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Archive - Jan 2, 2017

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.

Investigations into New Molecules That Could Potentially Treat Alzheimer's

This year, results have been published of two significant research studies about molecules that could potentially be used to treat Alzheimer's disease. The chief researcher in both studies was Dr. Yan Ivanenkov, the head of the Laboratory of Medical Chemistry and Bioinformatics at the Moscow Institute of Physics and Technology (MIPT). Papers on the two new molecules were published in Molecular Pharmaceutics and Current Alzheimer Research. Mark Veselov, another MIPT researcher, also participated in the second study. Both papers cover the study of neuroprotectors - antagonists to the 5-HT6R receptor. The latest research confirms that this target has a high therapeutic potential in the treatment of Alzheimer's disease. Preclinical studies on lab animals have shown that the two studied compounds have a high selectivity. Alzheimer's is one of the most widespread diseases in elderly people. People over the age of 60 are at the greatest risk of developing the disease, but it can also occur at a younger age. Patients suffer from loss of memory and cognitive functions; they become socially detached and lose their independence, and the body can no longer function properly, which inevitably leads to death. According to medical statistics, Alzheimer's is the cause of two out of every three cases of dementia in the elderly and it is a huge economic problem in developed countries. Scientists have not yet succeeded in finding an effective cure for Alzheimer's. Despite the fact that we know much about how the disease develops, we cannot say that we are even close to a solution. Pharmaceutical studies are still being conducted in order to be able to reduce the symptoms of the disease. In the first paper, specialists Alexander Ivashenko and Yan Lavrovsky from Alla Chem LLC, Avineuro Pharmaceuticals Inc., and R-Pharm Overseas Inc.