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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