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https://www.readbyqxmd.com/read/28272644/croconamides-a-new-dual-hydrogen-bond-donating-motif-for-anion-recognition-and-organocatalysis
#1
Anne Jeppesen, Bjarne E Nielsen, Dennis Larsen, Olivia M Akselsen, Theis I Sølling, Theis Brock-Nannestad, Michael Pittelkow
We introduce bis-aryl croconamides as a new member in the family of dual hydrogen bonding anion receptors. In this study a series of croconamides are synthesised, and the selectivity for anion binding is investigated (Cl(-) > Br(-) > I(-) in CH2Cl2). The croconamides exhibit different structures in the crystal phase depending on the substituents on the aromatic rings, and furthermore, the crystal structure revealed the presence of tautomers. DFT calculations elucidated the complex structures formed upon addition of anion to the croconamides, confirming the order of association constants towards the halogen anions...
March 8, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28245243/serelaxin-as-a-potential-treatment-for-renal-dysfunction-in-cirrhosis-preclinical-evaluation-and-results-of-a-randomized-phase-2-trial
#2
Victoria K Snowdon, Neil J Lachlan, Anna M Hoy, Patrick W F Hadoke, Scott I Semple, Dilip Patel, Will Mungall, Timothy J Kendall, Adrian Thomson, Ross J Lennen, Maurits A Jansen, Carmel M Moran, Antonella Pellicoro, Prakash Ramachandran, Isaac Shaw, Rebecca L Aucott, Thomas Severin, Rajnish Saini, Judy Pak, Denise Yates, Neelesh Dongre, Jeremy S Duffield, David J Webb, John P Iredale, Peter C Hayes, Jonathan A Fallowfield
BACKGROUND: Chronic liver scarring from any cause leads to cirrhosis, portal hypertension, and a progressive decline in renal blood flow and renal function. Extreme renal vasoconstriction characterizes hepatorenal syndrome, a functional and potentially reversible form of acute kidney injury in patients with advanced cirrhosis, but current therapy with systemic vasoconstrictors is ineffective in a substantial proportion of patients and is limited by ischemic adverse events. Serelaxin (recombinant human relaxin-2) is a peptide molecule with anti-fibrotic and vasoprotective properties that binds to relaxin family peptide receptor-1 (RXFP1) and has been shown to increase renal perfusion in healthy human volunteers...
February 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28220124/in-vivo-efficacy-of-umbilical-cord-blood-stem-cell-derived-nk-cells-in-the-treatment-of-metastatic-colorectal-cancer
#3
John P Veluchamy, Silvia Lopez-Lastra, Jan Spanholtz, Fenna Bohme, Nina Kok, Daniëlle A M Heideman, Henk M W Verheul, James P Di Santo, Tanja D de Gruijl, Hans J van der Vliet
Therapeutic monoclonal antibodies against the epidermal growth factor receptor (EGFR) act by inhibiting EGFR downstream signaling and by eliciting a natural killer (NK) cell-mediated antitumor response. The IgG1 mAb cetuximab has been used for treatment of RAS(wt) metastatic colorectal cancer (mCRC) patients, showing limited efficacy. In the present study, we address the potential of adoptive NK cell therapy to overcome these limitations investigating two allogeneic NK cell products, i.e., allogeneic activated peripheral blood NK cells (A-PBNK) and umbilical cord blood stem cell-derived NK cells (UCB-NK)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28153778/accelerating-the-clinical-development-of-protein-based-vaccines-for-malaria-by-efficient-purification-using-a-four-amino-acid-c-terminal-c-tag
#4
Jing Jin, Kathryn A Hjerrild, Sarah E Silk, Rebecca E Brown, Geneviève M Labbé, Jennifer M Marshall, Katherine E Wright, Sandra Bezemer, Stine B Clemmensen, Sumi Biswas, Yuanyuan Li, Aadil El-Turabi, Alexander D Douglas, Pim Hermans, Frank J Detmers, Willem A de Jongh, Matthew K Higgins, Rebecca Ashfield, Simon J Draper
Development of bespoke biomanufacturing processes remains a critical bottleneck for translational studies, in particular when modest quantities of a novel product are required for proof-of-concept Phase I/II clinical trials. In these instances the ability to develop a biomanufacturing process quickly and relatively cheaply, without risk to product quality or safety, provides a great advantage by allowing new antigens or concepts in immunogen design to more rapidly enter human testing. These challenges with production and purification are particularly apparent when developing recombinant protein-based vaccines for difficult parasitic diseases, with Plasmodium falciparum malaria being a prime example...
January 30, 2017: International Journal for Parasitology
https://www.readbyqxmd.com/read/28125304/omalizumab-for-treating-chronic-spontaneous-urticaria-an-expert-review-on-efficacy-and-safety
#5
Ana M Giménez-Arnau
Chronic spontaneous urticaria (CSU) is characterized by the recurrence of itchy hives and/or angioedema for greater than six weeks, with no known external trigger. Omalizumab, a humanized, recombinant, monoclonal anti-IgE antibody, is the only approved add-on therapy for H1-antihistamine refractory CSU patients. Areas covered: The objective of this article is to discuss the mechanism of action, pharmacokinetics and pharmacodynamics of omalizumab for the treatment of CSU. The review also summarizes efficacy and safety data from proof-of-concept, Phase II (X-QUISITE, MYSTIQUE), and pivotal Phase III omalizumab studies (ASTERIA I, ASTERIA II, and GLACIAL)...
January 26, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28062705/novel-p21-activated-kinase-4-pak4-allosteric-modulators-overcome-drug-resistance-and-stemness-in-pancreatic-ductal-adenocarcinoma
#6
Amro Aboukameel, Irfana Muqbil, William Senapedis, Erkan Baloglu, Yosef Landesman, Sharon Shacham, Michael Kauffman, Philip A Philip, Ramzi M Mohammad, Asfar S Azmi
The p21-activated kinase 4 (PAK4) is a key downstream effector of the Rho family GTPases and is found to be overexpressed in pancreatic ductal adenocarcinoma (PDAC) cells but not in normal human pancreatic ductal epithelia (HPDE). Gene copy number amplification studies in PDAC patient cohorts confirmed PAK4 amplification making it an attractive therapeutic target in PDAC. We investigated the antitumor activity of novel PAK4 allosteric modulators (PAM) on a panel of PDAC cell lines and chemotherapy-resistant flow-sorted PDAC cancer stem cells (CSC)...
January 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28032501/single-particle-ratiometric-pressure-sensing-based-on-double-sensor-colloidal-nanocrystals
#7
Monica Lorenzon, Valerio Pinchetti, Francesco Bruni, Wan Ki Bae, Francesco Meinardi, Victor I Klimov, Sergio Brovelli
Ratiometric pressure sensitive paints (r-PSPs) are all-optical probes for monitoring oxygen flows in the vicinity of complex or miniaturized surfaces. They typically consist of a porous binder embedding mixtures of a reference and a sensor chromophore exhibiting oxygen-insensitive and oxygen-responsive luminescence, respectively. Here, we demonstrate the first example of an r-PSP based on a single two-color emitter that removes limitations of r-PSPs based on chromophore mixtures such as different temperature dependencies of the two chromophores, cross-readout between the reference and sensor signals and phase segregation...
January 10, 2017: Nano Letters
https://www.readbyqxmd.com/read/27913075/the-photosensitivity-model-is-not-a-model-for-partial-focal-seizures-rebuttal
#8
Roger J Porter
New, more effective and less toxic medications are desperately needed for patients with partial (focal) epilepsy. Many hurdles prevent the appropriate study of promising compounds. One of these hurdles is the gap between Phase I and Phase II-the expensive proof of concept to suggest that human trials in partial seizure patients will be successful. A short-cut, the photoparoxysmal response (PPR) model has recently been used to increase confidence in moving a compound into Phase II and III. This shortcut has substantial limitations...
November 22, 2016: Epilepsy Research
https://www.readbyqxmd.com/read/27908525/the-photosensitivity-model-is-not-a-model-for-partial-focal-seizures
#9
Roger J Porter
New, more effective and less toxic medications are desperately needed for patients with partial (focal) epilepsy. Many hurdles prevent the appropriate study of promising compounds. One of these hurdles is the difficult gap between Phase I and Phase II-the expensive proof of concept to suggest that human trials in partial seizure patients will be successful. A short-cut, the photoparoxysmal response (PPR) model has recently been used to increase confidence in moving a compound into Phase II and III (K-N Trenite et al...
November 22, 2016: Epilepsy Research
https://www.readbyqxmd.com/read/27852560/safety-acceptability-and-use-of-a-smartphone-app-blueice-for-young-people-who-self-harm-protocol-for-an-open-phase-i-trial
#10
Paul Stallard, Joanna Porter, Rebecca Grist
BACKGROUND: Up to 18% of adolescents will engage in an act of self-harm before young adulthood, with the majority of acts occurring in private. Mobile apps may offer a way of providing support for young people at times of distress to prevent self-harm. OBJECTIVE: This is a proof-of-concept study designed to explore the safety, acceptability, feasibility, and usability of a smartphone app, BlueIce, with young people who are self-harming. METHODS: In this phase I open trial we will evaluate BlueIce, a smartphone app developed and coproduced with young people with lived experience of self-harm...
November 16, 2016: JMIR Research Protocols
https://www.readbyqxmd.com/read/27828010/quantitative-measurement-of-dynamic-nanostrain-based-on-a-phase-sensitive-optical-time-domain-reflectometer
#11
Yongkang Dong, Xi Chen, Erhu Liu, Cheng Fu, Hongying Zhang, Zhiwei Lu
A sensing system is proposed for quantitative measurement of large-range dynamic nanostrain based on a phase-sensitive optical time domain reflectometer, where the coherent detection and I/Q demodulation methods are employed to demodulate both the phase and the amplitude of the Rayleigh scattering light in real time. A nanopositioning translation stage is utilized to apply precise nanostrain to fiber. By measuring phase differences between two adjacent sections, the quantitative nanostrain with a large measurement range is demonstrated; this is also a method to measure the strain parameter of refractive index...
October 1, 2016: Applied Optics
https://www.readbyqxmd.com/read/27825799/combination-of-2-deoxy-d-glucose-and-metformin-for-synergistic-inhibition-of-non-small-cell-lung-cancer-a-reactive-oxygen-species-and-p-p38-mediated-mechanism
#12
Xiao-Bin Hou, Ting-Hui Li, Zhi-Peng Ren, Yang Liu
Targeting metabolism of lung cancer cells is a promising methodology for the treatment of lung cancer. In this regard, 2-Deoxy d-glucose (2-dDG) has been reported to inhibit cell proliferation by intervening the glycolytic pathway. However, phase I clinical trial of 2-dDG demonstrated cardiac side effects at higher dosage. Metformin (Met), on the other hand, has been reported to improve pathological response to chemotherapy in non-small cell lung cancer (NSCLC) patients. In this study, we propose that combination therapy of 2-dDG with Met will demonstrate enhanced cytotoxicity than either compound alone...
December 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27779402/detection-and-activity-profiling-of-synthetic-cannabinoids-and-their-metabolites-with-a-newly-developed-bioassay
#13
Annelies Cannaert, Jolien Storme, Florian Franz, Volker Auwärter, Christophe P Stove
Synthetic cannabinoids (SCs) are the largest group of compounds currently monitored in Europe by the EU Early Warning System on new psychoactive substances. Emerging recreational use of these products has led to multiple cases of adverse health effects and even death. In contrast to marijuana, where Δ(9)-tetrahydrocannabinol (Δ(9)THC) is metabolized to only one major active metabolite, it has been reported that several major phase I metabolites of SCs remain biologically active, exerting cannabinoid (CB) receptor affinity, potency, and efficacy greater than those of Δ(9)THC...
December 6, 2016: Analytical Chemistry
https://www.readbyqxmd.com/read/27737495/a-countermeasure-development-pipeline
#14
Calum A MacRae, Gerry Boss, Matthew Brenner, Robert E Gerszten, Sari Mahon, Randall T Peterson
We have developed an integrated pipeline for countermeasure discovery that, under the auspices of the National Institutes of Health Countermeasures Against Chemical Threats network, is one of the few efforts within academia that by design spans the spectrum from discovery to phase I. The successful implementation of this approach for cyanide would enable efficient proof-of-concept studies that would lay the foundation for a generalizable strategy for parallel mechanistic studies and accelerated countermeasure development in the face of new and emerging chemical threats...
August 2016: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/27731362/a-humanized-mouse-model-for-sequestration-of-plasmodium-falciparum-sexual-stages-and-in-vivo-evaluation-of-gametocytidal-drugs
#15
Yoann Duffier, Audrey Lorthiois, Pau Cisteró, Florian Dupuy, Grégory Jouvion, Laurence Fiette, Dominique Mazier, Alfredo Mayor, Catherine Lavazec, Alicia Moreno Sabater
The development of new drugs to disrupt malaria transmission requires the establishment of an in vivo model to address the biology of Plasmodium falciparum sexual stages (gametocytes). Herein we show that chemically immune-modulated NSG mice grafted with human erythrocytes support complete sexual development of P. falciparum parasites and generate high gametocytemia. Immunohistochemistry and RT-qPCR analyses indicate an enrichment of immature gametocytes in the bone marrow and the spleen, suggesting a sequestration mechanism reminiscent to that observed in humans...
October 12, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27722277/multinuclear-nmr-as-a-tool-for-studying-local-order-and-dynamics-in-ch3nh3pbx3-x-cl-br-i-hybrid-perovskites
#16
Claire Roiland, Gaelle Trippé-Allard, Khaoula Jemli, Bruno Alonso, Jean-Claude Ameline, Régis Gautier, Thierry Bataille, Laurent Le Pollès, Emmanuelle Deleporte, Jacky Even, Claudine Katan
We report on (207)Pb, (79)Br, (14)N, (1)H, (13)C and (2)H NMR experiments for studying the local order and dynamics in hybrid perovskite lattices. (207)Pb NMR experiments conducted at room temperature on a series of MAPbX3 compounds (MA = CH3NH3(+); X = Cl, Br and I) showed that the isotropic (207)Pb NMR shift is strongly dependent on the nature of the halogen ions. Therefore (207)Pb NMR appears to be a very promising tool for the characterisation of local order in mixed halogen hybrid perovskites. (207)Pb NMR on MAPbBr2I served as a proof of concept...
October 5, 2016: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/27687310/vectorized-gene-therapy-of-liver-tumors-proof-of-concept-of-tg4023-mva-fcu1-in-combination-with-flucytosine
#17
F Husseini, J-P Delord, C Fournel-Federico, J Guitton, P Erbs, M Homerin, C Halluard, C Jemming, C Orange, J-M Limacher, J-E Kurtz
BACKGROUND: TG4023 is a modified vaccinia virus Ankara (MVA) containing the yeast-originated transgene FCU1, expressing cytosine deaminase and uracil phosphoribosyltransferase enzymes that transform the prodrug flucytosine (5-FC) into cytotoxic 5-fluorouracil (5-FU) and 5-fluorouridine-5'-monophosphate (5-FUMP), respectively. This first-in-human study aimed to assess the maximum tolerated dose (MTD) of intra-tumoral (IT) TG4023 and the safety, feasibility, and proof-of-concept (PoC) of TG4023/5-FC combination to deliver high 5-FU concentrations in tumors...
September 29, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27663483/pharmacodynamic-endpoints-as-clinical-trial-objectives-to-answer-important-questions-in-oncology-drug-development
#18
Ralph E Parchment, James H Doroshow
Analyzing the molecular interplay between malignancies and therapeutic agents is rarely a straightforward process, but we hope that this special issue of Seminars has highlighted the clinical value of such endeavors as well as the relevant theoretical and practical considerations. Here, we conclude with both an overview of the various high-value applications of clinical pharmacodynamics (PD) in developmental therapeutics and an outline of the framework for incorporating PD analyses into the design of clinical trials...
August 2016: Seminars in Oncology
https://www.readbyqxmd.com/read/27661964/real-time-dynamic-strain-monitoring-of-optical-links-using-the-backreflection-of-live-psk-data
#19
H F Martins, K Shi, B C Thomsen, S Martin-Lopez, M Gonzalez-Herraez, S J Savory
A major cause of faults in optical communication links is related to unintentional third party intrusions (normally related to civil/agricultural works) causing fiber breaks or cable damage. These intrusions could be anticipated and avoided by monitoring the dynamic strain recorded along the cable. In this work, a novel technique is proposed to implement real-time distributed strain sensing in parallel with an operating optical communication channel. The technique relies on monitoring the Rayleigh backscattered light from optical communication data transmitted using standard modulation formats...
September 19, 2016: Optics Express
https://www.readbyqxmd.com/read/27622603/pd-1-blockade-in-hodgkin-s-lymphoma-learning-new-tricks-from-an-old-teacher
#20
Pamela Blair Allen, Leo I Gordon
INTRODUCTION: Classical Hodgkin's Lymphoma (cHL) is characterized by genetic reliance on the PD-1 pathway. Rapid accumulation of data describing the role and efficacy of PD-1 and its blockade warrants a focused review. AREAS COVERED: In this article, we will review the unique biologic features that predispose cHL to PD-1 inhibition, current data regarding the safety and efficacy of PD-1 inhibitors in the treatment of cHL, biomarkers of immune response, ongoing clinical trials with PD-1 inhibitors, as well as areas of uncertainty...
October 2016: Expert Review of Hematology
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