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https://www.readbyqxmd.com/read/29330466/target-engagement-imaging-of-parp-inhibitors-in-small-cell-lung-cancer
#1
Brandon Carney, Susanne Kossatz, Benjamin H Lok, Valentina Schneeberger, Kishore K Gangangari, Naga Vara Kishore Pillarsetty, Wolfgang A Weber, Charles M Rudin, John T Poirier, Thomas Reiner
Insufficient chemotherapy response and rapid disease progression remain concerns for small-cell lung cancer (SCLC). Oncologists rely on serial CT scanning to guide treatment decisions, but this cannot assess in vivo target engagement of therapeutic agents. Biomarker assessments in biopsy material do not assess contemporaneous target expression, intratumoral drug exposure, or drug-target engagement. Here, we report the use of PARP1/2-targeted imaging to measure target engagement of PARP inhibitors in vivo. Using a panel of clinical PARP inhibitors, we show that PARP imaging can quantify target engagement of chemically diverse small molecule inhibitors in vitro and in vivo...
January 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29329462/silibinin-from-silybum-marianum-stimulates-embryonic-stem-cell-vascular-differentiation-via-the-stat3-pi3-k-akt-axis-and-nitric-oxide
#2
Enas Hussein Ali, Fatemeh Sharifpanah, Maria Wartenberg, Heinrich Sauer
Silibinin, the bioactive compound of milk thistle (Silybum marianum), exerts tissue protective and regenerative effects that may include stem cell differentiation toward vascular cells. The purpose of the present study was to investigate whether silibinin stimulates blood vessel formation from mouse embryonic stem (ES) cells and to unravel the underlying signaling cascade. Vascular branching points were assessed by confocal laser scanning microscopy and computer-assisted image analysis of CD31-positive cell structures...
January 12, 2018: Planta Medica
https://www.readbyqxmd.com/read/29326997/evidence-of-lying-molecules-in-the-structure-of-the-most-condensed-phase-of-semi-fluorinated-alkane-monolayers
#3
Philippe Fontaine, Lisa Bardin, Marie-Claude Fauré, Eduardo J M Filipe, Michel Goldmann
Semifluorinated alkanes are known to form peculiar nano-structured monolayers on the surface of water. A comprehensive analysis of in situ Grazing Incidence Small Angle X-ray Scattering (GISAXS) proves that the structure of their condensed phase consists of domains of upright molecules surrounded by lying down molecules. Such a model explains the non-coalescence of the domains and is in agreement with the high resolution AFM images of monolayers at the surfaces of solid substrates. The interaction of the lying molecule dipoles with the dipole of the water surface is proposed to explain the observed structuration...
January 12, 2018: Nanoscale
https://www.readbyqxmd.com/read/29321282/nucleus-assembly-and-import-in-xenopus-laevis-egg-extract
#4
Pan Chen, Daniel L Levy
Xenopus egg extract represents a powerful cell-free biochemical tool for studying organelle assembly and function. Large quantities of cytoplasm can be isolated, and biochemical manipulation of extract composition and cell cycle state is relatively straightforward. In this protocol, we describe the reconstitution of nuclear assembly by adding a chromatin source to interphasic X. laevis egg extract. Intact nuclei assemble within 30-45 min of initiating the reaction, followed by nuclear growth. We also describe methods for imaging and quantifying nuclear import kinetics...
January 10, 2018: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/29320704/extracellular-vesicles-provide-a-means-for-tissue-crosstalk-during-exercise
#5
Martin Whitham, Benjamin L Parker, Martin Friedrichsen, Janne R Hingst, Marit Hjorth, William E Hughes, Casey L Egan, Lena Cron, Kevin I Watt, Rhiannon P Kuchel, Navind Jayasooriah, Emma Estevez, Tim Petzold, Catherine M Suter, Paul Gregorevic, Bente Kiens, Erik A Richter, David E James, Jørgen F P Wojtaszewski, Mark A Febbraio
Exercise stimulates the release of molecules into the circulation, supporting the concept that inter-tissue signaling proteins are important mediators of adaptations to exercise. Recognizing that many circulating proteins are packaged in extracellular vesicles (EVs), we employed quantitative proteomic techniques to characterize the exercise-induced secretion of EV-contained proteins. Following a 1-hr bout of cycling exercise in healthy humans, we observed an increase in the circulation of over 300 proteins, with a notable enrichment of several classes of proteins that compose exosomes and small vesicles...
January 9, 2018: Cell Metabolism
https://www.readbyqxmd.com/read/29320333/prostate-specific-membrane-antigen-pet-clinical-utility-in-prostate-cancer-normal-patterns-pearls-and-pitfalls
#6
Michael S Hofman, Rodney J Hicks, Tobias Maurer, Matthias Eiber
Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein that is overexpressed in prostate cancer. Radiolabeled small molecules that bind with high affinity to its active extracellular center have emerged as a potential new diagnostic standard of reference for prostate cancer, resulting in images with extraordinary tumor-to-background contrast. Currently, gallium 68 (68Ga)-PSMA-11 (or HBED-PSMA) is the most widely used radiotracer for PSMA positron emission tomography (PET)/computed tomography (CT) or PSMA PET/magnetic resonance (MR) imaging...
January 2018: Radiographics: a Review Publication of the Radiological Society of North America, Inc
https://www.readbyqxmd.com/read/29319181/the-small-gtpase-rhoa-regulates-the-limk1-2-cofilin-pathway-to-modulate-cytoskeletal-dynamics-in-oocyte-meiosis
#7
Xing Duan, Yu Zhang, Kun-Lin Chen, Hao-Lin Zhang, Lan-Lan Wu, Hong-Lin Liu, Zhen-Bo Wang, Shao-Chen Sun
LIM kinases (LIMK1/2) are LIM domain-containing serine/threonine/tyrosine kinases that mediate multiple cellular processes in mitosis. In the present study, we explored the functional roles and potential signaling pathway of LIMK1/2 during mouse oocyte meiosis. Disruption of LIMK1/2 activity and expression significantly decreased oocyte polar body extrusion. Live-cell imaging revealed that spindle migration was disturbed after both LIMK1 and LIMK2 knock down, and this might be due to aberrant distribution of actin filaments in the oocyte cytoplasm and cortex...
January 10, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29317344/redox-responsive-micelles-from-disulfide-bond-bridged-hyaluronic-acid-tocopherol-succinate-for-the-treatment-of-melanoma
#8
Junping Xia, Yunai Du, Liping Huang, Birendra Chaurasiya, Jiaheng Tu, Thomas J Webster, Chunmeng Sun
Nanotechnology-based chemotherapy is efficient in cancer treatment due to the targeted delivery of small molecules via nano-carriers, which are usually regarded as "inert". However, nano-materials are more preferred as carriers since many cause synergistic anti-tumor effects along with the drug cargo. In this study, a "bioactive" tocopherol succinate (TOS) was grafted to hyaluronic acid (HA) via of disulfide bonds to obtain HA-ss-TOS conjugates which can assemble into nano-micelles but dissociate when exposed to reducing environments in vitro and in vivo...
January 6, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29316454/realizing-highly-chemoselective-detection-of-h2s-in%C3%A2-vitro-and-in%C3%A2-vivo-with-fluorescent-probes-inside-core-shell-silica-nanoparticles
#9
Feiyi Wang, Ge Xu, Xianfeng Gu, Zhijun Wang, Zhiqiang Wang, Ben Shi, Cuifen Lu, Xueqing Gong, Chunchang Zhao
Hydrogen sulfide (H2S) is an appealing signaling molecule that plays fundamental roles in health and disease. However, H2S-mediated selective chemical transformations for the construction of imaging probes are limited, retarding the interrogation of H2S-related biological processes. Here, we present an alternative approach for engineering a new generation of efficient probes with a nonchemoselective moiety as a building block. To demonstrate our design concept, we developed a sulfoxide-functionalized BODIPY that exhibited a substantial redshift in its absorption and emission spectra upon reduction with H2S...
January 4, 2018: Biomaterials
https://www.readbyqxmd.com/read/29313656/pl-w18o49-tpz-nanoparticles-for-simultaneous-hypoxia-activated-chemotherapy-and-photothermal-therapy
#10
Peichen Zhao, Shuangshuang Ren, Yumei Liu, Wei Huang, Chao Zhang, Jian He
The combination of W18O49 and TPZ core has been first introduced into the preparation of PEG-PCL (PL) surrounded nanoparticles (NPs). The aim of using W18O49 is employing its capability of reacting with the absorbed O2 to generate reactive oxygen species (ROS) when exposed to a long wavelength laser at 808 nm to increase skin penetration and body tolerance. In this work, we have demonstrated that W18O49 unit gives rise to more hypoxic tumor microenvironment and activate the prodrug TPZ to achieve hypoxia-activated chemotherapy, which could be monitored by the intracellular ROS/hypoxia detection and in vivo PET imaging...
January 9, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29311692/surface-functionalization-of-electrospun-scaffolds-using-recombinant-human-decorin-attracts-circulating-endothelial-progenitor-cells
#11
Svenja Hinderer, Katrin Sudrow, Maria Schneider, Monika Holeiter, Shannon Lee Layland, Martina Seifert, Katja Schenke-Layland
Decorin (DCN) is an important small leucine-rich proteoglycan present in the extracellular matrix (ECM) of many organs and tissues. Endothelial progenitor cells (EPCs) are able to interact with the surrounding ECM and bind to molecules such as DCN. Here, we recombinantly produced full-length human DCN under good laboratory practice (GLP) conditions, and after detailed immunological characterization, we investigated its potential to attract murine and human EPCs (mEPCs and hECFCs). Electrospun polymeric scaffolds were coated with DCN or stromal cell-derived factor-1 (SDF-1α) and were then dynamically cultured with both cell types...
January 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29303272/comparative-analysis-of-small-molecule-diffusivity-in-different-fat-crystal-network
#12
Xiuhang Chai, Zong Meng, Peirang Cao, Jiang Jiang, Yuanfa Liu
Oil migration and fat recrystallization in fat-structured food materials can result in significant deterioration in food quality. Consequently, it is important to monitor and quantify the diffusivities of the migrants in fat crystal network. The diffusion coefficients of Nile red dye in liquid oils through fully hydrogenated palm kernel oil (FHPKO) / triolein (OOO) and fully hydrogenated soybean oil (FHSO) / triolein (OOO) systems were evaluated by the fluorescence recovery after photobleaching (FRAP) method...
January 5, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29298867/repeat-doses-of-antibody-to-serum-amyloid-p-component-clear-amyloid-deposits-in-patients-with-systemic-amyloidosis
#13
Duncan B Richards, Louise M Cookson, Sharon V Barton, Lia Liefaard, Thirusha Lane, David F Hutt, James M Ritter, Marianna Fontana, James C Moon, Julian D Gillmore, Ashutosh Wechalekar, Philip N Hawkins, Mark B Pepys
Systemic amyloidosis is a fatal disorder caused by pathological extracellular deposits of amyloid fibrils that are always coated with the normal plasma protein, serum amyloid P component (SAP). The small-molecule drug, miridesap, [(R)-1-[6-[(R)-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid (CPHPC)] depletes circulating SAP but leaves some SAP in amyloid deposits. This residual SAP is a specific target for dezamizumab, a fully humanized monoclonal IgG1 anti-SAP antibody that triggers immunotherapeutic clearance of amyloid...
January 3, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29296665/parallel-screening-for-rapid-identification-of-orthogonal-bioluminescent-tools
#14
Colin M Rathbun, William B Porterfield, Krysten A Jones, Marian J Sagoe, Monique R Reyes, Christine T Hua, Jennifer A Prescher
Bioluminescence imaging with luciferase enzymes and luciferin small molecules is a well-established technique for tracking cells and other biological features in rodent models. Despite its popularity, bioluminescence has long been hindered by a lack of distinguishable probes. Here we present a method to rapidly identify new substrate-selective luciferases for multicomponent imaging. Our strategy relies on parallel screening of luciferin analogues with panels of mutant enzymes. The compiled data set is then analyzed in silico to uncover mutually orthogonal sets...
December 27, 2017: ACS Central Science
https://www.readbyqxmd.com/read/29290789/acid-degradable-dextran-as-an-image-guided-sirna-carrier-for-cox-2-downregulation
#15
Zhihang Chen, Balaji Krishnamachary, Marie-France Penet, Zaver M Bhujwalla
Purpose: Effective in vivo delivery of siRNA to silence genes is a highly sought-after goal in the treatment of multiple diseases. Cyclooxygenase-2 (COX-2) is a major mediator of inflammation and its effective and specific downregulation has been of major interest to treat conditions ranging from auto-immune diseases to gastric inflammation and cancer. Here we developed a novel and efficient method to produce a multiple imaging reporter labeled cationic dextran nanopolymer with cleavable positive charge groups for COX-2 siRNA delivery...
2018: Theranostics
https://www.readbyqxmd.com/read/29287020/state-of-the-art-diagnosis-and-treatment-of-melanoma-optimal-multidetector-computed-tomographic-practice-to-identify-metastatic-disease-and-review-of-innovative-therapeutic-agents
#16
Blake C Jones, Evan J Lipson, Brandon Childers, Elliot K Fishman, Pamela T Johnson
The incidence of melanoma has risen dramatically over the past several decades. Oncologists rely on the ability of radiologists to identify subtle radiographic changes representing metastatic and recurrent melanoma in uncommon locations on multidetector computed tomography (MDCT) as the front-line imaging surveillance tool. To accomplish this goal, MDCT acquisition and display must be optimized and radiologist interpretation and search patterns must be tailored to identify the unique and often subtle metastatic lesions of melanoma...
December 28, 2017: Journal of Computer Assisted Tomography
https://www.readbyqxmd.com/read/29284087/surpassing-single-linewidth-active-tuning-with-photochromic-molecules-coupled-to-plasmonic-nanoantennas
#17
Wade M Wilson, Jon W Stewart, Maiken H Mikkelsen
Active plasmonic nanostructures with tunable resonances promise to enable smart materials with multiple functionalities, on-chip spectral-based imaging and low-power optoelectronic devices. A variety of tunable materials have been integrated with plasmonic structures, however, the tuning range in the visible regime has been limited to less than the linewidth of the resonance resulting in small on/off ratios. Here we demonstrate dynamic, reversible tuning of plasmon resonances up to 71 nm in the visible regime by incorporating photochromic molecules into plasmonic nanopatch antennas...
December 28, 2017: Nano Letters
https://www.readbyqxmd.com/read/29284070/evaluation-of-fluorescence-guided-surgery-agents-in-a-murine-model-of-soft-tissue-fibrosarcoma
#18
Andrew C Prince, Andrew S McGee, Herrick Siegel, Eben L Rosenthal, Nicole K Behnke, Jason M Warram
BACKGROUND AND OBJECTIVES: Soft tissue sarcomas (STS) are mesenchymal malignancies. Treatment mainstay is surgical resection with negative margins ± adjuvant treatment. Fluorescence-guided surgical (FGS) resection can delineate intraoperative margins; FGS has improved oncologic outcomes in other malignancies. This novel strategy may minimize resection-associated morbidity while improving local tumor control. METHODS: We evaluate the tumor-targeting specificity and utility of fluorescence-imaging agents to provide disease-specific contrast...
December 28, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/29283264/redesigning-the-coumarin-scaffold-into-small-bright-fluorophores-with-far-red-to-nir-emission-and-large-stokes-shifts-useful-for-cell-imaging
#19
Albert Gandioso, Roger Bresolí-Obach, Alba Nin-Hill, Manel Bosch, Marta Palau, Alex Galindo, Sara Contreras, Anna Rovira, Carme Rovira, Santi Nonell, Vicente Marchán
Among the palette of fluorescent organic molecules described up to now, coumarins are ideal candidates for developing cellular and molecular imaging tools due to their high cell permeability and minimal perturbation to the living system. However, blue to cyan fluorescence emission usually difficult in vivo applications due to the inherent toxicity and poor tissue penetration of short visible light wavelengths. Here we introduce a new family of coumarin-based fluorophores, nicknamed COUPY, with promising photophysical properties, including emission in the far-red/NIR region, large Stokes' shifts, high photostability, and excellent brightness...
December 28, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/29281824/single-molecule-quantification-of-translation-dependent-association-of-mrnas-with-the-endoplasmic-reticulum
#20
Franka Voigt, Hui Zhang, Xianying A Cui, Désirée Triebold, Ai Xin Liu, Jan Eglinger, Eliza S Lee, Jeffrey A Chao, Alexander F Palazzo
It is well established that mRNAs encoding secretory or membrane-bound proteins are translated on the surface of the endoplasmic reticulum (ER). The extent to which mRNAs that encode cytosolic proteins associate with the ER, however, remains controversial. To address this question, we quantified the number of cytosolic protein-encoding mRNAs that co-localize with the ER using single-molecule RNA imaging in fixed and living cells. We found that a small but significant number of mRNAs that encode cytosolic proteins associate with the ER and show that this interaction is translation dependent...
December 26, 2017: Cell Reports
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