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https://www.readbyqxmd.com/read/30326421/translating-the-anti-myeloma-activity-of-natural-killer-cells-into-clinical-application
#1
REVIEW
Cinzia Fionda, Helena Stabile, Rosa Molfetta, Alessandra Soriani, Giovanni Bernardini, Alessandra Zingoni, Angela Gismondi, Rossella Paolini, Marco Cippitelli, Angela Santoni
Natural Killer cells (NK) are innate effector cells with a critical role in immunosurveillance against different kinds of cancer cells, including Multiple Myeloma (MM). However, the number and/or function of these lymphocytes are strongly reduced during MM progression and in advanced clinical stages. A better understanding of the mechanisms controlling both MM and NK cell biology have greatly contributed to develop novel and combined therapeutic strategies in the treatment of this incurable hematologic malignancy...
October 10, 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/30326281/improving-diagnosis-and-case-management-of-patients-with-tuberculosis-a-review-of-gaps-needs-and-potential-solutions-in-accessing-laboratory-diagnostics
#2
Alfred Andama, Akos Somoskovi, Brinnon Mandel, David Bell, Cristina Gutierrez
Tuberculosis (TB) recently surpassed HIV/AIDS as the deadliest infectious disease. Despite some advancements in technologies and programs, TB remains a global health epidemic that, without significant gains in better diagnostic and management, will not abate. This review describes the molecular diagnostic gaps, needs, and potential solutions for improving access to diagnosis and management of patients with drug susceptible and drug resistant TB. The ultimate goal is to improve laboratory diagnostics and better individualized managementof detected TB, and make an important contribution toward eliminating this global epidemic...
October 13, 2018: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/30326272/engineering-a-bispecific-antibody-with-a-common-light-chain-identification-and-optimization-of-an-anti-cd3-epsilon-and-anti-gpc3-bispecific-antibody-ery974
#3
Hirotake Shiraiwa, Atsushi Narita, Mika Kamata-Sakurai, Takahiro Ishiguro, Yuji Sano, Naoka Hironiwa, Takashi Tsushima, Hiroaki Segawa, Toshiaki Tsunenari, Yosuke Ikeda, Yoko Kayukawa, Mizuho Noguchi, Tetsuya Wakabayashi, Akihisa Sakamoto, Hiroko Konishi, Taichi Kuramochi, Mika Endo, Kunihiro Hattori, Junichi Nezu, Tomoyuki Igawa
The antibody drug market is rapidly expanding, and various antibody engineering technologies are being developed to create antibodies that can provide better benefit to patients. Although bispecific antibody drugs have been researched for more than 30 years, currently only a limited number of bispecific antibodies have achieved regulatory approval. Of the few successful examples of industrially manufacturing a bispecific antibody, the "common light chain format" is an elegant technology that simplifies the purification of a whole IgG-type bispecific antibody...
October 13, 2018: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/30325956/peptidoglycan-potentiates-the-membrane-disrupting-effect-of-the-carboxyamidated-form-of-dms-da6-a-gram-positive-selective-antimicrobial-peptide-isolated-from-pachymedusa-dacnicolor-skin
#4
Sébastien Cardon, Emmanuelle Sachon, Ludovic Carlier, Thierry Drujon, Astrid Walrant, Estefanía Alemán-Navarro, Verónica Martínez-Osorio, Dominique Guianvarc'h, Sandrine Sagan, Yannick Fleury, Rodrigue Marquant, Christophe Piesse, Yvonne Rosenstein, Constance Auvynet, Claire Lacombe
The occurrence of nosocomial infections has been on the rise for the past twenty years. Notably, infections caused by the Gram-positive bacteria Staphylococcus aureus represent a major clinical problem, as an increase in antibiotic multi-resistant strains has accompanied this rise. There is thus a crucial need to find and characterize new antibiotics against Gram-positive bacteria, and against antibiotic-resistant strains in general. We identified a new dermaseptin, DMS-DA6, produced by the skin of the Mexican frog Pachymedusa dacnicolor, with specific antibacterial activity against Gram-positive bacteria...
2018: PloS One
https://www.readbyqxmd.com/read/30325856/accelerating-the-drug-delivery-pipeline-for-acute-and-chronic-pancreatitis-summary-of-the-working-group-on-drug-development-and-trials-in-acute-pancreatitis-at-the-national-institute-of-diabetes-and-digestive-and-kidney-diseases-workshop
#5
Maisam Abu-El-Haija, Anna S Gukovskaya, Dana K Andersen, Timothy B Gardner, Peter Hegyi, Stephen J Pandol, Georgios I Papachristou, Ashok K Saluja, Vikesh K Singh, Aliye Uc, Bechien U Wu
A workshop was sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases to focus on research gaps and opportunities on drug development for pancreatitis. This conference was held on July 25, 2018, and structured into 3 working groups (WG): acute pancreatitis (AP) WG, recurrent AP WG, and chronic pancreatitis WG. This article reports the outcome of the work accomplished by the AP WG to provide the natural history, epidemiology, and current management of AP; inform about the role of preclinical models in therapy selection; and discuss clinical trial designs with clinical and patient-reported outcomes to test new therapies...
November 2018: Pancreas
https://www.readbyqxmd.com/read/30325206/natural-products-and-their-derivatives-as-cyclooxygenase-2-inhibitors
#6
Priyanka Chandel, Ravindra K Rawal, Rupinder Kaur
From ancient times, natural products have been continuously used as therapeutic agents in the treatment of various ailments. Many drugs from the natural origin are available in the market as potent medicines. Over expression of cyclooxygenase-2 (COX-2) enzyme is associated with various physical disorders like various types of inflammations associated with cardiovascular diseases or malignancies. The COX-2 inhibitory activity of many active constituents derived from plants is well established in the literature...
October 16, 2018: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/30325031/using-open-tubular-capillary-electrochromatography-with-part-coating-column-for-binding-constants-determination-of-%C3%AE-2-adrenergic-receptor-with-seven-drugs
#7
Chunye Liu, Xuejiao Zhang, Hui Jing, Jingshui Zhang, Yanqing Miao, Xifeng Zhai, Songyi Chen
An open-tubular capillary electrochromatography (CEC) method has been developed for the determination of binding constants between β2 -adrenergic receptor (β2 -AR) and 7 drugs. β2 -AR was oriented immobilized onto one part of inner surface of capillary via microwave-assisted technical synthesis. According to the linear relationship between coating length and the apparent mobility of analyte, the binding constant (Kb ) can be obtained by related theories and equations. The order of Kb values between drugs such as adrenaline hydrochloride, norepinephrine bitartrate and propranolol hydrochloride with β2 -AR is well consistent with that reported in the literature...
October 16, 2018: Electrophoresis
https://www.readbyqxmd.com/read/30324916/itraconazole-and-thiophanate-methyl-fail-to-clear-tadpoles-naturally-infected-with-the-hypervirulent-lineage-of-batrachochytrium-dendrobatidis
#8
Andrés Fernández-Loras, Bárbara Martín-Beyer, Trenton W J Garner, Jaime Bosch
The emerging infectious disease chytridiomycosis, caused by the fungus Batrachochytrium dendrobatidis, is a major driver pushing many amphibian species to the brink of extinction. Substantial efforts to develop effective protocols that use antifungal drugs have had notable success. Here, we used the antifungal agents itraconazole and thiophanate-methyl, singly and in combination, in an attempt to treat common midwife toad Alytes obstetricans larvae naturally infected with the globalized hypervirulent lineage of B...
October 16, 2018: Diseases of Aquatic Organisms
https://www.readbyqxmd.com/read/30324898/3d-qsar-docking-molecular-dynamics-simulations-and-mm-gbsa-studies-of-extended-side-chain-of-the-antitubercular-drug-6s-2-nitro-6-4-trifluoromethoxy-benzyl-oxy-6-7-dihydro-5h-imidazo-2-1-b-1-3-oxazine
#9
Hemchandra Keshav Chaudhari, Akshta R Pahelkar
PA-824 analogues have been proposed on a promising approach for treating MDR/XDR tuberculosis. In order to understand the structural requirement of reported extended side chain analogues were studied to get insight into their structural requirements responsible for high affinity as a ligand-based pharmacophore, 3D-QSAR model have been developed. A structurally diverse set of 84 molecules was divided into 17 molecules of test set and rest of the 67 molecules of training set. The pharmacophore hypothesis yielded a statistically significant 3D-QSAR model, with a correlation coefficient of R2 = 0...
October 15, 2018: Infectious Disorders Drug Targets
https://www.readbyqxmd.com/read/30324817/novel-treatments-to-tackle-myelofibrosis
#10
Eran Zimran, Alla Keyzner, Camelia Iancu-Rubin, Ronald Hoffman, Marina Kremyanskaya
Despite the dramatic progress made in the treatment of patients with myelofibrosis since the introduction of the JAK1/2 inhibitor ruxolitinib, a therapeutic option that can modify the natural history of the disease and prevent evolution to blast-phase is still lacking. Recent investigational treatments including immunomodulatory drugs and histone deacetylase inhibitors benefit some patients but these effects have proven modest at best. Several novel agents do show promising activity in preclinical studies and early-phase clinical trials...
October 16, 2018: Expert Review of Hematology
https://www.readbyqxmd.com/read/30324629/mitochondria-mediated-apoptosis-was-induced-by-oleuropein-in-h1299-cells-involving-activation-of-p38-map-kinase
#11
Wang Wang, Jibing Wu, Qingyan Zhang, Xue Li, Xixi Zhu, Qiuying Wang, Shasha Cao, Linfang Du
Lung cancer is the main health threat in the world. Recently, oleuropein has been reported to have potent antioxidant and anticancer activities. However, the antitumor effects of oleuropein on H1299 cells are not well understood. Therefore, the purpose of this paper is tantamount to explore the effects of oleuropein on H1299 cells and its underlying mechanism that may be involved. Oleuropein treatment in H1299 cells resulted in cell cycle distribution at G2 /M arrest and apoptosis in a dose-dependent manner...
October 15, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/30324355/privacy-confidentiality-and-safety-considerations-for-conducting-geographic-momentary-assessment-studies-among-persons-who-use-drugs-and-men-who-have-sex-with-men
#12
Abby E Rudolph, April M Young, Jennifer R Havens
Geographic momentary assessments (GMA) collect real-time behavioral data in one's natural environment using a smartphone and could potentially increase the ecological validity of behavioral data. Several studies have evaluated the feasibility and acceptability of GMA among persons who use drugs (PWUD) and men who have sex with men (MSM), but fewer have discussed privacy, confidentiality, and safety concerns, particularly when illegal or stigmatized behavioral data were collected. This study explores perceptions regarding privacy, confidentiality, and safety of GMA research among PWUD and MSM recruited in three different settings (rural Appalachia, a mid-sized city in the South, and a mid-Atlantic city)...
October 15, 2018: Journal of Urban Health: Bulletin of the New York Academy of Medicine
https://www.readbyqxmd.com/read/30324224/risk-based-comparability-assessment-for-monoclonal-antibodies-during-drug-development-a-clinical-pharmacology-perspective
#13
Yanli Zhuang, Di Chen, Amarnath Sharma, Zhenhua Xu
Due to complexities in the structure, function, and manufacturing process of antibody-based therapeutic proteins, comparability assessment for supporting manufacturing changes can sometimes be a challenging task. Regulatory guidance recommends a hierarchical risk-based approach, starting with Chemistry, Manufacturing, and Controls (CMC) analytical characterizations, followed by non-clinical and/or clinical studies to ensure that any potential changes in quality attributes have no adverse impact on efficacy and safety of the product...
October 15, 2018: AAPS Journal
https://www.readbyqxmd.com/read/30323272/phosphoprotein-patterns-predict-trametinib-responsiveness-and-optimal-trametinib-sensitisation-strategies-in-melanoma
#14
Jan Rožanc, Theodore Sakellaropoulos, Asier Antoranz, Cristiano Guttà, Biswajit Podder, Vesna Vetma, Nicole Rufo, Patrizia Agostinis, Vaia Pliaka, Thomas Sauter, Dagmar Kulms, Markus Rehm, Leonidas G Alexopoulos
Malignant melanoma is a highly aggressive form of skin cancer responsible for the majority of skin cancer-related deaths. Recent insight into the heterogeneous nature of melanoma suggests more personalised treatments may be necessary to overcome drug resistance and improve patient care. To this end, reliable molecular signatures that can accurately predict treatment responsiveness need to be identified. In this study, we applied multiplex phosphoproteomic profiling across a panel of 24 melanoma cell lines with different disease-relevant mutations, to predict responsiveness to MEK inhibitor trametinib...
October 15, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/30323252/additivity-of-inhibitory-effects-in-multidrug-combinations
#15
D Russ, R Kishony
From natural ecology1-4 to clinical therapy5-8 , cells are often exposed to mixtures of multiple drugs. Two competing null models are used to predict the combined effect of drugs: response additivity (Bliss) and dosage additivity (Loewe)9-11 . Here, noting that these models diverge with increased number of drugs, we contrast their predictions with growth measurements of four phylogenetically distant microorganisms including Escherichia coli, Staphylococcus aureus, Enterococcus faecalis and Saccharomyces cerevisiae, under combinations of up to ten different drugs...
October 15, 2018: Nature Microbiology
https://www.readbyqxmd.com/read/30323025/controlled-infection-immunization-using-delayed-death-drug-treatment-elicits-protective-immune-responses-to-blood-stage-malaria-parasites
#16
Leanne M Low, Aloysious Ssemaganda, Xue Q Liu, Mei-Fong Ho, Victoria Ozberk, James Fink, Lana Sundac, Kylie Alcorn, Amy Morrison, Kevin O'Callaghan, John Gerrard, Danielle I Stanisic, Michael F Good
Naturally acquired immunity to malaria is robust and protective against all strains of the same species of Plasmodium. This develops as a result of repeated natural infection, taking several years to develop. Evidence suggests that apoptosis of immune lymphocytes due to uncontrolled parasite growth contributes to the slow acquisition of immunity. To hasten and augment the development of natural immunity, we studied controlled infection immunization (CII) using low dose exposure to different parasite species ( P...
October 15, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/30322601/reperfusion-changes-after-stroke-and-practical-approaches-for-neuroprotection
#17
REVIEW
Jae H Choi, John Pile-Spellman
Reperfusion is the first line of care in a growing number of eligible acute ischemic stroke patients. Early reperfusion with thrombolytic drugs and endovascular mechanical devices is associated with improved outcome and lower mortality rates compared with natural history. Reperfusion is not without risk, however, and may result in reperfusion injury, which manifests in hemorrhagic transformation, brain edema, infarct progression, and neurologic worsening. In this article, the functional and structural changes and underlying molecular mechanisms of ischemia and reperfusion are reviewed...
November 2018: Neuroimaging Clinics of North America
https://www.readbyqxmd.com/read/30322337/autophagy-a-new-strategy-for-host-directed-therapy-of-tuberculosis
#18
Seungwha Paik, Jin Kyung Kim, Chaeuk Chung, Eun-Kyeong Jo
Tuberculosis (TB), which is primarily caused by the major etiologic agent Mycobacterium tuberculosis (Mtb), remains a serious infectious disease worldwide. Recently, much effort has been made to develop novel/improved therapies by modulating host responses to TB (i.e., host-directed therapy). Autophagy is an intracellular catabolic process that helps maintain homeostasis or the removal of invading pathogens via a lysosomal degradation process. The activation of autophagy by diverse drugs or agents may represent a promising treatment strategy against Mtb infection, even to drug-resistant strains...
October 15, 2018: Virulence
https://www.readbyqxmd.com/read/30322273/design-optimization-characterization-and-in-vivo-evaluation-of-quercetin-enveloped-soluplus%C3%A2-p407-micelles-in-diabetes-treatment
#19
Juhi Singh, Pooja Mittal, Gunjan Vasant Bonde, Gufran Ajmal, Brahmeshwar Mishra
Quercetin (Qu), is a flavonoid known to have anti-diabetic effects owing to its antioxidant property, thus promoting regeneration of the pancreatic islets, ultimately increasing insulin secretion. But the therapeutic application of Qu is hampered by its low oral bioavailability and its unfavourable physicochemical characteristics. The present work aimed at formulation of Quercetin loaded Soluplus® micelles (SMs) so as to enhance its bioavailability and provide prolonged release for the management of diabetes...
October 16, 2018: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/30322136/structure-based-identification-of-potent-natural-product-chemotypes-as-cannabinoid-receptor-1-inverse-agonists
#20
Pankaj Pandey, Kuldeep K Roy, Haining Liu, Guoyi Ma, Sara Pettaway, Walid F Alsharif, Rama S Gadepalli, John M Rimoldi, Christopher R McCurdy, Stephen J Cutler, Robert J Doerksen
Natural products are an abundant source of potential drugs, and their diversity makes them a rich and viable prospective source of bioactive cannabinoid ligands. Cannabinoid receptor 1 (CB1) antagonists are clinically established and well documented as potential therapeutics for treating obesity, obesity-related cardiometabolic disorders, pain, and drug/substance abuse, but their associated CNS-mediated adverse effects hinder the development of potential new drugs and no such drug is currently on the market...
October 13, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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