Author Interviews, Biomarkers, Cancer Research, Prostate Cancer / 28.06.2016

MedicalResearch.com Interview with: [caption id="attachment_25655" align="alignleft" width="149"]Thomas Kislinger, PhD Senior Scientist at the Princess Margaret Cancer Centre University Health Network Associate Professor Department of Medical Biophysics University of Toronto Dr. Thomas Kislinger[/caption] Thomas Kislinger, PhD Senior Scientist at the Princess Margaret Cancer Centre University Health Network Associate Professor Department of Medical Biophysics University of Toronto MedicalResearch.com: What is the background for this study? Response: The goal of this study was to develop a non-invasive, prognostic biomarker that can address the worldwide clinical dilemma of over-treating low-risk prostate cancers. To accomplish this we developed highly accurate proteomics assays in urines collected after a digital rectal examination (termed post-DRE urines).
Author Interviews, Biomarkers, Heart Disease, JAMA, Personalized Medicine, UCSF / 21.06.2016

MedicalResearch.com Interview with: [caption id="attachment_25308" align="alignleft" width="150"]Peter Ganz, MD Chief, Division of Cardiology Director, Center of Excellence in Vascular Research Zuckerberg San Francisco General Hospital Maurice Eliaser Distinguished Professor of Medicine University of California, San Francisco Dr. Peter Ganz[/caption] Peter Ganz, MD Chief, Division of Cardiology Director, Center of Excellence in Vascular Research Zuckerberg San Francisco General Hospital Maurice Eliaser Distinguished Professor of Medicine University of California, San Francisco MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Ganz:  The research described in the JAMA paper involved measuring 1,130 different proteins in nearly 2000 individuals with apparently stable coronary heart disease, who were followed up to 11 years. Initially, two hundred different proteins were identified whose blood levels could be related to the risk of heart attacks, strokes, heart failure and death, and ultimately a combination of nine proteins was selected for a risk prediction model, based on their combined accuracy and sensitivity. Application of these findings to samples of patients with stable coronary heart disease demonstrated that some of those who were deemed clinically stable instead had a high risk of adverse cardiovascular outcomes, while other patients with the same clinical diagnosis had a very low risk. Thus, individuals who all carried the same clinical diagnosis of stable coronary heart disease had a risk of an adverse cardiovascular event that varied by as much as 10-fold, as revealed by analysis of the levels of the nine proteins in their blood. Given such large differences in risk and outcomes, patients could reasonably opt to be treated differently, depending on their level of risk. We hope that in the future, management of patients with stable angina will at least in part rely on risk assessment based on levels of blood proteins.
Author Interviews, Biomarkers, Cancer Research, Infections, Technology, University of Pittsburgh / 13.06.2016

MedicalResearch.com Interview with: [caption id="attachment_25161" align="alignleft" width="160"]Donald S. Burke, M.D. Dean of the University of Pittsburgh Graduate School of Public Health Director of the University of Pittsburgh Center for Vaccine Research Dr. Donald Burke[/caption] Donald S. Burke, M.D. Dean of the University of Pittsburgh Graduate School of Public Health Director of the University of Pittsburgh Center for Vaccine Research MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Burke: At the University of Pittsburgh we developed a unique method for detecting antibodies in the blood of patients in a proof-of-principle study that opens the door to development of simple diagnostic tests for diseases for which no microbial cause is known, including auto-immune diseases, cancers and other conditions. We used a technique pioneered by co-author Thomas Kodadek, Ph.D., of the Scripps Research Institute, that synthesizes random molecular shapes called “peptoids” hooked onto microscopic plastic beads. The technique can produce millions of molecular shapes. The peptoids are not organic, but if they match to the corresponding shape on an antibody, that antibody will connect to them, allowing the scientist to pull out that bead and examine that peptoid and its corresponding antibody. My team chemically generated a huge library of random molecular shapes. Then, using blood from HIV-infected patients and from non-infected people, we screened a million of these random molecular shapes to find the ones that bound only to antibodies present in the blood of HIV-infected patients, but not the healthy controls. No HIV proteins or structures were used to construct or select the peptoids, but the approach, nonetheless, successfully led to selection of the best molecular shapes to use in screening for HIV antibodies. We then resynthesized that HIV-antibody-targeting peptoid in mass and tested it by screening hundreds of samples from the Multicenter AIDS Cohort Study (MACS), a confidential research study of the natural history of treated and untreated HIV/AIDS in men who have sex with men (supported by the National Institutes of Health). Study co-author Charles Rinaldo, Ph.D., chair of Pitt Public Health’s Department of Infectious Diseases and Microbiology and director of the Pittsburgh arm of the MACS, selected the samples, but blinded the testers to which samples were HIV-positive or -negative. The test distinguished between the samples of HIV-positive blood and HIV-negative blood with a high degree of accuracy.
Author Interviews, Biomarkers, Pain Research / 13.06.2016

MedicalResearch.com Interview with: [caption id="attachment_24979" align="alignleft" width="142"]Dr. Gretchen Tietjen MD Professor and Chair of Neurology Director of UTMC Headache Treatment and Research Program Director of the UTMC Stroke Program Dr. Gretchen Tietjen[/caption] Dr. Gretchen Tietjen MD Professor and Chair of Neurology Director of UTMC Headache Treatment and Research Program Director of the UTMC Stroke Program MedicalResearch.com: What is the background for this study? Dr. Tietjen : C-reactive protein (CRP) is a well-established biomarker of inflammation. Elevated levels of CRP predict future cardiovascular events, such as myocardial infarction (heart attack) and stroke. Evidence linking higher CRP levels with migraine is limited and results from large population-based studies are conflicting. The National Health and Nutrition Examination Survey (NHANES) data for children and adolescents linked elevated CRP to headache, particularly in girls, and the Women’s Health Study showed an association of CRP with migraine in women over 45 years of age. In the Reykjavik study, CRP levels in persons with migraine were similar to levels in those without migraine. The aim of our study was to examine the relationship of CRP and migraine in a large population-based sample of over 9,000 young adults (24 to 32 years old) from The National Longitudinal Study of Adolescent to Adult Health (Add Health).
Author Interviews, Biomarkers, JAMA / 09.06.2016

MedicalResearch.com Interview with: [caption id="attachment_25081" align="alignleft" width="143"]Matthew D. Jankowich, MD Assistant Professor of Medicine Alpert Medical School of Brown University Staff physician at the Providence VA Medical Center Dr. Mathew Jankowich[/caption] Matthew D. Jankowich, MD Assistant Professor of Medicine Alpert Medical School of Brown University Staff physician at the Providence VA Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Jankowich: For some time, endothelin-1 has been known to cause vasoconstriction in the pulmonary circulation, and elevated endothelin-1 levels have been noted in patients with pulmonary arterial hypertension and decompensated congestive heart failure, as well as other advanced disease states. However, endothelin-1 has not been well studied in members of the general population. In our study, we examined plasma endothelin-1 levels in participants in the Jackson Heart Study and the relationship of plasma endothelin-1 levels to pulmonary hypertension, mortality and heart failure. We found increased odds of having pulmonary hypertension, defined as an echocardiography estimation of the pulmonary artery systolic pressure>40mmHg, in those participants with higher plasma endothelin-1 levels. Having higher endothelin-1 levels was also associated with an increased risk of both mortality and heart failure. Those participant with both high endothelin-1 levels (a level in the top 25%) and pulmonary hypertension were at the highest risk of mortality.
Author Interviews, Biomarkers, Colon Cancer / 07.06.2016

MedicalResearch.com Interview with: Gilles Jobin, MD, FRCP, MSc Chief of Gastroenterology Maisonneuve-Rosemont Hospital Associate Professor of Medicine University of Montreal Montréal, Qc MedicalResearch.com: What is the background for this study? Dr. Jobin: It is known that the immune system has a role to play in keeping the body free of cancer and tumor cells. There is a lot of scientific literature that shows that when someone has cancer, certain cells from the immune system do not function very well. These cells are called natural killer or NK cells and they are the first ones to respond when there is a virus, a bacteria or a tumor cell in the body. If the activity of these cells is very low, then there is a higher risk of someone developing a cancer, and if someone has cancer, there are greater chances that their NK cell activity is low. In the last few decades, a few tests have been developed to measure NK Cell activity but they have been used in research only because they were complicated and difficult to use. The current study measured NK Cell activity (NKA) with a new commercially available simple blood test to investigate its clinical application in the detection of colorectal cancer in patients presenting for prescribed colonoscopy. The aim of this study is to evaluate the sensitivity, specificity, positive and negative predictive values of this in vitro diagnostic device in patients with colorectal cancer (CRC) and adenomatous polyps (AP).
ASCO, Author Interviews, Biomarkers, Cancer Research, Cost of Health Care, Immunotherapy / 07.06.2016

MedicalResearch.com Interview with: Neil T. Mason, MBA Personalized Medicine Strategist Personalized Cancer Medicine Division of Population Science Moffitt Cancer Center MedicalResearch: What is the background for this study? What are the main findings? Response: Immune checkpoint inhibitors targeting PD-1 (nivolumab and pembrolizumab) and CTLA-4 (ipilimumab) have revolutionized the treatment of metastatic disease in melanoma and non-small cell lung cancer with additional indications showing positive results. These drugs have elicited profound and durable responses in a significant number of patients, but have been criticized for their high cost. Though the price of the drugs themselves can reach over $100,000 per year, they can also cause severe, life threatening toxicities that are difficult and expensive manage. This model utilizes patient data from a large, NCI-designated cancer center to estimate the average cost of treatment with immune checkpoint inhibitors based on average duration of treatment and reported incidence of major toxicities. Based on the model, PD-1 inhibitor therapies are less costly than ipilimumab due to the significantly higher cost per dose of ipilimumab and average treatment duration of less than a year for PD-1 inhibitors. Managing drug-related toxicities were estimated to contribute between $8,200 and $9,600 to the cost of therapy with nivolumab adding the most cost.
ASCO, Author Interviews, Biomarkers, Personalized Medicine, UCSD / 07.06.2016

MedicalResearch.com Interview with: [caption id="attachment_24655" align="alignleft" width="200"]Maria Schwaederle PharmD Clinical Research Scientist Center for Personalized Cancer Therapy UCSD Moores Cancer Center La Jolla, CA 92093 Dr. Maria Schwaederle[/caption] Maria Schwaederle PharmD Clinical Research Scientist Center for Personalized Cancer Therapy UCSD Moores Cancer Center La Jolla, CA 92093 MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Schwaederle: We performed this analysis with experts in the field, including but not limited to Drs Schilsky, Lee, Mendelsohn and Kurzrock, all known for their experience in the area of precision/personalized medicine. Historically, phase I trials (which are often first in human or highly experimental in other ways) were believed to be examining only toxicity. Our meta-analysis of 13,203 patients shows that in the era of precision medicine, this historical belief needs to be discarded. Second, it is the use of precision medicine that makes this belief outdated. Indeed, Phase I trials that utilized a biomarker-driven approach that is the essence of precision medicine had a median response rate of about 31%, which is higher than many FDA approved drugs, and this is in spite of the fact that phase I patients are a highly refractory group having failed multiple lines of conventional therapy. Importantly, however, it was not the use of targeted agents alone that was important. It was the biomarker-based approach where patients are matched to drugs. Without matching, response rates were dismal—about 5%.
Author Interviews, Biomarkers, Heart Disease, JAMA / 01.06.2016

MedicalResearch.com Interview with: [caption id="attachment_24827" align="alignleft" width="180"]Dr. med. Johannes Neumann Resident physician University Heart Center Hamburg Department of General and Interventional Cardiology Universitätsklinikum Hamburg-Eppendorf Hamburg Dr. Johannes Neumann[/caption] Dr. med. Johannes Neumann Resident physician University Heart Center Hamburg Department of General and Interventional Cardiology Universitätsklinikum Hamburg-Eppendorf Hamburg MedicalResearch.com: What is the background for this study? What are the main findings? Response: The early decision making in patients with suspected acute myocardial infarction is important. Current guidelines recommend measurement of cardiac troponin at admission and after 3 hours. In our study we evaluated the performance of a high-sensitivity troponin I assay with a rapid measurement after only 1 hour. We included 1040 patients with new onset chest pain and could show, that a low cutoff concentration of 6 ng/L after 1 hour allows safe rule-out of acute myocardial infarction. The results were comparable to the recommended 3-hour approach and were validated in 2 external cohorts. When using the 99th percentile to rule-out myocardial infarction, as recommended by current guidelines, the negative predictive value was much lower. Furthermore, a troponin I concentration above 6 ng/L in combination with an absolute change of 12 ng/L after 1 hour showed a high positive predictive value for the final diagnosis of myocardial infarction. This allows early decision making after only 1 hour.
Author Interviews, Biomarkers, Cancer Research, Genetic Research / 01.06.2016

MedicalResearch.com Interview with: Dr. Nicholas Turner Academic Consultant Medical Oncologist Team leader at the Breakthrough Breast Cancer Research Centre Institute of Cancer Research, London MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Turner: Prior laboratory research had identified that gastric cancers with a particular mutation, amplification of the gene FGFR2, were potential sensitive to a drug that inhibits FGFR2. We conducted a trial and showed that gastric cancers with this FGFR2 amplification respond to FGFR inhibition with a drug AZD4547. The amplification is rare, occurring in only a few percent of gastric cancers, so we designed a blood test to identify which patients have the amplification in their cancer, and we are not using the blood test to screen patients for the study.
Author Interviews, Biomarkers, Heart Disease, Women's Heart Health / 01.06.2016

MedicalResearch.com Interview with: Norman C. Wang, M.D., M.S., Assistant professor University of Pittsburgh School of Medicine Samar R. El Khoudary, Ph.D., M.P.H., Assistant professor of Epidemiology University of Pittsburgh Graduate School of Public Health MedicalResearch.com: What is the background for this study? What are the main findings? Response: We studied 252 middle-aged women with no known cardiovascular disease from the Study of Women’s Health Across the Nation [SWAN] Heart Study to determine if 5 blood biomarkers associated with abnormal inflammation/hemostasis were associated with increasing amounts of calcium detected in coronary arteries on computed tomography scans, or coronary artery calcium progression. Only higher blood levels of plasminogen activator inhibitor-1 was associated with coronary artery calcium progression.
Author Interviews, Biomarkers, Heart Disease, JAMA / 19.05.2016

MedicalResearch.com Interview with: [caption id="attachment_24511" align="alignleft" width="200"]Yvan Devaux, PhD Associate Head of Laboratory Cardiovascular Research Unit Department of Population Health Luxembourg Institute of Health Luxembourg Dr. Yvan Devaux[/caption] Yvan Devaux, PhD Associate Head of Laboratory Cardiovascular Research Unit Department of Population Health Luxembourg Institute of Health Luxembourg MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Devaux: Being able to predict outcome after cardiac arrest would allow tailoring healthcare and would represent a major step forward towards personalized medicine. However, available predictive tools suffer serious limitations and would benefit from novel biomarkers. The value of microRNAs (miRNAs) as biomarkers has been investigated in various clinical contexts and initial small-scale studies suggested that miRNAs might be useful indicators of outcome after cardiac arrest. Our work aimed at testing whether these molecules, and in particular the brain-enriched miR-124-3p, can be used to predict outcome after cardiac arrest. We found that, indeed, circulating levels of miR-124-3p measured 48h after cardiac arrest are robust predictors of neurological outcome and mortality. The strengths of the study are the use of a large multicenter international cohort (TTM-trial) and the collaboration between LIH and European partners (members of the TTM-trial and the Cardiolinc network) bringing complementary clinical and basic expertise.
Author Interviews, Biomarkers, Prostate Cancer, Urology / 12.05.2016

MedicalResearch.com Interview with: [caption id="attachment_24281" align="alignleft" width="150"]Jonathan Shoag MD Urology Resident at Cornell Department of Urology Dr. Jonathan Shoag[/caption] Jonathan Shoag MD Urology Resident at Cornell Department of Urology and [caption id="attachment_24282" align="alignleft" width="119"]Dr. Jim C. Hu MD Ronald Lynch Professor of Urologic Oncology Professor of Urology Director, Lefrak Center for Robotic Surgery Attending Urologist, New York-Presbyterian Hospital (Cornell campus) Dr. Jim Hu[/caption] Dr. Jim C. Hu MD Ronald Lynch Professor of Urologic Oncology Professor of Urology Director, Lefrak Center for Robotic Surgery Attending Urologist, New York-Presbyterian Hospital (Cornell campus) MedicalResearch.com: What is the background for this study? Response: Prostate Specific Antigen (PSA) is a blood test that is used to detect prostate cancers and to follow a cancer’s response to treatment. PSA was widely implemented as a screening tool for prostate cancer in the early 1990s, and became a routine test during an annual physical for men over 40. Doctors started using it because values above a “normal” threshold were associated with a greater risk of prostate cancer. Following the adoption of PSA screening in the early 1990s, there has been a large increase in the number of men diagnosed with cancer, and a decrease of approximately 50% in the rate of prostate cancer death. The PLCO trial was a large randomized trial designed and funded by the National Cancer Institute (NCI) to determine the effect of PSA screening on death from prostate cancer. The trial found that men randomized/assigned to prostate cancer screening had the same number of prostate cancer deaths as men in the control group of the trial, arguing that PSA screening does not decrease prostate cancer mortality. This was a major piece of evidence used by the United States Preventative Services Task Force (USPSTF) to form its 2012 recommendation against PSA screening. The argument was that in spite of the other evidence showing a benefit to PSA testing, including US epidemiologic trends, and another large randomized trial showing PSA screening was effective (the ERSPC), we now had good evidence showing no benefit to PSA testing in the US. Since 2012 we have seen dramatic declines in prostate cancer screening in the US as a result.
Author Interviews, Biomarkers, Cancer Research, Genetic Research, MD Anderson / 11.05.2016

MedicalResearch.com Interview with: [caption id="attachment_24254" align="alignleft" width="114"]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 Dr. Han Liang[/caption] 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.
Author Interviews, Biomarkers, JAMA, Pediatrics / 11.05.2016

MedicalResearch.com Interview with: Chris Adamopoulos MD and Angelo Livolsi MD Unit of Cardiopediatrics, Hautepierre University Hospital Strasbourg, France MedicalResearch.com: What is the background for this study? What are the main findings? Response: Apparent life-threatening events (ALTEs) predominantly affect children younger than one year. Fifty percent of these events remain unexplained, which causes great concern to parents and physicians. Yet, there is no easily detectable biomarker associated with these potentially serious, unexplained events. In our previous research we found a very high expression of muscarinic (parasympathetic) receptors in cardiac tissues of infants who died from sudden infant death syndrome (SIDS). In the present study we investigated the expression of the same muscarinic receptors in the peripheral blood of infants who experienced explained and unexplained life-threatening events at the highest end of severity. Our results showed that the infants who experienced unexplained severe events had strikingly higher receptor’s levels (20 to 50 times higher) than the infants with severe events of known cause.
Author Interviews, Biomarkers, Prostate Cancer / 11.05.2016

MedicalResearch.com Interview with: Dr. Michael K. Brawer, MD Northwest Prostate Institute Northwest Hospital Seattle, Washington MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Brawer: Prolaris (Cell Cycle Progression Test) is a prostate-cancer prognostic genetic tests that determines how aggressive is a patient’s cancer.  The goal is to reduce the over treatment of tumors that are likely to be harmless while still spotting those that are lethal.  Our key study at AUA (American Urological Society) is a meta-analysis of 440 prostate cancer patients with a Gleason score less than or equal to 6 who were tested with Prolaris.
Author Interviews, Biomarkers, Prostate Cancer / 02.05.2016

MedicalResearch.com Interview with: [caption id="attachment_23943" align="alignleft" width="143"]Stephen J. Freedland, MD Associate Director, Faculty Development Samuel Oschin Comprehensive Cancer Institute Co-Director, Cancer Genetics and Prevention Program Director, Center for Integrated Research in Cancer and Lifestyle Professor, Surgery Warschaw Robertson Law Families Chair in Prostate Cancer Cedars-Sinai, Los Angeles Dr. Stephen Freedland[/caption] Stephen J. Freedland, MD Associate Director, Faculty Development Samuel Oschin Comprehensive Cancer Institute Co-Director, Cancer Genetics and Prevention Program Director, Center for Integrated Research in Cancer and Lifestyle Professor, Surgery Warschaw Robertson Law Families Chair in Prostate Cancer Cedars-Sinai, Los Angeles  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Freedland:   PSA is a marker of prostate pathology.  While often used to screen for prostate cancer, it is not prostate specific and can be elevated due to inflammation or enlarged prostate or other reasons.  Whether it predicts the development of urinary symptoms is not clear.  Among men with minimal to no urinary symptoms, we found that the higher the PSA, the greater the risk of future development of urinary symptoms. MedicalResearch.com: What should clinicians and patients take away from your report? Dr. Freedland: The readers should know that if a man has an elevated PSA and a negative prostate biopsy, the higher the PSA, the greater the risk of future urinary symptoms.  These are men who may need closer follow-up.
AACR, Author Interviews, Biomarkers, Cancer Research, Personalized Medicine, Stanford / 01.05.2016

MedicalResearch.com Interview with: Dr. Elodie Sollier Chief Scientific Officer at Vortex Biosciences MedicalResearch.com: What is the background for this study? What are the main findings? Response: Circulating Tumor Cell (CTC) burden may be a useful biomarker of response to targeted therapy in PDX (Patient Derived Xenograft) mouse models. Vortex Biosciences’ technology has been proven to enrich CTCs from human blood, but use of the technology with mouse blood had not yet been explored. In this poster, human CTCs are isolated with both high efficiency and purity from xenograft model of breast cancer using Vortex’s technology. Circulating Tumor Cell enumeration increased as the tumor burden increased in the mouse demonstrating its utility as a biomarker for drug treatment response.
Author Interviews, Biomarkers, JAMA, Melanoma, Ophthalmology / 30.04.2016

MedicalResearch.com Interview with: [caption id="attachment_23925" align="alignleft" width="130"]MedicalResearch.com Interview with: William Harbour, MD Bascom Palmer Eye Institute, Sylvester Comprehensive Cancer Center Interdisciplinary Stem Cell Institute University of Miami Miller School of Medicine, Miami, Florida MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Harbour: Uveal melanoma (UM) is the most common primary cancer of the eye which has the fatal tendency to metastasis to the liver. The molecular landscape of UMs have been well characterized and can be categorized by gene expression profiling (GEP) into two molecular classes associated with metastatic risk: Class 1 (low risk) and Class 2 (high risk). The Class 2 profile is strongly associated with mutations in the tumor suppressor BAP1. This GEP-based test is the only prognostic test for UM to undergo a prospective multicenter validation, an it is available commercially as DecisionDX-UM (Castle Biosciences, Inc). It is routinely used in many North American centers. The identification of driver mutations in cancer has become a focus of precision medicine for prognostic and therapeutic decision making in oncology. In UM, thus far, only 5 genes have been reported to be commonly mutated: BAP1, GNA11, GNAQ, EIF1AX, and SF3B1. In this study, we analyzed the associations between these 5 mutations, and with GEP classification, clinicopathologic features, and patient outcomes. The study showed that GNAQ and GNA11 are mutually exclusive, probably occur early in tumor formation, and are not associated with prognosis. In contrast, BAP1, SF3B1, and EIF1AX, which are also nearly mutually exclusive, likely occur later in tumor formation and do have prognostic value in UM. MedicalResearch.com: What should clinicians and patients take away from your report? Dr. Harbour: These findings suggest that BAP1, SF3B1, and EIF1AX mutations may have clinical value as prognostic markers in UM. Since the GEP remains the most prognostic biomarker in UM, the mutational landscape could supplement the GEP for prognostication. Several of these markers are also potential therapeutic targets that could guide the selection of a specific treatment on an individual patient basis. MedicalResearch.com: What recommendations do you have for future research as a result of this study? Dr. Harbour: We will be conducting a prospective, 28 center study to evaluate the prognostic value of these mutations as well as another biomarker that we recently reported called PRAME. This could have clinical implications for precision medicine and may aid in the stratification of UM patients for clinical trials. MedicalResearch.com: Is there anything else you would like to add? Dr. Harbour: Mutations in GNAQ and GNA11 occur early in uveal melanoma development and are not prognostically significant. In contrast, mutations in BAP1, SF3B1 and EIF1AX occur later in tumor progression in a nearly mutually exclusive manner, and they are associated with high, intermediate and low metastatic risk, respectively. MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community. Citation: Decatur CL, Ong E, Garg N, et al. Driver Mutations in Uveal Melanoma: Associations With Gene Expression Profile and Patient Outcomes. JAMA Ophthalmol. Published online April 28, 2016. doi:10.1001/jamaophthalmol.2016.0903. Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions. More Medical Research Interviews on MedicalResearch.com Dr. J. William Harbour[/caption]
J. William Harbour, M.D.
Leader, Eye Cancer Site Disease Group
Sylvester Comprehensive Cancer Center University of Miami Miller School of Medicine
MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Harbour:  Uveal melanoma (UM) is the most common primary cancer of the eye which has the fatal tendency to metastasis to the liver. The molecular landscape of UMs have been well characterized and can be categorized by gene expression profiling (GEP) into two molecular classes associated with metastatic risk: Class 1 (low risk) and Class 2 (high risk). The Class 2 profile is strongly associated with mutations in the tumor suppressor BAP1. This GEP-based test is the only prognostic test for UM to undergo a prospective multicenter validation, an it is available commercially as DecisionDX-UM (Castle Biosciences, Inc).  It is routinely used in many North American centers. The identification of driver mutations in cancer has become a focus of precision medicine for prognostic and therapeutic decision making in oncology. In UM, thus far, only 5 genes have been reported to be commonly mutated:  BAP1, GNA11, GNAQ, EIF1AX, and SF3B1. In this study, we analyzed the associations between these 5 mutations, and with GEP classification, clinicopathologic features, and patient outcomes. The study showed that GNAQ and GNA11 are mutually exclusive, probably occur early in tumor formation, and are not associated with prognosis.  In contrast, BAP1, SF3B1, and EIF1AX, which are also nearly mutually exclusive, likely occur later in tumor formation and do have prognostic value in UM.
Author Interviews, Biomarkers, Dermatology / 28.04.2016

MedicalResearch.com Interview with: [caption id="attachment_23851" align="alignleft" width="200"]Professor Rudi Beyaert VIB - Inflammation Research Center Ghent University Department for Biomedical Molecular Biology Unit of Molecular Signal Transduction in Inflammation Technologiepark Ghent) Belgium Prof. Rudi Beyaert[/caption] Professor Rudi Beyaert VIB - Inflammation Research Center Ghent University Department for Biomedical Molecular Biology Unit of Molecular Signal Transduction in Inflammation Technologiepark Ghent) Belgium  MedicalResearch.com: What is the background for this study? What are the main findings? Prof. Beyaert: The interest of my laboratory is in understanding the molecular mechanisms that are responsible for the development of inflammatory diseases such as Crohn's disease, multiple sclerosis, rheumatoid arthritis and also psoriasis, which is the topic of the published study. We already know that genetic factors can determine the onset of these inflammatory diseases, but how these genetic factors drive an inflammatory response is still largely unclear. We were specifically interested in the CARD14 gene, because patients with mutations in CARD14 have a very high chance to develop psoriasis. Psoriasis-associated mutations in CARD14 trigger specific skin cells (keratinocytes) to produce and release large amounts of other proteins that recruit and activate specific white blood cells driving an inflammatory response. We now discovered that this effect is dependent on the physical interaction of CARD14 with the protease MALT1 in keratinocytes, leading to the activation of its enzymatic activity and the MALT1-mediated cleavage and inactivation of a number of cellular proteins that normally keep our immune system in check. Treatment of skin cells with small compound MALT1 inhibitors prevents the CARD14-induced production of several pro-inflammatory mediators.
Alzheimer's - Dementia, Author Interviews, Biomarkers / 27.04.2016

MedicalResearch.com Interview with: [caption id="attachment_23823" align="alignleft" width="149"]Dr Anne Poljak Leader of the Proteomics Group Centre for Healthy Brain Ageing (CHeBA) UNSW, Australia Dr. Anne Poljak[/caption] Dr Anne Poljak Leader of the Proteomics Group Centre for Healthy Brain Ageing (CHeBA) UNSW, Australia  MedicalResearch.com: What is the background for this study?  Dr Poljak: Amyloid-beta (Aβ) peptides are found in abundance in the plaque particles which build up in the Alzheimer’s brain and small blood vessels of the brain, and are therefore considered hallmark features of Alzheimer’s disease. However they are also found in blood which is a convenient body fluid for sampling purposes. We therefore wished to assay them in plasma samples from one of our longitudinal population based studies of older age individuals (70 – 90 years) – the Centre for Healthy Brain Ageing’s Sydney Memory and Ageing Study. Other research groups had previously measured these peptides in plasma, but there was controversy in the area because of differences in outcomes across laboratories. So one of the main questions was whether plasma levels of Aβ peptides have any relationship with what is happening in the brain, or are they a red-herring? We wanted to see how the levels we found would compare with the findings of others in relation to Alzheimer’s disease and mild cognitive impairment. A further question was how our plasma levels would relate to other clinical measures including cognition and brain volumetrics. One of the precautions we took was to use an assay kit with very well characterized antibodies, so we could be confident that our method was specific for the two full length Aβ peptides (Ab1-40 and Ab1-42).
AACR, Author Interviews, Biomarkers, Cancer Research, Colon Cancer, Technology / 27.04.2016

MedicalResearch.com Interview with: Dr. Elodie Sollier PhD Chief Scientific Officer at Vortex Biosciences MedicalResearch.com: What is the background for this study? What are the main findings? Response: Vortex Biosciences has developed a fast and simple way to isolate and collect intact circulating tumor cells (CTCs) directly from whole blood in less than an hour using a process based on microfluidics. To better understand the utility of the technology for the clinical setting, PCR-based Sanger sequencing was used to profile the mutations of CTCs isolated from blood from metastatic Colorectal cancer patients. The mutations were compared to primary tumor biopsies, secondary tumor biopsies and ctDNA. There are 3 primary take-aways:
  1. The Vortex technology captures CTCs with enough purity to perform sensitive and accurate PCR-based Sanger sequencing.
  2. Mutations present in primary and secondary tumors can be identified in both CTCs and ctDNA making liquid biopsies a valuable alternative to tissue biopsies.
  3. While there is general consistency of mutations identified, some mutations are only identified in CTCs while others only in ctDNA demonstrating how these are indeed complimentary.
Author Interviews, Biomarkers, Lancet, Pulmonary Disease / 25.04.2016

MedicalResearch.com Interview with: [caption id="attachment_23751" align="alignleft" width="200"]Danny MvBryan, MD Vice president, Clinical Development & Medical Affairs, Respiratory Boehringer Ingelheim Pharmaceuticals, Inc. Dr. Danny MvBryan[/caption] Danny McBryan, MD Vice president, Clinical Development & Medical Affairs, Respiratory Boehringer Ingelheim Pharmaceuticals, Inc. MedicalResearch.com: What is the background for this study? What are the main findings? Dr. MvBryan: The new post-hoc analysis from the WISDOM study shows a routine blood test could help identify the small minority of patients with severe or very severe COPD who may benefit from the addition of inhaled corticosteroids (ICS). This post-hoc analysis was recently published online in The Lancet Respiratory Medicine. For 80 percent of patients in the WISDOM study, the use of ICS on top of SPIRIVA HANDIHALER (a long-acting muscarinic antagonist – LAMA) and salmeterol (a long-acting beta-agonist – LABA) had no additional benefit in reducing the risk of exacerbations, compared to SPIRIVA HANDIHALER and the LABA without ICS. The post-hoc analysis shows that these patients can be easily identified by measuring the level of white blood cells, called eosinophils. Patients with levels lower than 4 percent (300 cells/µL) were associated with a lack of response to ICS. The WISDOM study evaluated stepwise withdrawal of inhaled corticosteroids (ICS) in severe to very severe COPD patients with a history of exacerbation. WISDOM was a 12-month, double-blind, parallel-group, active-controlled study in which all patients received triple therapy (tiotropium 18 μg once daily, salmeterol 50 μg twice daily and fluticasone 500 μg twice daily) for a six-week run-in period. Patients were randomized 1:1 to continue triple therapy or stepwise withdrawal of ICS over 12 weeks (dose reduction every six weeks). The WISDOM data show that in patients with severe to very severe COPD, the risk of moderate/severe exacerbations during one year of follow-up was non-inferior between those patients who continued on inhaled corticosteroids and those where ICS therapy was withdrawn in a stepwise manner.
Author Interviews, Biomarkers, Cancer Research, JAMA, University of Michigan / 21.04.2016

MedicalResearch.com Interview with: [caption id="attachment_23645" align="alignleft" width="100"]Alon Kahana, MD, PhD Associate Professor Kellogg Eye Center University of Michigan Dr. Alon Kahana[/caption] Alon Kahana, MD, PhD Associate Professor Kellogg Eye Center University of Michigan MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Kahana: Basal cell carcinoma is the most common cancer - more common than all other cancers combined. Fortunately, it is usually not aggressive, and can be easily treated surgically. However, when it is on the face, or when it has grown to a large size, it can become very disfiguring and even deadly. Basal cell carcinoma is diagnosed histopathologically, yet molecular diagnostics have proven value in a variety of cancers. In order to improve diagnosis and care, we set out to test whether histologically aggressive forms of basal cell carcinoma are associated with increased cell proliferation. Furthermore, we tested whether expression of the epigenetic regulator Ezh2 is associated with higher-grade carcinoma and/or with increased proliferation. The breakthrough discovery is that expression of Ezh2 correlates with high proliferation and with aggressive histologic features, suggesting that epigenetic regulators can be used both as markers of disease severity and targets of novel therapy.
AACR, Author Interviews, Biomarkers, Cancer Research, Melanoma / 20.04.2016

MedicalResearch.com Interview with: [caption id="attachment_23600" align="alignleft" width="200"]Michael A. Postow, MD Medical Oncologist Louis V. Gerstner, Jr. Graduate School of Biomedical Sciences (GSK) Memorial Sloan Kettering Dr. Michael Postow[/caption] Michael A. Postow, MD Medical Oncologist Louis V. Gerstner, Jr. Graduate School of Biomedical Sciences (GSK) Memorial Sloan Kettering MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Postow: Pembrolizumab has been shown to improve overall survival for patients with advanced melanoma compared to ipilimumab.  Patients with PD-L1 negative tumors still respond to pembrolizumab.  Responses to pembrolizumab were higher when patients had more PD-L1 in the tumor. MedicalResearch.com: What should clinicians and patients take away from your report? Dr. Postow: PD-L1 status cannot be used to select patients with melanoma to receive pembrolizumab vs. ipilimumab or even to be used to determine eligibility for immunotherapy in general.  PD-L1 “positivity” is a difficult definition and various cutoff points have been used in various studies to determine positivity.  We need more research to determine the significance of various cutoff definitions of “positive.”
AACR, Author Interviews, Biomarkers, Cancer Research / 19.04.2016

MedicalResearch.com Interview with: [caption id="attachment_23567" align="alignleft" width="145"]Marianne J. Ratcliffe, PhD Associate director of diagnostics AstraZeneca Alderley Park, UK Dr. Mariann Ratcliffe[/caption] Marianne J. Ratcliffe, PhD Associate director of diagnostics AstraZeneca Alderley Park, UK MedicalResearch.com: What is the background for this study? Dr. Ratcliffe: PD-L1 status is informative when considering monotherapy treatment and of growing importance when we consider that treatment decision will, in the near future also include combination therapy, an area of focus for AstraZeneca. The Ventana SP263 test has been developed with AstraZeneca, to support selection of PD-L1 testing within the Durvalumab programme, with full analytical validation at a 25% cut point derived from clinical data indicating this cut point best identifies patients more likely to respond to Durvalumab. The Ventana SP263 assay is commercially available in the US and the EU as a Class I device. The Dako 22C3 test has been approved as companion diagnostic for Pembrolizumab, and the Dako 28-8 has been released as a complementary diagnostic as an aid to physicians considering treatment with Nivolumab. What we didn’t know before our study was whether the three assays identify the same patients, and particularly how to cross compare patients identified with the different cut points specified for the different assays. It was therefore an important question to be addressed through a very thorough scientific assessment. MedicalResearch.com: What are the main findings? Dr. Ratcliffe: Our data, generated in 500 commercial samples, demonstrates that three commercially available PD-L1 tests achieved overall percentage agreement of >90%. This was achieved at multiple assay cut-offs. These results indicate that it may be possible to extrapolate the results from one test to that of another test. Further work is required to confirm this finding.
Author Interviews, Biomarkers, Lancet, Pulmonary Disease / 14.04.2016

MedicalResearch.com Interview with: Dr Henrik Watz MD Pulmonary Research Institute at Lung Clinic Grosshansdorf Airway Research Center North, German Center for Lung Research Grosshansdorf, Germany Medical Research: What is the background for this study? What are the main findings? Dr Watz : While bronchodilators are the mainstay therapy for all patients with COPD some patients benefit from the addition of inhaled corticosteroids in case of frequent exacerbations. So far only little data exist that help clinicians to better characterize those patients that may benefit from the continuation of inhaled corticosteroids on top of dual bronchodilation with a LABA and a LAMA. Post-hoc analyses of the WISDOM dataset suggest that those patients, who have blood eosinophil counts of 4 % or greater or 300 eosinophils per µL or more have less exacerbations, when inhaled corticosteroids are continued compared to patients, in whom inhaled corticosteroids are withdrawn. Patients with less than 4 % eosinophils or less than 300 eosinophils in peripheral blood, who represent 80 % of the study population in WISDOM, did not benefit from a continuation of inhaled corticosteroids.
Author Interviews, Biomarkers, Columbia, JAMA, Lung Cancer / 08.04.2016

MedicalResearch.com Interview with: [caption id="attachment_23298" align="alignleft" width="191"]Adrian G. Sacher, M.D. Assistant Professor of Medicine Thoracic Oncology & Phase I Drug Development Columbia University/New York-Presbyterian Hospital Dr. Adrian Sacher[/caption] Adrian G. Sacher, M.D. Assistant Professor of Medicine Thoracic Oncology & Phase I Drug Development Columbia University/New York-Presbyterian Hospital  MedicalResearch.com: What is the background for this study? Dr. Sacher: The aim of this prospective study was to determine the accuracy, turnaround time and robustness of ddPCR-based liquid biopsy for the detection of EGFR and KRAS mutations in patients with advanced non-small cell lung cancer (NSCLC). The detection of these mutations is key to selecting optimal therapy for patients with this disease. Currently, the standard of care is to perform tissue biopsies on patients in order to obtain material to detect these mutations and make decisions about treatment. Frequently, patients undergo multiple tissue biopsies during the course of their treatment. We sought to determine if liquid biopsy could quickly and accurately detect these mutations with the ultimate goal of understanding how to use these tests to select treatment for patients.