Dr. Andrea Wickremasinghe[/caption]
Andrea C. Wickremasinghe, MD
Neonatologist
Kaiser Santa Clara California
MedicalResearch.com: What is the background for this study?
Response: Neonatal jaundice is common and is often treated with phototherapy. Phototherapy is typically considered to be benign. In the past decade, phototherapy use has increased and it is sometimes started at bilirubin levels below recommended treatment thresholds. Beginning in the 1970’s, in-vitro and in-vivo studies have shown phototherapy to be associated with cellular changes implicated in the pathogenesis of cancer. Epidemiologic studies have yielded mixed results, with some studies showing associations between phototherapy and leukemia and other studies failing to show this association. In this study, we used a large statewide administrative dataset to investigate the relationship between neonatal phototherapy and cancer in the first year after birth.
Dr-Aurora-Perez-Cornago[/caption]
Aurora Perez-Cornago, PhD
Cancer Epidemiology Unit
Nuffield Department of Population Health
University of Oxford
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Excessive body size and adiposity have been proposed to influence
several metabolic and hormonal mechanisms that can promote cancer development.
We found that men who have greater adiposity have an elevated risk of
high grade prostate cancer, an aggressive form of the disease, and
prostate cancer death.
Dr. Michael Johnson[/caption]
Michael A. Johnson Ph.D
Associate Professor
Department of Chemistry
University of Kansas
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Johnson: We undertook these studies because chemotherapy induced cognitive dysfunction, also known as ‘chemobrain’, has become a major health issue in recent years. For example, up to a third of patients who have undergone chemotherapy treatment for breast cancer have reported symptoms of chemobrain. These symptoms may include loss of verbal and visual memory as well as decreased mental flexibility and difficulty focusing.
For this study, we wanted to understand how treatment with chemotherapeutic agents affects the ability of neurons to communicate. An impairment of neurotransmitter release would imply that communication is hindered. This inability to communicate normally could contribute to cognitive dysfunction.
We initially measured the release of dopamine in a region of the brain called the striatum. Our measurement of dopamine in this region was motivated by two key issues: its importance in cognitive function and our ability to measure it with high temporal resolution. From a cognitive standpoint, dopamine is important because the striatum helps translate signals, received from the cortex, into plans by forwarding wanted signals to other parts of the brain and suppressing unwanted signals. Fortunately, we can easily measure dopamine release using an electrochemical technique called fast-scan cyclic voltammetry. This method allows us to not only measure how much dopamine is released from a living brain slice, but also it affords us the capability to measure how quickly dopamine is taken back up. We also measured serotonin release using this method.
Our main finding was that the ability of neurons to release dopamine was impaired after carboplatin treatment. We also found that serotonin release was similarly impaired. These release impairments corresponded to a decrease in cognitive ability of the treated rats.
Dr. Robert Wong[/caption]
Robert Wong, M.D., M.S.
Attending Physician, Gastroenterology & Hepatology
Director, GI Education & Research
Highland Hospital I A member of Alameda Health System
Oakland, CA
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Wong: Colorectal cancer is a leading cause of morbidity and mortality in the United States. Early diagnosis through implementation of effective screening and surveillance programs leads to earlier staged tumor at time of diagnosis, which increases the treatment opportunities and improves overall survival. However, disparities in access to effective screening and surveillance can impair timely diagnosis and lead to advanced disease, limited treatment options and poor outcomes. The current study evaluated race/ethnicity-specific disparities in colorectal cancer epidemiology at a large urban safety net hospital and observed African American patients had significantly more advanced cancer stage at the time of diagnosis. Our study observed that African Americans were over 5 times more likely to have advanced stage 3-4 colon cancer at time of diagnosis compared with non-Hispanic white patients with colon cancer. While these findings are likely multifactorial, it sheds important light on race/ethnicity-specific disparities in colorectal cancer epidemiology and helps target future education and research to improve outcomes.
Dr. Sibaji Sarkar[/caption]
Sibaji Sarkar Ph.D
Instructor of medicine
Boston University School of Medicine
Boston
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Sarkar: Although breast and ovarian cancers have different clinical presentations, there are certain molecular events that are conserved between the two types of cancers. For example, mutation in a few genes, such as BRCA1, BRCA2, is an indicator of possible development of both breast and ovarian cancers. ARHI, a pro-apoptotic imprinted gene is epigenetically silenced in both breast and ovarian cancers. A similar pattern was observed in microRNA as well. There are also several genes which are differentially expressed in these two types of cancers but few of these striking resemblances led us to investigate whether they have a common origin. In this paper, we compared genetic and epigenetic events in both breast and ovarian cancers and we hypothesize that they may have similar origin (mechanism of formation of cancer progenitor cells), which should be regulated by epigenetic mechanism.
Nana Keum[/caption]
NaNa Keum, ScD|
Harvard T. H. Chan
School of Public Health Department of Nutrition
Departments of Nutrition and Epidemiology,
Harvard T.H. Chan School of Public Health
Boston, MA 02115
MedicalResearch.com: What is the background for this study?
Response: While general health benefits of physical activity are well-known, evidence on its specific benefits on cancer endpoints is limited and physical activity guidelines for cancer prevention lack details in terms of the optimal dose, type and intensity of physical activity.
MedicalResearch.com: What are the main findings?
Response: We found that the optimal exercise regime to prevent overall digestive system cancers may be to accumulate 30 MET-hours/week of physical activity primarily through aerobic exercise and regardless of its intensity.
Dr. Alejandro Sousa[/caption]
Alejandro Sousa, MD, PhD
Department of Urology, Comarcal Hospital
Monforte, Spain
MedicalResearch.com: What is the background for this study?
Dr. Sousa: Bladder Cancer management has remained stable over the past 25 years, with very little in the way of new therapies or approaches being developed. Traditional treatment using intravesical Mitomycin C for Non Muscle Invasive Bladder Cancer (NMIBC) patients is limited due it's low absorption levels. Device assisted therapies that deliver Chemo-hyperthermia offer a new hope, with the potential for improved outcomes and better disease management due the the increased drug activity and better efficacy. We wanted to investigate the optimal treatment regime for this new therapy and whether it provides a safe and effective alternative to current standard treatment.
Dr. James Welsh[/caption]
James S. Welsh, MS, MD, FACRO
President, American College of Radiation Oncology
Professor and Medical Director
Director of Clinical & Translational Research
Department of Radiation Oncology
Stritch School of Medicine Loyola University- Chicago
Cardinal Bernardin Cancer Center
Maywood, IL 60153
Chief of Radiation Oncology
Hines VA Medical Center
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Welsh: Cancer immunotherapy could represent a truly powerful means of addressing cancer. Although immunotherapy itself is not new, there are new agents and combinations of older agents (including radiation therapy) that could prove more successful than anything we have seen in many years. The data in melanoma thus far is quite encouraging and this preliminary success could possibly extend to many other malignancies as well.
Dr. Aaron Thrift[/caption]
Aaron Peter Thrift, Ph.D
Assistant Professor
Duncan Cancer Center
Department of Medicine, Gastroenterology Section
Baylor College of Medicine
Houston, TX, US
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Thrift: Patients with Barrett’s esophagus are at significantly higher risk of developing esophageal adenocarcinoma. Due to the continued rise in incidence of esophageal adenocarcinoma attention has turned to chemoprevention as a method to delay or halt the progression of Barrett’s esophagus to neoplasia, including invasive cancer. Acid suppressive medications, such as proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs), are commonly used in patients with gastroesophageal reflux disease (GERD), the primary risk factor for Barrett’s esophagus.
We contacted a nested case-control study involving 311 patients with Barrett’s esophagus who developed esophageal adenocarcinoma (cases) and 856 matched controls (patients with Barrett’s esophagus but who did not develop esophageal adenocarcinoma). Compared to never users, we found that Barrett’s esophagus patients taking PPIs and H2RAs had 69% and 45% lower risk of esophageal adenocarcinoma, respectively. The associations were independent of other risk factors for progression, including concomitant use of nonsteroidal anti-inflammatory drugs and statins.
MedicalResearch.com Interview with: Seungyoun Jung, ScD, Fellow and Joanne F. Dorgan Ph.D., M.P.H., Professor Department of Epidemiology & Public Health Division Director Of Cancer Epidemiology University of Maryland MedicalResearch.com: What is the background for this study? Response: Despite the strong evidence from the animal and experimental studies, the lack of association between fat intake and...
Dr. Ze'ev Ronai[/caption]
Ze'ev Ronai, Ph.D.
Chief Scientific Advisor and Professor
Sanford Burnham Prebys Medical Discovery Institute
NCI-designated Cancer Center
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Ronai: Our lab has been studying the role of the transcription factor ATF2 in melanoma, demonstrating it's oncogene function and the ability to attenuate melanoma development once inhibiting this transaction factor activity.
We set to examine the role of ATF2 using the genetic melanoma model of BRAF/PTEN to find that inactive ATF2 promotes melanoma development in this model.
To our great surprise the transcriptional-inactive form of ATF2 was sufficient to promote melanoma development when combined with mutant BRAF, pointing to the "super" oncogenic capacity of this protein.
Dr. Uras[/caption]
Dr. Iris Z Uras and Univ.-Prof. Dr. Veronika Sexl
[caption id="attachment_24559" align="alignleft" width="80"]
Dr. Sexl[/caption]
Institute of Pharmacology and Toxicology
University of Veterinary Medicine
Vienna
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults. Patients suffering from AML have poor prognosis and high mortality rate despite considerable advances in chemotherapy and hematopoietic stem cell transplantations. Up to 30% of patients with AML harbor an activating mutation in the FLT3 receptor tyrosine kinase (FLT3-ITD). Such mutations are associated with a high predisposition to relapse after remission. In a simplified way we can say that these tumor cells depend on FLT3: Is FLT3 blocked, cells die. Hence, FLT3 inhibitors are being developed as targeted therapy for FLT3-mutant AML; however, clinical responses are short-lived and their use is complicated by rapid development of resistance. This emphasizes the need for additional therapeutic targets.
Our study represents a novel therapeutic window to specifically target and kill AML cells with FLT3-ITD mutations. We found that the tumor-promoting enzyme CDK6 but not its close relative CDK4 directly regulates and initiates the production/transcription of FLT3 and thus lead to disease. The FDA-approved kinase inhibitor Palbociclib not only blocks the activity of CDK6 but in turn impairs FLT3 expression: Mutant AML cells die immediately. The treatment does not affect cells without the mutation.
The power of CDK6 inhibition in AML cells goes beyond FLT3: Palbociclib also stops production of the PIM1 kinase and thus overcomes the potential activation of survival pathways counteracting the effects of FLT3 inhibition.
Dr. Melissa Wilson[/caption]
Melissa A. Wilson, MD, PhD
Assistant professor of Medical Oncology
NYU Langone Perlmutter Cancer Center
MedicalResearch.com: What are the most common types of skin cancer?
Dr. Wilson: Basal cell carcinoma, squamous cell carcinoma and melanoma. With rare exception, all are related to sun exposure.
MedicalResearch.com: Are some types of skin cancer more serious than others?
Dr. Wilson: Melanoma is the most serious form of skin cancer, with the highest risk of developing into metastatic disease. Most basal cell and squamous cell carcinomas are superficial and not as invasive, so removal is the treatment. Rarely, these can cause invasive and metastatic disease, but this occurs infrequently. Melanoma is much more serious. Of course, the earlier melanoma is detected and the earlier stage that it is, is more predictive of a favorable outcome.
MedicalResearch.com: Who is most prone to skin cancer?
Dr. Wilson: Persons with excessive sun exposure, fair skin, light hair and blue eyes - although it can certainly occur in anyone.
Dr. Kapp[/caption]
Julie M. Kapp, MPH, PhD
Associate Professor
2014 Baldrige Executive Fellow
University of Missouri School of Medicine
Department of Health Management and Informatics
Columbia, MO 65212
MedicalResearch.com: What is the background for this study?
Dr. Kapp: For the past several decades the U.S. has had the highest obesity rate compared to high-income peer countries, and for many years people in the U.S. have had a shorter life expectancy. For female life expectancy at birth, the U.S. ranked second to last. At the same time, the U.S. has the third highest rate of mammography screening among peer countries, and the pink ribbon is one of the most widely recognized symbols in the U.S. While the death rate in females for coronary heart disease is significantly higher than that for breast cancer, at 1 in 7.2 deaths compared to 1 in 30, respectively, women have higher levels of worry for getting breast cancer.
Dr. Hormuzd Katki[/caption]
Hormuzd A. Katki, PhD
Division of Cancer Epidemiology and Genetics
National Cancer Institute
National Institutes of Health Department of Health and Human Services,
Bethesda, Maryland
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Katki: The National Lung Screening Trial (NLST) showed that 3 annual CT screens reduced lung cancer death by 20% in a subgroup of high-risk smokers. However, selecting smokers for screening based on their individual lung cancer risk might improve the effectiveness and efficiency of screening. We developed and validated new lung cancer risk tools, and used them to project the potential impact of different selection strategies for CT lung cancer screening.
We found that risk-based selection might substantially increase the number of prevented lung cancer deaths versus current subgroup-based guidelines. Risk-based screening might also improve the effectiveness of screening, as measured by reducing the number needed to screening to prevent 1 death. Risk-based screening might also improve the efficiency of screening, as measured by reducing the number of false-positive CT screens per prevented death.
Dr. Geoffrey Liu[/caption]
Dr. Geoffrey Liu, MD MSC
Princess Margaret Hospital/Ontario Cancer Institute
University of Toronto
Toronto, Ontario
Canada
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Liu: Cetuximab is a monoclonal antibody therapy used in metastatic colorectal cancer patients when other chemotherapy options have been exhausted. Currently, the only useful biomarker to determine whether metastatic colorectal cancer patients will benefit from the drug, cetuximab, is whether patients carry a RAS mutation in their tumours. We evaluated additional biomarkers using samples from a Phase III clinical trial led by the Canadian Cancer Trials Group and the Australasian Gastrointestinal Trials Group. Our study identified a germline, heritable biomarker, a FCGR2A polymorphism, that further identifies an additional subgroup of patients who would benefit most from receiving cetuximab. This is important because the drug does have toxicity and is expensive to use; patients who are found not to likely benefit from this drug can go on quickly to try other agents, including participation in clinical trials.
Dr. Debra Silverman[/caption]
Dr. Debra Silverman Sc.D
Branch Chief and Senior Investigator in the Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology & Genetics
National Cancer Institute
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Silverman: We know that bladder cancer mortality rates have been elevated in northern New England for at least five decades. Incidence patterns in Maine, New Hampshire and Vermont are similar—about 20% higher than those for the United States overall. Elevated rates have been observed in both men and women, suggesting the role of a shared environmental etiologic factor.
A unique feature of northern New England is that a high proportion of the population uses private wells as their primary source of drinking water. The well water may contain low-to-moderate levels of arsenic. There are two possible sources of this arsenic contamination:
Dr. Mathias Buttmann[/caption]
PD Dr. Mathias Buttmann
Senior Consultant Neurologist and Head of the Multiple Sclerosis Outpatient Clinic
University of Wuerzburg
Wuerzburg, Germany
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Buttmann: The synthetic anthracenedione mitoxantrone is approved for disease-modifying treatment of patients with aggressive forms of relapsing or secondary progressive multiple sclerosis (MS). It has been known for years that this DNA-intercalating agent increases the risk of acute myeloid leukemia. We performed a retrospective cohort study to investigate whether mitoxantrone also increases the risk for other types of malignancies. We included all 677 mitoxantrone-treated multiple sclerosis patients who were seen at our large German academic MS centre between 1994 and 2007 and collected follow-up information on the occurrence of malignancies, death and causes of death as of 2011. Follow-up was complete in 676 patients. The median age at mitoxantrone initiation was 41 years and the median follow-up duration was 8.7 years. We identified 37 patients with a malignancy after mitoxantrone initiation, among them 4 cases of acute myeloic leukemia and 7 cases of colorectal cancer.
Compared to the general population matched for sex, age and year of occurrence, we calculated an 1.5-fold increased incidence of any type of malignancy, a tenfold increased incidence of acute myeloic leukemia and a threefold increased incidence of colorectal cancer, while the incidence of other types of malignancies was not increased. Higher age at mitoxantrone initiation but neither higher cumulative mitoxantrone dose nor treatment with other immuosuppressive agents was identified as a malignancy risk factor. Fifty-five patients had died, among them 12 from a malignancy. Our study confirmed previous reports on an increased incidence of acute myeloic leukemia after mitoxantrone treatment and newly described an association between mitoxantrone therapy and an increased incidence of colorectal cancer.
Dr. Katarina Truvé[/caption]
Katarina Truvé PhD
Swedish University of Agricultural Sciences and
Kerstin Lindblad-Toh
Uppsala University
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Truvé: Gliomas are malignant brain tumors that are rarely curable. These tumors occur with similar frequencies in both dogs and humans. Gliomas in dogs are strikingly similar at the biological and imaging level to human tumor counterparts. Some dog breeds such as Boxer and Bulldog are at considerably higher risk of developing glioma. Since these breeds at high risk are recently related, they are most likely carrying shared genetic risk factors. Our goal was therefore to use the dog genome to locate genes that may be involved in the development of glioma in both dogs and humans. We found a strongly associated locus and identified three candidate genes, DENR, P2RX7 and CAMKK2 in the genomic region. We have shown that CAMKK2 is lower expressed in glioma tumors than normal tissue in both dogs and human, and it has been reported that the associated canine mutation in P2RX7 results in a decrease in receptor function.
Dr. Maryam Farvid[/caption]
MedicalResearch.com Interview with:
Maryam Farvid, Ph.D.
Visiting Scientist
Department of Global Health and Population
Harvard T.H. Chan School of Public Health
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Farvid: Breast cancer is one of the most frequently diagnosed cancers and is the second leading cause of cancer deaths among women in the United States. While we know many breast cancer risk factors, few of them are easily modified. Further, evidence suggests that exposure to carcinogens and anti-carcinogens in early life may play an important role. According to this study, what women eat as teens or young adults could affect their breast cancer risk in the future. Teenage girls who eat a lot of fruits may have a lower risk of breast cancer later in life. The risk of breast cancer among women who reported the highest amount of dietary fruits during high school, about 2.9 servings of fruit a day, was 25 percent lower, compared with those who had eaten the lowest amount, about 0.5 serving of fruit a day. We also analyzed individual fruit and vegetable intake and risk of breast cancer: greater consumption of apple, banana, and grapes during adolescence, as well as oranges and kale for young adult was significantly associated with a reduced risk.
Dr. Jonathan Shoag[/caption]
Jonathan Shoag MD
Urology Resident at
Cornell Department of Urology and
[caption id="attachment_24282" align="alignleft" width="119"]
Dr. Jim Hu[/caption]
Dr. Jim C. Hu MD
Ronald Lynch Professor of Urologic Oncology
Professor of Urology
Director, Lefrak Center for Robotic Surgery
Attending Urologist, New York-Presbyterian Hospital (Cornell campus)
MedicalResearch.com: What is the background for this study?
Response: Prostate Specific Antigen (PSA) is a blood test that is used to detect prostate cancers and to follow a cancer’s response to treatment. PSA was widely implemented as a screening tool for prostate cancer in the early 1990s, and became a routine test during an annual physical for men over 40. Doctors started using it because values above a “normal” threshold were associated with a greater risk of prostate cancer. Following the adoption of PSA screening in the early 1990s, there has been a large increase in the number of men diagnosed with cancer, and a decrease of approximately 50% in the rate of prostate cancer death.
The PLCO trial was a large randomized trial designed and funded by the National Cancer Institute (NCI) to determine the effect of PSA screening on death from prostate cancer. The trial found that men randomized/assigned to prostate cancer screening had the same number of prostate cancer deaths as men in the control group of the trial, arguing that PSA screening does not decrease prostate cancer mortality.
This was a major piece of evidence used by the United States Preventative Services Task Force (USPSTF) to form its 2012 recommendation against PSA screening. The argument was that in spite of the other evidence showing a benefit to PSA testing, including US epidemiologic trends, and another large randomized trial showing PSA screening was effective (the ERSPC), we now had good evidence showing no benefit to PSA testing in the US. Since 2012 we have seen dramatic declines in prostate cancer screening in the US as a result.
Dr. Vikas Gulani[/caption]
Dr. Vikas Gulani MD, PhD
Director, MRI, University Hospitals Case Medical Center
Associate Professor, Radiology
CWRU School of Medicine
Cleveland, OH
MedicalResearch.com: What is the background for this study?
Dr. Gulani: For men that have a suspicion for prostate cancer either via the prostate specific antigen (PSA) test or a digital rectal exam, the current standard of care is to perform a transrectal ultrasound (TRUS) guided biopsy to detect cancer. The problem with TRUS biopsy is that most tumors are not visible on ultrasound and hence many significant cancers are missed. At the same time this strategy detects a high number of low risk, indolent cancers, and leads to overtreatment of disease that would be better left untreated.
Diagnostic MRI and MRI-guided biopsy (cognitive, ultrasound-MR fusion, or in-gantry) have been shown to be effective in detecting clinically significant prostate cancer. However, despite these advantages there is reluctance to incorporate MRI into standard practice because it is perceived to be expensive. Our goal was to determine if this presumption is true, and evaluate the cost-effectiveness of the MRI-guided techniques most commonly used.
MedicalResearch.com: What are the main findings?
Dr. Gulani: We found that every MRI strategy we evaluated was cost-effective compared to standard biopsy. Cognitive MRI guided biopsy – where the operator performs an ultrasound biopsy based on knowledge of lesion location from the MRI – was the most cost-effective strategy compared to standard biopsy. In-gantry MRI yielded the highest net health benefits as measured in quality adjusted life years.
Dr. Han Liang[/caption]
Dr. Han Liang PhD
Associate Professor and Deputy Department Chair, Department of Bioinformatics and Computational Biology
The University of Texas MD Anderson Cancer Center
Faculty Member, Baylor College of Medicine
Houston, TX
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Liang: An individual’s sex has been long recognized as a key factor affecting the risk of cancer development and management. However, previous studies on the sex effect have been limited to individual genes, single molecular data types, and single cancer lineages.
We performed a comprehensive analysis of molecular differences between male and female patients in a diversity of cancer types and revealed two sex-effect groups.
One group contains a small number of sex-affected genes, whereas the other shows much more extensive sex-biased molecular signatures. More than half of clinically actionable genes (e.g., therapeutic targets or biomarkers) show sex-biased signatures.