AACR, Author Interviews, Genetic Research / 18.04.2018

MedicalResearch.com Interview with: Ed Liu, M.D President and CEO The Jackson Laboratory (JAX) MedicalResearch.com: What is the background for this study? What are the main findings? Response: A few years ago we and others identified a complex genomic instability profile commonly found in the genomes of breast, ovarian and endometrial carcinomas, which is characterized by hundreds of isolated head-to-tail duplications of DNA segments, called tandem duplications. We refer to this configuration as the tandem duplicator phenotype, or TDP. In this study, we perform a meta-analysis of over 2,700 cancer genomes from over 30 different tumor types and provide a detailed description of six different types of TDP, distinguished by the presence of tandem duplications of different sizes. Collectively, these profiles are found in ~50% of breast, ovarian and endometrial carcinomas as well as 10-30% of adrenocortical, esophageal, stomach and lung adeno-carcinomas. We show that distinct genetic abnormalities associate with the distinct TDPs, clearly suggesting that distinct molecular mechanisms are driving TDP formation. In particular, we provide strong evidence of a casual relationship between joint abrogation of the BRCA1 and TP53 tumor suppressor genes and the emergence of a short-span (~11 Kb) TDP profile. We also observe a significant association between hyper-activation of the CCNE1 pathway and TDP with medium-span (~230 Kb) tandem duplications, and between mutation of the CDK12 gene and medium- and large-span TDP (coexisting 230 Kb and 1.7 Kb tandem duplications). Importantly, we find that different forms of TDP result in the perturbation of alternative sets of cancer genes, with short-span TDP profiles leading to the loss of tumor suppressor genes via double transections, and larger-span TDP profiles resulting in the duplication (i.e. copy number gain) of oncogenes and gene regulatory elements, such as super-enhancers and disease-associated SNPs.  (more…)
Author Interviews, Blood Clots, Cancer Research / 17.04.2018

MedicalResearch.com Interview with: Dr. Jens Sundbøll Department of Clinical Epidemiology Aarhus University Hospital Aarhus, Denmark MedicalResearch.com: What is the background for this study? What are the main findings? Response: The incidence of acute peripheral arterial occlusion is approximately 1.5 cases per 10,000 person-years. In comparison, the incidence rate of deep venous thrombosis is about 5-10cases per 10,000 person-years. It has been established previously that deep venous thrombosis in the lower limb and pulmonary embolism may be presenting symptoms of cancer and is associated with a poor cancer prognosis. However, whether arterial thromboembolism of the lower limb also can represent prodromal symptoms of occult cancer and worsen cancer prognosis has never been investigated. (more…)
AACR, Author Interviews, Baylor College of Medicine Houston, Blood Pressure - Hypertension, Pancreatic / 17.04.2018

MedicalResearch.com Interview with: Zhensheng Wang, M.P.H., Ph.D. Postdoctoral Associate Duncan Cancer Center-Bondy Baylor College of Medicine Houston, TX MedicalResearch.com: What is the background for this study? Response: Our prior research consistently found a significant inverse association between circulating levels of soluble receptor for advanced glycation end products (sRAGE), an anti-inflammatory factor, and risk of pancreatic cancer. It has also been found that sRAGE levels or RAGE signaling are modulated by anti-hypertensive (anti-HT) medications, including angiotensin-converting-enzyme inhibitors (ACEi), β-blockers, and calcium channel blockers (CCBs). These medications have been shown in prior pre-clinical or experimental research to either increase sRAGE concentrations, decrease formation of advanced glycation end-products (AGEs), or dampen pro-inflammatory receptor for AGE (RAGE) signaling pathway. We therefore hypothesized that there would be an inverse association between use of anti-HT medications and risk of developing pancreatic cancer. Pancreatic cancer is a major public health concern in the United States, as it is the 4th leading cause of cancer-related mortality with an estimated of 43,090 deaths in 2017. Pancreatic cancer typically occurs in elderly individuals who also have chronic comorbid medical conditions, such as hypertension. Anti-HT medication use in individuals ≥ 18 years old has increased from 63.5% in 2001-2002 to 77.3% in 2009-2010, according to the National Health and Nutrition Examination Survey in the U.S. Therefore, it is of great public health significance to address the potential association between anti-HT medication use and risk of pancreatic cancer in the general population. (more…)
AACR, Author Interviews, Cancer Research / 17.04.2018

MedicalResearch.com Interview with: Mark E. Hatley, M.D., Ph.D. Assistant Member Molecular Oncology Division, Department of Oncology St. Jude Children's Research Hospital Memphis, TN 38105 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma occurring in children. Tumors appear histologically and genetically as undifferentiated skeletal muscle and are thus thought to solely originate from early skeletal muscle cells. However, tumors occur throughout the body, including sites devoid of skeletal muscle. In addition, tumor location is a key feature of staging and 40% of patients develop RMS in the head and neck. Interestingly, head and neck muscle development is distinct from the development of trunk and limb muscle. Previously we described a model of rhabdomyosarcoma which occurred specifically in the head and neck and originated from non-muscle cells. In this study we investigated how normal development programs are hijacked to drive rhabdomyosarcoma location. We demonstrated that RMS can originate from immature blood vessel cells that lie in between muscle fibers specifically in the head and neck. During development, these cells are hijacked, and become reprogrammed into rhabdomyosarcoma rather than mature endothelial cells. These RMS cells express factors important in head and neck muscle development. Our findings highlight that cell of origin contributes to RMS location and may explain why a high proportion of RMS occurs in the head and neck.  (more…)
Author Interviews, Cancer Research, JAMA / 16.04.2018

MedicalResearch.com Interview with: Lindor Qunaj BSc MD'19 Medical student, Warren Alpert Medical School of Brown University Brown Center for Biomedical Informatics Providence, Rhode Island MedicalResearch.com: What is the background for this study? What are the main findings? Response: Our study was motivated by growing concerns that incomplete or delayed release of clinical trial data may put patients at risk of harm or suboptimal treatment and slow the pace of biomedical innovation. Especially in a field as rapidly evolving as oncology, complete and timely dissemination of clinical trial results is critical to the advancement of both patient care and scientific discovery. In an analysis of press releases from eight large pharmaceutical companies, we found that the median delay from presumed availability of Phase 3 trial data to peer-reviewed publication or public posting of results was 300 days. Studies reporting positive findings were published more rapidly than those with negative results. (more…)
Author Interviews, Breast Cancer, JNCI, UT Southwestern / 16.04.2018

MedicalResearch.com Interview with: Yingfei Wang, Ph.D. and Weibo Luo, Ph.D. Department of Pathology UT Southwestern Medical Center Dallas TX 75390 MedicalResearch.com: What is the background for this study? Response: Breast cancer is the most commonly diagnosed cancer in women. Tumor metastasis is frequently found in breast cancer patients and causes more than 90% of cancer death. There is currently no cure for this deadly disease. We have known that breast tumor is not supplied with sufficient oxygen (a phenomenon known as hypoxia), which makes breast cancer cells more aggressive and may be responsible for tumor recurrence, metastasis, and therapy resistance. Hypoxia-inducible factor (HIF) is a master regulator frequently detected in the hypoxic regions and switches on many oncogenes needed for breast cancer cells to grow and spread around the body. The role of HIF in gene regulation is precisely controlled and shutting down of HIF’s activity would be a promising strategy for the treatment of metastatic breast cancer. (more…)
Author Interviews, Colon Cancer, Supplements / 13.04.2018

MedicalResearch.com Interview with: Nathalie Scheers PhD Asst. Professor Chalmers University of Technology Dept of Biology and Biological Engineering Food and Nutrition Science Göteborg, Sweden  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Many different forms of iron supplements are used to treat iron deficiency symptoms or as phosphate binders in patients with renal disease. two of these iron supplements, the chelates ferric citrate and ferric EDTA have been observed to drive colon cancer in mice. In the newly published study in Oncotarget, we are reporting our work on how these iron compounds differ compared to the simple salt ferrous sulphate, which is another common iron supplement. The main finding of this study was that ferric citrate and ferric EDTA promoted the cancer biomarker amphiregulin which in turn activated the MAP kinase ERK in gut epithelial cancer cells. There were no such effects in ferrous sulphate-treated cells.  (more…)
Author Interviews, Cancer Research, Cost of Health Care, JAMA, Pharmaceutical Companies / 09.04.2018

MedicalResearch.com Interview with: Aaron Mitchell, MD Division of Hematology/Oncology, Department of Medicine, Lineberger Comprehensive Cancer Center The Cecil G. Sheps Center for Health Services Research The University of North Carolina at Chapel Hill MedicalResearch.com: What is the background for this study? What are the main findings? Response: Financial relationships between physicians and the pharmaceutical industry are very common. However, we are just beginning to figure out whether these relationships may lead to potentially concerning changes in physician behavior - whether physicians tend to prescribe more of the drugs made by a company that has given them money. We decided to ask whether oncologists who receive money from drugmakers are more likely to use the cancer drugs made by companies that have given them money in the past. In studying two specific groups of cancer drugs, one for kidney cancer and one for chronic myeloid leukemia (CML), we found that oncologists who had received payments such as meals, consulting fees, travel & lodging expenses from the manufacturer of one of these drugs tended to use that drug more. When looking at oncologists who received payments for research, we found increased prescribing among the kidney cancer drugs but not the CML drugs. (more…)
Author Interviews, Cancer Research, Lung Cancer, PNAS / 08.04.2018

MedicalResearch.com Interview with: Nada Kalaany, PhD Harvard Medical School Boston Children's Hospital Boston, MA 02115 MedicalResearch.com: What is the background for this study? Response: ​ Non-small cell lung cancer (NSCLC) is the predominant form of lung cancer and the leading cause of cancer death in the US and worldwide. Over a quarter of NSCLC harbors activating mutations in the KRAS oncogene, which despite decades of attempts, has proven to be very difficult to target. KRAS has previously been demonstrated to directly bind to and activate the pro-proliferative kinase PI3K, which is typically activated by insulin/insulin-like growth factor1 (IGF1) signaling. KRAS-PI3K binding is required for KRAS-driven lung cancer formation and progression. However, whether this interaction is sufficient for lung tumor formation and whether additional input is required from insulin/IGF1 signaling, has remained largely controversial. (more…)
Author Interviews, JNCI, Lung Cancer, UT Southwestern / 04.04.2018

MedicalResearch.com Interview with: Amyn Habib, M.D. Associate Professor, Neurology & Neurotherapeutics UT Southwestern Medical Center MedicalResearch.com: What is the background for this study? Response: The epidermal growth factor receptor (EGFR) is expressed in most lung cancers and could play an important role in driving the growth of lung cancer.  Drugs are available that can block the activity of the EGFR. However, EGFR inhibitors are successful in only a small subset of lung cancers that have a mutant form of the EGFR, and do not work in the majority of lung cancers that have the normal form of the EGFR.  (more…)
Author Interviews, Colon Cancer, Genetic Research, JAMA / 03.04.2018

MedicalResearch.com Interview with: Heather Hampel, MS, LGC Associate Director, Division of Human Genetics Associate Director, Biospecimen Research Professor, Internal Medicine Licensed Genetic Counselor The Ohio State University Comprehensive Cancer Center Columbus, OH  4322 MedicalResearch.com:  What is the background for this study?  What are the main findings? Response: The background is that we had recently shown that some colorectal cancer patients who underwent traditional screening for Lynch syndrome were eventually found to have double somatic (two acquired) mutations in the MMR genes and they did not have Lynch syndrome at all. This was discovered after their tumor had already had MSI and/or IHC screening test, followed by MLH1 methylation and/or BRAF testing, followed by germline DNA testing on a blood sample from the patient for MMR gene mutations, then finally by sequencing their tumor. This gave us the idea to reverse the sequence and start with tumor sequencing since it might streamline testing, save time, and prevent several other tests. In addition, we knew that all stage IV colorectal cancer are already supposed to have tumor sequencing of the KRAS, NRAS, and BRAF genes and MSI testing for treatment purposes. Our hypothesis was that an upfront tumor sequencing test could replace all these separate tests with similar sensitivity and specificity. (more…)
AACR, Author Interviews, Cancer Research, Hepatitis - Liver Disease / 29.03.2018

MedicalResearch.com Interview with: Dr. Monica Kasting PhD first author Dr. Anna Giuliano PhD Susan. T. Vadaparampil, Ph.D., M.P.H. Senior Member/Professor Center for Infection Research in Cancer H. Lee Moffitt Cancer Center, Tampa, Florida.Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center, Tampa, Florida  MedicalResearch.com: What is the background for this study? What are the main findings?  Response: In the U.S., approximately 1 in 30 baby boomers are chronically infected with hepatitis C virus. Half of all cases of liver cancer are caused by hepatitis C and liver cancer is one of only three cancer types that are actually increasing in incidence in the US. Because of this, in 2012 the CDC issued a recommendation for universal screening for hepatitis C virus for everyone born between 1945 and 1965 (baby boomers). We wanted to look at the time period after that to see if the rates of screening in that population increased. From 2013-2015 screening among baby boomers only increased by 0.9% (from 11.8% to 12.7%) which indicates we still have a long way to go before we meet our goal of universal screening.  (more…)
AACR, Author Interviews, Microbiome, NYU, Pancreatic / 28.03.2018

MedicalResearch.com Interview with: Mautin Hundeyin MD Post-doctoral Research Fellow George Miller, MD is Principal Investigator and Director of the S. Arthur Localio Laboratory in the Department of Surgery at NYU School of Medicine MedicalResearch.com: What is the background for this study? What are the main findings? Response: Pancreatic ductal adenocarcinoma (PDA) is the devastating disease with grim prognosis. The microbiome has emerged as a contributor to oncogenesis in a number of intestinal tract malignancies. We found that PDA is associated with a distinct stage-specific gut and pancreatic microbiome that drives disease progression by inducing intra-tumoral immune suppression. Targeting the microbiome protects against oncogenesis, reverses intra-tumoral immune-tolerance, and enables efficacy for check-point based immunotherapy. These data have implications for understanding immune-suppression in pancreatic cancer and its reversal in the clinic.  (more…)
Author Interviews, Breast Cancer, Chemotherapy, JAMA, Novartis / 26.03.2018

MedicalResearch.com Interview with: Melanie E. Royce, MD, PhD Division of Hematology/Oncology University of New Mexico Comprehensive Cancer Center Albuquerque MedicalResearch.com: What is the background for this study? What are the main findings? Response: BOLERO-4 is an open label, single-arm, Phase II study that evaluates the combination of everolimus plus letrozole as a first-line treatment for hormone receptor (HR)-positive/human epidermal growth factor receptor (HER2)-negative advanced breast cancer patients, as well as the use of everolimus plus exemestane beyond initial progression. Results of the BOLERO-4 trial published in JAMA Oncology showed that everolimus in combination with endocrine therapy is an effective first-line treatment option for postmenopausal women with HR+/HER2- advanced breast cancer. A total of 202 patients received everolimus in combination with letrozole as first-line treatment between March 7, 2013 and December 17, 2014. Median progression-free survival (PFS) in the first-line setting was 22.0 months (95% CI 18.1-25.1) with an overall response rate of 45% (95% CI 38.1-52.2) and clinical benefit rate of 74% (95% CI 67.7-80.1). A total of 152 (75%) discontinued treatment, primarily due to disease progression (51%) or adverse events (16%). Data from a smaller number of patients in BOLERO-4 also show limited efficacy with continued everolimus, combined with exemestane, following disease progression. Second-line treatment was ongoing in 16 (32%) patients, while 34 (68%) had discontinued. The most frequent reason for second-line treatment discontinuation was disease progression (56%). In the second-line setting, median PFS was 3.7 months (95% CI 1.9-7.4) with an overall response of 6% (95% CI 1.3-16.5) and clinical benefit rate of 28% (95% CI 16.2-42.5). Safety findings from BOLERO-4 are consistent with previous studies of Afinitor in advanced breast cancer. The most common (≥ 20% incidence) first-line all-grade adverse events were stomatitis (69%), weight loss (44%), nausea (37%) and anemia (35%). Most were ‘low grade’ in severity (grade 1 or 2) and generally well managed. Safety findings show the most common (≥ 10% incidence) second-line adverse events were stomatitis (20%) and weight loss (20%). Lower rates of stomatitis in second-line were noted.  (more…)
Author Interviews, Cancer Research, Hepatitis - Liver Disease, JAMA / 26.03.2018

MedicalResearch.com Interview with: Sang Min Park MD, MPH, PhD Chief, Department of Family Medicine, Seoul National University College of Medicine Director, Health Promotion Center, Seoul National University Hospital Professor, Department of Biomedical Science & Family Medicine Seoul National University College of Medicine Seoul, Korea What is the background for this study? What are the main findings? Response: Chronic hepatitis B patients have a higher risk of hepatocellular carcinoma than the general population, which has been well-established and known to be caused by progression of hepatitis B infection into severe liver diseases. However, whether obesity-related carcinogenesis plays a central role in the development of hepatocellular carcinoma in chronic hepatitis B patients remained unclear. Therefore, we assessed the association between body mass index and risk of hepatocellular carcinoma in chronic hepatitis B patients, and stratified all analyses by sex using healthcare big data in the Republic of Korea. We found positive association of trends between body mass index and risk of hepatocellular carcinoma in both men and women with hepatitis B infection. The magnitude of the association in women was stronger than that of men. In the severely obese category, the hazard ratio for hepatocellular carcinoma was significantly higher in women compared to men. Our findings highlight that high body mass index is associated with risk of hepatocellular carcinoma in chronic hepatitis B patients, especially in women, which may be partially explained by higher fat content for the same unit of body mass index in women compared to men. (more…)
AACR, Author Interviews, Cancer Research, Melanoma / 24.03.2018

MedicalResearch.com Interview with: Gao Zhang, Ph.D. Staff scientist in the Herlyn Lab The Wistar Institute MedicalResearch.com: What is the background for this study? Response: The past 7 years have witnessed the great success in treating patients with unresectable or metastatic melanoma. Despite the breakthrough of molecularly targeted therapies and immune checkpoint blockade therapies, a majority of patients have experienced the rapid tumor recurrence and progression, following the dramatic regression. There is an urgent and unmet need to treat therapy-resistant tumors. (more…)
Author Interviews, Cancer Research, Dermatology, Environmental Risks, JAMA, Melanoma / 23.03.2018

MedicalResearch.com Interview with: John W. Epling, Jr., M.D., M.S.Ed., Task Force Member Dr. Epling is is a professor of Family and Community Medicine at the Virginia Tech Carilion School of Medicine in Roanoke, VA. He is also the Medical Director of Research for Family and Community Medicine, Medical Director of Employee Health and Wellness for the Carilion Clinic, and maintains an active clinical primary care practice.  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Skin cancer is the most common type of cancer in the U.S., affecting millions of people every year. The Task Force looked at the latest research to see if clinicians can help people prevent skin cancer by providing counseling about ways to reduce risk, including using sunscreen, wearing protective clothing, and avoiding sunlight during peak hours. Based on our review of the evidence, we found that counseling younger patients with a fair skin type and their parents is effective at encouraging these sun protective behaviors. By helping reduce their patients’ exposure to harmful UV rays, clinicians can decrease their risk for skin cancer. As such, we recommend that clinicians provide counseling to people who are six months to 24 years old and have a fair skin type. For adults over 24 with a fair skin type, clinicians should consider the individual’s risks for skin cancer when deciding whether or not to provide counseling.  (more…)
Author Interviews, Breast Cancer, Brigham & Women's - Harvard, Science, Weight Research / 22.03.2018

MedicalResearch.com Interview with: Dai Fukumura, M.D., Ph.D Associate Professor, Radiation Oncology Harvard Medical School Deputy Director, Edwin L. Steele Laboratory, Radiation Oncology, Massachusetts General Hospital Boston, MA      Dr. Joao Incio PhD Post-Doc, Edwin L. Steele Laboratory           Dr. Rakesh K. Jain PhD Andrew Werk Cook Professor of Tumor Biology and director of the Edwin L. Steele Laboratories for Tumor Biology Rradiation oncology department Massachusetts General Hospital and Harvard Medical School.   MedicalResearch.com: What is the background for this study?   Response: Based on promising data from preclinical studies and subsequent increase in progression-free survival in patients, anti-vascular endothelial growth factor (VEGF) therapy received accelerated approval for metastatic breast cancer. However, this approval was withdrawn in the United States based on the lack of overall survival benefit in several subsequent phase III studies in metastatic and adjuvant settings. Potential mechanisms of resistance to anti-VEGF therapy include the upregulation of alternative angiogenic and pro-inflammatory factors. Production of some of these factors has been shown to increase in obesity specifically in hypoxic adipose tissues including the breast. Given that up to 70% of breast cancer (BC) patients in the United States are overweight or obese, we addressed one simple but important question in this study: Is obesity contributing to anti-VEGF treatment resistance in breast cancer? (more…)
Author Interviews, Cancer Research, MRI, Prostate Cancer / 21.03.2018

MedicalResearch.com Interview with: Veeru Kasivisvanathan MBBS BSc MRCS MSc PGCert Lead for CPD, Division of Surgery and Interventional Science, UCL Academic Section Committee, British Association of Urological Surgeons Twitter: @veerukasi PRECISION Study Coordinator https://clinicaltrials.gov/ct2/show/NCT02380027   MedicalResearch.com: What is the background for this study? What are the main findings? 
  • We knew that there were limitations in the standard of care pathway for the diagnosis of prostate cancer, TRUS biopsy which missed harmful cancers and over diagnosed harmless cancers.
  • Emerging reports in the literature showed that using an alternative diagnostic pathway, MRI and MRI-targeted biopsy, showed promising prostate cancer detection rates
  • In 2012 we set out in an international working group to design a study that could change clinical practice and replace the standard of care with a pathway involving MRI 
(more…)
AACR, Author Interviews, Colon Cancer / 20.03.2018

MedicalResearch.com Interview with: Darren D. Browning, PhD | Professor Department of Biochemistry and Molecular Biology, Medical College of Georgia at Augusta University Georgia Cancer Center, Augusta, Georgia 30912-2100 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Cancer of the colon and rectum is one of the most commonly diagnosed and has a high mortality because it is often identified at an advanced stage. In the United States the average overall risk of having to deal with this disease at some point is around one in twenty-five, but the risk is much higher for people who have previously had polyps removed or if a close relative was diagnosed with colon cancer. The risk is even higher for patients with inflammatory bowel disease or heritable disorders such as familial adenomatous polyposis and lynch syndrome. While chemoprevention is clearly warranted, there are currently no drugs available that can reduce the risk for those predisposed to colorectal cancer. Previous work from our laboratory has shown that drugs like sildenafil that inhibit phosphodiesterase 5 (PDE5), have a profound effect on the epithelial lining of the intestine. Our recent work has shown that these drugs can prevent intestinal cancers in two different mouse models of human disease. While this class of drugs is best known for treating erectile dysfunction, due to a low side-effect profile they are also prescribed for long-term daily use to treat pulmonary arterial hypertension (PAH) and benign prostate hyperplasia (more…)
Author Interviews, Brain Cancer - Brain Tumors, Emory, PNAS, Technology / 16.03.2018

MedicalResearch.com Interview with: Lee Cooper, Ph.D. Assistant Professor of Biomedical Informatics Assistant Professor of Biomedical Engineering Emory University School of Medicine - Georgia Institute of Technology MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Gliomas are a form of brain tumor that are often ultimately fatal, but patients diagnosed with glioma may survive as few as 6 months to 10 or more years. Prognosis is an important determinant in selecting treatment, that can range from simply monitoring the disease to surgical removal followed by radiation treatment and chemotherapy. Recent genomic studies have significantly improved our ability to predict how rapidly a patient's disease will progress, however a significant part of this determination still relies on the visual microscopic evaluation of the tissues by a neuropathologist. The neuropathologist assigns a grade that is used to further refine the prognosis determined by genomic testing. We developed a predictive algorithm to perform accurate and repeatable microscopic evaluation of glioma brain tumors. This algorithm learns the relationships between visual patterns presented in the brain tumor tissue removed from a patient brain and the duration of that patient's survival beyond diagnosis. The algorithm was demonstrated to accurately predict survival, and when combining images of histology with genomics into a single predictive framework, the algorithm was slightly more accurate than models based on the predictions of human pathologists. We were also able to identify that the algorithm learns to recognize some of the same tissue features used by pathologists in evaluating brain tumors, and to appreciate their prognostic relevance. (more…)
ASCO, Author Interviews, Prostate, Prostate Cancer, Urology / 15.03.2018

MedicalResearch.com Interview with: https://www.churchillpharma.com/ Paul Nemeth, Ph.D. Sr. Vice President, Regulatory Affairs, Clinical Development & Quality Assurance Churchill Pharmaceuticals LLC King of Prussia, PA 19406 MedicalResearch.com: What is the background for this study? Response: In the STAAR study, 53 patients with metastatic castration-resistant prostate cancer (mCRPC) were randomized to receive YONSA, an abiraterone acetate fine particle formulation 500 mg once daily in combination with 4 mg of methylpresnisolone twice daily or 1,000 mg daily of the originator abiraterone acetate (OAA) in combination with 5 mg of prednisone twice daily for a period of 84 days.  Previous studies in healthy volunteers under fasted conditions had shown that single oral doses of 500 mg of YONSA are bioequivalent to single oral doses of 1,000 mg OAA and that a background of 4 mg of methylprednisolone twice daily on a single oral dose of 500 mg of YONSA results in the same extent of absorption as a background of 5 mg of prednisone twice daily on a single oral dose of 1,000 mg of OAA.  (more…)
Author Interviews, Primary Care, Prostate Cancer / 14.03.2018

MedicalResearch.com Interview with: Dr. Jason Profetto, MD, CCFP Family and Academic Medicine Chair, Clinical Skills Undergraduate Medical Education McMaster University MedicalResearch.com: What is the background for this study?  Response: The main reason that prompted me to investigate the issue of digital rectal exams in primary care for prostate screening was that it appeared to be rather dogmatic practice (continually practiced by many despite updated data suggesting a lack of benefit).  I was very curious to see if there was any data that suggested the digital rectal exams was indeed a useful indicator in primary practice (ie. Family Medicine) in detecting prostate cancer in asymptomatic men.  Intuitively, I didn’t believe the DRE was accurate mainly because in medical school it’s generally under-represented in clinical skills teaching and poorly taught and assessed (not just in Ontario, but also Canada).  As a result, it seemed bizarre to me that this specific clinical skills was being used as a routine measure in family medicine to screen for prostate cancer.  Also, for me this was a big issue as many men in my practice were used to having yearly “rectal exams” done and I thought it was time to really take a closer look at the research to see whether or not we can support this practice. MedicalResearch.com: What are the main findings? Response: The main findings suggest that the digital rectal exam is not helpful/accurate in detecting prostate cancer in asymptomatic men in family practice or primary care. (more…)
Author Interviews, Breast Cancer, JAMA, Schizophrenia / 13.03.2018

MedicalResearch.com Interview with: Chuanjun Zhuo, MD, PhD Department of Psychiatric Laboratory Department of Psychiatric Neuroimaging Faculty Tianjin Mental Health Center Tianjin, China  MedicalResearch.com: What is the background for this study? What are the main findings?  Response: According to previous epidemiological studies, women with schizophrenia may be associated with significantly increased risk of breast cancer. However, the results of these studies were not always consistent. In view of the fact that medical care for patients with schizophrenia is becoming multidisciplinary, we aimed to evaluate the risk of breast cancer in women with schizophrenia via a meta-analysis of relevant cohort studies. We included twelve cohorts and adopted the recently proposed prediction interval to evaluate the heterogeneity among the included studies. We found that schizophrenia was associated with about 30% increased risk of breast cancer incidence in women. However, significant heterogeneity existed of the included studies, which indicates that more extensive researches into the potential mechanisms underlying the associations between schizophrenia and breast cancer risk are needed. (more…)
Aging, Author Interviews, Cancer Research, Johns Hopkins / 12.03.2018

MedicalResearch.com Interview with: Hariharan Easwaran, PhD Assistant Professor of Oncology The Sidney Kimmel Comprehensive Cancer Center The Johns Hopkins University School of Medicine Bunting/Blaustein Cancer Research Building 1 Baltimore, MD 21287 MedicalResearch.com: What is the background for this study? What are the main findings?  Response: The interpretation of the information encoded in our DNA by the various cells in our body is mediated by a plethora of modifications of DNA and proteins that complex with DNA. DNA methylation is one such important modification, which is normally established in a very orchestrated fashion during development. All normal cells have a defined pattern of DNA methylation, which may vary by tissue type, but is consistent within tissues. This normal pattern is disrupted in all known cancers, and is considered a hallmark of cancers. (more…)
Author Interviews, Dermatology, JAMA, Melanoma / 11.03.2018

MedicalResearch.com Interview with: Aimilios Lallas, PhD First Department of Dermatology, School of Medicine Aristotle University Thessaloniki, Greece MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Our goal today is to recognize melanoma at the earliest stage, ideally before it invades the dermis and acquires metastatic potential. Melanoma-specific dermoscopic criteria have been tested mainly in the context of invasive melanoma. Although they were proven valid melanoma predictors, the question still remains if they are strong enough to diagnose melanoma in situ (MIS). Our aim was to investigate the diagnostic accuracy of dermoscopic criteria for the diagnosis of melanoma in situ. We identified 5 main positive dermoscopic indicators of MIS: atypical network, regression, irregular hyperpigmented areas, prominent skin markings and angulated lines.  (more…)
Author Interviews, JAMA, Prostate Cancer / 10.03.2018

MedicalResearch.com Interview with: Amar U. Kishan, MD Assistant Professor Department of Radiation Oncology University of California, Los Angeles MedicalResearch.com: What is the background for this study? Response: Patients with high risk prostate cancer have several curative treatment options: radical prostatectomy, external beam radiotherapy with androgen deprivation therapy, and external beam radiotherapy with a brachytherapy boost, also with androgen deprivation therapy (so-called extremely dose-escalated radiotherapy). Prior attempts at comparing long-term clinical outcomes between these treatment options have been hampered by the fact that standards of care have changed significantly with respect to the appropriate dose of radiation and the usage of androgen deprivation therapy. Therefore, many comparative effectiveness reports are in essence comparing apples with rotten oranges. Further, not all high risk prostate cancers are the same. Gleason score 9-10 disease is a particularly aggressive form of prostate cancer that is much more likely to metastasize and potentially cause death. Thankfully, this is a rarer type of prostate cancer -- but this also means that not much data are available specifically for this type of disease. Therefore, we launched a multi-institutional study of men with Gleason score 9-10 disease, including 1809 men treated across 12 institutions. All men were treated between 2000 and 2013 and therefore were more likely to have treatments that would be commensurate with modern standards.  (more…)
Author Interviews, Biomarkers, Prostate Cancer / 07.03.2018

MedicalResearch.com Interview with: Richard Martin Professor of Clinical Epidemiology Head of Section, Clinical Epidemiology & Public Health Population Health Sciences Bristol Medical School  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Screening for prostate cancer using the PSA test aims to detect prostate cancer at an early stage, before symptoms develop, when treatment can be offered that may avoid the risks of advanced cancer or may extend life. Evidence from a large European trial suggests that PSA screening at 2 to 4 yearly intervals could reduce prostate-cancer deaths by 20%. after 13 years of follow-up. However, there are problems with the accuracy of the PSA test and potential harmful consequences. In particular, using the PSA test to screen for prostate cancer results in some tested men being diagnosed with low-risk, harmless cancers that are unlikely to progress or require treatment.  This problem may be particularly exacerbated when using repeated PSA testing as a screening strategy. The CAP trial offered a one-off PSA test to men aged 50-69 years in the UK. The goal of this low-intensity, one-off PSA testing was to avoid unnecessary screening while still identifying men with high risk, aggressive cancers for whom screening and early detection can reduce morbidity and mortality. However, we found that after an average 10-years of follow-up, the PSA test still detected too many low-risk prostate cancers, while also missing cancers that did need treatment. After an average 10-years of follow-up, the group who had been screened had the same percentage of men dying from prostate cancer as those who had not been screened (0.29%).  (more…)
Author Interviews, Biomarkers, Breast Cancer, Cancer Research, Genetic Research / 26.02.2018

MedicalResearch.com Interview with: Maureen E. Murphy, Ph.D. Program Leader and Professor Molecular and Cellular Oncogenesis and Subhasree Basu PhD Postdoctoral researcher The Wistar Institute Philadelphia, PA 19104 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Unlike most other genes that are intimately involved in the cause of cancer, the p53 gene displays considerable genetic variation; in other words, p53 is unusual among cancer genes in that the amino acids in p53 protein can frequently differ amongst different populations and ethnic groups. Additionally, unlike most other tumor suppressor genes, when p53 is mutated in a tumor, as it is in 50% of human cancers, that mutant protein now has a positive function in cancer progression, changing tumor metabolism and promoting tumor metastasis. In this study, the authors analyze for the first time the impact of a common genetic variant in p53 (single nucleotide polymorphism, or SNP) in the ability of mutant p53 to promote tumor metabolism and metastasis, and they find significant differences.  (more…)
Author Interviews, Breast Cancer, Mammograms / 26.02.2018

MedicalResearch.com Interview with:

Stephen W. Duffy Professor of Cancer Screening Wolfson Institute of Preventive Medicine, Barts and The London School of Medicine and Dentistry Queen Mary University of London

MedicalResearch.com: What is the background for this study? What are the main findings? Response: The phenomenon of length bias, whereby screening has more chance of detecting slow growing tumours, has been known about for some years. This has led some colleagues to speculate that breast cancer screening only benefits those with slow-growing, less aggressive cancers, and does not reduce deaths from more aggressive, rapidly progressing cancers. In this study, we addressed this question directly using data from a randomised trial of mammographic screening. We calculated the reduction in mortality from grade 1 (less aggressive), grade 2 (intermediate) and grade 3 (most aggressive) cancers, as a result of screening. We found that the greatest reduction in breast cancer mortality was from the aggressive, fast-growing grade 3 cancers, contrary to what had been suspected.  (more…)