Biomarkers
25 Nov Inflammatory Biomarkers Found Linked to Risk of Mortality
MedicalResearch.com Interview with: Archana Singh-Manoux, PhD Research Professor (Directeur de Recherche) Epidemiology of ageing & age-related diseases INSERM,France MedicalResearch.com: What is the background for this study? What are the main findings? Response: A recent metabolomics study examined 106 biomarkers and found alpha-1-acid glycoprotein (AGP), an acute phase protein, to be the strongest predictor of five-year mortality. It is also unknown how well AGP compares with other sensitive, dynamic, and commonly measured markers of systemic inflammation, such as CRP and IL-6, as a predictor of mortality. We examined the association of these three inflammatory markers with short- and long-term mortality in a large sample of middle-aged adults, followed for 17 years. Our analysis of all-cause, cancer and cardiovascular mortality suggests that for all these outcomes IL-6 may be a better prognostic marker, both in the short and the long-term.28 Oct Biomarker NLR Found Not Predictive of Bladder Cancer Survival
Posted at 20:35h
in Author Interviews, Biomarkers, Cancer, Cancer Research, University of Pennsylvania
MedicalResearch.com Interview with:
[caption id="attachment_29147" align="alignleft" width="112"]
Dr. Eric Ojerholm[/caption]
Eric Ojerholm, MD
Resident, Radiation Oncology
Hospital of the University of Pennsylvania
MedicalResearch.com: What is the background for this study?
Response: Multiple studies reported that a blood test —the neutrophil-to-lymphocyte ratio (NLR)—might be a helpful biomarker for bladder cancer patients. If this were true, NLR would be very appealing because it is inexpensive and readily available. However, previous studies had several methodological limitations.
MedicalResearch.com: What did you do in this study
Response: We therefore put NLR to the test by performing a rigorous “category B” biomarker study—this is a study that uses prospectively collected biomarker data from a clinical trial. We used data from SWOG 8710, which was a phase III randomized trial that assessed surgery with or without chemotherapy for patients with muscle-invasive bladder cancer. We tested two questions.
First, could NLR tell us how long a bladder cancer patient would live after curative treatment?
Second, could NLR predict which patients would benefit from chemotherapy before surgery?
21 Oct Distinct Mutational Signatures Correlate With Increased Immune Activity in Pancreatic Cancer
MedicalResearch.com Interview with Dr. Ashton A. Connor, MD PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research Dr. Steven Gallinger MD, MSC Division of General Surgery Toronto General Hospital Toronto, ON MedicalResearch.com: What is the background for this study? What are the main findings? Response: The etiology of pancreatic ductal adenocarcinoma (i.e. "pancreatic cancer") and the relationship between the tumour and its characteristic dense, encroaching stroma are still poorly understood. Using whole genome sequencing in two large cohorts, we show that there are four fundamental mutational processes that give rise to pancreatic cancer. With expression data, we also show that the interaction between the tumour and the surrounding stroma varies with the type of mutational process found in the tumour. Specifically, tumours with defective DNA repair, either homologous recombination or mismatch repair deficiency, elicited strong anti-tumour immune responses, likely due to the relatively high numbers of neoantigens in these tumours. Individually, these concepts have been studied in other cancer types, but we are first to apply either of these to pancreatic cancer, and we also the first to integrate these two aspects of cancer biology for any tumour, to our knowledge.19 Oct New Technology Can Quickly Detect TB and Evaluate Therapeutic Efficacy
MedicalResearch.com Interview with: [caption id="attachment_29007" align="alignleft" width="200"]
Dr. Ying Kong[/caption]
Ying Kong Ph.D.
Assistant Professor
University of Tennessee Health Science Center
Department of Microbiology, Immunology, and Biochemistry
Memphis, TN 38163
MedicalResearch.com: What is the background for this study?
Response: Tuberculosis (TB) is a public health concern worldwide, with high morbidity and mortality. The causative agent of TB, M. tuberculosis, grows very slowly in culture. For research of TB, we need to quantitate bacterial numbers in order to evaluate drug and vaccine efficacy or to identify bacterial genes that are critical for survival in hosts or causing disease.
M. tuberculosis divides every ~20 hours, which is much slower than other bacteria such as E. coli and Salmonella typhimurium, which divide every 20 minutes. Conventionally, quantitation of M. tuberculosis needs to spread M. tuberculosis on agar plates and wait for four weeks to obtain visible colonies, and then to count colony forming units. For the fast-growing bacteria, it takes only 18 hours to obtain visible colonies on agar plates. We and other groups have developed fluorescent protein labeled M. tuberculosis strains in order to quantitate M. tuberculosis in real time by measuring fluorescence. In this way, we are able to estimate bacterial number right after fluorescence measurement, which only takes a few minutes. However, this technology is not a diagnostic tool for clinical use, because the M. tuberculosis strains that we used were recombinant strains transformed with fluorescent protein genes. Another imaging technology that we have developed, REF, is for diagnosis purpose, which has been described in details in our other papers (Xie H, et al. Rapid point-of-care detection of the tuberculosis pathogen using a BlaC-specific fluorogenic probe. Nat Chem. 2012 Oct;4(10):802-9. Cheng Y, et al. Fluorogenic probes with substitutions at the 2 and 7 positions of cephalosporin are highly BlaC-specific for rapid Mycobacterium tuberculosis detection. Angew Chem Int Ed Engl. 2014 Aug 25;53(35):9360-4.).
18 Oct Can NT-proBNP-guided therapy during hospital admission for acute heart failure reduce mortality and readmissions?
MedicalResearch.com Interview with: Susan Stienen, MD Department of Cardiology Academic Medical Center University of Amsterdam Amsterdam, the Netherland MedicalResearch.com: What is the background for this study? Response: Prognosis of patients admitted for and discharged after acute decompensated heart failure (ADHF) is poor, with a readmission and mortality rate of up to 50% of patients at 6 months. Previous studies demonstrated that a ≤30% NT-proBNP reduction from admission to discharge for ADHF is a strong predictor of HF readmissions and mortality, while those patients with a > 30% reduction in NT-proBNP had a far better prognosis. We conducted a randomized clinical trial in ADHF patients to study the effect of NT-proBNP-guided treatment with a target of NT-proBNP reduction of >30% from admission to discharge, versus conventional treatment. The guided arm used a therapy algorithm that included HF medication, review of rhythm problems and possible ischemia, and had a reminder of a possible indication for CRT-D. A total of 405 patients were randomized after an initial period of clinical stabilization, to receive NT-proBNP-guided or conventional therapy. Intention-to-treat analyses were performed in 404 patients.08 Oct Little Change in PSA Use After Taskforce Recommendation
MedicalResearch.com Interview with: Dr Ryan Hutchinson MD and Yair Lotan MD Department of Urology University of Texas Southwestern Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: The United States Preventative Services Task Force recommendation against PSA screening generated significant controversy. Research since then has relied heavily on survey data to examine the impact of the recommendation on PSA screening practices. In a hotly charged issue such as this, such data can carry significant bias. We examined a large, whole-institution data in the years before and after the USPSTF recommendations reflecting actual practice and found that the changes in PSA use at our institution, if any, were small. This is more consistent with behavior seen after the vast majority of practice recommendations.03 Oct Cell Biomarkers To Distinguish Deadly From Less Aggressive HPV Oral Cancers
MedicalResearch.com Interview with: [caption id="attachment_28510" align="alignleft" width="200"]
Dr. Elizabeth Franzmann[/caption]
Elizabeth Franzmann, M.D.
Scientific Founder and Chief Scientific Officer
Vigilant Biosciences
MedicalResearch.com: What is the background for this study?
Response: Head and neck cancer involves cancers of the oral cavity, oropharynx and larynx. It is difficult to treat. Part of the challenge is that it is distinguishing the patients with tumors that are going to behave aggressively from those with less aggressive disease. As a result, many patients undergo treatment that may be more intensive and morbid than they need while others need more aggressive treatment. Tissue markers associated with prognosis may be able to help clinicians differentiate patients who need more aggressive treatment from those whose treatment can be less intensive. CD44 is a cell surface glycoprotein and tumor-initiating marker. CD44 and another surface protein, EGFR, are involved in tumor extension and are associated with poor prognosis. Certain forms of Human Papillomavirus (HPV) are known to cause oropharyngeal cancer and are associated with a good prognosis. P16 is a surrogate marker for the kind of HPV that causes cancer. Understanding the relationships between how these markers are expressed in cancer tissue may direct patient treatment in the future.
27 Sep IL-33 May Be First Stand Alone Biomarker of Prostate Cancer Recurrence
MedicalResearch.com Interview with: Iryna Saranchova MD PhD candidate Michael Smith Laboratories Vancouver, BC MedicalResearch.com: What is the background for this study? • The immune system is efficient at identifying and halting the tumour emergence at early stages. However, when metastatic (sufficient to cause death) tumour appears, the immune system is no longer able to recognize the cancer cells and control their growth and spread. • Recent studies of solid cancers have shown considerable heterogeneity between different tumour types and several lines of evidence suggest that tumours are not only heterogeneous, but they constantly evolve during the disease progression and this often hampers the existing treatment methods. • It means that it is important to consider each patient’s mutational changes accumulated over time in antecedent primary, metastatic lesions and/or local recurrences. This approach will help to understand the mechanism of tumour development, create a background for specific treatment modality and prevent therapeutic failure with consequent systemic relapse of the disease • Therefore, in our project we were aiming to find possible immune markers of tumour transition from the primary stage to its metastatic form. For this purpose, we selected a special study model: two pairs of separate mouse tumour cell lines, where metastatic cells arose from the initial primary tumour.26 Sep Parkinson’s Disease Linked To Increase in Number of Inflammatory Markers
MedicalResearch.com Interview with: [caption id="attachment_28339" align="alignleft" width="200"]
Dr. Yong Cheng[/caption]
Yong Cheng, PhD, post-doc fellow
Section on Cellular Neurobiology
Eunice Kennedy Shriver National Institute of Child Health and Human Development
National Institutes of Health
Bethesda, Maryland
MedicalResearch.com: What is the background for this study?
Response: Parkinson’s disease is the second most neurodegenerative disease after Alzheimer’s disease. The symptoms of the disease are typically movement related. However, the nonmotor features in PD are increasingly recognized. Evidence suggests that inflammation may play a role in the development of AD, and a substantial number of studies have demonstrated altered levels of peripheral blood inflammatory cytokines in patients with Parkinson’s disease, but findings have been inconsistent for individual cytokines and between studies. Therefore, we undertook a systematic review of the scientific literature, using a meta-analysis to quantitatively summarize clinical data on blood cytokine levels in patients with PD, compared with healthy controls.
22 Sep Brain RAP is a Critical Mediator of Leptin Resistance and Obesity
Posted at 01:23h
in Author Interviews, Baylor College of Medicine Houston, Biomarkers, Weight Research
MedicalResearch.com Interview with:
[caption id="attachment_28232" align="alignleft" width="144"]
Dr. Makoto Fukuda[/caption]
Makoto Fukuda Ph.D.
Assistant Professor
Children's Nutrition Research Center
Department of Pediatrics
Baylor College of Medicine
Houston, Texas 77030
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: A hallmark characteristic of obesity is diminished actions of metabolic hormones that are critically required to maintain whole body energy balance and glucose homeostasis. Leptin is a crucial and powerful hormone that keeps body weight normal. It was hoped that leptin might be a “magic bullet” that could cure obesity. Shortly after the discovery, however, obese individuals were found to have little or no response to exogenously administered leptin, a state of “leptin resistance”. These observations created a central question to be addressed in the field, which would help our understanding of the core of pathophysiology of obesity. While we and other groups previously demonstrated that Epac, a signaling molecule known as a GTP/GDP exchange factor directly activated by cAMP, is involved in cellular leptin resistance, the role of brain Epac signaling in the whole body metabolism has not yet established.
We approached this question by using brain-specific knockout mice of Rap1, a direct activator of Epac. As expected from previous results, mice with brain-specific deficiency of Rap1 failed to develop leptin resistance even when they were challenged with a hypercaloric diet. What impressed us most in this study was that Rap1 in the brain plays a key role in the whole body metabolic control, beyond its role in controlling leptin sensitivity. Loss of brain Rap1 protects mice from diet-induced obesity and disordered glucose balance, whereas these knockout mice maintained a similar body weight to that of control mice on a normal regular diet. Further, pharmacological inhibition of this pathway reversed leptin resistance and reduced the body weight of dietary obese mice. At the cellular level, we found an unexpected link between Rap1 and endoplasmic reticulum (ER) stress that has emerged as a causative contributor to the development of leptin resistance.
21 Sep BDNF Is Potential Biomarker For Autism Spectrum Disorder
MedicalResearch.com Interview with: [caption id="attachment_28240" align="alignleft" width="150"]
Dr. Yong Cheng[/caption]
Dr. Yong Cheng, PhD
Postdoctoral Fellow
NIH
MedicalResearch.com: What is the background for this study?
Response: Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders which affect about 1 in 68 children in the United States, according to data from the Centers for Disease Control and Prevention. Brain-derived neurotrophic factor (BDNF) is an important moderator in neurodevelopment and neuroplasticity, and studies have suggested the involvement of BDNF in ASD. Although some clinical studies show abnormal expression of BDNF in children with ASD, findings have been inconsistent. Therefore, we undertook a systematic review of the scientific literature, using a meta-analysis to quantitatively summarize clinical data on blood BDNF levels in children with ASD, compared with healthy peers.
19 Sep New Onset Diabetes, Especially In Lean Patients, Can Be Marker of Pancreatic Cancer
MedicalResearch.com Interview with: Dr. Pavel Škrha Charles University, Prague Czech Republic MedicalResearch.com: What is the background for this study? What are the main findings? Response: Incidence of pancreatic cancer (PAC) is still increasing. The main problem is in the late diagnosis of the cancer. It was found, that diabetes mellitus was much more frequent in the pancreatic cancer patients than in the general population. DM can be already the first symptom of the disease (secondry T3cDM). In our study nearly 80 % of all the pancreatic cancer patients had DM/prediabetes and it was of new-onset (less than 2 years before the cancer diagnosis) in 73 % out of them. We have measured the current marker of PAC (CA 19-9) together with serum microRNA-196 and -200 (that we have chosen in the previous pilot study). All the markers were significantly elevated in the pancreatic cancer patients, without any difference between the subgroups according to DM presence/absence. While the sensitivity of CA 19-9 alone (to detect the cancer) was 85 % (specificity 73 %), combining all the three markers improved it to 95 % (specificity 77 %). In the pancreatic cancer group, there were only six patients with T1 or T2 stage (others had an advanced stage of the disease - T3, T4). While CA 19-9 alone identified only 2 patients of them, the combined test identified all the six patients (data not shown in the poster).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 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 Women Still Getting CA-125 and CT Testing After Ovarian Cancer, Despite Lack of Clear Benefit
Posted at 00:39h
in Author Interviews, Beth Israel Deaconess, Biomarkers, Cost of Health Care, Medical Imaging, Ovarian Cancer
MedicalResearch.com Interview with:
[caption id="attachment_26310" align="alignleft" width="120"]
Dr. Katharine M. Esselen[/caption]
Katharine Mckinley Esselen, M.D.
Instructor in Obstetrics, Gynecology and Reproductive Biology
Beth Israel Deaconess Medical Center
Brigham and Womens Hospital
MedicalResearch.com: What is the background for this study?
Response: There is no consensus on how to follow a patient in remission from ovarian cancer in order to detect recurrent disease. However, a 2009 randomized clinical trial demonstrated that using CA-125 blood tests for routine surveillance in ovarian cancer increases the use of chemotherapy and decreases patient’s quality of life without improving survival compared with clinical observation. Published guidelines categorize CA-125 tests as optional and discourage the use of radiographic imaging for routine surveillance. Thus, this study aims to examine the use of CA-125 tests and CT scans at 6 Cancer Centers and to estimate the economic impact of this surveillance testing for ovarian cancer.
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.
20 Jul Metastatic Prostate Cancer Surges: Could Reduced PSA Screening Be A Cause?
MedicalResearch.com Interview with: [caption id="attachment_26283" align="alignleft" width="80"]
Dr. Adam Weiner[/caption]
Dr. Adam Weiner MD
Urology Resident
Feinberg School of Medicine
Northwestern University
MedicalResearch.com: What is the background for this study?
Response: There has been a lot of controversy over the past decade regarding whether PSA screening for prostate cancer prevents death from prostate cancer. Accordingly, the US preventive services task force (USPSTF) recommended against PSA screening for older men in 2008 and for all men in 2012. This was mainly based on information from a large clinical trial in the US.
Recently it was discovered that men in the non-screening part of this trial received even more PSA screens than men in the screening part of the trial, suggesting the results were likely diluted.
In a large European trial, PSA screening was shown to reduce both death from prostate cancer and the number of men diagnosed with metastatic prostate cancer, an incurable and deadly form of prostate cancer.
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.