Biomarkers Tag
15 Sep RANK signaling-blockade reduces breast cancer recurrence by inducing tumor cell differentiation
MedicalResearch.com Interview with: [caption id="attachment_27944" align="alignleft" width="200"]
Dr. Eva Gonzalez Suarez[/caption]
Eva Gonzalez Suarez, PhD
Group Leader Transformation and Metastasis lab.
Cancer Epigenetics and Biology Program-PEBC
Institut d'Investigació Biomédica de Bellvitge-IDIBELL
Hospital Duran i Reynals Avinguda Gran Via de l'Hospitalet,
L'Hospitalet de Llobregat-Barcelona-Spain
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Thousands of cancer patients worldwide are taking RANKL inhibitors for the management of bone metastasis, based on the key role of RANKL and its receptor, RANK, driving osteoclastogenesis. RANK signaling pathway acts as a paracrine mediator of progesterone in mouse and human mammary epithelium. RANK expression is associated with poor prognosis in breast cancer even though its therapeutic potential remained unknown.
Complementary genetic and pharmacological approaches demonstrate that therapeutic inhibition of RANK signaling drastically reduces the cancer stem cell pool, decreases tumor and metastasis initiation and enhances sensitivity to chemotherapy in mouse models that closely resemble the clinical disease. Mechanistically, genome wide expression analyses showed that anti-RANKL therapy promotes differentiation of tumor cells into milk-producing cells, as observed during pregnancy.
13 Sep Penn Reports Successful Pilot Study of Liquid Biopsy To Monitor Advanced Lung Cancer
Posted at 19:58h
in Author Interviews, Biomarkers, Lung Cancer, Personalized Medicine, University of Pennsylvania
MedicalResearch.com Interview with:
[caption id="attachment_27877" align="alignleft" width="132"]
Dr. Erica Carpenter[/caption]
Erica L. Carpenter, MBA, PhD
Research Assistant Professor, Department of Medicine
Director, Circulating Tumor Material Laboratory
Division of Hematology/Oncology
Abramson Cancer Center
Perelman School of Medicine at the University of Pennsylvania
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The advent of precision medicine practices for cancer patients, including the use of drugs that target specific tumor mutations, has necessitated improved diagnostics with real-time molecular monitoring of patients' tumor burden. While biopsy material, obtained surgically or through fine needle aspirate, can provide tissue for next generation sequencing (NGS) and mutation detection, this requires an invasive often painful procedure for the patient. In many cases, especially in more advanced disease when multiple metastases are present, such tissue cannot be obtained or can only be obtained from a single tumor site, thus limiting the sensitivity of tissue-based biopsy.
Here we report on a prospective cohort of 102 consecutively enrolled patients with advanced non-small lung cancer (NSCLC) for whom a non-invasive liquid biopsy was used for real-time detection of therapeutically targetable mutations. Tissue samples were only obtainable for 50 of the 102 patients, and these tissue biopsies were analyzed using a 47-gene Next Generation Sequencing (NGS) panel at Penn's Center for Personalized Diagnostics. Concordance of results for the 50 patients who received both tests was close to 100% when the samples were obtained concurrently.
11 Sep Liquid Biopsies Hold Promise of Diagnosing Response to Chemotherapy
MedicalResearch.com Interview with: [caption id="attachment_27803" align="alignleft" width="200"]
Dr. Karen Reckamp[/caption]
Karen L. Reckamp, M.D.
Associate Professor
City of Hope Comprehensive Cancer Center
Duarte, CA 91010
MedicalResearch.com: What is the background for this study? What are the main findings?
Response:
• Approximately 60% of patients with non-small cell lung cancer (NSCLC) receiving EGFR tyrosine kinase inhibitors (TKIs) will develop TKI resistance through the acquisition of the EGFR T790M mutation.
• A major challenge for assessing EGFR mutation status in advanced NSCLC is the availability of suitable biopsy tissue for molecular testing, specifically for determination of the emergence of T790M following progression on initial EGFR TKI therapy.
• The objective of this study was to demonstrate that a highly sensitive and quantitative next-generation sequencing analysis of EGFR mutations is feasible from urine and plasma, providing comparable clinical information while potentially mitigating the issues associated with tissue biopsies.
• This blinded, retrospective study was conducted on matched tissue, urine and plasma specimens collected from 63 patients with Stage IIIB-IV NSCLC enrolled in the TIGER-X trial of rociletinib, an investigational 3rd generation tyrosine kinase inhibitor (TKI), targeting T790M.
09 Sep Storage Time Can Effect Plasma Biomarker Results
MedicalResearch.com Interview with: Stefan Enroth, Associate Professor, PhD Dept. of Immunology, Genetics & Pathology Uppsala University MedicalResearch.com: What is the background for this study? Response: One basic requirement of life science research is the quality of samples. Proper handling and rigorous biobanking of clinical samples is very important when for instance collecting samples for rare diseases, for monitoring individual variation in longitudinal studies and when conducting prospective studies of biomarkers and risk of developing for instance cardiovascular disease. In epidemiological studies using case and control cohorts, great care is taken to ensure that the cases and controls are matched in terms of for instance age, anthropometrics and lifestyle exposures such as smoking or alcohol consumption. Technical factors and sampling handling history are not as commonly used. There has been a lack of studies that systematically investigated the effects of for instance storage-time on a larger set of plasma proteins. With emerging high-throughput technologies enabling measurements of a high number of proteins simultaneously on a population level, biomarker research will enter a new era and the more knowledge we have on what factors that influence circulating biomarker levels - such as plasma proteins, the higher the chances are of finding new clinically important biomarkers for disease.08 Sep Despite Valuable Biomarkers Clinical Evaluation Still Important in Diagnosing Heart Attack
MedicalResearch.com Interview with: [caption id="attachment_27783" align="alignleft" width="95"]
Dr. Juan Sanchis[/caption]
Dr. Juan Sanchis
Full professor of Medicine
Cardiology Department, University Clinic
Hospital. Medicine Department, University of Valencia
Valencia. Spain
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Decision making in acute chest pain in the emergency departments
remains challenging despite the introduction of new troponin assays
(high-sensitivity assays) capable of detecting any amount of
myocardial damage.
The upper limit of normality of high-sensitivity
troponin is established at the 99th percentile of a normal reference
population. This is the limit for the diagnosis of acute myocardial
infraction. Detectable troponin levels below the 99th percentile,
though non diagnostic of acute myocardial infarction, might be
considered as of uncertain significance since some patients might
still suffer from unstable angina. Undetectable troponin (far below
the 99th percentile), however, could rule out unstable angina meaning
that such patients could safely be discharged from the emergency
department according to some studies. Therefore, if this were fully
demonstrated, clinical evaluation could play a secondary role.
We investigated clinical data in comparison to undetectable
high-sensitivity troponin in patients with normal high-senstivity
troponin levels (below the 99th percentile).
The main findings indicate that clinical data can guide decision making and perform at
least equally well as undetectable high-sensitivity troponin for
ruling out unstable angina, in patients presenting at the emergency
department with chest pain and normal troponin.
01 Sep Inflammatory Biomarkers May Presage Development of Alzheimer’s
MedicalResearch.com Interview with: [caption id="attachment_27583" align="alignleft" width="125"]
Prof. Paul Morgan[/caption]
Professor B. Paul Morgan
Director, Systems Immunity Research Institute
Institute of Infection and Immunity
School of Medicine
Cardiff University
MedicalResearch.com: What is the background for this study?
Response: Inflammation is a normal response of the body to infection or injury; however, it is well known that inflammation also has a dark side and when it escapes normal controls can cause disease. Some illnesses, like rheumatoid arthritis, have been known for many years to be caused by rogue inflammation and most of the drugs used to treat work by suppressing the inflammation (anti-inflammatories). More recently, it has become clear that inflammation is behind many other diseases that were previously thought of as diseases of ageing caused by wear and tear and lifestyle - these include heart disease and some brain diseases, notably Alzheimer's disease the commonest cause of dementia. Evidence that inflammation is one of the drivers of disease has come from many sources, including some where it was noticed that people on long-term anti-inflammatory drugs for other reasons appeared to be protected from developing Alzheimer's disease.
A problem is that Alzheimer's disease, despite the name, is not a single disease but rather a group of conditions with similar symptoms, and inflammation is likely to be a cause in only some of the patients; further, most of the inflammation might be occurring very early in the disease, even before symptoms are obvious. So, there is an urgent need for a simple test or set of tests that can be used in individuals with the very earliest hints of Alzheimer's disease - mild memory loss - that will pick out those who have brain inflammation and are most likely to develop Alzheimer's disease. It might then be possible to treat this select group with anti-inflammatory drugs that will reduce brain inflammation and slow or stop progression of the disease.
31 Aug Urinary Biomarkers Predict Progression of Acute Kidney Injury In Heart Failure
MedicalResearch.com Interview with: Xiaobing Yang, MD Division of Nephrology, Nanfang Hospital Southern Medical University MedicalResearch.com: What is the background for this study? Response: AKI is a common complication in patients with acute decompensated heart failure (ADHF) and associated with increased death and worse clinical outcomes. Early detecting which patients are going to suffer progressive AKI or proceed to death could help physicians to plan and initiate timely managements. We analyzed data and samples of 732 ADHF patients from a prospective, multicenter study in China. We demonstrated that kidney injury biomarkers, measured at the first time of AKI clinical diagnosis, could predict which patients were going to have AKI progression or worsening of AKI with death. Notably, three urinary biomarkers, including urinary angiotensinogen (uAGT), urinary neutrophil gelatinase-associated lipocalin (uNGAL), urinary IL-18 (uIL-18), were all able to forecast which patients with the earliest stages of AKI were most likely to suffer progressive AKI.29 Aug Inclusion of Risk Biomarkers Improves Stroke Prediction
MedicalResearch.com Interview with: Dr. Ashkan Shoamanesh MD FRCPC Assistant Professor Division of Neurology, Department of Medicine McMaster University and Dr. Jose Rafael Romero, MD Associate Professor of Neurology Boston University School of Medicine MedicalResearch.com: What is the background for this study? What are the main findings? Response: The Framingham Heart Study is a population-based study of individuals residing in the community. Identifying people who are at risk for stroke can help us determine who would benefit most from existing or new therapies to prevent stroke. As inflammatory pathways are believed to contribute to vascular disease and stroke, we tested whether circulating biomarkers of inflammation and endothelial dysfunction could improve the predictive ability of the Framingham Stroke Risk Profile score, a model that contains classical vascular risk factors such as high blood pressure and diabetes. Our main observation was that inclusion of 4 biomarkers (C-reactive protein, tumor necrosis factor receptor-2, total homocysteine, and vascular endothelial growth factor) in the Framingham Stroke Risk Profile improved its ability to predict a stroke (net reclassification improvement of 0.34 [0.12–0.57]).29 Aug EPICUP Uses Epigenetic Biomarkers To Identify Cancers of Unknown Primary
MedicalResearch.com Interview with: [caption id="attachment_27431" align="alignleft" width="200"]
Dr. Manel Esteller[/caption]
Dr. Manel Esteller
Director of the Epigenetics and Cancer Biology Program (PEBC)
Bellvitge Biomedical Research Institute
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Cancer of Unknown Primary (CUP) occurs when the patient is diagnosed with a metastasis but the primary tumor is not found. It accounts for around 5-10% of tumors around the world and the survival is very poor. Until now, only in 25% of cases the primary site was identified after diagnosis pipeline. We are showing herein that the use of epigenetic profiling, based in the determination of the chemical marks occurring in DNA that are tumor-type specific, reaches a diagnoses of 87% of cases.
18 Aug Circulating TMAO Levels Correlate with Coronary Plaque Vulnerability and Rupture
MedicalResearch.com Interview with: [caption id="attachment_27140" align="alignleft" width="132"]
Dr. Lemin Zheng[/caption]
Lemin Zheng, Ph.D.
Professor, Lab Director, and Principal Investigator The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine
Peking University Health Science Center
Beijing China
MedicalResearch.com: What is the background for this study?
Response: Optical coherence tomography (OCT) has been considered as an ideal tool to characterize accurately atherosclerotic plaques and has potential to detect plaque rupture due to high-resolution (10-20 μm) cross-sectional images of tissue with near infrared light (1-3). Trimethylamine-N-oxide (TMAO) is a gut microbiota-dependent-generated metabolite which is associated with cardiovascular risk by a pathway involving dietary ingestion of nutrients containing trimethylamine, including phosphatidylcholine, choline, and L-carnitine (4-6).
In the gut, choline, betaine and carnitine can be metabolized to trimethylamine (TMA) by gut flora microorganism. And TMA could be further oxidized to a proatherogenic species, TMAO, in the liver by flavin monooxygenases 3 (FMO3)4-6. These risk associations have been repeatedly shown in large observational trials (7-10).
05 Aug BMI1 Gene Expression May Predict Response To Lung Cancer Treatment
MedicalResearch.com Interview with: [caption id="attachment_26759" align="alignleft" width="200"]
Dr. Elena Levantini[/caption]
Dr. Elena Levantini, PhD
Beth Israel Deaconess Medical Center
Instructor, Medicine, Harvard Medical School
Research Associate, Hematology-Oncology
Beth Israel Deaconess Medical Center
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Lung cancer is one of the deadliest cancers in the world, accounting for 30% of tumor-related deaths. Like many solid tumours, lung cancer is very heterogeneous (consisting of cancer cells which behave and respond differently) and hence there is currently no single efficient drug which is able to treat all patients.
Levantini and colleagues previously showed that non-small cell lung cancer (NSCLC) tumor cells frequently express too little or none of a transcription factor called C/EBPα, a protein that regulates gene expression and cell proliferation in lung tissues. It’s also known to play a role in a form of leukemia, as well as liver cancer, squamous cell skin carcinomas, squamous cell cancers of the head and neck and other cancers. In their previous work, the scientists suspected that C/EBPα may act as a tumor suppressant in normal cells, but the mechanism by which its absence promoted lung cancer tumors remained unclear.
Dr. Levantini went on to develop a mouse model in which deleting C/EBPα resulted in NSCLC. Analysis of this model led to the discovery that C/EBPα suppressed lung tumor formation by inhibiting the expression of BMI1. Dr Levantini then demonstrated that reducing the levels of BMI1 in her mouse model by genetic means, or by using a drug reducing expression of BMI1, led to inhibition of tumor formation. This study has established an important link between C/EBPα and BMI1 for the first time.
05 Aug Biomarker May Predict Response to Common Leukemia Treatment
Posted at 13:11h
in Author Interviews, Biomarkers, Genetic Research, Leukemia, Personalized Medicine
MedicalResearch.com Interview with:
[caption id="attachment_26730" align="alignleft" width="200"]
Dr. Laura Eadie[/caption]
Dr Laura Eadie PhD
Post Doctoral Researcher
Affiliate Lecturer Discipline of Medicine
University of Adelaide
Summary: Researchers based at SAHMRI (South Australian Health and Medical Research Institute) in Adelaide, South Australia have recently demonstrated the significance of early increases in the expression of ABCB1 in predicting long-term response to imatinib therapy. Lead researcher, Dr Laura Eadie, has recently had these findings published in the journal Leukemia and says that she hopes “the evidence provided by the study could be used to inform better patient treatment in the future”.
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: ABCB1 (p-glycoprotein) is a membrane transporter known to be involved in the efflux of the tyrosine kinase inhibitors (TKIs) that are used to treat chronic myeloid leukaemia (CML). Overexpression of ABCB1 has also been demonstrated to cause resistance to the TKIs imatinib, nilotinib and dasatinib in vitro. Although studied previously in CML patients, the predictive value of ABCB1 in determining a patient’s long-term response to imatinib had not been realized ... until now.
Previous studies investigating ABCB1 as a predictive biomarker focused on expression levels of ABCB1 at one time point in isolation. For our study, we have measured the levels of ABCB1 at two separate time points specified in the TIDEL II trial protocol: day 1 (prior to the start of imatinib therapy) and day 22 (three weeks on imatinib). We then calculated the fold rise in ABCB1 expression levels at day 22 compared with day 1 and grouped patients about the median into high and low fold rise. When we compared molecular outcomes for patients within these two ABCB1 expression groups we noticed a striking difference in outcome to imatinib therapy.
25 Jul Breastfeeding May Correct Metabolic Abnormalities Linked To Diabetes
MedicalResearch.com Interview with: Dr. Sandra Hummel and Dr. Daniela Much Institute of Diabetes Research Helmholtz Center Munich German Research Center for Environmental Health Munich MedicalResearch.com: What is the background for this study? What are the main findings? Response: Gestational diabetes mellitus is associated with a seven-fold increased risk of developing type 2 diabetes postpartum. In 2012, we published that type 2 diabetes risk was markedly reduced up to 15 years after delivery in women with gestational diabetes if they breastfed for more than 3 months. However the underlying biological mechanisms are still unclear to date. Aim of this biomarker study was to identify the mechanism underlying the protective effect of prolonged lactation. At our study site in Munich, we enrolled 197 women with previous gestational diabetes participating in a postpartum assessment of glucose tolerance at a median time of 3.6 years after delivery. By using a targeted metabolomics approach (including a broad spectrum of lipids and amino acids), we identified lactation-associated biochemical changes in maternal plasma samples. Most interestingly, these metabolite signatures have been described with decreased risk for type 2 diabetes previously. Our results indicate that lactation-associated alterations persisted up to 11 years post-lactation.22 Jul Circulating Tumor DNA Size Enhances Liquid Biopsy Effectiveness
MedicalResearch.com Interview with: [caption id="attachment_26374" align="alignleft" width="133"]
Dr. Hunter Underhill[/caption]
Dr. Hunter R. Underhill MD, PhD
Department of Pediatrics, Division of Medical Genetics, Department of Radiology,
University of Utah, Salt Lake City, Utah
Department of Radiology and Department of Neurological Surgery
University of Washington
Seattle, Washington
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: When cells undergo cell death (i.e., apoptosis) the DNA has the potential to enter the circulation. This DNA is not contained within a cellular membrane and is known as "cell-free DNA." This is a naturally occurring process. The same process also occurs when malignant tumors grow and evolve. The deposition of cell-free DNA derived from tumors is known as "circulating tumor DNA." Analysis of circulating tumor DNA holds the promise of detecting, diagnosing, and monitoring response to therapy of cancers through a simple blood draw - the "liquid biopsy." The challenge has been isolation of circulating tumor DNA from the background of the naturally occurring cell-free DNA. This has been particularly difficult in non-metastatic solid tumors as circulating tumor DNA has been heretofore indistinguishable from normal cell-free DNA except for the occurrence of mutant alleles that commonly occur at a frequency below detection limits - the proverbial needle in a haystack.
Our study found a distinct size difference in DNA fragment length between circulating tumor DNA and cell-free DNA. Specifically, circulating tumor DNA is about 20-50 base pairs shorter than cell-free DNA originating from healthy cells. We were subsequently able to exploit this difference in size to enrich for circulating tumor DNA - essentially removing a large portion of the haystack that does not contain the needle to simplify the search.
13 Jul Analysis of Multiple MRI and PET Images Detects Earliest Signs of Alzheimer’s Disease
MedicalResearch.com Interview with: [caption id="attachment_26102" align="alignleft" width="200"]
Dr. Y. M. Medina[/caption]
Dr. Yasser Iturria Medina PhD
Post-doctoral fellow
Montreal Neurological Institute
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: We used over 200 peripheral molecular biomarkers, five different neuroimaging modalities and cognitive/clinical measurements to detect spatiotemporal abnormalities in subjects with dementia or with mild signs of cognitive deterioration. By means of a mathematical framework, we reordered all the biomarkers/descriptors considered, according to how much they change during the disease process. The results suggested that, contrary as suggested by more traditional clinical analyses, there are multiple early signs of neurodegeneration, at the molecular level and at the brain’s macroscopic and cognitive state. In particular, we observed notable early signs of generalized vascular dysregulation, which may be supporting the vascular hypothesis of Alzheimer’s disease. However, we still need to perform deeper analyzes, in order to clarify the complex causal mechanisms that trigger the disease.
11 Jul Circulating Tumor DNA Predicts Colon Cancer Relapse
MedicalResearch.com Interview with: [caption id="attachment_26009" align="alignleft" width="104"]
Dr. Jeanne Tie[/caption]
Jeanne Tie MBChB, FRACP, MD
Division of Systems Biology and Personalised Medicine, Walter and Eliza Hall Institute of Medical Research
Department of Medical Oncology, Western Health, St Albans, Victoria, Australia.
Department of Medical Oncology,
Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne
Parkville, Victoria, Australia
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: This study investigated the ability of circulating tumor DNA (ctDNA) in detecting residual microscopic cancer after surgery with curative intent in patients with stage II colon cancer. Although the majority of patients with stage II colon cancer are cured by surgery alone, our ability to accurately predict the risk of cancer relapse based on current clinical and pathological criteria is imprecise. Population-based study indicated that adjuvant chemotherapy is given to up to 40% of stage II colon cancer patients, meaning that we are over-treating a significant number of patients with cytotoxic therapy. A better indicator of residual disease and recurrence would be very useful clinically.
The current study collected tumor and blood samples from 230 patients with stage II colorectal cancer. A personalised assay was then designed to detect patient-specific tumor DNA in the plasma samples collected four to ten weeks after surgery. The presence of ctDNA (positive test) in the post-operative blood sample predicted recurrence in 100% of patients, while the relapse rate is only 10% in those with negative ctDNA test. We have also shown that the ctDNA test is a better predictor of recurrence than the standard clinic-pathological criteria.
13 Jun ‘Epi-Chip’ Aims To Reconstruct Entire Infection Exposure History From Drop of Blood
Posted at 19:43h
in Author Interviews, Biomarkers, Cancer Research, Infections, Technology, University of Pittsburgh
MedicalResearch.com Interview with:
[caption id="attachment_25161" align="alignleft" width="160"]
Dr. Donald Burke[/caption]
Donald S. Burke, M.D.
Dean of the University of Pittsburgh Graduate School of Public Health
Director of the University of Pittsburgh Center for Vaccine Research
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Burke: At the University of Pittsburgh we developed a unique method for detecting antibodies in the blood of patients in a proof-of-principle study that opens the door to development of simple diagnostic tests for diseases for which no microbial cause is known, including auto-immune diseases, cancers and other conditions.
We used a technique pioneered by co-author Thomas Kodadek, Ph.D., of the Scripps Research Institute, that synthesizes random molecular shapes called “peptoids” hooked onto microscopic plastic beads. The technique can produce millions of molecular shapes. The peptoids are not organic, but if they match to the corresponding shape on an antibody, that antibody will connect to them, allowing the scientist to pull out that bead and examine that peptoid and its corresponding antibody.
My team chemically generated a huge library of random molecular shapes. Then, using blood from HIV-infected patients and from non-infected people, we screened a million of these random molecular shapes to find the ones that bound only to antibodies present in the blood of HIV-infected patients, but not the healthy controls. No HIV proteins or structures were used to construct or select the peptoids, but the approach, nonetheless, successfully led to selection of the best molecular shapes to use in screening for HIV antibodies.
We then resynthesized that HIV-antibody-targeting peptoid in mass and tested it by screening hundreds of samples from the Multicenter AIDS Cohort Study (MACS), a confidential research study of the natural history of treated and untreated HIV/AIDS in men who have sex with men (supported by the National Institutes of Health). Study co-author Charles Rinaldo, Ph.D., chair of Pitt Public Health’s Department of Infectious Diseases and Microbiology and director of the Pittsburgh arm of the MACS, selected the samples, but blinded the testers to which samples were HIV-positive or -negative. The test distinguished between the samples of HIV-positive blood and HIV-negative blood with a high degree of accuracy.
13 Jun Inflammatory Biomarker CRP Elevated in Migraine
MedicalResearch.com Interview with: [caption id="attachment_24979" align="alignleft" width="142"]
Dr. Gretchen Tietjen[/caption]
Dr. Gretchen Tietjen MD
Professor and Chair of Neurology
Director of UTMC Headache Treatment and Research Program
Director of the UTMC Stroke Program
MedicalResearch.com: What is the background for this study?
Dr. Tietjen : C-reactive protein (CRP) is a well-established biomarker of inflammation. Elevated levels of CRP predict future cardiovascular events, such as myocardial infarction (heart attack) and stroke. Evidence linking higher CRP levels with migraine is limited and results from large population-based studies are conflicting. The National Health and Nutrition Examination Survey (NHANES) data for children and adolescents linked elevated CRP to headache, particularly in girls, and the Women’s Health Study showed an association of CRP with migraine in women over 45 years of age. In the Reykjavik study, CRP levels in persons with migraine were similar to levels in those without migraine. The aim of our study was to examine the relationship of CRP and migraine in a large population-based sample of over 9,000 young adults (24 to 32 years old) from The National Longitudinal Study of Adolescent to Adult Health (Add Health).
09 Jun Biomarker Endothelin-1 Associated with Pulmonary Hypertension and Heart Failure
MedicalResearch.com Interview with: [caption id="attachment_25081" align="alignleft" width="143"]
Dr. Mathew Jankowich[/caption]
Matthew D. Jankowich, MD
Assistant Professor of Medicine
Alpert Medical School of Brown University
Staff physician at the Providence VA Medical Center
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Jankowich: For some time, endothelin-1 has been known to cause vasoconstriction in the pulmonary circulation, and elevated endothelin-1 levels have been noted in patients with pulmonary arterial hypertension and decompensated congestive heart failure, as well as other advanced disease states. However, endothelin-1 has not been well studied in members of the general population. In our study, we examined plasma endothelin-1 levels in participants in the Jackson Heart Study and the relationship of plasma endothelin-1 levels to pulmonary hypertension, mortality and heart failure. We found increased odds of having pulmonary hypertension, defined as an echocardiography estimation of the pulmonary artery systolic pressure>40mmHg, in those participants with higher plasma endothelin-1 levels. Having higher endothelin-1 levels was also associated with an increased risk of both mortality and heart failure. Those participant with both high endothelin-1 levels (a level in the top 25%) and pulmonary hypertension were at the highest risk of mortality.
07 Jun Simple Blood Test May Help Assess Risk of Colorectal Cancer
MedicalResearch.com Interview with: Gilles Jobin, MD, FRCP, MSc Chief of Gastroenterology Maisonneuve-Rosemont Hospital Associate Professor of Medicine University of Montreal Montréal, Qc MedicalResearch.com: What is the background for this study? Dr. Jobin: It is known that the immune system has a role to play in keeping the body free of cancer and tumor cells. There is a lot of scientific literature that shows that when someone has cancer, certain cells from the immune system do not function very well. These cells are called natural killer or NK cells and they are the first ones to respond when there is a virus, a bacteria or a tumor cell in the body. If the activity of these cells is very low, then there is a higher risk of someone developing a cancer, and if someone has cancer, there are greater chances that their NK cell activity is low. In the last few decades, a few tests have been developed to measure NK Cell activity but they have been used in research only because they were complicated and difficult to use. The current study measured NK Cell activity (NKA) with a new commercially available simple blood test to investigate its clinical application in the detection of colorectal cancer in patients presenting for prescribed colonoscopy. The aim of this study is to evaluate the sensitivity, specificity, positive and negative predictive values of this in vitro diagnostic device in patients with colorectal cancer (CRC) and adenomatous polyps (AP).07 Jun Biomarker Based Chemotherapy Approach Improved Outcomes
MedicalResearch.com Interview with: [caption id="attachment_24655" align="alignleft" width="200"]
Dr. Maria Schwaederle[/caption]
Maria Schwaederle PharmD
Clinical Research Scientist
Center for Personalized Cancer Therapy
UCSD Moores Cancer Center
La Jolla, CA 92093
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Schwaederle: We performed this analysis with experts in the field, including but not limited to Drs Schilsky, Lee, Mendelsohn and Kurzrock, all known for their experience in the area of precision/personalized medicine.
Historically, phase I trials (which are often first in human or highly experimental in other ways) were believed to be examining only toxicity. Our meta-analysis of 13,203 patients shows that in the era of precision medicine, this historical belief needs to be discarded. Second, it is the use of precision medicine that makes this belief outdated.
Indeed, Phase I trials that utilized a biomarker-driven approach that is the essence of precision medicine had a median response rate of about 31%, which is higher than many FDA approved drugs, and this is in spite of the fact that phase I patients are a highly refractory group having failed multiple lines of conventional therapy.
Importantly, however, it was not the use of targeted agents alone that was important. It was the biomarker-based approach where patients are matched to drugs. Without matching, response rates were dismal—about 5%.
01 Jun Heart Attack Can Be Ruled-Out in One Hour with High-Sensitivity Troponin I Assay
MedicalResearch.com Interview with: [caption id="attachment_24827" align="alignleft" width="180"]
Dr. Johannes Neumann[/caption]
Dr. med. Johannes Neumann
Resident physician
University Heart Center Hamburg
Department of General and Interventional Cardiology
Universitätsklinikum Hamburg-Eppendorf
Hamburg
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The early decision making in patients with suspected acute myocardial infarction is important. Current guidelines recommend measurement of cardiac troponin at admission and after 3 hours. In our study we evaluated the performance of a high-sensitivity troponin I assay with a rapid measurement after only 1 hour. We included 1040 patients with new onset chest pain and could show, that a low cutoff concentration of 6 ng/L after 1 hour allows safe rule-out of acute myocardial infarction. The results were comparable to the recommended 3-hour approach and were validated in 2 external cohorts. When using the 99th percentile to rule-out myocardial infarction, as recommended by current guidelines, the negative predictive value was much lower. Furthermore, a troponin I concentration above 6 ng/L in combination with an absolute change of 12 ng/L after 1 hour showed a high positive predictive value for the final diagnosis of myocardial infarction. This allows early decision making after only 1 hour.
01 Jun Potential New Treatment for Poor Prognosis Gastric Cancer Identified
MedicalResearch.com Interview with: Dr. Nicholas Turner Academic Consultant Medical Oncologist Team leader at the Breakthrough Breast Cancer Research Centre Institute of Cancer Research, London MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Turner: Prior laboratory research had identified that gastric cancers with a particular mutation, amplification of the gene FGFR2, were potential sensitive to a drug that inhibits FGFR2. We conducted a trial and showed that gastric cancers with this FGFR2 amplification respond to FGFR inhibition with a drug AZD4547. The amplification is rare, occurring in only a few percent of gastric cancers, so we designed a blood test to identify which patients have the amplification in their cancer, and we are not using the blood test to screen patients for the study.01 Jun Inflammatory Biomarkers Predictive of Coronary Artery Calcium in Women at Midlife
MedicalResearch.com Interview with: Norman C. Wang, M.D., M.S., Assistant professor University of Pittsburgh School of Medicine Samar R. El Khoudary, Ph.D., M.P.H., Assistant professor of Epidemiology University of Pittsburgh Graduate School of Public Health MedicalResearch.com: What is the background for this study? What are the main findings? Response: We studied 252 middle-aged women with no known cardiovascular disease from the Study of Women’s Health Across the Nation [SWAN] Heart Study to determine if 5 blood biomarkers associated with abnormal inflammation/hemostasis were associated with increasing amounts of calcium detected in coronary arteries on computed tomography scans, or coronary artery calcium progression. Only higher blood levels of plasminogen activator inhibitor-1 was associated with coronary artery calcium progression.19 May microRNA Biomarkers Predictive of Outcomes After Cardiac Arrest
MedicalResearch.com Interview with: [caption id="attachment_24511" align="alignleft" width="200"]
Dr. Yvan Devaux[/caption]
Yvan Devaux, PhD
Associate Head of Laboratory
Cardiovascular Research Unit
Department of Population Health
Luxembourg Institute of Health
Luxembourg
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Devaux: Being able to predict outcome after cardiac arrest would allow tailoring healthcare and would represent a major step forward towards personalized medicine. However, available predictive tools suffer serious limitations and would benefit from novel biomarkers.
The value of microRNAs (miRNAs) as biomarkers has been investigated in various clinical contexts and initial small-scale studies suggested that miRNAs might be useful indicators of outcome after cardiac arrest.
Our work aimed at testing whether these molecules, and in particular the brain-enriched miR-124-3p, can be used to predict outcome after cardiac arrest.
We found that, indeed, circulating levels of miR-124-3p measured 48h after cardiac arrest are robust predictors of neurological outcome and mortality.
The strengths of the study are the use of a large multicenter international cohort (TTM-trial) and the collaboration between LIH and European partners (members of the TTM-trial and the Cardiolinc network) bringing complementary clinical and basic expertise.
01 May Monitoring Circulating Tumor Cells May Further Personalized Cancer Treatment
Posted at 19:41h
in AACR, Author Interviews, Biomarkers, Cancer Research, Personalized Medicine, Stanford
MedicalResearch.com Interview with:
Dr. Elodie Sollier
Chief Scientific Officer at Vortex Biosciences
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Circulating Tumor Cell (CTC) burden may be a useful biomarker of response to targeted therapy in PDX (Patient Derived Xenograft) mouse models. Vortex Biosciences’ technology has been proven to enrich CTCs from human blood, but use of the technology with mouse blood had not yet been explored. In this poster, human CTCs are isolated with both high efficiency and purity from xenograft model of breast cancer using Vortex’s technology. Circulating Tumor Cell enumeration increased as the tumor burden increased in the mouse demonstrating its utility as a biomarker for drug treatment response.
27 Apr Relationship Between Plasma Aβ Levels, Cognitive Function and Brain Volumetrics
MedicalResearch.com Interview with: [caption id="attachment_23823" align="alignleft" width="149"]
Dr. Anne Poljak[/caption]
Dr Anne Poljak
Leader of the Proteomics Group
Centre for Healthy Brain Ageing (CHeBA)
UNSW, Australia
MedicalResearch.com: What is the background for this study?
Dr Poljak: Amyloid-beta (Aβ) peptides are found in abundance in the plaque particles which build up in the Alzheimer’s brain and small blood vessels of the brain, and are therefore considered hallmark features of Alzheimer’s disease. However they are also found in blood which is a convenient body fluid for sampling purposes. We therefore wished to assay them in plasma samples from one of our longitudinal population based studies of older age individuals (70 – 90 years) – the Centre for Healthy Brain Ageing’s Sydney Memory and Ageing Study.
Other research groups had previously measured these peptides in plasma, but there was controversy in the area because of differences in outcomes across laboratories. So one of the main questions was whether plasma levels of Aβ peptides have any relationship with what is happening in the brain, or are they a red-herring? We wanted to see how the levels we found would compare with the findings of others in relation to Alzheimer’s disease and mild cognitive impairment. A further question was how our plasma levels would relate to other clinical measures including cognition and brain volumetrics. One of the precautions we took was to use an assay kit with very well characterized antibodies, so we could be confident that our method was specific for the two full length Aβ peptides (Ab1-40 and Ab1-42).
25 Apr Eosinophil Count Identifies COPD Patients Who May Benefit From Inhaled Steroids
MedicalResearch.com Interview with: [caption id="attachment_23751" align="alignleft" width="200"]
Dr. Danny MvBryan[/caption]
Danny McBryan, MD
Vice president, Clinical Development & Medical Affairs, Respiratory
Boehringer Ingelheim Pharmaceuticals, Inc.
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. MvBryan: The new post-hoc analysis from the WISDOM study shows a routine blood test could help identify the small minority of patients with severe or very severe COPD who may benefit from the addition of inhaled corticosteroids (ICS). This post-hoc analysis was recently published online in The Lancet Respiratory Medicine.
For 80 percent of patients in the WISDOM study, the use of ICS on top of SPIRIVA HANDIHALER (a long-acting muscarinic antagonist – LAMA) and salmeterol (a long-acting beta-agonist – LABA) had no additional benefit in reducing the risk of exacerbations, compared to SPIRIVA HANDIHALER and the LABA without ICS.
The post-hoc analysis shows that these patients can be easily identified by measuring the level of white blood cells, called eosinophils. Patients with levels lower than 4 percent (300 cells/µL) were associated with a lack of response to ICS.
The WISDOM study evaluated stepwise withdrawal of inhaled corticosteroids (ICS) in severe to very severe COPD patients with a history of exacerbation. WISDOM was a 12-month, double-blind, parallel-group, active-controlled study in which all patients received triple therapy (tiotropium 18 μg once daily, salmeterol 50 μg twice daily and fluticasone 500 μg twice daily) for a six-week run-in period. Patients were randomized 1:1 to continue triple therapy or stepwise withdrawal of ICS over 12 weeks (dose reduction every six weeks).
The WISDOM data show that in patients with severe to very severe COPD, the risk of moderate/severe exacerbations during one year of follow-up was non-inferior between those patients who continued on inhaled corticosteroids and those where ICS therapy was withdrawn in a stepwise manner.
21 Apr Biomarker Expression Linked to Aggressive Basal Cell Skin Cancer
MedicalResearch.com Interview with: [caption id="attachment_23645" align="alignleft" width="100"]
Dr. Alon Kahana[/caption]
Alon Kahana, MD, PhD
Associate Professor
Kellogg Eye Center
University of Michigan
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Kahana: Basal cell carcinoma is the most common cancer - more common than all other cancers combined. Fortunately, it is usually not aggressive, and can be easily treated surgically. However, when it is on the face, or when it has grown to a large size, it can become very disfiguring and even deadly. Basal cell carcinoma is diagnosed histopathologically, yet molecular diagnostics have proven value in a variety of cancers. In order to improve diagnosis and care, we set out to test whether histologically aggressive forms of basal cell carcinoma are associated with increased cell proliferation.
Furthermore, we tested whether expression of the epigenetic regulator Ezh2 is associated with higher-grade carcinoma and/or with increased proliferation. The breakthrough discovery is that expression of Ezh2 correlates with high proliferation and with aggressive histologic features, suggesting that epigenetic regulators can be used both as markers of disease severity and targets of novel therapy.