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Brandon Leonard, Toni M Brand, Rachel A O'Keefe, Eliot Lee, Yan Zang, Jacquelyn D Kemmer, Hua Li, Jennifer R Grandis, Neil E Bhola
Cetuximab, the FDA-approved anti-EGFR antibody for head and neck squamous cell carcinoma (HNSCC), has displayed limited efficacy due to the emergence of intrinsic and acquired resistance. We and others have demonstrated that cetuximab resistance in HNSCC is driven by alternative receptor tyrosine kinases (RTK) including HER3, MET, and AXL. In an effort to overcome cetuximab resistance and circumvent toxicities associated with the administration of multiple RTK inhibitors, we sought to identify a common molecular target that regulates expression of multiple RTK...
May 23, 2018: Cancer Research
Qin Guo, Tanja Grimmig, Gabriel Gonzalez, Anita Giobbie-Hurder, Gretchen Berg, Nolan Carr, Brian J Wilson, Pallavi Banerjee, Jie Ma, Jason S Gold, Bisweswar Nandi, Qin Huang, Ana Maria Waaga-Gasser, Christine G Lian, George F Murphy, Markus H Frank, Martin Gasser, Natasha Y Frank
ATP-binding cassette member B5 (ABCB5) mediates multidrug resistance (MDR) in diverse malignancies and confers clinically relevant 5-fluorouracil resistance to CD133-expressing cancer stem cells (CSCs) in human colorectal cancer (CRC). Because of its recently identified roles in normal stem cell maintenance, we hypothesized that ABCB5 might also serve MDR-independent functions in CRC. Here, in a prospective clinical study of 142 CRC patients, we found that ABCB5 mRNA transcripts previously reported not to be significantly expressed in healthy peripheral blood mononuclear cells are significantly enriched in patient peripheral blood specimens compared with non-CRC controls and correlate with CRC disease progression...
May 22, 2018: Journal of Biological Chemistry
Joana Maria Mendes Pereira, Arminda Neves, Pedro Alfaiate, Mónica Santos, Henrique Aragão, João C Sousa
PURPOSE: Comparison of biometric measurements and calculation of intraocular lens with a new biometer (Pentacam®-AXL, Oculus, Germany) and a reference biometer (Lenstar LS 900®, Haag-Streit AG, Switzerland), in order to assess the agreement between these two devices. SETTING: Centro Hospitalar de Leiria, Portugal Materials and methods: Prospective, institutional study, in which measurements of axial length, anterior chamber depth from the corneal epithelium and endothelium to the anterior surface of the lens (anterior chamber depth ext and anterior chamber depth int), central corneal thickness and keratometry readings of the flattest and steepest meridians (K1 and K2) were obtained with the two systems...
May 1, 2018: European Journal of Ophthalmology
Jianping He, Jianzhuang Chen, Shaoliang Lin, Dechao Niu, Jina Hao, Xiaobo Jia, Nan Li, Jinlou Gu, Yongsheng Li, Jianlin Shi
A pillar[5]arene-based nonionic polyrotaxane (PR) with star-poly(ε-caprolactone) (S-PCL) as the axle, pillar[5]arene (DEP5) as the wheel and adamantane as the end-capped group is designed and synthesized. The resulting PR is subsequently assembled with β-cyclodextrin end-capped pH-stimulated poly (acrylic acid) (CD-PAA) via a host-guest interaction to form the supramolecular pseudo-block polymer PR-PAA. This supramolecular pseudo-block polymer could self-assemble in aqueous solution to produce PR-PAA based supramolecular vesicular nanoparticles (PR-SVNPs), which presents significantly enhanced drug loading capacity (DLC, 45...
May 22, 2018: Biomacromolecules
Min Yu, Wenjing Li, Qianqian Wang, Yan Wang, Fei Lu
Nuclear receptor NR1D2 is originally characterized as the repressor of genes involved in circadian rhythm. Recently, it is documented that NR1D2 is overexpressed in various cancers. However, the pathways and biological functions that NR1D2 involved in cancers remain poorly understood. Here, we reported that NR1D2 was abundant in human glioblastoma (GBM) tissue and cell lines but not primary human astrocytes. Silencing of NR1D2 changed the morphology of GBM cells, inhibited cell proliferation and motility, whereas had no effects on apoptosis...
May 18, 2018: Oncogene
María Jesús Gómez, Eduardo Corral, Cristina Castejón, Juan Carlos García-Prada
Crack detection for railway axles is key to avoiding catastrophic accidents. Currently, non-destructive testing is used for that purpose. The present work applies vibration signal analysis to diagnose cracks in real railway axles installed on a real Y21 bogie working on a rig. Vibration signals were obtained from two wheelsets with cracks at the middle section of the axle with depths from 5.7 to 15 mm, at several conditions of load and speed. Vibration signals were processed by means of wavelet packet transform energy...
May 17, 2018: Sensors
Hunain Alam, Na Li, Shilpa S Dhar, Sarah J Wu, Jie Lv, Kaifu Chen, Elsa R Flores, Laura Baseler, Min Gyu Lee
Lung adenocarcinoma (LUAD) is a major form of lung cancer, which is the leading cause of cancer death. Histone methylation reader proteins mediate the effect of histone methylation, a hallmark of epigenetic and transcriptional regulation of gene expression. However, their roles in LUAD are poorly understood. Here our bioinformatic screening and analysis in search of an LUAD-promoting histone methylation reader protein show that heterochromatin protein 1γ (HP1γ; also called CBX3) is among the most frequently overexpressed and amplified histone reader proteins in human LUAD, and that high HP1γ mRNA levels are associated with poor prognosis in LUAD patients...
May 15, 2018: Cancer Research
Judie B Alimonti, Maria Ribecco-Lutkiewicz, Caroline Sodja, Anna Jezierski, Danica B Stanimirovic, Qing Liu, Arsalan S Haqqani, Wayne Conlan, Mahmud Bani-Yaghoub
Zika virus (ZIKV) is a flavivirus that is highly neurotropic causing congenital abnormalities and neurological damage to the central nervous systems (CNS). In this study, we used a human induced pluripotent stem cell (iPSC)-derived blood brain barrier (BBB) model to demonstrate that ZIKV can infect brain endothelial cells (i-BECs) without compromising the BBB barrier integrity or permeability. Although no disruption to the BBB was observed post-infection, ZIKV particles were released on the abluminal side of the BBB model and infected underlying iPSC-derived neural progenitor cells (i-NPs)...
May 15, 2018: Fluids and Barriers of the CNS
Valeria Zanichelli, Luca Dallacasagrande, Arturo Arduini, Andrea Secchi, Giulio Ragazzon, Serena Silvi, Alberto Credi
Catenanes with desymmetrized ring components can undergo co-conformational rearrangements upon external stimulation and can form the basis for the development of molecular rotary motors. We describe the design, synthesis and properties of a [2]catenane consisting of a macrocycle-the 'track' ring-endowed with two distinct recognition sites (a bipyridinium and an ammonium) for a calix[6]arene-the 'shuttle' ring. By exploiting the ability of the calixarene to thread appropriate non-symmetric axles with directional selectivity, we assembled an oriented pseudorotaxane and converted it into the corresponding oriented catenane by intramolecular ring closing metathesis...
May 11, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Jordi Codony-Servat, Silvia García-Roman, Miguel Ángel Molina-Vila, Jordi Bertran-Alamillo, Ana Giménez-Capitán, Santiago Viteri, Andrés F Cardona, Erik d'Hondt, Niki Karachaliou, Rafael Rosell
INTRODUCTION: Mutations in EGFR correlate with impaired response to immune checkpoint inhibitors and the development of novel immunotherapeutic approaches for EGFR mutant non-small cell lung cancer (NSCLC) is of particular interest. Immunization against EGF has demonstrated efficacy in a phase III trial including unselected NSCLC patients, but little was known about the mechanisms involved in the effects of the anti-EGF antibodies generated by vaccination (anti-EGF VacAbs) or their activity in tumor cells with EGFR mutations...
May 8, 2018: Journal of Thoracic Oncology
Lorenzo Casimiro, Jessica Groppi, Massimo Baroncini, Marcello La Rosa, Alberto Credi, Serena Silvi
Among the plethora of photochromes reported so far, azobenzene has been proven to be the most suitable photoswitch for molecular systems and materials, due to its highly efficient and clean E-Z photoisomerization. Here we report two ammonium-based molecular axles bearing one or two p-cyanoazobenzene units at the extremities, able to form pseudorotaxanes with a crown ether macrocycle. The photochemistry of these compounds was studied in the isolated forms and in the pseudorotaxanes, showing that the functionalization speeds up the threading process without affecting the photochemical properties of the system...
May 3, 2018: Photochemical & Photobiological Sciences
Stephen M Keable, Oleg A Zadvornyy, Lewis E Johnson, Bojana Ginovska, Andrew J Rasmussen, Karamatullah Danyal, Brian J Eilers, Gregory A Prussia, Axl X LeVan, Simone Raugei, Lance C Seefeldt, John W Peters
Nitrogenase is the enzyme that reduces atmospheric dinitrogen (N2 ) to ammonia (NH3 ) in biological systems. It catalyzes a series of single-electron transfers from the donor iron protein (Fe protein) to the molybdenum-iron protein (MoFe protein) that contains the iron-molybdenum cofactor (FeMo-co) sites where N2 is reduced to NH3 The [8Fe-7S] P-cluster in the MoFe protein functions in nitrogenase catalysis as an intermediate electron carrier between the external electron donor, the Fe protein, and the FeMo-co sites of the MoFe protein...
May 2, 2018: Journal of Biological Chemistry
Tiina A Jokela, Agnete S T Engelsen, Agata Rybicka, Fanny A Pelissier Vatter, James C Garbe, Masaru Miyano, Crina Tiron, Dan Ferariu, Lars A Akslen, Martha R Stampfer, James B Lorens, Mark A LaBarge
The existence of rare cancer cells that sporadically acquire drug-tolerance through epigenetic mechanisms is proposed as one mechanism that drives cancer therapy failure. Here we provide evidence that specific microenvironments impose non-sporadic expression of proteins related to epithelial plasticity and drug resistance. Microarrays of robotically printed combinatorial microenvironments of known composition were used to make cell-based functional associations between microenvironments, which were design-inspired by normal and tumor-burdened breast tissues, and cell phenotypes...
2018: Frontiers in Cell and Developmental Biology
Marie-Anne Goyette, Stéphanie Duhamel, Léo Aubert, Ariane Pelletier, Paul Savage, Marie-Pier Thibault, Radia Marie Johnson, Peter Carmeliet, Mark Basik, Louis Gaboury, William J Muller, Morag Park, Philippe P Roux, Jean-Philippe Gratton, Jean-François Côté
AXL is activated by its ligand GAS6 and is expressed in triple-negative breast cancer cells. In the current study, we report AXL expression in HER2-positive (HER2+ ) breast cancers where it correlates with poor patient survival. Using murine models of HER2+ breast cancer, Axl, but not its ligand Gas6, was found to be essential for metastasis. We determined that AXL is required for intravasation, extravasation, and growth at the metastatic site. We found that AXL is expressed in HER2+ cancers displaying epithelial-to-mesenchymal transition (EMT) signatures where it contributes to sustain EMT...
May 1, 2018: Cell Reports
Stephen D P Fielden, David A Leigh, Charlie T McTernan, Borja Pérez-Saavedra, Iñigo J Vitorica-Yrezabal
We report the synthesis of crown ether-ammonium, amide and amine [2]rotaxanes via transition state stabilization of axle-forming reactions. In contrast to the two-step "clipping" and "capping" strategies generally used for rotaxane synthesis, here the components assemble into the interlocked molecule in a single, reagent-less, step under kinetic control. The crown ether accelerates the reaction of the axle-forming components through the cavity to give the threaded product in a form of metal-free active template synthesis...
May 3, 2018: Journal of the American Chemical Society
Rundong Zhao, Fei Qi, Yan-Ling Zhao, Klaus E Hermann, Rui-Qin Zhang, Michel A Van Hove
Periodic chains of molecular gears in which molecules couple with each other and rotate on surfaces have been previously explored by us theoretically using ab initio simulation tools. Based on the knowledge and experience gained about the interactions between neighboring molecular gears, we here explore the transmission of rotational motion and energy over larger distances, namely through a longer chain of gear-like passive "slave" molecules. Such microscopic gears exhibit quite different behaviors compared to rigid cogwheels in the macroscopic world, due to their structural flexibility affecting intermolecular interaction...
May 1, 2018: Journal of Physical Chemistry Letters
Arthur Baumann, Antoni Sánchez-Ferrer, Leandro Jacomine, Philippe Martinoty, Vincent Le Houerou, Falko Ziebert, Igor M Kulić
Responsive materials1-3 have been used to generate structures with built-in complex geometries4-6 , linear actuators7-9 and microswimmers10-12 . These results suggest that complex, fully functional machines composed solely from shape-changing materials might be possible 13 . Nonetheless, to accomplish rotary motion in these materials still relies on the classical wheel and axle motifs. Here we explore geometric zero-energy modes to elicit rotary motion in elastic materials in the absence of a rigid wheel travelling around an axle...
April 30, 2018: Nature Materials
Kelong Zhu, Giorgio Baggi, Stephen J Loeb
Mechanically interlocked molecules such as rotaxanes and catenanes comprise two or more components whose motion relative to each other can be controlled. A [2]rotaxane molecular shuttle, for example, consists of an axle bearing two recognition sites and a single macrocyclic wheel that can undergo a to-and-fro motion along the axle-shuttling between the recognition sites. The ability of mechanically interlocked molecules to undergo this type of large-amplitude change is the core mechanism behind almost every interlocked molecular switch or machine, including sophisticated mechanical systems such as a molecular elevator and a peptide synthesizer...
April 30, 2018: Nature Chemistry
Diederik Roke, Sander J Wezenberg, Ben L Feringa
The field of synthetic molecular machines has quickly evolved in recent years, growing from a fundamental curiosity to a highly active field of chemistry. Many different applications are being explored in areas such as catalysis, self-assembled and nanostructured materials, and molecular electronics. Rotary molecular motors hold great promise for achieving dynamic control of molecular functions as well as for powering nanoscale devices. However, for these motors to reach their full potential, many challenges still need to be addressed...
April 30, 2018: Proceedings of the National Academy of Sciences of the United States of America
David Leigh, Lucian Pirvu, Fredrik Schaufelberger, Daniel J Tetlow, Liang Zhang
We report on a rotaxane-like architecture secured by the in situ tying of an overhand knot in the tris(2,6-pyridyldicarboxamide) region of the axle through complexation with a lanthanide ion (Lu3+). The increase in steric bulk caused by the knotting entanglement locks a crown ether onto the thread. Removal of the lutetium ion unties the knot and, if the axle binding site for the ring is deactivated, the macrocycle spontaneously de-threads. If the binding interaction is switched on again, the crown ether re-threads over the 10 nm length of the untangled strand...
April 30, 2018: Angewandte Chemie
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