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Archive - 2017

January 4th

Vaccine Shows Promising Results for Early-Stage Breast Cancer Patients: HER2-Targeted Dendritic Cell Vaccines Stimulate Immune Responses and Regression of HER2-Expressing Early-Stage Breast Tumors

Deregulation and inhibition of the immune system contributes to cancer development. Many therapeutic strategies aim to re-stimulate the immune system to recognize cancer cells and target them for destruction. Researchers from the Moffitt Cancer Center in Florida report that a dendritic cell vaccine that targets the HER2 protein on breast cancer cells is safe and effectively stimulates the immune system leading to regression of early-stage breast cancer. The HER2 protein is over-expressed in 20-25% of all breast cancer tumors and is associated with aggressive disease and poor prognosis. Researchers have previously shown that immune cells are less able to recognize and target cancer cells that express HER2 as breast cancer progresses into a more advanced and invasive stage. This suggests that strategies that can re-stimulate the immune system to recognize and target HER2 early during cancer development may be effective treatment options. The researchers previously developed a vaccine that helps the immune system recognize the HER2 protein on breast cancer cells. Their approach involves creating the vaccine from immune cells called dendritic cells that are harvested from each individual patient to create a personalized vaccine. In order to determine if the HER2-dendritic cell vaccine is safe and effective, the researchers performed a clinical trial in 54 women who have HER2-expressing early-stage breast cancer. The dendritic cell vaccines were prepared by isolating dendritic cells from each patients' blood and exposing them to fragments of the HER2 protein. Patients were injected with a dose of their personal dendritic cell vaccine once a week for six weeks into either a lymph node, the breast tumor, or into both sites.

Reduced Blood Flow in Broca’s Area of Brain Associated with Stuttering

A study led by researchers at Children's Hospital Los Angeles (CHLA) demonstrates what lead investigator Bradley Peterson, M.D., calls "a critical mass of evidence" of a common underlying lifelong vulnerability in both children and adults who stutter. The scientists discovered that regional cerebral blood flow is reduced in the Broca's area - the region in the frontal lobe of the brain linked to speech production - in persons who stutter. More severe stuttering is associated with even greater reductions in blood flow to this region. In addition, a greater abnormality of cerebral blood flow in the posterior language loop, associated with processing words that we hear, correlates with more severe stuttering. This finding suggests that a common pathophysiology throughout the neural "language" loop that connects the frontal and posterior temporal lobe likely contributes to stuttering severity. Dr. Peterson, who is Director of the Institute for the Developing Mind at CHLA and a professor of the Keck School of Medicine at the University of Southern California, says that such a study of resting blood flow, or perfusion, has never before been conducted in persons who stutter. His team also recently published a study using proton magnetic resonance spectroscopy to look at brain regions in both adults and children who stutter. Those findings demonstrated links between stuttering and changes in the brain circuits that control speech production, as well as those supporting attention and emotion. The present blood flow study adds significantly to the findings from that prior study and furthermore suggests that disturbances in the speech processing areas of the brain are likely of central importance as a cause of stuttering. According to Dr.

Promising New Small Molecule Stops Spread of Melanoma by Up to 90 Percent

Michigan State University (MSU) researchers have discovered that a chemical compound, and potential new drug, reduces the spread of melanoma cells by up to 90 percent. The man-made, small-molecule drug compound goes after a gene's ability to produce RNA molecules and certain proteins in melanoma tumors. This gene activity in melanoma causes the disease to spread but the compound can shut it down. Up until now, few other compounds of this kind have been able to accomplish this. "It's been a challenge developing small-molecule drugs that can block this gene activity that works as a signaling mechanism known to be important in melanoma progression," said Richard Neubig (photo), M.D., Ph.D., Pharmacology Professor, Chairperson of Pharmacology/Toxicology at MSU, and co-author of the study. "Our chemical compound is actually the same one that we've been working on to potentially treat the disease scleroderma, which now we've found works effectively on this type of cancer." Scleroderma is a rare and often fatal autoimmune disease that causes the hardening of skin tissue, as well as organs such as the lungs, heart and kidneys. The same mechanisms that produce fibrosis, or skin thickening, in scleroderma also contribute to the spread of cancer. Small-molecule drugs make up over 90 percent of the drugs on the market today and Dr. Neubig's co-author Dr. Kate Appleton, a postdoctoral student, said the findings are an early discovery that could be highly effective in battling the deadly skin cancer. It's estimated about 10,000 people die each year from the disease. The new findings have been published in the January 2017 issue of Molecular Cancer Therapeutics.

January 3rd

Modestly Increased Consumption of Zinc Can Have Profound Positive Effect on Cellular Health

A new study by researchers from the UCSF Benioff Children's Hospital Oakland Research Institute (CHORI) shows that a modest 4 milligrams of extra zinc a day in the diet can have a profound, positive impact on cellular health that helps fight infections and diseases. This amount of zinc is equivalent to what biofortified crops like zinc rice and zinc wheat can add to the diet of vulnerable, nutrient deficient populations. The study, published in the American Journal of Clinical Nutrition, was led by CHORI Senior Scientist Janet King, PhD. Dr. King and her team are the first to show that a modest increase in dietary zinc reduces oxidative stress and damage to DNA. "We were pleasantly surprised to see that just a small increase in dietary zinc can have such a significant impact on how metabolism is carried out throughout the body," says Dr. King. "These results present a new strategy for measuring the impact of zinc on health and reinforce the evidence that food-based interventions can improve micronutrient deficiencies worldwide." The open-access AJCN article is titled “A Moderate Increase in Dietary Zinc Reduces DNA Strand Breaks in Leukocytes and Alters Plasma Proteins Without Changing Plasma Zinc Concentrations.” Zinc is ubiquitous in our body and facilitates many functions that are essential for preserving life. It plays a vital role in maintaining optimal childhood growth, and in ensuring a healthy immune system. Zinc also helps limit inflammation and oxidative stress in our body, which are associated with the onset of chronic cardiovascular diseases and cancers. Around much of the world, many households eat polished white rice or highly refined wheat or maize flours, which provide energy but do not provide enough essential micronutrients such as zinc.

Researchers Uncover Mechanism for Cancer-Killing Properties of Indian Pepper Plant; Work Is “Spectacular Demonstration of the Power of X-Ray Crystallography”

University of Texas (UT) Southwestern Medical Center scientists have uncovered the chemical process behind anti-cancer properties of a spicy Indian pepper plant called the long pepper, for which suspicions of medicinal properties date back thousands of years. The secret lies in a chemical called piperlongumine (PL), which has shown activity against many cancers including prostate, breast, lung, colon, lymphoma, leukemia, primary brain tumors, and gastric cancer. Using x-ray crystallography, UTSMC researchers were able to create molecular structures that show how the chemical is transformed after being ingested. PL is converted to hPL (hydrolyzed PL), an active drug that silences a gene called GSTP1. The GSTP1 gene produces a detoxification enzyme that is often overly abundant in tumors. “We are hopeful that our structure will enable additional drug development efforts to improve the potency of PL for use in a wide range of cancer therapies,” said Kenneth Westover (photo), M.D., Ph.D., Assistant Professor of Biochemistry and Radiation Oncology. “This research is a spectacular demonstration of the power of x-ray crystallography.” The long pepper, a plant native to India, is found in southern India and southeast Asia. Although rare in European fare, it is commonly found in Indian stores and used as a spice or seasoning in stews and other dishes. It dates back thousands of years in the Indian subcontinent tied to Ayurveda, one of the world’s oldest medical systems, and was referred to by Hippocrates, the ancient Greek physician known as the father of medicine.

Highest-Sensitivity Liquid Biopsy Test for EGFR-T790M Resistance Mutation in Lung Cancer Presented by Exosome Diagnostics

Exosome Diagnostics, Inc., has recently presented data that sets a new standard for EGFR-T790M resistance mutation detection in lung cancer, with the highest sensitivity reported to date. This test is being developed to improve care and outcomes for the large population of patients who can benefit from second-line EGFR tyrosine kinase inhibitor (TKI) therapy but are missed with currently available tissue and liquid biopsy tests. Clinical validation data from a cohort of 160 patients, the largest of its kind in this patient population, was presented in plenary session during the recent AACR-EORTC-NCI meeting in Munich, Germany. ExoDx® Lung(T790M) has been optimally designed for ExosomeDx’s high-throughput biomarker testing platform that is being deployed in 2017. This news was reported in a press release from Exosome Diagnostics issued on December 21, 2016. Twenty percent of non-small cell lung cancer (NSCLC) patients test positive for an EGFR driver mutation (approximately 45,000 patients in the U.S. alone) and receive EGFR TKI therapy. Unfortunately, most will develop a resistance to EGFR TKI therapy. Tissue biopsies are the current standard for identifying T790M resistance. If a patient tests positive, they are eligible for treatment with a second-line EGFR TKI therapy. Unfortunately, a tissue biopsy is not always a viable option for a large percentage of these patients. Non-invasive liquid biopsies have emerged as a viable alternative for patients unable to have a tissue biopsy procedure. Clinical studies have demonstrated that the FDA-approved cobas® test for liquid biopsy, only identifies 59% of patients who will respond to a second-line EGFR TKI therapy. This is a direct result of lack of sensitivity and inability to test challenging intrathoracic disease.

New Imaging Technique Enables Scientists to View Individual Retinal Ganglion Cells (RGCs); Advance May Allow Earlier Diagnosis and Treatment of Glaucoma, Other Eye Diseases

Researchers at the University of Rochester Medical Center in New York have developed a new imaging technique that could revolutionize how eye health and disease are assessed. The group is first to be able to make out individual cells at the back of the eye that are implicated in vision loss in diseases like glaucoma. The researchers hope their new technique could prevent vision loss via earlier diagnosis and treatment for these diseases. In a study highlighted in PNAS, Ethan A. Rossi, Ph.D., now Assistant Professor of Ophthalmology at the University of Pittsburgh School of Medicine, describes a new method to non-invasively image the human retina, a layer of cells at the back of the eye that are essential for vision. The group, led by David Williams, Ph.D., Dean for Research in Arts, Sciences, and Engineering and the William G. Allyn Chair for Medical Optics at the University of Rochester, was able to distinguish individual retinal ganglion cells (RGCs), which bear most of the responsibility of relaying visual information to the brain. There has been a longstanding interest in imaging RGCs because their death causes vision loss in glaucoma, the second leading cause of acquired blindness worldwide. Despite great efforts, no one has successfully captured images of individual RGCs, in part because they are nearly perfectly transparent. Instead of imaging RGCs directly, glaucoma is currently diagnosed by assessing the thickness of the nerve fibers projecting from the RGCs to the brain. However, by the time retinal nerve fiber thickness has changed detectably, a patient may have lost 100,000 RGCs or more. "You only have 1.2 million RGCs in the whole eye, so a loss of 100,000 is significant," said Dr. Williams. "The sooner we can catch the loss, the better our chances of halting disease and preventing vision loss."

January 2nd

Nanohyperthermia Softens Tumors to Improve Treatment

The mechanical resistance of tumors and collateral damage of standard treatments often hinder efforts to defeat cancers. However, a team of researchers from the CNRS, the French National Institute of Health and Medical Research (INSERM), Paris Descartes University, and Paris Diderot University has successfully softened malignant tumors by heating them. This method, called nanohyperthermia, makes the tumors more vulnerable to therapeutic agents. First, carbon nanotubes (CNTs) are injected directly into the tumors. Then, laser irradiation activates the nanotubes, while the surrounding healthy tissue remains intact. The team’s work was published online on January 1, 2017 in Theranostics. The open-access article is titled “Tumor Stiffening, a Key Determinant of Tumor Progression, Is Reversed by Nanomaterial-Induced Photothermal Therapy.” Researchers are increasingly turning their attention to the mechanical factors affecting tumor development. Tumors stiffen due to the abnormal organization of the collagen fibers and extracellular matrix (ECM) that hold cells from the same tissue together. In addition to being a marker of malignancy, such stiffening may help cancer cells proliferate and metastasize. Furthermore, the ECM forms a physical barrier that limits tumor penetration by therapeutic agents. Various treatments attempt to disrupt the structure of tumors but are double-edged swords: as ECM is common to tumors and healthy organs, degrading it does as much harm as good. Yet the research team found a way around this problem for mouse tumors. After being directly injected into the tumors, CNTs were activated with near-infrared light. The laser only acts on areas of CNT concentration, heating the CNTs up.

Special Issue of Biological Psychiatry Devoted to Dopamine Hypothesis of Schizophrenia

Biological Psychiatry presents a special issue (January 1, 2017), "The Dopamine Hypothesis of Schizophrenia,” dedicated to recent advances in understanding the role of dopamine signaling in schizophrenia. The issue, organized by Anissa Abi-Dargham, M.D., of Stony Brook University, New York, and a deputy editor of Biological Psychiatry, compiles seven reviews that summarize current knowledge and provide new insights. The dopamine hypothesis of schizophrenia has been revised numerous times since clinical observations first implicated the neurotransmitter decades ago, and dopamine alterations are some of the most well-established research findings in schizophrenia. "Unlike any other neurobiological hypothesis of the disease, the dopamine hypothesis has confirmatory evidence from in vivo studies in patients and from pharmacological therapies," Dr. Abi-Dargham said. Despite this, researchers have yet to fully understand when and how dopamine alterations arise in the brain, or their relationship with the diversity of symptoms in the disease. "This issue highlights the complexity of the findings in patients with the disorder, and raises the possibility that dopamine alterations can lead to a vast array of consequences on the circuitry, on learning and behavior, that can explain the vast array of symptom clusters," Dr. Abi-Dargham said. The body of work collated in the issue ranges from human studies to animal models. Neuroimaging, genetic, and molecular imaging studies have helped elucidate the regional differences of dopamine dysfunction throughout the brain, and detailed timing of dopamine alterations in relation to development, symptom onset, and other neurobiological alterations in the disease.

New “OptoDroplet” Tool Shines Light on Protein Condensation and Phase Transition in Living Cells

A tool that uses light to manipulate matter inside living cells is being used to help scientists understand how proteins assemble into different liquid and gel-like solid states, a key to understanding many critical cellular operations. Marvels of complexity, cells host many thousands of simultaneous chemical reactions. Some reactions happen inside specialized compartments, called organelles. Certain organelles, however, lack any membrane to wall themselves off from the rest of the matter floating within cells. These membrane-less organelles somehow persist as self-contained structures amidst a cellular sea of water, proteins, nucleic acids, and other molecules. Scientists at Princeton University have developed a new tool -- dubbed “optoDroplet” -- that offers unprecedented access to manipulating and understanding the chemistry that allows membrane-less organelles to function. "This optoDroplet tool is starting to allow us to dissect the rules of physics and chemistry that govern the self-assembly of membrane-less organelles," said Clifford Brangwynne, Ph.D., an Assistant Professor of Chemical and Biological Engineering at Princeton and senior author of a paper published online in Cell on December 29, 2016. "The basic mechanisms underlying this process are very poorly understood, and if we get a handle on it, there might be a hope for developing interventions and treatments for devastating diseases connected with protein aggregation, such as ALS." The Cell article is titled “Spatiotemporal Control of Intracellular Phase Transitions Using Light-Activated optoDroplets.” Previous research has demonstrated that membrane-less organelles assemble within the cell by a process known as a phase transition: examples of familiar phase transitions include water vapor condensing into dew droplets or liquid water freezing into solid ice.