Author Interviews, Biomarkers, Diabetes, Pancreatic / 19.09.2016
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).
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.
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).
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.
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%.
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.
Dr. Yvan Devaux[/caption]
Yvan Devaux, PhD
Associate Head of Laboratory
Cardiovascular Research Unit
Department of Population Health
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 
