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https://www.readbyqxmd.com/read/29454096/jak-stat-inhibitors-and-other-small-molecule-cytokine-antagonists-for-the-treatment-of-allergic-disease
#1
REVIEW
Michael D Howell, Carolyn Fitzsimons, Paul Smith
OBJECTIVE: To provide an overview of janus kinase (JAK), chemoattractant receptor-homologous molecule expressed on T-helper 2 cells (CRTH2), and phosphodiesterase 4 (PDE4) inhibitors in allergic disorders. DATA SOURCES: PubMed literature review. STUDY SELECTIONS: Articles included in this review discuss the emerging mechanism of action of small molecule inhibitors and their utilization in atopic dermatitis (AD), asthma, and allergic rhinitis (AR)...
February 14, 2018: Annals of Allergy, Asthma & Immunology
https://www.readbyqxmd.com/read/29454094/synergistic-activity-of-bet-inhibitor-bi-894999-with-plk-inhibitor-volasertib-in-aml-in-vitro-and-in-vivo
#2
Ulrike Tontsch-Grunt, Dorothea Rudolph, Irene Waizenegger, Anke Baum, Daniel Gerlach, Harald Engelhardt, Melanie Wurm, Fabio Savarese, Norbert Schweifer, Norbert Kraut
Interactions between a new potent Bromodomain and extraterminal domain (BET) inhibitor BI 894999 and the polo-like kinase (PLK) inhibitor volasertib were studied in acute myeloid leukemia cell lines in vitro and in vivo. We provide data for the distinct mechanisms of action of these two compounds with a potential utility in AML based on gene expression, cell cycle profile and modulation of PD biomarkers such as MYC and HEXIM1. In contrast to BI 894999, volasertib treatment neither affects MYC nor HEXIM1 expression, but augments and prolongs the decrease of MYC expression caused by BI 894999 treatment...
February 14, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29453983/aldolase-a-overexpression-is-associated-with-poor-prognosis-and-promotes-tumor-progression-by-the-epithelial-mesenchymal-transition-in-colon-cancer
#3
Feng Ye, Yixing Chen, Lu Xia, Jiabian Lian, Shuyu Yang
There is increasing evidence that glycolysis is involved in cancer progression. Aldolase is a glycolytic enzyme that catalyzes the reversible conversion of fructose-1,6-bisphosphate to glyceraldehyde-3-phosphate and dihydroxyacetone phosphate. Disruption of the aldolase genes also plays a role in the progression of multiple types of cancer. However, the underlying mechanism of the action of aldolases in colon cancer progression remains elusive. In this study, aldolase A expression was investigated and found to be upregulated along with human colon cancer progression and metastasis at both the mRNA and protein levels in human colon cancer tissues...
February 14, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29453896/the-anti-malarial-mefloquine-inhibits-nf-%C3%AE%C2%BAb-signaling-and-induces-apoptosis-in-colorectal-cancer-cells
#4
Xin Xu, Jun Wang, Kunkun Han, Shaoyan Li, Feng Xu, Yili Yang
The NF-κB signaling pathway is activated in many colorectal cancer (CRC) cells and in the tumor microenvironment, which plays a critical role in cancer initiation, development, and response to therapies. We found in the present study that the widely used antimalarial drug mefloquine was a NF-κB inhibitor that blocked the activation of IκBα kinase, leading to the reduction of IκBα degradation, decrease of p65 phosphorylation, and suppressed expression of NF-κB target genes in colorectal cancer cells. We also found that mefloquine induced growth arrest and apoptosis of colorectal cancer cells harboring phosphorylated p65 in culture and mice...
February 17, 2018: Cancer Science
https://www.readbyqxmd.com/read/29453736/reproductive-epidemiology-of-glial-tumors-may-reveal-novel-treatments-high-dose-progestins-or-progesterone-antagonists-as-endocrino-immune-modifiers-against-glioma
#5
REVIEW
Meric A Altinoz, Aysel Ozpinar, Ilhan Elmaci
Female gender, contraceptives, and menopausal hormone replacement treatments containing progesterone analogues associate with higher risk of meningiomas yet with lower risk of gliomas. Progesterone receptor (PR) expression and mifepristone treatment was highly discussed for meningiomas. However, much less is known in regard to progesterone actions in gliomas despite PR expression strongly correlates with their grade. Meningiomas and gliomas may grow faster during gestation; but paradoxically, parousity reduces lifetime risk of gliomas which can be explained with dichotomous cell growth-stimulating and inhibitory actions of progesterone at low versus high levels...
February 17, 2018: Neurosurgical Review
https://www.readbyqxmd.com/read/29453548/-big-data-from-clinical-routine
#6
REVIEW
U Mansmann
BACKGROUND: Over the past 100 years, evidence-based medicine has undergone several fundamental changes. Through the field of physiology, medical doctors were introduced to the natural sciences. Since the late 1940s, randomized and epidemiological studies have come to provide the evidence for medical practice, which led to the emergence of clinical epidemiology as a new field in the medical sciences. Within the past few years, big data has become the driving force behind the vision for having a comprehensive set of health-related data which tracks individual healthcare histories and consequently that of large populations...
February 16, 2018: Zeitschrift Für Rheumatologie
https://www.readbyqxmd.com/read/29453405/widespread-use-of-incorrect-pcr-ramp-rate-negatively-impacts-multidrug-resistant-tuberculosis-diagnosis-mtbdrplus
#7
B Derendinger, M de Vos, R R Nathavitharana, T Dolby, J A Simpson, P D van Helden, R M Warren, G Theron
The scale-up of rapid drug resistance testing for TB is a global priority. MTBDRplus is a WHO-endorsed multidrug-resistant (MDR)-TB PCR assay with suboptimal sensitivities and high indeterminate rates on smear-negative specimens. We hypothesised that widespread use of incorrect thermocycler ramp rate (speed of temperature change between cycles) impacts performance. A global sample of 72 laboratories was surveyed. We tested 107 sputa from Xpert MTB/RIF-positive patients and, separately, dilution series of bacilli, both at the manufacturer-recommended ramp rate (2...
February 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29453321/inhibition-of-cd95-cd95l-signaling-with-apg101-prevents-invasion-and-enhances-radiation-therapy-for-glioblastoma
#8
Jonas Blaes, Carina M Thomé, Philipp-Niclas Pfenning, Petra Rübmann, Felix Sahm, Antje Wick, Theresa Bunse, Torsten Schmenger, Jaromir Sykora, Andreas von Deimling, Benedikt Wiestler, Christian Merz, Manfred Jugold, Uwe Haberkorn, Amir Abdollahi, Jürgen Debus, Christian Gieffers, Claudia Kunz, Martin Bendszus, Michael Kluge, Michael Platten, Harald Fricke, Wolfgang Wick, Dieter Lemke
CD95 (Fas/APO-1), a death receptor family member, activity has been linked to tumorigenicity in multiple cancers, including glioblastoma multiforme (GBM). A phase II clinical trial on relapsed glioblastoma patients demonstrated that targeted inhibition of CD95 signaling via the CD95 ligand (CD95L) binding and neutralizing Fc-fusion protein APG101 (asunercept) prolonged patient survival. While CD95 signaling may be relevant for multiple aspects of tumor growth, the mechanism of action of APG101 in glioblastoma is not clear...
February 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29453313/multigene-profiling-of-ctcs-in-mcrpc-identifies-a-clinically-relevant-prognostic-signature
#9
Udit Singhal, Yugang Wang, James Henderson, Yashar S Niknafs, Yuanyuan Qiao, Amy Gursky, Alexander Zaslavsky, Jae-Seung Chung, David C Smith, R Jeffrey Karnes, S Laura Chang, Felix Y Feng, Ganesh S Palapattu, Russell S Taichman, Arul M Chinnaiyan, Scott A Tomlins, Todd M Morgan
The trend towards precision-based therapeutic approaches dictated by molecular alterations offers substantial promise for men with metastatic castration resistant prostate cancer (mCRPC). However, current approaches for molecular characterization are primarily tissue based, necessitating serial biopsies to understand changes over time and are limited by the challenges inherent to extracting genomic material from predominantly bone metastases. Therefore, a circulating tumor cell (CTC)-based assay was developed to determine gene expression across a panel of clinically relevant and potentially actionable prostate cancer related genes...
February 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29452987/cell-therapy-for-peripheral-artery-disease
#10
REVIEW
Nikolaos G Frangogiannis
Patients with severe peripheral artery disease (PAD) who are not candidates for revascularization have poor prognosis. Cell therapy using peripheral blood-derived or bone marrow-derived mononuclear cells, mesenchymal stem cells, or marker-specific subsets of bone marrow cells with angiogenic properties may hold promise for no-option PAD patients. Injected cells may exert beneficial actions by enhancing local angiogenesis (either through maturation of endothelial progenitors, or through secretion of angiogenic mediators), or by transducing cytoprotective signals that preserve tissue structure...
February 13, 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29452520/the-clinical-trials-transformation-initiative-methodology-supporting-the-mission
#11
Amy Corneli, Zachary Hallinan, Gerrit Hamre, Brian Perry, Jennifer C Goldsack, Sara B Calvert, Annemarie Forrest
The mission of the Clinical Trials Transformation Initiative, a public-private partnership co-founded by the U.S. Food and Drug Administration and Duke University, is to develop and drive adoption of practices that will increase the quality and efficiency of clinical trials. The Clinical Trials Transformation Initiative works collaboratively with key stakeholders, implements "fit-for-purpose" evidence-gathering projects, and develops actionable recommendations and tools to address the challenges faced by the clinical trials enterprise...
February 2018: Clinical Trials: Journal of the Society for Clinical Trials
https://www.readbyqxmd.com/read/29452364/4-phenylbutyrate-suppresses-the-unfolded-protein-response-without-restoring-protein-folding-in-saccharomyces-cerevisiae
#12
Chi Thanh Mai, Quynh Giang Le, Yuki Ishiwata-Kimata, Hiroshi Takagi, Kenji Kohno, Yukio Kimata
Accumulation of unfolded secretory proteins in the endoplasmic reticulum (ER), namely ER stress, is hazardous to eukaryotic cells and promotes the unfolded protein response (UPR). Ire1 is an ER-located transmembrane protein that senses ER stress and triggers the UPR. According to previous in vitro experiments, 4-phenylbutyrate (4-PBA) works as a chemical molecular chaperone. Since 4-PBA attenuates the UPR in mammalian tissue cultures, this chemical may have clinical potential for restoring ER-stressing conditions...
February 14, 2018: FEMS Yeast Research
https://www.readbyqxmd.com/read/29451901/the-novel-antibiotic-rhodomyrtone-traps-membrane-proteins-in-vesicles-with-increased-fluidity
#13
Dennapa Saeloh, Varomyalin Tipmanee, Kin Ki Jim, Marien P Dekker, Wilbert Bitter, Supayang P Voravuthikunchai, Michaela Wenzel, Leendert W Hamoen
The acylphloroglucinol rhodomyrtone is a promising new antibiotic isolated from the rose myrtle Rhodomyrtus tomentosa, a plant used in Asian traditional medicine. While many studies have demonstrated its antibacterial potential in a variety of clinical applications, very little is known about the mechanism of action of rhodomyrtone. Preceding studies have been focused on intracellular targets, but no specific intracellular protein could be confirmed as main target. Using live cell, high-resolution, and electron microscopy we demonstrate that rhodomyrtone causes large membrane invaginations with a dramatic increase in fluidity, which attract a broad range of membrane proteins...
February 16, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29451894/trade-off-between-synergy-and-efficacy-in-combinations-of-hiv-1-latency-reversing-agents
#14
Vipul Gupta, Narendra M Dixit
Eradicating HIV-1 infection is difficult because of the reservoir of latently infected cells that gets established soon after infection, remains hidden from antiretroviral drugs and host immune responses, and retains the capacity to reignite infection following the cessation of treatment. Drugs called latency-reversing agents (LRAs) are being developed to reactivate latently infected cells and render them susceptible to viral cytopathicity or immune killing. Whereas individual LRAs have failed to induce adequate reactivation, pairs of LRAs have been identified recently that act synergistically and hugely increase reactivation levels compared to individual LRAs...
February 16, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29451665/mirror-therapy-a-potential-intervention-for-pain-management
#15
Priscilla G Wittkopf, Mark I Johnson
The consequences of chronic pain and associated disabilities to the patient and to the health care system are well known. Medication is often the first treatment of choice for chronic pain, although side effects and high costs restrict long-term use. Inexpensive, safe and easy to self-administer non-pharmacological therapies, such as mirror therapy, are recommended as adjuncts to pain treatment. The purpose of this review is to describe the principles of use of mirror therapy so it can be incorporated into a health care delivery...
November 2017: Revista da Associação Médica Brasileira
https://www.readbyqxmd.com/read/29451637/facing-death-in-the-clinical-practice-a-view-from-nurses-in-mexico
#16
Ma Luisa Marván, Luis F Oñate-Ocaña, Patricio Santillán-Doherty, Asunción Álvarez-Del Río
OBJECTIVE: To explore the views of nurses on death in their practice, and their perception about physicians' actions dealing with terminally ill patients. MATERIALS AND METHODS: Two hundred ninety-five nurses with experience caring for terminally ill patients responded to a questionnaire developed for this study. RESULTS: The majority of participants considered that terminally ill patients should know about their prognosis. Although nearly all nurses said that when a patient brings up the subject and they talk with the patient about death, several of the nurses find it difficult to establish a relationship with these patients...
November 2017: Salud Pública de México
https://www.readbyqxmd.com/read/29451287/computational-identification-of-the-binding-mechanism-of-a-triple-reuptake-inhibitor-amitifadine-for-the-treatment-of-major-depressive-disorder
#17
Weiwei Xue, Panpan Wang, Gao Tu, Fengyuan Yang, Guoxun Zheng, Xiaofeng Li, Xiaoxu Li, Yuzong Chen, Xiaojun Yao, Feng Zhu
Amitifadine, the only drug ever clinically tested in Phase 3 for treating depression, is a triple reuptake inhibitor (TRI) that simultaneously interacts with human monoamine transporters (MATs) including hSERT, hNET and hDAT. This novel multi-target strategy improves drug efficacy and reduces the toxic side effects of drugs. However, the binding modes accounting for amitifadine's polypharmacological mode of action are still elusive, and extensive exploration of the amitifadine-target interactions between amitifadine and MATs is urgently needed...
February 16, 2018: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29451277/tivozanib-a-new-treatment-option-for-renal-cell-carcinoma
#18
L Saes, F A L M Eskens
Tivozanib is a tyrosine kinase inhibitor that targets all vascular endothelial growth factor receptors (VEGFRs), causing inhibition of angiogenesis. It has recently been approved by the European Medicines Agency (EMA) for first-line treatment of adult patients with advanced renal cell carcinoma (RCC) and for adult patients who are VEGFR and mammalian target of rapamycin (mTOR) pathway inhibitor-naive, following disease progression after one prior treatment with cytokine therapy for advanced RCC. This review will focus on mechanisms of action, early drug development and results of published and ongoing clinical trials of tivozanib...
November 2017: Drugs of Today
https://www.readbyqxmd.com/read/29451274/helicase-primase-inhibitor-amenamevir-for-herpesvirus-infection-towards-practical-application-for-treating-herpes-zoster
#19
K Shiraki
Valacyclovir and famciclovir enabled successful systemic therapy for treating herpes simplex virus (HSV) and varicella zoster virus (VZV) infection by their phosphorylation with viral thymidine kinase. Helicase-primase inhibitors (HPIs) inhibit the progression of the replication fork, an initial step in DNA synthesis to separate the double strand into two single strands. The HPIs amenamevir and pritelivir have a novel mechanism of action, once-daily administration with nonrenal excretory characteristics, and clinical efficacy for genital herpes...
November 2017: Drugs of Today
https://www.readbyqxmd.com/read/29451071/childhood-emotional-invalidation-and-right-hemispheric-mu-suppression-during-a-pain-empathy-task-an-eeg-study
#20
Kirsten Arnett, Alexandra Roach, Meredith Elzy, Laura Jelsone-Swain
Empathy is a critical aspect of social behavior, and impairment in empathic processing is linked to hindered social interactions and several disorders. Despite much interest in this topic, our understanding of the developmental and neural involvement for empathic processing is limited. Recent evidence suggests the Mirror Neuron System (MNS) may play a role in this behavior, and that mu rhythm suppression found over the sensorimotor cortices may be a proxy for the MNS. Therefore, we aimed to measure mu rhythm oscillations in response to empathic processing during observation of painful action-based situations using electroencephalogram (EEG)...
February 16, 2018: Social Neuroscience
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