancer endorse the use of commercially available genomic tools for men considering active surveillance.[1] It has been previously shown that the 22-gene genomic classifier, Decipher, accurately predicts the likelihood of metastasis and prostate cancer specific mortality when measured on tissue from radical prostatectomy specimens.[2] In multiple validation studies, it performed with higher accuracy and discrimination compared to clinical risk factors alone. The current study[3] is the first to examine whether the use of Decipher might aid decision making when measured on biopsy tissue at the time of diagnosis. Men with available needle biopsy samples were identified from a study cohort that previously had Decipher performed on their matched radical prostatectomy tissue. In this cohort of mixed low, intermediate and high risk men, Biopsy Decipher predicted the risk of metastasis 10 years post RP with high accuracy, outperforming NCCN clinical risk categorization, biopsy Gleason score and pre-operative PSA. Furthermore, this study showed that Decipher reclassified 46% of patients into lower or higher risk classification compared to NCCN classification alone. The study also showed that Biopsy Decipher can identify men that are at high risk for adverse pathology as defined by the presence of primary Gleason pattern 4 or greater. (more…)
Author Interviews, Breast Cancer, Cancer Research, Genetic Research / 06.03.2016

MedicalResearch.com Interview with: Rong Li, Ph.D., Professor Holder of the Tom C. & H. Frost Endowment Department of Molecular Medicine Institute of Biotechnology Co-Leader, Cancer Development and Progression Program Cancer Therapy & Research Center University of Texas Health Science Center at San Antonio  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Li: The breast cancer susceptibility gene BRCA1 is well known for its function in double strand break DNA repair. However, the ubiquitous role of BRCA1 in DNA repair may not be sufficient to explain its tissue-specific tumor suppressor function in vivo. Using the “awesome power” of mouse genetics, we identified a previously unappreciated crosstalk between BRCA1 and a transcription regulator in mammary gland development. Importantly, we provide compelling evidence that this BRCA1 function is independent of its well-established DNA repair activity. MedicalResearch.com: What should clinicians and patients take away from your report? Dr. Li: The newly identified DNA repair-independent function of BRCA1 may provide new tools and targets for early prevention of BRCA1-associated breast cancer. (more…)
Author Interviews, Genetic Research, Heart Disease, JACC / 04.03.2016

MedicalResearch.com Interview with: Silvia G Priori ,MD, PhD and Andrea Mazzanti, MD Medical Research: What is the background for this study? What are the main findings? Response: The study investigates a novel therapeutic approach for Long QT Syndrome type 3: a malignant varian of long QT Syndrome a disease in which the risk of arrhythmias is proportional to the prolongation of QT interval. LAQT3 is caused by gain of function mutations in the gene SCN5A that encode for the alpha subunit of the cardiac sodium channel. These mutations increase the late sodium current (INa late) that prolongs the QT interval and predisposes the heart to develop life-threatening ventricular arrhythmias. In 1996 we demonstrated in an animal model of Long QT Syndrome type 3 that administration of mexiletine was able to shorten QT interval and the same results were obtained in LQT3 patients treated with mexiletine : these data provided rational for the adoption in clinical practice guidelines to recommend the use of mexiletine to shorten QT interval in LQT3 patients with the expectation that shortening QT interval would reduce the risk of arrhythmic death. In this setting, our study is the first to provide data in support of the view that mexiletine shortens QT interval and reduces the probability to experience arrhythmic events. (more…)
ASCO, Author Interviews, Biomarkers, Breast Cancer, Chemotherapy, Genetic Research, Journal Clinical Oncology / 03.03.2016

MedicalResearch.com Interview with: Oleg Gluz, MD West German Study Group Breast Center Niederrhein Evangelical Hospital Bethesda Moenchengladbach, Germany MedicalResearch.com: What is the background for this study? Dr. Gluz: PlanB trial is a Phase III chemotherapy study performed in patients with clinically high risk HER2 negative breast cancer. After early amendement, Recurrence Score (Oncotype Dx) as a selection criterion for or against chemotherapy together with central pathology review were included into the study. Patients with very low RS of below 12 and up to 3 positive lymph nodes were recommended to omit chemotherapy based on the low genomic recurrence risk. Chemotherapy was omitted in about 15% of all patients. For the first time we present prospective data comparing a genomical tool (Oncotype Dx) and an independent central pathology review for grade, ER, PR, and Ki-67 from a large phase III study combined with an exploratory analysis on early relapse risk. MedicalResearch.com: What are the main findings? Dr. Gluz: The study has two major findings: We have found a significant discordance in risk assessment between prognostic tools (grade by local and central lab, Oncotype Dx, Ki-67). Patients treated by endocrine therapy alone based on very low Recurrence Score had an excellent disease free survival of 97% after 3 years of follow up. (more…)
Author Interviews, Genetic Research, MD Anderson, Nature, Prostate Cancer / 01.03.2016

MedicalResearch.com Interview with Dr. Dingxiao Zhang Ph.D Department of Epigenetics and Molecular Carcinogenesis University of Texas MD Anderson Cancer Center Smithville, TX 78957, USA MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Zhang: Prostate cancer (PCa) is a heterogeneous malignancy harboring phenotypically and functionally diverse subpopulations of cancer cells. To better understand PCa cell heterogeneity, it is crucial to dissect the biology of normal prostate epithelial lineages. The background for the current study is to annotate the gene expression profiles of normal prostate epithelial cells, through which we hope to gain insight on Prostate cancer subtypes and the cellular heterogeneity in PCa. The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. In this study, we have performed a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing. One of our major findings is that the differential gene expression profiles in basal versus luminal prostate epithelial cells account for their distinct functional properties. Specifically, basal cells preferentially express gene categories associated with stem cells, MYC-transcriptional program, neurogenesis, and ribosomal RNA (rRNA) biogenesis regulated by Pol I. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene expression profile is enriched in advanced, anaplastic, castration-resistant, and metastatic prostate cancers. Therefore, we link the cell-type specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features. (more…)
Author Interviews, Genetic Research, Sleep Disorders / 28.02.2016

MedicalResearch.com Interview with: Alice Gregory PhD Department of Psychology Goldsmiths, University of London London, UK Medical Research: What is the background for this study? What are the main findings? Dr. Gregory: Sleep paralysis involves a total inability to move just as someone is falling asleep or waking up. This experience typically ends within seconds to minutes and is not usually a sign of any wider problem – yet it can be extremely frightening. This is in part because this experience is often accompanied by hallucinations. To understand what is happening during episode of sleep paralysis it is useful to understand that there are different stages of sleep. One distinction is between Rapid Eye Movement (REM) and Non-Rapid Eye Movement (NREM) sleep. During REM sleep the body is paralysed. Dreaming often occurs during REM sleep, so it has been proposed that this paralysis keeps us safe, by preventing us from ‘acting out our dreams’. During an episode of sleep paralysis, someone may have woken up but has retained certain features of REM sleep (specifically the paralysis and sometimes dream-related hallucinations). While sleep paralysis is rather common and the public seem incredibly interested in learning more about this, it is surprising that there is such little research on this topic. Certain risk factors for sleep paralysis have been proposed previously, such as experiencing stress. However, those suffering from this experience are keen for more information, which is currently unavailable. For this reason, we wanted to see whether we could identify other factors which were associated with sleep paralysis. Furthermore, in reviewing the literature, we were stunned that while it seems obvious that genetic differences between people are likely to be important in explaining why certain people experience sleep paralysis and others do not – there was almost no work on this topic. We decided to investigate this further as well. (more…)
Author Interviews, Genetic Research, UCLA / 26.02.2016

MedicalResearch.com Interview with: April D. Pyle PhD Associate Professor, Microbiology, Immunology & Molecular Genetics Molecular Biology Institute Center for Duchenne Muscular Dystrophy Edythe Broad Center of Regenerative Medicine and Stem Cell Research University of California, Los Angeles, CA Medical Research: What is the background for this study? What are the main findings? Dr. Pyle: We have developed a CRISPR/Cas9 gene editing platform that is applicable for approximately 60 percent of Duchenne muscular dystrophy patients. Duchenne is a devastating muscle wasting disorder affecting approximately1 in 5000 boys worldwide. It is caused by lack of the dystrophin protein. In our study, we demonstrate that we can restore the dystrophin reading frame by deleting up to 725kb of the DMD gene between exons 45 and 55, the largest deletion shown to date in this gene, which results in a functional dystrophin protein being expressed. We demonstrated feasibility of this platform in Duchenne patient-derived human induced pluripotent stem cells differentiated to skeletal and cardiac muscle cells. (more…)
Author Interviews, Breast Cancer, Genetic Research, JAMA / 25.02.2016

MedicalResearch.com Interview with: Dr. Shoshana Rosenberg ScD, MPH Department of Medical Oncology Dana-Farber Cancer Institute Boston, Massachusetts Medical Research: Why would BRCA testing rates have increased among younger women with cancer?   Dr. Rosenberg: There has been increasing awareness surrounding genetic testing for breast cancer in more recent years, likely contributing to the trend that we saw over time  in our cohort. This has included more media attention, most notably Angelina Jolie’s sharing her story in 2013. Medical Research: Is this increase in testing a good thing? Dr. Rosenberg: Young women who are diagnosed with breast cancer should be getting tested so the fact that an increasing proportion of women have been undergoing BRCA testing in recent years indicates patients (and the physicians who treat them) are following recommendations. (more…)