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July 6th, 2019

Triplet-Targeted Therapy Improves Survival for Patients with Advanced Colorectal Cancer and BRAF Mutations; Phase III Trial Results May Change Standard of Care for Up to 15% of Colorectal Cancer Patients

The three-drug combination of encorafenib, binimetinib, and cetuximab significantly improved overall survival (OS) in patients with BRAF-mutated metastatic colorectal cancer (mCRC), according to results of the BEACON CRC Phase III clinical trial led by researchers at The University of Texas (UT) MD Anderson Cancer Center. The treatment combination resulted in a median OS of 9 months for the combination therapy compared to 5.4 months for current standard-of-care treatment. Objective response rate (ORR) for the triplet-targeted therapy was 26 percent compared to just two percent for standard therapy. BEACON CRC is the first and only Phase III trial designed to test BRAF/MEK combination targeted therapies in patients with mCRC and the BRAF V600E mutation. BRAF mutations are estimated to occur in up to 15 percent of patients with mCRC, with V600E being the most common BRAF mutation and representing a poor prognosis for these patients. The trial results was reported on July 6at the European Society for Medical Oncology (ESMO) World Congress on Gastrointestinal Cancer 2019 (https://www.esmo.org/Conferences/ESMO-World-GI-2019) in Barcelona, Spain, by principal investigator Scott Kopetz, MD, Associate Professor of Gastrointestinal Medical Oncology at MD Anderson. The title of the report abstract is BEACON CRC: a randomized, 3-Arm, phase 3 study of encorafenib and cetuximab with or without binimetinib vs. choice of either irinotecan or FOLFIRI plus cetuximab in BRAF V600E–mutant metastatic colorectal cancer. "This study builds on a decade of research into the tumor biology of BRAF-mutated colorectal cancer, and reflects a rationale combination to address the vulnerabilities unique to this tumor," said Dr. Kopetz.

Strain of Oncolytic Common Cold Virus (Coxsackievirus A21) Could Revolutionize Treatment of Bladder Cancer

A strain of the common cold virus has been found to potentially target, infect, and destroy cancer cells in patients with bladder cancer, a new study published online on July 4, 2019 in Clinical Cancer Research reports. No trace of the cancer was found in one patient following treatment with the virus. In the majority of the other 14 treated patients, evidence of cancer cell death was observed. The title of the article is “Viral Targeting of Non-Muscle Invasive Bladder Cancer and Priming of Anti-Tumour Immunity Following Intravesical Coxsackievirus A21.” Researchers from the University of Surrey and Royal Surrey County Hospital investigated the safety and tolerability of exposure to the oncolytic (“cancer-killing”) virus coxsackievirus (CVA21), a naturally occurring strain of the common cold virus, in fifteen patients with non-muscle invasive bladder cancer (NMIBC). NMIBC is found in the tissue of the inner surface of the bladder and is the tenth most common cancer in the UK with approximately 10,000 people each year diagnosed with the illness. Current treatments for this cancer are problematic. Transurethral resection, an invasive procedure that removes all visible lesions, has a high tumor recurrence rate ranging from 50 per cent to 70 per cent as well as a high tumor progression rate between 10 per cent and 20 per cent over a period of two to five years. Another common course of treatment, immunotherapy with Bacille Calmette-Guerin (BCG), a live bacterium used to treat bladder cancer, has been found to have serious side effects in one third of NMIBC patients, while one third do not respond to the treatment at all. During this pioneering study, fifteen NMIBC patients, one week prior to pre-scheduled surgery to remove their tumors, received CVA21 via a catheter in the bladder.

July 4th

Tiny Molecular Change Reverses Prediabetes in Obese Mice; Remarkable Results Point to Potential Diabetes Drug Target and Highlight Possible Role for Ceramides in Sensing Nutrition

A small chemical change -- shifting the position of two hydrogen atoms -- makes the difference between mice that are healthy and mice with insulin resistance and fatty liver, major risk factors for diabetes and heart disease. Making the change prevented the onset of these symptoms in mice fed a high-fat diet and reversed prediabetes in obese mice. The scientists changed the trajectory of metabolic disease by deactivating an enzyme called dihydroceramide desaturase 1 (DES1). Doing so stopped the enzyme from removing the final hydrogens from a fatty lipid called ceramide, having an effect of lowering the total amount of ceramides in the body. The finding highlights a role for ceramides in metabolic health and pinpoints DES1 as a "druggable" target that could be used to develop new therapies for metabolic disorders such as prediabetes, diabetes, and heart disease -- that affect the health of hundreds of millions of Americans. Scientists at University of Utah Health and Merck Research Laboratories led the research, published online in Science on July 4, 2019. The article is titled “Targeting a Ceramide Double Bond Improves Insulin Resistance and Hepatic Steatosis.” "We have identified a potential therapeutic strategy that is remarkably effective, and underscores how complex biological systems can be deeply affected by a subtle change in chemistry," says Scott Summers (at right in photo), PhD, Chair of Nutrition and Integrative Physiology at U of Utah Health, who was co-senior author on the study with David Kelley, MD, formerly of Merck Research Laboratories. "Our work shows that ceramides have an influential role in metabolic health," says Dr. Summers. "We're thinking of ceramides as the next cholesterol." This isn't the first time that Dr.

Scientists Apply Bacterial Homing Capability to Enable Stem Cells to Home to Heart Tissue; Approach Offers “Enormous Potential” for Millions Suffering from Heart Disease Around the Globe

In a world first, scientists have found a new way to direct stem cells to heart tissue. The findings, led by researchers at the University of Bristol in the UK and published recently in Chemical Science, could radically improve the treatment for cardiovascular disease, which causes more than a quarter of all deaths in the UK. The open-access article is titled “Designer Artificial Membrane Binding Proteins to Direct Stem Cells to the Myocardium.” To date, trials using stem cells, which are taken and grown from the patient or donor and injected into the patient's heart to regenerate damaged tissue, have produced promising results. However, while these next-generation cell therapies are on the horizon, significant challenges associated with the distribution of the stem cells have remained. High blood flow in the heart combined with various “tissue sinks” that circulating cells come into contact with, means the majority of the stem cells end up in the lungs and spleen. Now, researchers from Bristol's School of Cellular and Molecular Medicine have found a way to overcome this by modifying stem cells with a special protein so the stem cells “home” to heart tissue. Dr. Adam Perriman, the study's lead author, Associate Professor in Biomaterials, UKRI Future Leaders Fellow and founder of the cell therapy technology company CytoSeek (https://www.cytoseek.uk/), explained: "With regenerative cell therapies, where you are trying to treat someone after a heart attack, the cells rarely go to where you want them to go. Our aim is to use this technology to re-engineer the membrane of cells, so that when they're injected, they'll home to specific tissues of our choice.”

June 29th

New, Low-Cost OCT Retinal Scanner Could Help Prevent Blindness Worldwide; Duke-Led Effort Creates Portable, Much Cheaper Device Nearly As Accurate As Current Very Costly Standard-of-Care OCT Instruments

Biomedical engineers at Duke University in North Carolina have developed a low-cost, portable optical coherence tomography (OCT) scanner that promises to bring the vision-saving technology to underserved regions throughout the United States and abroad. Thanks to a redesigned, 3D-printed spectrometer, the scanner is 15 times lighter and smaller than current commercial systems (image shows example of a typically bulky current commercial system) and is made from parts costing less than a tenth the retail price of commercial systems -- all without sacrificing imaging quality. In its first clinical trial, the new OCT scanner produced images of 120 retinas that were 95 percent as sharp as those taken by current commercial systems, which was sufficient for accurate clinical diagnosis. The results were published online on June 28, 2019 in Translational Vision Science & Technology, an ARVO journal. The open-access article is titled “First Clinical Application of Low-Cost OCT." In use since the 1990s, OCT imaging has become the standard of care for the diagnosis of many retinal diseases, including macular degeneration and diabetic retinopathy, as well as for glaucoma. However, OCT is rarely included as part of a standard screening exam because machines can cost more than $100,000 -- meaning that usually only larger eye centers have them. "Once you have lost vision, it's very difficult to get it back, so the key to preventing blindness is early detection," said Adam Wax, PhD, Professor of Biomedical Engineering at Duke. "Our goal is to make OCT drastically less expensive so more clinics can afford the devices, especially in global health settings." OCT is the optical analogue of ultrasound, which works by sending sound waves into tissues and measuring how long the waves take to come back.

Archaeological Mystery Solved with Modern Genetics -- Y Chromosomes Reveal Population Boom and Bust in Ancient Japan

Researchers at the University of Tokyo conducted a census of the Japanese population of approximately 2,500 years ago using the Y chromosomes of men living on the main islands of modern-day Japan. This is the first time that analysis of modern genomes has estimated the size of an ancient human population before they were met by a separate ancient population. The research was published online on June 17, 2019 in Scientific Reports. The open-access article is titled “Analysis of Whole Y-Chromosome Sequences Reveals the Japanese Population History in the Jomon Period.” "Evidence at archaeological dig sites has been used to estimate the size of ancient human populations, but the difficulty and unpredictability of finding those sites is a big limitation. Now we have a method that uses a large amount of modern data," said Associate Professor Jun Ohashi, PhD, an expert in human evolutionary genetics and leader of the research team that performed the analysis. The current theory on human migrations into Japan is that the original inhabitants, the Jomon people, were met about 2,500 years ago by a separate group coming mainly from the Korean Peninsula, the Yayoi people. Archaeologists have identified fewer Jomon sites from the Late Jomon Period, the era immediately before the Yayoi arrival. Global temperatures and sea levels dropped during that period, which could have made life more difficult for the hunter-gatherer Jomon people. When the Yayoi people arrived, they brought wet rice farming to Japan, which would have led to a more stable food supply for the remaining Jomon people living with the new Yayoi migrants. The lesser amount of archaeological remains from the Late Jomon Period could be evidence of an actual population decline, or just that the archaeological dig sites have not yet been found. Dr.

June 21st

Cancer-Sniffing Dogs 97% Accurate in Identifying Lung Cancer in Blood Serum of Patients Versus Controls

Three beagles successfully showed they are capable of identifying lung cancer by scent, a first step in identifying specific biomarkers for the disease. Researchers say the dogs' abilities may lead to development of effective, safe, and inexpensive means for mass cancer screening. After eight weeks of training, the beagles--chosen for their superior olfactory receptor genes--were able to distinguish between blood serum samples taken from patients with malignant lung cancer and healthy controls with 97% accuracy. The double-blind study was published online on June 17, 2019 in The Journal of the American Osteopathic Association. The open-access article is titled “Accuracy of Canine Scent Detection of Non–Small Cell Lung Cancer in Blood Serum.” "We're using the dogs to sort through the layers of scent until we identify the tell-tale biomarkers," says Thomas Quinn, DO, Professor at Lake Erie College of Osteopathic Medicine and lead author on this study. "There is still a great deal of work ahead, but we're making good progress." The dogs were led into a room with blood serum samples at nose level. Some samples came from patients with non-small cell lung cancer; others were drawn from healthy controls. After thoroughly sniffing a sample, the dogs sat down to indicate a positive finding for cancer or moved on if none was detected. Dr. Quinn and his team are nearing completion of a second iteration of the study. This time the dogs are working to identify lung, breast, and colorectal cancer using samples of patients' breath, collected by the patient breathing into a face mask. Researchers say findings suggest the dogs are as effective detecting cancer using this method.

June 17th

Schizophrenia: Adolescence Is Game-Changer--Researchers Discover That Development of Hippocampus Is Severely Impacted in Adolescence at Time of First Psychotic Symptoms

Schizophrenia causes hallucinations and memory or cognition problems in those who have it. This psychiatric illness affects 0.5% of the general population, and it can be related to genetic abnormalities of chromosome 22, known as 22q11 deletion syndrome. However, not everyone who has this deletion syndrome necessarily develops psychotic symptoms. So, what triggers the illness? Researchers at the University of Geneva (UNIGE), Switzerland, have provided an initial answer after observing and analyzing several years of patients with deletion syndrome. The scientists found that the size of the hippocampus (image), the area of the brain responsible for memory and emotions, was smaller than normal but followed the same developmental curve as in healthy subjects. Yet, when the first psychotic symptoms appear - generally in adolescence - the hippocampus atrophies dramatically. The new results, which were reported online on June 4, 2019 in Molecular Psychiatry, open up new avenues for understanding the causes of schizophrenia. The article is titled “Positive Psychotic Symptoms Are Associated with Divergent Developmental Trajectories of Hippocampal Volume During Late Adolescence in Patients With 22q11ds.” 22q11 deletion syndrome is a neurogenetic disorder that targets chromosome 22. Thirty percent of people affected by the syndrome end up developing psychotic symptoms specific to schizophrenia, such as auditory hallucinations, memory problems, disorders affecting their perception of reality, and difficulties in social interactions characterized by strong paranoia.

Large Elk Populations in Yellowstone Elk Have Means to Adapt Their Migration Times to Changing Climate Cues; Migratory Shifts May Have Unknown Ripple Effects Throughout the Region

Every spring, tens of thousands of elk follow a wave of green growth up onto the high plateaus in and around Yellowstone and Grand Teton national parks, where they spend the summer calving and fattening on fresh grass. And every fall, the massive herds migrate back down into the surrounding valleys and plains, where lower elevations provide respite from harsh winters. These migratory elk rely primarily on environmental cues, including a retreating snowline and the greening grasses of spring, to decide when to make these yearly journeys, shows a new study led by University of California (UC), Berkeley, researchers. The study combined GPS tracking data from more than 400 animals in nine major Yellowstone elk populations with satellite imagery to create a comprehensive model of what drives these animals to move. "We found that the immediate environment is a very effective predictor of when migration occurs," said Gregory Rickbeil, PhD, who conducted the analysis as a postdoctoral researcher in Dr. Arthur Middleton's lab at UC Berkeley. This is in contrast with some other species, such as migratory birds, which rely on changing day length to decide when to move, Dr. Rickbeil pointed out. The results, published in the July 2019 issue of Global Change Biology, suggest that, as climate change reshapes the weather and environment of the park, elk should have the means to adjust their migratory patterns to match the new conditions.

June 16th

Non-Invasive Prenatal Diagnosis for Fetal Sickle Cell Disease (SCD) Moves a Step Closer; Researchers Develop Test to Detect SCD by Next-Generation Sequencing of Cell-Free Fetal DNA in Mother’s Bloodstream

Sickle cell disease (SCD) is a form of anemia that is inherited when both parents are carriers of a mutation in the hemoglobin gene. Currently, this disease can only be diagnosed in pregnancy by carrying out an invasive test that has a small risk of miscarriage and is therefore sometimes declined by parents. Now, researchers from Guy's and St Thomas' NHS Foundation Trust and Viapath Analytics, London, UK, in collaboration with non-invasive healthcare company Nonacus Ltd., Birmingham, UK, have developed a non-invasive prenatal test for the disease, and this test was described on June 16, 2019 at the annual conference of the European Society of Human Genetics (ESHG) (https://2019.eshg.org/) (June 15-18). The abstract (C08.5) of this presentation is titled “Non-Invasive Prenatal Diagnosis of Sickle Cell Disease by Next-Generation Sequencing of Cell-Free DNA.” Julia van Campen, PhD, research scientist at Guy's and St Thomas', explains: “We have developed a method of testing for SCD using cell-free fetal DNA -- DNA from the fetus that circulates in the maternal bloodstream. Although cell-free fetal DNA testing is already available for some disorders, technical difficulties have hampered the development of such a test for SCD, despite it being one of the most commonly requested prenatal tests in the UK.” In couples that are at risk of having a baby with SCD, each partner carries a mutation in the hemoglobin gene, which means that any fetus has a one in four chance of inheriting both mutations and therefore being affected by SCD. Non-invasive prenatal diagnosis (NIPD) of conditions that are inherited in this way is difficult. "The development of a non-invasive prenatal assay for sickle cell disease has been attempted before and, until now, has not been successful, "says Dr.