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Different Exosome Cargo in Males and Females May Relate to Different Susceptibility to Osteoarthritis

Researchers have more evidence that males and females are different, this time in the fluid that helps protect the cartilage in their knee joints. They have found in the synovial fluid of this joint, clear differences in the messages cells are sending and receiving via tiny pieces of RNA, called microRNA, in males and females with the common and debilitating condition osteoarthritis. The differences may help explain why the disease is more common in women as it points toward a more targeted way to diagnose and treat this “wear and tear” arthritis, said Dr. Sadanand Fulzele, bone biologist in the Department of Orthopaedic Surgery at the Medical College of Georgia (MCG) at Augusta University. Osteoarthritis, which affects more than 30 million Americans, is fundamentally a destruction of the cartilage that provides padding between our bones. “It’s a huge problem,” says Dr. Monte Hunter, Chair of the MCG Department of Orthopedic Surgery and a coauthor of the study published online on May 17, 2017 in Scientific Reports. The open-access article is titled “Gender-Specific Differential Expression of Exosomal miRNA in Synovial Fluid of Patients with Osteoarthritis.” Today’s treatment of osteoarthritis addresses symptoms, like inflammation and pain, and the bottom line for some patients is knee replacement. Clinicians like Hunter would like to provide patients additional options for diagnosing and treating this common malady of aging. Synovial fluid is known to provide clues about joint health, so MCG researchers decided to look at what messages cells in the region were sending and receiving by looking inside traveling compartments in the fluid called exosomes, says Dr. Fulzele, corresponding author. “What we found is there is no change in the number of exosomes, but a change in the microRNA cargo they carry,” Dr. Fulzele says.

New Pestivirus Identified in Shaking Piglets in Austria

Some newly born piglets shiver even when they are kept warm. So-called “shaking piglets” have symptoms that resemble those of the classical swine fever, with extensive damage to the brain and the spinal cord. The viral origin of the disease was clarified only recently with the discovery in Europe and the USA of an atypical porcine pestivirus. Researchers at the Vetmeduni Vienna have now discovered a further new virus in shaking piglets on an Austrian farm. The pathogenic agent is related to the Australian Bungowannah virus and more distantly to the classical swine fewer virus. Because of the symptoms it causes, the new virus is termed LINDA virus (Lateral shaking Inducing NeuroDegenerative Agent). Its discovery was announced in the July 2017 issue of “Emerging Infectious Diseases.” The open-access article is titled “Novel Pestivirus Species in Pigs, Austria, 2015.” In 2015, an Austrian pig breeder observed a number of new-born “shaking piglets” on his farm. Such piglets suffer from a disease in which heavy damage to the brain and spinal cord causes severe shaking. The condition is associated with huge financial losses for the farm. It is believed to be caused by an atypical porcine pestivirus (APPV) that was recently discovered in Europe and the USA. Scientists at the Vetmeduni Vienna have subsequently found the virus in Austria. Because of the pronounced symptoms on this particular farm, experts at the University Clinic for Swine checked whether the animals were infected with the recently described APPV. Despite comprehensive and highly specific tests, neither APPV nor another pathogen known to cause the disease could be found.

Point-of-Care Device for Rapid Detection of Sepsis

A new portable device can quickly find markers of deadly, unpredictable sepsis infection from a single drop of blood. A team of researchers from the University of Illinois and Carle Foundation Hospital in Urbana, Illinois, completed a clinical study of the device, which is the first to provide rapid, point-of-care measurement of the immune system's response, without any need to process the blood. This can help doctors identify sepsis at its onset, monitor infected patients, and could even point to a prognosis, said research team leader Dr. Rashid Bashir, a Professor of Bioengineering at the U. of I. and the Interim Vice Dean of the Carle Illinois College of Medicine. The research findings were published online on July 3, 2017 in Nature Communications. The open-access article is titled “A Point-of-Care Microfluidic Biochip for Quantification of CD64 Expression from Whole Blood for Sepsis Stratification.” Sepsis is triggered by an infection in the body. The body's immune system releases chemicals that fight the infection, but also cause widespread inflammation that can rapidly lead to organ failure and death. Sepsis strikes roughly 20 percent of patients admitted to hospital intensive care units, yet it is difficult to predict the inflammatory response in time to prevent organ failure, said Dr. Karen White, an intensive care physician at Carle Foundation Hospital. Dr. White led the clinical side of the study. "Sepsis is one of the most serious, life-threatening problems in the ICU. It can become deadly quickly, so a bedside test that can monitor patient's inflammatory status in real time would help us treat it sooner with better accuracy," Dr. White said. Sepsis is routinely detected by monitoring patients' vital signs - blood pressure, oxygen levels, temperature, and others.

TERRA RNA Promotes Repair of Shortened Telomeres

Researchers at the Institute of Molecular Biology (IMB) and Johannes Gutenberg University Mainz (JGU) have further uncovered the secrets of telomeres, the caps that protect the ends of our chromosomes. They discovered that an RNA molecule called TERRA helps to ensure that very short (or broken) telomeres get fixed again. The work, which was published in the June 29,2017 issue of Cell, provides new insights into cellular processes that regulate cell senescence and survival in aging and cancer. The Cell article is titled “Telomere Length Determines TERRA and R-1 Loop Regulation Through the Cell Cycle.” Telomeres protect the ends of our chromosomes, much like the plastic cap at the end of a shoelace that prevents the lace from unravelling. Over a cell's lifetime, telomeres get gradually shorter with each cell division and therefore the protective cap becomes less and less effective. If the telomeres get too short, it is a signal for the cell that its genetic material is compromised and the cell stops dividing. Telomere shortening and reduced cell division are considered a hallmark of aging and likely contribute to the aging process. However, telomere shortening is also a defense mechanism against cancer because highly proliferative cells can only divide when their telomeres do not shorten. Therefore, telomere shortening is a double-edged sword and has to be carefully regulated to strike a balance between aging and cancer prevention. When a telomere accidentally gets cut short early in a cell's lifetime, it needs to be fixed so that the cell doesn't become senescent too early. "In the life of a cell, you have to find some sort of balance between cancer prevention and aging.

BioQuick News Wins 2017 APEX Publishing Excellence Award

BioQuick Online News (TM) (http://www.bioquicknews.com) has recently been awarded an APEX 2017 Award for Publishing Excellence in the category of Electronic Media: Electronic Publications. BioQuick has won seven previous APEX Publishing Excellence Awards in the years 2010-2016, i.e., one in every year of its existence. BioQuick presently features over 4,000 online articles on major life science advances in the last eight years and articles on topics of interest are readily accessible by means of the publication’s powerful search engine. New articles are published on a daily basis. BioQuick has readers in over 160 countries and includes a Japanese language edition (http://www.biomarket.jp/bioquicknews/) directed by Yoshimitsu Obata, M.S., in Tokyo (http://wwwwBioMarket.jp). BioQuick currently offers free and open access to all of its content. To learn more about the highly competitive international APEX Publishing Awards, please visit the awards web site at (http://www.apexawards.com). One indicator of the overall quality of the competition is the high caliber of organizations numbering among the winners. This year, these winners include the American Society of Clinical Oncology (ASCO), American Society for Clinical Chemistry, National Science Foundation (NSF), University of Michigan Comprehensive Cancer Care Center, American Academy of Pediatrics, American Academy of Dermatology, Hospital for Special Surgery, College of American Pathologists, Sandia National Laboratories, and NASA. Other winners also include the WGBH Education Foundation, Detroit Medical News, Society of Women Engineers, Frontline Medical News, AARP Magazine, Ford Motor Company, US Tennis Association (USTA), National Football League (NFL), China Airlines, and the Walt Disney World Resort.

Study Sheds Light on How Ovarian Cancer Spreads

With 20,000 diagnoses each year, ovarian cancer is the ninth most common cancer and fifth leading cause of cancer death among women in the United States. So many women die from ovarian cancer because it often goes undetected until it has spread within the pelvis and abdomen, by which point it is difficult to treat and usually fatal. A team of researchers from the University of California, Riverside, and the University of Notre Dame are studying the molecular mechanisms by which ovarian cancer metastasizes to uncover new therapeutic opportunities. In their latest paper, published in the journal Oncogene, the scientists used live imaging and electron microscopy to study the cellular activities associated with successful metastasis, including the expression of a group of proteins called cadherins, which help cells bind together. Because these proteins enable cancer cells to anchor to new sites in the body, it may be possible to disrupt metastasis by blocking cadherin-mediated binding. The research was led by Mark Alber, PhD, a Distinguished Professor of Applied Mathematics at UC Riverside, and M. Sharon Stack, PhD, a Kleiderer-Pezold Professor of Biochemistry and Director of Notre Dame Harper Cancer Research Institute. As primary ovarian tumors metastasize, they shed both single cells and clusters of cells, called multicellular aggregates (MCAs), into the pelvis and abdomen. To study exactly how metastasis occurs, the researchers quantified the interactions between epithelial ovarian cancer (EOC) cells and three-dimensional models of the abdomen wall. They showed that when EOC cells acquired N-cadherin (Ncad), an event that occurs in human EOC tumors, they could penetrate and attach to the abdomen wall.

Whole Genome Sequencing of Healthy Primary Care Patients Reveals That Significant Percentage Carry Rare Genetic Disease Risks; Results of MedSeq Project Published

Whole genome sequencing involves the analysis of all three billion pairs of letters in an individual's DNA and has been hailed as a technology that will usher in a new era of predicting and preventing disease. However, the use of genome sequencing in healthy individuals is controversial because no one fully understands how many patients carry variants that put them at risk for rare genetic conditions and how they, and their doctors, will respond to learning about these risks. In a new paper published online on June 26, 2017 in the Annals of Internal Medicine by investigators at Brigham and Women's Hospital and Harvard Medical School, along with collaborators at Baylor College of Medicine, report the results of the 4-year, NIH-funded MedSeq Project, the first-ever randomized trial conducted to examine the impact of whole genome sequencing in healthy primary care patients. The article is titled “The Impact of Whole-Genome Sequencing on the Primary Care and Outcomes of Healthy Adult Patients: A Pilot Randomized Trial.” In the MedSeq Project, 100 healthy individuals and their primary care physicians were enrolled and randomized so that half of the patients received whole genome sequencing and half did not. Nearly 5,000 genes associated with rare genetic conditions were expertly analyzed in each sequenced patient, and co-investigators from many different disciplines including clinical genetics, molecular genetics, primary care, ethics, and law were involved in analyzing the results. Researchers found that among the 50 healthy primary care patients who were randomized to receive genome sequencing, 11 (22 percent) carried genetic variants predicted to cause previously undiagnosed rare disease.

HUNTINGTON'S DISEASE: Enrollment in Phase 1/2a Study of IONIS-HTT Rx in Patients with HD Completed and Open-Label Extension Study to Open in 2H 2017; Anti-Sense Drug Designed to Reduce Production of All Forms of HTT, Including Mutant HTT

On June 22, 2017, Ionis Pharmaceuticals, Inc. (NASDAQ: IONS) announced completion of enrollment in the Phase 1/2a randomized, placebo-controlled, dose escalation study of IONIS-HTTRx in patients with Huntington's disease (HD). Dosing in the final patient cohort continues, and Ionis plans to report top-line results from this study around year-end 2017. The safety and tolerability profile of IONIS-HTTRx in the completed cohorts of the Phase 1/2a study supports its continued development. Patients who complete the Phase 1/2a study will be eligible to participate in an open-label extension (OLE) study that Ionis plans to initiate in the next several months. Roche, Ionis' partner for this drug, continues to advance and support the program. IONIS-HTTRx is the first therapy in clinical development targeting the cause of HD by reducing the production of the toxic mutant huntingtin protein (mHTT) from the mutated huntingtin gene. "We are encouraged by the safety profile of IONIS-HTTRx we have observed to date in the completed dosing cohorts in the Phase 1/2a study. Upon completion and full analysis of this study, the next step for this program will be to conduct a study to investigate whether decreasing mutant huntingtin protein with IONIS-HTTRx can slow the progression of this terrible disease," said C. Frank Bennett, PhD, Senior Vice President of Research at Ionis Pharmaceuticals. "We believe that IONIS-HTTRx, which is designed to reduce the production of all forms of the huntingtin (HTT) protein – the known cause of HD, represents the most promising opportunity to address this significant unmet medical need.

FDA Grants Pre-Market Approval to Thermo Fisher Scientific for First NGS-Based Companion Diagnostic Test for Biomarkers Associated with Three FDA-Approved Therapies for Non-Small Cell Lung Cancer (NSCLC)

On June 22, 2017, Thermo Fisher Scientific announced that the U.S. Food and Drug Administration (FDA) had granted premarket approval to the company for the first next-generation sequencing (NGS)-based test that simultaneously screens tumor samples for biomarkers associated with three FDA-approved therapies for non-small cell lung cancer (NSCLC). Lung cancer is the leading cause of cancer-related deaths in the U.S., with NSCLC accounting for 85 percent of all lung cancers. The Oncomine Dx Target Test simultaneously evaluates 23 genes clinically associated with NSCLC. Following FDA approval, results from analysis of three of these genes can now be used to identify patients who may be eligible for treatment with one of the following: the combined therapy of Tafinlar® and Mekinist®, XALKORI®, or IRESSA®. With this test, physicians can now match patients to these therapies in days instead of several weeks, which it often takes when screening samples one biomarker at a time. "For people battling non-small cell lung cancer, time is critical and days matter," said Joydeep Goswami, President of Clinical Next-Generation Sequencing and Oncology at Thermo Fisher. "The Oncomine Dx Target Test rapidly guides oncologists toward the right targeted therapy, with the goal of improving patient outcomes and the cost-efficiency of treatments." LabCorp's Diagnostics and Covance Businesses, NeoGenomics Laboratories, and Cancer Genetics, Inc., are among the first laboratories that will offer the Oncomine Dx Target Test as a service to oncologists.

Five-Gene Assay Detects Neuroblastoma with Greater Sensitivity; Improved Disease Assessment Aids Prediction of Relapse in Children

Investigators at The Saban Research Institute of Children's Hospital Los Angeles have developed and tested a new biomarker assay for quantifying disease and detecting the presence of neuroblastoma even when standard evaluations yield negative results for the disease. In a study, led by Araz Marachelian, MD, of the Children's Center for Cancer and Blood Diseases, researchers provide the first systematic comparison of standard imaging evaluations versus the new assay that screens for five different neuroblastoma-associated genes and determine that the new assay improves disease assessment and provides prediction of disease progression. Results of the study were published on May 30, 2017 in Clinical Cancer Research. The article is titled “Expression of Five Neuroblastoma Genes in Bone Marrow or Blood of Patients with Relapsed/Refractory Neuroblastoma Provides a New Biomarker for Disease and Prognosis.” Neuroblastoma is a cancer of the nervous system that exists outside the brain and typically is diagnosed in children 5 years or age or younger. Forty-five percent of patients have high-risk, metastatic tumors (stage 4) when diagnosed. While children with neuroblastoma often respond to therapy and many are declared to be in a "remission" based on standard tests, many will still relapse. "Clearly, there is some remaining tumor in the body that we cannot detect with standard tests and physicians have a hard time predicting if a patient is likely to relapse," said Dr. Marachelian, who is Medical Director of the New Approaches to Neuroblastoma (NANT) consortium, headquartered at CHLA. The new assay, which was developed in the laboratories of Robert Seeger, MD, and Shahab Asgharzadeh, MD, at CHLA, tests for five different genes (CHGA, DCX, DDC, PHOX2B, and TH) that are specific to neuroblastoma.

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