Advanced Prostate Cancer: Androgen-Receptor Testing May Guide Selection of Treatment

MedicalResearch.com Interview with:

Diagram_showing_prostate_cancer_that_has_spread_to_the_bones_CRUK_183.svg.png

Prostate cancer that has metastasized to the bone: Wikipedia Image

Vincenza Conteduca, MD, PhD
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) Srl – IRCCS
Meldola , Italy

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

Response: In our previous publications, we showed that the study of plasma cell-free DNA holds promise for improving treatment choice in metastatic castration-resistant prostate cancer (mCRPC). Specifically, we demonstrated that the detection in plasma of aberrations (copy number alterations and/or point somatic mutations) of androgen receptor (AR), using an easy and robust multiplex droplet digital PCR method, predicted an adverse outcome in mCRPC patients treated with second-generation AR-directed therapies (abiraterone or enzalutamide) in both settings: chemotherapy-naïve and post-docetaxel.

This current multi-institution work builds on our previous discoveries. We investigated the association of androgen receptor status and survival in men treated with docetaxel. Moreover, we performed an exploratory analysis in patients treated with docetaxel or AR-directed therapies as first-line therapy.

Interestingly, we observed that plasma AR-gained patients do not have a worse outcome compared to AR-normal patients when treated with docetaxel as first-line therapy. This introduces the opportunity to use plasma to select for docetaxel in preference to androgen receptor-directed therapies in AR gained mCRPC patients.

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Panel of Salivary RNA Biomarkers Could Identify Autism

MedicalResearch.com Interview with:

Steven D. Hicks, M.D.,Ph.D Department of Pediatrics Penn State College of Medicine Hershey, PA

Dr. Hicks

Steven D. Hicks, M.D.,Ph.D
Department of Pediatrics
Penn State College of Medicine
Hershey, PA

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

Response: Since autism has both genetic and environmental underpinnings, my colleagues and I suspected that transcriptional elements (e.g. regulatory RNA molecules) might be different in the saliva of children with autism compared to peers without autism. We used a non-biased approach to analyze saliva from 372 children, and allowed machine learning techniques to inform which RNA elements best predicted autism status. To our surprise, microbial RNA levels and human RNA levels were equally powerful in predicting which children had autism. This may be because some children with autism eat restricted diets, resist tooth brushing, or put foreign objects in their mouths. The end result was a panel of 32 RNAs (20 human and 12 bacterial) that identified autism with 87% accuracy. Interestingly, when we tested the panel in a completely separate set of 84 children (including children from a different geographic region) the accuracy remained 88%. 

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Serum Neurofilament Biomarker Helps Determine if Brain Function Will Recover After Cardiac Arrest

MedicalResearch.com Interview with:

Dr-Marion Moseby-Knappe

Dr. Moseby-Knappe

Marion Moseby-Knappe, MD
Neurologist and Researcher
Center for Cardiac Arrest at Lund University and
Skane University Hospital
Lund, Sweden

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

Response: Our research focuses on improving methods for examining unconscious patients treated on intensive care units after cardiac arrest. If a patient does not wake up within the first days after cardiac arrest, physicians need to evaluate how likely it is that the patient will awaken at all and to which extent there is brain injury.

According to European and American guidelines, decisions on further medical treatment of cardiac arrest patients should always be based on a combination of examinations and not only one single method. Various methods are combined when assessing the patient such as examining different neurologic reflexes, head scans (computed tomography or magnetic resonance imaging), other specialist examinations (electroencephalogram or somatosensory evoked potentials) or blood markers.

Our research focuses on patients included in the largest cardiac arrest trial to date, the Targeted Temperature Management after Out-of-Hospital Cardiac Arrest (TTM) Trial.

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Gene Signature Blood Test Can Diagnose TB and Treatment Response

MedicalResearch.com Interview with:
"Mycobacterium tuberculosis Bacteria, the Cause of TB" by NIAID is licensed under CC BY 2.0Purvesh Khatri, Ph.D.
Associate Professor
Stanford Institute for Immunity, Transplantation and Infection (ITI)
Stanford Center for Biomedical Informatics Research (BMIR)
Department of Medicine
Stanford University
Stanford, CA 94305

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

Response: We have previously described a 3-gene signature for distinguishing patients with active tuberculosis (ATB) from those with other diseases, latent mycobacterium tuberculosis (LTB) infection, and healthy controls (Sweeney et al. Lancet Respir Med 2016).

The current study in JAMA Network Open is a follow up study to validate the 3-gene signature in 3 additional independent cohorts that were prospectively collected.

Using these 3 cohorts we have now showed that the 3-gene signature

(1) can identify patients with LTB that will progress to ATB about 6 months prior to diagnosis of active tuberculosis.

(2) can identify patients with ATB in active screening, and

(3) can identify patients with ATB at diagnosis that have higher likelihood of persistent lung inflammation due to subclinical ATB at the end of treatment.  Continue reading

Computer Algorithm Can Distinguish Dangerous From Manageable Prostate Cancer

MedicalResearch.com Interview with:

Davide Pellacani Ph.D. Postdoctoral Fellow, Eaves' Lab Terry Fox Laboratory, BC Cancer Research Centre Vancouver, BC

Dr. Pellacani

Davide Pellacani Ph.D.
Postdoctoral Fellow, Eaves’ Lab
Terry Fox Laboratory,
BC Cancer Research Centre
Vancouver, BC

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

Response: Prostate cancer is characterized by frequent DNA methylation changes compared to normal tissue. Nevertheless, understanding which of those changes lead to the acquisition of malignant proprieties is complicated by the predominance of cells with luminal features in prostate cancers.

In this study we generated DNA methylation maps of two distinct cell populations found within prostate cancer samples (called basal and luminal) and their normal counterparts. These datasets clearly showed that many of the common DNA methylation changes found in prostate cancer are present in luminal cells from both cancer and normal tissues. These changes are not necessarily cancer-specific, and are likely due to the bias associated with analyzing tissues in bulk, where most cancer cells have luminal-like features.

We used these datasets to derive two cancer-specific and phenotype-independent DNA methylation signatures: one specific to prostate cancer luminal cells, and one composed of changes measured in both luminal and basal cancer cells.

We then validated the potential clinical utility of these signatures by testing their ability to distinguish prostate cancer from normal samples, and tumours that have already escaped the prostate from those that have not, using the publicly available dataset from The Cancer Genome Atlas.

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TumorScan May Become a Universal Screening Blood Test For Cancer

MedicalResearch.com Interview with:

Professor Diana Anderson Established Chair in Biomedical Sciences The University of Bradford Richmond Road Bradford West Yorkshire

Prof Anderson

Prof. Diana Anderson
Established Chair in Biomedical Sciences
The University of Bradford Richmond Road Bradford West Yorkshire

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

Response: I have worked in this field for over 40 years both as a research scientist in industry and as a university-based researcher. It has always been my ambition to develop a relatively simple and affordable test to predict if a person is sensitive to cancer. In fact, in 1974, I was appointed as Head of Mutagenesis Studies at ICI’s Central Toxicology Laboratory in Manchester, UK, and I was looking at developing a short-term test to predict cancer even back then.

Our ‘universal’ cancer test is different from other ‘universal’ tests being developed, because ours is not looking for a specific biomarker or mutation. Ours is a generic test for cancer in an individual, regardless of any underlying mechanism that’s causing their cancer.

It is known that levels of damage to the DNA in the cellular genome can correlate with cancer and this is what we set out to investigate with the Comet assay.

Of the available tests to detect damage to the genome the Comet assay is very straightforward. This assay was primarily developed as a method to measure DNA damage. Briefly, cells are embedded in agarose on a microscope slide and lysed to remove membranes leaving supercoiled DNA loops, breaks in which after alkaline treatment and alkaline electrophoresis move towards a positive charge. The DNA is stained with a fluorescent dye and visualised by fluorescent microscopy. The image is like Haley‘s comet and the greater number of breaks the greater is the migration to the anode and the greater the damage.  Continue reading

New Point-of-Care Troponin Assay Can Rapidly Rule Out Heart Attack

MedicalResearch.com Interview with:

Dr John W Pickering, BSc(Hons), PhD, BA(Hons) Associate Professor , Senior Research Fellow in Acute Care Emergency Care Foundation, Canterbury Medical Research Foundation, Canterbury District Health Board |  Christchurch Hospital Research Associate Professor | Department of Medicine University of Otago Christchurch

Prof. Pickering

Dr John W Pickering, BSc(Hons), PhD, BA(Hons)
Associate Professor , Senior Research Fellow in Acute Care
Emergency Care Foundation, Canterbury Medical Research Foundation, Canterbury District Health Board |  Christchurch Hospital
Research Associate Professor | Department of Medicine
University of Otago Christchurch

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

Response: The assessment of patients with suspected myocardial infarction is one of the most common tasks in the emergency department. Most patients assessed (80 to 98% depending on the health system) are ultimate not diagnosed with an MI.   High-sensitivity troponin assays have been shown to have sufficient precision at low concentrations to allow very early rule-out of myocardial infarction. However, these are lab-based assays which typically result in a delay from blood sampling before the result is available and the physician is able to return to a patient to make a decision to release the patient or undertake further investigation. Point-of-care assays provide results much quicker, but have to-date not had the analytical characteristics that allow precise measurements at low concentrations.

In this pilot study we demonstrated that a single measurement with a new point-of-care assay (TnI-Nx; Abbott Point of Care) which can measure low troponin concentrations, could safely be used to rule-out myocardial infarction a large proportion of patients (57%). The performance was at least comparable to the high-sensitivity troponin I assay, if not a little better (44%).

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Proteomics Leads to Discovery of Ovarian Cancer Protein Biomarker

MedicalResearch.com Interview with:

Site of Ovarian Cancer - Wikipedia Image

Site of Ovarian Cancer – Wikipedia Image

Fabian Coscia PhD
Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, German and
Ernst Lengyel MD PhD
Department of Obstetrics and Gynecology
Section of Gynecologic Oncology
University of Chicago, Chicago, IL 


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

Response: Ovarian cancer is a very aggressive disease. Only one in six patients survives more than 10 years after the first diagnosis. This high mortality is primarily because the disease is usually detected late in its course, when the tumor has already spread from the ovaries to the surrounding organs in the abdomen.

In an interdisciplinary collaboration between the Max Planck Institute of Biochemistry in Martinsried, Munich, the University of Chicago and the University of Copenhagen, we performed deep tissue proteomics on archived biobank material to identify drivers of long-term patient survival.  Continue reading

Clinical Chemistry Score Helps Rule Out Diagnosis of Heart Attack

MedicalResearch.com Interview with:

Peter Kavsak, PhD, FCACB, FAACC, FCCS Professor, Pathology and Molecular Medicine McMaster University 

Prof.. Kavsak

Peter Kavsak, PhD, FCACB, FAACC, FCCS
Professor, Pathology and Molecular Medicine
McMaster University 

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

Response: For patients who present to the hospital with symptoms suggestive of acute coronary syndrome (ACS) the preferred blood test to help physicians in making a diagnosis is cardiac troponin.

Recent studies have demonstrated that a very low or undetectable cardiac troponin level when measured with the newest generation of blood tests (i.e., the high-sensitivity cardiac troponin tests) in this population may rule-out myocardial infarction (MI or a heart attack) on the initial blood sample collected in the emergency department, thus enabling a faster decision and foregoing the need for subsequent serial measurements of cardiac troponin over several hours as recommended by the guidelines. The problem with this approach, however, is that using high-sensitivity cardiac troponin alone to do this has not reliably been demonstrated to achieve a sensitivity >99% for detecting MI, which is the estimate that most physicians in this setting consider as safe for discharge.

Our study goal was to compare the diagnostic performance of a simple laboratory algorithm using common blood tests (i.e., a clinical chemistry score (CCS) consisting of glucose, estimated glomerular filtration rate (eGFR), and either high-sensitivity cardiac troponin I or T) to high-sensitivity cardiac troponin alone for predicting MI or death within the first month following the initial blood work. Continue reading

Kidney Cancer: Biomarker Linked to Detection and Progression

MedicalResearch.com Interview with:

Dr. David Muller, PhD  Faculty of Medicine, School of Public Health Research Fellow in Epidemiology and Biostatistics Imperial College London

Dr. Muller

Dr. David C. Muller PhD
Faculty of Medicine, School of Public Health
Research Fellow in Epidemiology and Biostatistics
Imperial College, London

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

Response: Our colleagues in the U.S. have been working on KIM-1 for years, particularly in the context of chronic kidney disease. Recently they found that KIM-1 is also elevated at the time of diagnosis of kidney cancer.

We wanted to see if KIM-1 concentrations could predict the chances of a future diagnosis of kidney cancer. We found that KIM-1 was a strong predictor of being diagnosis with kidney cancer in the next 5 years. We also found that higher pre-diagnostic KIM-1 was associated with worse survival after diagnosis.  Continue reading

Gastric Cancer: Gene Mutation Predictive of Response to Immunotherapy

MedicalResearch.com Interview with:

Wei Zhang, Ph.D. Hanes and Willis Family Professor in Cancer Director Cancer Genomics and Precision Oncology Wake Forest Baptist Comprehensive Cancer Center Winston-Salem, NC  27157-1082

Prof. Zhang

Wei Zhang, Ph.D.
Hanes and Willis Family Professor in Cancer
Director
Cancer Genomics and Precision Oncology
Wake Forest Baptist Comprehensive Cancer Center
Winston-Salem, NC  27157-1082

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

Response: Gastric cancer is a leading cause of cancer-related death worldwide. Infection by the Helicobacter pylori is the major cause of gastric cancer, which accounts for more than 60% of cases. Despite progress in helicobacter pylori eradication and early cancer diagnosis, the five-year survival rate of gastric cancer remains less than 30%. Gastric cancer is one of the most common cancer types in Asia but the incidence for gastric cancer has seen a steadily increase in the United States in recent years.

Immunotherapy treatment has shown remarkable benefit for some cancer patients whereas others experience toxicities. It is important to identify markers that help oncologists decide which patient would benefit from this promising new treatment strategy. It has been suggested that gastric cancer that is positive for Epstein-Barr Virus is likely more responsive to immunotherapy but only about 10% of gastric cancer patients belong to this category. More potential markers are urgently needed for clinical practice.

There is accumulating evidence that high tumor mutation load, which means there are high numbers of gene mutations in the tumor, can provide a signal to activate immune response systems thus rendering tumors more sensitive to immunotherapy.

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New Biomarkers Predictive of Atrial Fibrillation Outcome

MedicalResearch.com Interview with:

John D Horowitz, MBBS, PhD. Director of Cardiology/Clinical Pharmacology Queen Elizabeth Hospital University of Adelaide Australia

Dr. Horowitz

John D Horowitz, MBBS, PhD.
Director of Cardiology/Clinical Pharmacology
Queen Elizabeth Hospital
University of Adelaide
Australia 

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

Response:  Atrial fibrillation (AF) describes intermittent or permanent episodes of irregular pulse, due to rapid electrical activity within the atria (filling chambers) of the heart. During AF, the atria quiver, rather than contract, and the response of the ventricles is often rapid, resulting in palpitations and an increased risk of development of heart failure. AF may occur at any age, but is most common in ageing patients (typically over 75 years). The primary importance of AF is that it markedly increases the risk of thrombus formation in the atrium, with the resultant problem that these thrombi may dislodge (embolise), and commonly block arteries in the brain, causing strokes. Hence patients with AF are usually treated with anticoagulants.

Although AF often occurs in patients with prior damage to their hearts and atrial distension, there has been evidence for about the past 8 years that AF also is caused, at least in part, by inflammatory changes: two components have been identified as possible causes for this inflammation: lack of nitric oxide (NO) effect[ NO is  an anti-inflammatory chemical formed by all tissues in the body],  and excess activity of the pro-inflammatory enzyme myeloperoxidase (MPO).  High concentrations of ADMA, which inhibits NO formation, may result from effects of MPO on tissues. SDMA, which is closely related to ADMA, also exerts pro-inflammatory effects and tends to suppress NO formation.

The currently reported study began with the design of the ARISTOTLE trial, an investigation of the (then) novel anticoagulant apixaban as an alternative to warfarin therapy, as a means of preventing strokes in patients with AF. It was elected to perform a substudy to investigate the potential role of ADMA and SDMA as modulators of risk in patients with atrial fibrillation.

This substudy, performed in just over 5000 patients from the ARISTOTLE trial, essentially asked two questions:

(1) There are several indices of stroke risk in patients with atrial fibrillation, such as the CHADS2 score. These all rely on patient characteristics (eg age, presence of diabetes) rather than chemical changes. We postulated that there would be a direct relationship between clinically based risk scores and ADMA/SDMA concentrations.

(2) More ambitiously, we postulated that ADMA and SDMA concentrations would represent INDEPENDENT risk markers for major adverse effects in atrial fibrillation patients on anticoagulant treatment, namely stroke, major bleeding and risk of mortality. 

ADMA/SDMA concentrations were determined in Adelaide, Australia, while statistical analyses were performed in Uppsala, Sweden.

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Novel Mechanisms and Clinical Aspects for an Aggressive Prostate Cancer Risk Locus Uncovered

MedicalResearch.com Interview with:

Gong-Hong Wei, PhD Professor, Academy Research Fellow Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu University of Oulu, Finland

Dr. Gong-Hong Wei,

Gong-Hong Wei, PhD
Professor, Academy Research Fellow
Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu
University of Oulu, Finland

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

Response: Prostate cancer is the second most common cancer and the fifth leading cause of cancer-related death in men, with more than 1,100,000 new cases diagnosed and 300,000 deaths yearly around the globe. Among the risk factors for prostate cancer development, the genetic heritability of prostate cancer has been reported near 60%. Over the past decade, genome-wide association studies have identified more than 150 independent single nucleotide polymorphisms (SNPs) associated with prostate cancer risk. However, we know very little mechanisms accounting for these associations.

SNP rs11672691 at the chromosome 19q13 locus has been found not only associated with prostate cancer risk but also aggressiveness, a form of prostate cancer often with worse prognosis and eventually progression to incurable stage. However, how this genomic variant accounts for prostate cancer severity remains totally unknown. Here we found the association of rs11672691 with additional clinical features of aggressive prostate cancer in an independent cohort of patients with prostate cancer, and discovered a rs11672691-mediated gene regulatory network including several novel genes, HOXA2, CEACAM21 and PCAT19, likely causing prostate cancer progression to incurable stage. In particular, the risk G (guanine) allele of rs11672691 was associated with higher RNA levels of PCAT19 and CEACAM21, and poor prognosis in prostate cancer patients. Rs11672691 G allele enhances chromatin binding of HOXA2 to regulate the expression of CEACAM21 and PCAT19. Using the CRISPR-Cas9 genome editing method, we revealed that rs11672691 genotype directly influence HOXA2 in regulating PCAT19 and CEACAM21 expression, and prostate cancer cellular phenotype.

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Non-Invasive Liquid Biopsy Can Detect Deep Seated Infections

MedicalResearch.com Interview with:

David K. Hong, M.D. VP Medical Affairs and Clinical Development at Karius

Dr. Hong


David K. Hong, M.D.

VP Medical Affairs and Clinical Development at Karius

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

Response: Invasive fungal infections (IFI) are a cause of significant mortality and morbidity in immunocompromised patients. The diagnosis of IFIs is challenging, and often requires an invasive biopsy in order to identify the causal pathogen. There is a need for non-invasive methods of fungal identification to help guide targeted anti-fungal therapy.

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Gene Biomarker Can Predict Brain Tumor Patients Who Have Better Outcomes

MedicalResearch.com Interview with:

Arnab Chakravarti MD Professor and Chair of Radiation Oncology Arthur G. James Cancer Hospital and Richard J. Solove Research Institute The Ohio State University Comprehensive Cancer Center

Dr. Chakravarti

Arnab Chakravarti MD
Professor and Chair of Radiation Oncology
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
The Ohio State University Comprehensive Cancer Center

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

Response: Historically, the treatment for grade two gliomas has been a black box without really a standard-of-care therapy. In the past, it was really dealer’s choice, where it was based upon physician and patient preference. Either radiation alone, radiation plus chemotherapy, or chemotherapy alone, there wasn’t really any data to guide therapeutic decision-making. Then about three years ago the landmark study RTOG 9802 was published, which demonstrated a survival benefit with the addition of chemotherapy to radiation versus radiation alone. That became the standard of care for the treatment of grade two gliomas.

One of the tricky issues with regards to these tumors is that there’s a wide range of outcomes.

There are patients that succumb to disease within months, others that live decades. It’s very
important to personalize care for the individual patient and that’s why biomarkers, prognostic and predictive biomarkers are so important. The 9802 study showed us for the general population of patients that the addition of chemotherapy to radiation improved outcomes versus radiation alone.

The patient population that was selected for our study were the high-risk low-grade glioma
patients. Patients who are generally over the age of 40, tumor sizes that exceeded 6 cm in terms of maximum dimension, tumors that invaded the corpus callosum, astrocytic histology of patients with neurological symptoms. These are typically the patients that were included in the study. Really the main objective of this study was to determine the efficacy of treatment compared to historical controls. Continue reading

Trial of Antibody Immunotherapy in Parkinson’s Disease

MedicalResearch.com Interview with:

Joseph Jankovic, MD Professor of Neurology  Distinguished Chair in Movement Disorders  Director, Parkinson’s Disease Center  and Movement Disorders Clinic  Department of Neurology                                    Baylor College of Medicine  Baylor St. Luke’s Medical Center at the McNair Campus Houston, TX 77030-4202

Dr. Jankovic

Joseph Jankovic, MD
Professor of Neurology
Distinguished Chair in Movement Disorders
Director, Parkinson’s Disease Center
and Movement Disorders Clinic
Department of Neurology
Baylor College of Medicine
Baylor St. Luke’s Medical Center at the McNair Campus
Houston, TX 77030-4202

 

MedicalResearch.com: What should readers take away from your study? 

  • First demonstration of an anti-α-synuclein antibody immunotherapy in patients with Parkinson’s Disease.
  • Robust target engagement led to mean reduction of up to 97% in serum free α-synuclein levels.
  • Central Nervous System penetration is supported by a dose-dependent increase in PRX002/RG7935 levels in Cerebral Spinal Fluid.
  • All dose levels of PRX002/RG7935 had acceptable safety and tolerability profiles, meeting the primary objective of this study
  • Data support ongoing PASADENA Phase 2 clinical study of PRX002/RG7935 (NCT03100149)  

Citation:

Jankovic J, Goodman I, Safirstein B, et al. Safety and Tolerability of Multiple Ascending Doses of PRX002/RG7935, an Anti–α-Synuclein Monoclonal Antibody, in Patients With Parkinson DiseaseA Randomized Clinical TrialJAMA Neurol. Published online June 18, 2018. doi:10.1001/jamaneurol.2018.1487 

 

 

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Biochemical Test Promises To Aid in Diagnosis of ASD

MedicalResearch.com Interview with:

Juergen Hahn Professor and Department Head Department of Biomedical Engineering Department of Chemical & Biological Engineering Center for Biotechnology and Interdisciplinary Studies Rensselaer Polytechnic Institute

Prof. Hahn

Juergen Hahn,  Professor and Department Head
Department of Biomedical Engineering Department of Chemical & Biological Engineering Center for Biotechnology and Interdisciplinary Studies Rensselaer
Polytechnic Institute 

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

Response: Autism Spectrum Disorder (ASD) encompasses a large group of early‐onset developmental disorders that are collectively characterized by deficits in social interaction and communication as well as the expression of restricted, repetitive behaviors and interests. ASD is currently estimated to affect 1 in 59 children in the US. Despite this high prevalence, relatively little is know about the pathophysiology of ASD. The result of this is that no lab test exists for ASD and the diagnosis is based upon observations of the child. The average age of diagnosis is 4 years of age, but it is generally acknowledged that diagnosis at 2 years of age is possible and desirable. Continue reading

Synovial tissue profiling in autoantibody positive at risk individuals reveals gene signatures associated with later development of rheumatoid arthritis

MedicalResearch.com Interview with:

Dr. Lisa van Baarsen PhD Principal Investigator at the Amsterdam Rheumatology and Immunology Cente Academic Medical Center the Netherlands.

Dr. van Baarsen

Dr. Lisa van Baarsen PhD
Principal Investigator at the Amsterdam Rheumatology and Immunology Cente
Academic Medical Center
the Netherlands 

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

Response: The discovery that autoantibodies can be present years before the onset of clinical symptoms of rheumatoid arthritis (RA) enables us to study autoantibody positive individuals who are at risk of developing RA. In patients with established disease the target tissue of RA, the synovial joints, is characterized by cellular infiltration and inflammation. Moreover, successful therapy decreases this synovial inflammation. In the past, our department already showed (PMID: 21177292; PMID: 24574210) that in autoantibody positive at risk individuals there is no overt cellular infiltration present in the synovium.

In the current study we performed a so called discovery-based approach to investigate at a genome-wide gene expression level (using microarrays) whether the synovium is altered at a molecular level before onset of rheumatoid arthritis.

Our molecular and microscopic studies on synovial biopsies obtained from autoantibody positive individuals indeed revealed interesting differences between those at risk individuals who developed disease after follow up and those who did not. Continue reading

PDL1 Amplification Linked To Positive Response to Checkpoint Blockers

MedicalResearch.com Interview with

Aaron Goodman, MD Hematologist/Medical Oncologist Assistant Professor of Medicine UC San Diego Health

Dr. Goodman

Aaron Goodman, MD
Hematologist/Medical Oncologist
Assistant Professor of Medicine
UC San Diego Health 

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

Response: Response rates to PD-1/PD-L1 blockade in solid tumors are reported at 10-20%.  Remarkably, response rates of 65% to 87% have been reported in patients with refractory classical Hodgkin lymphoma treated with checkpoint inhibitors.

In nodular sclerosing Hodgkin lymphoma, amplification of the chromosomal region 9p24.1, which contains the genes PD-L1 (CD274)PDCD1LG2 (PD-L2)and JAK2, is directly correlated with increased expression of these proteins on Reed–Sternberg cells.

Overall, 105 of 108 (97%) biopsies from patients with newly diagnosed classical Hodgkin lymphoma have increased PD-L1 and PDCD1LG2 copy numbers.  The prevalence and utility of PD-L1amplification as a response biomarker to PD-1/PD-L1 blockade is unknown in other tumors.

We sought to determine the prevalence and utility of PD-L1 amplification as a response biomarker to PD-1/PD-L1 blockade in solid tumors.  Continue reading

New Test Can Identify Asthma With Nasal Brush Biomarker

MedicalResearch.com Interview with:
Dr. Supinda Bunyavanich MD

Pediatric Allergy and Immunology
Physician and researcher at the Icahn School of Medicine.

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

Response: In this study, we report on an accurate asthma biomarker we have developed based on a simple nasal brush.

Nasal Brush-based Classifier of Asthma

Asthma is a chronic respiratory disease that affects 10% of children and adults in the U.S. Mild to moderate asthma can be difficult to diagnose because symptoms change over time and can be complicated by other respiratory conditions. Given the high prevalence of asthma, there is high potential impact of improved diagnostic tools on reducing morbidity and mortality from asthma.

Current diagnostic tools for asthma, including spirometry and bronchoscopy, require specialized equipment and expertise to operate properly. Many individuals, particularly young children, have difficulty with pulmonary function testing because it requires, coordinated, forced breaths into a device. Spirometry results are unreliable when done with poor technique. Bronchoscopy is not practical for mild to moderate symptoms. For these reasons, asthma is often diagnosed and managed based on self-reporting of symptoms  This can be unreliable, resulting in repeated doctor visits and even trips to the ER. Thus, a biomarker test for asthma that is easy to implement and interpret is highly desirable for the diagnosis and management of asthma. Continue reading

Urinary Biomarkers Identify Early Problems With Hip Replacements

MedicalResearch.com Interview with:

Rick Sumner, PhD, FAAA The Mary Lou Bell McGrew Presidential Professor for Medical Research Chair, Department of Cell & Molecular Medicine (formerly, Anatomy and Cell Biology) Rush University Medical Center Chicago, IL  60612

Dr. Sumner

Rick Sumner, PhD, FAAA
The Mary Lou Bell McGrew Presidential Professor for Medical Research
Chair, Department of Cell & Molecular Medicine (formerly, Anatomy and Cell Biology)
Rush University Medical Center
Chicago, IL  60612

 

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

Response: The main cause of failure for total hip replacements is implant loosening which is often a consequence of particle-induced peri-implant osteolysis. Unfortunately, this condition is usually not diagnosed until it has progressed to the point of needing a revision surgery.

We discovered two biomarkers that may be useful for identifying at risk patients much earlier than is currently possible. Continue reading

PlaqueTec Liquid Biopsies Give Alternative Data To Systemic Biomarkers

MedicalResearch.com Interview with:
PlaqueTec liquid biopsiesDr. Nick West, MD
PlaqueTec Chief Medical Officer and Consultant Interventional Cardiologist
Royal Papworth Hospital NHS Foundation Trust  

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

Response: Recent data have identified residual inflammatory risk as a potential therapeutic target to modulate future risk of coronary and vascular events independent of cholesterol lowering1. This approach has now been validated by the CANTOS study, showing reduction of peripheral blood levels of high-sensitivity CRP (hsCRP) and consequent reduction of the occurrence of major cardiac events in patients who had sustained a myocardial infarction2,3. Although controversy continues to rage regarding the relevance of ‘vulnerable plaque’ versus ‘vulnerable patient’ in the causation of acute coronary events, evolving data suggest a complex interplay between a proinflammatory milieu and ‘vulnerable’ plaque phenotypes 4,5 .

We used a novel dedicated intracoronary sampling catheter, the PlaqueTec Liquid Biopsy SystemTM (LBS), and sought to correlate systemic inflammatory indices with degree of local coronary inflammatory activity. The LBS has previously been validated to safely delineate the presence of gradients of inflammatory biomolecules in human coronary artery disease6. We measured blood levels of a large panel of inflammatory biomolecules using multiplexed assays in peripheral blood and in coronary-derived blood samples after balloon dilatation of coronary stenoses during coronary angioplasty, and assessed systemic levels of hsCRP by ELISA.

MedicalResearch.com: What are the main findings? 

Response: Statistical analysis using K-means indicated our patient population (n=23), predominantly patients with stable angina, segregated into 2 discrete clusters of high and low overall coronary inflammatory states. However, when compared with peripheral (systemic) levels of the same inflammatory biomolecules in each cluster, there was no meaningful relationship. Additionally, there was no difference between median hsCRP measurements between the 2 clusters. Taken together, these data suggest that simply measuring peripheral markers of inflammation may not be able to determine local inflammatory activity within the coronary artery itself. 

MedicalResearch.com: What should readers take away from your report?
What recommendations do you have for future research as a result of this work?

Response: These data provide interesting and hypothesis-generating data that explore the mechanisms of benefit in vascular risk by reducing systemic inflammation; rather than hsCRP acting as a simple ‘barometer’ for likelihood of events, it appears that presence of coronary inflammation may be an independent entity. Further studies are needed to address the complex relationship between systemic and coronary inflammation, and their respective interaction with ‘vulnerable’ plaque phenotypes in modulating patient events.

Disclosures: Dr West acts as a consultant to, and holds equity in, PlaqueTec Ltd.

Citations:

  1. Ridker PM. Residual inflammatory risk: addressing the obverse side of the atherosclerosis prevention coin. Eur Heart J 2016; 37: 1720-22.
  2. Ridker PM, Everett BM, Thuren T et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med 2017; 377: 1119-31.
  3. Ridker PM, MacFadyen JG, Everett BM et al. Relationship of C-reactive protein reduction to cardiovascular event reduction following treatment with canakinumab: a secondary analysis from the CANTOS randomissed controlled trial. Lancet 2018; 391: 319-28.
  4. Libby P, Pasterkamp G. Requiem for the vulnerable plaque. Eur Heart J 2015; 36: 2984-7.
  5. Hansson GK, Libby P, Tabas I. Inflammation and plaque vulnerability. J Intern Med 2015; 278: 483-93.
  6. West NEJ, Corrigan JP, Owen RHG et al. Percutaneous sampling of local biomolecule gradients across coronary artery atherosclerotic plaques. J Am Coll Cardiol Basic Trans Science 2017; 2: 646-54.

Citation:

PlaqueTec Data Presented at EAS Show Lack of Correlation 
between Localised Coronary Artery Inflammatory Biomarker Expression and Systemic Elevation of Biomarkers including hsCRP

 

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Amyloid Biomarker Predictive of Mortality in Non-STEMI Heart Attack

MedicalResearch.com Interview with:

Prof. Dr. med. Konstantinos Stellos,MD, FAHA, FESC Cardiovascular Research Centre, Institute of Genetic Medicine Newcastle upon Tyne United Kingdom

Prof. Stellos

Prof. Dr. med. Konstantinos Stellos,MD, FAHA, FESC
Cardiovascular Research Centre, Institute of Genetic Medicine
Newcastle upon Tyne
United Kingdom

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

 

Response: Risk stratification of patients with a non-ST-segment elevation acute coronary syndrome (NSTE-ACS) remains a major challenge in clinical cardiology. Risk stratification is important to identify patients at high risk, to whom an early coronary intervention with optimal adjunctive medical therapy shall be applied to reduce that risk. Conversely, it is equally important to identify patients at low risk, to whom a potentially hazardous invasive therapy or a multi-drug administration shall be avoided. Current ACC/AHA and ESC guidelines agree in a standardized approach that uses Global Registry of Acute Coronary Events (GRACE) score, a well validated scoring system, to calculate a patient’s risk and guide triage and management decisions.

Amyloid-β (Aβ) 1-40 and 1-42 peptides (Aβ40 and Aβ42), are proteolytic fragments of a larger protein, the amyloid precursor protein (APP) cleaved by β- and γ-secretases, found in typical brain amyloid deposits in Alzheimer’s disease. Many lines of evidence support a role of Aβ40 in cardiovascular disease as a peptide with pro-inflammatory and pro-thrombotic properties. Most cardiovascular risk factors seem to affect APP metabolism and thus, Aβ production and its soluble circulating APP770 isoform are elevated in patients with ACS_ENREF_15, suggesting a role for Aβ40 in the triggering and outcome of ACS in stable CAD patients. Although vascular inflammation is considered as a hallmark in the pathophysiologic pathways of coronary artery disease (CAD) and novel mechanisms are continuously recognized in its pathogenesis, no inflammatory marker is currently recommended for risk stratification of patients with NSTE-ACS individually or as a component of the GRACE score. This may partly explain the moderate discriminative ability of GRACE score in some studies, especially in older patients and those after early percutaneous coronary intervention (PCI).

In this retrospective study, we used data from two independent prospective cohorts, the Heidelberg study (n=1,145) and the validation multicenter international APACE (Advantageous Predictors of Acute Coronary Syndrome Evaluation, n=734) study and determined the clinical prognostic and reclassification value of baseline circulating Aβ40 levels in the prediction of mortality over the GRACE risk score in patients with NSTE-ACS across a median follow-up of 21.9 ( Heidelberg cohort) and 24.9 months (APACE cohort), respectively.

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Can a Pill Plus Infrared Light Replace Mammograms?

MedicalResearch.com Interview with:

Greg Thurber, PhD Assistant Professor Department of Chemical Engineering Assistant Professor Department of Biomedical Engineering University of Michigan 

Dr. Thurber

Greg Thurber, PhD
Assistant Professor
Department of Chemical Engineering
Assistant Professor
Department of Biomedical Engineering
University of Michigan 

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

Response: Most current disease screening strategies rely on either blood tests, where the physician can obtain information on specific disease molecules but has no idea where they originated in the body, or anatomical imaging, where the physician can see changes in the structure of tissues but doesn’t have any molecular information. We wanted to develop a method that could provide both molecular information and an image of where these molecules were located. We know from decades of research in cancer that this is a molecular disease, so providing molecular information to the physician will help improve detection and diagnosis. Breast cancer screening provides an excellent opportunity to apply this approach to improve detection. Currently, estimates indicate that we are overspending $4 billion per year on the overdiagnosis and overtreatment of breast cancer because we cannot accurately determine which patients need treatment and which can be safely monitored with no intervention. Despite this problem with overdiagnosis, however, screening saves lives…we simply need a better way.

Molecular imaging has the capability of providing both molecular information and the location within the body. However, most of these techniques are expensive and use ionizing radiation, meaning there is a small risk of actually causing cancer. This is not acceptable for screening large numbers of otherwise healthy patients. To avoid this risk and provide a safe, inexpensive, and relatively easy method for patients to undergo screening, we decided to develop near-infrared fluorescent imaging agents that can be taken as a pill. The goal is for the patient to simply take a pill a day or two before their visit, and then the physician shines near-infrared light on the breast tissue to detect tumors where they ‘light up’ by giving off a different color of light.

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New Biomarker Could Change Lung Cancer Treatment Paradigm

MedicalResearch.com Interview with:
Ryo Nagashio, Ph.D.

Department of Molecular Diagnostics
School of Allied Health Sciences, Kitasato University
Japan.

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

Response: Lung cancer is the leading cause of cancer deaths in both men and women in the United States and worldwide. The disease is associated with a poor prognosis because most lung cancers are only diagnosed at an advanced stage. The identification of patients at an early stage of cancer when it can be treated surgically is extremely important to improve prognosis.

Current biomarkers for lung cancer include carcinoma embryonic antigen (CEA), sialyl Lewis X antigen (SLX), SCC antigen, and cytokeratin fragment (CYFRA) 21-1, but these are not sensitive enough to detect tumors early.

The results of our study provide evidence that the CKAP4 protein may be a novel early sero-diagnostic marker for lung cancer. Across disease stages I-IV, the sensitivities of serum CEA, CYFRA, and SCCa are reported with 30-52, 17-82, and 24-39 percent, respectively. In this study, the sensitivity of serum CKAP4 was 81 percent in the training set and 69 percent in the validation set. These rates are higher than those of the current sero-diagnostic markers. Furthermore, the sensitivity of serum CKAP4 was also high even in stage I non-small cell lung cancer.

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