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https://www.readbyqxmd.com/read/27933467/osteosarcoma-overview
#1
REVIEW
Brock A Lindsey, Justin E Markel, Eugenie S Kleinerman
Osteosarcoma (OS) is the most common primary malignancy of bone and patients with metastatic disease or recurrences continue to have very poor outcomes. Unfortunately, little prognostic improvement has been generated from the last 20 years of research and a new perspective is warranted. OS is extremely heterogeneous in both its origins and manifestations. Although multiple associations have been made between the development of osteosarcoma and race, gender, age, various genomic alterations, and exposure situations among others, the etiology remains unclear and controversial...
December 8, 2016: Rheumatology and Therapy
https://www.readbyqxmd.com/read/27933281/pet-imaging-of-urokinase-type-plasminogen-activator-receptor-upar-in-prostate-cancer-current-status-and-future-perspectives
#2
REVIEW
Dorthe Skovgaard, Morten Persson, Andreas Kjaer
Overexpression of urokinase-type plasminogen activator receptors (uPAR) represents an important biomarker for aggressiveness in most common malignant diseases, including prostate cancer (PC). Accordingly, uPAR expression either assessed directly in malignant PC tissue or assessed directly in plasma (intact/cleaved forms)-provides independent additional clinical information to that contributed by PSA, Gleason score, and other relevant pathological and clinical parameters. In this respect, non-invasive molecular imaging by positron emission tomography (PET) offers a very attractive technology platform, which can provide the required quantitative information on the uPAR expression profile, without the need for invasive procedures and the risk of missing the target due to tumor heterogeneity...
2016: Clinical and Translational Imaging: Reviews in Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/27932557/quantitative-parameters-in-psma-targeted-pet-imaging-with-18f-dcfpyl-variability-in-normal-organ-uptake
#3
Xin Li, Steven P Rowe, Jeffrey P Leal, Michael A Gorin, Mohamad E Allaf, Ashley E Ross, Kenneth J Pienta, Martin A Lodge, Martin G Pomper
PURPOSE: (18)F-DCFPyL is a small-molecule inhibitor of the prostate-specific membrane antigen (PSMA) that has shown promise for evaluation of primary and metastatic prostate cancer (PC) using positron emission tomography (PET). Measuring the variability in normal organ uptake of (18)F-DCFPyL is necessary to understand its biodistribution, aid image interpretation, judge the reliability of scan quantification, and to provide a basis for therapeutic monitoring. METHODS: 65 consecutive (18)F-DCFPyL PET/CT scans from 64 patients with a history of PC were analyzed...
December 8, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/27930299/imaging-the-he2-quantum-halo-state-using-a-free-electron-laser
#4
Stefan Zeller, Maksim Kunitski, Jörg Voigtsberger, Anton Kalinin, Alexander Schottelius, Carl Schober, Markus Waitz, Hendrik Sann, Alexander Hartung, Tobias Bauer, Martin Pitzer, Florian Trinter, Christoph Goihl, Christian Janke, Martin Richter, Gregor Kastirke, Miriam Weller, Achim Czasch, Markus Kitzler, Markus Braune, Robert E Grisenti, Wieland Schöllkopf, Lothar Ph H Schmidt, Markus S Schöffler, Joshua B Williams, Till Jahnke, Reinhard Dörner
Quantum tunneling is a ubiquitous phenomenon in nature and crucial for many technological applications. It allows quantum particles to reach regions in space which are energetically not accessible according to classical mechanics. In this "tunneling region," the particle density is known to decay exponentially. This behavior is universal across all energy scales from nuclear physics to chemistry and solid state systems. Although typically only a small fraction of a particle wavefunction extends into the tunneling region, we present here an extreme quantum system: a gigantic molecule consisting of two helium atoms, with an 80% probability that its two nuclei will be found in this classical forbidden region...
December 6, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27929465/using-multi-fluorinated-bile-acids-and-in-vivo-magnetic-resonance-imaging-to-measure-bile-acid-transport
#5
Jessica Felton, Kunrong Cheng, Anan Said, Aaron C Shang, Su Xu, Diana Vivian, Melissa Metry, James E Polli, Jean-Pierre Raufman
Along with their traditional role as detergents that facilitate fat absorption, emerging literature indicates that bile acids are potent signaling molecules that affect multiple organs; they modulate gut motility and hormone production, and alter vascular tone, glucose metabolism, lipid metabolism, and energy utilization. Changes in fecal bile acids may alter the gut microbiome and promote colon pathology including cholerrheic diarrhea and colon cancer. Key regulators of fecal bile acid composition are the small intestinal Apical Sodium-dependent Bile Acid Transporter (ASBT) and fibroblast growth factor-19 (FGF19)...
November 27, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27928466/metabolic-positron-emission-tomography-imaging-of-cancer-pairing-lipid-metabolism-with-glycolysis
#6
EDITORIAL
Sandi A Kwee, John Lim
The limitations of fluorine-18 fluorodeoxy-D-glucose (FDG) in detecting some cancers has prompted a longstanding search for other positron emission tomography (PET) tracers to complement the imaging of glycolysis in oncology, with much attention paid to lipogenesis based on observations that the production of various lipid and lipid-containing compounds is increased in most cancers. Radiolabeled analogs of choline and acetate have now been used as oncologic PET probes for over a decade, showing convincingly improved detection sensitivity over FDG for certain cancers...
November 28, 2016: World Journal of Radiology
https://www.readbyqxmd.com/read/27924155/versatile-ph-response-micelles-with-high-cell-penetrating-helical-diblock-copolymers-for-photoacoustic-imaging-guided-synergistic-chemo-photothermal-therapy
#7
Shengyu Shi, Yajing Liu, Yu Chen, Zhihuang Zhang, Yunsheng Ding, Zongquan Wu, Jun Yin, Liming Nie
With high optical absorption efficiency, near infrared (NIR) dyes have been proposed as theranostic agents for fluorescence imaging, photoacoustic imaging (PAI), and photothermal therapy (PTT). However, inherent hydrophobicity and short circulation time of small molecule hinder the further biomedical application. Herein smart amphiphilic copolymer was synthesized containing IR780/camptothecin@poly(ε-caprolactone) (IR780/CPT@PCL) as core, helical poly(phenyl isocyanide) (PPI) blocks as shell with the pH-responsive rhodamine B (RhB) moieties in the core-shell interface...
2016: Theranostics
https://www.readbyqxmd.com/read/27920086/a-role-for-mitotic-bookmarking-of-sox2-in-pluripotency-and-differentiation
#8
Cédric Deluz, Elias T Friman, Daniel Strebinger, Alexander Benke, Mahé Raccaud, Andrea Callegari, Marion Leleu, Suliana Manley, David M Suter
Mitotic bookmarking transcription factors remain bound to chromosomes during mitosis and were proposed to regulate phenotypic maintenance of stem and progenitor cells at the mitosis-to-G1 (M-G1) transition. However, mitotic bookmarking remains largely unexplored in most stem cell types, and its functional relevance for cell fate decisions remains unclear. Here we screened for mitotic chromosome binding within the pluripotency network of embryonic stem (ES) cells and show that SOX2 and OCT4 remain bound to mitotic chromatin through their respective DNA-binding domains...
December 5, 2016: Genes & Development
https://www.readbyqxmd.com/read/27919658/quinolizinium-as-a-new-fluorescent-lysosomotropic-probe
#9
Emmanouil Zacharioudakis, Tatiana Cañeque, Raúl Custodio, Sebastian Müller, Ana M Cuadro, Juan J Vaquero, Raphaël Rodriguez
We have synthesized a collection of quinolizinium fluorescent dyes for the purpose of cell imaging. Preliminary biological studies in human U2OS osteosarcoma cancer cells have shown that different functional groups appended to the cationic quinolizinium scaffold efficiently modulate photophysical properties but also cellular distribution. While quinolizinium probes are known nuclear staining reagents, we have identified a particular quinolizinium derivative salt that targets the lysosomal compartment. This finding raises the question of predictability of specific organelle targeting from structural features of small molecules...
November 24, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27911291/a-metal-free-method-for-producing-mri-contrast-at-amyloid-%C3%AE
#10
Silvia Hilt, Tang Tang, Jeffrey H Walton, Madhu Budamagunta, Izumi Maezawa, Tamás Kálai, Kálmán Hideg, Vikrant Singh, Heike Wulff, Qizhi Gong, Lee-Way Jin, Angelique Louie, John C Voss
Alzheimer's disease (AD) is characterized by depositions of the amyloid-β (Aβ) peptide in the brain. The disease process develops over decades, with substantial neurological loss occurring before a clinical diagnosis of dementia can be rendered. It is therefore imperative to develop methods that permit early detection and monitoring of disease progression. In addition, the multifactorial pathogenesis of AD has identified several potential avenues for AD intervention. Thus, evaluation of therapeutic candidates over lengthy trial periods also demands a practical, noninvasive method for measuring Aβ in the brain...
November 26, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27906406/crystallization-assisted-nano-lens-array-fabrication-for-highly-efficient-and-color-stable-organic-light-emitting-diodes
#11
Young-Sam Park, Kyung-Hoon Han, Jehan Kim, Doo-Hee Cho, Jonghee Lee, Yoonjay Han, Jong Tae Lim, Nam Sung Cho, Byounggon Yu, Jeong-Ik Lee, Jang-Joo Kim
To date, all deposition equipment has been developed to produce planar films. Thus lens arrays with a lens diameter of <1 mm have been manufactured by combining deposition with other technologies, such as masks, surface treatment, molding etc. Furthermore, a nano-lens array (NLA) with a sufficiently small lens diameter (<1 μm) is necessary to avoid image quality degradation in high resolution displays. In this study, an organic NLA made using a conventional deposition technique - without combining with other techniques - is reported...
December 1, 2016: Nanoscale
https://www.readbyqxmd.com/read/27899451/real-time-spatial-and-temporal-mapping-of-the-distribution-of-c-di-gmp-during-biofilm-development
#12
Harikrishnan A S Nair, Saravanan Periasamy, Yang Liang, Staffan Kjelleberg, Scott A Rice
Bis-(3 ́-5 ́)-cyclic dimeric guanosine monophosphate (c-di-GMP) is a dynamic intracellular signaling molecule that plays a central role in the biofilm life cycle. Current methodologies for the quantification of c-di-GMP are typically based on chemical extraction, representing end-point measurements. Chemical methodologies also fail to take into consideration the physiological heterogeneity of the biofilm and thus represents an average c-di-GMP concentration across the entire biofilm. To address these problems, a ratiometric, image-based quantification method has been developed based on expression of the green fluorescence protein (GFP) under the control of the c-di-GMP responsive cdrA promoter (1)...
November 29, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27890855/linker-stability-influences-the-anti-tumor-activity-of-acetazolamide-drug-conjugates-for-the-therapy-of-renal-cell-carcinoma
#13
Samuele Cazzamalli, Alberto Dal Corso, Dario Neri
Small molecule-drug conjugates (SMDCs) are increasingly being considered as an alternative to antibody-drug conjugates (ADCs) for the selective delivery of anticancer agents to the tumor site, sparing normal tissues. Carbonic anhydrase IX (CAIX) is a membrane-bound enzyme, which is over-expressed in the majority of renal cell carcinomas and which can be efficiently targeted in vivo, using charged derivatives of acetazolamide, a small heteroaromatic sulfonamide. Here, we show that SMDC products, obtained by the coupling of acetazolamide with monomethyl auristatin E (MMAE) using dipeptide linkers, display a potent anti-tumoral activity in mice bearing xenografted SKRC-52 renal cell carcinomas...
November 24, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/27885812/a-whole-animal-chemical-screen-approach-to-identify-modifiers-of-intestinal-neutrophilic-inflammation
#14
Stefan H Oehlers, Maria Vega Flores, Christopher J Hall, Liuyang Wang, Dennis C Ko, Kathryn E Crosier, Philip S Crosier
By performing two high-content small molecule screens on DSS- and TNBS-induced zebrafish enterocolitis models of inflammatory bowel disease, we have identified novel anti-inflammatory drugs from the John Hopkins Clinical Compound Library that suppress neutrophilic inflammation. Live imaging of neutrophil distribution was used to assess the level of acute inflammation and concurrently screen for off-target drug effects. Supporting the validity of our screening strategy, most of the anti-inflammatory drug hits were known antibiotics or anti-inflammatory agents...
November 25, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27885682/fractional-laser-assisted-drug-uptake-impact-of-time-related-topical-application-to-achieve-enhanced-delivery
#15
Christina A Banzhaf, Daniel Thaysen-Petersen, Christiane Bay, Peter A Philipsen, Mette Mogensen, Tarl Prow, Merete Haedersdal
BACKGROUND AND OBJECTIVE: Ablative fractional laser (AFXL) is acknowledged to increase uptake of topically applied agents in skin. AFXL channels gradually close over time, which may impair this capability. The time frame for applying a drug after AFXL exposure remains to be established. The aim of this study, was to investigate the importance of time-related topical application after AFXL exposure and to relate resultant uptake in skin with AFXL channel morphology and skin integrity. STUDY DESIGN/MATERIALS AND METHODS: Buttock skin of healthy volunteers (n = 11) was exposed to 10,600 nm fractional CO2 laser using 5% density, 120 μm beam diameter, 15 mJ pulse energy...
November 25, 2016: Lasers in Surgery and Medicine
https://www.readbyqxmd.com/read/27882694/fused-bicyclic-caspase-1-inhibitors-assembled-by-copper-free-strain-promoted-alkyne-azide-cycloaddition-spaac
#16
Linghui Qian, Chong-Jing Zhang, Ji'en Wu, Shao Q Yao
Challenges exist in the development of potent and selective small-molecule inhibitors against caspase-1. Herein, by making use of the copper-free strain-promoted alkyne-azide cycloaddition (SPAAC) reaction between difluorinated cyclooctynes (DIFOs) and various azide-containing compounds, we showed for the first time that potential caspase-1 inhibitors could be rapidly synthesized. The resulting fused bicyclic compounds structurally resembled the central portion (P2 -P3 ) of Pralnacasan (a well-known small molecule caspase-1 inhibitor), with diversity at the P4 -position of the parental inhibitor conveniently installed from the azide component...
November 24, 2016: Chemistry: a European Journal
https://www.readbyqxmd.com/read/27879373/novel-molecular-add-on-based-on-evans-blue-confers-superior-pharmacokinetics-and-transforms-drugs-to-theranostic-agents
#17
Haojun Chen, Orit Jacobson, Gang Niu, Ido Weiss, Dale O Kiesewetter, Yi Liu, Ying Ma, Hua Wu, Xiaoyuan Chen
: One of the major design considerations for a drug is its pharmacokinetics in the blood. A drug with short half-life in the blood is less available at a target organ. Such a limitation dictates treatment with either high doses or more frequent doses, both of which may increase the likelihood of undesirable side effects. To address the need for additional methods to improve the blood half-life of drugs and molecular imaging agents, we developed an "add-on" molecule that contains three groups: (i) truncated Evans Blue (EB) dye molecule that binds to albumin with low micromolar affinity and provides prolonged half-life in the blood; (ii) a metal chelate that allows radiolabeling for imaging and radiotherapy; and (iii) a maleimide for easy conjugation to drug molecules...
November 22, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/27873206/discovery-of-rna-binding-small-molecules-using-small-molecule-microarrays
#18
Colleen M Connelly, Fardokht A Abulwerdi, John S Schneekloth
New methods to identify RNA-binding small molecules open yet unexplored opportunities for the pharmacological modulation of RNA-driven biology and disease states. One such approach is the use of small molecule microarrays (SMMs). Typically, SMMs are generated by spatially arraying and covalently linking a library of small molecules to a glass surface. Next, incubation of the arrays with a fluorescently labeled RNA reveals binding interactions that are detected upon slide imaging. The relative ease with which SMMs are manufactured enables the screening of multiple oligonucleotides in parallel against tens of thousands of small molecules, providing information about both binding and selectivity of identified RNA-small molecule interactions...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27873198/fabrication-of-bio-function-preserved-saccharide-microarray-chips-with-cyanuric-chloride-as-a-rotatable-linker
#19
Yi Chen, Chanjuan Liu, Xiao Wang
Microarray-based saccharide chips possess an inherent property of high throughput but remain hard to use in practice due mainly to their fabrication problems, which have led to many strategies proposed but nearly none can immobilize small saccharides without losing their bio-affinity. Herein introduced is an easy strategy able to directly immobilize all intact saccharides on solid surface with excellent preservation of their molecular recognition ability. The core idea is to anchor a saccharide molecule on a universally rotatable molecular frame to free its spatial adjustment during molecular recognition process...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27872870/nanoscale-organization-of-synaptic-adhesion-proteins-revealed-by-single-molecule-localization-microscopy
#20
Ingrid Chamma, Florian Levet, Jean-Baptiste Sibarita, Matthieu Sainlos, Olivier Thoumine
The advent of superresolution imaging has created a strong need for both optimized labeling strategies and analysis methods to probe the nanoscale organization of complex biological structures. We present a thorough description of the distribution of synaptic adhesion proteins at the nanoscopic scale, namely presynaptic neurexin-[Formula: see text] ([Formula: see text]), and its two postsynaptic binding partners neuroligin-1 (Nlg1) and leucine-rich-repeat transmembrane protein 2 (LRRTM2). We monitored these proteins in the membrane of neurons by direct stochastic optical reconstruction microscopy, after live surface labeling with Alexa647-conjugated monomeric streptavidin...
October 2016: Neurophotonics
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