Author Interviews, Biomarkers / 09.09.2016

MedicalResearch.com Interview with: Stefan Enroth, Associate Professor, PhD Dept. of Immunology, Genetics & Pathology Uppsala University MedicalResearch.com: What is the background for this study? Response: One basic requirement of life science research is the quality of samples. Proper handling and rigorous biobanking of clinical samples is very important when for instance collecting samples for rare diseases, for monitoring individual variation in longitudinal studies and when conducting prospective studies of biomarkers and risk of developing for instance cardiovascular disease. In epidemiological studies using case and control cohorts, great care is taken to ensure that the cases and controls are matched in terms of for instance age, anthropometrics and lifestyle exposures such as smoking or alcohol consumption. Technical factors and sampling handling history are not as commonly used. There has been a lack of studies that systematically investigated the effects of for instance storage-time on a larger set of plasma proteins. With emerging high-throughput technologies enabling measurements of a high number of proteins simultaneously on a population level, biomarker research will enter a new era and the more knowledge we have on what factors that influence circulating biomarker levels - such as plasma proteins, the higher the chances are of finding new clinically important biomarkers for disease. (more…)
Author Interviews, Biomarkers, Heart Disease / 08.09.2016

MedicalResearch.com Interview with: Dr. Juan Sanchis Full professor of Medicine Cardiology Department, University Clinic Hospital. Medicine Department, University of Valencia Valencia. Spain MedicalResearch.com: What is the background for this study? What are the main findings? Response: Decision making in acute chest pain in the emergency departments remains challenging despite the introduction of new troponin assays (high-sensitivity assays) capable of detecting any amount of myocardial damage. The upper limit of normality of high-sensitivity troponin is established at the 99th percentile of a normal reference population. This is the limit for the diagnosis of acute myocardial infraction. Detectable troponin levels below the 99th percentile, though non diagnostic of acute myocardial infarction, might be considered as of uncertain significance since some patients might still suffer from unstable angina. Undetectable troponin (far below the 99th percentile), however, could rule out unstable angina meaning that such patients could safely be discharged from the emergency department according to some studies. Therefore, if this were fully demonstrated, clinical evaluation could play a secondary role. We investigated clinical data in comparison to undetectable high-sensitivity troponin in patients with normal high-senstivity troponin levels (below the 99th percentile). The main findings indicate that clinical data can guide decision making and perform at least equally well as undetectable high-sensitivity troponin for ruling out unstable angina, in patients presenting at the emergency department with chest pain and normal troponin. (more…)
Alzheimer's - Dementia, Author Interviews, Biomarkers / 01.09.2016

MedicalResearch.com Interview with: Professor B. Paul Morgan Director, Systems Immunity Research Institute Institute of Infection and Immunity School of Medicine Cardiff University MedicalResearch.com: What is the background for this study? Response: Inflammation is a normal response of the body to infection or injury; however, it is well known that inflammation also has a dark side and when it escapes normal controls can cause disease. Some illnesses, like rheumatoid arthritis, have been known for many years to be caused by rogue inflammation and most of the drugs used to treat work by suppressing the inflammation (anti-inflammatories). More recently, it has become clear that inflammation is behind many other diseases that were previously thought of as diseases of ageing caused by wear and tear and lifestyle - these include heart disease and some brain diseases, notably Alzheimer's disease the commonest cause of dementia. Evidence that inflammation is one of the drivers of disease has come from many sources, including some where it was noticed that people on long-term anti-inflammatory drugs for other reasons appeared to be protected from developing Alzheimer's disease. A problem is that Alzheimer's disease, despite the name, is not a single disease but rather a group of conditions with similar symptoms, and inflammation is likely to be a cause in only some of the patients; further, most of the inflammation might be occurring very early in the disease, even before symptoms are obvious. So, there is an urgent need for a simple test or set of tests that can be used in individuals with the very earliest hints of Alzheimer's disease - mild memory loss - that will pick out those who have brain inflammation and are most likely to develop Alzheimer's disease. It might then be possible to treat this select group with anti-inflammatory drugs that will reduce brain inflammation and slow or stop progression of the disease. (more…)
Author Interviews, Biomarkers, Heart Disease, Kidney Disease / 31.08.2016

MedicalResearch.com Interview with: Xiaobing Yang, MD Division of Nephrology, Nanfang Hospital Southern Medical University MedicalResearch.com: What is the background for this study? Response: AKI is a common complication in patients with acute decompensated heart failure (ADHF) and associated with increased death and worse clinical outcomes. Early detecting which patients are going to suffer progressive AKI or proceed to death could help physicians to plan and initiate timely managements. We analyzed data and samples of 732 ADHF patients from a prospective, multicenter study in China. We demonstrated that kidney injury biomarkers, measured at the first time of AKI clinical diagnosis, could predict which patients were going to have AKI progression or worsening of AKI with death. Notably, three urinary biomarkers, including urinary angiotensinogen (uAGT), urinary neutrophil gelatinase-associated lipocalin (uNGAL), urinary IL-18 (uIL-18), were all able to forecast which patients with the earliest stages of AKI were most likely to suffer progressive AKI. (more…)
Author Interviews, Neurology, Stroke / 29.08.2016

MedicalResearch.com Interview with: Dr. Ashkan Shoamanesh MD FRCPC Assistant Professor Division of Neurology, Department of Medicine McMaster University and Dr. Jose Rafael Romero, MD Associate Professor of Neurology Boston University School of Medicine MedicalResearch.com: What is the background for this study? What are the main findings? Response: The Framingham Heart Study is a population-based study of individuals residing in the community. Identifying people who are at risk for stroke can help us determine who would benefit most from existing or new therapies to prevent stroke. As inflammatory pathways are believed to contribute to vascular disease and stroke, we tested whether circulating biomarkers of inflammation and endothelial dysfunction could improve the predictive ability of the Framingham Stroke Risk Profile score, a model that contains classical vascular risk factors such as high blood pressure and diabetes. Our main observation was that inclusion of 4 biomarkers (C-reactive protein, tumor necrosis factor receptor-2, total homocysteine, and vascular endothelial growth factor) in the Framingham Stroke Risk Profile improved its ability to predict a stroke (net reclassification improvement of 0.34 [0.12–0.57]). (more…)
Author Interviews, Biomarkers, Cancer Research, Genetic Research, Lancet / 29.08.2016

MedicalResearch.com Interview with: Dr. Manel Esteller Director of the Epigenetics and Cancer Biology Program (PEBC) Bellvitge Biomedical Research Institute MedicalResearch.com: What is the background for this study? What are the main findings? Response: Cancer of Unknown Primary (CUP) occurs when the patient is diagnosed with a metastasis but the primary tumor is not found. It accounts for around 5-10% of tumors around the world and the survival is very poor. Until now, only in 25% of cases the primary site was identified after diagnosis pipeline. We are showing herein that the use of epigenetic profiling, based in the determination of the chemical marks occurring in DNA that are tumor-type specific, reaches a diagnoses of 87% of cases. (more…)
Author Interviews, Biomarkers, Heart Disease, Microbiome / 18.08.2016

MedicalResearch.com Interview with: Lemin Zheng, Ph.D. Professor, Lab Director, and Principal Investigator The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine Peking University Health Science Center Beijing  China MedicalResearch.com: What is the background for this study? Response: Optical coherence tomography (OCT) has been considered as an ideal tool to characterize accurately atherosclerotic plaques and has potential to detect plaque rupture due to high-resolution (10-20 μm) cross-sectional images of tissue with near infrared light (1-3). Trimethylamine-N-oxide (TMAO) is a gut microbiota-dependent-generated metabolite which is associated with cardiovascular risk by a pathway involving dietary ingestion of nutrients containing trimethylamine, including phosphatidylcholine, choline, and L-carnitine (4-6). In the gut, choline, betaine and carnitine can be metabolized to trimethylamine (TMA) by gut flora microorganism. And TMA could be further oxidized to a proatherogenic species, TMAO, in the liver by flavin monooxygenases 3 (FMO3)4-6. These risk associations have been repeatedly shown in large observational trials (7-10). (more…)
Author Interviews, Beth Israel Deaconess, Biomarkers, Lung Cancer, Science / 05.08.2016

MedicalResearch.com Interview with: Dr. Elena Levantini, PhD Beth Israel Deaconess Medical Center Instructor, Medicine, Harvard Medical School Research Associate, Hematology-Oncology Beth Israel Deaconess Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: Lung cancer is one of the deadliest cancers in the world, accounting for 30% of tumor-related deaths. Like many solid tumours, lung cancer is very heterogeneous (consisting of cancer cells which behave and respond differently) and hence there is currently no single efficient drug which is able to treat all patients. Levantini and colleagues previously showed that non-small cell lung cancer (NSCLC) tumor cells frequently express too little or none of a transcription factor called C/EBPα, a protein that regulates gene expression and cell proliferation in lung tissues. It’s also known to play a role in a form of leukemia, as well as liver cancer, squamous cell skin carcinomas, squamous cell cancers of the head and neck and other cancers. In their previous work, the scientists suspected that C/EBPα may act as a tumor suppressant in normal cells, but the mechanism by which its absence promoted lung cancer tumors remained unclear. Dr. Levantini went on to develop a mouse model in which deleting C/EBPα resulted in NSCLC. Analysis of this model led to the discovery that C/EBPα suppressed lung tumor formation by inhibiting the expression of BMI1. Dr Levantini then demonstrated that reducing the levels of BMI1 in her mouse model by genetic means, or by using a drug reducing expression of BMI1, led to inhibition of tumor formation. This study has established an important link between C/EBPα and BMI1 for the first time. (more…)
Author Interviews, Biomarkers, Genetic Research, Leukemia, Personalized Medicine / 05.08.2016

MedicalResearch.com Interview with: Dr Laura Eadie PhD Post Doctoral Researcher Affiliate Lecturer Discipline of Medicine University of Adelaide Summary: Researchers based at SAHMRI (South Australian Health and Medical Research Institute) in Adelaide, South Australia have recently demonstrated the significance of early increases in the expression of ABCB1 in predicting long-term response to imatinib therapy. Lead researcher, Dr Laura Eadie, has recently had these findings published in the journal Leukemia and says that she hopes “the evidence provided by the study could be used to inform better patient treatment in the future”. MedicalResearch.com: What is the background for this study? What are the main findings? Response: ABCB1 (p-glycoprotein) is a membrane transporter known to be involved in the efflux of the tyrosine kinase inhibitors (TKIs) that are used to treat chronic myeloid leukaemia (CML). Overexpression of ABCB1 has also been demonstrated to cause resistance to the TKIs imatinib, nilotinib and dasatinib in vitro. Although studied previously in CML patients, the predictive value of ABCB1 in determining a patient’s long-term response to imatinib had not been realized ... until now. Previous studies investigating ABCB1 as a predictive biomarker focused on expression levels of ABCB1 at one time point in isolation. For our study, we have measured the levels of ABCB1 at two separate time points specified in the TIDEL II trial protocol: day 1 (prior to the start of imatinib therapy) and day 22 (three weeks on imatinib). We then calculated the fold rise in ABCB1 expression levels at day 22 compared with day 1 and grouped patients about the median into high and low fold rise. When we compared molecular outcomes for patients within these two ABCB1 expression groups we noticed a striking difference in outcome to imatinib therapy. (more…)
Author Interviews, Biomarkers, Diabetes, Diabetologia, OBGYNE / 25.07.2016

MedicalResearch.com Interview with: Dr. Sandra Hummel and Dr. Daniela Much Institute of Diabetes Research Helmholtz Center Munich German Research Center for Environmental Health Munich MedicalResearch.com: What is the background for this study? What are the main findings? Response: Gestational diabetes mellitus is associated with a seven-fold increased risk of developing type 2 diabetes postpartum. In 2012, we published that type 2 diabetes risk was markedly reduced up to 15 years after delivery in women with gestational diabetes if they breastfed for more than 3 months. However the underlying biological mechanisms are still unclear to date. Aim of this biomarker study was to identify the mechanism underlying the protective effect of prolonged lactation. At our study site in Munich, we enrolled 197 women with previous gestational diabetes participating in a postpartum assessment of glucose tolerance at a median time of 3.6 years after delivery. By using a targeted metabolomics approach (including a broad spectrum of lipids and amino acids), we identified lactation-associated biochemical changes in maternal plasma samples. Most interestingly, these metabolite signatures have been described with decreased risk for type 2 diabetes previously. Our results indicate that lactation-associated alterations persisted up to 11 years post-lactation. (more…)
Author Interviews, Biomarkers, Cancer Research / 22.07.2016

MedicalResearch.com Interview with: Dr. Hunter R. Underhill MD, PhD Department of Pediatrics, Division of Medical Genetics, Department of Radiology, University of Utah, Salt Lake City, Utah Department of Radiology and Department of Neurological Surgery University of Washington Seattle, Washington MedicalResearch.com: What is the background for this study? What are the main findings? Response: When cells undergo cell death (i.e., apoptosis) the DNA has the potential to enter the circulation. This DNA is not contained within a cellular membrane and is known as "cell-free DNA." This is a naturally occurring process. The same process also occurs when malignant tumors grow and evolve. The deposition of cell-free DNA derived from tumors is known as "circulating tumor DNA." Analysis of circulating tumor DNA holds the promise of detecting, diagnosing, and monitoring response to therapy of cancers through a simple blood draw - the "liquid biopsy." The challenge has been isolation of circulating tumor DNA from the background of the naturally occurring cell-free DNA. This has been particularly difficult in non-metastatic solid tumors as circulating tumor DNA has been heretofore indistinguishable from normal cell-free DNA except for the occurrence of mutant alleles that commonly occur at a frequency below detection limits - the proverbial needle in a haystack. Our study found a distinct size difference in DNA fragment length between circulating tumor DNA and cell-free DNA. Specifically, circulating tumor DNA is about 20-50 base pairs shorter than cell-free DNA originating from healthy cells. We were subsequently able to exploit this difference in size to enrich for circulating tumor DNA - essentially removing a large portion of the haystack that does not contain the needle to simplify the search. (more…)
Author Interviews, Biomarkers, CT Scanning, McGill, MRI, Nature / 13.07.2016

MedicalResearch.com Interview with: Dr. Yasser Iturria Medina PhD Post-doctoral fellow Montreal Neurological Institute MedicalResearch.com: What is the background for this study? What are the main findings? Response: We used over 200 peripheral molecular biomarkers, five different neuroimaging modalities and cognitive/clinical measurements to detect spatiotemporal abnormalities in subjects with dementia or with mild signs of cognitive deterioration. By means of a mathematical framework, we reordered all the biomarkers/descriptors considered, according to how much they change during the disease process. The results suggested that, contrary as suggested by more traditional clinical analyses, there are multiple early signs of neurodegeneration, at the molecular level and at the brain’s macroscopic and cognitive state. In particular, we observed notable early signs of generalized vascular dysregulation, which may be supporting the vascular hypothesis of Alzheimer’s disease. However, we still need to perform deeper analyzes, in order to clarify the complex causal mechanisms that trigger the disease. (more…)
Author Interviews, Biomarkers, Colon Cancer, Science / 11.07.2016

MedicalResearch.com Interview with: Jeanne Tie MBChB, FRACP, MD Division of Systems Biology and Personalised Medicine, Walter and Eliza Hall Institute of Medical Research Department of Medical Oncology, Western Health, St Albans, Victoria, Australia. Department of Medical Oncology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne Parkville, Victoria, Australia MedicalResearch.com: What is the background for this study? What are the main findings? Response: This study investigated the ability of circulating tumor DNA (ctDNA) in detecting residual microscopic cancer after surgery with curative intent in patients with stage II colon cancer. Although the majority of patients with stage II colon cancer are cured by surgery alone, our ability to accurately predict the risk of cancer relapse based on current clinical and pathological criteria is imprecise. Population-based study indicated that adjuvant chemotherapy is given to up to 40% of stage II colon cancer patients, meaning that we are over-treating a significant number of patients with cytotoxic therapy. A better indicator of residual disease and recurrence would be very useful clinically. The current study collected tumor and blood samples from 230 patients with stage II colorectal cancer. A personalised assay was then designed to detect patient-specific tumor DNA in the plasma samples collected four to ten weeks after surgery. The presence of ctDNA (positive test) in the post-operative blood sample predicted recurrence in 100% of patients, while the relapse rate is only 10% in those with negative ctDNA test. We have also shown that the ctDNA test is a better predictor of recurrence than the standard clinic-pathological criteria. (more…)
Author Interviews, Biomarkers, Cancer Research, Infections, Technology, University of Pittsburgh / 13.06.2016

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Biomarkers, Pain Research / 13.06.2016

MedicalResearch.com Interview with: 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). (more…)
Author Interviews, Biomarkers, JAMA / 09.06.2016

MedicalResearch.com Interview with: 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. (more…)
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). (more…)
ASCO, Author Interviews, Biomarkers, Personalized Medicine, UCSD / 07.06.2016

MedicalResearch.com Interview with: 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%. (more…)
Author Interviews, Biomarkers, Heart Disease, JAMA / 01.06.2016

MedicalResearch.com Interview with: 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. (more…)
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. (more…)
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. (more…)
Author Interviews, Biomarkers, Heart Disease, JAMA / 19.05.2016

MedicalResearch.com Interview with: 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. (more…)
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. (more…)
Alzheimer's - Dementia, Author Interviews, Biomarkers / 27.04.2016

MedicalResearch.com Interview with: 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). (more…)
Author Interviews, Biomarkers, Lancet, Pulmonary Disease / 25.04.2016

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Biomarkers, Cancer Research, JAMA, University of Michigan / 21.04.2016

MedicalResearch.com Interview with: 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. (more…)
AACR, Author Interviews, Biomarkers, Cancer Research, Melanoma / 20.04.2016

MedicalResearch.com Interview with: 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.” (more…)
Author Interviews, Biomarkers, Columbia, JAMA, Lung Cancer / 08.04.2016

MedicalResearch.com Interview with: 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. (more…)