Author Interviews, Cancer Research, Cost of Health Care / 08.04.2015

MedicalResearch.com Interview with: Stacie B. Dusetzina PhD Assistant professor in the Eshelman School of Pharmacy and the Gillings School of Global Public Health University of North Carolina at Chapel Hill Member of the Lineberger Comprehensive Cancer CenterMedicalResearch.com Interview with: Stacie B. Dusetzina PhD Assistant professor in the Eshelman School of Pharmacy and the Gillings School of Global Public Health University of North Carolina at Chapel Hill Member of the Lineberger Comprehensive Cancer Center Medical Research: What is the background for this study? What are the main findings? Dr. Dusetzina: Charges for health services — the amounts providers request before payments are negotiated — have not been widely known for services delivered in physicians’ offices. Charges can be considered the maximum amount that would be paid by a person without insurance who does not or is unable to negotiate for a lower price. In this study we used recently released data from the Medicare Provider Utilization and Payment Public Use File and other sources to measure what physicians charged for chemotherapy drugs delivered intravenously in 2012 and the amounts reimbursed by Medicare and private health plans for the same services. We found that uninsured cancer patients may be asked to pay from 2 to 43 times what Medicare pays for chemotherapy drugs. Medicare and insurers don’t pay the sticker price of health care. They pay a discounted rate. However, uninsured patients don’t have the bargaining power, or they may not try to negotiate for a better price. On average, Medicare paid approximately 40 percent of the charged amounts for chemotherapy drugs. Private insurers paid nearly 57 percent of the charged amounts on average. We also looked at what cancer patients were asked to pay for an office visit. Uninsured patients may be asked to pay from $129 to $391, depending on the complexity of the visit. Medicare paid between $65 and $188 and private insurance paid between $78 and $246 for the same visits. (more…)
Author Interviews, Cancer Research / 08.04.2015

MedicalResearch.com Interview with: Dr. Riccardo Capocaccia Evaluative Epidemiology Unit Department of Preventive and Predictive Medicine Fondazione Istituto Nazionale Tumori Milan, Italy Medical Research: What is the background for this study? What are the main findings? Dr. Capocaccia: Life expectancy of cancer patients is usually provided at diagnosis, as a measure of cancer burden. However, no systematic data are available on life expectancy at different times after diagnosis, as a measure of the residual impact of the disease in survivors. At diagnosis, young patients face a higher loss in life expectancy, with respect to cancer-free people of the same age, than older ones. Thereafter, life expectancy gradually approaches, but hardly reaches,  that of all patients of the general population. (more…)
Author Interviews, Cancer Research, Nature, NYU / 03.04.2015

MedicalResearch.com Interview with: Alka Mansukhani Ph.D. Associate Professor Department of Microbiology NYU Langone Medical CenterMedicalResearch.com Interview with: Alka Mansukhani Ph.D. Associate Professor Department of Microbiology Member of the Laura and Isaac Perlmutter Cancer Center NYU Langone Medical Center Medical Research: What is the background for this study? What are the main findings? Dr. Mansukhani: Osteosarcoma is a highly aggressive pediatric bone cancer that is almost always advanced at diagnosis. Treatment outcomes have not improved in three decades and 40% of patients eventually succumb to the disease. A few years ago we identified that normal bone stem cells relied on the function of a gene called Sox2 to remain immature an self-renew. We went on to find that osteosarcoma cancer stem cells, that arise from immature bone cells, express high levels of Sox2. Like their normal counterparts, these cancer cells also need Sox2. Sox2 maintains the stemness properties of the cancer cells as well as their ability to form tumors in mice. Depleting Sox2 resulted in cells that had reduced tumor-forming potential and instead, were able to become mature bone cells. http://www.stbaldricks.org/blog/post/new-discovery-may-hold-the-key-to-destroying-osteosarcoma/ In this new study we have identified the mechanism by which Sox2 maintains the properties of osteosarcoma cancer stem cells. Sox2 inactivates the growth restraining function of the well-known tumor suppressive hippo pathway. Hippo signaling restrains the activity of a potent oncogene, YAP. In the osteosarcoma stem cells, Sox2 directly represses two genes (Nf2 and WWC1) in the hippo pathway and thereby unleashes the growth promoting activity of YAP. Like Sox2, YAP is required to maintain the tumorigenic properties of osteosarcoma cells. Consistently, we found high YAP and low NF2 and WWC1 expression in human osteosarcoma tissues. Our study makes a direct connection between Sox2 and repression of hippo signaling to enable YAP activity in osteosarcomas. This mechanism also operates in glioblastoma, an aggressive brain tumor. (more…)
Author Interviews, Prostate Cancer / 05.03.2015

M. Minhaj Siddiqui, MD Director of Urologic Robotic Surgery Assistant Professor of Surgery - Urology University of Maryland School of Medicine Baltimore MD 21201MedicalResearch.com Interview with: M. Minhaj Siddiqui, MD Director of Urologic Robotic Surgery Assistant Professor of Surgery - Urology University of Maryland School of Medicine Baltimore MD 21201 Medical Research: What is the background for this study? Response: A history of testicular cancer has been suggested to have an association with an increased risk of developing prostate cancer (PCa) in epidemiologic studies. We hypothesized that there may be an increased risk of developing intermediate to high-risk prostate cancer as well. Medical Research: What are the main findings? Response: 147,044 men with melanoma and 32,435 men with testicular cancer were identified. Prostate cancer was diagnosed in 3,205 men in total. The cumulative incidence of all prostate cancer by age 80 was 2.8% in the control melanoma cohort and 12.6% in the case cohort of men with history of testicular cancer (p<0.0001 for KM survival curves, Figure 1). For intermediate/high-risk disease, the incidence was 1.1% versus 5.8% for each cohort respectively (p<0.0001 for KM survival curves, Figure 2). No association with prostate cancer was seen with non-seminomatous versus seminomatous germ cell tumors. Upon multivariate analysis, testis cancer was associated with an increased risk of all prostate cancer (HR 4.7, p<0.0001) and intermediate/high-risk PCa (HR 5.2, p<0.0001) when controlling for race and radiation history. (more…)
Author Interviews, Cancer Research, JAMA, Race/Ethnic Diversity, Vanderbilt / 24.02.2015

Dr. Wei Zheng, MD, PhD Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TennesseeMedicalResearch.com Interview with: Dr. Wei Zheng, MD, PhD Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee   Medical Research: What is the background for this study? What are the main findings? Dr. Wei Zheng: Substantial progress has been made in the diagnosis and treatment of cancer, resulting in a steady improvement in cancer survival. However, the degree of improvement by age, race and sex remains unclear. We quantified the differences in the improvement of cancer survival by race, age, and sex over the last two decades. We used cancer diagnosis and follow-up data from more than 1 million cancer patients, collected in nine SEER registries, to investigate trends in improved survival for seven major cancers in the United States by age, race, and sex between 1990 and 2010. We found that elderly patients experienced a smaller improvement in survival for cancers of the colon/rectum, breast, prostate, lung, and liver than their younger counterparts. In particular, the age-related disparities were most pronounced for those cancers with the greatest advancements in diagnosis and treatment over the past two decades, including cancers of colon/rectum, breast and prostate. African Americans experienced poorer survival than whites for all cancers. Because of a greater improvement in prostate cancer survival in African Americans than for whites, the racial difference in the survival of this cancer decreased during the study period. For ovarian cancer, however, the survival rate declined in African Americans but slightly increased in whites, leading to a wider racial gap in the survival of this deadly cancer. No apparent disparities in survival improvement by sex were noted. (more…)
Author Interviews, BMJ, Cancer Research / 20.02.2015

Dr Cristina Renzi Department of Epidemiology and Public Health, University College London, Health Behaviour Research Centre, London, UKMedicalResearch.com Interview with: Dr Cristina Renzi Department of Epidemiology and Public Health, University College London, Health Behaviour Research Centre, London, UK MedicalResearch: What is the background for this study? What are the main findings? Dr. Renzi: Only a minority of symptomatic individuals undergoing cancer investigations are diagnosed with cancer and more than 80% receive an 'all-clear' or non-cancer diagnosis (here called a 'false alarm'). This makes it important to consider the possible unintended consequences of a false alarm. Several studies have shown that investigations for a suspected cancer can have negative psychological effects, even for individuals ultimately diagnosed with a benign condition. In addition, an association between false alarms and subsequent delayed diagnosis has been reported for various cancers, with both patients and healthcare providers contributing to delays. Our review published by BMJ Open focused on 19 research papers which reported information on false alarms and subsequent symptom attribution or help-seeking. By integrating the available evidence from qualitative, quantitative and mixed methods studies this review allowed us to identify areas that need to be addressed in order to reduce the risk of delayed help-seeking after a previous false alarm. In particular, over-reassurance and under-support of patients can be an unintended consequence of a false alarm leading to delays in help-seeking, even years later, if patients notice possible symptoms of the disease again. The review, funded by Cancer Research UK, looked only at adult patients who had a false alarm after raising concerns about their symptoms; the effect of a false alarm might be different in patients who are investigated for suspected cancer following cancer screening. (more…)
Author Interviews, Cancer Research, Cost of Health Care, JAMA, University of Pennsylvania / 13.02.2015

Ezekiel Jonathan Emanuel MD PhD Department of Medical Ethics and Health Policy Perelman School of Medicine and Department of Health Care Management The Wharton School University of Pennsylvania Philadelphia, PAMedicalResearch.com Interview with: Ezekiel Jonathan Emanuel MD PhD Department of Medical Ethics and Health Policy Perelman School of Medicine and Department of Health Care Management The Wharton School University of Pennsylvania Philadelphia, PA Editor’s note: Dr. Emanuel is a medical oncologist as well as director of the department of Medical Ethics and Health Policy at the University of Pennsylvania. Dr. Emanuel was kind enough to answer several questions regarding his most recent study, published in the new JAMA Oncology journal, Patient Demands and Requests for Cancer Tests and Treatments. Medical Research: What is the background for this study? What are the main findings? Dr. Emanuel: The genesis for this study is twofold. One, the first referenced article, by John Tilbert1 discussed how physicians explain US health care costs. In this study, physicians felt patients, insurance companies, drug companies, government regulations and malpractice lawyers...all were more to blame than doctors themselves for the high cost of US health care. Secondly, I give lots of presentations to doctors who offer two explanations for escalating health care costs: fear of malpractice litigation, and demanding patients, who request extensive testing and drugs. We decided to see whether the impression doctors frequently held of patients’ demands driving up health care costs, had been previously investigated. We could find no article to substantiate this belief. In addition, demanding patients were not common in my medical experience. In our study we included 5050 patient encounters. We asked the clinician coming out of the encounter, did the patient make a demand or request? (By asking immediately after the doctor left the examination room, there was little risk of inaccurate recall of the specifics of visit). In 8.7% there was a patient request and of these, over 70% were deemed clinically appropriate as determined by the physician (i.e. a request for pain medication, palliative care or imaging to address a new symptom or finding). In only 1% of all encounters (50/5050) was a clinically inappropriate request made as determined by the doctor, and the doctors hardly filled any of these inappropriate requests (total of 7 of 5050 encounters). We concluded that it is pretty rare for patients to make demands or requests, at least in this oncology setting, and even less common for the demands to be complied with by the doctor. Therefore it seems unlikely to us that health care costs are significantly driven by inappropriate patient requests. It is possible that there are more or different patient demands in other health care settings but we were very surprised to find no difference in patient requests based on patient-income, i.e. wealthier, more educated patients made no more demands than patients of lesser means. (more…)
Author Interviews, Cancer Research, JAMA, MD Anderson, Outcomes & Safety / 12.02.2015

Kenneth L. Kehl, MD Division of Cancer Medicine, MD Anderson Cancer Center Houston, TexasMedicalResearch.com Interview with: Kenneth L. Kehl, MD Division of Cancer Medicine, MD Anderson Cancer Center Houston, Texas Medical Research: What is the background for this study? What are the main findings? Response: Prior studies have demonstrated that most patients with cancer wish to participate in their treatment decisions.  We studied a cohort of patients with lung or colorectal cancer and assessed whether patient involvement in decision-making was associated with perceived quality of care or ratings of physician communication.  We found that patients who described a more shared decision-making process gave higher ratings of their care quality and physician communication.  This effect was independent of patients' stated preferences regarding involvement in decision-making. (more…)
Author Interviews, Genetic Research, Leukemia, NEJM, Personalized Medicine / 11.02.2015

David G. Kent, Ph.D From the Cambridge Institute for Medical Research and Wellcome Trust–Medical Research Council Stem Cell Institute University of CambridgeMedicalResearch.com Interview with: David G. Kent, Ph.D From the Cambridge Institute for Medical Research and Wellcome Trust–Medical Research Council Stem Cell Institute University of Cambridge Medical Research: What is the background for this study? What are the main findings? Dr. Kent: Cancers are the result of the sequential acquisition of errors in the genetic code.  Most studies have focused on the sum of these mutations (e.g., A+B+C = cancer) but no study in patients has asked the question of whether or not the order of genetic mutations impacts the disease (e.g., does A to AB equal B to BA).  We studied patients with chronic blood disorders (known as myeloproliferative neoplasms, or MPNs) that are precursors to cancer to access the earliest stages of tumour development and studied whether or not the order of mutation acquisition impacted disease.  We studied patients with mutations in two genes (JAK2 and TET2) and showed that the order of acquisition of these mutations impacted timing of clinical presentation, disease subtype, frequency of thrombotic events, and differed in their response to targeted therapy in the lab. (more…)
Author Interviews, Cancer Research, NEJM, Thyroid / 11.02.2015

Dr. Martin S. Schlumberger MD Department of Nuclear Medicine and Endocrine Oncology Centre de Référence Tumeurs Réfractaires de la Thyroïde Institut Gustave Roussy and University Paris-Sud Villejuif, FranceMedicalResearch.com Interview with: Dr. Martin S. Schlumberger MD Department of Nuclear Medicine and Endocrine Oncology Centre de Référence Tumeurs Réfractaires de la Thyroïde Institut Gustave Roussy and University Paris-Sud Villejuif, France   Medical Research: What is the background for this study? What are the main findings? Dr. Schlumberger: Patients with advanced refractory thyroid cancer is rare (4-5 patients/million population) but portends a poor prognosis with a median overall survival of 3-5 years from the diagnosis of metastases. Before the availability of kinase inhibitors there was no effective treatment, and for this reason placebo was used as control in SELECT trial. This trial showed an improvement of PFS lenvatinib vs placebo (hazard ratio: 0.21; 99% CI: 0.14–0.31, P<0.001; median PFS: 18.3 vs 3.6 months, respectively) and objective response rate of 65% with some complete responses. Time to response was short (2 months). Similar benefits were observed in naive patients and in patients who had been treated with another tyrosine kinase inhibitor, demonstrating the absence of cross resistance. Toxicity was significant and could be controlled with dose reduction and symptomatic treatment. Medical Research: What should clinicians and patients take away from your report? (more…)
Author Interviews, MD Anderson / 10.02.2015

Dihua Yu, M.D., Ph.D. Hubert L. & Olive Stringer Distinguished Chair in Basic Science Professor and Deputy Chair Department of Molecular and Cellular Oncology Co-Director, Center of Biological Pathways The Univ. Texas MD Anderson Cancer Center Houston, TX 77030MedicalResearch.com Interview with: Dihua Yu, M.D., Ph.D. Hubert L. & Olive Stringer Distinguished Chair in Basic Science Professor and Deputy Chair Department of Molecular and Cellular Oncology Co-Director, Center of Biological Pathways The Univ. Texas MD Anderson Cancer Center Houston, TX 77030 Medical Research: What is the background for this study? Dr. Yu: Transforming growth factor β (TGF-β) functions as a tumor suppressor in premalignant cells but may also function as a metastasis promoter in cancer cells. This study aimed to understand how the growth factor makes this switch between tumor suppressor to tumor promoter. Medical Research: What are the main findings? Dr. Yu: We reported that 14-3-3ζ overexpression (14-3-3ζ+++) can switch TGF-β’s function from tumor suppressor to metastasis promoter by changing Smad partners. Specifically, 14-3-3ζ+++ led to destabilization of p53, a Smad determinant in pre-malignant cells, thus disrupting p53/Smad complex, and consequently inhibiting TGF-β-induced p21 expression and cytostatic function in non-malignant human mammary epithelial cells (HMECs). On the contrary, 14-3-3ζ+++ stabilized Gli2, a Smad partner in cancer cells, and Gli2 complexed with Smads to promote TGF-β-induced parathyroid hormone-related protein (PTHrP) expression, which enhanced breast cancer bone metastasis. Remarkably, both transcriptomic analyses and clinical pathology data indicated that 14-3-3ζ+++ is associated with the loss of TGF-β’s tumor suppressor function and the gain of its metastasis promoter function by changing contextual partners of Smads. Taken together, we have identified 14-3-3ζ as a novel molecular switch of TGF-β’s function by altering Smad partners from p53 in pre-malignant cells to Gli2 in cancer cells. The study provided important answers to the long-standing questions of how and when TGF-β switches its functional roles from a tumor suppressor to a metastasis promoter. The findings established a scientific base for a new strategy of selectively targeting TGF-β signaling in cancer by inhibiting the cancer-specific Smad partner without blocking TGF-β’s tumor suppressor function in normal tissues. (more…)
Author Interviews, Breast Cancer, NYU / 05.02.2015

Agnel Sfeir PhD Assistant Professor Skirball Institute - NYU New York, NY 10016MedicalResearch.com Interview with: Agnel Sfeir PhD Assistant Professor  Skirball Institute - NYU New York, NY 10016 Medical Research: What is the background for this study? What are the main findings? Dr. Sfeir: The main finding of this study, published in the journal Nature, is that inhibiting the action of a particular enzyme dramatically slows the growth of tumor cells tied to BRCA1 and BRCA2 genetic mutations which, in turn, are closely tied to breast and ovarian cancers. This discovery about the enzyme — called polymerase theta, or PolQ — resulted from efforts to answer a fundamental biological question: How do cells prevent the telomere ends of linear chromosomes, which house our genetic material, from sticking together? Cell DNA repair mechanisms can stitch together telomeres broken as part of cell metabolism. But such fusions, the researchers say, compromise normal cell growth and survival. In the purest biological sense, our findings (in experiments in mice and human cells) show how this particular enzyme, which we know is active in several tumors, promotes unwanted telomere fusions by inserting whole segments of DNA via a disruptive DNA repair pathway termed alt-NHEJ. It was quite remarkable to find that by blocking PolQ action, cancer cell growth was cut by more than half. Additional experiments confirmed that PolQ is needed to activate the alt-NHEJ pathway of DNA repair. Unlike the main, error-free pathway — or HDR pathway — the alt-NHEJ pathway does not use a related chromosome’s genetic material as a template to meticulously correct any damaged genetic material. As such, alt-NHEJ is highly likely to leave coding mistakes. (more…)
Author Interviews, Cancer Research, Pediatrics / 02.02.2015

MedicalResearch.com Interview with: Kate A O’Neill Department of Paediatrics University of Oxford Children’s Hospital John Radcliffe Hospital Oxford UK MedicalResearch.com: What is the background for this study? Dr. O'Neill: Cancer affects around 1 in 500 children under the age of 15. Although the diagnosis and treatment of these diseases have seen major advances over the past few decades, survivors often experience health complications later in life, and cancer remains the main cause of disease related death in children in the developed world. The identification of risk factors for a number of adult cancers has allowed awareness and screening campaigns aimed at preventing disease. For the majority of childhood cancers, however, we still do not know what causes them, and so similar preventative measures are at present not possible. Incidence rates for many childhood cancers peak within the first few years of life, suggesting that the causative events occur early. For childhood leukaemia, it has even been shown that pre-malignant cells are already present at birth, indicating the disease may originate in utero. Studies exploring potential prenatal risk factors for childhood leukaemia have consistently found that children with the disease have higher birthweights than children who do not, and it is now widely accepted that the faster a foetus grows, the higher the risk of developing leukaemia in childhood. Leukaemia is the most common childhood cancer, accounting for approximately one third of all cases. Other childhood cancers are rarer, and it is consequently harder to perform similar risk association studies. The aim of this study was to compile information on large enough numbers of cases and controls to allow the analysis of risk associations between birthweight and all types of childhood cancer. Furthermore, we compiled data in different countries (USA and UK) to allow the comparison of results from two independent populations. MedicalResearch.com: What are the main findings? Dr. O'Neill: We found that with each 0.5kg (1.1lb) increase in birthweight, the risk of childhood cancer increased by 6%. Compared to babies with average birthweights (3-3.49kg, or 6.6lb -7.7lb), babies with clinically high birthweights (4kg, or 8.8lb, and above) had an increased risk of between 16% and 20%. These increased risks were strongest for certain cancers:
  • Leukaemias
  • Tumours of the central nervous system
  • Renal tumours
  • Soft tissue sarcoma
  • Neuroblastoma
  • Lymphoma
  • Germ cell tumours
  • Malignant melanomas
Hepatic tumours showed the reverse association, with risk increasing as birthweight decreased. Retinoblastoma, an embryonal tumour, and malignant bone tumours, which occur predominantly in adolescents, did not associate with birthweight. Our results were strikingly similar between USA and UK populations. Furthermore, birthweight appeared act independently of other factors that are known or suspected to associate with birthweight and/or childhood cancer (gestational age, birth order, plurality, maternal age and race/ethnicity). In summary, we found that approximately half of all childhood cancers are associated with birthweight. The association with a diversity of otherwise unrelated cancers indicates that in utero tissue growth and development has an underlying and potentially key role in the development of malignancy in childhood. (more…)
Author Interviews, Cancer Research, Psychological Science / 31.01.2015

Miss Charlotte Vrinten, MSc, BA, BSc Research psychologist Cancer Research UK Health Behaviour Research Centre Department of Epidemiology and Public Health University College LondonMedicalResearch.com Interview with: Miss Charlotte Vrinten, MSc, BA, BSc Research psychologist Cancer Research UK Health Behaviour Research Centre Department of Epidemiology and Public Health University College London Medical Research: What is the background for this study? What are the main findings? Response: Many people are afraid of getting cancer, but fear doesn’t have the same effect on everyone.  For some people, cancer fear motivates them to get checked up, for others it puts them off finding out whether they have cancer.  No-one before has worked out why fear might have such opposite effects.  We hypothesized that it might be due to how people experience fear, because some fearful people tend to worry a lot about cancer, while others feel physically uncomfortable thinking about it.  In our study, instead of using a combined measure of cancer fear as is often done, we distinguished these different aspects of fear to see whether they had different effects on people’s decisions about cancer screening.  We found that the effect of cancer fear depended on the type of fear: worriers were more likely to want to get screened for colon cancer, but those who felt uncomfortable thinking about cancer were 12% less likely to go for the test. Twelve percent may not seem like a lot, but given that tens of thousands of people are eligible for this type of screening, it means a big difference in the number of people actually having the test. (more…)
Author Interviews, Breast Cancer, Scripps / 25.01.2015

Dr. Patrick Griffin PhD Professor and Chairman Department of Molecular Therapeutics Director of the Translational Research Institute Scripps Research Institute, Jupiter, FloridaMedicalResearch.com Interview with: Dr. Patrick Griffin PhD Professor and Chairman Department of Molecular Therapeutics Director of the Translational Research Institute Scripps Research Institute, Jupiter, Florida MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Griffin: We identified a novel synthetic compound known as SR1848 that sharply inhibits the activity and expression of “liver receptor homolog-1” or LRH-1, a protein that plays an important role in the progression of breast and pancreatic cancers. Our new study shows that SR1848 removes LRH1 from DNA, shutting down expression of LRH-1 target genes, and halts cell proliferation. It’s a novel compound that appears to be a promising chemical scaffold for fighting tumors that are non-responsive to standard therapies. (more…)
Author Interviews, Brigham & Women's - Harvard, Cancer Research, Science / 19.01.2015

Lee Zou, Ph.D. Professor of Pathology, Harvard Medical School The Jim & Ann Orr MGH Research Scholar Associate Scientific Director, MGH Cancer CenterMedicalResearch.com Interview with: Lee Zou, Ph.D. Professor of Pathology, Harvard Medical School The Jim & Ann Orr MGH Research Scholar Associate Scientific Director, MGH Cancer Center Medical Research: What is the background for this study? What are the main findings? Dr. Lee Zou: Cancer cells must rely on telomerase or the alternative lengthening of telomere (ALT) pathway to maintain telomeres and bypass replicative senescence. The ALT pathway is active in about 10-15% of human cancers, and it is particularly prevalent in specific cancer types, such as osteosarcoma, glioblastoma, and neuroendocrine pancreatic tumors. ALT is a recombination-mediated process. Whether the reliance of cancer cells on  alternative lengthening of telomere can be exploited therapeutically was not known. In our study, we discovered that the ATR kinase is a key regulator of alternative lengthening of telomere. We found that ATR inhibitors disrupt ALT effectively. Furthermore, we found that ATR inhibitors selectively kill ALT-positive cancer cells in a panel of caner cell lines. These findings have suggested the first rational therapeutic strategy for the treatment of ALT-positive cancer. (more…)
Author Interviews, Cancer Research, Dermatology / 13.01.2015

MedicalResearch.com Interview with : Cédric Blanpain, MD, PhD Professor of Stem Cell and Developmental Biology WELBIO, Interdisciplinary Research Institute (IRIBHM) Université Libre de Bruxelles Belgium MedicalResearch.com : What is the background for this study? What are the main findings? Dr. Blanpain: Squamous cell carcinoma (SCC) represents the second most frequent skin cancer with more than half million new patients affected every year in the world. Cancer stem cells (CSCs) are a population of cancer cells that have been described in many different cancers including skin SCCs and that feed tumor growth. These cells could be resistant to therapy thus being responsible for tumor relapse after therapy. However, still very little is known about the mechanisms that regulate Cancer stem cells functions. In a new study published and making the cover of Cell Stem Cell, researchers led by Pr. Cédric Blanpain, MD/PhD, professor and WELBIO investigator at the IRIBHM, Université libre de Bruxelles, Belgium, report the mechanisms regulating the different functions of Twist1 controlling skin tumour initiation, cancer stem cell function and tumor progression. Benjamin Beck and colleagues used state of the art genetic mouse models to dissect, the functional role and molecular mechanisms by which Twist1 controls tumor initiation, cancer stem cell function and tumor progression. In collaboration with Dr Sandrine Rorive and Pr Isabelle Salmon from the department of Pathology at the Erasme Hospital, ULB and the group of Jean-Christophe Marine (VIB, KUL Leuven), they demonstrated that while Twist1 is not expressed in the normal skin, Twist1 deletion prevents skin cancer formation demonstrating the essential role of Twist1 during tumorigenesis. The authors demonstrate that different levels of Twist1 are necessary for tumor initiation and progression. Low level of Twist1 is required for the initiation of benign tumors, while higher level of Twist1 is necessary for tumor progression. They also demonstrate that Twist1 is essential for tumor maintenance and the regulation of cancer stem cell function. The researchers also uncovered that the different functions of Twist1 are regulated by different molecular mechanisms, and identified a p53 independent role of Twist1 in regulating cancer stem cell functions. (more…)
Author Interviews, Cancer Research, Technology / 12.01.2015

Oleh Taratula, Ph. D. Assistant Professor of Pharmaceutics Department of Pharmaceutical Sciences College of Pharmacy Oregon State University Corvallis, OR 97331-3507MedicalResearch.com Interview with: Oleh Taratula, Ph. D. Assistant Professor of Pharmaceutics Department of Pharmaceutical Sciences College of Pharmacy Oregon State University Corvallis, OR 97331-3507 Medical Research: What is the background for this study? What are the main findings? Dr. Taratula: Our research group is focused on the development of novel nanotechnology-based approaches to treat different cancers, including ovarian cancer. For many cancers, surgery is a first choice of treatment. For example, only optimal surgical resection of most abdominal metastases can significantly reduce ovarian cancer recurrence and, therefore, improve patient survival. However, it is challenging to remove most of the cancer tumors and residual cancer cells eventually may lead to cancer relapse. Therefore, our aim is to develop a nanomedicine platform, which could help surgeons achieve maximal tumor resection, using the intraoperative guidance with real-time near infrared (NIR) fluorescence signal. Moreover, we expect that the same nanoplatform could further enhance surgical outcomes by combinatorial phototherapy to be performed intraoperatively after tumor resection to eradicate unresected cancer cells. Our data published in Nanoscale is the first step towards our main goal. At this point, by utilizing naphthalocyanine, we have developed a single-agent-based nanomedicine platform capable of both NIR fluorescence imaging and combinatorial phototherapy. Naphthalocyanine is a commercially available compound, but its potential clinical application is limited by low water solubility and aggregation. Especially, aggregation diminishes the imaging ability and phototherapeutic efficacy of this compound. To address these shortcomings, we discovered that the loading of naphthalocyanine into the dendrimers significantly enhances water solubility, prevents aggregation and preserves imaging and therapeutic abilities. Our data demonstrated that naphthalocyanine-based nanoplatform can generate a NIR fluorescence signal in the cancer tumors, required for elimination of autofluorescence from healthy tissue and body fluids. Furthermore, our results also indicated that the developed nanoplatform is an efficient therapeutic agent which, upon exposure to NIR light, destroys chemotherapy-resistant ovarian cancer tumors by producing both heat and toxic reactive oxygen species. Finally, many organic fluorophores, including naphthalocyanine, can undergo photobleaching under exposure to light, which could be misinterpreted as a lack of fluorescence signal during the surgery. We demonstrated that the dendrimer encapsulated naphthalocyanine exhibits extremely high photostability and could overcome the above mentioned issue. (more…)
Author Interviews, Cancer Research, PNAS, UCSD / 31.12.2014

MedicalResearch.com Interview with: Annie Samraj and Ajit Varki MDDr. Annie Samraj MD Postdoc Fellow Varki Lab and Ajit VAjit Varki MD Distinguished Professor of Medicine and Cellular & Molecular Medicine Co-Director, Center for Academic Research and Training in Anthropogeny (CARTA) Co-Director, Glycobiology Research and Training Center (GRTC) University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0687.arki MD Distinguished Professor of Medicine and Cellular & Molecular Medicine , Co-Director, Center for Academic Research and Training in Anthropogeny, Co-Director, Glycobiology Research and Training Center University of California, San Diego, La Jolla, CA Medical Research: What is the background for this study? What are the main findings? Dr. Varki: For the past decade, there has been increasing evidence that people who consume red meat (beef, pork, lamb) are at a higher risk for certain kinds of cancers. Although red meat is a high quality source of protein, iron and vitamins, too much consumption may be harmful to humans. While there are other hypotheses under consideration, we focused on a non-human sugar molecule called Neu5Gc in red meat that could explain the link to cancer risk. We extensively studied various foods and concluded that red meat (particularly beef) is rich in Neu5Gc. In contrast poultry, fish steaks and hen eggs have little or no Neu5Gc. From previous studies, we knew that animal-derived Neu5Gc could be incorporated into human tissues. In this study, we hypothesized that eating red meat could lead to inflammation if the body’s immune system targets the foreign Neu5Gc. Chronic inflammation is also known to instigate or promote tumor progression. To test this hypothesis, we used mice engineered to be similar to humans in that they lacked Neu5Gc, and also produced antibodies against it. When these mice were fed Neu5Gc, they developed systemic inflammation. Tumor formation increased fivefold and Neu5Gc accumulated in the tumors, proving the hypothesis. None of the various control groups of mice showed this effect. (more…)
Author Interviews, Cancer Research / 30.12.2014

Paul Dent PhD Massey Cancer Center, Departments of Biochemistry and Molecular Biology Virginia Commonwealth University, Richmond, VA 23298MedicalResearch.com Interview with: Paul Dent PhD Massey Cancer Center, Departments of Biochemistry and Molecular Biology Virginia Commonwealth University, Richmond, VA 23298 Medical Research: What is the background for this study? What are the main findings? Dr. Dent: I have worked on understanding how the drug OSU-03012 (AR-12) kills cancer cells since 2005. The drug was originally advertised as an inhibitor of PDK1 in the PI3 kinase pathway. We found that PDK1 inhibition could not be the major way in which the drug worked. We found that the drug killed brain cancer cells through endoplasmic reticulum stress signaling. And in 2012 we published that OSU-03012 destabilized the chaperone protein GRP78, without significantly altering its transcription. Loss of GRP78 was responsible for the prolonged intense endoplasmic reticulum stress signal, that was toxic. In 2014 we published that OSU-03012 + Viagra / Cialis synergized to kill brain cancer cells. We hypothesized that Viagra / Cialis might enhance the anti-GRP78 effect of OSU-03012; and this was proven to be true. We discovered that the OSU-03012 + Viagra combination, but not OSU-03012 alone, reduced expression of other chaperone proteins, such as HSP70, GRP94. In mice, the combination was not toxic to "normal" tissues, but was toxic to tumor cells. In human patients the drug was found to be safe in a phase I trial, with plasma levels of up to 8 microM, and patients on trial for up to 9 months. (more…)
Author Interviews, Cancer Research, University of Michigan / 04.12.2014

MedicalResearch.com Interview with: Silvana Papagerakis M.S., M.D., Ph.D. Research Assistant Professor, Department of Otolaryngology-Head and Neck SurgeryDirector, Oral, Head and Neck Cancer Invasion and Metastasis Laboratory Ann Arbor MI Silvana Papagerakis M.S., M.D., Ph.D. Research Assistant Professor, Department of Otolaryngology-Head and Neck Surgery Director, Oral, Head and Neck Cancer Invasion and Metastasis Laboratory, Ann Arbor MI MedicalResearch: What is the background for this study? What are the main findings? Dr. Papagerakis: We had suspicions that these medications somehow had a favorable impact on patient outcomes. This led us to review our large cohort of patients and screen them for common medications, focusing on antacids. In fact, our study did show that people taking antacids are doing better. What this study makes clear is that these medications may be more beneficial to the patients than just controlling side effects of chemotherapy or radiation treatment for head and neck cancer. (more…)
Author Interviews, Cancer Research / 02.12.2014

Dr. Pan Pantziarka Anticancer Fund, Brussels Belgium The George Pantziarka TP53 Trust, London, UKMedicalResearch.com Interview with: Dr. Pan Pantziarka Anticancer Fund, Brussels Belgium The George Pantziarka TP53 Trust, London, UK MedicalResearch: What is the background for this study? Dr. Pantziarka: The background of this study is that it is part of a series of investigations by the Repurposing Drugs in Oncology (ReDO) project into well-known non-cancer drugs which have evidence of activity that may be useful in cancer therapies. These drugs include mebendazole, itraconazole, diclofenac, nitroglycerin and cimetidine. (more…)
Author Interviews, Cancer Research / 30.11.2014

Charles Brenner, PhD Roy J. Carver Chair & Head of Biochemistry Departments of Biochemistry & Internal Medicine Carver College of Medicine University of Iowa Iowa City, IA 52242MedicalResearch.com Interview with: Charles Brenner, PhD Roy J. Carver Chair & Head of Biochemistry Departments of Biochemistry & Internal Medicine Carver College of Medicine University of Iowa Iowa City, IA  52242 Medical Research: What is the background for this study? What are the main findings? Dr. Brenner: KRAS mutations are extremely common in human malignancies. The KRAS gene is an oncogene that drives cell growth pathways and that leads to silencing and inactivation of tumor suppressor genes. It was known that KRAS mutant cancer cells silence tumor suppressor genes but the precise mechanism for gene silencing was not known. In this study, we discovered that KRAS mutations turn off the TET1 gene. TET1 functions as an "eraser" of gene silencing marks. When KRAS mutations occur, the TET1 eraser isn't expressed any longer, and a series of tumor suppressor genes become silenced. This is an essential part of the aggressiveness of KRAS-dependent cancers and is controlled by the ERK pathway that is turned on by KRAS. In short, KRAS turns on ERK, which turns off TET1. When TET1 is off, a set of tumor suppressor genes are also turned off, which drives cancer formation. (more…)
Author Interviews, Cancer Research, Lancet / 28.11.2014

Dr Claudia Allemani PhD FHEA MFPH Senior Lecturer in Cancer Epidemiology Cancer Research UK Cancer Survival Group Department of Non-Communicable Disease Epidemiology London School of Hygiene and Tropical Medicine, London UKMedicalResearch.com Interview with: Dr Claudia Allemani PhD FHEA MFPH Senior Lecturer in Cancer Epidemiology Cancer Research UK Cancer Survival Group Department of Non-Communicable Disease Epidemiology London School of Hygiene and Tropical Medicine, London UK Medical Research: What is the background for this study? Dr. Allemani:  Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control. The first CONCORD study was published in 2008.1 It brought together data from 101 cancer registries in 31 countries, and included 1.9 million patients diagnosed during 1990-94 with a cancer of the colon, rectum, breast or prostate and followed up to the end of 1999. It revealed very wide international differences in five-year survival, and it confirmed the well-known racial discrepancy in cancer survival in the USA. CONCORD-2 is the most comprehensive international comparison of trends in population-based cancer patient survival to date. It extends the first study in three ways:
  • it covers 10 common cancers: collectively, these account for almost two-thirds (63%) of all cancer patients diagnosed each year in both developed and developing countries
  • it includes data on more than 25 million cancer patients, provided by 279 cancer registries in 67 countries, in 40 of which the data provide complete (100%) coverage of the national population
  • it examines trends in cancer survival for patients diagnosed over the 15-year period 1995-2009 (more…)
Author Interviews, Cancer Research, Cannabis / 19.11.2014

MedicalResearch.com Interview with: Dr Wai Liu Senior Research Fellow St George's University of London London,  SW17 Medical Research: What is the background for this study? What are the main findings? Dr. Liu: It has been known for some time that certain chemicals called cannabinoids that are isolated from the cannabis plant possess anticancer action through the ability to enhance/engage apoptosis and autophagy. These effects are both dependent and independent upon the cognate receptors. These are found at relatively high levels in brain cells. Brain tumors tend to express these at high levels and so we felt these would be good candidates. The main findings of the current study is the ability that combining the cannabinoids THC and CBD with irradiation can cause a reduction in tumor that is greater than the sum of the individual treatments. That is, when using doses of irradiation or cannabinoids individually, the effects were minimal; however, if they were used simultaneously, the effect was synergistic, and tumor growth was significantly impeded. (more…)
Author Interviews, Cancer Research, Omega-3 Fatty Acids / 13.11.2014

James J. DiNicolantonio, PharmD Associate Editor BMJ Open Heart Cardiovascular Research Scientist Saint Luke's Mid America Heart InstituteMedicalResearch.com Interview with: James J. DiNicolantonio, PharmD Associate Editor BMJ Open Heart Cardiovascular Research Scientist Saint Luke's Mid America Heart Institute Medical Research: What is the background for this study? What are the main findings? Dr. DiNicolantonio: Daily low-dose aspirin has been shown to decrease the risk for cancer in a meta-analysis of randomized controlled trials, which is likely attributable to its ability to modestly decrease the activity of cyclooxygenase-2 (cox-2), an enzyme which contributes importantly to the genesis and progression of adenocarcinomas. Adenocarcinomas are cancer of the glands, the most common type of breast cancer (invasive ductal carcinoma) is an adenocarcinoma, additionally many cancers of the lung, intestine, esophagus, colon are adenocarcinomas. We show that an ample dietary intake of long-chain omega-3 fats—the type prominent in fatty fish—would oppose cox-2 activity.  Additionally, we cite numerous evidence that a higher intake of long-chain omega-3 fats has been found to reduce the risk for numerous types of cancer - especially when looking at trials that excluded fried or preserved fish (or fish high in omega-6), excluded trials with a high background intake of omega-6, and included trials where the "high" intake group - actually ate 2 servings of fish or more per week. Additionally, basic science as well as randomized data showing that long-chain omega-3s can reduce the number and size of colon polyps supports this argument. (more…)
Author Interviews, Cancer Research, End of Life Care, JAMA / 12.11.2014

Ziad Obermeyer, MD, MPhil Emergency Medicine, Brigham & Women's Hospital Assistant Professor, Harvard Medical SchoolMedicalResearch.com Interview with: Ziad Obermeyer, MD, MPhil Emergency Medicine, Brigham & Women's Hospital Assistant Professor, Harvard Medical School Medical Research: What is the background for this study? What are the main findings? Dr. Obermeyer: More patients with cancer use hospice today than ever before, but there are indications that care intensity outside of hospice is increasing, and length of hospice stay decreasing. We examined how hospice affects health care utilization and costs and found that, in a sample of elderly Medicare patients with advanced cancer, hospice care was associated with significantly lower rates of both health care utilization and total costs during the last year of life. Patients who did not enroll in hospice had considerably more aggressive care in their last year of life—most of it related to acute complications like infections and organ failure, and not directly related to cancer-directed treatment. Hospice and non-hospice patients had similar patterns of health care utilization until the week of hospice enrollment, when care began to diverge. Ultimately, non-hospice patients were five times more likely to die in hospitals and nursing homes. These differences in care contributed to a statistically-significant difference in total costs of $8,697 over the last year of life ($71,517 for non-hospice and $62,819 for hospice). (more…)