Annals Internal Medicine, Author Interviews, Biomarkers, Heart Disease / 19.04.2017

MedicalResearch.com Interview with: Martin P. Than, MBBS Emergency Department, Christchurch Hospital and Dr John W Pickering, PhD Associate Professor Senior Research Fellow in Acute Care Emergency Care Foundation, Canterbury Medical Research Foundation, Canterbury District Health Board | Christchurch Hospital Research Associate Professor | Department of Medicine | University of Otago Christchurch New Zealand MedicalResearch.com: What is the background for this study? Response: Patients being investigated for possible acute coronary syndrome comprise one of the largest groups of patients presenting to emergency rooms. Troponin assays have developed such that they can now measure with greater accuracy much lower concentrations of troponin. A large retrospective registry based study and a couple of smaller prospective studies suggested that patients with a very low concentrations of troponin T (below the current limit of detection of 5 ng/L) measured with Roche Diagnostic’s high-sensitivity troponin T (hsTnT) assay on presentation to the emergency department (ie single blood draw) are very unlikely to be having a myocardial infarction (MI). Our study gathers the current best evidence for using concentrations below the limit of detection in conjunction with no evidence of new ischaemia on ECG to safely risk stratify patients to a very low-risk group for MI and, therefore, potentially identify patients safe for early discharge. (more…)
Author Interviews, Biomarkers, Brain Injury / 06.04.2017

MedicalResearch.com Interview with: Sergey A. Dryga, PhD, MBA Chief Scientific Officer BioDirection, Inc.  MedicalResearch.com: What is the background for this study? What are the main findings? Response: When patients have suffered a head injury, they typically undergo a series of subjective cognitive tests to confirm a diagnosis of a concussion or other traumatic brain injury. In many cases these tests are inaccurate and inconsistent, increasing the risk of misdiagnosis. In other cases, patients may undergo an unnecessary CT scan, which is costly and exposes them to radiation. Early, objective diagnostic testing of patients who have experienced a head injury can support more rapid and appropriate treatment decisions while potentially reducing the use of unnecessary CT scans or other forms of intervention. We know that protein biomarkers, including S100 calcium binding protein beta (S100β) and glial fibrillary acidic protein (GFAP), are released from the brain into the bloodstream immediately following a concussion or other traumatic brain injury. The Tbit™ System is a new medical device based on a nanotechnology biosensor that rapidly detects and accurately measures these protein biomarkers. The system includes a disposable cartridge and portable analyzer designed for testing using a single drop of blood at the earliest stages of a concussion. This pre-clinical study was designed to evaluate the ability of the Tbit System to screen traumatic brain injury patients for a CT positive or CT negative test. Frozen plasma samples were collected from a total of 100 patients who had undergone CT scans post hospital admission. The Tbit System demonstrated 100% sensitivity with no false negative results, and a 41% specificity level. (more…)
Author Interviews, Biomarkers, Heart Disease / 31.03.2017

MedicalResearch.com Interview with: Szilard Voros, MD, FACC, FSCCT, FAHA CEO of Global Genomics Group  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Atherosclerotic coronary artery disease (ASCAD) is the leading cause of death and morbidity in the United States and worldwide, despite relatively successful medical therapies such as statins, like Zocor or Lipitor. A significant majority of patients with ASCAD present with sudden cardiac arrest, and the clinical evaluation of those patients who present with chest pain to their physicians is very inefficient. Based on current clinical guidelines, patients who present to their physician with complaints of new onset chest pain or its equivalent, such as exertional dyspnea should be assessed for the probability of the presence of significant ASCAD based on simple clinical predictors. Approximately 60% of such patients have an intermediate probability, and they are typically referred for initial non-invasive evaluation, such as a stress test with cardiac imaging, or for some other type of non-invasive test. Strikingly, no more that 5% of such stress tests performed in the United States are actually positive, and even when patients with positive stress test are taken for invasive coronary angiography, no more than 40% have significant ASCAD. A blood test that could serve as first step, as a “gatekeeper”, to non-invasive evaluation, would be highly desirable. Global Genomics Group, or G3, has performed one of the largest, unbiased, mass-spectrometry-based discovery studies in over 1,000 patients who underwent detailed cardiac CT to assess the presence or absence of ASCAD, by measuring over 1,000 metabolites from the blood. Using sophisticated bioinformatics tools, the researchers identified 8 important metabolites that were significantly abnormal in patients with ASCAD, and generated a biomarker signature for the detection of ASCAD based on those analytes, called “knowPLAQUETM”. The biomarker signature was generated in approximately 800 subjects, and was validated in an independent set of approximately 400 subjects, showing an area under the curve (“AUC”) of 0.82 for the diagnosis of Atherosclerotic coronary artery disease. This biomarker signature can be adapted relatively easily on commercial mass spectrometry platforms, and the researchers anticipate that this signature may be available for physicians to use by 2018. In addition to its diagnostic power, this biomarker signature also has uncovered important biological insights for the development of ASCAD, which can be leveraged for therapeutic purposes. (more…)
Author Interviews, Biomarkers, Heart Disease, JAMA / 30.03.2017

MedicalResearch.com Interview with: Stefan Kiechl, MD and Karin Willeit, MD Department of Neurology Medical University Innsbruck Innsbruck, Austria  MedicalResearch.com: What is the background for this study? Response: Atrial fibrillation (AF) is the most common cardiac arrhythmia and a major contributor to thromboembolic stroke and population morbidity and mortality. Aside from well-established risk factors such as age, heart failure, and hypertension, inflammation has been suggested to play a significant role in the pathogenesis of AF. This is evidenced by histologic studies that found marked inflammatory infiltrates in atrial biopsies of AF patients and by epidemiological studies demonstrating an association of circulatory inflammation markers with incident AF. Of note, an increased endocardial expression of vascular intercellular adhesion molecule 1 (VCAM-1), a mediator of leukocyte trafficking, during rapid atrial pacing was demonstrated which was shown to contribute to an inflammatory and prothrombotic environment within atrial tissue. Because it is still unclear whether inflammation related to AF is primarily a systemic or localized phenomenon, we sought to examine the association of 13 baseline inflammation markers with incident atrial fibrillation in the prospective population-based Bruneck Study and to replicate key findings in a second cohort, the SAPHIR Study. (more…)
ALS, Author Interviews, Biomarkers, Neurology / 24.03.2017

MedicalResearch.com Interview with: Mary-Louise Rogers, PhD Senior Research Fellow, Lab Head, Motor Neurone Disease and Neurotrophic Research Laboratory, Department of Human Physiology, Centre for Neuroscience, Flinders University, School of Medicine, South Australia, Australia MedicalResearch.com: What is the background for this study? What are the main findings? Response: ALS is a fatal neurodegenerative disease in which motor neurons, cells that control muscle activity such as walking, talking and breathing, gradually die off, resulting in paralysis. There is no cure for ALS. In a groundbreaking study published in the journal Neurology, and led by Mary-Louise Rogers, Ph.D., senior research fellow at Flinders University, Australia, and Michael Benatar, M.D., Ph.D, University of Miami, Miller School of Medicine,  have identified concentrations of p75ECD, the extracellular domain on the common neurotrophin receptor p75, as the first biological fluid-based biomarker for ALS progression. . Neurotrophin receptor p75 is a growth factor receptor for neurotrophins whom promote the survival of nerve cells. Under normal circumstances, it is highly expressed on motor neurons during development but decreases after birth. Following nerve injury, however, the expression of p75 is increased and the extracellular domain of p75 is detectable in urine. Dr Rogers and her Doctoral student Stephanie Shepheard hypothesized and then showed, that p75ECD is excreted into the urine of SOD1 mice, the most commonly used animal model of ALS. These findings empowered further investigation of p75ECD, showing raised levels in the urine of patients with ALS and that it might have potential as an ALS biomarker. (more…)
Author Interviews, Biomarkers, Cancer Research, Genetic Research, Nature, UCSD / 07.03.2017

MedicalResearch.com Interview with: Kun Zhang, PhD Professor UCSD Department of Bioengineering La Jolla, CA 92093-0412 MedicalResearch.com: What is the background for this study? What are the main findings? Response: We have been interested in a type of chemical modification on the DNA, called CpG methylation, for years. This is like a decoration of DNA molecules that is specific to the cell type or tissue type. We were particularly interested in studying how such decoration spread along the DNA molecules. In this study, we did a very comprehensive search of the entire human genome for various human cell types and tissue types, and found close to 150,000 regions (called MHB in this study) in which adjacent CpG share the same decoration. We then went on to find out how many of such regions are unique to each normal cell/tissue type, and how many are specific to cancers. Then we took some of these highly informative regions as “biomarkers”, and showed that we can detect the absence or presence of cancer, and, in the latter case, where the tumor grow, in a patient’s blood. (more…)
Allergies, Asthma, Author Interviews, Biomarkers, Sleep Disorders / 07.03.2017

MedicalResearch.com Interview with: Rauno Joks, MD Associate Professor of Clinical Medicine Chief, Division of Allergy & Immunology Program Director, Allergy &Immunology Fellowship SUNY Downstate Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: There are circadian and circannular patterns to many diseases, including allergy and asthma. Humans spend roughly one-third of their lifetimes asleep. Your immune system never sleeps, but shifts its activity when you sleep. It is known that asthma disease activity can be worse at night - the reasons for this are complex, and may involve changes in allergic responses. We found, in a preliminary study of both adults with and without asthma, that longer duration of nighttime sleep was associated with lower levels of exhaled nitric oxide, a biomarker which is elevated in exhaled breath of those with allergic asthma. This may carry over into the afternoon as well, but the sample size was too small to fully conclude that. (more…)
Author Interviews, Biomarkers, Genetic Research, PLoS, Prostate Cancer / 23.02.2017

MedicalResearch.com Interview with: G. Andrés Cisneros, Ph.D. Associate Professor Department of Chemistry Center for Advanced Scientific Computing and Modeling, University of North Texas MedicalResearch.com: What is the background for this study? What are the main findings? Response: The accurate maintenance of DNA is crucial, if DNA damage is not addressed it can lead to various diseases including cancer. Therefore, the question arises about what happens if enzymes in charge of DNA repair are themselves mutated. We previously developed a method to perform targeted searches for cancer-related SNPs on genes of interest called HyDn-SNP-S. This method was applied to find prostate-cancer SNPs on DNA dealkylases in the ALKB family of enzymes. Our results uncovered a particular mutation on ALKBH7, R191Q, that is significantly associated with prostate cancer. Subsequent computer simulations and experiments indicate that this cancer mutation results in a decreased ability of ALKBH7 to bind its co-factor, thus impeding its ability to perform its native function. (more…)
Author Interviews, JAMA, Prostate Cancer / 20.02.2017

MedicalResearch.com Interview with: Neeraj Agarwal, MD Associate Professor, Division of Oncology, Department of Medicine University of Utah School of Medicine MedicalResearch.com: What is the background for this study? Response: Biomarkers predicting response to cancer therapy help guide physicians personalize medicine. Significant advances have been made in the development of therapeutic biomarkers in various malignancies, but not in prostate cancer. Dr. Nima Sharifi’s group at the Cleveland Clinic recently discovered that a germline inherited polymorphic variant (1245A→C) in the HSD3B1 gene correlates with shorter duration of response to androgen deprivation therapy (ADT) in hormone sensitive prostate cancer (HSPC). HSD3B1 gene encodes the enzyme 3β-hydroxysteroid dehydrogenase-1 (3βHSD1), which catalyzes adrenal androgen precursors into dihydrotestosterone, the most potent androgen. The authors found that the variant allele of HSD3B1 led to decreased progression-free survival in a dose-dependent manner in post-prostatectomy biochemical recurrence and metastatic HSPC (mHSPC). These results needed external validation before application in the clinic. In our study, we sought to provide the first independent validation of these results in patients with mHSPC. (more…)
Author Interviews, Heart Disease, JACC, Pharmacology / 15.02.2017

MedicalResearch.com Interview with: Gavin Y Oudit, MD, PhD, FRCPC Associate Professor, Department of Medicine, University of Alberta Clinician-Scientist Mazankowski Alberta Heart Institute Canada Research Chair in Heart Failure Division of Cardiology Edmonton, Alberta Heart specialist Gavin Oudit and his research team discovered a molecule — angiotensin converting enzyme 2 (ACE2)—that works to restore balance to the pathways responsible for chronic and acute heart failure, including in hearts from patients with advanced heart failure who underwent heart transplants. In developing the new drug, Oudit and his team discovered to an extent not seen before how the renin-angiotensin system (RAS), which regulates the body’s sodium balance, fluid volume, and blood pressure, is at play in both acute and chronic heart failure. In collaboration with Dr. Oudit, recombinant human ACE2 was made by Apeiron Biologics, purchased by GlaxoSmithKline, and has recently completed phase II clinical trial. (more…)
Author Interviews, Biomarkers, Cancer Research / 15.02.2017

MedicalResearch.com Interview with: Edwin Posadas, MD, FACP, KM Director, Translational Oncology Program Medical Director, Urologic Oncology Program Samuel Oschin Comprehensive Cancer Institute Clinical Chief, Division of Hematology/Oncology Associate Professor, Department of Medicine Cedars-Sinai MedicalResearch.com: What is the background for this study? What are the main findings of your work so far? Response: The technology we are using is called a NanoVelcro assay. This is a nanotechnology that can be used to isolate rare cells and cell-like particles in the blood stream. We have focused the use of the NanoVelcro on isolating circulating tumor cells (or CTCs). This technology is about 10 times more sensitive than that currently used in clinics. More importantly, because of some modification in our approach, we can now not only capture CTCs, but also examine them under the microscope and even analyze them using advanced molecular techniques. In this way, we take a classic and modern approach to our work. We firmly believe that there is much to be learned by studying the shapes of these CTCs. We in the cancer field have long known that shape and cellular function are intimately related. In fact, a young pathologist in our group readily recognized that patients with the most aggressive cancers had CTCs with small nuclei, which we verified in a larger study. We are now exploring the importance of these shape variations in CTCs by coupling this classic microscopy-driven approach with RNA characterizations, giving us insight into the molecular nature of the CTC. My collaborator, UCLA Professor Hsian-Rong Tseng, PhD, is a brilliant engineer who has found ways of altering the system to allow us to capture and release live cells for analysis. By using this system, we believe that one day we may be able to avoid performing invasive tissue biopsies to study a cancer. (more…)
Author Interviews, Biomarkers, Heart Disease, JAMA / 12.02.2017

MedicalResearch.com Interview with: Frederick L. Ruberg, MD Director, Cardiovascular Medicine Fellowship Training Program Director, Pilot Grants Program, Boston University Clinical and Translational Science Institute Director, Advanced Cardiac Imaging Program Section of Cardiovascular Medicine Department of Medicine Department of Radiology Boston Medical Center  MedicalResearch.com: What is the background for this study? What are the main findings? Response: ATTR cardiac amyloidosis is an under-recognized cause of congestive heart failure in older adults that results from the deposition of misfolded TTR protein in the heart. One cause of ATTR cardiac amyloidosis is a genetic abnormality, inherited from an affected patient’s parent, that causes the protein TTR to misfold. The most common genetically inherited cause of ATTR amyloidosis in the US is called Val122Ile (V122I), named for the specific mutation in the TTR gene, that is seen in approximately 3.5% of US African Americans. ATTR cardiac amyloidosis was once an untreatable disease, but now new drugs are in different stages of clinical trial testing. Thus, recognition is important to get patients on the right treatments. One of the principal reasons why the disease is under-recognized is that doctors don’t have proven and available diagnostic tests that can be applied in the outpatient clinic. This study demonstrated that a new point-of-care diagnostic test, using measurement of a blood protein called retinol binding protein 4 (RBP4) and other standard of care test information, can accurately diagnose ATTR cardiac amyloidosis. We demonstrated the validity of this test in two separate cohorts of patients with proven ATTR cardiac amyloidosis due to the Val122Ile mutation and control patients with heart failure but without amyloidosis. (more…)
Author Interviews, Biomarkers, Breast Cancer, Cancer Research / 14.01.2017

MedicalResearch.com Interview with: Ulrich Pfeffer, PhD Head of the Functional Genomics lab IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro Genova, Italy MedicalResearch.com: What is the background for this study? What are the main findings? Response: In recent years our knowledge on genetic variants that are associated with the risk to develop breast cancer has grown substantially. In addition to the two breast cancer genes, BRCA1 and BRCA2 we know approximately 100 other genes that are present in the population in two variants. In the presence of a single of these variants the breast cancer risk is slightly increased and several variants together determine a significant increase in risk. We also know that certain variants are associated with specific subtypes of breast cancer such as the estrogen receptor positive breast cancer. We show in our work for the first time that some of these variants are more frequent in breast cancers that carry a specific somatic, non-inherited, mutation. In particular, we show this for the most frequent somatic mutation in breast cancer, PIK3CA, a gene involved in the control of tumor metabolism and many other aspects, a fundamental gene. The knowledge of this association tells us a lot on cancer biology. But most important, it might help to design specific prevention strategies. Since when you carry a germline allele that is associated with a specific somatic mutation you know your risk of a specific molecular type of breast cancer and eventually you can do something specific to prevent it. (more…)
Author Interviews, Biomarkers, Critical Care - Intensive Care - ICUs, Infections, JAMA, Pediatrics / 11.01.2017

MedicalResearch.com Interview with: Halden F. Scott MD, Assistant Professor Departments of Pediatrics and Emergency Medicine University of Colorado School of Medicine MedicalResearch.com: What is the background for this study? Response: Sepsis, a dysregulated immune response to infection, is a leading cause of death for children. Survival depends on rapid diagnosis and timely delivery of life-saving resuscitative care, including fluids and antibiotics. However, it can be challenging to make an early diagnosis of sepsis in children. Millions of children present for emergency care of infection and fever every year, most of whom will not develop sepsis. Tools that assist providers in distinguishing the sickest children with infection at an early stage could enable the early delivery of life-saving treatments. Lactate is a clinically-available laboratory test that has played a critical role in improving the diagnosis and treatment of sepsis in adults. Sepsis may cause lactate levels to rise in the blood during sepsis, through reduced delivery of oxygen to the tissues, as well as through changes in how energy is produced and in how lactate is cleared by the kidney and liver. Data about lactate in pediatric sepsis, particularly early levels and whether it is associated with mortality, have been limited. (more…)
Aging, Author Interviews, Biomarkers / 09.01.2017

MedicalResearch.com Interview with: Paola Sebastiani PhD Department of Biostatistics Boston University School of Public Health Boston, MA 02118 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Human life expectancy has increased steadily in the last century and has led to a growth of the elderly population and a need for prevention strategies and interventions that promote healthy aging. A challenge in assessing the effect of such interventions is ‘what to measure’ because people can age very differently from one another. Our study used 19 blood biomarkers that include for example cholesterol level and hemoglobin A1C to discover 26 biological signatures of aging in approximately 4,700 participants of the Long Life Family Study. These signatures are essentially patterns of values of the 19 biomarkers and we showed that one of these signatures is associated with better physical and cognitive functions, and reduced risk for disease and mortality compared to the most common signature in the study. Additional signatures predict varying risk for diabetes, cardiovascular and other aging-related diseases. We replicated these results in an independent data set. The associations of these biomarker signatures with physical and cognitive functions, and risk for morbidity and mortality support the conclusion that they capture different form of biological aging. (more…)
Author Interviews, Biomarkers, JAMA, Multiple Sclerosis / 07.01.2017

MedicalResearch.com Interview with: Prof Rogier Q Hintzen Neurologist/immunologist Head MS Centre ErasMS Dept of Neurology Erasmus MC, Rotterdam MedicalResearch.com: What is the background for this study? What are the main findings? Response: Years ago, we identified soluble (s) CD27 as a biomarker for T cell activation in body fluids, as part of my PhD study. (J Immunol. 1991 Jul 1;147(1):29-35.) As we presume the neuropathology seen in MS is guided by T cells we were interested to be able to quantify the activity of such cells in a given patient. Cerebrospinal fluid (CSF) is as close as we can get to the site of the disease process in MS, therefore we focus on biomarkers in this compartment. We found clearly elevated levels of sCD27 in CSF of Multiple Sclerosis patients versus non-inflammatory controls. In this study we investigated whether at the moment of first attack of suspected Multiple Sclerosis, quantification of CSF sCD27 can predict further progression in to a diagnosis of MS and whether sCD27 levels are correlated with later attack frequency. Indeed, we found that high sCD27 measured at this early stage predicts a more rapid diagnosis of Multiple Sclerosis and a more aggressive disease course. (more…)
Author Interviews, Biomarkers, Heart Disease, JACC / 04.01.2017

MedicalResearch.com Interview with: Prof. Michele Emdin, MD, PhD, FESC Associate Professor of Cardiovascular Medicine Director, Cardiology & Cardiovascular Medicine Division Fondazione Toscana Gabriele Monasterio per la Ricerca Medica e di Sanità Pubblica CNR-Regione Toscana with the collaboration of Dr. Alberto Aimo, MD Institute of Life Sciences Scuola Superiore Sant'Anna - Sant'Anna School of Advanced Studies Pisa, Italy MedicalResearch.com: What is the background for these meta-analyses? Response: Soluble suppression of tumorigenicity 2 (sST2) is a novel and promising biomarker of heart failure (HF). It has been extensively studied in both stable chronic (CHF) and acute HF (AHF), demonstrating substantial potential as a predictor of prognosis in both settings (Dieplinger et al., 2015). An International Consensus Panel (Januzzi et al., 2015) and latest American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines (Yancy et al., 2013) support the use of sST2 assay for risk stratification in both CHF and AHF patients. By contrast, European Society of Cardiology guidelines do not provide specific recommendations on sST2 (Ponikowski et al., 2016). Because of ambiguity due to discordant conclusions and to the absence of a thorough revision of the literature and of rigorous meta-analyses of published studies up-to-date, we felt it worthwhile to carefully examine and meta-analyze evidence supporting measurement of sST2, in order to assess the prognostic role of this biomarker in CHF and AHF. Most of the groups originally publishing on the topic all over the world and representing the Gotha of clinical research on cardiovascular biomarker, accepted to directly contribute allowing the main Authors to achieve novel information by a guided statistical reappraisal, The final results furnish clinically significant support to the use of sST2 as a risk stratification tool either in the acute or in the chronic heart failure setting. (more…)
AACR, Author Interviews, Biomarkers, Breast Cancer, Chemotherapy / 26.12.2016

MedicalResearch.com Interview with: Helena Jernström, PhD Associate Professor in Experimental Oncology Study Coordinator for Graduate studies Division of Oncology and Pathology Coordinator of the programmes in statistics and epidemiology for doctoral students at the Medical Faculty, Lund University Division of Oncology and Pathology, Department of Clinical Sciences, Lund Lund University Cancer Center/Kamprad Lund, Sweden MedicalResearch.com: What is the background for this study? Response: There is a need for better predictive markers to guide selection of therapy in breast cancer patients. Estrogen receptor beta (ER-beta) may confer prognostic information beyond what is currently obtained by the established clinical markers, including ER-alpha, which is routinely evaluated. (more…)
Author Interviews, Biomarkers, Pediatrics, Pulmonary Disease / 02.12.2016

MedicalResearch.com Interview with: Prof. Henrik Verder Department of Pediatrics Holbaek University Hospital Denmark MedicalResearch.com: What is the background for this study? What are the main findings? Response: Respiratory Distress Syndrome (RDS) is a major cause of mortality and morbidity in premature infants. It can be effectively treated with surfactant, a therapy which reduces the effort needed to expand the lungs during inspiration and allow gas exchange to take place. Early surfactant treatment can help prevent the onset and impact of RDS, however, prophylactic treatment has been shown to be harmful and only necessary in half of all pre-term infants. This study provided data validating the efficacy of a lung maturity test (LMT) in identifying infants at risk of respiratory distress syndrome (RDS) who could benefit from early surfactant treatment. (more…)
Alcohol, Author Interviews, Biomarkers, Genetic Research / 28.11.2016

MedicalResearch.com Interview with: Chunyu Liu, PhD The Population Sciences Branch, Division of Intramural Research The Framingham Heart Study, National Heart, Lung and Blood Institute Framingham, MA Department of Biostatistics Boston University School of Public Health Boston, MA MedicalResearch.com: What is the background for this study? What are the main findings? Response: Excessive alcohol consumption contributes to many diseases as well as to injuries and deaths. The lack of reliable measures of alcohol intake is a major obstacle to the diagnosis and treatment of alcohol-related diseases. Our study has identified a group of DNA markers in blood that could provide the basis for a reliable blood test to detect heavy alcohol use. (more…)
Author Interviews, Biomarkers, Immunotherapy, Pancreatic / 21.10.2016

MedicalResearch.com Interview with Dr. Ashton A. Connor, MD PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research Dr. Steven Gallinger MD, MSC Division of General Surgery Toronto General Hospital Toronto, ON MedicalResearch.com: What is the background for this study? What are the main findings? Response: The etiology of pancreatic ductal adenocarcinoma (i.e. "pancreatic cancer") and the relationship between the tumour and its characteristic dense, encroaching stroma are still poorly understood. Using whole genome sequencing in two large cohorts, we show that there are four fundamental mutational processes that give rise to pancreatic cancer. With expression data, we also show that the interaction between the tumour and the surrounding stroma varies with the type of mutational process found in the tumour. Specifically, tumours with defective DNA repair, either homologous recombination or mismatch repair deficiency, elicited strong anti-tumour immune responses, likely due to the relatively high numbers of neoantigens in these tumours. Individually, these concepts have been studied in other cancer types, but we are first to apply either of these to pancreatic cancer, and we also the first to integrate these two aspects of cancer biology for any tumour, to our knowledge. (more…)
Author Interviews, Biomarkers, Cancer, Prostate Cancer, UT Southwestern / 08.10.2016

MedicalResearch.com Interview with: Dr Ryan Hutchinson MD and Yair Lotan MD Department of Urology University of Texas Southwestern Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: The United States Preventative Services Task Force recommendation against PSA screening generated significant controversy. Research since then has relied heavily on survey data to examine the impact of the recommendation on PSA screening practices. In a hotly charged issue such as this, such data can carry significant bias. We examined a large, whole-institution data in the years before and after the USPSTF recommendations reflecting actual practice and found that the changes in PSA use at our institution, if any, were small. This is more consistent with behavior seen after the vast majority of practice recommendations. (more…)
Author Interviews, Biomarkers, Cancer Research, ENT, HPV / 03.10.2016

MedicalResearch.com Interview with: Elizabeth Franzmann, M.D. Scientific Founder and Chief Scientific Officer Vigilant Biosciences MedicalResearch.com: What is the background for this study? Response: Head and neck cancer involves cancers of the oral cavity, oropharynx and larynx. It is difficult to treat. Part of the challenge is that it is distinguishing the patients with tumors that are going to behave aggressively from those with less aggressive disease. As a result, many patients undergo treatment that may be more intensive and morbid than they need while others need more aggressive treatment. Tissue markers associated with prognosis may be able to help clinicians differentiate patients who need more aggressive treatment from those whose treatment can be less intensive. CD44 is a cell surface glycoprotein and tumor-initiating marker. CD44 and another surface protein, EGFR, are involved in tumor extension and are associated with poor prognosis. Certain forms of Human Papillomavirus (HPV) are known to cause oropharyngeal cancer and are associated with a good prognosis. P16 is a surrogate marker for the kind of HPV that causes cancer. Understanding the relationships between how these markers are expressed in cancer tissue may direct patient treatment in the future. (more…)
Author Interviews, Biomarkers, Cancer Research, Prostate Cancer, Science / 27.09.2016

MedicalResearch.com Interview with: Iryna Saranchova MD PhD candidate Michael Smith Laboratories Vancouver, BC MedicalResearch.com: What is the background for this study? • The immune system is efficient at identifying and halting the tumour emergence at early stages. However, when metastatic (sufficient to cause death) tumour appears, the immune system is no longer able to recognize the cancer cells and control their growth and spread. • Recent studies of solid cancers have shown considerable heterogeneity between different tumour types and several lines of evidence suggest that tumours are not only heterogeneous, but they constantly evolve during the disease progression and this often hampers the existing treatment methods. • It means that it is important to consider each patient’s mutational changes accumulated over time in antecedent primary, metastatic lesions and/or local recurrences. This approach will help to understand the mechanism of tumour development, create a background for specific treatment modality and prevent therapeutic failure with consequent systemic relapse of the disease • Therefore, in our project we were aiming to find possible immune markers of tumour transition from the primary stage to its metastatic form. For this purpose, we selected a special study model: two pairs of separate mouse tumour cell lines, where metastatic cells arose from the initial primary tumour. (more…)
Author Interviews, Biomarkers, JAMA, NIH, Parkinson's / 26.09.2016

MedicalResearch.com Interview with: Yong Cheng, PhD, post-doc fellow Section on Cellular Neurobiology Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health Bethesda, Maryland MedicalResearch.com: What is the background for this study? Response: Parkinson’s disease is the second most neurodegenerative disease after Alzheimer’s disease. The symptoms of the disease are typically movement related. However, the nonmotor features in PD are increasingly recognized. Evidence suggests that inflammation may play a role in the development of AD, and a substantial number of studies have demonstrated altered levels of peripheral blood inflammatory cytokines in patients with  Parkinson’s disease, but findings have been inconsistent for individual cytokines and between studies. Therefore, we undertook a systematic review of the scientific literature, using a meta-analysis to quantitatively summarize clinical data on blood cytokine levels in patients with PD, compared with healthy controls. (more…)
Author Interviews, Autism, Biomarkers, JAMA, NIH, Pediatrics / 21.09.2016

MedicalResearch.com Interview with: Dr. Yong Cheng, PhD Postdoctoral Fellow NIH MedicalResearch.com: What is the background for this study? Response: Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders which affect about 1 in 68 children in the United States, according to data from the Centers for Disease Control and Prevention. Brain-derived neurotrophic factor (BDNF) is an important moderator in neurodevelopment and neuroplasticity, and studies have suggested the involvement of BDNF in ASD. Although some clinical studies show abnormal expression of BDNF in children with ASD, findings have been inconsistent. Therefore, we undertook a systematic review of the scientific literature, using a meta-analysis to quantitatively summarize clinical data on blood BDNF levels in children with ASD, compared with healthy peers. (more…)
Author Interviews, Biomarkers, Diabetes, Pancreatic / 19.09.2016

MedicalResearch.com Interview with: Dr. Pavel Škrha Charles University, Prague Czech Republic MedicalResearch.com: What is the background for this study? What are the main findings? Response: Incidence of pancreatic cancer (PAC) is still increasing. The main problem is in the late diagnosis of the cancer. It was found, that diabetes mellitus was much more frequent in the pancreatic cancer patients than in the general population. DM can be already the first symptom of the disease (secondry T3cDM). In our study nearly 80 % of all the pancreatic cancer patients had DM/prediabetes and it was of new-onset (less than 2 years before the cancer diagnosis) in 73 % out of them. We have measured the current marker of PAC (CA 19-9) together with serum microRNA-196 and -200 (that we have chosen in the previous pilot study). All the markers were significantly elevated in the pancreatic cancer patients, without any difference between the subgroups according to DM presence/absence. While the sensitivity of CA 19-9 alone (to detect the cancer) was 85 % (specificity 73 %), combining all the three markers improved it to 95 % (specificity 77 %). In the pancreatic cancer group, there were only six patients with T1 or T2 stage (others had an advanced stage of the disease - T3, T4). While CA 19-9 alone identified only 2 patients of them, the combined test identified all the six patients (data not shown in the poster). (more…)
AACR, Author Interviews, Biomarkers, Breast Cancer / 15.09.2016

MedicalResearch.com Interview with: Eva Gonzalez Suarez, PhD Group Leader Transformation and Metastasis lab. Cancer Epigenetics and Biology Program-PEBC Institut d'Investigació Biomédica de Bellvitge-IDIBELL Hospital Duran i Reynals Avinguda Gran Via de l'Hospitalet, L'Hospitalet de Llobregat-Barcelona-Spain MedicalResearch.com: What is the background for this study? What are the main findings? Response: Thousands of cancer patients worldwide are taking RANKL inhibitors for the management of bone metastasis, based on the key role of RANKL and its receptor, RANK, driving osteoclastogenesis. RANK signaling pathway acts as a paracrine mediator of progesterone in mouse and human mammary epithelium. RANK expression is associated with poor prognosis in breast cancer even though its therapeutic potential remained unknown. Complementary genetic and pharmacological approaches demonstrate that therapeutic inhibition of RANK signaling drastically reduces the cancer stem cell pool, decreases tumor and metastasis initiation and enhances sensitivity to chemotherapy in mouse models that closely resemble the clinical disease. Mechanistically, genome wide expression analyses showed that anti-RANKL therapy promotes differentiation of tumor cells into milk-producing cells, as observed during pregnancy. (more…)
Author Interviews, Biomarkers, Lung Cancer, Personalized Medicine, University of Pennsylvania / 13.09.2016

MedicalResearch.com Interview with: Erica L. Carpenter, MBA, PhD Research Assistant Professor, Department of Medicine Director, Circulating Tumor Material Laboratory Division of Hematology/Oncology Abramson Cancer Center Perelman School of Medicine at the University of Pennsylvania MedicalResearch.com: What is the background for this study? What are the main findings? Response: The advent of precision medicine practices for cancer patients, including the use of drugs that target specific tumor mutations, has necessitated improved diagnostics with real-time molecular monitoring of patients' tumor burden. While biopsy material, obtained surgically or through fine needle aspirate, can provide tissue for next generation sequencing (NGS) and mutation detection, this requires an invasive often painful procedure for the patient. In many cases, especially in more advanced disease when multiple metastases are present, such tissue cannot be obtained or can only be obtained from a single tumor site, thus limiting the sensitivity of tissue-based biopsy. Here we report on a prospective cohort of 102 consecutively enrolled patients with advanced non-small lung cancer (NSCLC) for whom a non-invasive liquid biopsy was used for real-time detection of therapeutically targetable mutations. Tissue samples were only obtainable for 50 of the 102 patients, and these tissue biopsies were analyzed using a 47-gene Next Generation Sequencing (NGS) panel at Penn's Center for Personalized Diagnostics. Concordance of results for the 50 patients who received both tests was close to 100% when the samples were obtained concurrently. (more…)
Author Interviews, Biomarkers, Cancer Research, Lung Cancer / 11.09.2016

MedicalResearch.com Interview with: Karen L. Reckamp, M.D. Associate Professor City of Hope Comprehensive Cancer Center Duarte, CA 91010 MedicalResearch.com: What is the background for this study? What are the main findings? Response: • Approximately 60% of patients with non-small cell lung cancer (NSCLC) receiving EGFR tyrosine kinase inhibitors (TKIs) will develop TKI resistance through the acquisition of the EGFR T790M mutation. • A major challenge for assessing EGFR mutation status in advanced NSCLC is the availability of suitable biopsy tissue for molecular testing, specifically for determination of the emergence of T790M following progression on initial EGFR TKI therapy. • The objective of this study was to demonstrate that a highly sensitive and quantitative next-generation sequencing analysis of EGFR mutations is feasible from urine and plasma, providing comparable clinical information while potentially mitigating the issues associated with tissue biopsies. • This blinded, retrospective study was conducted on matched tissue, urine and plasma specimens collected from 63 patients with Stage IIIB-IV NSCLC enrolled in the TIGER-X trial of rociletinib, an investigational 3rd generation tyrosine kinase inhibitor (TKI), targeting T790M. (more…)