Racial Differences in Plasma Biomarker May Partially Explain Stroke Disparities

MedicalResearch.com Interview with:

Pankaj Arora MD, FAHA Assistant Professor, Cardiology Division University of Alabama at Birmingham Section Editor, Circulation: Cardiovascular Genetics American Heart Association

Dr. Arora

Pankaj Arora MD, FAHA
Assistant Professor, Cardiology Division
University of Alabama at Birmingham
Section Editor, Circulation: Cardiovascular Genetics
American Heart Association 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Natriuretic peptides are hormones produced by the heart in response to increased wall stress in the atria and ventricles. It is well known that blacks have increased prevalence of cardiovascular disease which contributes to racial disparities in outcomes.

In the current work, we tested the hypothesis that black race is a natriuretic peptide deficiency state using a stratified random cohort of 4,415 participants selected from the REGARDS study (a national population-based cohort study evaluating racial and geographic disparities in stroke in US adults aged ≥45 years of age or older). Next, we looked for published results on the percentage difference in N-terminal proB-type NP (NTproBNP) levels by race in participants free of cardiovascular disease from other population cohorts. Lastly, we explored whether association of natriuretic peptides with all-cause mortality and CV mortality in apparently healthy individuals from REGARDS differs by race.

We found that in multivariable adjustment, NTproBNP levels were up to 27% lower in black individuals as compared with white individuals in the REGARDS study. We pooled our results and found that in meta-analysis of the 3 cohorts, NTproBNP levels were 35% lower in black individuals than white individuals (more than 13,000 individuals in total). Lastly, we found that the higher NTproBNP levels were associated with higher incidence of all-cause mortality, and cardiovascular mortality in healthy blacks and white individuals, and this association did not differ by race.

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Micro RNAs in Saliva May Predict Severity of Concussion Injuries

MedicalResearch.com Interview with:

Dr. Steven D. Hicks,  M.D., Ph.D Penn State Health

Dr. Hicks

Dr. Steven D. Hicks,  M.D., Ph.D
Penn State Health

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Previous research has shown that small epigenetic molecules called microRNAs are altered in the blood after a traumatic brain injury. Our own pilot research showed that microRNAs were also changed in the saliva after brain injury and that some of these changes mirrored changes in cerebrospinal fluid. In this study we investigated whether salivary microRNA patterns after a concussion could be used to predict the duration and character of symptoms one month after injury.

We found that levels of five microRNAs predicted presence of symptoms one month later with greater accuracy (~85%) than standard surveys of symptom burden (~65%). Interestingly, one of the predictive salivary microRNAs (miR-320c) targets pathways involved in synaptic plasticity and was significantly correlated with attention difficulties one month after concussive injury.   Continue reading

High-Sensitivity Cardiac Troponin I Can Identify Low Risk Chest Pain Patients

MedicalResearch.com Interview with:

Dr Andrew R. Chapman BHF Clinical Research Fellow University of Edinburgh Chancellors Building Edinburgh 

Dr. Chapman

Dr Andrew R. Chapman
BHF Clinical Research Fellow
University of Edinburgh
Chancellors Building
Edinburgh 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: High-sensitivity cardiac troponin tests allow accurate measurement of cardiac troponin in the bloodstream. Currently, guidelines recommend we evaluate patients with suspected myocardial infarction using these tests, by looking for levels which are above the upper reference limit (99th centile). These troponin measurements are taken on arrival, and often repeated after admission to hospital up to six hours later. When levels are below this limit, the diagnosis of myocardial infarction is ruled out. However, using such a high limit in patients on arrival to hospital may not be safe, as lower risk stratification thresholds has been shown to reduce missed events,  and in these patients admission to hospital for repeat testing may not be necessary. However, there is no consensus as to the optimal threshold for use in practice.

In a worldwide study of 23,000 patients from 9 countries, we have shown when high-sensitivity cardiac troponin I concentrations are below a risk stratification threshold of 5 ng/L at presentation, patients are at extremely low risk of myocardial infarction or cardiac death at 30 days, with fewer than 1 in 200 patients missed. Importantly, this threshold identifies almost 50% of all patients as low risk after a single blood test. As admission or observation of these patients is estimated to cost as much as $11 billion per year in the United States, this strategy has major potential to improve the efficiency of our practice.

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Personality Changes Can Signal Incomplete Recovery After Traumatic Brain Injury

MedicalResearch.com Interview with:

Prof.dr. J van der Naalt PhD Department of Neurology University Medical Center Groningen Groningen, The Netherlands

Prof J van der Naalt

Prof.dr. J van der Naalt PhD
Department of Neurology University Medical Center Groningen
Groningen, The Netherlands

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Mild traumatic brain injury occurs frequently and is one of the leading cause of morbidity in adults worldwide. It is a major social-economic problem with one in three patients had persistent complaints several months after injury that interfere with resumption of daily activities and work.

One of the most important questions concerns the finding that some patients recover without complaints and others do not after sustaining a mild traumatic brain injury. In a follow-up study with more than 1000 participants we found that personality factors are a major factor in the recovery process. In particular coping, that is the way patients adapt to persistent complaints, is important next to emotional distress and impact of the injury.

In an add-on study with fMRI we found that in the early phase after injury, the interaction between specific brain networks was temporarily changed. However, when regarding persistent posttraumatic complaints , specific personality characteristics significantly determine long term outcome.

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Defective Viral Genomes May Indicate Greater Flu Virus Severity

MedicalResearch.com Interview with:
Ana Falcón
Department of Molecular and Cellular Biology
National Center for Biotechnology
Spanish National Research Council (CNB-CSIC)
Madrid, Spain

MedicalResearch.com: What is the background for this study?

Response: Influenza A virus (IAV) infection can be severe or even lethal in toddlers, the elderly and patients with certain medical conditions. Infection of apparently healthy individuals nonetheless accounts for many severe disease cases and deaths, suggesting that viruses with increased pathogenicity co-circulate with pandemic or epidemic viruses.

IAV virulence and pathogenesis are dependent on complex, multigenic mechanisms involving the viral genetic characteristics, the host conditions, the virus-host interactions, and the host response to the infection. Influenza virus pathogenicity has been studied in depth for many years, and several amino acid changes have been identified as virulence determinants, however, a general pathogenicity determinant has not been characterized.

A proportion of influenza virus particles have defective genome RNAs (Defective Viral Genomes-DVGs) due to internal deletions of viral segments. The DVGs have the 3’ and 5’ ends of the parental RNA segments, and most have a single, large central deletion that generates viral RNAs of 180–1000 nucleotides. The presence of DVGs potentiates the host response in cultured cells and in animal models and leads to attenuated infection, possibly through recognition of double-stranded RNA by receptors that activate antiviral signaling cascades.

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Any Detectable High-Sensitivity Cardiac Troponin T Level Associated With Adverse Outcomes

MedicalResearch.com Interview with:
Martin Holzmann PhD

Department of Medicine
Functional Area of Emergency Medicine,
Karolinska University Hospital, Huddinge
Stockholm, Sweden

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: There has been a few studies in the general population that indicate that subjects with detectable and elevated high-sensitivity troponin T (hs-cTnT) levels have an increased risk of death and cardiovascular disease. However, in clinical practice troponins are not used for anything else than to rule in or rule out myocardial infarction in the emergency department. In addition, in a previous publication we have shown that patients with persistently elevated troponin levels are rarely investigated or followed-up to exclude heart disease. Therefore, we wanted to investigate how the association between different levels of hs-cTnT are associated with outcomes in patients with chest pain but no MI or other acute reasons for having an acutely elevated troponin level.

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Older Men Continue To Have PSA Screening Despite Benefits Unlikely To Outweigh Risks

MedicalResearch.com Interview with:
Zahava Berkowitz, MSPH, MSc
Statistician
Division of Cancer Prevention and Control
Centers for Disease Control and Prevention

MedicalResearch.com: What is the background for this study?

Response: The US Preventive Services Task Force 2017 draft prostate cancer screening recommendations  suggest that clinicians inform men aged 55–69 years about the potential benefits and harms of PSA-based screening for prostate cancer.

The CDC conducted an analysis using the National Health Interview Surveys in 2005, 2008, 2010, 2013, and 2015 to describe trends in the receipt of routine PSA testing in the past year by age group (40–54, 55–69, ≥70 years) and by risk group. We compared routine PSA screening among higher risk men (defined as African American men or men with a family history of prostate cancer) with other men. The analysis was conducted because CDC wanted to examine how the guidelines affect men at higher risk. The 2017 guideline did not include specific guidelines for African American men who have a higher incidence of prostate cancer than white men, more likely to develop prostate cancer at a young age, more likely to have a high-risk diagnosis and die from prostate cancer.

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Refined Biomarker Model Can Guage Risk of Alzheimer’s In Patients With Mild Cognitive Impairment

MedicalResearch.com Interview with:
Ingrid S. van Maurik, MSc
Department of Neurology and Alzheimer Center
Department of Epidemiology and Biostatistics
Amsterdam Neuroscience
VU University Medical Center
Amsterdam, the Netherlands

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: CSF and MRI biomarkers are increasingly used in clinical practice, but their diagnostic and prognostic value is not perfect. Furthermore, criteria do not specify how to deal with conflicting or borderline results, or how to take patient characteristics into account. Therefore, optimal use of these biomarkers in clinical practice remains challenging.

As part of the ABIDE project, we constructed biomarker-based prognostic models (CSF, MRI and combined) that enable prediction of future Alzheimer’s disease, or any type of dementia, in individual patients with mild cognitive impairment. When using these models, any value can be entered for the variables, resulting in personalized probabilities with confidence intervals.

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New Biomarker Has Potential For Sideline Diagnosis of Traumatic Brain Injury

MedicalResearch.com Interview with:

Dr-Adrian-Harel.jpg

Dr. Adrian Harel

Dr. Adrian Harel, PhD
Chief Executive Officer
Medicortex Finland

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Every 15 seconds, someone in the United States suffers a new head injury. Of the 2.5M people treated in hospital emergency rooms each year, 80,000 become permanently disabled because of TBI. Currently, there are no reliable diagnostic tests to assess the presence or severity of an injury on-site, nor are there any pharmaceutical therapies that could stop the secondary injury from spreading. Accurate diagnostics would benefit especially mild cases of TBI (concussions), which, if occurring repeatedly, may cause neurodegenerative conditions such as Chronic Traumatic Encephalopathy (which is typical for athletes in NFL and Ice-hockey).

We have performed extensive preclinical research comparing fluid biopsies from normal and injured lab animals. The results showed some unique biomarkers released as a biodegradation products after head injury. The data served as the basis and confirmation for our patent applications to protect the biomarker concept.

Medicortex has completed a clinical proof-of-concept trial in collaboration with Turku University Hospital (Tyks). Samples from 12 TBI patients and 12 healthy volunteers were collected and analyzed for the presence and for the level of the biomarker in state-of-the-art laboratories. The study demonstrated the diagnostic potential of the new biomarker in humans and it confirmed the prior preclinical findings. This was a significant milestone for Medicortex.

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Blood Biomarkers Signal Multiple Organ Dysfunction Syndrome After Critical Injuries

MedicalResearch.com Interview with:

Dr. Joanna Shepherd Centre for Trauma Sciences Blizard Institute Queen Mary, University of London

Dr. Shepherd

Dr. Joanna Shepherd
Centre for Trauma Sciences
Blizard Institute
Queen Mary, University of London

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Recent advances in resuscitation and treatment of life-threatening critical injuries means that patients with previously unsurvivable injuries are now surviving to reach hospital.  However, many of these patients develop Multiple Organ Dysfunction Syndrome (MODS), which is a failure of several organs including the lung, heart, kidney, and liver.

We studied immune cell genes in the blood of critically injured patients within the first few minutes to hours after injury, a period called the ‘hyperacute window’. We found a small and specific response to critical injury during this window that then evolved into a widespread immune reaction by 24 hours.  The development of MODS was linked to changes in the hyperacute window, with central roles for innate immune cells (including natural killer cells and neutrophils) and biological pathways associated with cell death and survival.  By 24 hours after injury, there was widespread immune activation present in all critically injured patients, but the MODS signal had either reversed or disappeared.

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Targeting CD44s May Make Glioblastoma More Sensitive To Clinical Treatment

MedicalResearch.com Interview with:

Chonghui Cheng, M.D., Ph.D. Associate Professor Department of Molecular & Human Genetics Lester & Sue Smith Breast Center Baylor College of Medicine Houston, TX77030

Dr. Cheng

Chonghui Cheng, M.D., Ph.D.
Associate Professor
Department of Molecular & Human Genetics
Lester & Sue Smith Breast Center
Baylor College of Medicine
Houston, TX77030

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Understanding the mechanisms that give cancer cells the ability to survive and grow opens the possibility of developing improved treatments to control or cure disease. In the case of glioblastoma multiforme, the deadliest type of brain cancer, abnormal EGFR signaling is frequently observed.

Treatment with the EGFR inhibitor erlotinib attempts to kill cancer cells. However, the clinical benefit of treatment with this and other EGFR inhibitors has been limited by the development of drug resistance.

Scientists at Baylor College of Medicine discovered that the molecule CD44s seems to give cancer cells a survival advantage. Eliminating this advantage by reducing the amount of CD44s resulted in cancer cells being more sensitive to the deadly effects of the drug erlotinib.

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Potential Blood Biomarker Predicts Course of Huntington’s Disease

MedicalResearch.com Interview with:

Dr Edward Wild PhD MRC Clinician Scientist Huntington's Disease Centre UCL Institute of Neurology Honorary Consultant Neurologist National Hospital for Neurology & Neurosurgery, London UK

Dr. Wild

Dr Edward Wild PhD
MRC Clinician Scientist
Huntington’s Disease Centre
UCL Institute of Neurology
Honorary Consultant Neurologist
National Hospital for Neurology & Neurosurgery,
London UK

MedicalResearch.com: What is the background for this study?

Response: Having a readily accessible and sensitive biomarker, that is representative of ongoing neuropathology, could facilitate therapeutic development for Huntington’s disease. Neurofilament light (NfL) protein is one of the component that makes up the cytoskeleton of neurons. It is released when neuronal damage or death occurs and can be quantified in blood.

MedicalResearch.com: WWhat are the main findings?

Response: We carried out a retrospective cohort analysis of samples from the TRACK-HD study – a multisite longitudinal observational study of HD patients. NfL was quantified in plasma from 298 participants at baseline and follow-up. NfL was significantly higher in HD compared to healthy controls and increased with disease stage. Baseline levels of plasma NfL predicted clinical progression, including cognitive and functional decline, and the rate of global and regional brain atrophy. Premanifest individuals who converted to manifest  Huntington’s disease in the three years of the study had significantly higher levels of plasma NfL at baseline. These associations remained significant after adjustment for the combined interaction of age and CAG, currently the best predictor of age of onset of Huntington’s disease. In a separate cohort, levels of NfL in plasma and CSF were highly correlated.

MedicalResearch.com: What should clinicians and patients take away from your report?

Response: Despite decades of research, no substance in blood has shown any power to predict disease progression of Huntington’s disease. In addition, no substance has been shown to be increased as in premanifest subjects over 10 years from their predicted onset suggesting it may have potential for detecting the earliest signs of HD before overt symptoms manifest.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: We hope that quantifying NfL will be incorporated into all future observational studies of  Huntington’s disease and potentially retrospectively where blood or CSF samples have been banked. We feel it should also be used in current and future clinical trials as an efficacy marker to assess whether a drug is slowing neuronal damage, at the very least as an exploratory end point. 

MedicalResearch.com: Is there anything else you would like to add?

Response: At the moment we do not have enough information for this blood test to be of clinical relevance and prognosis of a patient. A lot more research needs to be done before it could be use on an individual basis in the clinic.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation: Lauren M Byrne, Filipe B Rodrigues, Kaj Blennow, Alexandra Durr, Blair R Leavitt, Raymund A C Roos, Rachael I Scahill, Sarah J Tabrizi, Henrik Zetterberg, Douglas Langbehn, Edward J Wild. Neurofilament light protein in blood as a potential biomarker of neurodegeneration in Huntington’s disease: a retrospective cohort analysisThe Lancet Neurology, 2017; DOI: 10.1016/S1474-4422(17)30124-2

http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(17)30124-2/fulltext

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

 

 

 

An Ultra-Early Inflammatory Biomarker of Traumatic Brain Injury

MedicalResearch.com Interview with:

Dr Lisa J Hill PhD Institute of Inflammation and Ageing Research Fellow Neuroscience and Ophthalmology Institute of Inflammation and Ageing College of Medical and Dental Sciences University of Birmingham UK

Dr. Hill

Dr Lisa J Hill PhD
Institute of Inflammation and Ageing
Research Fellow
Neuroscience and Ophthalmology
Institute of Inflammation and Ageing
College of Medical and Dental Sciences
University of Birmingham UK 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Traumatic brain injury (TBI) is the leading cause of death and disability among young adults and, according to the World Health Organization, by 2020 TBI will become the world’s leading cause of neurological disability across all age groups.  Early and correct diagnosis of traumatic brain injury is one of the most challenging aspects faced by clinicians. Being able to detect compounds in the blood that help to determine how severe the brain injury is would be of great benefit to patients and aid in their treatment.  Inflammatory markers are particularly suited for biomarker discovery as TBI leads to very early alterations in inflammatory proteins.  The discovery of reliable biomarkers for the management of TBI would improve clinical interventions.

We collected blood samples from 30 injured patients within the first hour of injury prior to the patient arriving at hospital and analysed them. Analysis of protein biomarkers from blood taken within the first hour of injury has never been carried out until now. We used a panel of 92 inflammation-associated human proteins when analysing the blood samples. The analysis identified three inflammatory proteins, known as CST5AXIN1 and TRAIL, as novel biomarkers of TBI.

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Fecal Testing Better At Detecting Colon Cancer Than Advanced Atypical Changes

MedicalResearch.com Interview with:

Anastasia Katsoula, MD MSc Aristotle University of Thessaloniki Greece 

Dr. Katsoula

Anastasia Katsoula, MD MSc
Aristotle University of Thessaloniki
Greece 

MedicalResearch.com: What is the background for this study?

Response: Early detection of colorectal cancer (CRC) has proven to be effective in reduction of cancer-related mortality. Fecal immunochemical testing (FIT) has been recently advocated for population-based screening for CRC in average-risk individuals due to its high accuracy and potential for adherence, based on results from previous systematic reviews and meta-analyses in average-risk populations. However, the potential role of FIT for screening of subjects at increased risk for CRC has not yet been elucidated, hence colonoscopy is currently the only recommended screening option for subjects at increased risk of CRC. We performed a systematic review and meta-analysis to explore the diagnostic accuracy of FIT for CRC or advanced neoplasia (AN) in patientswith personal or familial history of CRC, using colonoscopy as the reference standard.

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Circulating Cell Scoring System Identifies High Risk Prostate Cancer

MedicalResearch.com Interview with:

Dr. Yong-Jie Lu Reader in Medical Oncology Centre for Molecular Oncology Barts Cancer Institute - a CR-UK Centre of Excellence Queen Mary University of London John Vane Science Centre, Charterhouse Square, LONDON

Dr. Yong-Jie Lu

Dr. Yong-Jie Lu MBBS, MD, PhD
Reader in Medical Oncology
Centre for Molecular Oncology
Barts Cancer Institute – a CR-UK Centre of Excellence
Queen Mary University of London
John Vane Science Centre, Charterhouse Square
London

MedicalResearch.com: What is the background for this study?

Response: Identifying/monitoring the occurrence of metastasis and the prediction of the length that a patient may survive with a prostate cancer is critical for doctors to select the proper treatment, aiming to achieve the best control of the cancer with a balance of quality of life. Currently this is achieved mainly by analysing the cancer tissues acquired through very invasive procedures or by expensive imaging techniques, most of which expose the patient to toxic radioactive materials.

Circulating tumour cells (CTCs), which play a key role in the metastasis process, have been shown for their potential to be used for cancer prognosis by a simple blood sample analysis. However, previous CTC studies mainly detect the epithelial type of CTCs. Using the ParsortixTM (ANGLE plc) cell-size and deformability based CTC isolation system, we analysed not only epithelial CTCs, but also CTCs with epithelial-mesenchymal transition (EMT), a cellular process associated with cancer invasion and metastasis.

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Comprehensive Study of Metabolic Inhibitors Reveals the Anti-Tumor Efficacy of Phenformin in Pancreatic Cancer

MedicalResearch.com Interview with:

Dr-Rajesh-Kumar.jpg

Dr. Rajesh Kumar NV

Rajesh Kumar NV, Ph.D.
Instructor of Oncology and Pathology,
Johns Hopkins University School of Medicine, Baltimore, MD, USA
Current affiliation
Senior Manager, Human Therapeutics Division,
Intrexon Corporation
Germantown, MD

MedicalResearch.com: What is the background for this study?

Response: Pancreatic ductal adenocarcinoma (a.k.a. pancreatic cancer) is one of the most deadly of all types of cancer and currently the third leading cause of cancer-related death in United States. Current therapeutic options for pancreatic cancer involve combination cytotoxic chemotherapy, which yield only minimal survival benefit. A multitude of Phase III clinical trials have failed to demonstrate efficacy, largely due to the aggressive growth of pancreatic tumors. Metabolic reprogramming is a hallmark of cancer cells, including pancreatic cancer. Altered metabolism is central to the pathogenesis of pancreatic cancer and contributes to promotion of proliferation, survival, invasiveness and chemo-resistance of cancer cells. Pharmacologic strategies targeting cancer metabolism might therefore represent a promising approach towards the development of effective drugs against pancreatic cancer.

We utilized a clinically relevant and genetically characterized platform of patient-derived pancreatic cancer xenografts, which we originally created from the freshly resected pancreatic cancer tissues of patients, to explore the in vivo anti-tumor efficacy of a panel metabolic inhibitors and investigated whether mutational status, gene expression and metabolite profile of tumors correlate with the sensitivity to metabolic inhibitors. To our knowledge, this is the largest preclinical trial which enrolled a large number of animals (over 500 mice) with established human pancreatic tumors for the comprehensive evaluation of key metabolic inhibitors in pancreatic cancer.  Continue reading

Cholesterol Uptake Capacity, a New Indicator of HDL Functionality, for Cardiovascular Risk Stratification in the Real World.

MedicalResearch.com Interview with:
Amane Harada, PhD
Senior Researcher
Central Research Laboratories, Sysmex Corporation
Kobe, Japan

Ryuji Toh, MD, PhD Associate Professor Division of Evidence-based Laboratory Medicine Kobe University Graduate School of MedicineRyuji Toh, MD, PhD
Associate Professor
Division of Evidence-based Laboratory Medicine
Kobe University Graduate School of Medicine
Kobe, Japan 


MedicalResearch.com: What is the background for this study?

Response: High-density lipoprotein (HDL) exhibits a variety of anti-atherogenic functions including anti-inflammatory and anti-oxidative functions as well as promoting reverse cholesterol transport. However, it has been reported that HDL may lose its anti-atherogenic properties and become “dysfunctional” HDL under pathological conditions.

Recent studies have demonstrated that cholesterol efflux capacity of HDL is a better predictor of CVD than HDL-C, suggesting that not only the quantity, but also the quality of HDL may significantly modulate and predict the progression of cardiovascular disease.

However, the conventional procedure for efflux capacity assay requires radiolabeling and cells, and the procedures are time consuming. Therefore, its clinical application is impractical.

To solve those problems, we have recently developed a new assay system to evaluate the capacity of HDL to accept cholesterol, named “uptake capacity”.

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Vascular Biomarker Predicts Death or Pulmonary Morbidity in Premature Infants

MedicalResearch.com Interview with:

Jegen Kandasamy MD Division of Neonatology Assistant Professor/Director, Rare Disease Program and Congenital Anomalies Program University of Alabama at Birmingham Birmingham, Alabama

Dr. Kandasamy

Jegen Kandasamy MD
Division of Neonatology
Assistant Professor/Director, Rare Disease Program and Congenital Anomalies Program
University of Alabama at Birmingham
Birmingham, Alabama 

MedicalResearch.com: What is the background for this study?

Response: Preterm infants, especially those that are born with a birth weight of 750 grams or less, are prone to a lung disease called bronchopulmonary dysplasia (BPD) because the development of lungs in these infants takes place in an environment that has more oxygen than that available in utero. Recently, pulmonary blood vessel growth and function has been hypothesized to play a causal role in the pathogenesis of BPD. Vascular endothelial cell function has been shown to affect hyperoxia-induced lung damage in animal studies. An important source of human vascular endothelial cells is the umbilical cord of newborn infants. These human umbilical venous endothelial cells (HUVEC) have been used to measure endothelial cell function in various diseases but never in diseases related to the newborn infants from whom they were derived.

In addition, the mitochondria in various cells in our body respond to oxygen toxicity by creating, as well as consuming, reactive oxygen species (ROS) that mediate most of the effects of oxygen-induced damage. Therefore, we designed this study to measure mitochondrial function in vascular endothelial cells obtained from the umbilical cords of prematurely born infants at the time of their birth. We then compared these mitochondrial functional measures between infants who later died or developed BPD versus those who survived without BPD.

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Genomic Profile Can Improve Confidence in Active Surveillance of Prostate Cancer

MedicalResearch.com Interview with:

Bela S. Denes, MD, FACS Senior Director Medical Affairs UROLOGY Genomic Health Inc. Redwood City, CA. 94063

Dr. Bela S. Denes

Bela S. Denes, MD, FACS
Senior Director Medical Affairs
UROLOGY
Genomic Health Inc.
Redwood City, CA. 94063

MedicalResearch.com: What is the background for this study?

Response: This is a prospective community based non-interventional study designed to provide information on the utility of Oncotype GPS in the management of men presenting with a new diagnosis of clinically localized low risk prostate cancer. We sought to understand the impact of incorporating a molecular marker into the shared treatment decision in practices already well versed in Active Surveillance (AS) as measured by persistence on surveillance at 2 years as well as a number of patient reported outcomes. The current publication reports on the results of a one year pre-specified interim analysis.

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Salivary Biomarker May Lead To Spit Test For Early Diagnosis of Alzheimer’s Disease

MedicalResearch.com Interview with:

Ali Yilmaz, PhD Beaumont Research Institute Beaumont Health, Royal Oak, MI

Dr. Yilmaz

Ali Yilmaz, PhD
Beaumont Research Institute
Beaumont Health, Royal Oak, MI

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Alzheimer’s disease (AD) is a neurodegenerative disorder that is characterized by the accumulation of β-amyloid plaques and tau tangles. Mild cognitive impairment (MCI) is progressive degree of impairment that is greater than might be attributed to normal age-related cognitive decline, but is not so severe as to merit a diagnosis of dementia. MCI is thought to be a transitional state between normal aging and AD sufferers phenotypically converting to AD at a rate of 10% per year. Currently there is no cure and few reliable diagnostic biomarkers for AD. As we live longer there is an ever increasing demand for valid and reliable biomarkers of Alzheimer’s disease; not only because it will help clinicians recognize the disease in its earliest symptomatic stages but will also be important for developing novel treatment of AD. Using 1D H NMR metabolomics, we biochemically profiled saliva samples collected from healthy-controls (n = 12), mild cognitive impairment (MCI) sufferers (n = 8), and Alzheimer’s disease (AD) patients (n = 9). We accurately identified significant concentration changes in 22 metabolites in the saliva of MCI and AD patients compared to controls.

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New Prostate Cancer Specific Assay May Reduce Need For Biopsies

MedicalResearch.com Interview with:

Eric A. Klein, MD</strong> Chairman, Glickman Urological and Kidney Institute Cleveland Clinic

Dr. Klein

Eric A. Klein, MD
Chairman, Glickman Urological and Kidney Institute
Cleveland Clinic

MedicalResearch.com: Which of these results did you find most interesting or surprising?

Response: What’s most interesting is that the IsoPSA assay redefines how PSA is measured, which links it more closely to the underlying biology of cancer. Current assays measure only the concentration of PSA, which can be affected by conditions other than cancer – BPH most commonly, but also infection and inflammation – which limits its diagnostic accuracy for finding cancer. Its been known for several decades that PSA exists in multiple different forms in the bloodstream in patients with prostate cancer.

These novel molecules arise because cancer cells have deranged cellular metabolism that result in the generation of new species of PSA, making their measurement more tightly linked to the presence or absence of cancer and even the presence of high grade cancer (where cellular metabolism is even more disordered).

The IsoPSA assay is the first assay to measure all of these isoforms and thus has better diagnostic accuracy for cancer.

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TeloView Measures Genomic Stability To Predict Disease Aggressiveness

MedicalResearch.com Interview with:

3D SignaturesJason Flowerday, CEO
Director of 3D Signatures 

MedicalResearch.com: What is the background for 3D Signatures?

Response: 3D Signatures, and its clinical lab tests, which incorporate its proprietary TeloViewTM software analytics, is the culmination of over 20 years of ground-breaking research conducted by Dr. Sabine Mai and her colleagues. It is the only technology in the world that quantifies genomic instability, which is the hallmark of cancer and other proliferative diseases at the whole-cell level.

By measuring the degree of genomic instability from different tissues, TeloViewTM has produced clinically actionable distinctions in the stage of disease, rate of progression of disease, drug efficacy, and drug toxicity. The technology is well developed and supported by 22 clinical studies on over 2,000 patients on 13 different cancers including Alzheimer’s disease. The results have been exceptional and represent a universal biomarker platform across all disease areas that the company has investigated to date.

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Saliva Test Can Predict Concussion Duration in Children

MedicalResearch.com Interview with:

Steven Daniel Hicks, MD, PhD Assistant Professor, Division of Academic General Pediatrics College of Medicine Penn State Health

Dr. Hicks

Steven Daniel Hicks, MD, PhD
Assistant Professor, Division of Academic General Pediatrics
College of Medicine
Penn State Health

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: There are about 3 million concussions in the US each year and the majority occur in children. Parents of children with concussions commonly cite length of recovery as a major concern, but pediatricians have no objective or accurate tests for addressing this concern.

Our research group previously identified small regulatory molecules called microRNAs that were altered in both the spinal fluid and saliva in children with traumatic brain injuries. In this study we investigated whether those microRNAs could predict duration of concussion symptoms. In 52 children with concussion we found a set of microRNAs that predict whether concussion symptoms would last beyond one month with over 80% accuracy. This was significantly more accurate than survey based tools such as the sports concussion assessment tool or a modified concussion clinical risk score. Interestingly, the microRNAs with predictive accuracy targeted pathways involved in brain repair and showed correlations with specific concussion symptoms.

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Granzyme B Probe Plus PET Scanning Helps Determine Response To Immunotherapy

MedicalResearch.com Interview with:

Ben Larimer, PhD research fellow in lab of Umar Mahmood, MD, PhD Massachusetts General Hospital Professor, Radiology, Harvard Medical School

Dr. Ben Larimer

Ben Larimer, PhD research fellow in lab of
Umar Mahmood, MD, PhD

Massachusetts General Hospital
Professor, Radiology, Harvard Medical School

MedicalResearch.com: What is the background for this study? What are the main findings?

Response:
Although immunotherapies such as checkpoint inhibitors have revolutionized cancer treatment, unfortunately they only work in a minority of patients. This means that most people who are put on a checkpoint inhibitor will not benefit but still have the increased risk of side effects. They also lose time they could have spent on other therapies. The ability to differentiate early in the course of treatment patients who are likely to benefit from immunotherapy from those who will not greatly improves individual patient care and helps accelerate the development of new therapies.

The main purpose of our study was to find a way to separate immunotherapy responders from non-responders at the earliest time point possible, and develop an imaging probe that would allow us to distinguish this non-invasively.

Granzyme B is a protein that immune cells use to actually kill their target. They keep it locked up in special compartments until they get the right signal to kill, after which they release it along with another protein called perforin that allows it to go inside of tumor cells and kill them. We designed a probe that only binds to granzyme B after it is released from immune cells, so that we could directly measure immune cell killing. We then attached it to a radioactive atom that quickly decays, so we could use PET scanning to noninvasively image the entire body to see where immune cells were actively releasing tumor-killing granzyme B.

We took genetically identical mice and gave them identical cancer and then treated every mouse with checkpoint inhibitors, which we knew would result in roughly half of the mice responding, but we wouldn’t know which ones until their tumors began to shrink. A little over a week after giving therapy to the mice, and before any of the tumors started to shrink, we injected our imaging probe and performed PET scans. When we looked at the mice by PET imaging, they fell into two groups. One group had high PET uptake, meaning high levels of granzyme B in the tumors, the other group had low levels of PET signal in the tumors. When we then followed out the two groups, all of the mice with high granzyme B PET uptake ended up responding to the therapy and their tumors subsequently disappeared, whereas those with low uptake had their tumors continue to grow.

We were very excited about this and so we expanded our collaboration with co-authors Keith Flaherty and Genevieve Boland to get patient samples from patients who were on checkpoint inhibitor therapy to see if the same pattern held true in humans. When we looked at the human melanoma tumor samples we saw the same pattern, high secreted granzyme levels in responders and much lower levels in non-responders.

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GeneStrat Test Provides Quick Analysis of Genetic Lung Cancer Mutations

MedicalResearch.com Interview with:
Hestia Mellert, PhD

Director, Molecular Product Development
Biodesix: Making Medicine Personal
Boulder, CO

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Identifying specific genetic mutations in non-small cell lung cancer patients helps clinicians choose the best treatment options; specific therapies that target mutations can improve patient outcomes, including reducing the risk of death or lessening the severity of the disease. However, nearly 80% of cancer patients do not have genetic mutation results available at initial oncology consultation; up to 25% of patients begin treatment before receiving their results. These factors hinder physicians’ ability to pursue optimal treatment strategies.

This study found that a blood-based assay, the GeneStrat test, provides results in 72 hours for 94% of patients, which expands testing options, and supports faster treatment decisions by physicians.

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Xpert HCV Viral Load Test Can Detect Active Hepatitis C Infection From Fingerstick

MedicalResearch.com Interview with:

Jason Grebely PhD Associate Professor Senior Research Fellow (UNSW) Viral Hepatitis Clinical Research Program

Dr. Grebely

Jason Grebely PhD
Associate Professor
Senior Research Fellow (UNSW)
Viral Hepatitis Clinical Research Program

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Globally, testing and diagnosis of hepatitis C virus infection remain low. Although point of care tests for HCV infection exist, but many of these tests only measure HCV antibodies (previous exposure), not HCV RNA (active infection). Given that 25% of individuals spontaneously clear HCV infection, efforts to enhance diagnosis of chronic HCV infection and improve the HCV care cascade requires enhanced uptake of HCV RNA testing.

We conducted the first evaluation of the Xpert HCV Viral Load test (manufactured by Cepheid) – a point-of-care hepatitis C virus test that can detect active infection – from a finger-stick sample of blood. We established that there is good sensitivity and specificity of the Xpert HCV Viral Load point-of-care test using blood samples collected by finger-stick in participants attending drug health and homelessness services in Australia.

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New Platform Aims To Improve Cancer Markers Braf p.V600E/K Mutations

MedicalResearch.com Interview with:

Thurai Moorthy Ph.D.</strong> President, MultiGEN Diagnostics Greensboro, NC 27405

Dr. Moorthy

Thurai Moorthy Ph.D.
President, MultiGEN Diagnostics
Greensboro, NC 27405

MedicalResearch.com: What is the background for this study?

Response: As more cancer related genetic markers are reported, there is a need for appropriate molecular tests to meet clinical expectations. These expectations include detection at very low amount in a heterogeneous cell population, such as Formalin Fixed Paraffin embedded (FFPE) tumor biopsies.

Braf p.V600E/K mutations are cancer-specific markers found in a variety of cancers. There are several drugs in use, and more drugs are being developed, which are prescribed only to those patients whose tumor carries either of these (Braf p.V600E/K) mutations.

Hence, detection of Braf p. V600E/K is critical in the treatment of cancer patients. In this regard, we developed a new platform technology, Allele Specific Multiplex Sequencing (ASMS, for the detection of cancer markers from biopsy samples. As a demonstration project, we tested the new platform technology for the detection of Braf p.V600E/K using tumor samples (FFPE) previously tested by two presently used methods.

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Rapid Rule-Out of Acute Myocardial Infarction With a Single High-Sensitivity Cardiac Troponin T Measurement

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.

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Pre-Clinical Study of Tbit™ System for Detection of Traumatic Brain Injury

MedicalResearch.com Interview with:

Sergey A. Dryga, PhD, MBA Chief Scientific Officer BioDirection, Inc.

Dr. Sergey Dryga

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.

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Model of RAF Inhibitor Action Provides Roadmap For Resistant Colon and Thyroid Cancer Treatment

MedicalResearch.com Interview with:

Poulikos I. Poulikakos, PhD Assistant Professor Department of Oncological Sciences Department of Dermatology The Tisch Cancer Institute Icahn School of Medicine at Mount Sinai

Dr. Poulikakos

Poulikos I. Poulikakos, PhD
Assistant Professor
Department of Oncological Sciences
Department of Dermatology
The Tisch Cancer Institute
Icahn School of Medicine at Mount Sinai

MedicalResearch.com: What is the background for this study?

Response: Mutations in the oncoprotein kinase BRAF are found in about 8% of human tumors, including more than 50% of melanomas. Small molecule RAF inhibitors prolonged survival of melanoma patients with mutant-BRAF tumors, but resistance limits their effectiveness. Further, RAF inhibitors showed only modest efficacy in patients with colorectal and thyroid mutant-BRAF tumors. Previous studies have suggested that the complex biochemical mechanisms of action of RAF inhibitors account for both sensitivity and major mechanisms of resistance to these drugs. Recently, a number of next generation RAF inhibitors have entered preclinical or clinical development, but the most appropriate clinical context for their use remained elusive.

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IQuity Developing RNA-Based Disease Activity Test for Multiple Sclerosis

MedicalResearch.com Interview with:

Dr. Chase Spurlock, Ph.D. Executive Officer at IQuity, Inc Nashville, Tennessee

Dr. Chase Spurlock

Dr. Chase Spurlock, Ph.D.
Executive Officer at IQuity, Inc
Nashville, Tennessee

IQuity is working to further develop RNA technologies that can be used to diagnose and treat Multiple Sclerosis. IQuity hopes to develop a ‘disease activity test’, which would help physicians determine when a patient is likely to relapse so that treatments can be timed for best effect.

 

MedicalResearch.com: What is the background for IQuity? What are its goals and mission?

Response: IQuity, Inc. is a biotechnology company that focuses on the research and development of innovative specialty diagnostic technology, specifically for autoimmune diseases. Our research has shown that autoimmune patients have distinct RNA expression patterns in their blood, and we have figured out how to leverage machine learning methods to analyze these RNA expression patterns and test for the presence of diseases like multiple sclerosis, IBS/IBD (Crohn’s and ulcerative colitis) and fibromyalgia. We collected patient samples from around the globe to match their RNA profiles against healthy and sick patient profiles we identified through our previous research. These tests led to the development of IQIsolate, our technology that informs the suite of tests which, when used even at the earliest onset of symptoms, can give providers information to rule in or rule out a suspected autoimmune disease with more than 90% accuracy.

Our mission is to relentlessly pursue innovation in specialized diagnostic and analytic technology, identifying complicated autoimmune and autoimmune-related diseases at the earliest signs of symptoms. We strive to enable providers to diagnose early and treat sooner in the disease progression to improve long-term outcomes, lower the overall cost of lifelong autoimmune diseases and minimize the uncertainty and fear patients experience during prolonged diagnosis periods.

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First Diagnostic Blood Test for Coronary Artery Plaque Detection

MedicalResearch.com Interview with:

Szilard Voros, MD, FACC, FSCCT, FAHA CEO of Global Genomics Group

Dr. Voros

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.

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Biomarker VCAM-1 Associated With New Onset Atrial Fibrillation

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.

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Gene Expression-based Breast Cancer Index Can Improve Decision Making For ER+ Patients

MedicalResearch.com Interview with:

Tara Sanft, MD Assistant Professor of Medicine (Medical Oncology) Medical Director of Adult Survivorship Yale Cancer Center Survivorship Clinic

Dr. Tara Sanft

Tara Sanft, MD
Assistant Professor of Medicine (Medical Oncology)
Medical Director of Adult Survivorship
Yale Cancer Center Survivorship Clinic 

MedicalResearch.com: What is the background for this study?

Response: Previous studies have demonstrated the benefit of extended endocrine therapy (EET) for hormone receptor-positive (HR+) breast cancer in preventing late relapse, however that benefit is limited to 3-5% of women where late recurrence was prevented or staved off. However, EET has become common practice and as a result we are exposing many patients to risks of side effects and toxicities associated with anti-estrogen therapies when they may not be benefitting, and, conversely may not be treating the patients that might actually benefit. There is a real need to better identify the patients who are both at most risk of late distant recurrence, and most likely to benefit from EET.

This prospective study included 141 patients with a mean age of 62. In the study, 83% of patients were postmenopausal, 73% were stage I.

Breast Cancer Index (BCI) is a gene expression-based test and is the only currently available validated biomarker that is both prognostic for late distant recurrence and predictive for likelihood of benefit from EET. The purpose of this prospective study was to assess the impact of BCI on: physician EET recommendations; physician confidence; patient satisfaction, anxiety, and decision-conflict; and the cost impact of BCI.

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ALS: Urinary p75ECD as a Prognostic, Disease Progression, and Pharmacodynamic Biomarker

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

Dr. Rogers

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.

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Regular, Long-term Resistance Training or Jump-Training Increases Bone Mass

MedicalResearch.com Interview with:

Pamela S. Hinton, Ph.D. Associate Professor & Director of Graduate Studies Department of Nutrition and Exercise Physiology Columbia MO 65211

Dr. Hinton

Pamela S. Hinton, Ph.D.
Associate Professor & Director of Graduate Studies
Department of Nutrition and Exercise Physiology
Columbia MO 65211

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: This study builds on our previous work showing that weight-bearing, high-impact physical activity throughout the lifespan is associated with greater bone mass in men.  We previously conducted a 12-month randomized trial of the effectiveness of resistance training versus jump training to increase bone mass in men with low bone density of the hip or lumbar spine.

The current study is a follow up study investigating how exercise might work to increase bone mass.

The main findings are that exercise reduced circulating levels of a bone protein that inhibits bone formation (sclerostin) and increased levels of insulin-like growth factor-I (IGF-I), a hormone with osteogenic effects.

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70-Gene Signature Changes 50% of Breast Cancer Chemotherapy Advice

MedicalResearch.com Interview with:
Anne Kuijer, MD

Departments of Surgery and Radiology
University Medical Center Utrecht and
Thijs van Dalen, PhD
Department of Surgery
Netherlands Cancer Institute, Amsterdam

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: In recent years it has become evident that clinicopathological factors fail to accurately determine prognosis in hormone receptor positive early stage breast cancer patients at intermediate risk of developing metastases. Gene-expression profiles, such as the 70-gene signature (MammaPrint) are therefore increasingly used for chemotherapy decision-making. In the current multicentre study we assessed the impact of 70-gene signature use on chemotherapy decisions in these patients. We demonstrated that, without the use of the 70-gene signature, half of patients was advised chemotherapy, which reflects the current controversy regarding chemotherapy benefit. Use of the 70-gene signature changed the chemotherapy advice in half of all patients and adherence to the 70-gene signature result was high.

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Gene “Decorations” Can Serve as Blood Biomarkers To Detect Cancer

MedicalResearch.com Interview with:

Kun Zhang, PhD Professor UCSD Department of Bioengineering La Jolla, CA 92093-0412

Dr. Kun Zhang

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.

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Sleep Duration and Exhaled Nitric Oxide in Asthma and Health Adults

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.

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Genetic Variant of p53 Gene May Explain Increased Breast Cancer Risk in African American Women

MedicalResearch.com Interview with:

Maureen E. Murphy, Ph.D. Professor and Program Leader, Molecular and Cellular Oncogenesis Program Associate Vice President for Faculty Affairs Associate Director for Education and Career Development The Wistar Institute Philadelphia, PA 19104

Dr. Murphy

Maureen E. Murphy, Ph.D.
Professor and Program Leader, Molecular and Cellular Oncogenesis Program
Associate Vice President for Faculty Affairs
Associate Director for Education and Career Development
The Wistar Institute
Philadelphia, PA 19104

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The Murphy group discovered a coding-region variant of the p53 tumor suppressor gene, called Pro47Ser, that exists in individuals of African descent. In previous studies this group reported that this amino acid change reduces the ability of p53 to function as a tumor suppressor.

In this study, African American women from two different large cohorts were assessed for the incidence of the Pro47Ser variant in pre-menopausal breast cancer. A modest but statistically significant association was found between Pro47Ser and pre-menopausal breast cancer.

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Genetic Defect in DNA Repair Enzyme Linked to Prostate Cancer

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.

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5-alpha reductase inhibitors For BPH Linked to Higher, Not Lower, PSA Levels

MedicalResearch.com Interview with:
Teemu J Murtola, MD, PhD, adjunct professor
University of Tampere, Faculty of Medicine and Life Sciences
Tampere University Hospital, Department of Urology
Tampere, Finland

MedicalResearch.com: What is the background for this study?

Response: A previous study called Prostate Cancer Prevention Trial
(PCPT) showed that finasteride, which belongs to a drug group called
5alpha-reductase inhibitors lowers serum PSA and increases sensitivity
of PSA to detect high-grade prostate cancer in men who had little or
no symptoms of the lower urinary tract. We postulated that this effect
would increase the accuracy and benefits of PSA-based prostate cancer
screening.

Finnish Randomized Study of Screening for Prostate Cancer was a large
trial of over 80,000 men randomized either to be screened for prostate
cancer with a PSA test at 4-year intervals or to be followed for
prostate cancer incidence and mortality via national registries. Three
consecutive screening rounds were commenced between 1996-2008. In the
current study we compared the effects of PSA-based screening on
prostate cancer risk and mortality separately among men who were using
5alpha-reductase inhibitors finasteride or dutasteride and among men
who were not.

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Genomic Testing Can Improve Confidence in Prostate Cancer Treatment Strategy

MedicalResearch.com Interview with:

Dr. John L. Gore, MD Associate Professor Adjunct Associate Professor-Surgery Department of Urology University of Washington

Dr. John Gore

Dr. John L. Gore, MD
Associate Professor
Adjunct Associate Professor-Surgery
Department of Urology
University of Washington

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The rationale for our study derives from the uncertainty that both patients and clinicians confront when trying to make decisions about adjuvant therapy for prostate cancers found to have aggressive pathologic features at the time of radical prostatectomy. There is level 1 evidence in support of adjuvant radiation therapy in this setting, but several factors restrain providers from recommending adjuvant radiation. We found that interjecting a genomic test that predicts the risk of clinical metastases 5 years after surgery impacts the treatment recommended and helps men and clinicians feel more confident in the decision they are making or recommending.

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21-Gene Expression Assay May Clarify Need For Chemotherapy in Early Breast Cancer

MedicalResearch.com Interview with:

Carlos H. Barcenas M.D., M.Sc. Assistant Professor Department of Breast Medical Oncology MD Anderson Cancer Center

Dr. Carlos Barcenas

Carlos H. Barcenas M.D., M.Sc.
Assistant Professor
Department of Breast Medical Oncology
MD Anderson Cancer Center

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Over the last decade we have realized that we were over-treating many early stage breast cancer patients. In addition to the chemotherapy’s obvious side effects, there are also long term complications for breast cancer survivors. Since 2005, we are using a 21-gene-expression assay that predicts the risk of distant recurrence among early stage breast cancer patients. In 2015, initial results from the international clinical trial, TAILORx, found that women with hormone receptor positive, HER2 and lymph node negative early stage disease that had a low recurrence score (RS) of 0-10 from this assay could have chemotherapy omitted altogether. While these findings changed care for women with a low RS, questions remain regarding the management of women with an intermediate RS, defined by this trial as a RS of 11-25. For our retrospective, single-institution study we identified 1,424 stage I and II breast cancer patients with hormone receptor positive, HER2 and lymph node negative treated between 2005 and 2011 who underwent the 21-gene expression assay. The RS distribution was: 297 (21 percent) scored 0–10; 894 (63 percent) scored 11-25; and 233 (16 percent) scored >25.

Of those groups, 1.7, 15 and 73.4 percent received chemotherapy, respectively. With a median follow up of 58 months, those with a RS of 11-25 had an invasive disease-free survival (IDFS) rate at five years of 92.6 percent, regardless if patients received chemotherapy or not. Among those patients who did not receive chemotherapy, the estimated rates of IDFS and overall survival was 93 percent and 98 percent, respectively, which was comparable to those who did receive chemotherapy.

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New ‘Blood Biopsies’ with Experimental Device to Speed Cancer Diagnosis and Predict Disease Spread

MedicalResearch.com Interview with:

Edwin Posadas, MD, FACP, KM Director, Translational Oncology Program Medical Director, Urologic Oncology Program Samuel Oschin Comprehensive Cancer Institute

Dr. Edwin Posadas

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.

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New Blood Test May Screen For ATTR Cardiac Amyloidosis

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

Dr. Frederick Ruberg

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.

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Hair Cortisol in the Evaluation of Cushing Syndrome

MedicalResearch.com Interview with:
Mihail Zilbermint, M.D.
Endocrinologist, Office of the Scientific Director

Mihail Zilbermint, M.D. Endocrinologist, Office of the Scientific Director Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health

Eunice Kennedy Shriver
National Institute of Child Health and Human Development
National Institutes of Health 

MedicalResearch.com: What is the background for this study?

Response: Diagnosing Cushing Syndrome is often difficult and challenging.  Diagnosing hypercortisolemia, could require the use of a combination of any of these tests: 24-hour free urine cortisol monitoring, an overnight dexamethasone suppression test, and measurement of late night salivary cortisol.  Cortisol levels may change daily, requiring that testing be repeated.  Undiagnosed and untreated Cushing Syndrome greatly increases morbidity and mortality risk.

Cortisol levels can be detected in hair samples.  Much like hemoglobin A1C is a long-term indicator of blood glucose levels, efforts have been made to determine if hair cortisol could serve as a long-term measure of the body’s glucocorticoid levels.  We sought to compare the results of cortisol levels for Cushing Syndrome patients with data from data on cortisol in hair segments, to gain further information on the role of sampling hair cortisol as an initial or supportive method for diagnosing Cushing Syndrome.

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Gene Variant That Controls Tumor Metabolism Linked To Breast Cancer Risk

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

Dr. Ulrich Pfeffer

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.

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DNA Methylation Allows Head and Neck Tumors To Be SubClassified

MedicalResearch.com Interview with:

Jacek Majewski PhD Associate Professor Department of Human Genetics McGill University and Genome Quebec Innovation Centre Montreal, Canada

Dr. Jacek Majewski

Jacek Majewski PhD
Associate Professor
Department of Human Genetics
McGill University and Genome Quebec Innovation Centre
Montreal, Canada 

MedicalResearch.com: What is the background for this study?

Response: Our lab, in collaboration with Dr. Nada Jabado, has been investigating the molecular genetics of pediatric glioblastoma – a deadly brain cancer. Several years ago, in the majority of our patients’ tumors we discovered mutations in genes that encode histone proteins. Those mutations disrupt the epigenome – that is the way the DNA is modified, silenced, or activated in the cancer cells. It appears that epigenome-modifying mutations are particularly important in pediatric cancers, and our hypothesis is that they act by diverting the normal developmental pathways into unrestrained proliferation. Many other studies have highlighted the significance of epigenome disruption in a number of cancers.

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Fall in PSA Best Predictor of Mortality After Prostate Cancer Treatment

MedicalResearch.com Interview with:

Trevor Royce MD MS
Resident, Harvard Radiation Oncology Program

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Clinical trials in early prostate cancer take more than a decade to report on.

Multiple early reporting endpoints have been proposed, but which one is best, remains unknown, until now. Of all the possible early endpoints examined, to date, how low a PSA blood test falls to, after treatment with radiation and hormonal therapy, appears to be the best, specifically, if the PSA doesn’t get below half a point, that patient is very likely to die of prostate cancer if given standard treatment for recurrence.

Those men deserve prompt enrollment on clinical trials in order to properly save their life.

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