Author Interviews, Biomarkers, Genetic Research, Infections, NEJM, UCSF / 13.06.2019

MedicalResearch.com Interview with: [caption id="attachment_49751" align="alignleft" width="150"]Dr. Charles Chiu, M.D./Ph.D. Professor, Laboratory Medicine and Medicine / Infectious Diseases Director, UCSF-Abbott Viral Diagnostics and Discovery Center Associate Director, UCSF Clinical Microbiology Laboratory UCSF School of Medicine Dr. Chiu[/caption] Dr. Charles Chiu, M.D./Ph.D. Professor, Laboratory Medicine and Medicine / Infectious Diseases Director, UCSF-Abbott Viral Diagnostics and Discovery Center Associate Director, UCSF Clinical Microbiology Laboratory UCSF School of Medicine MedicalResearch.com: What is the background for this study? Would you describe what is meant by metagenomic sequencing? Response: Metagenomic next-generation sequencing (mNGS) is the use of technology to generate millions of sequence reads to diagnose infection sin patients by characterizing the full range of potential pathogens (bacteria, viruses, fungi, and parasites) in a single sample. Although shown to be a promising diagnostic tool for  infectious diseases in case reports and limited case series (Chiu and Miller Nature Reviews Genetics 20, 341-355 (2019)), to date the “real-life” utility of this approach for patient care has hitherto not been demonstrated.  This study is the first prospective, multi-center study of clinical mNGS testing for the diagnosis of neurological infections in acutely ill hospitalized patients presenting with meningitis and/or encephalitis.
Author Interviews, Bayer, Biomarkers, Colon Cancer / 05.06.2019

MedicalResearch.com Interview with: Joseph Germino, M.D., PhD Vice President US Medical Affairs Oncology Bayer Healthcare Pharmaceuticals Whippany, N.J. 07981 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Regorafenib is an oral multi-kinase inhibitor that potently blocks multiple protein kinases involved in tumor angiogenesis (VEGFR1, -2, -3, TIE2), oncogenesis (KIT, RET, RAF-1, BRAF), metastasis (VEGFR3, PDGFR, FGFR) and tumor immunity (CSF1R). This prospective pharmacokinetic (PK) ancillary study is part of a prospective phase II study evaluating treatment response with regorafenib in patients with chemorefractory metastatic colorectal cancer (mCRC) called TEXAN, which aimed to investigate correlations between overall survival (OS) and regorafenib, or its enterohepatic cycle-dependent active metabolites M-2 and M-5 concentrations. As measured by LC-MS/MS, the main findings showed that regorafenib, M-2 and M-5 were respectively 1.99 (1.03-2.73), 1.44 (0.89-2.49) and 1.61 (0.79-2.37) mg/L during the first cycle at day 15 (C1D15) and 1.90 (1.10-2.76), 1.29 (0.77-2.24) and 1.17 (0.45-2.42) mg/L at during the second cycle at day 15 (C2D15). 
ASCO, Author Interviews, Biomarkers, Melanoma, NYU / 02.06.2019

MedicalResearch.com Interview with: [caption id="attachment_49317" align="alignleft" width="200"]David Polsky, MD, PhDDermatologist and Director of the Digmented Lesion Service Dr. Polsky[/caption] David Polsky, MD, PhD Dermatologist and Director of the Digmented Lesion Service Mahrukh M. Syeda, MS Research Associate Ronald O. Perelman Department of Dermatology NYU Langone Health MedicalResearch.com: What is the background for this study? Response: Several studies of metastatic melanoma patients have demonstrated that measuring circulating tumor DNA (ctDNA) associates with their disease burden and survival.  Generally, patients with detectable pre-treatment ctDNA levels and/or detectable ctDNA at various time intervals after starting treatment have shorter survivals than patients with lower pre-treatment or on-treatment ctDNA levels.  Studies have varied in their methods to detect ctDNA, the thresholds chosen to call a sample positive or negative, and the follow up time point for measurement, if any. In this study, we examined pre-treatment and week 4 on-treatment plasma samples from patients enrolled in Combi-D, the Phase III, randomized, double-blind trial of the BRAF and MEK inhibitors Dabrafenib and Trametinib, which led to FDA approval of the combination therapy for patients with unresectable stage III/IV melanoma. Only patients with BRAF V600E or V600K mutations identified from tumor genotyping were enrolled in the clinical trial.
Author Interviews, Biomarkers, Cancer Research, Colon Cancer, JAMA, Karolinski Institute / 13.05.2019

MedicalResearch.com Interview with: [caption id="attachment_49076" align="alignleft" width="150"]Louise OlssonSenior researcherDepartment of Molecular Medicine and SurgeryColorectal SurgeryKarolinski InstituteStockholm, Sweden Dr. Olsson[/caption] Louise Olsson MD PhD Senior researcher Department of Molecular Medicine and Surgery Colorectal Surgery Karolinski Institute Stockholm, Sweden  MedicalResearch.com: What is the background for this study? What are the main findings? Response: I read a very interesting paper back in 2006 “Detection and quantification of mutation in the plasma of patients with colorectal cancer”. Only some 60 % of patients with early colorectal cancer were detectable in this way whereas patients with stage IV disease all had a high concentration of APC mutations in their plasma. So the prospects of using the method for example, screening of primary colorectal cancer seemed limited but I thought wow, this is the test to detect recurrences and generalized disease during follow-up after surgery for colorectal cancer. After some discussion we started to collect plasma samples from patients at the hospital where I worked and that´s how my research began.
Alzheimer's - Dementia, Author Interviews, Biomarkers, Neurological Disorders, Neurology, University of Pennsylvania / 08.05.2019

MedicalResearch.com Interview with: Lauren McCollum, MDCognitive and Behavioral Neurology FellowPenn Memory Center / Cognitive Neurology DivisionLauren McCollum, MD Cognitive and Behavioral Neurology Fellow Penn Memory Center / Cognitive Neurology Division MedicalResearch.com: What is the background for this study?   Response: Alzheimer’s Disease (AD) is a heterogenous condition, with considerable variability in cognitive symptoms and progression rates. One major reason for this heterogeneity is “mixed pathology,” – i.e., both AD- and non-AD pathology. Examples of non-AD pathology include cerebrovascular disease (CVD), Lewy Bodies, and TDP-43. Pathologically, Alzheimer’s Disease is defined by characteristic amyloid plaques and neurofibrillary tangles, which can be assessed for in living patients with CSF- or PET-based biomarkers for amyloid and tau, respectively. Classically, amyloid deposition begins years or even decades before pathologic tau accumulation, which is in turn associated with brain atrophy and cognitive decline. The recently developed NIA-AA “ATN” research framework allows for the classification of individuals with regard to 3 binary biomarkers: Amyloid (A), Tau (T), and Neurodegeneration (N). An individual’s ATN biomarker status indicates where along the “Alzheimer’s Disease continuum” they lie. Additionally, some ATN statuses are on the “typical AD” continuum, while others are not. Research has shown that 15-30% of cognitively normal older adults have elevated amyloid. It stands to reason that some portion of cognitively impaired individuals with elevated amyloid and neurodegeneration have something other than AD driving their neuronal injury. Within the context of the ATN research framework, this subset of people is the A+T-N+ group (i.e., people who have elevated amyloid and neurodegeneration, but are tau-negative), as amyloid alone (that is, amyloid without tau) is not thought to cause significant cognitive impairment or brain atrophy. Our hypothesis was that, compared to A+T+N+ (a set of typical-AD biomarkers), A+T-N+ have cognitive and neuroimaging profiles that deviate from a typical Alzheimer’s Disease pattern – i.e., with less memory loss and less atrophy in AD-signature regions – and may have biomarkers suggestive of alternate non-AD pathologies [e.g., white matter hyperintensities (WMHs), a marker of CVD].
Author Interviews, Biomarkers, Multiple Sclerosis / 30.04.2019

MedicalResearch.com Interview with: [caption id="attachment_48900" align="alignleft" width="140"]Prof. Bernhard Hemmer MD PhDDirector of the Neurology ClinicTechnische Universität München Prof. Hemmer[/caption] Prof. Bernhard Hemmer MD PhD Director of the Neurology Clinic Technische Universität München  MedicalResearch.com: What is the background for this study? What are the main findings?  Response: The course of multiple sclerosis (MS) is still highly unpredictable and reliable markers to predict disability progression are largely missing. We found that patients with a high IgG Index, which means that the produce large amount of IgG within the CNS, have a higher risk of disease worsening during the first 4 years. I would consider patients with an elevated IgG index at a higher risk to run a more severe disease course. The marker could be used together with others to guide treatment decisions after multiple sclerosis diagnosis.
Author Interviews, Biomarkers, Lancet, OBGYNE, Pediatrics / 01.04.2019

MedicalResearch.com Interview with: [caption id="attachment_48296" align="alignleft" width="200"]MedicalResearch.com Interview with:Catalin S. Buhimschi MD, MMS, MBAProfessor of Obstetrics and GynecologyDivision of Maternal Fetal MedicineDirector of ObstetricsDepartment of Obstetrics and GynecologyChicago, IL, 60612 Dr. Buhimschi[/caption] Catalin S. Buhimschi MD, MMS, MBA Professor of Obstetrics and Gynecology Division of Maternal Fetal Medicine Director of Obstetrics Department of Obstetrics and Gynecology Chicago, IL, 60612 MedicalResearch.com: What is the background for this study? What are the main findings? Response: In 2008, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal–Fetal Medicine Units Network published the results of a randomized controlled trial of magnesium sulfate for the prevention of cerebral palsy (CP). The results of this trial suggested that fetal exposure to magnesium sulfate before anticipated early preterm delivery did not reduce the combined risk of moderate to severe cerebral palsy or death, although the rate of cerebral palsy was reduced among survivors. As such, the search for a biomarker or a therapeutic solution to prevent CP had to continue. We are grateful to the NICHD for giving us access to the umbilical cord blood samples retrieved at the time of birth for the infants enrolled, who were also followed for 2 years postnatally. We discovered that fetus’s ability to switch-on haptoglobin (Hp) expression in response to inflammation was associated with reduction of intra-ventricular hemorrhage (IVH) and/or death, and cerebral palsy and/or death. Fetuses unable to mount such a response in-utero had an increased risk of adverse outcomes.
Author Interviews, Biomarkers, OBGYNE / 20.03.2019

MedicalResearch.com Interview with: [caption id="attachment_48001" align="alignleft" width="125"]Dr. Kara Rood MDMaternal-fetal Medicine PhysicianThe Ohio State University Wexner Medical Center Dr. Rood[/caption] Dr. Kara Rood MD Maternal-fetal Medicine Physician The Ohio State University Wexner Medical Center MedicalResearch.com: What is the background for this study? What are the main findings?  Response: This is a simple, rapid, non-invasive test for early recognition of preeclampsia.  MedicalResearch.com: What should readers take away from your report? Response: Aid in timely diagnosis to help provide closer observations to pregnancies with complicated by preeclampsia, to prevent the devastating adverse pregnancies outcomes for mom's and babies that can occur when pregnancies become complicated by preeclampsia.
Author Interviews, Biomarkers, BMJ, Heart Disease / 18.03.2019

MedicalResearch.com Interview with: [caption id="attachment_47901" align="alignleft" width="158"]Prof. Nick Curzen  BM(Hons) PhD FRCPProfessor of Interventional Cardiology/Consultant CardiologistUniversity Hospital SouthamptonSouthampton Prof. Curzen[/caption] Prof. Nick Curzen  BM(Hons) PhD FRCP Professor of Interventional Cardiology/Consultant Cardiologist University Hospital Southampton Southampton MedicalResearch.com: What is the background for this study? Response: The commonest blood test now used to assess whether a patient has had a heart attack or not is called high sensitivity troponin (hs trop).  The test is supplied with an Upper Limit of Normal, which is based upon results from relatively healthy people.  When doctors take the hs trop, they then use this ULN to decide if the patient had has a heart attack. This study set out to see what the hs trop level is in a large number of patients attending the hospital for any reason, either inpatient or outpatient, in most of whom there was no clinical suspicion of heart attack at all.  We therefore took hs trop measurements on 20,000 consecutive patients attending our hospital and having a blood sample for any reason. 
AACR, Author Interviews, Biomarkers, MD Anderson / 05.03.2019

MedicalResearch.com Interview with: [caption id="attachment_47785" align="alignleft" width="200"]Vassiliki Papadimitrakopoulou, MDProfessor of MedicineDepartment of Thoracic/Head and Neck Medical OncologyMD Anderson Cancer Center in Houston Dr. Papadimitrakopoulou[/caption] Vassiliki Papadimitrakopoulou, MD Professor of Medicine Department of Thoracic/Head and Neck Medical Oncology MD Anderson Cancer Center in Houston MedicalResearch.com: What is the background for this study? What are the main findings? Response: 30% of patients with newly diagnosed advanced NSCLC can be treated successfully with targeted therapies, often yielding higher response rates than chemotherapy or immune checkpoint inhibitors. Selecting first-line therapy for patients with NSCLC requires assessment of an expanding list of guideline-recommended genomic biomarkers (EGFR, ALK, ROS1, BRAF, RET, MET amplification and exon 14 skipping, and ERBB2, with NTRK newly added) Standard-of-care (SOC) testing relies on tissue, which is limited by biopsy-related risks, specimen insufficiency, and lab processing duration, which hamper timely optimal treatment selection -          NILE is a large, prospective, multicenter, head-to-head study of SOC tissue-based genomic testing to plasma-based comprehensive cfDNA genomic testing (Guardant360®). For the four biomarkers with FDA approved therapies, up to 34% of patients were tested by SOC tissue testing versus 95% with cfDNA testing. NILE met its primary endpoint - cfDNA performed similar to tissue in the detection of guideline-recommended biomarkers and cfDNA results were delivered significantly faster than SOC tissue testing (median 9 days vs. 15 days).Using cfDNA testing first, 87% of patients with a guideline-recommended biomarker would have been detected, compared to 67% if SOC tissue testing was first.
Author Interviews, Biomarkers, CT Scanning, JAMA, Lung Cancer, Medical Imaging / 01.03.2019

MedicalResearch.com Interview with: [caption id="attachment_47730" align="alignleft" width="200"]Martin C. Tammemägi   PhDSenior Scientist | Cancer Care Ontario | Prevention & Cancer Control | Scientific Lead | Lung Cancer Screening Pilot for People at High RiskProfessor (Epidemiology) | Brock University | Department of Health SciencesOntario  Canada Dr. Tammemägi[/caption] Martin C. Tammemägi PhD Senior Scientist Cancer Care Ontario | Prevention & Cancer Control Scientific Lead Lung Cancer Screening Pilot for People at High Risk Professor (Epidemiology) | Brock University Department of Health Sciences Ontario, Canada MedicalResearch.com: What is the background for this study? Response: Some prediction models can accurately predict lung cancer risk (probability of developing lung cancer during a specified time). Good model predictors include sociodemographic, medical and exposure variables. In recent years, low dose computed tomography (LDCT) lung cancer screening has become widespread in trials, pilots, demonstration studies, and public health practice. It appears that screening results provides added valuable, independent predictive information regarding future lung cancer risk, aside from the lung cancers directly detected from the diagnostic investigations resulting from positive screens.
Author Interviews, Biomarkers, Johns Hopkins, NIH, Pulmonary Disease, Transplantation / 29.01.2019

MedicalResearch.com Interview with: [caption id="attachment_47206" align="alignleft" width="142"]Sean Agbor-Enoh, M.D., Ph.D. Co-Director/Staff Clinician Laboratory of Transplantation Genomics National Heart, Lung, and Blood Institute National Institutes of Health Dr. Agbor-Enoh[/caption] Sean Agbor-Enoh, M.D., Ph.D. Co-Director/Staff Clinician Laboratory of Transplantation Genomics National Heart, Lung, and Blood Institute National Institutes of Health MedicalResearch.com: What is the background for this study? Response: People who receive organ transplants may develop acute or chronic rejection, in which the body’s immune system attacks the transplanted organ. While acute rejection is treatable and reversible, chronic rejection is not and remains the most common cause for organ transplant loss. Lung transplant recipients have the shortest survival rates among patients who get solid organ transplantation of any kind—only about half live past five years. This poor survival rate among lung transplant recipients is due in part to a high incidence of chronic rejection. Existing tools for detecting signs of rejection, such as biopsy, either require the removal of small amounts of lung tissue or are not sensitive enough to discern the severity of the rejection. Building upon earlier work, our research team developed a simple blood test that can detect when a newly transplanted lung is being rejected by a patient, even when no outward signs of the rejection are evident.  The test could make it possible for doctors to intervene faster to prevent or slow down so-called chronic rejection—which is severe, irreversible, and often deadly—in those first critical months after lung transplantation. This same test might also be useful for monitoring rejection in other types of organ transplants. Called the donor-derived cell-free DNA test, the experimental test begins with obtaining a few blood droplets taken from the arm of the transplant recipient. A special set of machines then sorts the DNA fragments in the blood sample, and in combination with computer analysis, determines whether the fragments are from the recipient or the donor and how many of each type are present.  Because injured or dying cells from the donor release lots of donor DNA fragments into the bloodstream compared to normal donor cells, higher amounts of donor DNA indicate a higher risk for transplant rejection in the recipient.
Author Interviews, Biomarkers, Cancer Research / 28.11.2018

MedicalResearch.com Interview with: [caption id="attachment_46241" align="alignleft" width="200"]Ricardo Alvarez MD MSc Medical Director of the Breast Cancer Center Director of Cancer Research Cancer Treatment Centers of America, CTCA Atlanta Dr. Alvarez[/caption] Ricardo Alvarez MD MSc Medical Director of the Breast Cancer Center Director of Cancer Research Cancer Treatment Centers of America, CTCA Atlanta MedicalResearch.com: What is the background for this study? What are the main findings? Response: “The background of this study comes from five years of experience in one of our precision medicine programs that was launched in 2013 and this is the experience of a group of personnel from a hospital that helps physicians in five different hospitals that are a part of the CTCA network and for physicians who order a next generation sequencing test. In this particular report, we have only one vendor, and that is Foundation Medicine and we analyze three different genomic platforms, Foundation One test, Foundation Act and Foundation One Hem. In total, approximately 8,800 tests have been analyzed and that was the presentation at ESMO 2018. It’s important that the Precision Medicine Program (PMed) helps physicians to identify actionable and potentially actionable targets for the result of this test so patients can be treated with targeted therapy, and this can be done by selecting clinical trials or recommending patients to be treated off-label agents. When we say off label, meaning that they are not specifically FDA-approved drugs for this indication that we are treating.”
Author Interviews, Biomarkers, Endocrinology, Prostate Cancer / 14.11.2018

MedicalResearch.com Interview with: [caption id="attachment_45946" align="alignleft" width="200"]Diagram_showing_prostate_cancer_that_has_spread_to_the_bones_CRUK_183.svg.png Prostate cancer that has metastasized to the bone: Wikipedia Image[/caption] Vincenza Conteduca, MD, PhD Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) Srl - IRCCS Meldola , Italy MedicalResearch.com: What is the background for this study? What are the main findings? Response: In our previous publications, we showed that the study of plasma cell-free DNA holds promise for improving treatment choice in metastatic castration-resistant prostate cancer (mCRPC). Specifically, we demonstrated that the detection in plasma of aberrations (copy number alterations and/or point somatic mutations) of androgen receptor (AR), using an easy and robust multiplex droplet digital PCR method, predicted an adverse outcome in mCRPC patients treated with second-generation AR-directed therapies (abiraterone or enzalutamide) in both settings: chemotherapy-naïve and post-docetaxel. This current multi-institution work builds on our previous discoveries. We investigated the association of androgen receptor status and survival in men treated with docetaxel. Moreover, we performed an exploratory analysis in patients treated with docetaxel or AR-directed therapies as first-line therapy. Interestingly, we observed that plasma AR-gained patients do not have a worse outcome compared to AR-normal patients when treated with docetaxel as first-line therapy. This introduces the opportunity to use plasma to select for docetaxel in preference to androgen receptor-directed therapies in AR gained mCRPC patients.
Author Interviews, Autism, Biomarkers, Genetic Research / 12.11.2018

MedicalResearch.com Interview with: [caption id="attachment_45911" align="alignleft" width="153"]Steven D. Hicks, M.D.,Ph.D Department of Pediatrics Penn State College of Medicine Hershey, PA Dr. Hicks[/caption] Steven D. Hicks, M.D.,Ph.D Department of Pediatrics Penn State College of Medicine Hershey, PA MedicalResearch.com: What is the background for this study? What are the main findings? Response: Since autism has both genetic and environmental underpinnings, my colleagues and I suspected that transcriptional elements (e.g. regulatory RNA molecules) might be different in the saliva of children with autism compared to peers without autism. We used a non-biased approach to analyze saliva from 372 children, and allowed machine learning techniques to inform which RNA elements best predicted autism status. To our surprise, microbial RNA levels and human RNA levels were equally powerful in predicting which children had autism. This may be because some children with autism eat restricted diets, resist tooth brushing, or put foreign objects in their mouths. The end result was a panel of 32 RNAs (20 human and 12 bacterial) that identified autism with 87% accuracy. Interestingly, when we tested the panel in a completely separate set of 84 children (including children from a different geographic region) the accuracy remained 88%. 
Author Interviews, Biomarkers, Heart Disease, JAMA / 05.11.2018

MedicalResearch.com Interview with: [caption id="attachment_45623" align="alignleft" width="143"]Robin M. Shaw, MD, PhD Wasserman Foundation Chair in Cardiology in honor of S. Rexford Kennamer MD Division of Cardiology, Smidt Heart Institute Department of Medicine, Cedars-Sinai Medical Center, Division of Cardiology, Department of Medicine University of California, Los Angeles, California Dr. Shaw[/caption] Robin M. Shaw, MD, PhD Wasserman Foundation Chair in Cardiology in honor of S. Rexford Kennamer MD Division of Cardiology, Smidt Heart Institute Department of Medicine, Cedars-Sinai Medical Center, Division of Cardiology, Department of Medicine University of California, Los Angeles, California MedicalResearch.com: What is the background for this study? What are the main findings? Response: At present, doctors do not have a clinical tool that assesses the biochemical health of heart muscle.  Biomarkers are available that tests the amount of fluid in the heart, and whether a heart is overloaded (which can be resolved with diuretics).  However, we don’t have biomarkers that assess the state of heart muscle itself.  As a result, doctors can use biomarkers to determine whether, when a patient has trouble breathing, there is heart failure present. However, biomarkers do not work when the patient does not have symptoms or when we already know the patient has heart failure and are trying to make clinical management decisions about the condition. Current biomarkers also don’t work to assess the health of the heart before symptoms develop which is to detect cellular changes in muscle before overall heart function is impaired. The new biomarker, CS, address the above unmet needs.  CS is based on cBIN1 which is a heart muscle protein that is essential for the heart to both contract and relax.  cBIN1 decrease when hearts are stressed such as in heart failure.  cBIN1 is also released into the blood stream, so it can be detected from a simple blood draw.  CS is determined from the inverse of cBIN1, so low cBIN1 in blood will give a high CS signal.  A low cBIN1, or a high CS, indicates failing heart muscle, and an increased likelihood for being admitted to the hospital with acute heart failure within the next twelve months. 
Author Interviews, Biomarkers, Infections, JAMA, Stanford / 29.10.2018

MedicalResearch.com Interview with: "Mycobacterium tuberculosis Bacteria, the Cause of TB" by NIAID is licensed under CC BY 2.0Purvesh Khatri, Ph.D. Associate Professor Stanford Institute for Immunity, Transplantation and Infection (ITI) Stanford Center for Biomedical Informatics Research (BMIR) Department of Medicine Stanford University Stanford, CA 94305 MedicalResearch.com: What is the background for this study? What are the main findings? Response: We have previously described a 3-gene signature for distinguishing patients with active tuberculosis (ATB) from those with other diseases, latent mycobacterium tuberculosis (LTB) infection, and healthy controls (Sweeney et al. Lancet Respir Med 2016). The current study in JAMA Network Open is a follow up study to validate the 3-gene signature in 3 additional independent cohorts that were prospectively collected. Using these 3 cohorts we have now showed that the 3-gene signature (1) can identify patients with LTB that will progress to ATB about 6 months prior to diagnosis of active tuberculosis. (2) can identify patients with ATB in active screening, and (3) can identify patients with ATB at diagnosis that have higher likelihood of persistent lung inflammation due to subclinical ATB at the end of treatment. 
Author Interviews, Biomarkers, Cancer Research, Prostate Cancer / 28.10.2018

MedicalResearch.com Interview with: [caption id="attachment_45534" align="alignleft" width="128"]Davide Pellacani Ph.D. Postdoctoral Fellow, Eaves' Lab Terry Fox Laboratory, BC Cancer Research Centre Vancouver, BC Dr. Pellacani[/caption] Davide Pellacani Ph.D. Postdoctoral Fellow, Eaves' Lab Terry Fox Laboratory, BC Cancer Research Centre Vancouver, BC MedicalResearch.com: What is the background for this study? What are the main findings? Response: Prostate cancer is characterized by frequent DNA methylation changes compared to normal tissue. Nevertheless, understanding which of those changes lead to the acquisition of malignant proprieties is complicated by the predominance of cells with luminal features in prostate cancers. In this study we generated DNA methylation maps of two distinct cell populations found within prostate cancer samples (called basal and luminal) and their normal counterparts. These datasets clearly showed that many of the common DNA methylation changes found in prostate cancer are present in luminal cells from both cancer and normal tissues. These changes are not necessarily cancer-specific, and are likely due to the bias associated with analyzing tissues in bulk, where most cancer cells have luminal-like features. We used these datasets to derive two cancer-specific and phenotype-independent DNA methylation signatures: one specific to prostate cancer luminal cells, and one composed of changes measured in both luminal and basal cancer cells. We then validated the potential clinical utility of these signatures by testing their ability to distinguish prostate cancer from normal samples, and tumours that have already escaped the prostate from those that have not, using the publicly available dataset from The Cancer Genome Atlas.
Author Interviews, Biomarkers, Endocrinology, JCEM, OBGYNE, Yale / 25.10.2018

MedicalResearch.com Interview with: [caption id="attachment_45459" align="alignleft" width="150"]Valerie A. Flores, MD Clinical Instructor Division of Reproductive Endocrinology & Infertility Department of Obstetrics, Gynecology & Reproductive Sciences Yale School of Medicine - Yale New Haven Hospital Dr. Flores[/caption] Valerie A. Flores, MD Clinical Instructor Division of Reproductive Endocrinology & Infertility Department of Obstetrics, Gynecology & Reproductive Sciences Yale School of Medicine - Yale New Haven Hospital MedicalResearch.com: What is the background for this study? What are the main findings? Response: Endometriosis is a debilitating gynecologic disease that affects 1 in 10 reproductive-aged women, causing pain and infertility.  It is a hormonally dependent disorder— estrogens promote growth of endometriosis, while progesterone inhibits estrogen-dependent proliferation. Although progestin-based therapies (including combined oral contraceptives) are first-line therapy in the management of endometriosis-associated pain, response to progestins is variable and currently unpredictable.
Author Interviews, Biomarkers, Cancer Research, FASEB / 21.10.2018

MedicalResearch.com Interview with: [caption id="attachment_45374" align="alignleft" width="133"]Professor Diana Anderson Established Chair in Biomedical Sciences The University of Bradford Richmond Road Bradford West Yorkshire Prof Anderson[/caption] Prof. Diana Anderson Established Chair in Biomedical Sciences The University of Bradford Richmond Road Bradford West Yorkshire MedicalResearch.com: What is the background for this study? Response: I have worked in this field for over 40 years both as a research scientist in industry and as a university-based researcher. It has always been my ambition to develop a relatively simple and affordable test to predict if a person is sensitive to cancer. In fact, in 1974, I was appointed as Head of Mutagenesis Studies at ICI’s Central Toxicology Laboratory in Manchester, UK, and I was looking at developing a short-term test to predict cancer even back then. Our ‘universal’ cancer test is different from other ‘universal’ tests being developed, because ours is not looking for a specific biomarker or mutation. Ours is a generic test for cancer in an individual, regardless of any underlying mechanism that’s causing their cancer. It is known that levels of damage to the DNA in the cellular genome can correlate with cancer and this is what we set out to investigate with the Comet assay. Of the available tests to detect damage to the genome the Comet assay is very straightforward. This assay was primarily developed as a method to measure DNA damage. Briefly, cells are embedded in agarose on a microscope slide and lysed to remove membranes leaving supercoiled DNA loops, breaks in which after alkaline treatment and alkaline electrophoresis move towards a positive charge. The DNA is stained with a fluorescent dye and visualised by fluorescent microscopy. The image is like Haley‘s comet and the greater number of breaks the greater is the migration to the anode and the greater the damage. 
Abbott, Author Interviews, Biomarkers, Heart Disease, JAMA / 20.10.2018

MedicalResearch.com Interview with: [caption id="attachment_45305" align="alignleft" width="137"]Dr John W Pickering, BSc(Hons), PhD, BA(Hons) 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 Prof. Pickering[/caption] Dr John W Pickering, BSc(Hons), PhD, BA(Hons) 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 MedicalResearch.com: What is the background for this study? What are the main findings? Response: The assessment of patients with suspected myocardial infarction is one of the most common tasks in the emergency department. Most patients assessed (80 to 98% depending on the health system) are ultimate not diagnosed with an MI.   High-sensitivity troponin assays have been shown to have sufficient precision at low concentrations to allow very early rule-out of myocardial infarction. However, these are lab-based assays which typically result in a delay from blood sampling before the result is available and the physician is able to return to a patient to make a decision to release the patient or undertake further investigation. Point-of-care assays provide results much quicker, but have to-date not had the analytical characteristics that allow precise measurements at low concentrations. In this pilot study we demonstrated that a single measurement with a new point-of-care assay (TnI-Nx; Abbott Point of Care) which can measure low troponin concentrations, could safely be used to rule-out myocardial infarction a large proportion of patients (57%). The performance was at least comparable to the high-sensitivity troponin I assay, if not a little better (44%).
Author Interviews, Biomarkers, Ovarian Cancer / 25.09.2018

MedicalResearch.com Interview with: [caption id="attachment_44766" align="alignleft" width="200"]Site of Ovarian Cancer - Wikipedia Image Site of Ovarian Cancer - Wikipedia Image[/caption] Fabian Coscia PhD Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, German and Ernst Lengyel MD PhD Department of Obstetrics and Gynecology Section of Gynecologic Oncology University of Chicago, Chicago, IL  MedicalResearch.com: What is the background for this study? Response: Ovarian cancer is a very aggressive disease. Only one in six patients survives more than 10 years after the first diagnosis. This high mortality is primarily because the disease is usually detected late in its course, when the tumor has already spread from the ovaries to the surrounding organs in the abdomen. In an interdisciplinary collaboration between the Max Planck Institute of Biochemistry in Martinsried, Munich, the University of Chicago and the University of Copenhagen, we performed deep tissue proteomics on archived biobank material to identify drivers of long-term patient survival. 
Author Interviews, Biomarkers, Cancer Research, Immunotherapy, Melanoma, Nature / 11.09.2018

MedicalResearch.com Interview with: [caption id="attachment_39763" align="alignleft" width="200"]Melanoma CDC/ Carl Washington, M.D., Emory Univ. School of Medicine; Mona Saraiya, MD, MPH This image depicts the gross appearance of a cutaneous pigmented lesion, which had been diagnosed as superficial spreading malignant melanoma (SSMM).  Reminder: Melanoma can take many forms. Not all look like this. Have your skin examined for skin cancer.[/caption] Dr. Noam Auslander PhD National Cancer institute and the Center for Bioinformatics and Computational Biology University of Maryland, College Park MedicalResearch.com: What is the background for this study? Response: Immunotherapy – specifically immune checkpoint blockage (ICB) therapy – has been shown to be very effective in treating melanoma. However, only some patients with advanced tumors currently benefit from ICB therapies, while others are completely resistant and hence can be spared from the associated side effects and costs. Hence, predicting which patients are most likely to respond is an important challenge that can have great clinical benefits.  
AACR, Author Interviews, Biomarkers, Colon Cancer / 05.09.2018

MedicalResearch.com Interview with: [caption id="attachment_44230" align="alignleft" width="200"]Andrea Sottoriva, PhD, MSc Reader in Cancer Evolutionary Dynamics | Evolutionary Genomics & Modelling Lab Centre for Evolution and Cancer | The Institute of Cancer Research London Dr. Sottoriva[/caption] Dr. Andrea Sottoriva, PhD Centre for Evolution and Cancer, The Institute of Cancer Research, London, United Kingdom MedicalResearch.com: What is the background for this study? Would you briefly explain what is meant by a liquid biopsy? Response: Cetuximab is a targeted treatment available for metastatic colorectal cancer patients. Unfortunately, although many patients benefit from Cetuximab, after an initial response to the treatment many patients relapse and become resistant to the drug. We know that this resistance is due to the tumour evolving and adapting to therapy. Liquid biopsies allow to look for residual cancer DNA in the blood of a patient and hence monitor the emergence of resistance over time. We used blood samples take every 4 weeks (quite frequently for this type of study) to monitor the evolution of the cancers under treatment and see if there were some measurements that would predict if and when patients will relapse.
Author Interviews, Biomarkers, Cancer Research, Journal Clinical Oncology, Lymphoma, Stanford / 23.08.2018

MedicalResearch.com Interview with: Dr. David Kurtz, MD/PhD, Instructor and Dr. Ash Alizadeh MD/PhD, Associate Professor Division of Oncology, Department of Medicine Stanford University Medical Center  MedicalResearch.com: What is the background for this study? What are the main findings?  Response: This work investigates the utility of circulating tumor DNA - a type of liquid biopsy - in diffuse large B-cell lymphoma, the most common blood cancer in adults. Liquid biopsies are an emerging technology to track cancers from a simple blood draw. Here, using a cohort of over 200 patients from 6 centers across North America and Europe, we asked if circulating tumor DNA could be used to detect lymphoma in patients, and more importantly, could it be used to identify responders and non-responders. 
Author Interviews, Biomarkers, CMAJ, Heart Disease / 20.08.2018

MedicalResearch.com Interview with: [caption id="attachment_43913" align="alignleft" width="137"]Peter Kavsak, PhD, FCACB, FAACC, FCCS Professor, Pathology and Molecular Medicine McMaster University  Prof.. Kavsak[/caption] Peter Kavsak, PhD, FCACB, FAACC, FCCS Professor, Pathology and Molecular Medicine McMaster University  MedicalResearch.com: What is the background for this study? Response: For patients who present to the hospital with symptoms suggestive of acute coronary syndrome (ACS) the preferred blood test to help physicians in making a diagnosis is cardiac troponin. Recent studies have demonstrated that a very low or undetectable cardiac troponin level when measured with the newest generation of blood tests (i.e., the high-sensitivity cardiac troponin tests) in this population may rule-out myocardial infarction (MI or a heart attack) on the initial blood sample collected in the emergency department, thus enabling a faster decision and foregoing the need for subsequent serial measurements of cardiac troponin over several hours as recommended by the guidelines. The problem with this approach, however, is that using high-sensitivity cardiac troponin alone to do this has not reliably been demonstrated to achieve a sensitivity >99% for detecting MI, which is the estimate that most physicians in this setting consider as safe for discharge. Our study goal was to compare the diagnostic performance of a simple laboratory algorithm using common blood tests (i.e., a clinical chemistry score (CCS) consisting of glucose, estimated glomerular filtration rate (eGFR), and either high-sensitivity cardiac troponin I or T) to high-sensitivity cardiac troponin alone for predicting MI or death within the first month following the initial blood work.
Author Interviews, Biomarkers, Cancer Research, Gastrointestinal Disease, JAMA / 10.08.2018

MedicalResearch.com Interview with: [caption id="attachment_43809" align="alignleft" width="134"]Wei Zhang, Ph.D. Hanes and Willis Family Professor in Cancer Director Cancer Genomics and Precision Oncology Wake Forest Baptist Comprehensive Cancer Center Winston-Salem, NC  27157-1082 Prof. Zhang[/caption] Wei Zhang, Ph.D. Hanes and Willis Family Professor in Cancer Director Cancer Genomics and Precision Oncology Wake Forest Baptist Comprehensive Cancer Center Winston-Salem, NC  27157-1082 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Gastric cancer is a leading cause of cancer-related death worldwide. Infection by the Helicobacter pylori is the major cause of gastric cancer, which accounts for more than 60% of cases. Despite progress in helicobacter pylori eradication and early cancer diagnosis, the five-year survival rate of gastric cancer remains less than 30%. Gastric cancer is one of the most common cancer types in Asia but the incidence for gastric cancer has seen a steadily increase in the United States in recent years. Immunotherapy treatment has shown remarkable benefit for some cancer patients whereas others experience toxicities. It is important to identify markers that help oncologists decide which patient would benefit from this promising new treatment strategy. It has been suggested that gastric cancer that is positive for Epstein-Barr Virus is likely more responsive to immunotherapy but only about 10% of gastric cancer patients belong to this category. More potential markers are urgently needed for clinical practice. There is accumulating evidence that high tumor mutation load, which means there are high numbers of gene mutations in the tumor, can provide a signal to activate immune response systems thus rendering tumors more sensitive to immunotherapy.
Author Interviews, Biomarkers, Heart Disease, JACC / 09.08.2018

MedicalResearch.com Interview with: [caption id="attachment_43632" align="alignleft" width="200"]John D Horowitz, MBBS, PhD. Director of Cardiology/Clinical Pharmacology Queen Elizabeth Hospital University of Adelaide Australia Dr. Horowitz[/caption] John D Horowitz, MBBS, PhD. Director of Cardiology/Clinical Pharmacology Queen Elizabeth Hospital University of Adelaide Australia  MedicalResearch.com: What is the background for this study? What are the main findings? Response:  Atrial fibrillation (AF) describes intermittent or permanent episodes of irregular pulse, due to rapid electrical activity within the atria (filling chambers) of the heart. During AF, the atria quiver, rather than contract, and the response of the ventricles is often rapid, resulting in palpitations and an increased risk of development of heart failure. AF may occur at any age, but is most common in ageing patients (typically over 75 years). The primary importance of AF is that it markedly increases the risk of thrombus formation in the atrium, with the resultant problem that these thrombi may dislodge (embolise), and commonly block arteries in the brain, causing strokes. Hence patients with AF are usually treated with anticoagulants. Although AF often occurs in patients with prior damage to their hearts and atrial distension, there has been evidence for about the past 8 years that AF also is caused, at least in part, by inflammatory changes: two components have been identified as possible causes for this inflammation: lack of nitric oxide (NO) effect[ NO is  an anti-inflammatory chemical formed by all tissues in the body],  and excess activity of the pro-inflammatory enzyme myeloperoxidase (MPO).  High concentrations of ADMA, which inhibits NO formation, may result from effects of MPO on tissues. SDMA, which is closely related to ADMA, also exerts pro-inflammatory effects and tends to suppress NO formation. The currently reported study began with the design of the ARISTOTLE trial, an investigation of the (then) novel anticoagulant apixaban as an alternative to warfarin therapy, as a means of preventing strokes in patients with AF. It was elected to perform a substudy to investigate the potential role of ADMA and SDMA as modulators of risk in patients with atrial fibrillation. This substudy, performed in just over 5000 patients from the ARISTOTLE trial, essentially asked two questions: (1) There are several indices of stroke risk in patients with atrial fibrillation, such as the CHADS2 score. These all rely on patient characteristics (eg age, presence of diabetes) rather than chemical changes. We postulated that there would be a direct relationship between clinically based risk scores and ADMA/SDMA concentrations. (2) More ambitiously, we postulated that ADMA and SDMA concentrations would represent INDEPENDENT risk markers for major adverse effects in atrial fibrillation patients on anticoagulant treatment, namely stroke, major bleeding and risk of mortality.  ADMA/SDMA concentrations were determined in Adelaide, Australia, while statistical analyses were performed in Uppsala, Sweden.
Author Interviews, Biomarkers, NYU, Pediatrics, Pulmonary Disease / 29.07.2018

MedicalResearch.com Interview with: [caption id="attachment_43557" align="alignleft" width="200"]Dr. Mikhail Kazachkov MD Director of Pediatric Pulmonology Hassenfeld Children’s Hospital NYU Langone Medical Center Dr. Kazachkov[/caption] Dr. Mikhail Kazachkov MD Director of Pediatric Pulmonology Hassenfeld Children’s Hospital NYU Langone Medical Center  MedicalResearch.com: What is the background for this study? How common is the problem of chronic cough in children?  Is it more common in children with allergies, asthma or reflux? Response: Chronic cough is one of the leading causes of pediatric referrals to subspecialty physicians.  Its prevalence in the general pediatric population may approach 3% (Galassi et al, Epidemiol. Prev. 2005;29,Suppl.:9–13). It is important to recognize that the main causes of chronic cough in children are completely different for those in adults.  Specifically, gastroesophageal reflux and postnasal drip are not considered to be important causes of cough in children.  Cough variant asthma, although is a common cause of cough in adults, does not seem to be frequently diagnosed and a cause of chronic cough in children. The main cause of chronic wet cough in children is protracted bacterial bronchitis (Chang et al, Chest. 2017 Apr;151:884-890).  It is important to recognize that neurologically impaired children have completely different pathogenesis of chronic cough, which is mostly related to aspiration into the lower airway and development of aspiration-related lung disease.
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