Author Interviews, Cancer Research, Fertility, OBGYNE, Technology / 19.11.2015

MedicalResearch.com Interview with: Kutluk Oktay, MD, PhD. Professor of Obstetrics & Gynecology, Medicine, and Cell Biology & Anatomy Director, Division of Reproductive Medicine & Institute for Fertility Preservation Innovation Institute for Fertility and In Vitro Fertilization New York Medical College, Valhalla, NY Medical Research: What is the background for this study? What are the main findings? Dr. Oktay: Cancer treatments cause infertility and early menopause in a growing number of young women around the world and US. One of the strategies to preserve fertility, which was developed by our team, is to cryopreserve ovarian tissue before chemotherapy and later transplant it back to the patient when they are cured of the cancer and ready to have children. However, success of ovarian transplantation has been limited due to limitation in blood flow to grafts. In this study we described a new approach which seems to improve graft function. The utility of an extracellular tissue matrix and robotic surgery seems to enhance graft function. With this approach both patients conceived with frozen embryos to spare and one has already delivered. (more…)
Author Interviews, Cancer Research, Genetic Research, JAMA / 14.11.2015

MedicalResearch.com Interview with: Samuel Klempner, M.D. Assistant Professor Division of Hematology/Oncology UC Irvine Health Orange, CA 92868  Medical Research: What is the background for this study? What are the main findings? Dr. Klempner: The background for our series is the concept that little is known about the genetic landscape of rare tumors such as acinic cell tumors, and that understanding genetic changes in tumors can identify treatment options.  This paradigm can, and should, be extended beyond rare tumor types and many researchers are currently studying various tumor types.  Another important background idea is that tumor genomic alterations may be more important than that anatomic site of origin. For example, I would argue that a breast cancer that harbors an EGFR mutation common to lung cancer could be treated similar to a lung cancer based on the genomic changes. In our study we found another way that the BRAF protein and its downstream signaling may become activated through duplicating part of the protein called the kinase domain.  This genetic event causes the pathway to be always "on" which is not normal, and likely drives cancer growth.  However, BRAF kinase domain duplication appears sensitive to currently available drugs that target the BRAF pathway, as evidenced by the response in our patient.  Thus, finding this change is important and may be able to guide a more personalized therapy choice.  Importantly, we found BRAF kinase domain duplication across multiple different tumor types, suggesting this may be a recurrent event in some cancers.  A very similar finding, involving duplication of the EGFR kinase domain, was also just reported (Cancer Discovery 2015;5:1155-1163) lending further validation to this mechanism of pathway activation in cancer. (more…)
AACR, Author Interviews, Lymphoma, MD Anderson / 12.11.2015

MedicalResearch.com Interview with: Dr. Jatin J. Shah, MD Associate Professor, Department of Lymphoma/Myeloma Assistant Professor, Lymphoma/Myeloma Division of Cancer Medicine The University of Texas, MD Anderson Cancer Center Houston, TX  Medical Research: What is the background for this study? What are the main findings? Dr. Shah: The ubiquitin-proteasome system (UPS) is one of the key regulatory systems in our body’s cells. It controls the destruction of the majority of cellular proteins, which can be involved in making cells grow, expand, or die, among other functions. Defects in the UPS can result in a number of diseases, including cancer, for example by destroying too quickly the proteins that cause cells to die. The UPS has already been shown to be a rational target for cancer therapy: the approved drugs bortezomib and carfilzomib inhibit the proteasome itself, thus causing cancer cells to die. However, by completely blocking the proteasome, which is at the ‘end’ of the UPS, these drugs block the destruction of 100% of proteins, and can cause side effects. By contrast, blocking the NEDD8-activating enzyme (NAE) stops the cellular processes that are responsible for only approximately 20% of proteins being degraded by the UPS – including proteins of relevance to cancer development. Previous studies of pevonedistat in animals have shown that inhibiting NAE alters the ability of a cancer cell to repair its DNA after it is damaged; this leads to the death of cancer cells. The man finding is this was the first reported study of pevonedistat in patients with multiple myeloma or lymphoma. It demonstrated that pevonedistat hits its target in cancer cells, exerted anticipated pharmacodynamic effects, and has modest activity as a single-agent in heavily pretreated patients with relapsed/refractory lymphoma. (more…)
AACR, Author Interviews, Cancer, Cancer Research, University Texas / 10.11.2015

MedicalResearch.com Interview with: Xifeng Wu, M.D., Ph.D, Professor, Epidemiology Stephanie Melkonian, Ph.D University of Texas M. D. Anderson Cancer Center Medical Research: What is the background for this study? What are the main findings? Response: This study examines dietary intake of meat-cooking mutagens and genetic risk factors associated with kidney cancer in a population of 659 kidney cancer patients and 699 matched healthy control subjects from the community. We calculated the intake of several cancer-causing carcinogens that are produced when certain types of meat are cooked over an open flame and at high temperatures resulting in the burning, smoking or charring of the meat (for example, during barbequing or pan-frying). We found that kidney cancer patients consumed more red and white meat when compared to the healthy individuals, and also had higher intake of these cancer-causing chemicals created through the meat cooking process. These results suggest that meat intake, and the way we cook our meat, may potentially be linked to risk of kidney cancer. Additionally, we found that individuals with certain genetic variants were more likely to be susceptible to the harmful effects of the cancer-causing mutagens created during the process of cooking meat. (more…)
Author Interviews, Brigham & Women's - Harvard, Cancer Research, Immunotherapy, NEJM / 05.11.2015

MedicalResearch.com Interview with: Toni Choueiri, MD Clinical Director, Lank Center for Genitourinary Oncology Director, Kidney Cancer Center Senior Physician Dana Farber Cancer Institute Associate Professor of Medicine Harvard Medical School Medical Research: What is the background for this study? What are the main findings? Dr. Choueiri: In the METEOR trial, we aimed to compare cabozantinib, a novel VEGFR, MET, AXL inhibitor to everolimus, a standard 2nd line option in advanced RCC. There is an unmet in this setting. Cabozantinib resulted in a median PFS of 7.4 months compared to 3.8 months with everolimus. Responses also were 4-times higher with cabozantinib-treated patients. At the interim OS analysis, there was a strong trend favoring cabozantinib.  (more…)
Author Interviews, Cancer Research, JAMA, MD Anderson / 05.11.2015

MedicalResearch.com Interview with: William N. William Jr., MD Associate Professor Chief, Head and Neck Section Department of Thoracic / Head and Neck Medical Oncology The University of Texas M. D. Anderson Cancer Center Houston, TX Medical Research: What is the background for this study? What are the main findings? Dr. William: Oral pre-malignant lesions are often characterized as white and/or red patches in the mouth and are considered risk factors for oral cancer. This is why it might be best for people to go get oral cancer screening done if they suspect that there might be a problem. However, not all oral pre-malignant lesions will turn into cancer, but when this happens, surgery is usually recommended, many times leading to serious speech and swallowing dysfunction. Chemoprevention is the use of compounds to prevent cancers from happening before they occur. One of the greatest challenges in developing chemopreventive agents is to identify the population at highest cancer risk. The Erlotinib Prevention of Oral Cancer (EPOC) trial involved 379 patients at five sites across the country. All had premalignant lesions in their mouths. Following study enrollment, participants were evaluated for LOH, a chromosomal abnormality characterized by the loss of chromosomal regions, which include tumor suppressor genes. Patients who tested positive for LOH were considered to be at high risk for oral cancer and were randomized to receive either erlotinib (an EGFR inhibitor drug) or a placebo for one year. The study’s primary endpoint was to determine if fewer patients treated with erlotinib would develop oral cancer, compared to those that received placebo. The EPOC study demonstrated that LOH predicted a higher oral cancer risk. LOH-negative patients had a three-year cancer-free survival rate of 87 percent compared to 74 percent for the LOH-positive group. However, patients who took erlotinib showed no statistical difference in terms of cancer-free survival rates after three years: 74 percent for participants given erlotinib compared to 70 percent for those taking placebo. Patients with both LOH and EGFR copy number gains had the highest incidence of cancer, but still did not benefit from erlotinib. (more…)
Author Interviews, Cancer Research, Dermatology, JAMA / 05.11.2015

MedicalResearch.com Interview with: Dr. Brad A. Bryan Ph.D Assistant Professor Biomedical Sciences Texas A&M University Health Science Center, Houston, TX Department of Biomedical Sciences Texas Tech University Health Sciences Center Medical Research: What is the background for this study? What are the main findings? Dr. Bryan: In 2008 it was serendipitously discovered that the beta blocker propranolol was effective in treating a common benign pediatric vascular tumor called infantile hemangioma.  Over the past few years, my lab has been working on elucidating the molecular mechanisms underlying this pediatric tumor and part of this research involved uncovering how propranolol selectively inhibited these tumors.  At the same time these studies were taking place, other members of my lab were working on pre-clinical drug development for a malignant vascular tumor called angiosarcoma.  Patients with angiosarcoma are faced with very few effective treatment options and abysmal survival rates, so we decided to see if the efficacy of beta blockade observed in infantile hemangiomas transferred to angiosarcomas.  Using preclinical in vitro and in vivo assays, we demonstrated that propranolol was very effective at inducing cell death, blocking migration, and inhibiting tumor growth in our angiosarcoma models.  This work was subsequently published in Plos One (Stiles et al., 2013).  I then collaborated with Dr. William Chow from San Francisco to test propranolol off-label (propranolol is FDA approved to treat high blood pressure, heart dysrhythmias, thyrotoxicosis, and essential tremors) in a patient suffering from a rapidly expanding angiosarcoma covering a large portion of his face.  In the window between diagnosis of the tumor and the start of chemotherapy, we placed the patient on oral propranolol.  The redness of the tumor very rapidly lessened and remarkably by only one week of treatment the tumor margins appeared to significantly shrink.  We examined biospies of the tumor before and after only one week of propranolol and found that the proliferation of the tumor cells was markedly decreased following beta blockade.  After a combination of propranolol, chemotherapy, and radiation that lasted several months, the patient had no detectable metabolically active tumor or distant metastases. We published these findings in JAMA Dermatology (Chow et al., 2015). (more…)
Author Interviews, Chemotherapy, Lymphoma, NEJM / 04.11.2015

Jia Ruan, M.D., Ph.D. Associate Professor of Clinical Medicine Weill Cornell Medicine Lymphoma Program Division of Hematology & Medical Oncology New York, NY 10021MedicalResearch.com Interview with: Jia Ruan, M.D., Ph.D. Associate Professor of Clinical Medicine Weill Cornell Medicine Lymphoma Program Division of Hematology & Medical Oncology New York, NY 10021   Medical Research: What is the background for this study? What are the main findings? Dr. Ruan: Mantle cell lymphoma is an uncommon subtype of non-Hodgkin lymphoma that primarily affects elderly populations. Conventional chemotherapy regimens are generally not curative, and may not be tolerated by many patients, underscoring the need for treatment alternatives.  Previous experience with immunomodulatory compound lenalidomide has shown favorable activity and was well tolerated in patients with relapsedMantle cell lymphoma.  We evaluated the efficacy and safety of the biologic combination with lenalidomide plus rituximab as initial treatment for mantle-cell lymphoma (MCL). The main findings of the study showed that the combination was effective and generally well tolerated when given as induction and maintenance treatment. The overall response rate was 92%, with complete response rate of 64% in the 36 evaluable patients. Median duration of response has not been reached at a median follow up of 30 months.   Treatment was outpatient-based and quality-of-life was preserved for most patients. (more…)
Author Interviews, Cancer Research, Personalized Medicine / 04.11.2015

Timothy Humphrey DPhil. CRUK/MRC Oxford institute for Radiation Oncology University of Oxford, UKMedicalResearch.com Interview with Timothy Humphrey DPhil. CRUK/MRC Oxford institute for Radiation Oncology University of Oxford, UK Medical Research: What is the background for this study? What are the main findings? Response: Multiple mutations resulting in loss of a particular histone mark (H3K36me3) are frequently found in a number of cancer types. These include mutations resulting in loss of the tumour suppressor SETD2 (which trimethylates H3K36) and over-expression of the oncogene KDM4A (which demethylates H3K36me3), which together are observed in more than 10% of a number of cancer types. Notably, loss of H3K36me3 has been reported in more than 50% of pediatric high-grade gliomas. While loss of this histone mark is associated with poor prognosis, there is no targeted therapy yet. Following observations made in fission yeast, we have found a new way to selectively target H3K36me3-deficient cancers using the WEE1 inhibitor, AZD1775. Surprisingly, treatment of H3K36me3-deficient cancer cells with the WEE1 inhibitor resulted in S-phase arrest. Further analysis revealed ribonucleotide reductase to be the target of this synthetic lethal interaction, thereby leading to dNTP starvation, replication fork collapse and cell death. (more…)
Author Interviews, Cancer Research, Microbiome / 04.11.2015

MedicalResearch.com Interview with: Simba Gill Ph.D CEO, Evelo Therapeutics MedicalResearch: Evelo Therapeutics, a new company focuses on leveraging the power of the microbiome to develop novel therapies for cancer. Evelo is pioneering Oncobiotic™ therapeutics, a new modality in cancer therapy based on the cancer microbiome. Dr. Gill, CEO of  Evelo Therapeutics began his career at Celltech, focused on antibody research. Dr. Gill earned his Ph.D. from King’s College, London, and his MBA from INSEAD. Medical Research:  What is a microbiome? How do microbiomes play a role in health and disease? Dr. Gill: The microbiome is the collection of trillions of bacteria, funguses, viruses and other microbes that live on and within the human body. There are different clusters of microbes in different parts of the body, including the skin, mouth, large intestine, and vagina. Recently we have learned that our microbial populations shift depending on changes to an individual’s health and wellness. The makeup of one’s microbiome has a strong influence on one’s health, immune response, and metabolic state. (more…)
Author Interviews, Biomarkers, Brigham & Women's - Harvard, Cancer Research / 03.11.2015

MedicalResearch.com Interview with: Bakhos A. Tannous, Ph.D Associate Professor of Neurology Harvard Medical School Director, Experimental Therapeutics and Molecular Imaging Lab Director, Interdepartmental Neuroscience Center Director, MGH Viral Vector Development Facility Massachusetts General Hospital Charlestown, MA 02129 Medical Research: What is the background for this study? What are the main findings? Dr. Tannous: In recent years, it has become apparent that, in addition to their role in promoting blood clotting, platelets take up protein and RNA molecules from tumors, possibly playing a role in tumor growth and metastasis. Working with our collaborators Dr. Thomas Wurdinger and Pieter Wesseling at the VU Medical Center, Amsterdam, the Netherlands, we found that the RNA profiles of tumor-educated platelets – those that have taken up molecules shed by tumors – can (1) distinguish healthy individuals and patients with six different types of cancer, (2) determine the location of the primary tumor and (3) identify tumors carrying mutations that can guide therapeutic decision making and personalized medicine. (more…)
Author Interviews, Cancer Research, Cognitive Issues, Journal Clinical Oncology, Memory / 03.11.2015

MedicalResearch.com Interview with: Dr Janette Vardy  BMed (Hons), PhD, FRACP A.Prof of Cancer Medicine University of Sydney Medical Oncologist ,Concord Cancer Centre Concord Repatriation & General Hospital Concord, Australia  Medical Research: What is the background for this study? Dr. Vardy: Many patients complain that their memory and concentration is not as good after chemotherapy.  Most of the studies have been in younger women with breast cancer, and are often limited by small sample sizes and short term follow up.    This is the largest longitudinal cohort study assessing impacts of cancer and its treatment on cognitive function. We evaluated changes in cognitive function in 289 men and women with localized colorectal cancer (CRC), comparing those who received chemotherapy to those who did not require chemotherapy, 73 with metastatic disease, and a group of 72 healthy controls.?The localized CRC patients were assessed at baseline (soon after diagnosis and prior to any chemotherapy), 6, 12 and 24 months.  The healthy controls and metastatic group were assessed at baseline, 6 and 12 months.  We also examined underlying mechanisms. (more…)
Author Interviews, Cancer Research, End of Life Care, Nursing / 30.10.2015

Dr-Hsien-SeowMedicalResearch.com Interview with: Dr. Hsien Seow, PhD Associate Professor Department of Oncology Cancer Care Ontario Research Chair in Health Services Research Associate Member, Department of Clinical Epidemiology & Biostatistics McMaster University Canadian Institutes of Health Research Young Investigator Hamilton, Ontario Medical Research: What is the background for this study? What are the main findings? Dr. Seow: Despite being commonplace in healthcare systems, little research has described the effectiveness of publicly-provided generalist homecare nursing to reduce unnecessary acute care use at end-of-life, such as emergency department (ED) visits. It is also unclear how homecare nursing intent, which varies by standard care or end-of-life, affects this relationship. Our study examined a population-based cohort of cancer decedents in Ontario, Canada who used homecare nursing in their last six months of life. Specifically, we examined the relationship between homecare nursing rate in a given week on the ED visit rate in the subsequent week. In our cohort of 54,576 decedents, there was a temporal association between receiving end-of-life nursing in a given week during the last six months of life, and of more standard nursing in the last month of life, with a reduced ED rate in the subsequent week. Homecare nursing for those who are receving end of life care will find that it can provide immediate assistance when needed. (more…)
Author Interviews, Cancer, Cancer Research, JAMA / 29.10.2015

Jiemin Ma, PhD, MHS Director of Surveillance and Health Services Research American Cancer SocietyMedicalResearch.com Interview with: Jiemin Ma, PhD, MHS Director of Surveillance and Health Services Research American Cancer Society Medical Research: What is the background for this study? What are the main findings? Dr. Ma: This study is an analysis of long-term trends in mortality for all causes combined and for 6 leading causes of death, including heart disease, cancer, stroke, chronic obstructive pulmonary disease (COPD), unintentional injuries, and diabetes, in the United States from 1969 through 2013. We found that death rates for all causes and for five of these 6 leading causes (except COPD) decreased during this time period, although the rate of decrease appears to have slowed for heart disease, stroke, and diabetes. COPD death rates doubled during this time period, although the rate began to decrease in men since 1999. (more…)
Author Interviews, Cancer Research, Education, JAMA / 29.10.2015

MedicalResearch.com Interview with: Vinay Prasad, MD MPH Assistant Professor of Medicine Division of Hematology Oncology in the Knight Cancer Institute Department of Public Health and Preventive Medicine Senior Scholar in the Center for Health Care Ethics Oregon Health and Sciences University Portland, Oregon 97239   Medical Research: What is the background for this study? What are the main findings? Dr. Prasad: We wanted to get some information about when and which cancer drugs were called "game changer" or "breakthrough" or "revolutionary".  What we found was surprising.  The use of these grandiose terms, or superlatives, was common in news articles.  They occurred across many classes of medication, were used for approved and unapproved drugs, and some of the use was questionable. (more…)
Author Interviews, Cancer Research, CDC, Gender Differences, Race/Ethnic Diversity / 24.10.2015

MedicalResearch.com Interview with: Dr. Simple Singh MD Epidemiologist Division of Cancer Prevention and Control CDC  Medical Research: What is the background for this study? Dr. Singh: This report provides official federal statistics on the occurrence of cancer for 2011 and trends for 1999–2011 as reported by CDC and the National Cancer Institute (NCI). Cancer incidence data are from population-based cancer registries that participate in CDC’s National Program of Cancer Registries (NPCR) and NCI’s Surveillance, Epidemiology, and End Results (SEER) program reported as of November 2013. Cancer mortality data are from death certificate information reported to state vital statistics offices in 2013 and compiled into a national file for the entire United States by CDC’s National Center for Health Statistics’ (NCHS) National Vital Statistics System (NVSS). This report is a part of the first-ever Summary of Notifiable Noninfectious Conditions and Disease Outbreaks — United States, which encompasses various surveillance years but is being published in 2015. Medical Research: What are the main findings? Dr. Singh: In 2011, approximately 1.5 million invasive cancers were diagnosed in the United States, an annual incidence rate of 451 cases per 100,000 persons. In the same year, approximately 576,000 persons died of cancer nationally, an annual death rate of 169 deaths per 100,000 persons. Cancer incidence and death rates increase with age. Overall, 54% of cancer cases and 69% of cancer deaths in 2011 occurred among persons aged ≥65 years. Among men in 2011, blacks had the highest cancer incidence and death rates in the United States, and American Indians/Alaska Natives and Asians/Pacific Islanders had the lowest cancer incidence and death rates. Among women in 2011, whites had the highest cancer incidence rates and blacks had the highest cancer death rates. American Indians/ Alaska Natives had the lowest cancer incidence rates, and Asians/Pacific Islanders had the lowest cancer death rates. By state, overall (all cancer sites combined) cancer incidence rates in 2011 ranged from 374 to 509 cases per 100,000 persons, and overall cancer death rates ranged from 126 to 201 deaths per 100,000 persons. Four cancer sites accounted for half of all cases diagnosed in 2011, including 209,292 prostate cancers, 220,097 female breast cancers, 207,339 lung and bronchus cancers (110,322 among men and 97,017 among women), and 135,260 colon and rectum cancers (70,099 among men and 65,161 among women). These four sites also accounted for half of cancer deaths in 2011, including 156,953 lung cancer deaths, 51,783 colon and rectum cancer deaths, 40,931 female breast cancer deaths, and 27,970 prostate cancer deaths. During 1999–2011, cancer incidence rates declined from 485 cancer cases per 100,000 population in 1999 to 444 cases in 2011. Although lung cancer incidence declined steadily among men from 1999 to 2011, it increased among women from 1999 to 2005 and has since declined from 2005 to 2011. Prostate cancer incidence declined from 170 cases per 100,000 men in 1999 to 128 cases in 2011. Colorectal cancer incidence declined from 57 cases per 100,000 persons in 1999 to 40 cases in 2011. Female breast cancer incidence declined from 135 cases per 100,000 women in 1999 to 121 cases in 2005, increased to 125 cases in 2009, and declined again to 122 cases in 2011. During 1999–2011, cancer death rates declined from 201 deaths per 100,000 persons in 1999 to 169 deaths in 2011; during the same period, death rates declined for each of the top four cancers. (more…)
Author Interviews, Cancer Research, MD Anderson, Nature / 23.10.2015

MedicalResearch.com Interview with: Dihua Yu, M.D., Ph.D. Professor and Deputy Chair Dept.  of Molecular and Cellular Oncology Hubert L. and Olive Stringer Distinguished Chair in Basic Science University Distinguished Teaching Professor Co-Director, Center of Biological Pathways Univ. of TX MD Anderson Cancer Center Houston, TX 77030 Medical Research: What is the background for this study? What are the main findings? Dr. Yu: Metastasis is the number one cause of cancer-related mortality. Despite the continuous advancement of modern medicine in better controlling primary cancer progress, brain metastasis incidence constantly and steadily increases. Major neoplastic diseases such as melanoma, lung, breast, and colon cancers have high incidences of brain metastases. One-year survival after diagnosis of brain metastasis is less than 20%. Cancer cells dynamically interacts with specific organ microenvironments to establish metastasis as depicted by the “seed and soil” hypothesis. Many research have focused on how tumor cells modulate the metastatic microenvironment, but the reciprocal effect of the organ microenvironment on tumor cells has been overlooked. The brain tissue is very distinct from primary tumor environment for metastatic cancer cells. Brain metastasis frequently manifests in the late stages of cancer, and a long period of dormancy often precedes relapse. This implies that additional regulations imposed by the brain microenvironment are essential for metastatic colonization and outgrowth. Yet it is unclear when and how disseminated tumor cells acquire the essential traits from the brain microenvironment that primes their subsequent metastatic outgrowth. (more…)
Author Interviews, BMJ, Cancer Research, Occupational Health / 21.10.2015

MedicalResearch.com Interview with:, David Richardson PhD Associate Professor Epidemiology Gillings School of Global Public Health UNC Medical Research: What is the background for this study? Dr. Richardson:  The International Nuclear Workers Study (INWORKS) combines three cohorts from France, the United Kingdom, and the United States of America. INWORKS follows on from an earlier 15-Country Study but focuses on the three countries that provided the majority of the most informative data on early nuclear workers (1940’s onward). The use of data from just 3 countries, instead of 15, reduces the organisational requirements – and therefore financial burden – associated with the greater number of countries but the cohort selection (of the three main contributing countries) means that the power of the INWORKS study is not a concern. INWORKS uses information from the French, UK and US cohorts that has been updated since the 15-Country study was published. The overall purpose of the study is to improve the understanding of health risks associated with protracted, low-level exposure to ionising radiation. (more…)
Author Interviews, Baylor University Medical Center Dallas, Biomarkers, BMJ, Cancer Research / 20.10.2015

Ajay Goel, Ph.D. Investigator/Professor Director, Center for Gastrointestinal Research Director, Center for Epigenetics, Cancer Prevention and Cancer Genomics Baylor Research Institute and Charles A. Sammons Cancer Center Baylor University Medical Center Dallas, TX 75246MedicalResearch.com Interview with: Ajay Goel, Ph.D. Investigator/Professor Director, Center for Gastrointestinal Research Director, Center for Epigenetics, Cancer Prevention and Cancer Genomics Baylor Research Institute and Charles A. Sammons Cancer Center Baylor University Medical Center Dallas, TX 75246 Medical Research: What is the background for this study? What are the main findings? Dr. Goel: Colorectal cancer (CRC) remains one of the most common and lethal malignancies worldwide, and is the second leading cause of cancer-related deaths in the United States. Although there are some improvements in cancer treatments, such as development of novel chemotherapeutic drugs and technical advances in invasive treatment for metastatic lesion, there is a clear need for prognostic biomarkers that can identify high-risk patients, who can benefit from intensive post-treatment surveillance protocols for early detection of recurrence. Small nucleolar RNAs (snoRNAs) are one of the largest groups of single-stranded small ncRNAs, and in the past, snoRNAs were recognized for housekeeping functions due to their roles in rRNA maturation, while causing a relatively low impact on cellular homeostasis. However, recent evidence has revealed a new and previously unrecognized role of snoRNAs in the control of cell fate and oncogenesis in various cancers. The main finding of this study is to firstly demonstrate the clinical impact of snoRNA expression as a predictive biomarker of recurrence and poor prognosis in patients with Colorectal cancer. This study for the first time showed that higher levels of SNORA42 were associated with overall and disease-free survival, and emerged as a risk factor for the return of cancer in another part of the body. It was also correlated with high risk of recurrence and shorter survival in a smaller sample of bowel cancer patients in early stages of their disease. (more…)
Anemia, Author Interviews, Cancer Research, University Texas / 16.10.2015

MedicalResearch.com Interview with: Anil K. Sood, M.D. Professor of Gynecologic Oncology and Reproductive Medicine The University of Texas MD Anderson Cancer Center Medical Research: What is the background for this study? What are the main findings? Dr. Sood: Erythropoietin is an important drug for managing anemia, but concerns have surfaced that it might promote cancer growth. The data with the conventional epo-receptor were not convincing with regard to an explanation for why tumor growth might increase. Therefore, we considered whether there could be an alternative receptor to explain these findings. We carried out a systematic search and identified EphB4 as the alternative receptor that explained the increased tumor growth in response to epo. (more…)
Author Interviews, Cancer Research, End of Life Care, Journal Clinical Oncology / 07.10.2015

Holly G. Prigerson, Ph.D. Irving Sherwood Wright Professor in Geriatrics Professor of Sociology in Medicine Director, Center for Research on End of Life Care Weill Cornell Medical College New York Presbyterian Hospital New York City, New YorkMedicalResearch.com Interview with: Holly G. Prigerson, Ph.D. Irving Sherwood Wright Professor in Geriatrics Professor of Sociology in Medicine Director, Center for Research on End of Life Care Weill Cornell Medical College New York Presbyterian Hospital New York City, New York 10065 Medical Research: What is the background for this study? What are the main findings? Dr. Prigerson: Research has revealed that a majority of terminally ill cancer patients do not realize that they are dying. We wanted to know if terminally ill patients would report wanting to know their life expectancy, how many oncologists shared their life expectancy estimate for the patient with them, and how that prognostic disclosure affected the patient’s accuracy.  We found that 71% of terminally ill cancer patients wanted to know their life expectancy, but only 17.6% were told it by their oncologist. Those who were told were much more realistic than those who were not told, about 17 months closer to their actual survival time from out baseline assessment. Oncologists who shared the prognosis did not psychologically injure patients (eg make them significantly more anxious or depressed) nor was their relationship harmed. (more…)
Author Interviews, Cancer Research / 28.09.2015

M.A. Frouws, Study Coordinator ASPIRIN trial MD PhD Candidate Datacenter Heelkunde, K6-R Leiden University Medical Center Leiden, the NetherlandsMedicalResearch.com Interview with: M.A. Frouws, Study Coordinator ASPIRIN trial MD PhD Candidate Datacenter Heelkunde, K6-R Leiden University Medical Center Leiden, the Netherlands Medical Research: What is the background for this study? What are the main findings? Response: The effect of aspirin on cancer survival has been the topic of many studies for a few decades. Epidemiological evidence shows a dual role in the relation between aspirin and cancer; both preventative and therapeutic effects are suggested. The biological mechanism of the effect of aspirin on cancer is still part of debate. However research up until now was mainly done at a single tumor location, mostly colorectal cancer. Since little is known about the etiology of the effect of aspirin, we have undertaken in this study. The aim of this study was to investigate the effect of the use of aspirin after diagnosis on survival in patients with cancer from the gastrointestinal tract. Stratification in specific localizations in the entire gastro intestinal tract could lead to new insights towards the effect of aspirin as a therapeutic agent. We studied 13.715 patients and found a really significant survival benefit in patients taking aspirin after diagnosis of gastrointestinal malignancies, except for pancreatic cancer. Survival in patients with gastro intestinal malignancies taking aspirin after diagnosis showed to be twice as high as patients not taking aspirin. At five years after diagnosis, 75% of patients were alive who took aspirin, versus 42% of the patient group not taking aspirin. This effect persisted after correcting for several confounding factors, including age, disease stage and comorbidity. (more…)
Author Interviews, Cancer Research, CDC, Occupational Health / 24.09.2015

Robert D. Daniels Ph.D Division of Surveillance, Hazard Evaluations, and Field Studies National Institute for Occupational Safety and Health Cincinnati, OhioMedicalResearch.com Interview with: Robert D. Daniels Ph.D Division of Surveillance, Hazard Evaluations, and Field Studies National Institute for Occupational Safety and Health Cincinnati, Ohio Medical Research: What is the background for this study? Dr. Daniels: In 2010, National Institute for Occupational Safety and Health (NIOSH) researchers, with funding assistance from the U.S. Fire Administration, launched a multi-year study to examine whether fire fighters have a higher risk of cancer and other causes of death due to job exposures. Our study was designed to address limitations of previous fire fighter cancer research. ? We included a significantly larger population. With more than 30,000 career fire fighters who served in Chicago, Philadelphia, and San Francisco Fire Departments between 1950 and 2010, it is the largest study of United States fire fighters ever undertaken. In addition, both non-white and female fire fighters are represented. ? We looked not only at deaths from cancer, but also at the diagnosis of certain kinds of cancer, such as testicular and prostate cancer, which have higher survival rates. We also examined other causes of death to better understand the risk for various cancers and illnesses among fire fighters compared to the general public. ? We also examined the relation between cancer and several proxies of exposure, such as the number of fire runs, time spent at fires, and duration of employment of each firefighter (Dahm et al. 2015). The study was conducted in two parts. The first part was aimed to answer the question: “Is cancer associated with firefighting?” by comparing firefighter cancer risk to that of the general population. The second part focused on the question: “Are higher-exposed firefighters more at risk?” Findings from both parts have been published in the journal, Occupational and Environmental Medicine (Daniels et al. 2014, 2015). (more…)
Author Interviews, Cancer Research, PLoS / 22.09.2015

Dr. Cristiano Ferlini, MD Director of Biomedical Research Rudy and Sally Ruggles Chief of cancer research Western Connecticut Health Network Research InstituteMedicalResearch.com Interview with: Dr. Cristiano Ferlini, MD Director of Biomedical Research Rudy and Sally Ruggles Chief of cancer research Western Connecticut Health Network Research Institute Medical Research: What is the background for this study? Dr. Ferlini: Our aim is to understand why some cancer patients respond well to conventional treatment while others suffer progressive disease.  Nextgen sequencing technologies provide data that shed light on the mechanisms underlying differences in clinical outcome. However, analyses utilizing these data have been focused on human genes. This is to be expected given that the subjects under investigation are indeed humans. We adopted a novel approach in this and a prior study which involved in-depth, comprehensive mapping of microRNA sequences in human cancers to viral genes to assess their presence and significance. Medical Research: What are the main findings? Dr. Ferlini: We discovered a surprising number of viral microRNA sequences in a wide variety of cancer tissues. We also documented an interplay between these viral microRNAs and genes related to anticancer immunity. Both viruses and cancers share a common goal of suppressing the immune system to promote their own survival. Synergistic immunosuppression seems particularly relevant for the Epstein Barr virus, an unfortunate fact given its ubiquity in human populations. After the acute phase of EBV infection, the virus persists indefinitely in a dormant state inside B lymphocytes. When cancers grow, they create a protected microenvironment in which  anticancer immunity is suppressed.  We have obtained evidence suggesting that when EBV infected B cells circulate within these domains, the virus becomes reactivated and produces microRNAs which further amplify immunosuppressive genes. (more…)
Author Interviews, Cancer Research, Cost of Health Care / 21.09.2015

Steven L. D'Amato, BSPharm, BCOP President and Executive Director New England Cancer Specialists Scarborough, Maine Association of Community Cancer CenteMedicalResearch.com Interview with: Steven L. D'Amato, BSPharm, BCOP President and Executive Director New England Cancer Specialists Scarborough, Maine Association of Community Cancer Centers Medical Research: What is the background for this study? What are the main findings? Response: The Trends in Cancer Programs annual survey, which began in 2009, provides key insight into nationwide developments in the business of cancer care. It’s a joint project between the Association of Community Cancer Centers and Lilly Oncology.  The goals of the survey are to:
  • Provide ACCC with information to help guide its education and advocacy mission
  • Assist member organizations to understand nationwide developments in the business of cancer care
  • Assist members in evaluating their own cancer program’s performance relative to similar organizations through a consistent and meaningful benchmark.
This year’s key findings show that patient-centered services – like nurse navigation, psychological counseling, survivorship care and palliative care – are continuing to grow in U.S. cancer programs. However, the biggest challenge facing cancer centers is reimbursement for these types of services. Additionally, mirroring what we are seeing in the industry in general, measurement is becoming more and more important. More cancer programs are now using quality metrics to show payers the value of care provided. More information about our findings can be viewed here: http://www.accc-cancer.org/surveys/pdf/Trends-in-Cancer-Programs-2015.pdf. (more…)
Author Interviews, Cancer Research, Leukemia, Lymphoma / 17.09.2015

Angelica Loskog, PhD Professor of Immunotherapy (adjunct) Dept of Immunology, Genetics and Pathology Uppsala University Uppsala SwedenMedicalResearch.com Interview with: Angelica Loskog, PhD Professor of Immunotherapy (adjunct) Dept of Immunology, Genetics and Pathology Uppsala University Uppsala Sweden Medical Research: What is the background for this study? What are the main findings? Dr. Loskog: CAR T cells have shown remarkable effect in patients with B cell malignancy in the US using 2nd generation CAR T cells. Acute leukemia (ALL) seems easier to treat than lymphomas and one of the reasons may be difficulties for CAR T cells to penetrate a solid lesion or due to a higher local presence of immunosuppressive cells within a lesion. As one of the first centers outside US we are evaluating 3rd generation CAR T cells in both lymphoma and ALL aiming to compare the responses and investigating biological reasons for the different responses. So far we have treated 11 patients and 6 of them had initial complete responses. Unfortunately, some progressed later. (more…)
Author Interviews, Cancer Research, Case Western, Colon Cancer, Genetic Research / 16.09.2015

Ahmad M. Khalil, PhD Department of Genetics School of Medicine Case Western Reserve University Cleveland, Ohio 44106-4955 MedicalResearch.com Interview with: Ahmad M. Khalil, PhD Department of Genetics School of Medicine Case Western Reserve University Cleveland, Ohio 44106-4955 Medical Research: What is the background for this study? What are the main findings? Dr. Khalil: DNA in human cells is modified chemically by methylation. The process of DNA methylation plays important roles in protecting human DNA and ensures proper gene expression.  In cancer cells, the process of DNA methylation becomes deregulated, however, the mechanisms of how this occurs are not known.  In our study, we have uncovered a novel mechanism on how colon cancer cells change their DNA methylation, and consequently, become more tumorigenic. We specifically identified a long non-coding RNA that interacts with and regulates the enzyme that modifies DNA with methylation - the enzyme is called DNMT1. This lncRNA become suppressed in colon tumors, which we believe is a key step in loss of DNA methylation in colon cancer cells. (more…)
Author Interviews, Biomarkers, Cancer Research / 03.09.2015

Kenneth R. Shroyer, MD, PhD The Marvin Kuschner Professor and Chair Department of Pathology Stony Brook Medicine Stony Brook, NY MedicalResearch.com Interview with: Kenneth R. Shroyer, MD, PhD The Marvin Kuschner Professor and Chair Department of Pathology Stony Brook Medicine Stony Brook, NY     Medical Research: What is the background for this study? What are the main findings? Dr. Shroyer: Patients that appear to have the same type of cancer often respond very differently to treatment; while some patients appear to go into long-term regression or are cured, others follow a rapid downhill course and ultimately die of their disease. This suggests that there are fundamental differences between tumors at the biologic level that are not detected by current clinical measures. In this study, we report the unexpected finding that cancer patients that have high levels of a protein called Keratin 17 (K17) have decreased long-term survival when compared to patients that express little to no K17 in their tumors. In addition, we found that K17 enters the nucleus of tumor cells to mediate the degradation of the master regulator of cell division and tumor growth key tumor suppressor protein, p27. Furthermore, we identified that K17 increases the resistance of tumor cells to chemotherapy. These are critical findings because this is the first report that a keratin is an oncoprotein that can enter the nucleus to promote the development of cancer and resistance to chemotherapy. (more…)
Author Interviews, Cancer Research, Melatonin, Sleep Disorders / 03.09.2015

MedicalResearch.com Interview with: Charlotte Lund Rasmussen Research Unit, Department of Palliative Medicine Bispebjerg Hospital, Copenhagen, Denmark Medical Research: What is the background for this study? What are the main findings? Response: We see that patients with advanced cancer often suffer from fatigue, pain, depression, insomnia and other symptoms, which can have a profound impact on quality of life. Melatonin is a neurohormone and its secretion is closely tied to the circadian rhythm making it a regulator of the sleep-cycle. Studies have shown that cancer patients have lower levels of melatonin than healthy controls, which may contribute to their fatigue and lowered quality of life. Furthermore, previous studies have found a possible effect of melatonin in cancer therapy, and non-clinical trials have shown melatonin to inhibit cell division in tumors. To our knowledge, no trials to date have investigated the effects of melatonin on fatigue. Given the role of melatonin in the sleep cycle, the lowered levels of melatonin noted among cancer patients, and results from previous studies, we wanted to investigate melatonin’s effect on fatigue among patients with advanced cancer. The primary objective of our study was to determine whether oral melatonin administered at night would reduce physical fatigue in patients with advanced cancer who were being treated in a palliative care facility. The effect of melatonin on other cancer-related symptoms including mental fatigue, insomnia, pain, emotional function, loss of appetite, and overall QoL were also investigated. In this trial we tested a dose of 20 mg of melatonin taken orally at night. However, melatonin did not improve physical fatigue in patients with advanced cancer. Furthermore, we were unable to identify improvements in any other cancer-related symptoms. (more…)
Author Interviews, Cancer Research, Genetic Research / 02.09.2015

Sameek Roychowdhury, MD, PhD Assistant Professor, Internal Medicine, College of Medicine Assistant Professor, Department of Pharmacology, College of Pharmacy Department of Internal Medicine Division of Medical Oncology Wexner Medical Center The Ohio State UniversityMedicalResearch.com Interview with: Sameek Roychowdhury, MD, PhD Assistant Professor, Internal Medicine, College of Medicine Assistant Professor, Department of Pharmacology College of Pharmacy Department of Internal Medicine Division of Medical Oncology Wexner Medical Center The Ohio State University Medical Research: What is the background for this study? What are the main findings? Dr. Roychowdhury: Precision cancer medicine is a new paradigm to match patients to therapies based on the molecular alterations in their cancer. Novel genomic testing of cancer using next generation sequencing can reveal numerous mutations for each patient across many genes and types of cancer, and this requires detailed time-intensive interpretation. Driver mutations can confer a selective growth or survival advantage to cancer cells, while passenger mutations do not. Cancer Driver Log, or CanDL, is meant to aid interpretation of mutations by providing the latest literature evidence for individual driver mutations, and thereby aiding pathologists, lab directors, and oncologists in interpreting mutations found in their patient’s cancer. (more…)