Author Interviews, Biomarkers, Breast Cancer / 20.03.2016
Biomarker of Mutant Stromal Cells May Detect Breast Cancer Early
MedicalResearch.com Interview with:
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Dr. Lan Ko[/caption]
Lan Ko MD PhD
Augusta University
Cancer Center
Augusta, GA 30912, USA
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Lan Ko: Cancer development hijacks normal cell differentiation. Understanding the normal is where we could begin to unlock the secret of cancer. In normal breast tissue, stem or progenitor cells produce supporting stromal cells in normal breast development. In breast cancer, the progenitor cells are mutated leaving mutant stromal cell offspring with altered activities to induce tumor. Mutant stem or progenitor cells may have longer lifespan than their mutant descendents so that they can fuel cancer growth for years. Eliminating those mutant progenitors at the source, at least in theory, will efficiently stop cancer.
Each subgroup of breast tumor stromal cells has been previously described by other scientists. However, the connections among these cells were unclear in the past. Like blind men feeling elephant, we scientists are often obscured from seeing the entire picture. The finding of mutant breast tumor stromal cells using GT198 as a marker provides a critical puzzle piece that fits the rest of puzzle together. When cancer problems can be viewed in multiple aspects with great simplicity, their connections emerge. We now know why breast cancer stromal cells are important, and how should we target them.
Dr. Lan Ko[/caption]
Lan Ko MD PhD
Augusta University
Cancer Center
Augusta, GA 30912, USA
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Lan Ko: Cancer development hijacks normal cell differentiation. Understanding the normal is where we could begin to unlock the secret of cancer. In normal breast tissue, stem or progenitor cells produce supporting stromal cells in normal breast development. In breast cancer, the progenitor cells are mutated leaving mutant stromal cell offspring with altered activities to induce tumor. Mutant stem or progenitor cells may have longer lifespan than their mutant descendents so that they can fuel cancer growth for years. Eliminating those mutant progenitors at the source, at least in theory, will efficiently stop cancer.
Each subgroup of breast tumor stromal cells has been previously described by other scientists. However, the connections among these cells were unclear in the past. Like blind men feeling elephant, we scientists are often obscured from seeing the entire picture. The finding of mutant breast tumor stromal cells using GT198 as a marker provides a critical puzzle piece that fits the rest of puzzle together. When cancer problems can be viewed in multiple aspects with great simplicity, their connections emerge. We now know why breast cancer stromal cells are important, and how should we target them.
Dr. R. Jeffrey Karnes[/caption]
MedicalResearch.com Interview with:
R. Jeffrey Karnes MD
Department of Urology, Mayo Clinic,
Rochester, MN 55905
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Karnes: Cancer recurrence following radical prostatectomy is a concern for men undergoing definitive surgical treatment for prostate cancer. Approximately 20-35% of patients develop a rising prostate specific antigen following radical prostatectomy for clinically localized prostate cancer. PSA monitoring is an important tool for cancer surveillance; however, a standard PSA cutpoint to indicate biochemical recurrence has yet to be established. Over 60 different definitions have been described in literature. This variation creates confusion for the patients and clinicians. By studying a large group of patients who underwent radical prostatectomy at Mayo Clinic, we found that a PSA cutpoint of 0.4 ng/mL is the optimal definition for biochemical recurrence.
Dr. Stefan Verlohren[/caption]
Stefan Verlohren, MD, PhD
Consultant and Senior Lecturer
Maternal-Fetal Medicine
Klinik für Geburtsmedizin / Department of Obstetrics
Charité Campus Mitte
Berlin
Medical Research: What is the background for this study? What are the main findings?
Dr. Verlohren: Preeclampsia affects 2–5% of pregnancies worldwide, and is a potentially life threatening syndrome for both mother and child. Treatment options for preeclampsia are very limited, with delivery being the only ‘cure’; however, early detection and monitoring are beneficial for improving maternal and fetal outcomes. Development of preeclampsia is very difficult to predict: its clinical presentation is variable and its signs and symptoms overlap with other conditions. There has been an unmet medical need for improved prediction of preeclampsia, i.e. predicting which women will develop 
Dr. Leclercq[/caption]
MedicalResearch.com Interview with:
Florence Leclercq, MD, PhD
Department of Cardiology
Arnaud de Villeneuve Hospital
University hospital of Montpellier
Montpellier,France
Medical Research: What is the background for this study? What are the main findings?
Response: Patients with history of coronary artery disease (CAD) are considered as a population with high risk of further coronary events. However, frequent pre-existing ECG changes observed in these patients result in difficulty interpreting new ECG aspects in case of chest discomfort. Furthermore, anxiety frequently induced non-cardiac causes of chest pain in these patients, leading to unjustified admission to cardiology units. Moreover, levels of troponin are usually higher in patients with previous CAD compared to patients without history of angina, resulting in difficulty interpreting baseline values in this population. Conversely, copeptin may be influenced by the severity of myocardial ischemia and resulting endogenous stress, and could be a useful additional marker to exclude severe coronary stenosis in high-risk patients with recent chest pain.
This propective monocentric study evaluates the incremental value of copeptin associated with high-sensitivity cardiac T troponin (hs-cTnT) to exclude severe coronary stenosis in 96 patients with coronary artery disease (CAD) and acute chest pain.
Mean age of patients was 60 +/- 13.8 years and the mean time between chest pain onset and blood samples of copeptin was 4.2 +/-2.7 hours. According to clinical decision, coronary angiography was performed in 71 patients (73.9 %) and severe stenosis diagnosed in 14 of them (14.6%). No ischemia was detected on SPECT imaging (n=25). Among the 69 patients with a negative kinetic of hs-cTnT and a negative baseline copeptin, 5 (7.4%) had a severe stenosis (NPV 0.93; 95% CI: 0.87-0.99), 4 of them related to in-stent restenosis (NPV for exclusion of native coronary stenosis: 0.98; 95% CI: 0.93-1).
We can conclude that in patients with preexisting CAD, and once Acute Myocardial Infarction (AMI) is excluded, copeptin increases the NPV of 
Dr. McHugh[/caption]
MedicalResearch.com Interview with:
Leo McHugh, Ph.D.
Director, Bioinformatics
Immunexpress
Seattle, Washington
Medical Research: What is the background for this study? What are the main findings?
Dr. McHugh: Sepsis is the leading cause of child mortality in the world, and in developing countries kills more adults than breast cancer, prostate cancer and HIV combined. Approximately 30% of people admitted to ICU have sepsis, and up to 50% of these patients die. It’s a major cost burden also, costing the US health system $17 billion per year. The best way to reduce costs and improve patient outcomes is to detect sepsis early and with confidence, so that appropriate treatments can be applied. Each hour delay in the detection of sepsis has been reported to correspond to an 8% increase in mortality. So the need for a rapid and accurate diagnostic is recognized. Traditional methods rely on detection of the specific pathogen causing the infection, and these methods often take more than 24 hours, and find a pathogen in only 30% of clinically confirmed cases because they’re trying to detect a minuscule amount of pathogen or pathogenic product in the blood. Our approach was to use the host’s own immune system, which is highly tuned to respond to the presence of pathogens. Around 30% of all genes are dysregulated in sepsis, so there is a huge signal base to draw from. The trick with using multi marker host response is to pick out the specific combination of gene expression patterns that cover the broad range of patients that present with sepsis and who may present either early or late in the episode, thus with different gene activation patterns.
This paper describes a simple combination of such genes that can be used to detect sepsis and performs over the full range of patients irrespective of stage of infection or severity of infection. In it’s current format, the test is manual and takes 4-6 hours, and is a great advance on the current tools, however the methods we’ve used are specifically designed to meet requirements to port this assay onto a fully automated Point of Care platform that could deliver a result in under 90 minutes.
Dr. Daniels[/caption]
MedicalResearch.com Interview with:
Lori Daniels, MD, MAS, FACC
Professor of Medicine
Director, Coronary Care Unit
UCSD Division of Cardiology
Sulpizio Cardiovascular Center
La Jolla, CA
Medical Research: What is the background for this study?
Dr. Daniels: A large number of individuals who are at risk for developing cardiovascular disease (CVD) may not be identified as “at risk” by traditional screening methods. Blood-based biomarkers provide a possible way, in conjunction with traditional risk factor screening, to assess risk in individuals. Two such biomarkers which are gaining widespread attention are NT-proBNP and cardiac troponin T (TnT). NT-proBNP is secreted by cardiac muscle cells in response to stretch, while TnT is consider a marker of cardiac cellular damage. Previous studies have shown that each of these markers is associated with long-term risk of cardiovascular outcomes in the general population. Race and ethnicity have been shown to affect the levels of these markers, and whether these markers are equally predictive of future cardiovascular risk in various ethnic groups has not been well studied.
The Multi-Ethnic Study of Atherosclerosis (MESA) is an NIH-funded, multicenter, prospective, population-based study of white, black, Hispanic, and Chinese individuals without clinical CVD at baseline. Participants had blood drawn at a baseline study visit in 2000-2002, and again several years later, in 2004-2005. They have been followed for the development of CVD since then.
The purpose of this study was to learn whether NT-proBNP (single and serial measures) and TnT are predictive of incident cardiovascular disease in a diverse cohort of 5592 participants from the MESA. We also wanted to learn whether the addition of these biomarkers to established CVD risk prediction scores, including the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) Pooled Cohort Risk Equation and the Framingham Risk Score, could improve performance of the risk score.
