Abuse and Neglect, Cancer Research, Fertility, Immunotherapy / 27.03.2017

MedicalResearch.com Interview with: Kenneth S. K. Tung, M.D. Professor of Pathology and Microbiology Director of UVA Research Histology Core Beirne B. Carter Center for Immunology Research University of Virginia MedicalResearch.com: What is the background for this study? Response: The immune system needs to see tissue antigens to avoid responding to them in order to prevent autoimmune disease development. The current dogma, stated in all Immunology and Reproductive Biology textbooks, considers the sperm antigens in the testis to be exempted from this process. They are considered totally hidden behind a tissue barrier, and are invisible to the immune system. Because sperm antigens are treated as foreign molecules, they should stimulate strong immune response when employed in cancer vaccines against antigens common to sperm and cancers. It is also believed that sperm molecules are protected by local factors that inhibit inflammation, whereas systemic mechanisms such as regulatory T cells would not exist. The paradigm has restrained ongoing research on systemic tolerance to sperm, and the need to understanding systemic regulation in infertility research.  (more…)
Author Interviews, Cancer Research, Genetic Research, JAMA / 24.03.2017

MedicalResearch.com Interview with: Heikki Joensuu, MD Department of Oncology Helsinki University Hospital University of Helsinki Helsinki, Finland  MedicalResearch.com: What is the background for this study? Response: The randomized Scandinavian Sarcoma Group (SSG) XVIII trial compared three years of adjuvant imatinib to one year of adjuvant imatinib as adjuvant treatments of patients who had undergone macroscopically complete surgery for a GIST with a high risk for tumor recurrence. In this trial, patients treated with 3 years of imatinib had improved overall survival as compared to those who were allocated to one year of adjuvant imatinib. In 2 other randomized trials that compared either 1 year of adjuvant imatinib to one year or placebo, or 2 years of adjuvant imatinib to observation, no improvement in overall survival was found, although in all three trials adjuvant imatinib improved recurrence-free survival (RFS). The reasons for the discrepant findings with respect of overall survival in the 3 trials have been unclear. (more…)
Author Interviews, Breast Cancer, Cancer Research, Genetic Research, Race/Ethnic Diversity, Yale / 16.03.2017

MedicalResearch.com Interview with: Cary P. Gross, MD Section of General Internal Medicine Yale University School of Medicine New Haven, CT MedicalResearch.com: What is the background for this study? What are the main findings? Response: Prior work has demonstrated racial and socioeconomic disparities in breast cancer diagnosis, treatment, and outcomes.  As the oncology field has progressed over the past decade, the use of genetic testing to guide treatment decisions is one of the most exciting new developments. Our team was concerned that these new gene tests, which can offer important benefits, may have the potential to exacerbate disparities further.  That is, if there is unequal access to gene testing among patients for whom it is recommended, then our progress against cancer will not be equitably shared among people of all races and ethnicities. (more…)
Author Interviews, Biomarkers, Cancer Research, Genetic Research, Nature, UCSD / 07.03.2017

MedicalResearch.com Interview with: Kun Zhang, PhD Professor UCSD Department of Bioengineering La Jolla, CA 92093-0412 MedicalResearch.com: What is the background for this study? What are the main findings? Response: We have been interested in a type of chemical modification on the DNA, called CpG methylation, for years. This is like a decoration of DNA molecules that is specific to the cell type or tissue type. We were particularly interested in studying how such decoration spread along the DNA molecules. In this study, we did a very comprehensive search of the entire human genome for various human cell types and tissue types, and found close to 150,000 regions (called MHB in this study) in which adjacent CpG share the same decoration. We then went on to find out how many of such regions are unique to each normal cell/tissue type, and how many are specific to cancers. Then we took some of these highly informative regions as “biomarkers”, and showed that we can detect the absence or presence of cancer, and, in the latter case, where the tumor grow, in a patient’s blood. (more…)
Author Interviews, BMJ, Cancer Research, Imperial College, Pediatrics, Weight Research / 01.03.2017

MedicalResearch.com Interview with: Dr Maria Kyrgiou MSc, PhD, MRCOG Clinical Senior Lecturer & Consultant in Gynaecologic Oncology IRDB - Department of Surgery and Cancer, Imperial College London West London Gynaecological Cancer Centre, Queen Charlotte's & Chelsea-Hammersmith Hospital, Imperial Healthcare NHS Trust  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Obesity has become a major public health challenge and it's prevalence worldwide has more than doubled amongst women n the last four decades. Excess body weight has been associated with an increased risk of developing and dying from numerous cancers. Although the reported associations may be potentially causal, some of the associations may be flawed due to inherent study biases such as residual confounding and selective reporting of positive results. We included 204 meta-analyses investigating associations between adiposity and the development or death from 36 primary cancers and their sub-types. Adiposity was associated with a higher risk of developing esophageal adenocarcinoma, gastric cardia, colon and rectal cancer in men, biliary tract system, pancreatic, postmenopausal breast among HRT non-users, endometrial, ovarian, and kidney cancer and multiple myeloma. (more…)
Author Interviews, Cancer Research, JAMA, Pediatrics, Radiation Therapy / 01.03.2017

MedicalResearch.com Interview with: Lucie Turcotte, MD, MPH University of Minnesota Masonic Children's Hospital Division of Pediatric Hematology-Oncology Assistant Professor Minneapolis, MN 55455 MedicalResearch.com: What is the background for this study? What are the main findings? Response: We have observed dramatic improvements in the number of survivors of childhood cancer over the last 60 years. As more children are surviving, we have identified many important late health consequences of cancer therapy. One of the most devastating of these late health consequences is the diagnosis of a second cancer. As we have identified late effects, such as second cancers, we have modified therapy in an effort to prevent long-term sequelae of therapy, while still maintaining superior survival rates. For this study, we utilized data from the Childhood Cancer Survivor Study (CCSS), which is a cohort of more than 23,000 survivors of childhood cancer from multiple centers in North America, who were initially diagnosed between 1970 and 1999. Our analysis focused on elucidating whether survivors diagnosed more recently were experiencing fewer second cancers, and determining whether a reduction in second cancers could be associated with treatment modifications. The most important finding from this study is that the reductions in therapeutic radiation exposure that occurred between 1970-1999 resulted in a significant reduction in the second cancers experienced by survivors of childhood cancer. (more…)
Author Interviews, Cancer Research, Heart Disease, JAMA / 24.02.2017

MedicalResearch.com Interview with: Philip C. Haycock, PhD MRC Integrative Epidemiology Unit University of Bristol Bristol, England MedicalResearch.com: What is the background for this study? What are the main findings? Response: The direction and causal nature of the association of telomere length with risk of cancer and other diseases is uncertain. In a Mendelian randomization study of 83 non-communicable diseases, including 420,081 cases and 1,093,105 controls, we found that longer telomeres were associated with increased risk for several cancers but reduced risk for some other diseases, including cardiovascular diseases. (more…)
Author Interviews, Baylor College of Medicine Houston, Breast Cancer, Dermatology, JAMA / 15.02.2017

MedicalResearch.com Interview with: Julie Rani Nangia, M.D. Assistant Professor Breast Center - Clinic Baylor College of Medicine Houston, TX, US MedicalResearch.com: What is the background for this study? What are the main findings? Response: This study was fueled by the feedback from women undergoing chemotherapy treatment for breast cancer. One of the most distressing side effects of their treatment is hair loss. It robs them of their anonymity and, for many, their femininity. Scalp cooling therapy has been available for a few years in the UK, but has faced obstacles in FDA clearance in the states. The makers of the scalp cooling device used in this study, Paxman Coolers Ltd., have a personal connection to breast cancer, as the company founder’s wife passed away from the disease. This was the first randomized scalp cooling study, and it shows that the Paxman Hair Loss Prevention System is an effective therapy for reducing chemotherapy-induced alopecia. The results show a 50% increase in hair preservation of grade 0 or 1, meaning use of a scarf or wig is not necessary, in patients who received the scalp cooling therapy as opposed to those who did not. (more…)
Author Interviews, Biomarkers, Cancer Research / 15.02.2017

MedicalResearch.com Interview with: Edwin Posadas, MD, FACP, KM Director, Translational Oncology Program Medical Director, Urologic Oncology Program Samuel Oschin Comprehensive Cancer Institute Clinical Chief, Division of Hematology/Oncology Associate Professor, Department of Medicine Cedars-Sinai MedicalResearch.com: What is the background for this study? What are the main findings of your work so far? Response: The technology we are using is called a NanoVelcro assay. This is a nanotechnology that can be used to isolate rare cells and cell-like particles in the blood stream. We have focused the use of the NanoVelcro on isolating circulating tumor cells (or CTCs). This technology is about 10 times more sensitive than that currently used in clinics. More importantly, because of some modification in our approach, we can now not only capture CTCs, but also examine them under the microscope and even analyze them using advanced molecular techniques. In this way, we take a classic and modern approach to our work. We firmly believe that there is much to be learned by studying the shapes of these CTCs. We in the cancer field have long known that shape and cellular function are intimately related. In fact, a young pathologist in our group readily recognized that patients with the most aggressive cancers had CTCs with small nuclei, which we verified in a larger study. We are now exploring the importance of these shape variations in CTCs by coupling this classic microscopy-driven approach with RNA characterizations, giving us insight into the molecular nature of the CTC. My collaborator, UCLA Professor Hsian-Rong Tseng, PhD, is a brilliant engineer who has found ways of altering the system to allow us to capture and release live cells for analysis. By using this system, we believe that one day we may be able to avoid performing invasive tissue biopsies to study a cancer. (more…)
Author Interviews, Cancer Research, JAMA, MD Anderson, Orthopedics / 12.02.2017

MedicalResearch.com Interview with: Gabriel N. Hortobagyi, MD, FACP, FASCO Professor, Department of Breast Medical Oncology Division of Cancer Medicine The University of Texas MD Anderson Cancer Center Houston, TX 77230-1439  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Bisphosphonates have been commercially available for several decades as supportive care for patients with bone metastases. They reduce the frequency and severity of bone-related complications. While the optimal dose and short-term scheduling of zoledronic acid (and previously, pamidronate) have been determined, there has been no research to determine how long these drugs need to be maintained nor the optimal dose and schedule beyond the first year of therapy. These questions are particularly important for this family of drugs, since they are incorporated into bone and not excreted from the body for many years. We set out to determine whether a reduction in the frequency of administration of zoledronic acid (every 12 weeks) was able to maintain the therapeutic efficacy of this intervention when compared to the “standard” schedule of administration (every 4 weeks). It was a prospective, randomized, non-inferiority trial that recruited patients with metastatic breast cancer with bone metastases and who had previously received 9 or more doses of zoledronic acid or pamidronate. The primary endpoint was the proportion of patients with one or more skeletal-related events. Four hundred and sixteen patients were randomized in a 1:1 ratio. The two groups were comparable at baseline. After the first year of follow-up, there was no statistically significant difference in SRE rate between the two arms, confirming the non-inferiority fo the every-12-week schedule of zoledronic acid. (more…)
Author Interviews, Cancer Research, Heart Disease, PNAS, UT Southwestern / 09.02.2017

MedicalResearch.com Interview with: Lawrence Lum, Ph.D. Associate Professor Virginia Murchison Linthicum Scholar in Medical Research UT Southwestern Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: Scarring of the adult heart due to excessive fibrotic responses is common after a heart attack, or following radiation therapy for the treatment of certain cancers. We have identified an anti-cancer agent currently in clinical development called WNT-974 that decreases fibrotic responses and improves heart function following myocardial infarction in mice. This unexpected observation was the outcome of a study focused on identifying unwanted adult tissue toxicities associated with this class of chemicals. (more…)
Author Interviews, Cancer Research, Fertility, OBGYNE, Pediatrics / 30.01.2017

MedicalResearch.com Interview with: Tamar Wainstock, PhD Department of Public Health; Faculty of Health Sciences Ben-Gurion University of the Negev ISRAEL MedicalResearch.com: What is the background for this study? Response: There is a controversy in the medical literature regarding the possible association between infertility or infertility treatments, and the long-term offspring neoplasm risk: while some studies have found such an association, others have not. Since the number of offspring conceived following treatments are growing, and as they age, it is critical to clarify this possible association. (more…)
Author Interviews, Cancer Research, Nature / 24.01.2017

MedicalResearch.com Interview with: Dr. Hua Lu MS PhD Department of Biochemistry & Molecular Biology Reynolds and Ryan Families Chair in Translation Cancer Tulane Cancer Center Tulane University School of Medicine New Orleans, Louisiana 70112 MedicalResearch.com: What is the background for this study? What are the main findings? Response: It has been well appreciated and acknowledged that p53 is the most important tumor suppressor in human body. However, approximately 50% of human cancers still sustain the wild type form of its gene, and also oddly, some cancers, such as breast cancer, which contain wild type p53, are often less sensitive to chemotherapy than those harbor mutated p53. Although a number of oncoproteins, including MDM2 and MDMX (MDM4), have been shown to be highly expressed and to inactivate p53 in those wild type p53-containing cancers, more molecules need to be discovered to keep p53 in control in order to let cancer cells to proliferate and growth. Our study as described in our recent publication in Nature Communications unveils a new p53 target gene that encodes pleckstrin homology domain-containing protein (PHLDB3) as another p53 inhibitor in a negative feedback fashion. Interestingly and mechanistically, PHLDB3 can work with MDM2 by boosting its E3 ubiquitin ligase activity, consequently leading to degradation of p53. Biologically, PHLDB3 can promote cancer cell proliferation and growth in culture and in xenograft tumor models by in part inactivating p53 activity. More interestingly, PHLDB3 is highly amplified and expressed in a number of human cancers, such as pancreatic, prostate, colon and breast cancers. High expression of PHLDB3 is well correlated with the wild type status of p53 in certain portion of breast cancer. These findings uncover PHLDB3 as another oncoprotein that can promote cancer growth by partially inactivate p53, and thus might serve as a potential target for future development of anti-cancer therapy. Our study also suggests that PHLDB3 has a p53-independent function important for cancer growth. (more…)
Author Interviews, Cancer Research, Immunotherapy, NEJM, Transplantation / 19.01.2017

MedicalResearch.com Interview with: Kenar D. Jhaveri, MD Professor of Medicine Division of Kidney Diseases and Hypertension Hofstra Northwell School of Medicine, 100 Community Drive, Great Neck, NY 11021 MedicalResearch.com: What is the background for this study? What are the main findings? Response: The immune check point inhibitors are novel anti cancer agents being used rapidly in various cancers. Many cancers don’t allow our natural immune system to attack the cancer. These immunotherapy agents “activate” the immune system to attack the cancer. These agents have been reported to cause multiple end organ side effects as noted by this recent NYT article. We also recently reported the known renal effects of immunotherapy. In the kidney transplant patient who is on immunosuppressive agents, the physicians need to keep the immune system suppressed to preserve the kidney. When one of these agents are used for a cancer in a kidney transplant patient, prior reports have suggested severe rejection episodes and loss of the transplanted kidney. Our case in the NEJM is the first report of a preventive strategy used to allow for simultaneous treatment of cancer and preventive rejection of the kidney. We used a regimen of steroids and sirolimus( an anti-proliferative agent that is used to treat cancer and also is an immunosuppresant) along with the immunotherapy. The cancer started regressing and the kidney did not reject. (more…)
Author Interviews, Biomarkers, Cancer Research, ENT / 13.01.2017

MedicalResearch.com Interview with: Jacek Majewski PhD Associate Professor Department of Human Genetics McGill University and Genome Quebec Innovation Centre Montreal, Canada  MedicalResearch.com: What is the background for this study? Response: Our lab, in collaboration with Dr. Nada Jabado, has been investigating the molecular genetics of pediatric glioblastoma – a deadly brain cancer. Several years ago, in the majority of our patients’ tumors we discovered mutations in genes that encode histone proteins. Those mutations disrupt the epigenome - that is the way the DNA is modified, silenced, or activated in the cancer cells. It appears that epigenome-modifying mutations are particularly important in pediatric cancers, and our hypothesis is that they act by diverting the normal developmental pathways into unrestrained proliferation. Many other studies have highlighted the significance of epigenome disruption in a number of cancers. (more…)
Author Interviews, Cancer Research / 06.01.2017

MedicalResearch.com Interview with: Rebecca Siegel, MPH Strategic Director, Surveillance Information Services American Cancer Society, Inc. 250 Williams St. Atlanta, GA 30303 MedicalResearch.com: What is the bottom line for incidence and mortality trends? Response: The bottom line for cancer mortality is that in contrast to many other major causes of death, cancer death rates continue to decline, dropping by 25% from 1991 to 2014. This translates to about 2 million fewer cancer deaths over this time period than would be expected if cancer death rates had remained at their peak. Death rates are the best measure of progress against disease. Cancer incidence rates also dropped in men over the past decade of data, whereas in women they are flat. The drop in men is because of large declines for the top 3 cancers (prostate, lung, and colorectum), which account for more than 40% of cancers diagnosed in men. The stable trend in women is largely because declines in lung and colorectal cancers are offset by a flat trend for both breast and uterine corpus (i.e., endometrial) cancers, which combined account for almost 40% of cases in women, as well as rapid increases for thyroid cancer over the past decade -- increasing by almost 5% annually. Importantly, thyroid incidence rates have stabilized in the past few data years because of modifications in diagnostic criteria. (more…)
Author Interviews, Cancer Research, JAMA, Orthopedics / 06.01.2017

MedicalResearch.com Interview with: Charles L. Shapiro, MD Professor of Medicine Co-Director of Dubin Breast Center Director of Translational Breast Cancer Research Director of Cancer Survivorship, Tisch Cancer Institute Mount Sinai Health System Division of Hematology / Medical Oncology: Tisch Cancer Institute New York, NY 10029 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Metastases to bone are frequent in many cancers and cause pain, pathological fractures, necessitate surgical and/or radiation treatments, cause spinal chord compression that can lead to paralysis, and significantly increase health care costs. Zoledronic acid, a bisphosphonate that inhibits bone resorption, is used in standard practice because it reduces the risks skeletal-related events including cancer-related pathological fractures, the need for surgery and/or radiation to bone metastases, and spinal chord compression in patients with breast cancer, prostate cancer and multiple myeloma. However, the optimal dosing interval for zoledronic acid is unknown and based on prior studies and empiricism it is administered monthly along with anti-cancer treatments. In this trial, over 1800 breast cancer, prostate cancer and multiple myeloma patients with bone metastases were randomized to the standard dosing interval of monthly zoledronic acid versus every 3-months zoledronic acid for a duration of two years. The results overall, and in each specific disease site, show that giving zoledronic acid once every 3-months as opposed to monthly did not result in any increase in skeletal-related events. (more…)
Author Interviews, Biomarkers, Cancer Research, JAMA / 29.12.2016

MedicalResearch.com Interview with David A Mankoff, MD, PhD Gerd Muehllehner Professor of Radiology Attending Physician University of Pennsylvania Health System PET Center Director Vice-Chair of Research, Department of Radiology University of Pennsylvania MedicalResearch.com: What is the background for this study? What are the main findings? Response: This review was designed to describe the current status of molecular imaging, especially positron emission tomography (PET) as a clinical tool for helping to direct precision oncology. We found that while there had been a number of promising methods tested in small, single research studies, the number of new molecular imaging tests translated to the clinic was small. In addition, the application of molecular methods as tools for therapeutic decision making (versus use for disease detections and staging) was even smaller. We noted that some recently published studies, including a few large multi-center trials, indicated the considerable potential of new molecular imaging tests to identify therapeutic targets for cancer treatment, to evaluate early response to targeted cancer therapy, and to predict downstream outcomes such as progression free survival. We made some observations and recommendations in the review for directing these potentially powerful imaging tools towards use as biomarkers for precision oncology. (more…)
Author Interviews, Cancer Research, Immunotherapy, Nature, Technology, University of Michigan / 27.12.2016

MedicalResearch.com Interview with: James Moon, PhD John Gideon Searle Assistant Professor University of Michigan Dept. of Pharmaceutical Sciences and Biomedical Engineering Biointerfaces Institute Ann Arbor, MI, 48109 MedicalResearch.com: What is the background for this study? Response: The field of cancer immunotherapy has recently made a breakthrough with the clinical success of immune checkpoint inhibitors, which work by removing the brakes on immunosuppressed T-cells. However, these approaches generally work by augmenting pre-existing T-cell immunity and benefit only a subset of patients. In addition, because the majority of somatic mutations in cancer cells are unique to each patient, cancer immunotherapy may benefit from a personalized approach. (more…)
Author Interviews, Cancer Research / 27.12.2016

MedicalResearch.com Interview with: Dr. Richard Quek MBBS, MRCP, FAMS Senior Consultant, Medical Oncology Parkway Cancer Centre Singapore MedicalResearch.com: What is the background for this study? Response: Angiosarcoma is an uncommon form of aggressive soft tissue sarcoma (STS). It comprises of 2 distinct subgroups of patients: one originating from the skin - typically scalp, seen predominantly in elderly patients while the second subgroup affects younger patients and tends to originate from visceral organs including the liver and breasts. Angiosarcoma may also develop as a complication of prior radiation treatment. Prognosis in patient is poor, with survival generally less than 1 year in those with advanced or unresectable disease. Optimal treatment remains unclear; most published series on angiosarcoma tends to be small singlecenter studies. In our previous Asian STAR study evaluating epidemiology, treatment patterns and outcomes in Asian patients diagnosed with STS [J Clin Oncol 33, 2015 (suppl; abstract 10549)], we found that angiosarcoma represented 7% of the cohort, a proportion higher than what we would have expected from published series coming out of the west and hence our interest in this subject. (more…)
Author Interviews, Cancer Research, Columbia, Genetic Research, Personalized Medicine / 23.12.2016

MedicalResearch.com Interview with: Dr. Kai Wang Zilkha Neurogenetic Institute, University of Southern California Institute for Genomic Medicine, Columbia University MedicalResearch.com: What is the background for this study? What are the main findings? Response: Cancer is a genetic disease caused by a small number of “driver mutations” in the cancer genome that drive disease initiation and progression. To understand such mechanism, there are increasing community efforts in interrogating cancer genomes, transcriptomes and proteomes by high-throughput technologies, generating huge amounts of data. For example, The Cancer Genome Atlas (TCGA) project has already made public 2.5 petabytes of data describing tumor and normal tissues from more than 11,000 patients. We were interested in using such publicly available genomics data to predict cancer driver genes/variants for individual patients, and design an "electronic brain” called iCAGES that learns from such information to provide personalized cancer diagnosis and treatment. iCAGES is composed of three consecutive layers, to infer driver variants, driver genes and drug treatment, respectively. Unlike most other existing tools that infer driver genes from a cohort of patients with similar cancer, iCAGES attempts to predict drivers for individual patient based on his/her genomic profile. What we have found is that iCAGES outperforms other tools in identifying driver variants and driver genes for individual patients. More importantly, a retrospective analysis on TCGA data shows that iCAGES predicts whether patients respond to drug treatment and predicts long-term survival. For example, we analyzed two groups of patients and found that using iCAGES recommend drugs can increase patients’ survival probability by 66%. These results suggest that whole-genome information, together with transcriptome and proteome information, may benefit patients in getting optimal and precise treatment. (more…)
Author Interviews, Cancer Research, End of Life Care / 23.12.2016

MedicalResearch.com Interview with: Yu Uneno, M.D. Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University Kyoto city, Kyoto Japan MedicalResearch.com: What is the background for this study? What are the main findings? Response: Prognosis prediction is one of the most important issues to make an optimal treatment decision for both cancer patients and health care professionals. Previous prognosis prediction models were developed using data from single time point (at the baseline, for example), limiting the use of the models at the similar situation. Recently, we have developed the Six Adaptable Prognostic (SAP) models which can be repeatedly used at any time point after the initiation of treatment for patients with cancer receiving chemotherapy. Those models use only three laboratory items (albumin, neutrophil, lactate dehydrogenase) which are routinely monitored in daily clinical practice. (more…)
Author Interviews, Cancer Research, Nature, Wistar / 20.12.2016

MedicalResearch.com Interview with: Cecilia Caino, Ph.D. The Wistar Institute 3601 Spruce Street Philadelphia, PA 19104 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Mitochondria have recently experienced a resurgence of interest in the field of cellular biology. Traditionally known for their role in energy production and in programmed cell death, mitochondria are more broadly recognized as signaling hubs and biosynthetic factories. Not surprisingly, mitochondria have been linked to several hallmarks of cancer, including evasion of apoptosis, tissue invasion and metastasis and abnormal metabolic pathways. It has become clear that mitochondria quality control and metabolism-regulated shape changes are dysregulated in cancer. Recent studies identified a novel therapy-resistance mechanism that involves mitochondrial subcellular re-localization and is responsible for enhanced metastatic potential of cancer cells. In this context, the molecular regulators of mitochondrial trafficking in cancer are largely unknown. Through analysis of shRNA screening results, we identified Syntaphilin (SNPH), which is considered to moderate mitochondrial trafficking in neurons, as a non-neuronal tissue specific factor to suppress cancer cell invasion. Using multi-disciplinary cell biological, real time imaging, in vivo studies and human clinical studies, SNPH was revealed to block cell motility and tumor metastasis by regulation of reprogramming of mitochondrial dynamics. We provided evidence from public databases and clinical samples that SNPH levels are decreased in different types of human tumors and low SNPH levels correlate with worse patient prognosis. Overall this study demonstrated a new mechanism by which tumor cell invasion is regulated by a SNPH-mediated pathway. (more…)
Aging, Author Interviews, Cancer Research, Genetic Research / 16.12.2016

MedicalResearch.com Interview with: Jerry W. Shay PhD Professor Department of Cell Biology, UT Southwestern Medical Center MedicalResearch.com: What did you find? Response: Telomeres are the ends of chromosomes and they gradually shortened with every cell division. There have been multiple studies proposing that shortened telomeres correlate with human aging. Most cancers overcome the shortening of telomeres and aging by activating the enzyme, telomerase. Surprisingly, the human telomerase gene (hTERT) is very close to the telomere on chromosome 5p. During human development telomerase is active until about 18 weeks of gestation. It has been a mystery until this present work of what actually causes telomerase to become silenced. We found in this current work that when telomeres are long during development the telomere loops over and helps to silence the telomerase gene. However, as we age and telomeres get progressively shorter, then telomerase becomes permissive for activation and possibly initiation of cancer. This study in part explain why most cancers are in the 65 and older segment of the population. (more…)
Aging, Author Interviews, Cancer Research, Global Health, JAMA / 06.12.2016

MedicalResearch.com Interview with: Christina Fitzmaurice, MD, MPH Assistant Professor Department of Medicine, Division of Hematology Institute for Health Metrics and Evaluation University of Washington Seattle, WA MedicalResearch.com: What is the background for this study? What are the main findings? Response: Cancer is the second leading cause of death worldwide behind cardiovascular diseases. We found that cancer cases increased by 33% from 13.1 million cases in 2005 to 17.5 million in 2015. The largest driver behind this increase was an aging population, followed by a growing population worldwide. The smallest factor contributing to this increase was a rise in cancer incidence rates. Because of increasing life expectancy and better control of communicable diseases cancer will remain a major burden in the foreseeable future. Adjusting and building health systems that can appropriately deal with this challenge is only possible with good data on the burden of cancer. In our study we estimate the number of cancer cases, and cancer deaths over time for 32 cancers in 195 countries and territories from 1990 to 2015. We also estimate how many years of life were lost due to cancer as well as disability adjusted life years and a summary measure that combines these two into disability adjusted life years. (more…)
Author Interviews, Cancer Research, Cost of Health Care, JAMA, Johns Hopkins / 02.12.2016

MedicalResearch.com Interview with: Dr. Amol K. Narang, MD Instructor of Radiation Oncology and Molecular Radiation Sciences Johns Hopkins Sidney Kimmel Comprehensive Cancer Center MedicalResearch.com: What is the background for this study? Response: We know that cancer care is becoming increasingly expensive in the U.S., but the financial impact on patients in the form of out-of-pocket expenses is not well understood, in part because of the lack of data sources that track this information. As such, we used the Health and Retirement study, a national panel study that closely tracks the out-of-pocket medical expenditures of older Americans, to understand the level of financial strain that Medicare patients experience after a new diagnosis of cancer. We further investigated what factors were associated with high financial strain and what type of health services were driving high costs in this population. (more…)
Author Interviews, Cancer Research, Nature / 01.12.2016

MedicalResearch.com Interview with: Sudarshan Anand, PhD Department of Cell, Developmental and Cancer Biology Department of Radiation Medicine Oregon Health and Science University Portland, Oregon MedicalResearch.com: What is the background for this study? What are the main findings? Response: Almost half of all cancer patients receive radiation therapy during the course of their disease. While the impact of radiation on the cancer cells has been well studied in experimental models, its effects on the accessory cells that are present in the tumor are not well known. One of the major interests of our lab is studying these accessory cells of the tumor aka “the tumor microenvironment”. These group of cells consists of blood vessel cells, fibroblasts and immune cells that are normal cells that have been recruited by the tumor and generally support tumor growth. The goal of this study was to understand the impact of radiation (and broadly DNA damaging agents) on the blood vessel cells in the tumor. We focused on a specific type of molecule called microRNAs (miRs) in these cells. miRs are small RNA molecules that bind to dozens of messenger RNAs and the production of proteins. We discovered a group of microRNAs that was induced in blood vessel cells by radiation, a chemotherapy agent cisplatin and peroxide an agent that mimics oxidative stress that is often present in cancers. We found that the top candidate on this list was a microRNA that mimicked radiation by inducing DNA damage and eventually killing the blood vessel cells. Administering this microRNA, either within a tumor or using a specific nanoparticle that delivers cargo to the tumor blood vessels, decreased tumor growth in mouse models of breast cancer, brain cancer and colorectal cancer. We found that the efficacy of this agent was a result of its ability to suppress a protein TREX1, that is often mutated in human lupus. In other words, this microRNA was able to create some of the immune and inflammatory features of lupus within a tumor and induce proteins that triggered cell death on tumor cells. Overall, our work illustrates how the tumor accessory cells respond to radiation and highlights the cross-talk between different accessory cells and the tumor cells. (more…)
Author Interviews, Cancer Research, Dermatology, JAMA, UCLA / 22.11.2016

MedicalResearch.com Interview with: Albert Yoon-Kyu Han, PhD Class of 2017 Medical Scientist Training Program David Geffen School of Medicine at UCLA MedicalResearch.com: What is the background for this study? What are the main findings? Response: Squamous cell carcinoma (SCC) of the lip makes up a large portion of oral cancers (25%). Most of the demographic and prognostic indicators for lip SCC are only available through retrospective case series. Thus, we used the national cancer database (Surveillance, Epidemiology, and End Results, or SEER) to examine the incidence, treatment, and survival of patients with lip SCC. The main findings of this study were that lip Squamous cell carcinoma predominantly affects white men in their mid-60s. We also found that the determinants of survival for lip SCC include age at diagnosis, primary site, T stage, and N stage. More specifically, on the primary site, SCC of the upper and lower lip had similar survival, whereas SCC of the oral commissure was associated with decreased survival. (more…)
Author Interviews, BMJ, Cancer Research, Cost of Health Care, Imperial College / 11.11.2016

MedicalResearch.com Interview with: Peter Wise MD Charing Cross Hospital and Imperial College School of Medicine London, UK MedicalResearch.com: What is the background for this analysis? Response: As a medical ethicist, I wished to know how much patients with advanced – metastatic – cancer knew about the drugs that were being used to treat it. What were their perceptions of likely treatment success and how did that tally with our knowledge of what drugs could actually achieve – and at what cost to the body and to the pocket. Did patients actually have a choice – and how did the drugs get approved for use in the first place? (more…)