Author Interviews, Cancer Research, JAMA / 11.03.2016

MedicalResearch.com Interview with: [caption id="attachment_22567" align="alignleft" width="133"]Joseph Unger, PhD, MS SWOG Statistical Center Assistant Member, Public Health Sciences Division, Fred Hutchinson Cancer Research Center Affiliate Assistant Professor, Health Services Research, University of Washington Seattle, WA 98109-1024 Dr. Joseph Unger[/caption] Joseph Unger, PhD, MS SWOG Statistical Center Assistant Member, Public Health Sciences Division, Fred Hutchinson Cancer Research Center Affiliate Assistant Professor, Health Services Research, University of Washington Seattle, WA  98109-1024 MedicalResearch.com: What is the background for this study? Dr. Unger: The rate at which trials are positive has previously been examined, and the relationship between trial results and publication rates in the context of publication bias has also been studied. But the comparative scientific impact of positive vs negative clinical trials using citation data has not been investigated We used the phase III trial database of SWOG, a major national cooperative clinical trials group, in combination with its trial publication database and citation data from Google Scholar, to compare the scientific impact of positive vs negative phase III cancer clinical treatment trials.
Author Interviews, BMJ, Cancer Research, Colon Cancer, Psychological Science / 09.03.2016

[caption id="attachment_22507" align="alignleft" width="164"]Benedicte Kirkøen, PhD candidate Bowel Cancer Screening in Norway – a pilot study Cancer Registry of Norway (Kreftregisteret) Benedicte Kirkøen[/caption] MedicalResearch.com Interview with: Benedicte Kirkøen, PhD candidate Bowel Cancer Screening in Norway – a pilot study Cancer Registry of Norway (Kreftregisteret) MedicalResearch.com: What is the background for this study? Response: Randomised controlled trials have demonstrated that screening for colorectal cancer (CRC) can reduce CRC related mortality, but the total benefit and harm of national cancer screening programmes are under debate. Saving relatively few lives requires a large number of people to be screened. Most people who attend screening will never develop cancer, but may be exposed to potential psychological stress by participation. Cancer is one of the largest threats to peoples’ health, and participating in screening for cancer might therefore cause anxiety. In Norway, colorectal cancer incidence has nearly tripled since the 1950s, and currently a large randomised pilot study of a national screening programme (Bowel Cancer Screening in Norway) is investigating the effect of screening on reduction in CRC incidence and mortality. As part of an evaluation of the benefits and harms of the pilot, we investigated the psychological effect of screening participation in a large group of participants. Of particular interest to us were participants who received a positive screening result and were referred to colonoscopy.
Author Interviews, Chemotherapy, Pancreatic, Vanderbilt / 07.03.2016

MedicalResearch.com Interview with: [caption id="attachment_22400" align="alignleft" width="129"]Alexander A. Parikh, M.D., M.P.H. Associate Professor of Surgery Director of Hepatobiliary, Pancreatic and GI Surgical Oncology Director, Vanderbilt Pancreas Center Vanderbilt University Medical Center Nashville, TN Dr. Alexander Parikh[/caption] Alexander A. Parikh, M.D., M.P.H. Associate Professor of Surgery Director of Hepatobiliary, Pancreatic and GI Surgical Oncology Director, Vanderbilt Pancreas Center Vanderbilt University Medical Center Nashville, TN MedicalResearch.com: What is the background for this study? Dr. Parikh: Although adjuvant chemotherapy has been proven to increase survival after successful resection of pancreatic cancer and has become the standard of care worldwide, the use of adjuvant chemoradiation is more controversial. The vast majority of randomized trials have failed to show a significant improvement in survival with the use of chemoradiation after pancreatic cancer resection. Furthermore, our own report from the multi-institutional Central Pancreatic Consortium (CPC) published several years ago failed to show a benefit in the use of chemoradiation except in high-risk groups such as lymph node positive disease. The purpose of the current study was to investigate the patterns of recurrence with the use of adjuvant chemotherapy or chemoradiation in hopes of explaining some of these differences. It was our hypothesis that systemic chemotherapy would prevent distant recurrence (and perhaps local) while chemoradiation would only prevent local recurrence and thereby have less impact on overall survival. MedicalResearch.com: What are the main findings? Dr. Parikh: The main findings demonstrated that adjuvant chemotherapy led to an improvement in both local and distant recurrence with a corresponding improvement in overall survival while chemoradiation only led to an improvement in local recurrence but not distant nor overall survival.
Author Interviews, Dental Research, Esophageal, Infections / 02.03.2016

MedicalResearch.com Interview with: [caption id="attachment_22280" align="alignleft" width="160"]Dr. Huizhi Wang Assistant Professor Department of Oral Immunology and Infectious Diseases University of Louisville School of Dentistry Louisville, KY Dr. Huizhi Wang[/caption] Dr. Huizhi Wang Assistant Professor Department of Oral Immunology and Infectious Diseases University of Louisville School of Dentistry Louisville, KY  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Wang: Esophageal cancer is the eighth most frequent tumor and sixth leading cause of cancer death worldwide, characterized by rapid development and poor prognosis, including high mortality. Whereas the majority of cases occur in Asia, particularly in central China, recent data suggest that the frequency of new cases is rising in Western Europe and the USA. Mounting evidence suggests a causal relationship between specific bacterial infections and the development of certain malignancies. However, the possible role of the keystone periodontal pathogen, Porphyromonas gingivalis, in esophageal squamous cell carcinoma (ESCC) was unknown before our study. We found P. gingivalis infects epithelium of cancerous tissues up to 61%, as compared with 12% of adjacent tissues and non-infected in normal esophageal mucosa. A similar distribution of lysine-specific gingipain, a catalytic endoprotease uniquely secreted by P. gingivalis, and P. gingivalis DNA was observed. Moreover, we found infection of P. gingivalis was positively associated with the multiple clinicopathologic characteristics, including differentiation status, metastasis, and overall survival rate. 
Author Interviews, Cancer Research, Diabetes, Diabetologia / 01.03.2016

MedicalResearch.com Interview with: [caption id="attachment_22195" align="alignleft" width="160"]Bendix Carstensen Bendix Carstensen[/caption] Bendix Carstensen Department of Clinical Epidemiology Steno Diabetes Center Gentofte Medical Research: What is the background for this study? What are the main findings? Response: It has long been known that all diabetes patients have elevated risk of cancer (10-15%). Patients on insulin slightly more (20-25%). Type 1 patients is only a small fraction (10%) of all diabetes patients, but they ALL take insulin. If insulin has a role in cancer occurrence it would be expected to be particularly pronounced in type 1 patients, and increasing by duration. But it is not, the risk of cancer is 15% elevated (if we disregard prostate, breast and other cancers only occurring in one of the sexes), and there is no increase in the excess risk by duration of insulin use. Breast cancer risk is 10% lower and prostate cancer risk some 40% lower. Overall there is very little increased cancer risk - 1% for men 7% for women.
Author Interviews, Cancer Research, Colon Cancer, Journal Clinical Oncology, Radiation Therapy / 26.02.2016

MedicalResearch.com Interview with: [caption id="attachment_22068" align="alignleft" width="133"]Dr Guy van Hazel Clinical Professor of Medicine, School of Medicine and Pharmacology, University of Western Australia Dr. Guy van Hazel[/caption] Dr Guy van Hazel Clinical Professor of Medicine, School of Medicine and Pharmacology, University of Western Australia  Medical Research: What is the background for this study? What are the main findings? Dr. van Hazel: The SIRFLOX study is based on original work by Dr Bruce Gray and myself almost two decades ago, when we studied the combination of Selective Internal Radiation Therapy (SIRT) with Y-90 resin microspheres – which was absolutely new at the time – with hepatic artery chemotherapy. This study showed an increase in liver control with the addition of SIRT [Gray B et al. Ann Oncol 2001; 12: 1711–1720.]. We then proceeded to initiate a trial comparing systemic SIRT plus 5-FU/LV according to the Mayo Clinic regimen compared to the Mayo Clinic regimen alone, but unfortunately this had to be abandoned because new chemotherapy became available which made it unethical to offer the control arm. However, in those patients who were treated up to that point with SIRT plus 5-FU/LV [van Hazel G et al. J Surg Oncol 2004; 88: 78–85.] we did see a very high response rates compared to the control arm, with an impressive survival of 29 months. We subsequently did a phase l/ll study of modified FOLFOX6 with or without SIRT and again found very high response rates [Sharma R et al. J Clin Oncol 2007; 25: 1099–1106.].  This led us to launch the SIRFLOX study in 2007.
Author Interviews, Cancer Research, Esophageal, Lung Cancer, Radiology, Surgical Research, University of Michigan / 25.02.2016

MedicalResearch.com Interview with: [caption id="attachment_22050" align="alignleft" width="133"]Mark A. Healy, MD Department of Surgery Center for Healthcare Outcomes & Policy, University of Michigan Ann Arbor, MI Dr. Mark Healy[/caption] Mark A. Healy, MD Department of Surgery Center for Healthcare Outcomes & Policy, University of Michigan Ann Arbor, MI   Medical Research: What is the background for this study? What are the main findings? Dr. Healy: In our study, we found high overall use of PET as a primary study for recurrence detection in lung and esophageal cancers, with substantial hospital-based variation in the use of PET. Despite this, there was not a significant difference in survival for patients across high and low PET use hospitals.
Author Interviews, BMJ, Cancer Research, OBGYNE / 24.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21992" align="alignleft" width="150"]Jiangrong Wang PhD Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm, Sweden Dr. Jianrong Wang[/caption] Jiangrong Wang PhD Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm, Sweden Medical Research: What is the background for this study? What are the main findings? Dr. Wang: Cervical screening has been proved to effectively suppress the occurrence of cervical cancer, since it detects not only cervical cancer at early stages, but also precursor lesions that can be treated before progressing to invasive cancers. However, cervical screening has mainly reduced the occurrence of squamous cell cervical cancer, the most common type of invasive cervical cancer, but not adenocarcinoma of the cervix which originates from glandular cells. Although there is a well-known connection between adenocarcinoma in situ and invasive adenocarcinoma, questions remain on the magnitude of the cancer risk after detection of the glandular intraepithelial lesion-atypical glandular cells (AGC). We also wanted to study whether the current clinical management after detection of glandular abnormalities reduced the cancer risk as much as the standard management for squamous intraepithelial lesions does. Our findings show that 2.6% of women with  intraepithelial lesion-atypical glandular cells as the first abnormality developed invasive cervical cancer after 15 years of follow up and 74% of the cancers were adenocarcinoma. A moderately high proportion of women with AGC had prevalent cancer (diagnosed within 6 months from AGC), while there was considerably high incidence of cervical cancer within 0.5-6.5 years after a detection of AGC. The incidence of cervical cancer following AGC was significantly higher than for high-grade squamous intraepithelial lesions, and this increased risk remained even after having histology assessment in the initial half year.

The high risk of cervical cancer associated with AGC implies that the current clinical management following AGC does not prevent cervical cancer as sufficiently as the management for squamous intraepithelial lesions does.

 

Author Interviews, Cancer Research, Cost of Health Care, End of Life Care / 19.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21847" align="alignleft" width="130"]Melissa Garrido, PhD Assistant Professor / Research Health Science Specialist GRECC, James J Peters VA Medical Center, Bronx, NY Brookdale Department of Geriatrics & Palliative Medicine Icahn School of Medicine at Mount Sinai, New York, NY Dr. Melissa Garrido[/caption] Melissa Garrido, PhD Assistant Professor / Research Health Science Specialist GRECC, James J Peters VA Medical Center, Bronx, NY Brookdale Department of Geriatrics & Palliative Medicine Icahn School of Medicine at Mount Sinai, New York, NY Medical Research: What is the background for this study? What are the main findings? Response: Medical costs for people with serious illnesses are rapidly rising in the United States. Concerns about medical debt and bankruptcy are especially relevant when deciding whether to begin or maintain a treatment that may have limited benefit to a patient’s survival or quality of life. Among patients with advanced cancer, one such decision is the choice of whether to use additional chemotherapy when the disease has not responded to an initial line or lines of chemotherapy. In this study, we used data from a prospective study of patients with advanced cancer and their caregivers to examine the relationship between chemotherapy use at study entry (median of four months before death) and estimated costs of healthcare other than chemotherapy in the last week of life. Medical Research: What is the background for this study? What are the main findings? Dr. Garrido: Among patients with end-stage cancer, those who received chemotherapy in the months before death had higher estimated costs of care in the last week of life.  We did not find evidence that this relationship was explained by patients’ preferences for care, do-not-resuscitate orders, or discussions of care preferences.
Author Interviews, Cancer Research, Columbia, Genetic Research / 19.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21808" align="alignleft" width="169"]Jeanine D'Armiento, M.D., Ph.D. Associate Professor of Medicine in Anesthesiology Director of the Center for Molecular Pulmonary Disease in Anesthesiology and Physiology and Cellular Biophysics Director, Center for LAM and Rare Lung Disease New York, NY 10032 Dr. Jeanine D'Armiento[/caption] Jeanine D'Armiento, M.D., Ph.D. Associate Professor of Medicine in Anesthesiology Director of the Center for Molecular Pulmonary Disease in Anesthesiology and Physiology and Cellular Biophysics Director, Center for LAM and Rare Lung Disease New York, NY 10032 Medical Research: What is the background for this study? What are the main findings? Dr. D'Armiento: I am the Director of the Center for Lymphangiomyomatosis (LAM) and Rare Lung Disease at Columbia University; the Center focuses on this proliferative lung disease, which arises spontaneously or as the pulmonary manifestation of the Tuberous Sclerosis Complex (TSC). We have one of the largest cohorts of these patients in the country. Through an understanding of the pathogenesis of LAM our research aims to identify novel therapeutic targets of the disease to improve the care of these patients. Building on our previous research we demonstrated that the HMGA2 gene and its signaling pathway (the route of information which begins an action within cells), are required to produce tumors in the lung and kidneys in individuals with Tuberous Sclerosis Complex.
Author Interviews, Cancer Research, Geriatrics, Lung Cancer, Nature / 12.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21559" align="alignleft" width="180"]Chiara Ambrogio, PhD Experimental Oncology Group CNIO-Centro Nacional de Investigaciones Oncológicas (Spanish National Cancer Research Centre) Melchor Fernández Almagro nº3 Madrid Spain Dr. Chiara Ambrogio[/caption] Chiara Ambrogio, PhD Experimental Oncology Group CNIO-Centro Nacional de Investigaciones Oncológicas (Spanish National Cancer Research Centre) Melchor Fernández Almagro nº3 Madrid Spain  Medical Research: What is the background for this study? Dr. Ambrogio: The majority of preclinical studies aimed at discovering new therapeutic strategies for lung adenocarcinoma have been conducted so far in full-blown tumors. We wanted to try a new approach by studying early lung lesions in a KRasG12V mouse model in order to bypass the problems imposed by tumor heterogeneity in later stages of the disease. We reasoned that the analysis of the first steps of lung adenocarcinoma development would help us in identifying valuable targets for therapeutic intervention.  Medical Research: What are the main findings? Dr. Ambrogio: 1) We performed gene expression analysis of KRasG12V-driven mouse lung hyperplasias (≤ 500 cells) and we compared it to the gene expression profile of full-blown lung adenocarcinoma. We found that the aggressive nature of this tumor type is determined earlier than what predicted by histopathological criteria. 2) The analysis of transcriptional changes in early lesions allowed us to identify DDR1 as a drugable target in KRasG12V-driven lung adenocarcinoma. We validated its potential as a therapeutic target both genetically and pharmacologically by means of a selective DDR1 inhibitor. We demonstrated that the co-inhibition of DDR1 and NOTCH pathway, a key player in DDR1-mediated survival, exerted additive therapeutic effect. 3) We confirmed these results in human lung adenocarcinoma by reporting, for the first time, the development of an orthotopic Patient-Derived Xenograft (PDX) model as the ideal platform for the preclinical evaluation of new therapeutic strategies.
Author Interviews, Cancer Research, Radiation Therapy, Stem Cells / 11.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21484" align="alignleft" width="120"]Erina Vlashi, PhD Assistant Professor Department of Radiation Oncology David Geffen School of Medicine at UCLA Los Angeles, CA 90095-1714 Dr. Erina Vlashi[/caption] Erina Vlashi, PhD Assistant Professor Department of Radiation Oncology David Geffen School of Medicine at UCLA Los Angeles, CA 90095-1714 Medical Research: What is the background for this study? What are the main findings? Dr. Vlashi: It has been known for quite some time that head and neck squamous cell carcinomas (HNSCC) that test positive for human papilloma virus (HPV) respond to radiation therapy more favorably than HPV-negative HNSCCs. Our team reviewed a cohort of 162 patients with a head and neck squamous carcinoma diagnosis over a two-year period, and confirmed that the outcomes were correlated with the patient's HPV status. The work that followed was prompted by a discovery we had made earlier in breast cancer suggesting that breast cancer cells that manage to survive radiation therapy have the capacity to convert into more de-differentiated, therapy-resistant cells with characteristics of cancer stem cells, and that the degree of this conversion depended on the type of breast cancer: the more aggressive types of breast cancer being more prone to the therapy-induced phenotype conversion. So, we hypothesized that this therapy-induced conversion phenomenon may especially be at play in  head and neck squamous cell carcinomas given the clinical observation that HPV-positive HNSCCs respond to radiation therapy much more favorably than HPV-negative HNSCCs, despite optimum treatment modalities. And indeed, that is what we found: tumor cells derived from a panel of  head and neck squamous cell carcinomas cell lines that do not respond well to radiation therapy have an enhanced ability to convert the cells that survive radiation into more aggressive cells, cancer stem-like cells that will resist the next round of radiation therapy. 
Author Interviews, Cancer Research, Dermatology, Transplantation / 09.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21418" align="alignleft" width="180"]Claire M. Vajdic, PhD Center for Big Data Research in Health University of New South Wales Australian Graduate School of Management Bldg, Sydney Australia. Dr. Claire Vajdic[/caption] Claire M. Vajdic, PhD Center for Big Data Research in Health University of New South Wales Australian Graduate School of Management Bldg, Sydney Australia on behalf of the authors. Medical Research: What is the background for this study? Dr. Vajdic: Lip cancer is one of the most common cancers in solid organ transplant recipients. Iatrogenic immunosuppression is a strong risk factor for lip cancer but the dose-related association between individual immunosuppressive agents and risk of lip cancer has not been examined. Therefore, we investigated the association between the type, dose and duration of immunosuppressive therapy and lip cancer risk in Australian liver, heart and lung transplant recipients.
Author Interviews, Cancer Research, Heart Disease, Journal Clinical Oncology / 07.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21310" align="alignleft" width="200"]Saro H. Armenian, DO, MPH Associate Professor Departments of Pediatrics and Population Sciences City of Hope Comprehensive Cancer Center Director of the Childhood Cancer Survivorship Clinic Duarte, CA Dr. Saro Armenian[/caption] Saro H. Armenian, DO, MPH Associate Professor Departments of Pediatrics and Population Sciences City of Hope Comprehensive Cancer Center Director of the Childhood Cancer Survivorship Clinic Duarte, CA     Medical Research: What is the background for this study? What are the main findings? Dr. Armenian: There are an estimated 14 million cancer survivors living in the U.S. today, and this number is expected to reach 19 million by 2024. Among these cancer survivors, nearly two-thirds will have survived more than five years beyond their cancer diagnosis, and two out of every five will be considered a ten-year survivor, contributing to a growing population of aging cancer survivors. Until now, very little was known about the cardiovascular health of adult long-term cancer survivors. For the current study, we relied on diagnosis/procedures routinely recorded in a large integrative healthcare system that includes racially/ethnically and socioeconomically diverse members who are broadly representative of the residents in Southern California. Cardiovascular outcomes were captured from a wide variety of healthcare delivery settings (inpatient and outpatient, primary and sub-specialty care). Importantly, cancer survivors included in the current study continued to receive their primary and subspecialty care within this system well-beyond their initial cancer diagnosis (5- and 10-year retention rate: 81% and 70%, respectively), providing us with reliable population-based estimates of long-term cardiovascular disease (CVD) risk. We found an up to 70% higher risk of CVD (ischemic heart disease, stroke, or cardiomyopathy/ heart failure) in patients diagnosed with breast, kidney, lung/bronchus, multiple myeloma, non-Hodgkin lymphoma, and ovarian cancer when compared with an age- sex- and zip-code matched non-cancer controls. Cancer survivors who had multiple modifiable risk factors such as hypertension, diabetes, dyslipidemia were at highest risk of developing cardiovascular disease  later in life, irrespective of cancer diagnosis. Importantly, cancer survivors who developed CVD were significantly more likely to die from all causes when compared to cancer survivors who did not develop CVD. While the reasons for these findings are not clear, it is possible that the presence of CVD can markedly diminish treatment options or planned duration of therapy at the time of cancer recurrence, thus compromising the optimal long-term management of a cancer patient.
Author Interviews, Cancer Research, Heart Disease, JAMA, Pharmacology / 06.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21344" align="alignleft" width="200"]Jonathan Douxfils Pharm.D. - Ph.D. Research assistant Faculty of Medicine - Department of Pharmacy NAmur Research Institute for LIfe Sciences (NARILIS) Namur Thrombosis and Hemostasis Center (NTHC) Dr. Jonathan Douxfils[/caption] Jonathan Douxfils Pharm.D. - Ph.D. Research assistant Faculty of Medicine - Department of Pharmacy NAmur Research Institute for LIfe Sciences (NARILIS) Namur Thrombosis and Hemostasis Center (NTHC) Medical Research: What is the background for this study? What are the main findings? Dr. Douxfils: We decided to perform this study based on the release of the FDA regarding the risk of arterial occlusive events associated with ponatinib. We then hypothesize that the risk was not only restricted to ponatinib but also to other TKIs. This study shows that dasatinib, nilotinib and ponatinib increase the risk of vascular occlusive events compared to imatinib. Medical Research: What should clinicians and patients take away from your report? Dr. Douxfils: We suggest that patients treated with these molecules should be more frequently monitored, i.e. by an intensive support of associated comorbidities. In addition, even if they appear to have a better efficacy in terms of molecular response, new generation TKIs does not improve the overall survival at one year. As we have not access to individual data, it was impossible to clearly identify categories of patients for whom the risk of cardiovascular occlusive events is predominant. Therefore, the intensive monitoring proposed should be applied to all patients treated with these molecules. Regarding the choice of the therapy, the physician should certainly consider the goals of the treatment. For elderly patients, improving survival is the main objective and in this context, imatinib remains an excellent choice. For patients with a life expectancy greater than 10 years in whom we aim to achieve a deep molecular response to potentially reach a point of treatment cessation, dasatinib and nilotinib could be preferred. However, the choice of dasatinib or nilotinib as first-line treatments should involve a screening for potential risk factors such as diabetes, prior vascular occlusive events or any risk that could increase these adverse events. For second- and third-line treatments, the choice of the treatment has to be based on mutational analysis, previous adverse events, and the medical condition of the patient. Thus, in case of intolerance or resistance, the switch to one of the other TKIs approved for first-line therapy is an option. If treatment failure still occurs, a more potent TKI, i.e. bosutinib, is preferred. Importantly, ponatinib is reserved to patients with the T315I mutation and must be avoided in patients with good prognosis.
Author Interviews, Brain Cancer - Brain Tumors, Genetic Research, Pediatrics, University of Pennsylvania / 04.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21295" align="alignleft" width="112"]Dr. Adam C. Resnick, Ph.D Assistant Professor of Neurosurgery Faculty, Abramson Cancer Center Director of Children's Brain Tumor Tissue Consortium Division of Neurosurgery Director, CHOP/PENN Department of Neurosurgery Brain Tumor Tissue BiorepositoryDirector for Neurosurgical Translational Research, Division of Neurosurgery Children's Hospital of Philadelphia Dr. Adam Resnick[/caption] Dr. Adam C. Resnick, Ph.D Assistant Professor of Neurosurgery Faculty, Abramson Cancer Center Director of Children's Brain Tumor Tissue Consortium Division of Neurosurgery Director, CHOP/PENN Department of Neurosurgery Brain Tumor Tissue BiorepositoryDirector for Neurosurgical Translational Research, Division of Neurosurgery Children's Hospital of Philadelphia   [caption id="attachment_21297" align="alignleft" width="150"]Payal Jain, PhD Candidate Division of Neurosurgery, Children's Hospital of Philadelphia Department of Neurosurgery Cell and Molecular Biology Graduate Group Gene Therapy and Vaccines Program Perelman School of Medicine University of Pennsylvania Philadelphia, Pennsylvania Payal Jain[/caption] Payal Jain, PhD Candidate Division of Neurosurgery, Children's Hospital of Philadelphia Department of Neurosurgery Cell and Molecular Biology Graduate Group Gene Therapy and Vaccines Program Perelman School of Medicine University of Pennsylvania Philadelphia, Pennsylvania   Medical Research: What is the background for this study? What are the main findings? Response: This study originates from our long-standing interest in studying pediatric low-grade gliomas (PLGGs), which are the most commonly diagnosed brain tumor in children. While several PLGGs have been found to harbor mutations/gene fusions driving the mitogen-associated protein kinase (MAPK) pathway leading to clinical trials testing MAPK inhibitors, these tumors remain poorly categorized and not enough is known about specific genetic mutations driving different tumor sub-types and the potential for specific targeted therapeutics. Our current study encompasses analysis of the largest combined genomic dataset of pediatric low-grade gliomas samples.  In doing this we, identified the MYB-QKI gene fusion, a non-MAPK related event, as the common genetic event driving a rare PLGG sub-type, called angiocentric gliomas. We have reported a novel tri-partite mechanism by which MYB-QKI mediates its oncogenic effect, this being the first report of a single gene rearrangement utilizing three different paths to cause cancer.
  • First, this gene rearrangement activates MYB, which is a proto-oncogene that is normally not expressed in the developed brain.
  • Second, we found that the rearrangement leads to translocation of QKI-related enhancers close to MYB’s promoters, thereby driving MYB-QKI expression in these tumors. Furthermore, MYB-QKI can also regulate its expression in a positive feedback loop.
  • Third, the tumor suppressor activities of QKI are disrupted in MYB-QKI. Such collaboration of genetic and epigenetic dysregulation in a single genetic rearrangement has previously not been reported.
Cancer Research / 03.02.2016

MedicalResearch.com [caption id="attachment_21268" align="alignleft" width="133"]Prof. Norbert Stefan, MD Department of Molecular Epidemiology German Institute of Human Nutrition Potsdam-Rehbruecke Nuthetal, Germany Prof. Norbert Stefan[/caption] Prof. Norbert Stefan, MD Department of Molecular Epidemiology German Institute of Human Nutrition Potsdam-Rehbruecke Nuthetal, Germany MedicalResearch: What is the background for this study? Prof. Stefan: Cardiovascular disease, type 2 diabetes, and cancer are among the most important causes of morbidity and mortality worldwide. Although the body mass index and waist circumference are established variables that help to predict the risk of these disease, adult height also predicts mortality independently of adiposity measures. However, compared to these risk factors, it has been somewhat neglected in clinical practice. Based on the finding that in recent decades the height of children and adults has steadily increased throughout the world, the question arises whether this secular trend in height might be a marker of a yet not well understood mechanism that affects not only stature, but also the development of cardiometabolic disease and cancer.  MedicalResearch: What are the main findings? Prof. Stefan: We summarized and interpreted data from different areas of research and also could provide some novel data to better understand the causes of the worldwide increase in height and its relationships with cardiometabolic disease and incidence of cancer. There is strong epidemiological evidence that tall people, in comparison to short people, have a lower risk of cardiovascular disease and type 2 diabetes but have a higher cancer risk. Per 6.5 cm in height the risk of cardiovascular mortality decreases by six percent, but cancer mortality, by contrast, increases by four percent. We suspect that the increase in body height is a marker of overnutrition of high-calorie food rich in animal protein during different stages of growth. Thus, already in utero, lifelong programming might take place that until now has mainly been established for the insulin-like growth factor 1 and 2 and the IGF-1/2 system. Among other consequences, activation of this system causes the body to become more sensitive to insulin action, thus positively influencing the lipid metabolism. Accordingly, our new data show that tall people are more sensitive to insulin and have lower fat content in the liver, which may explain their lower risk for cardiovascular disease and type 2 diabetes. However, this activation of the IGF-1/2 system and other signaling pathways may be related to an increased risk of certain cancers, especially breast cancer, colon cancer, and melanoma because cell growth is permanently activated.
Author Interviews, Brigham & Women's - Harvard, Cancer Research, Lancet, Pediatrics, Radiation Therapy / 02.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21220" align="alignleft" width="120"]Dr. Torunn Yock, MD Director, Pediatric Radiation Oncology Associate Professor, Harvard Medical School Radiation Oncology Quality Assurance Massachusetts General Hospital, Proton Center Boston, MA Dr. Torunn Yock[/caption] Dr. Torunn Yock, MD Director, Pediatric Radiation Oncology Associate Professor, Harvard Medical School Radiation Oncology Quality Assurance Massachusetts General Hospital, Proton Center Boston, MA Medical Research: What is the background for this study? Dr. Yock: Proton radiotherapy is a highly targeted form of radiation therapy that can spare normal tissues better than standard x-ray/photon based radiotherapy. Because, all side effects from radiotherapy come from radiation dose to normal healthy tissues, it is widely believed that proton radiotherapy has great potential to mitigate the side effects of treatment, both acute and long term side effects. There have been many planning studies that show that proton radiation can achieve a more highly conformal dose distribution and appear to spare 50% or more normal tissue from unnecessary irradiation.  However, there have been only a handful of retrospective studies that report disease control and side effects of treatment. While the technology looked promising, the definitive clinical data has been lacking to date. Because of this lack of clinical outcome data, the role and benefit of proton radiotherapy has been a subject of great debate in the oncology community.  Critics assert that proton radiotherapy is expensive and unproven and therefore a leading culprit in escalating costs of oncologic health care. Proponents assert that when used in the appropriate patient setting, the margin of benefit in terms of improved health outcomes, outweighs the increased cost of treatment. We embarked on this study to answer help answer the call for prospectively collected clinical outcome data to better define the most appropriate role for proton radiotherapy. Importantly, this study addresses both disease control and side effects of treatment in a pediatric medulloblastoma cohort of children. Medical Research: What are the main findings? Dr. Yock: This study shows that disease control in the pediatric medulloblastoma population is very much the same as that which is achieved by photon based radiotherapy treatments. However, more importantly, late side effects commonly attributed to radiotherapy such as neurocognitive decline over time and hearing loss appear to be improved compared with published photon treated cohorts of pediatric medulloblastoma patients.  Additionally, adverse late side effects on the cardiopulmonary, GI, and reproductive systems were essentially eliminated.
Author Interviews, BMJ, Colon Cancer, Gastrointestinal Disease, Global Health / 31.01.2016

MedicalResearch.com Interview with: [caption id="attachment_21039" align="alignleft" width="200"]Dr. Melina Arnold Section of Cancer Surveillance International Agency for Research on CancerLyon, France Dr. Melina Arnold[/caption] Dr. Melina Arnold Section of Cancer Surveillance International Agency for Research on Cancer Lyon, France MedicalResearch.com: What is the background for this study? What are the main findings?  Dr. Arnold: In this study, we looked at patterns and time trends in the incidence in and mortality from colorectal cancer on the global scale. In the analyses, we used data from the Globocan database, Cancer Incidence in Five Continents, both hosted by the International Agency for Research on Cancer (IARC), and the World Health Organisation mortality database. We documented a ten-fold variation in colorectal cancer incidence and mortality rates worldwide. We also found distinct gradients across human development levels, meaning that changes in patterns and trends of this cancer could be linked to economic development and that the adoption of a Western lifestyle may have a role. While incidence and mortality rates are on the increase in many countries in socioeconomic transition, stabilizing or decreasing trends are seen in highly-developed countries where rates remain among the highest in the world. These observations point to widening disparities and an increasing burden in transitioning countries.
Author Interviews, Cancer, Colon Cancer, Surgical Research / 29.01.2016

More on Colon Cancer on MedicalResearch.com [caption id="attachment_21070" align="alignleft" width="133"]Samantha Hendren, MD, MPH Associate Professor of Surgery Colorectal Surgery University of Michigan Dr. Samantha Hendren[/caption] MedicalResearch.com Interview with: Samantha Hendren, MD, MPH Associate Professor of Surgery Colorectal Surgery University of Michigan  Medical Research: What is the background for this study? What are the main findings? Response: We studied colorectal cancer nationally, and found that about 1 in 7 colorectal cancer patients in the U.S. (that is, 14.7%) is diagnosed before the age of 50.  We also found that these younger colorectal cancer patients were diagnosed when their cancers were more advanced (higher “stage”, meaning more of them had spread to lymph nodes and/or to other organs).  Part of the reason for this is that these young patients are often diagnosed only after their cancers start to cause symptoms such as anemia, bowel bleeding or a blockage in the colon. The age of 50 is when screening for colorectal cancer is started in the U.S.  This study means that a pretty large proportion of colorectal cancers are  happening in people who are too young to receive screening tests.  To put this in context, breast cancer screening often begins at age 40, and less than 5% of invasive breast cancers occur in women under that age. Our study found that about 15% of colorectal cancers are diagnosed before the screening age of 50. Fortunately, the young patients with colorectal cancer do a little better than you might predict, knowing that they are diagnosed at a worse cancer “stage”.  For the young patients under 50, about 68% survived 5 years, while about 67% of the patients 50 and older survived 5 years.  It looks like patients’ young age helps them in their cancer treatment and survival; our study found that treatment may be a bit more aggressive in the younger patients.
Author Interviews, Cancer Research, Genetic Research, PNAS / 28.01.2016

MedicalResearch.com Interview with: [caption id="attachment_21043" align="alignleft" width="150"]Nina Bhardwaj, MD, PhD and Director of Immunotherapy and professor of Hematology and Medical Oncology Dr. Nina Bhardwaj[/caption] Nina Bhardwaj, MD, PhD and Director of Immunotherapy and professor of Hematology and Medical Oncology [caption id="attachment_21044" align="alignleft" width="130"]Benjamin Greenbaum, PhD Assistant Professor The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai Dr. Benjamin Greenbaum[/caption] Benjamin Greenbaum, PhD Assistant Professor The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai   Medical Research: How did the discovery of the group of non-coding RNA molecules in cancer cells that sets off an immune response come about? Dr. Greenbaum: Our work is a collaboration between my lab, which is computational, and the Bhardwaj lab, focused on cancer immunology. I had previously made the observation that certain RNA viruses were avoiding certain motifs, such as CpG dinucleotide containing motifs, and the Bhardwaj lab tested whether those motifs could set off an immune response. Recent work had shown that tumors transcribe unusual RNA with immunological consequences, so we investigated whether the same sort of approaches we had used for viral RNA worked here. Dr. Bhardwaj: It has recently become clear that, due to epigenetic alterations, tumors transcribe non-coding RNAs that are typically silenced. Often such RNA emanates from the “dark matter” genome. Many of these regions consist of repetitive elements and endogenous retroelements that are rarely transcribed in normal tissue. At the same time, due to immunotherapy, understanding the role of the immune system and immune activation in tumors has become critically important. The activation of specific elements of the innate immune system in a tumor may have either beneficial or detrimental effects for patients. Moreover, recent work has suggested that endogenous element activation can lead to improved immunotherapy outcomes. Therefore, it is critically important to understand the nature of innate immune activation in tumors and what triggers are responsible for these responses. We have been developing methods to detect abnormal patterns in viral RNA that may indicate activation of the innate immune system. We have found that patterns of motif usage avoided in the evolution of viruses, such as influenza, indicate RNA features that provoke an innate immune response. The innate immune system is capable of sensing motifs in viruses. We tested directly whether these avoided patterns are immunostimulatory. Medical Research: What are the main findings? Dr. Bhardwaj: We used a novel quantitative approach, derived from methods in statistical physics, to characterize all of the non-coding RNA transcribed by normal tissue and compared them to the non-coding RNA found in tumors. We found that while the non-coding RNA transcribed in normal tissue displays patterns of motif usage consisting with that of coding RNA, the RNA transcribed in tumors, yet rarely found in normal tissue, can have motif usage more typically associated with viral and bacterial genomes. We predicted a handful of such RNA are immunostimulatory and validated this prediction in antigen presenting cells. We then showed that this sensing may come from a subset of the innate immune system associated with pathogen RNA sensing. We called these RNA “i-ncRNA”, for immunostimulatory non-coding RNA.
Author Interviews, Cancer Research, Infections / 27.01.2016

[caption id="attachment_20980" align="alignleft" width="176"]Yvonne Kapila, DDS, PhD Professor, Division of Periodontics Department of Periodontics and Oral Medicine University of Michigan School of Dentistry Ann Arbor, MI 48109-1078 Dr. Yvonne Kapila[/caption] MedicalResearch.com Interview with: Yvonne Kapila, DDS, PhD Professor, Division of Periodontics Department of Periodontics and Oral Medicine University of Michigan School of Dentistry Ann Arbor, MI   Medical Research: What is the background for this study? What are the main findings? Dr. Kapila: Our research showed that the preservative nisin induces cancer cell death. When tested on normal control cells to see if they were affected, the control cells were not affected. Thus, the most recent project began in order to find out more details as to why this occurred. We used a cancer mouse model (head and neck cancer) to show that nisin can retard tumor growth and extent the life of these mice. Another thing that we published about the preservative is nisin’s role on biofilms. Biofilms are communities of bacteria that can cause diseases. Nisin has been tested in bacterial biofilms that contain bacteria that cause gum disease and dental decay and nisin has been found to be effective in this setting as well. In laboratory settings, nisin is also cytotoxic to superbugs, including the most resistant bugs found in hospitals, and therefore nisin holds promise for several therapeutic applications.
Author Interviews, Cancer Research, Genetic Research, Personalized Medicine, UCLA / 24.01.2016

[caption id="attachment_20891" align="alignleft" width="143"]Dr. Chirag Patil, MD American Board Certified Neurosurgeon, Brain & Spine Tumor Program Lead Investigator, Precision Medicine Initiative Against Brain Cancer Program Director, Neurosurgical Residence training program Director, Center for Neurosurgical Outcomes Research – Cedars-Sinai Medical Center, Los Angeles, California Dr. Chirag Patil[/caption] MedicalResearch.com Interview with: Dr. Chirag Patil, MD American Board Certified Neurosurgeon Brain & Spine Tumor Program Lead Investigator, Precision Medicine Initiative Against Brain Cancer Program Director, Neurosurgical Residence training program Director, Center for Neurosurgical Outcomes Research Cedars-Sinai Medical Center, Los Angeles, California MedicalResearch.com Editor’s note: Dr. Patil’s research is focused on developing a method of personalized cancer treatment through the harnessing of genome wide mutational analysis of a specific patient’s cancer. MedicalResearch.com: Would you tell us a little about yourself and your research interests? Dr. Patil: I am a Stanford-trained, Board Certified Neurosurgeon and cancer researcher at Cedars-Sinai Medical Center in Los Angeles, California. I primarily focus on the care of patients with malignant brain tumors, particularly glioblastomas. I received my undergraduate degree from Cornell, followed by a medical degree from the University of California, San Francisco (UCSF), where I was a Regent’s scholar. I completed a residency in neurosurgery and a fellowship in stereotactic radiology at Stanford University. I also have a master’s degree in epidemiology with a focus on clinical trial design and mathematical modeling from Stanford. MedicalResearch.com: Can you tell us about some of your research interests? Dr. Patil: I am keenly interested in and focused on developing precision science-powered novel brain tumor therapies, immuno-therapies, and patient-centered “big data” outcomes research. I lead the recently-funded Cedars-Sinai Precision Medicine Initiative Against Brain Cancer, which utilizes tumor genomics to build a mathematical computer model, i.e., a virtual cancer cell of each patient’s unique tumor. The White House and several other stakeholders have taken keep interest in this research initiative as an example of a leading precision medicine program.
Author Interviews, HPV, JAMA / 22.01.2016

[caption id="attachment_20757" align="alignleft" width="125"]Ilir Agalliu, M.D., Sc.D. Assistant Professor, Department of Epidemiology & Population Health and Department of Urology Albert Einstein College of Medicine Jack and Pearl Resnick Campus Bronx, NY Dr. Ilir Agalliu[/caption] More on HPV on MedicalResearch.com  MedicalResearch.com Interview with: Ilir Agalliu, M.D., Sc.D. Assistant Professor, Department of Epidemiology & Population Health and Department of Urology Albert Einstein College of Medicine Jack and Pearl Resnick Campus Bronx, NY Medical Research: What is the background for this study? Dr. Burk: We performed this study since we had previously detected an unusually high prevalence of HPV types found on the skin and skin cancers in the oral cavity in addition to HPV16 and other high-risk (HR) types (as defined by their association with cervix cancer) (see Journal of Infectious Diseases 204:787, 2011). We wished to determine if these types were associated with risk of head and neck cancers (HNSCCs). In addition, we wished to determine if HPV detection preceded the diagnosis of HNSCCs and might serve as a biomarker. Currently there are no good screening tests for HNSCC. Dr. Agalliu: To-date, there have been no prospective studies examining the temporal relationship between oral HPV detection and risk of head and neck squamous cell carcinoma (HNSCC). In this manuscript we examined prospectively associations between detection of a wide spectrum of oral HPVs (alpha, beta and gamma) with incident HNSCC in a nested case-control study among ~100,000 participants who provided mouthwash samples in the American Cancer Society-CPS II cohort and the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Dr. Agalliu: Oral HPV16 detection, which preceded cancer development on average for 4 years, was associated with a 22-fold increased risk for incident oropharyngeal cancer. Detection of other oral HPVs (beta1 HPV5, and gamma11 and 12 species) were associated with a 3.3 to 5.5-fold higher risk of  head and neck squamous cell carcinoma after adjustment for smoking, alcohol and HPV16. Associations of beta and gamma HPVs, which have been identified in the skin, with risk of HNSCC suggest a broader role for HPVs in HNSCC etiology.
Author Interviews, Cancer Research, PNAS / 21.01.2016

[caption id="attachment_20795" align="alignleft" width="149"]Dr. Elizabeth Murchison Menzies Institute for Medical Research University of Tasmania Save the Tasmanian Devil Program Tasmanian Department of Primary Industries, Parks, Water and the Environment Hobart Australia Department of Veterinary Medicine University of Cambridge, Cambridge UK Dr. Murchison[/caption] MedicalResearch.com Interview with: Dr. Elizabeth Murchison Menzies Institute for Medical Research University of Tasmania Save the Tasmanian Devil Program Tasmanian Department of Primary Industries, Parks, Water and the Environment Hobart Australia Department of Veterinary Medicine University of Cambridge, Cambridge UK Medical Research: What is the background for this study? Dr. Murchison: Transmissible cancers are cancers that can be transmitted between individuals by the transfer of living cancer cells. Transmissible cancers emerge only very rarely in nature, and until now only three examples were known. One of the three known naturally occurring transmissible cancers affects Tasmanian devils, the world’s largest carnivorous marsupial. This disease, which causes disfiguring facial tumours, was first observed in the late 1990s, and since then the disease has spread widely through the Tasmanian devil population. This transmissible cancer first emerged as a cancer in a single individual Tasmanian devil that probably lived about 30 years ago; this devil’s cancer cells have continued to survive by transmitting between hosts by biting. Medical Research: What are the main findings? Dr. Murchison: In late 2014, routine monitoring of the Tasmanian devil population led to the discovery of a male devil with facial tumours that resembled the known Tasmanian devil transmissible facial cancer. However, genetic analysis of this tumour indicated that the tumour in this devil was derived from a second transmissible cancer that was genetically unrelated to the first transmissible cancer in this species. Indeed, the genetic profile of this second cancer indicated that it had originally emerged from a male animal. This second cancer has subsequently been found in nine additional devils in the same part of Tasmania.
ASCO, Author Interviews, Cancer Research, Lymphoma / 18.01.2016

More Cancer Research on MedicalResearch.com [caption id="attachment_20709" align="alignleft" width="156"]Erin E. Hahn, PhD, MPH Research Scientist Southern California Permanente Medical Group Kaiser Permanente Research Department of Research & Evaluation Pasadena, CA 91101 Dr. Erin Hahn[/caption] MedicalResearch.com Interview with: Erin E. Hahn, PhD, MPH Research Scientist Southern California Permanente Medical Group Kaiser Permanente Research Department of Research & Evaluation Pasadena, CA 91101 Medical Research: What is the background for this study? Dr. Hahn:  Adolescent and young adults, or AYAs, who are diagnosed and treated for Hodgkin lymphoma have very high overall survival rates. However, these patients are at high risk for short and long term health issues related to their cancer treatment, including cancer recurrence, cardiac and pulmonary problems, and developing new primary cancers. Some of these issues arise during treatment and persist over time, called long-term effects, and some develop years later, called late effects. Evidence and consensus based guidelines are available from organizations like the National Comprehensive Cancer Network and the Children’s Oncology Group to help manage the post treatment care of  Adolescent and young adults Hodgkin lymphoma survivors. Examining adherence to guidelines is an important part of high quality care, and can help us find and address gaps in care. Guideline recommended care for these patients includes: oncology visits, imaging and labs, preventive care, counseling and education, risk based screening for late effects. Risk-based screening is based on a patient’s treatment. The type of health screening a patient needs is determined by the treatment exposure they had, such as certain types of chemotherapy or high-dose radiation that have known late effects  Medical Research: What are the main findings? Dr. Hahn: For this pilot study, I was interested to see if post-treatment  Adolescent and young adults Hodgkin lymphoma patients in an integrated health care system received recommended short and long term care. The study setting is Kaiser Permanente Southern California (KPSC). KPSC provides care for almost 4 million members with 14 medical centers, and they have a long-standing electronic medical record. For our population, we included AYA patients diagnosed with classical Hodgkin lymphoma between 15 and 39 years of age, diagnosed between 2000 and 2010. We wanted to find patients who were diagnosed, treated, and followed for at least 2 years within this single system. We have a sample of 354 patients, which is great. It has been traditionally difficult to find and follow these patients/obtain accurate medical information that isn’t only self-report data. We were able to extract chemotherapy, radiation, and other care details from the electronic medical record. We first looked at receipt of short term recommended care, within the first year after treatment had ended. We looked specifically at oncology visits, use of recommended CT scan and lab tests, and preventive care, such as the flu vaccine. The great majority of patients had the recommended oncology visits, CT scan, and lab tests. However, receipt of the flu vaccine was lower, at 20%. When we looked at a composite measure of all 4 recommended services, only about half of the patients received all four recommended services within the first year after treatment. We also looked at use of a longer term recommended service for cardiac issues. Cardiac screening is recommended for patients who are 10 years out from their treatment and who received high-dose anthracyclines, plus radiation to the chest. This is the highest risk group for cardiac damage. Almost everyone received annual blood pressure screening, but only about 30% received screening with an electrocardiogram, echocardiogram, or MUGA scan.
Author Interviews, Cancer Research, Technology / 15.01.2016

[caption id="attachment_20678" align="alignleft" width="200"]Elena V. Batrakova, Ph.D. Associate Professor Center for Nanotechnology in Drug Delivery Division of Molecular Pharmaceutics Eshelman School of Pharmacy University of North Carolina at Chapel Hill Chapel Hill, NC Dr. Elena Batrakova[/caption] More on Cancer Research on MedicalResearch.com MedicalResearch.com Interview with: Elena V. Batrakova, Ph.D. Associate Professor Center for Nanotechnology in Drug Delivery Division of Molecular Pharmaceutics Eshelman School of Pharmacy University of North Carolina at Chapel Hill Chapel Hill, NC  Medical Research: What is the background for this study? What are the main findings? Dr. Batrakova: Deep down I was always was fascinated by the ability of biological systems to deliver various compounds to the disease sites. I believe, we have a lot to learn from living things. For example, immune cells, macrophages can feel inflammation and travel to this sited to deal with the problem, for example, kill bacteria, virus, or regenerate and support dying cells. So, when I realized that specific and targeted transport of therapeutics to cancer cells is very difficult task, I turned to nature. Exosomes are naturally occurring vesicles (bubbles) that offer distinct advantages that uniquely position them as highly effective drug carriers. They consist of cellular membranes with multiple sticky proteins on their surface. Exosomes by nature specialize in cell-cell communication and provide an approach for the delivery drugs to target disease sites. Plus, exosomes released by patient’s white blood cells are not immunogenic, because they are part of the immune system, so these tiny bubbles can be used for very precise and effective delivery of anticancer drugs to treat metastases, as well as primary tumors.
Author Interviews, Cancer Research / 14.01.2016

More on Protein Kinases on MedicalResearch.com MedicalResearch.com Interview with: Dr Angus Cameron Kinase Biology Laboratory Barts Cancer Institute at Queen Mary University of London and Professor Peter Parker Protein Phosphorylation Laboratory The Francis Crick Institute Medical Research: What is the background for this study? What are the main findings? Response: A particular family of candidate targets for cancer therapies (the three members of the protein kinase, or PKN, family) have been largely overlooked in terms of our understanding of their roles in normal biology and also in disease. Since any programme to develop new treatments is well informed by understanding the normal roles of the drug targets in non-tumour settings, our research teams ‘knocked-out’ these genes in a model mammalian system, in mice, and observed the effect. A key finding is that whilst two of the protein kinases, PKN1 and PKN3, are not necessary for mammalian development or adulthood, for PKN2 there is an absolute requirement in embryo development, but evidence of little requirement in adulthood. Our teams then analysed in some detail the genetics and pathology of the developmental defects for PKN2 knock-outs. This established the importance of PKN2 in mesenchymal cell survival and proliferation during development. Mesenchymal cells are dynamic contractile cells which provide structure and shape to the developing embryo. This finding has profound effects on multiple developmental events. Mesenchymal cells are also important in many connective tissue conditions, including fibrosis of the lungs, and in cancer where mesenchymal cells can support invasion of cancer cells into tissues.
Author Interviews, Cancer Research, JAMA, Transplantation / 11.01.2016

[caption id="attachment_20526" align="alignleft" width="180"]Sergio A. Acuna, MD Graduate Student at St. Michael's Hospital and IHPME University of Toronto Dr.  Sergio Acuna[/caption] MedicalResearch.com Interview with: Sergio A. Acuna, MD Graduate Student at St. Michael's Hospital and IHPME University of Toronto Medical Research: What is the background for this study? Dr. Acuna: Solid organ transplant recipients are known to be at greater risk of developing cancers compared to the general population; however, because they are also at high increased risk of mortality from non-cancer causes, the risk of cancer morality in this population is unclear. As previous studies on this topic have reported disparate findings, the cancer mortality risk in this population remained uncertain. Medical Research: What are the main findings? Dr. Acuna: Our study provides conclusive evidence that solid organ transplant recipients are at increased risk of cancer mortality. Our findings demonstrate that solid organ transplant recipients are at increased risk of cancer death compared to the general population regardless of age, transplanted organ, and year of transplantation, and indicate cancer is a substantial cause of death in this population.
Author Interviews, Cancer Research, Heart Disease, Pediatrics / 07.01.2016

[caption id="attachment_20386" align="alignleft" width="200"]Daniel A. Mulrooney, MD, MS Cancer Survivorship Jude Children's Research Hospital TN 38105-3678 Dr. Daniel Mulrooney[/caption] MedicalResearch.com Interview with: Daniel A. Mulrooney, MD, MS Cancer Survivorship Jude Children's Research Hospital TN 38105-3678 Medical Research: What is the background for this study? What are the main findings?  Dr. Mulrooney:  This is a cross-sectional analysis performed in the St. Jude Lifetime Cohort Study (SJLIFE), an ongoing study designed to facilitate longitudinal evaluation of health outcomes among adults previously treated for childhood cancer.  Following patients over the life spectrum can be challenging making it difficult to understand the long-term health effects of childhood cancer therapy.  Previous studies have relied on self-report, registry, or death certificate data.  Our study is novel because we clinically evaluated cancer survivors on the St. Jude campus and identified substantial, asymptomatic cardiac disease (cardiomyopathy, coronary artery disease, valvular disease, and conduction/rhythm disorders).
  • Cardiomyopathy was present in 7.4% of survivors and newly identified by screening in 4.7%.
  • Coronary artery disease was present in 3.8% of survivors and newly identified by screening in 2.2%.
  • Valvular disease (regurgitation or stenosis) was present in 28% of survivors and newly identified by screening in 24.8%.
  • Conduction or rhythm abnormalities were present in 4.4% of survivors and newly identified by screening in 1.4%.
The prevalence of these cardiac findings might be expected in an older population but not necessarily in this young adult (median age at time of study 31 years, range: 18-60) population.