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https://www.readbyqxmd.com/read/28936468/gfp-grb2-translocation-assay-using-high-content-imaging-to-screen-for-modulators-of-egfr-signaling
#1
Julia Petschnigg, Robin Ketteler
High-content screening is a useful tool to understand complex cellular processes and to identify genes, proteins or small molecule compounds that modulate such pathways. High-content assays monitor the function of a protein or pathway by visualizing a change in an image-based readout, such as a change in the localization of a reporter protein. Examples of this can be the translocation of a fluorescently tagged protein from the cytoplasm to the nucleus or to the plasma membrane. One protein that is known to undergo such translocation is the Growth Factor Receptor-bound protein 2 (GRB2) that is recruited to the plasma membrane upon stimulation of a growth factor receptor and subsequently undergoes internalization...
September 5, 2017: Bio-protocol
https://www.readbyqxmd.com/read/28935537/affibody-molecules-for-the-molecular-imaging-and-targeted-drug-delivery-in-the-management-of-breast-cancer
#2
REVIEW
Anindita De, Gowthamarajan Kuppusamy, Veera Venkata Satyanarayana Reddy Karri
Breast cancer is one of the leading reasons for the morbidity and mortality of cancer related death globally. The modern therapies are basically the combination of the breast-preserving surgeries or ablation with or without node biopsy or destroying the carcinoma cells adjuvant with chemotherapy, radiotherapy, hormonal or biological therapies depending upon the nature of the receptor of the cancerous cells, nature of the lymph node, as well as the tendency of the recurrence. For decade's carcinoma management suffered by the limitation of imagining, targeting and penetrability problem associated with management and cure of this deadly disease leads to unwanted chemo-toxicity and side effects...
September 18, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28931522/three-dimensional-morphometric-analysis-of-the-renal-vasculature
#3
Zohaib Khan, Jennifer P Ngo, Bianca Le, Roger G Evans, James Todd Pearson, Bruce S Gardiner, David W Smith
Vascular topology and morphology is critical in the regulation of blood flow and the transport of small solutes including oxygen, carbon dioxide, nitric oxide and hydrogen sulfide. Renal vascular morphology is particularly challenging as many arterial walls are partially wrapped by the walls of veins. In the absence of a precise characterization of three-dimensional branching vascular geometry, accurate computational modeling of the intrarenal transport of small diffusible molecules is impossible. An enormous manual effort was required to achieve a relatively precise characterization of rat renal vascular geometry, highlighting the need for an automated method for analysis of branched vasculature morphology to allow characterization of the renal vascular geometry of other species, including humans...
September 20, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28927531/discriminating-rna-variants-with-single-molecule-allele-specific-fish
#4
REVIEW
Martyna O Urbanek, Wlodzimierz J Krzyzosiak
DNA mutations of various types often affect the cellular localization and function of gene products. The role of mutant transcripts in the pathogenesis of human disease is increasingly recognized. Among the pathogenic RNA variants are transcripts with single nucleotide substitutions, small insertions or deletions, aberrantly or alternatively spliced transcripts and RNAs derived from fused genes. To discriminate among transcripts, particularly those of low abundance, showing small or large sequence differences, a highly sensitive and specific RNA imaging method is required...
July 2017: Mutation Research
https://www.readbyqxmd.com/read/28926956/carbonic-anhydrase-inhibition-and-the-management-of-hypoxic-tumors
#5
REVIEW
Claudiu T Supuran
Hypoxia and acidosis are salient features of many tumors, leading to a completely different metabolism compared to normal cells. Two of the simplest metabolic products, protons and bicarbonate, are generated by the catalytic activity of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1), with at least two of its isoforms, CA IX and XII, mainly present in hypoxic tumors. Inhibition of tumor-associated CAs leads to an impaired growth of the primary tumors, metastases and reduces the population of cancer stem cells, leading thus to a complex and beneficial anticancer action for this class of enzyme inhibitors...
September 16, 2017: Metabolites
https://www.readbyqxmd.com/read/28925688/live-cell-imaging-of-mitochondrial-autophagy-with-a-novel-fluorescent-small-molecule
#6
Hidefumi Iwashita, Satoru Torii, Noriyoshi Nagahora, Munetaka Ishiyama, Kosei Shioji, Kazumi Sasamoto, Shigeomi Shimizu, Kentaro Okuma
There has been a growing interest in mitophagy, mitochondria-selective autophagy, which plays an essential role in maintaining intracellular homeostasis. We have developed a small-molecule fluorescent probe, Mtphagy Dye, for visualizing mitophagy, which was readily synthesized from a known perylene derivative, perylene-3,4-dicarboxylic anhydride. Mtphagy Dye has suitable fluorescent properties for detecting mitochondrial acidification during mitophagy in the long-wavelength region that does not damage mitochondria...
September 21, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28925395/small-molecules-targeted-to-the-microtubule-hec1-interaction-inhibit-cancer-cell-growth-through-microtubule-stabilization
#7
M Ferrara, G Sessa, M Fiore, F Bernard, I A Asteriti, E Cundari, G Colotti, S Ferla, M Desideri, S Buglioni, D Trisciuoglio, D Del Bufalo, A Brancale, F Degrassi
Highly expressed in cancer protein 1 (Hec1) is a subunit of the kinetochore (KT)-associated Ndc80 complex, which ensures proper segregation of sister chromatids at mitosis by mediating the interaction between KTs and microtubules (MTs). HEC1 mRNA and protein are highly expressed in many malignancies as part of a signature of chromosome instability. These properties render Hec1 a promising molecular target for developing therapeutic drugs that exert their anticancer activities by producing massive chromosome aneuploidy...
September 18, 2017: Oncogene
https://www.readbyqxmd.com/read/28924668/synthesis-of-janelia-fluor-halotag-and-snap-tag-ligands-and-their-use-in-cellular-imaging-experiments
#8
Jonathan B Grimm, Timothy A Brown, Brian P English, Timothée Lionnet, Luke D Lavis
The development of genetically encoded self-labeling protein tags such as the HaloTag and SNAP-tag has expanded the utility of chemical dyes in microscopy. Intracellular labeling using these systems requires small, cell-permeable dyes with high brightness and photostability. We recently discovered a general method to improve the properties of classic fluorophores by replacing N,N-dimethylamino groups with four-membered azetidine rings to create the "Janelia Fluor" dyes. Here, we describe the synthesis of the HaloTag and SNAP-tag ligands of Janelia Fluor 549 and Janelia Fluor 646 as well as standard labeling protocols for use in ensemble and single-molecule cellular imaging...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28920432/plk1-targeted-fluorescent-tumor-imaging-with-high-signal-background-ratio
#9
Ji-Ting Hou, Kyung-Phil Ko, Hu Shi, Wen Xiu Ren, Peter Verwilst, Seyoung Koo, Jin Yong Lee, Sung-Gil Chi, Jong Seung Kim
As significantly expressed during cell division, polo-like kinase 1 (PLK1) plays crucial roles in numerous mitotic events and has attracted interest as a potential therapeutic marker in oncological drug discovery. We prepared two small molecular fluorescent probes, 1 and 2, conjugated to SBE13 (a type II PLK1 inhibitor) to investigate the PLK1-targeted imaging of cancer cells and tumors. Enzymatic docking studies, molecular dynamics simulations, in vitro and in vivo imaging experiments, all supported the selective targeting and visualization of PLK1 expressing cells by probes 1 and 2, and probe 2 was successfully demonstrated to image PLK1-upregualted tumors with a remarkable signal to background ratios...
September 18, 2017: ACS Sensors
https://www.readbyqxmd.com/read/28920426/methotrexate-camptothecin-prodrug-nanoassemblies-as-a-versatile-nanoplatform-for-biomodal-imaging-guided-self-active-targeted-and-synergistic-chemotherapy
#10
Yang Li, Jinyan Lin, Jinyuan Ma, Liang Song, Huirong Lin, Bowen Tang, Dengyue Chen, Guanghao Su, Shefang Ye, Xuan Zhu, Fang-Hong Luo, Zhenqing Hou
"All-in-one" carrier-free-based nano-multi-drug self-delivery system could combine triple advantages of small molecules, nanoscale characteristics, and synergistic combination therapy together. Researches have showed that dual-acting small molecular methotrexate (MTX) could target and kill the folate receptors-overexpressing cancer cells. Inspired by this mechanism, a novel collaborative "early-phase tumor-selective targeting and late-phase synergistic anticancer" approach was developed for the self-assembly of chemotherapeutic drug-drug conjugate, which showed various advantages of more simplicity, efficiency, and flexibility over the conventional approach that was only based on single or combination cancer chemotherapy...
September 18, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28916621/-64-cu-labeled-repebody-molecules-for-imaging-of-epidermal-growth-factor-receptor-expressing-tumors
#11
Ayoung Pyo, Misun Yun, Hyeon-Sik Kim, Tae-Yoon Kim, Joong-Jae Lee, Jung Young Kim, Sunwoo Lee, Seong Young Kwon, Hee-Seung Bom, Hak-Sung Kim, Dong-Yeon Kim, Jung-Joon Min
The epidermal growth factor receptor (EGFR) is a member of the erbB family of receptors and is overexpressed in many tumor types. A repebody is a newly designed non-antibody protein scaffold for tumor targeting that contains leucine-rich repeat modules. In this study, three (64)Cu-labeled anti-EGFR repebodies with different chelators were synthesized, and their biological characteristics were assessed in cultured cells and tumor-bearing mice. Methods: Repebodies (rEgAs) were synthesized with the chelators p-SCN-Bn-NOTA, DOTA-NHS ester, or p-SCN-Bn-DTPA in 1...
September 15, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28900238/limitations-of-qdot-labelling-compared-to-directly-conjugated-probes-for-single-particle-tracking-of-b-cell-receptor-mobility
#12
Libin Abraham, Henry Y Lu, Rebeca Cardim Falcão, Joshua Scurll, Timothy Jou, Brian Irwin, Reza Tafteh, Michael R Gold, Daniel Coombs
Single-particle tracking (SPT) is a powerful method for exploring single-molecule dynamics in living cells with nanoscale spatiotemporal resolution. Photostability and bright fluorescence make quantum dots (Qdots) a popular choice for SPT. However, their large size could potentially alter the mobility of the molecule of interest. To test this, we labelled B cell receptors on the surface of B-lymphocytes with monovalent Fab fragments of antibodies that were either linked to Qdots via streptavidin or directly conjugated to the small organic fluorophore Cy3...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28898952/temperature-responsive-fluorescent-polymer-nanoparticles-trfnps-for-cellular-imaging-and-controlled-releasing-of-drug-to-living-cells
#13
Ziang Zhang, Di Zhang, Lin Wei, Xi Wang, Yueling Xu, Hung-Wing Li, Ming Ma, Bo Chen, Lehui Xiao
Recent studies have demonstrated that drug delivery by using functional nanomaterials with imaging capability could afford plenty of insightful information for the better control of the delivery process. In this work, we developed temperature responsive fluorescent nanoparticles (TRFNPs) for drug delivery and cellular imaging. The TRFNP was fabricated by one-pot co-precipitation of thermal sensitive amphiphilic block copolymers polystyrene-b-poly(N-isopropyl acrylamide) (PS-b-PNIPAM) and fluorescent conjugated polymer poly [(9,9-dioctylfluorenyl-2,7-diyl)-alt-co-(1,4-benzo(2,1',3)-thiadiazole)] (PFBT) in the presence of desired small guest molecules...
September 1, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28898567/multicolor-photo-crosslinkable-aiegens-toward-compact-nanodots-for-subcellular-imaging-and-sted-nanoscopy
#14
Xiaofeng Fang, Xuanze Chen, Rongqin Li, Zhihe Liu, Haobin Chen, Zezhou Sun, Bo Ju, Yifei Liu, Sean Xiao-An Zhang, Dan Ding, Yujie Sun, Changfeng Wu
Aggregation induced emission (AIE) has attracted considerable interest for the development of fluorescence probes. However, controlling the bioconjugation and cellular labeling of AIE dots is a challenging problem. Here, this study reports a general approach for preparing small and bioconjugated AIE dots for specific labeling of cellular targets. The strategy is based on the synthesis of oxetane-substituted AIEgens to generate compact and ultrastable AIE dots via photo-crosslinking. A small amount of polymer enriched with oxetane groups is cocondensed with most of the AIEgens to functionalize the nanodot surface for subsequent streptavidin bioconjugation...
September 12, 2017: Small
https://www.readbyqxmd.com/read/28891033/targeted-alpha-therapy-of-mcrpc-dosimetry-estimate-of-213-bismuth-psma-617
#15
Clemens Kratochwil, Karl Schmidt, Ali Afshar-Oromieh, Frank Bruchertseifer, Hendrik Rathke, Alfred Morgenstern, Uwe Haberkorn, Frederik L Giesel
PURPOSE: PSMA-617 is a small molecule targeting the prostate-specific membrane antigen (PSMA). In this work, we estimate the radiation dosimetry for this ligand labeled with the alpha-emitter (213)Bi. METHODS: Three patients with metastatic prostate cancer underwent PET scans 0.1 h, 1 h, 2 h, 3 h, 4 h and 5 h after injection of (68)Ga-PSMA-617. Source organs were kidneys, liver, spleen, salivary glands, bladder, red marrow and representative tumor lesions...
September 11, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28888009/synthesis-and-evaluation-of-the-cytotoxic-and-anti-proliferative-properties-of-zno-quantum-dots-against-mcf-7-and-mda-mb-231-human-breast-cancer-cells
#16
Roshini A, Srikanth Jagadeesan, Young-Jae Cho, Jong-Hwan Lim, Kyung Hyun Choi
Current trends in therapeutic research are the application of nanomaterial carriers for cancer therapy. One such molecule, ZnO, originally used in diagnosis and as a drug carrier, is gaining importance for its biological properties. Here, we report for the first time, the scope of ZnO QDs for enhanced cytotoxicity against MCF-7 and metastatic MDA-MB-231 human breast cancer cells. Unlike other ZnO nanostructures, ZnO QDs are dispersed and small sized (8-10nm) which is believed to greatly increase the cellular uptake...
December 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28882182/-s-crizotinib-induces-apoptosis-in-human-non-small-cell-lung-cancer-cells-by-activating-ros-independent-of-mth1
#17
Xuanxuan Dai, Guilong Guo, Peng Zou, Ri Cui, Weiqian Chen, Xi Chen, Changtian Yin, Wei He, Rajamanickam Vinothkumar, Fan Yang, Xiaohua Zhang, Guang Liang
BACKGROUND: Non-small cell lung cancer (NSCLC) accounts for approximately 80-85% of all lung cancers and is usually diagnosed at an advanced stage with poor prognosis. Targeted therapy has produced unprecedented outcomes in patients with NSCLC as a number of oncogenic drivers have been found. Crizotinib, a selective small-molecule inhibitor, has been widely used for the treatment of NSCLC patients with ALK gene rearrangements. A recent study has also shown that (S)-enantiomer of crizotinib exhibits anticancer activity by targeting the protein mutT homologue (MTH1)...
September 7, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28881089/intra-vs-intermolecular-hydrogen-bonding-solvent-dependent-conformational-preferences-of-a-common-supramolecular-binding-motif-from-1h-nmr-and-vcd-spectra
#18
Daniel P Demarque, Christian Merten
When predicting binding properties of small molecules or larger supramolecular aggregates, intra- and intermolecular hydrogen bonds are often considered the most important factor. Spectroscopic techniques such as 1H-NMR spectroscopy are typically utilized to characterize such binding events, but interpretation is often qualitative and follows chemical intuition. In this study, we compare the effects of intramolecular hydrogen bonding and solvation on two chiral 2,6-pyridinediyl-dialkylamides. In comparison with 1H-NMR spectroscopy, VCD spectroscopy proved to be more sensitive to conformational changes...
September 7, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28879763/hydrogelation-of-a-naphthalene-diimide-appended-peptide-amphiphile-and-its-application-in-cell-imaging-and-intracellular-ph-sensing
#19
Nilotpal Singha, Purnima Gupta, Bapan Pramanik, Sahnawaz Ahmed, Antara Dasgupta, Anindita Ukil, Debapratim Das
This study reports the self-assembly and application of a naphthalene diimide (NDI)-appended peptide amphiphile (PA). H-bonding among the peptide moiety in conjunction with π-stacking between NDI, and hydrophobic interactions within the alkyl chain are the major driving forces behind the stepwise aggregation of the PA to form hydrogel. The PA produced efficient self-assemblies in water, forming nano-fibrous network which further formed self-supportive hydrogel. The molecule followed three step self-assembly mechanism...
September 7, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28879503/asthma-phenotypes-and-endotypes-implications-for-personalised-therapy
#20
Katrina Dean, Robert Niven
Asthma is increasingly recognised as a heterogeneous group of diseases with similar clinical presentations rather than a singular disease entity. Asthma was historically categorised by clinical symptoms; however, newer methods of subgrouping, describing and categorising the disease have sub-defined asthma. These sub-definitions are intermittently called phenotypes or endotypes, but the real meanings of these words are poorly understood. Novel treatments are currently and increasingly available, partly in the monoclonal antibody environment, and also some physical therapies (bronchial thermoplasty), but additionally small molecules are not far away from clinical practice...
September 6, 2017: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
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