Allergies, Asthma, Author Interviews, Biomarkers, Sleep Disorders / 07.03.2017 Interview with: Rauno Joks, MD Associate Professor of Clinical Medicine Chief, Division of Allergy & Immunology Program Director, Allergy &Immunology Fellowship SUNY Downstate Medical Center What is the background for this study? What are the main findings? Response: There are circadian and circannular patterns to many diseases, including allergy and asthma. Humans spend roughly one-third of their lifetimes asleep. Your immune system never sleeps, but shifts its activity when you sleep. It is known that asthma disease activity can be worse at night - the reasons for this are complex, and may involve changes in allergic responses. We found, in a preliminary study of both adults with and without asthma, that longer duration of nighttime sleep was associated with lower levels of exhaled nitric oxide, a biomarker which is elevated in exhaled breath of those with allergic asthma. This may carry over into the afternoon as well, but the sample size was too small to fully conclude that. (more…)
Author Interviews, Biomarkers, Breast Cancer, Genetic Research, Race/Ethnic Diversity, Wistar / 28.02.2017 Interview with: Maureen E. Murphy, Ph.D. Professor and Program Leader, Molecular and Cellular Oncogenesis Program Associate Vice President for Faculty Affairs Associate Director for Education and Career Development The Wistar Institute Philadelphia, PA 19104 What is the background for this study? What are the main findings? Response: The Murphy group discovered a coding-region variant of the p53 tumor suppressor gene, called Pro47Ser, that exists in individuals of African descent. In previous studies this group reported that this amino acid change reduces the ability of p53 to function as a tumor suppressor. In this study, African American women from two different large cohorts were assessed for the incidence of the Pro47Ser variant in pre-menopausal breast cancer. A modest but statistically significant association was found between Pro47Ser and pre-menopausal breast cancer. (more…)
Author Interviews, Biomarkers, Genetic Research, PLoS, Prostate Cancer / 23.02.2017 Interview with: G. Andrés Cisneros, Ph.D. Associate Professor Department of Chemistry Center for Advanced Scientific Computing and Modeling, University of North Texas What is the background for this study? What are the main findings? Response: The accurate maintenance of DNA is crucial, if DNA damage is not addressed it can lead to various diseases including cancer. Therefore, the question arises about what happens if enzymes in charge of DNA repair are themselves mutated. We previously developed a method to perform targeted searches for cancer-related SNPs on genes of interest called HyDn-SNP-S. This method was applied to find prostate-cancer SNPs on DNA dealkylases in the ALKB family of enzymes. Our results uncovered a particular mutation on ALKBH7, R191Q, that is significantly associated with prostate cancer. Subsequent computer simulations and experiments indicate that this cancer mutation results in a decreased ability of ALKBH7 to bind its co-factor, thus impeding its ability to perform its native function. (more…)
Author Interviews, Biomarkers, Pharmacology, Prostate Cancer / 19.02.2017 Interview with: Teemu J Murtola, MD, PhD, adjunct professor University of Tampere, Faculty of Medicine and Life Sciences Tampere University Hospital, Department of Urology Tampere, Finland What is the background for this study? Response: A previous study called Prostate Cancer Prevention Trial (PCPT) showed that finasteride, which belongs to a drug group called 5alpha-reductase inhibitors lowers serum PSA and increases sensitivity of PSA to detect high-grade prostate cancer in men who had little or no symptoms of the lower urinary tract. We postulated that this effect would increase the accuracy and benefits of PSA-based prostate cancer screening. Finnish Randomized Study of Screening for Prostate Cancer was a large trial of over 80,000 men randomized either to be screened for prostate cancer with a PSA test at 4-year intervals or to be followed for prostate cancer incidence and mortality via national registries. Three consecutive screening rounds were commenced between 1996-2008. In the current study we compared the effects of PSA-based screening on prostate cancer risk and mortality separately among men who were using 5alpha-reductase inhibitors finasteride or dutasteride and among men who were not. (more…)
Author Interviews, Biomarkers, Genetic Research, Personalized Medicine, Prostate Cancer / 17.02.2017 Interview with: Dr. John L. Gore, MD Associate Professor Adjunct Associate Professor-Surgery Department of Urology University of Washington What is the background for this study? What are the main findings? Response: The rationale for our study derives from the uncertainty that both patients and clinicians confront when trying to make decisions about adjuvant therapy for prostate cancers found to have aggressive pathologic features at the time of radical prostatectomy. There is level 1 evidence in support of adjuvant radiation therapy in this setting, but several factors restrain providers from recommending adjuvant radiation. We found that interjecting a genomic test that predicts the risk of clinical metastases 5 years after surgery impacts the treatment recommended and helps men and clinicians feel more confident in the decision they are making or recommending. (more…)
Author Interviews, Biomarkers, Breast Cancer, Genetic Research / 17.02.2017 Interview with: Carlos H. Barcenas M.D., M.Sc. Assistant Professor Department of Breast Medical Oncology MD Anderson Cancer Center What is the background for this study? What are the main findings? Response: Over the last decade we have realized that we were over-treating many early stage breast cancer patients. In addition to the chemotherapy’s obvious side effects, there are also long term complications for breast cancer survivors. Since 2005, we are using a 21-gene-expression assay that predicts the risk of distant recurrence among early stage breast cancer patients. In 2015, initial results from the international clinical trial, TAILORx, found that women with hormone receptor positive, HER2 and lymph node negative early stage disease that had a low recurrence score (RS) of 0-10 from this assay could have chemotherapy omitted altogether. While these findings changed care for women with a low RS, questions remain regarding the management of women with an intermediate RS, defined by this trial as a RS of 11-25. For our retrospective, single-institution study we identified 1,424 stage I and II breast cancer patients with hormone receptor positive, HER2 and lymph node negative treated between 2005 and 2011 who underwent the 21-gene expression assay. The RS distribution was: 297 (21 percent) scored 0–10; 894 (63 percent) scored 11-25; and 233 (16 percent) scored >25. Of those groups, 1.7, 15 and 73.4 percent received chemotherapy, respectively. With a median follow up of 58 months, those with a RS of 11-25 had an invasive disease-free survival (IDFS) rate at five years of 92.6 percent, regardless if patients received chemotherapy or not. Among those patients who did not receive chemotherapy, the estimated rates of IDFS and overall survival was 93 percent and 98 percent, respectively, which was comparable to those who did receive chemotherapy. (more…)
Author Interviews, Biomarkers, Cancer Research / 15.02.2017 Interview with: Edwin Posadas, MD, FACP, KM Director, Translational Oncology Program Medical Director, Urologic Oncology Program Samuel Oschin Comprehensive Cancer Institute Clinical Chief, Division of Hematology/Oncology Associate Professor, Department of Medicine Cedars-Sinai What is the background for this study? What are the main findings of your work so far? Response: The technology we are using is called a NanoVelcro assay. This is a nanotechnology that can be used to isolate rare cells and cell-like particles in the blood stream. We have focused the use of the NanoVelcro on isolating circulating tumor cells (or CTCs). This technology is about 10 times more sensitive than that currently used in clinics. More importantly, because of some modification in our approach, we can now not only capture CTCs, but also examine them under the microscope and even analyze them using advanced molecular techniques. In this way, we take a classic and modern approach to our work. We firmly believe that there is much to be learned by studying the shapes of these CTCs. We in the cancer field have long known that shape and cellular function are intimately related. In fact, a young pathologist in our group readily recognized that patients with the most aggressive cancers had CTCs with small nuclei, which we verified in a larger study. We are now exploring the importance of these shape variations in CTCs by coupling this classic microscopy-driven approach with RNA characterizations, giving us insight into the molecular nature of the CTC. My collaborator, UCLA Professor Hsian-Rong Tseng, PhD, is a brilliant engineer who has found ways of altering the system to allow us to capture and release live cells for analysis. By using this system, we believe that one day we may be able to avoid performing invasive tissue biopsies to study a cancer. (more…)
Author Interviews, Biomarkers, Heart Disease, JAMA / 12.02.2017 Interview with: Frederick L. Ruberg, MD Director, Cardiovascular Medicine Fellowship Training Program Director, Pilot Grants Program, Boston University Clinical and Translational Science Institute Director, Advanced Cardiac Imaging Program Section of Cardiovascular Medicine Department of Medicine Department of Radiology Boston Medical Center What is the background for this study? What are the main findings? Response: ATTR cardiac amyloidosis is an under-recognized cause of congestive heart failure in older adults that results from the deposition of misfolded TTR protein in the heart. One cause of ATTR cardiac amyloidosis is a genetic abnormality, inherited from an affected patient’s parent, that causes the protein TTR to misfold. The most common genetically inherited cause of ATTR amyloidosis in the US is called Val122Ile (V122I), named for the specific mutation in the TTR gene, that is seen in approximately 3.5% of US African Americans. ATTR cardiac amyloidosis was once an untreatable disease, but now new drugs are in different stages of clinical trial testing. Thus, recognition is important to get patients on the right treatments. One of the principal reasons why the disease is under-recognized is that doctors don’t have proven and available diagnostic tests that can be applied in the outpatient clinic. This study demonstrated that a new point-of-care diagnostic test, using measurement of a blood protein called retinol binding protein 4 (RBP4) and other standard of care test information, can accurately diagnose ATTR cardiac amyloidosis. We demonstrated the validity of this test in two separate cohorts of patients with proven ATTR cardiac amyloidosis due to the Val122Ile mutation and control patients with heart failure but without amyloidosis. (more…)
Author Interviews, Biomarkers, Endocrinology, NIH / 10.02.2017 Interview with: Mihail Zilbermint, M.D. Endocrinologist, Office of the Scientific Director Mihail Zilbermint, M.D. Endocrinologist, Office of the Scientific Director Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health What is the background for this study? Response: Diagnosing Cushing Syndrome is often difficult and challenging.  Diagnosing hypercortisolemia, could require the use of a combination of any of these tests: 24-hour free urine cortisol monitoring, an overnight dexamethasone suppression test, and measurement of late night salivary cortisol.  Cortisol levels may change daily, requiring that testing be repeated.  Undiagnosed and untreated Cushing Syndrome greatly increases morbidity and mortality risk. Cortisol levels can be detected in hair samples.  Much like hemoglobin A1C is a long-term indicator of blood glucose levels, efforts have been made to determine if hair cortisol could serve as a long-term measure of the body’s glucocorticoid levels.  We sought to compare the results of cortisol levels for Cushing Syndrome patients with data from data on cortisol in hair segments, to gain further information on the role of sampling hair cortisol as an initial or supportive method for diagnosing Cushing Syndrome. (more…)
Author Interviews, Biomarkers, Breast Cancer, Cancer Research / 14.01.2017 Interview with: Ulrich Pfeffer, PhD Head of the Functional Genomics lab IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro Genova, Italy What is the background for this study? What are the main findings? Response: In recent years our knowledge on genetic variants that are associated with the risk to develop breast cancer has grown substantially. In addition to the two breast cancer genes, BRCA1 and BRCA2 we know approximately 100 other genes that are present in the population in two variants. In the presence of a single of these variants the breast cancer risk is slightly increased and several variants together determine a significant increase in risk. We also know that certain variants are associated with specific subtypes of breast cancer such as the estrogen receptor positive breast cancer. We show in our work for the first time that some of these variants are more frequent in breast cancers that carry a specific somatic, non-inherited, mutation. In particular, we show this for the most frequent somatic mutation in breast cancer, PIK3CA, a gene involved in the control of tumor metabolism and many other aspects, a fundamental gene. The knowledge of this association tells us a lot on cancer biology. But most important, it might help to design specific prevention strategies. Since when you carry a germline allele that is associated with a specific somatic mutation you know your risk of a specific molecular type of breast cancer and eventually you can do something specific to prevent it. (more…)
Author Interviews, Biomarkers, Cancer Research, ENT / 13.01.2017 Interview with: Jacek Majewski PhD Associate Professor Department of Human Genetics McGill University and Genome Quebec Innovation Centre Montreal, Canada What is the background for this study? Response: Our lab, in collaboration with Dr. Nada Jabado, has been investigating the molecular genetics of pediatric glioblastoma – a deadly brain cancer. Several years ago, in the majority of our patients’ tumors we discovered mutations in genes that encode histone proteins. Those mutations disrupt the epigenome - that is the way the DNA is modified, silenced, or activated in the cancer cells. It appears that epigenome-modifying mutations are particularly important in pediatric cancers, and our hypothesis is that they act by diverting the normal developmental pathways into unrestrained proliferation. Many other studies have highlighted the significance of epigenome disruption in a number of cancers. (more…)
Author Interviews, Biomarkers, JAMA, Prostate Cancer, Radiation Therapy / 13.01.2017 Interview with: Trevor Royce MD MS Resident, Harvard Radiation Oncology Program What is the background for this study? What are the main findings? Response: Clinical trials in early prostate cancer take more than a decade to report on. Multiple early reporting endpoints have been proposed, but which one is best, remains unknown, until now. Of all the possible early endpoints examined, to date, how low a PSA blood test falls to, after treatment with radiation and hormonal therapy, appears to be the best, specifically, if the PSA doesn’t get below half a point, that patient is very likely to die of prostate cancer if given standard treatment for recurrence. Those men deserve prompt enrollment on clinical trials in order to properly save their life. (more…)
Author Interviews, Biomarkers, Critical Care - Intensive Care - ICUs, Infections, JAMA, Pediatrics / 11.01.2017 Interview with: Halden F. Scott MD, Assistant Professor Departments of Pediatrics and Emergency Medicine University of Colorado School of Medicine What is the background for this study? Response: Sepsis, a dysregulated immune response to infection, is a leading cause of death for children. Survival depends on rapid diagnosis and timely delivery of life-saving resuscitative care, including fluids and antibiotics. However, it can be challenging to make an early diagnosis of sepsis in children. Millions of children present for emergency care of infection and fever every year, most of whom will not develop sepsis. Tools that assist providers in distinguishing the sickest children with infection at an early stage could enable the early delivery of life-saving treatments. Lactate is a clinically-available laboratory test that has played a critical role in improving the diagnosis and treatment of sepsis in adults. Sepsis may cause lactate levels to rise in the blood during sepsis, through reduced delivery of oxygen to the tissues, as well as through changes in how energy is produced and in how lactate is cleared by the kidney and liver. Data about lactate in pediatric sepsis, particularly early levels and whether it is associated with mortality, have been limited. (more…)
Aging, Author Interviews, Biomarkers / 09.01.2017 Interview with: Paola Sebastiani PhD Department of Biostatistics Boston University School of Public Health Boston, MA 02118 What is the background for this study? What are the main findings? Response: Human life expectancy has increased steadily in the last century and has led to a growth of the elderly population and a need for prevention strategies and interventions that promote healthy aging. A challenge in assessing the effect of such interventions is ‘what to measure’ because people can age very differently from one another. Our study used 19 blood biomarkers that include for example cholesterol level and hemoglobin A1C to discover 26 biological signatures of aging in approximately 4,700 participants of the Long Life Family Study. These signatures are essentially patterns of values of the 19 biomarkers and we showed that one of these signatures is associated with better physical and cognitive functions, and reduced risk for disease and mortality compared to the most common signature in the study. Additional signatures predict varying risk for diabetes, cardiovascular and other aging-related diseases. We replicated these results in an independent data set. The associations of these biomarker signatures with physical and cognitive functions, and risk for morbidity and mortality support the conclusion that they capture different form of biological aging. (more…)
Author Interviews, Biomarkers, JAMA, Multiple Sclerosis / 07.01.2017 Interview with: Prof Rogier Q Hintzen Neurologist/immunologist Head MS Centre ErasMS Dept of Neurology Erasmus MC, Rotterdam What is the background for this study? What are the main findings? Response: Years ago, we identified soluble (s) CD27 as a biomarker for T cell activation in body fluids, as part of my PhD study. (J Immunol. 1991 Jul 1;147(1):29-35.) As we presume the neuropathology seen in MS is guided by T cells we were interested to be able to quantify the activity of such cells in a given patient. Cerebrospinal fluid (CSF) is as close as we can get to the site of the disease process in MS, therefore we focus on biomarkers in this compartment. We found clearly elevated levels of sCD27 in CSF of Multiple Sclerosis patients versus non-inflammatory controls. In this study we investigated whether at the moment of first attack of suspected Multiple Sclerosis, quantification of CSF sCD27 can predict further progression in to a diagnosis of MS and whether sCD27 levels are correlated with later attack frequency. Indeed, we found that high sCD27 measured at this early stage predicts a more rapid diagnosis of Multiple Sclerosis and a more aggressive disease course. (more…)
Author Interviews, Biomarkers, Heart Disease, JACC / 04.01.2017 Interview with: Prof. Michele Emdin, MD, PhD, FESC Associate Professor of Cardiovascular Medicine Director, Cardiology & Cardiovascular Medicine Division Fondazione Toscana Gabriele Monasterio per la Ricerca Medica e di Sanità Pubblica CNR-Regione Toscana with the collaboration of Dr. Alberto Aimo, MD Institute of Life Sciences Scuola Superiore Sant'Anna - Sant'Anna School of Advanced Studies Pisa, Italy What is the background for these meta-analyses? Response: Soluble suppression of tumorigenicity 2 (sST2) is a novel and promising biomarker of heart failure (HF). It has been extensively studied in both stable chronic (CHF) and acute HF (AHF), demonstrating substantial potential as a predictor of prognosis in both settings (Dieplinger et al., 2015). An International Consensus Panel (Januzzi et al., 2015) and latest American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines (Yancy et al., 2013) support the use of sST2 assay for risk stratification in both CHF and AHF patients. By contrast, European Society of Cardiology guidelines do not provide specific recommendations on sST2 (Ponikowski et al., 2016). Because of ambiguity due to discordant conclusions and to the absence of a thorough revision of the literature and of rigorous meta-analyses of published studies up-to-date, we felt it worthwhile to carefully examine and meta-analyze evidence supporting measurement of sST2, in order to assess the prognostic role of this biomarker in CHF and AHF. Most of the groups originally publishing on the topic all over the world and representing the Gotha of clinical research on cardiovascular biomarker, accepted to directly contribute allowing the main Authors to achieve novel information by a guided statistical reappraisal, The final results furnish clinically significant support to the use of sST2 as a risk stratification tool either in the acute or in the chronic heart failure setting. (more…)
Author Interviews, Biomarkers, Cancer Research, JAMA / 29.12.2016 Interview with David A Mankoff, MD, PhD Gerd Muehllehner Professor of Radiology Attending Physician University of Pennsylvania Health System PET Center Director Vice-Chair of Research, Department of Radiology University of Pennsylvania What is the background for this study? What are the main findings? Response: This review was designed to describe the current status of molecular imaging, especially positron emission tomography (PET) as a clinical tool for helping to direct precision oncology. We found that while there had been a number of promising methods tested in small, single research studies, the number of new molecular imaging tests translated to the clinic was small. In addition, the application of molecular methods as tools for therapeutic decision making (versus use for disease detections and staging) was even smaller. We noted that some recently published studies, including a few large multi-center trials, indicated the considerable potential of new molecular imaging tests to identify therapeutic targets for cancer treatment, to evaluate early response to targeted cancer therapy, and to predict downstream outcomes such as progression free survival. We made some observations and recommendations in the review for directing these potentially powerful imaging tools towards use as biomarkers for precision oncology. (more…)
AACR, Author Interviews, Biomarkers, Breast Cancer, Chemotherapy / 26.12.2016 Interview with: Helena Jernström, PhD Associate Professor in Experimental Oncology Study Coordinator for Graduate studies Division of Oncology and Pathology Coordinator of the programmes in statistics and epidemiology for doctoral students at the Medical Faculty, Lund University Division of Oncology and Pathology, Department of Clinical Sciences, Lund Lund University Cancer Center/Kamprad Lund, Sweden What is the background for this study? Response: There is a need for better predictive markers to guide selection of therapy in breast cancer patients. Estrogen receptor beta (ER-beta) may confer prognostic information beyond what is currently obtained by the established clinical markers, including ER-alpha, which is routinely evaluated. (more…)
Author Interviews, Biomarkers, Multiple Sclerosis / 19.12.2016 Interview with: Charles Bangham PhD ScD Division of Infectious Diseases, Department of Medicine Imperial College London London, UK What is the background for this study? Response: Multiple sclerosis (MS) is a neurological disease of the brain and spinal cord, often beginning in the 20s and 30s which can cause both attacks (relapses) and disability over time. Most people with the condition have intermittent episodes of illness at first, but about two-thirds go on to develop a progressive form, known as secondary progressive MS. In this form, there is a gradual loss of nerve cells in the brain, resulting in shrinkage of the brain and progressive disability. Neither the initiating cause of  Multiple sclerosis nor the reasons for this brain shrinkage are known, and existing treatments for the early phase of the condition are unsatisfactory. (more…)
Author Interviews, Biomarkers, Infections, JAMA, Neurological Disorders / 12.12.2016 Interview with: Zanusso Gianluigi M.D.Ph.D. Department of Neurosciences, Biomedicine and Movement Sciences University of Verona Verona, Italy What is the background for this study? What are the main findings? Response: To determine RT-QuIC assay sensitivity and specificity in cerebrospinal fluid and olfactory mucosa in a large group of patients with a clinical diagnosis of probable, possible or suspect Creutzfeldt–Jakob disease (CJD) and controls. In these patients, RT-QuIC testing of CSF and olfactory mucosa provided a specificity and sensitivity of 100%. A softer swab for olfactory mucosa sampling provided the same sensitivity as using a brush . (more…)
Author Interviews, Biomarkers, Pediatrics, Pulmonary Disease / 02.12.2016 Interview with: Prof. Henrik Verder Department of Pediatrics Holbaek University Hospital Denmark What is the background for this study? What are the main findings? Response: Respiratory Distress Syndrome (RDS) is a major cause of mortality and morbidity in premature infants. It can be effectively treated with surfactant, a therapy which reduces the effort needed to expand the lungs during inspiration and allow gas exchange to take place. Early surfactant treatment can help prevent the onset and impact of RDS, however, prophylactic treatment has been shown to be harmful and only necessary in half of all pre-term infants. This study provided data validating the efficacy of a lung maturity test (LMT) in identifying infants at risk of respiratory distress syndrome (RDS) who could benefit from early surfactant treatment. (more…)
Alcohol, Author Interviews, Biomarkers, Genetic Research / 28.11.2016 Interview with: Chunyu Liu, PhD The Population Sciences Branch, Division of Intramural Research The Framingham Heart Study, National Heart, Lung and Blood Institute Framingham, MA Department of Biostatistics Boston University School of Public Health Boston, MA What is the background for this study? What are the main findings? Response: Excessive alcohol consumption contributes to many diseases as well as to injuries and deaths. The lack of reliable measures of alcohol intake is a major obstacle to the diagnosis and treatment of alcohol-related diseases. Our study has identified a group of DNA markers in blood that could provide the basis for a reliable blood test to detect heavy alcohol use. (more…)
Author Interviews, Biomarkers, BMJ, Heart Disease / 25.11.2016 Interview with: Archana Singh-Manoux, PhD Research Professor (Directeur de Recherche) Epidemiology of ageing & age-related diseases INSERM,France 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. (more…)
Author Interviews, Biomarkers, Cancer, Cancer Research, University of Pennsylvania / 28.10.2016 Interview with: Eric Ojerholm, MD Resident, Radiation Oncology Hospital of the University of Pennsylvania 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. 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? (more…)
Author Interviews, Biomarkers, Immunotherapy, Pancreatic / 21.10.2016 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 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. (more…)
Author Interviews, Biomarkers, Infections, Technology / 19.10.2016 Interview with: Ying Kong Ph.D. Assistant Professor University of Tennessee Health Science Center Department of Microbiology, Immunology, and Biochemistry Memphis, TN 38163 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.). (more…)
Author Interviews, Biomarkers, Heart Disease / 18.10.2016 Interview with: Susan Stienen, MD Department of Cardiology Academic Medical Center University of Amsterdam Amsterdam, the Netherland 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. (more…)
Author Interviews, Biomarkers, Cancer, Prostate Cancer, UT Southwestern / 08.10.2016 Interview with: Dr Ryan Hutchinson MD and Yair Lotan MD Department of Urology University of Texas Southwestern Medical Center 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. (more…)
Author Interviews, Biomarkers, Cancer Research, ENT, HPV / 03.10.2016 Interview with: Elizabeth Franzmann, M.D. Scientific Founder and Chief Scientific Officer Vigilant Biosciences 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. (more…)