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https://www.readbyqxmd.com/read/29054694/the-resilient-brain-and-the-guardians-of-sleep-new-perspectives-on-old-assumptions
#1
REVIEW
Liborio Parrino, Anna Elisabetta Vaudano
Resilience is the capacity of a system, enterprise or a person to maintain its core purpose and integrity in the face of dramatically changed circumstances. In human physiology, resilience is the capacity of adaptively overcoming stress and adversity while maintaining normal psychological and physical functioning. In this review, we investigate the resilient strategies of sleep. First, we discuss the concept of brain resilience, highlighting the modular structure of small-world networking, neuronal plasticity and critical brain behavior...
October 17, 2017: Sleep Medicine Reviews
https://www.readbyqxmd.com/read/29051065/dihydroergotamine-mesylate-loaded-dissolving-microneedle-patch-made-of-polyvinylpyrrolidone-for-management-of-acute-migraine-therapy
#2
Cetin Tas, Jessica C Joyce, Hiep X Nguyen, Padmanabhan Eangoor, Jennifer S Knaack, Ajay K Banga, Mark R Prausnitz
Migraine is a widespread neurological disease with negative effects on quality of life and productivity. Moderate to severe acute migraine attacks can be treated with dihydroergotamine mesylate (DHE), an ergot derivative that is especially effective in non-responders to triptan derivatives. To overcome limitations of current DHE formulations in subcutaneous injection and nasal spray such as pain, adverse side effects and poor bioavailability, a new approach is needed for DHE delivery enabling painless self-administration, quick onset of action, and high bioavailability...
October 16, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29050231/a-phase-i-study-of-foretinib-plus-erlotinib-in-patients-with-previously-treated-advanced-non-small-cell-lung-cancer-canadian-cancer-trials-group-ind-196
#3
Natasha B Leighl, Ming-Sound Tsao, Geoffrey Liu, Dongsheng Tu, Cheryl Ho, Frances A Shepherd, Nevin Murray, John R Goffin, Garth Nicholas, Shingo Sakashita, Zhuo Chen, Lucia Kim, Jean Powers, Lesley Seymour, Glenwood Goss, Penelope A Bradbury
PURPOSE: MET and AXL mediate resistance to EGFR TKI in NSCLC. Foretinib, a MET/RON/AXL/TIE-2/VEGFR kinase inhibitor may overcome EGFR kinase resistance. This dose escalation study combined foretinib and erlotinib in advanced pretreated NSCLC patients. EXPERIMENTAL DESIGN: The primary endpoint was to define the RP2D of foretinib plus erlotinib as continuous oral daily dosing. Secondary objectives included safety, pharmacokinetics, response and potential biomarkers of response including EGFR, KRAS genotype, MET, AXL expression, and circulating HGF levels...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29046826/incorporation-of-functional-elements-enhances-the-antitumor-capacity-of-car-t-cells
#4
REVIEW
Le Qin, Ruocong Zhao, Peng Li
As chimeric antigen receptor (CAR) T cells have displayed an unprecedented efficacy in the treatment of CD19-positive malignances, it is believed that this cell therapy will be a milestone in the history of mankind's conquering of cancer. However, there are some issues that restrict CAR T cells from reaching their optimal anti-tumor capacity, especially in the treatment of solid tumors. Inhibitory cytokines, immune checkpoint molecules, hypoxia and other adverse factors have been reported to be involved in this process...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/29040664/coumestrol-induces-mitochondrial-dysfunction-by-stimulating-ros-production-and-calcium-ion-influx-into-mitochondria-in-human-placental-choriocarcinoma-cells
#5
Whasun Lim, Changwon Yang, Muhah Jeong, Fuller W Bazer, Gwonhwa Song
STUDY QUESTION: Does coumestrol inhibit proliferation of human placental choriocarcinoma cells? SUMMARY ANSWER: Coumestrol promotes cell death in the choriocarcinoma cells by regulating ERK1/2 MAPK and JNK MAPK signaling pathways and through disruption of Ca2+ and ROS homeostasis. WHAT IS KNOWN ALREADY: A number of patients who suffer from choriocarcinomas fail to survive due to delayed diagnosis or a recurrent tumor and resistance to traditional chemotherapy using platinum-based agents and methotrexate...
October 11, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/29039736/a-novel-central-nervous-system-penetrating-protease-inhibitor-overcomes-human-immunodeficiency-virus-1-resistance-with-unprecedented-am-to-pm-potency
#6
Manabu Aoki, Hironori Hayashi, Kalapala Venkateswara Rao, Debananda Das, Nobuyo Higashi-Kuwata, Haydar Bulut, Hiromi Aoki-Ogata, Yuki Takamatsu, Ravikiran S Yedidi, David A Davis, Shin-Ichiro Hattori, Noriko Nishida, Kazuya Hasegawa, Nobutoki Takamune, Prasanth R Nyalapatla, Heather L Osswald, Hirofumi Jono, Hideyuki Saito, Robert Yarchoan, Shogo Misumi, Arun K Ghosh, Hiroaki Mitsuya
Antiretroviral therapy for HIV-1 infection/AIDS has significantly extended the life expectancy of HIV-1-infected individuals and reduced HIV-1 transmission at very high rates. However, certain individuals who initially achieve viral suppression to undetectable levels may eventually suffer treatment failure mainly due to adverse effects and the emergence of drug-resistant HIV-1 variants. Here, we report GRL-142, a novel HIV-1 protease inhibitor containing an unprecedented 6-5-5-ring-fused crown-like tetrahydropyranofuran, which has extremely potent activity against all HIV-1 strains examined with IC50 values of attomolar-to-picomolar concentrations, virtually no effects on cellular growth, extremely high genetic barrier against the emergence of drug-resistant variants, and favorable intracellular and central nervous system penetration...
October 17, 2017: ELife
https://www.readbyqxmd.com/read/29034071/apigenin-in-cancer-therapy-anti-cancer-effects-and-mechanisms-of-action
#7
REVIEW
Xiaohui Yan, Miao Qi, Pengfei Li, Yihong Zhan, Huanjie Shao
Apigenin is a common dietary flavonoid that is abundantly present in many fruits, vegetables and Chinese medicinal herbs and serves multiple physiological functions, such as strong anti-inflammatory, antioxidant, antibacterial and antiviral activities and blood pressure reduction. Therefore, apigenin has been used as a traditional medicine for centuries. Recently, apigenin has been widely investigated for its anti-cancer activities and low toxicity. Apigenin was reported to suppress various human cancers in vitro and in vivo by multiple biological effects, such as triggering cell apoptosis and autophagy, inducing cell cycle arrest, suppressing cell migration and invasion, and stimulating an immune response...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/29032490/myeloid-derived-suppressor-cells-in-the%C3%A2-tumor-microenvironment-current-knowledge-and-future-perspectives
#8
REVIEW
Maria Ibáñez-Vea, Miren Zuazo, Maria Gato, Hugo Arasanz, Gonzalo Fernández-Hinojal, David Escors, Grazyna Kochan
The current knowledge on tumor-infiltrating myeloid-derived suppressor cells (MDSCs) is based mainly on the extensive work performed in murine models. Data obtained for human counterparts are generated on the basis of tumor analysis from patient samples. Both sources of information led to determination of the main suppressive mechanisms used by these cell subsets in tumor-bearing hosts. As a result of the identification of protein targets responsible for MDSCs suppressive activity, different therapeutics agents have been used to eliminate/reduce their adverse effect...
October 14, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/29031923/deae-dextran-coated-paclitaxel-nanoparticles-act-as-multifunctional-nano-system-for-intranuclear-delivery-to-triple-negative-breast-cancer-through-vegf-and-notch1-inhibition
#9
Anita K Bakrania, Bhavesh C Variya, Lalji V Rathod, Snehal S Patel
Triple negative breast cancer revolution has identified a plethora of therapeutic targets making it apparent that a single target for its treatment could be rare hence creating an urge to develop robust technologies for combination drug therapy. Paclitaxel, hailed as the most significant advancement in chemotherapy faces several underpinnings due to its low solubility and permeability. Advancing research has demonstrated the role of interferons in cancer. DEAE-Dextran, an emerging molecule with evidence of interferon induction was utilized in the present study to develop a nanoformulation in conjugation with paclitaxel to target multiple therapeutic pathways, with diminution of paclitaxel adverse effects and develop a specific targeted nano system...
October 11, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/29031620/targeting-non-small-cell-lung-cancer-with-small-molecule-egfr-tyrosine-kinase-inhibitors
#10
REVIEW
Mahaveer Singh, Hemant R Jadhav
Epidermal growth factor (EGFR) tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib, show excellent clinical efficacy for patients with non-small cell lung cancer (NSCLC) with EGFR mutations, including Exon 19 deletion and single-point substitution, and L858R of exon 21. The reason for the reduction in effectiveness of these EGFR TKIs is the T790M gatekeeper mutation in the ATP-binding pocket of Exon 20, which increases the affinity of EGFR for ATP. Newer EGFR TKIs, such as afatinib, osimertinib, rociletinib, EGF816 and ASP8273, selectively target T790M mutants, sparing wild-type EGFR...
October 12, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/29020960/perspectives-in-immunotherapy-meeting-report-from-the-immunotherapy-bridge-napoli-november-30th-2016
#11
Paolo A Ascierto, Bruno Daniele, Hans Hammers, Vera Hirsh, Joseph Kim, Lisa Licitra, Rita Nanda, Sandro Pignata
The complex interactions between the immune system and tumors lead the identification of key molecules that govern these interactions: immunotherapeutics were designed to overcome the mechanisms broken by tumors to evade immune destruction. After the substantial advances in melanoma, immunotherapy currently includes many other type of cancers, but the melanoma lesson is essential to progress in other type of cancers, since immunotherapy is potentially improving clinical outcome in various solid and haematologic malignancies...
October 11, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29020448/preparation-of-tc99m-labeled-pseudomonas-bacteriophage-without-adversely-impacting-infectivity-or-biodistribution
#12
Derek Holman, Matthew P Lungren, Jonathan Hardy, Christopher H Contag, Francis G Blankenberg
Bacteriophages (phages) are ubiquitous viruses which have adapted to infect and replicate within target bacteria, their only known hosts, in a strain specific fashion with minimal cross infectivity. The recent steep rise in antibiotic resistance throughout the world has renewed interest in adapting phages for the imaging and treatment of bacterial infection in humans. In this article, we describe the current limitations surrounding the radiolabeling of phage for the imaging and treatment of bacterial infection and methods to overcome these difficulties...
October 11, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28983018/phase-1-study-of-the-anti-cd22-immunotoxin-moxetumomab-pasudotox-for-childhood-acute-lymphoblastic-leukemia
#13
MULTICENTER STUDY
Alan S Wayne, Nirali N Shah, Deepa Bhojwani, Lewis B Silverman, James A Whitlock, Maryalice Stetler-Stevenson, Weili Sun, Meina Liang, Jie Yang, Robert J Kreitman, Mark C Lanasa, Ira Pastan
Novel therapies are needed to overcome chemotherapy resistance for children with relapsed/refractory acute lymphoblastic leukemia (ALL). Moxetumomab pasudotox is a recombinant anti-CD22 immunotoxin. A multicenter phase 1 study was conducted to determine the maximum-tolerated cumulative dose (MTCD) and evaluate safety, activity, pharmacokinetics, and immunogenicity of moxetumomab pasudotox in children, adolescents, and young adults with ALL (N = 55). Moxetumomab pasudotox was administered as a 30-minute IV infusion at doses of 5 to 50 µg/kg every other day for 6 (cohorts A and B) or 10 (cohort C) doses in 21-day cycles...
October 5, 2017: Blood
https://www.readbyqxmd.com/read/28978851/future-prospects-of-hemostatic-treatment-for-hemophilia-patients
#14
Keiji Nogami
In the treatment of hemophilia patients, factor (F) VIII or FIX product prophylaxis results in arthropathy prevention and quality of life (QOL) improvement. Serious issues concerning hemostatic treatment of hemophilia include frequent intravenous administration of products, inhibitor development, and hemostatic treatment of patients with inhibitors. To overcome these challenges, products with extended half-life were developed. Furthermore, alternative products based on new concepts of hemostatic therapy were developed...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28975097/ameliorative-effect-of-vitamin-e-on-trichloroethylene-induced-nephrotoxicity-in-rats
#15
Mojgan Heydari, Massumeh Ahmadizadeh, Kambiz Ahmadi Angali
BACKGROUND: 1,1,2-Trichloroethylene (TCE) is an important organic solvent which is widespread in the environment. Work place exposure to TCE has been associated adverse effects in many organs including kidney. Vitamin E is an antioxidant that can overcome oxidative stress. OBJECTIVES: The aim of the present study is to examine the role of vitamin E against destructive effects of TCE on rat kidney. MATERIALS AND METHODS: A total of 35 male Wistar rats were randomly divided into seven groups of equal number in each...
July 2017: Journal of Nephropathology
https://www.readbyqxmd.com/read/28971908/comparison-of-up-front-treatments-for-newly-diagnosed-immune-thrombocytopenia-a-systematic-review-and-network-meta-analysis
#16
Yasuyuki Arai, Tomoyasu Jo, Hiroyuki Matsui, Tadakazu Kondo, Akifumi Takaori-Kondo
Corticosteroids such as prednisolone and dexamethasone have been established as up-front therapy for the treatment of newly diagnosed immune thrombocytopenia. Recent studies have indicated that other treatments such rituximab or thrombopoietin receptor agonist can also be effective choices. We performed a systematic review and network meta-analysis to establish a clinically meaningful hierarchy of the efficacy and safety of treatment for newly diagnosed primary immune thrombocytopenia in adults. Randomized controlled trials evaluating medical treatments for newly diagnosed immune thrombocytopenia were included...
September 29, 2017: Haematologica
https://www.readbyqxmd.com/read/28966072/sunitinib-dose-escalation-after-disease-progression-in-metastatic-renal-cell-carcinoma
#17
Jacques Raphael, Alia Thawer, Georg A Bjarnason
PURPOSE: Previous pharmacologic studies demonstrated that higher sunitinib exposure is associated with improved clinical outcomes in patients with metastatic renal cell carcinoma (mRCC). We aimed to assess the efficacy and toxicity of sunitinib dose-escalation in mRCC patients progressing on the standard 50mg dose. METHODS: A single-institution retrospective review was conducted on mRCC patients, treated outside trials with a 50mg sunitinib dose given on an individualized schedule between October 2009 and January 2016, who subsequently progressed on imaging...
September 28, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28963058/new-tools-for-understanding-coping-and-resilience
#18
REVIEW
Michael V Baratta, Steven F Maier
In humans, many of the factors determining vulnerability and resilience to the impact of an adverse event revolve around coping factors. This mini-review focuses on the neural mechanisms by which coping reduces the impact of adverse events, as studied in an animal model, and discusses some of the challenges of linking neural circuit activity with stressor outcome. We highlight several approaches for probing circuit function with cell-type and pathway-specificity that overcome some of the limitations of traditional neuroscience techniques and will likely yield a more detailed and comprehensive understanding of how the brain regulates stress-responsive structures when coping behaviors are engaged...
September 27, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28962645/simplifying-drug-package-leaflets-written-in-spanish-by-using-word-embedding
#19
Isabel Segura-Bedmar, Paloma Martínez
BACKGROUND: Drug Package Leaflets (DPLs) provide information for patients on how to safely use medicines. Pharmaceutical companies are responsible for producing these documents. However, several studies have shown that patients usually have problems in understanding sections describing posology (dosage quantity and prescription), contraindications and adverse drug reactions. An ultimate goal of this work is to provide an automatic approach that helps these companies to write drug package leaflets in an easy-to-understand language...
September 29, 2017: Journal of Biomedical Semantics
https://www.readbyqxmd.com/read/28954791/mii-vitalise-a-pilot-randomised-controlled-trial-of-a-home-gaming-system-nintendo-wii-to-increase-activity-levels-vitality-and-well-being-in-people-with-multiple-sclerosis
#20
Sarah Thomas, Louise Fazakarley, Peter W Thomas, Sarah Collyer, Sarah Brenton, Steve Perring, Rebecca Scott, Fern Thomas, Charlotte Thomas, Kelly Jones, Jo Hickson, Charles Hillier
OBJECTIVES: While the health and well-being benefits of physical activity are recognised, people with multiple sclerosis (MS) often face greater barriers than the general population. The Nintendo Wii potentially offers a fun, convenient way of overcoming some of these. The aim was to test the feasibility of conducting a definitive trial of the effectiveness and cost-effectiveness of Mii-vitaliSe; a home-based, physiotherapist-supported Nintendo Wii intervention. DESIGN: A single-centre wait-list randomised controlled study...
September 27, 2017: BMJ Open
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