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Nucleolin

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https://www.readbyqxmd.com/read/28345871/in-vivo-targeting-and-positron-emission-tomography-imaging-of-tumor-with-intrinsically-radioactive-metal-organic-frameworks-nanomaterials
#1
Daiqin Chen, Dongzhi Yang, Casey Dougherty, Weifei Lu, Hongwei Wu, Xianran He, Ting Cai, Marcian E Van Dort, Brian D Ross, Hao Hong
Nanoscale metal-organic frameworks (nMOF) materials represent an attractive tool for various biomedical applications. Due to the chemical versatility, enormous porosity, and tunable degradability of nMOFs, they have been adopted as carriers for delivery of imaging and/or therapeutic cargos. However, the relatively low stability of most nMOFs has limited practical in vivo applications. Here we report the production and characterization of an intrinsically radioactive UiO-66 nMOF (89Zr-UiO-66) with incorporation of positron-emitting isotope zirconium-89 (89Zr)...
March 27, 2017: ACS Nano
https://www.readbyqxmd.com/read/28338097/the-cellular-protein-hnrnp-a2-b1-enhances-hiv-1-transcription-by-unfolding-ltr-promoter-g-quadruplexes
#2
Matteo Scalabrin, Ilaria Frasson, Emanuela Ruggiero, Rosalba Perrone, Elena Tosoni, Sara Lago, Martina Tassinari, Giorgio Palù, Sara N Richter
G-quadruplexes are four-stranded conformations of nucleic acids that act as cellular epigenetic regulators. A dynamic G-quadruplex forming region in the HIV-1 LTR promoter represses HIV-1 transcription when in the folded conformation. This activity is enhanced by nucleolin, which induces and stabilizes the HIV-1 LTR G-quadruplexes. In this work by a combined pull-down/mass spectrometry approach, we consistently found hnRNP A2/B1 as an additional LTR-G-quadruplex interacting protein. Surface plasmon resonance confirmed G-quadruplex specificity over linear sequences and fluorescence resonance energy transfer analysis indicated that hnRNP A2/B1 is able to efficiently unfold the LTR G-quadruplexes...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28332494/pten%C3%AE-is-an-alternatively-translated-isoform-of-pten-that-regulates-rdna-transcription
#3
Hui Liang, Xi Chen, Qi Yin, Danhui Ruan, Xuyang Zhao, Cong Zhang, Michael A McNutt, Yuxin Yin
PTEN is a critical tumour suppressor that is frequently mutated in human cancer. We have previously identified a CUG initiated PTEN isoform designated PTENα, which functions in mitochondrial bioenergetics. Here we report the identification of another N-terminal extended PTEN isoform, designated PTENβ. PTENβ translation is initiated from an AUU codon upstream of and in-frame with the AUG initiation sequence for canonical PTEN. We show that the Kozak context and a downstream hairpin structure are critical for this alternative initiation...
March 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28323037/a-phosphorylation-wide-sncrna-screen-reveals-protein-functional-effector-sncrnas-pfernas-in-human-lung-somatic-cells
#4
Tyler Gable, Yuyan Wang, David Clark, Priti Kumari, Amol Carl Shetty, Li Mao, Yuping Mei
We recently reported that PIWI-interacting RNAs likes (piR-Ls) could regulate functions of the interacting phosphorylated proteins (p-Proteins). In addition, except for writers and erasers, functional efficacy of p-Proteins on their readers still remains unknown. We, therefore, reasoned there was a type of sncRNAs which could regulate functional efficacy of p-Proteins. Here, we profiled sncRNAs interacting with phosphorylated -Ser, -Thr and -Tyr residues in 3 HBE and 4 lung SCC cell lines, investigated effects and mechanisms of phosphorylated-residue-interacting sncRNAs...
March 16, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28315324/nucleolin-protects-macrophages-from-oxldl-induced-foam-cell-formation-through-up-regulating-abca1-expression
#5
Yuanbin Li, Bimei Jiang, Pengfei Liang, Zhongyi Tong, Meidong Liu, Qinglan Lv, Yanjuan Liu, Xuanyou Liu, Yuting Tang, Xianzhong Xiao
Our recent studies have indicated that nucleolin, as a multifunctional RNA-binding protein, exerts protective effects in the myocardial cells and endothelial cells under the condition of oxidative stress. However, the function of nucleolin and its potential mechanism in macrophage-derived foam cell formation remain largely unexplored. ApoE-/- mice were fed with a high-fat diet (HFD) for 10-24 weeks. Protein expression was measured by western blotting or immunofluorescence, and gene expression at the mRNA level was detected by qRT-PCR...
March 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28300561/nucleolin-is-a-nuclear-target-of-heparan-sulfate-derived-from-glypican-1
#6
Fang Cheng, Mattias Belting, Lars-Åke Fransson, Katrin Mani
The recycling, S-nitrosylated heparan sulfate (HS) proteoglycan glypican-1 releases anhydromannose (anMan)-containing HS chains by a nitrosothiol-catalyzed cleavage in endosomes that can be constitutive or induced by ascorbate. The HS-anMan chains are then transported to the nucleus. A specific nuclear target for HS-anMan has not been identified. We have monitored endosome-to-nucleus trafficking of HS-anMan by deconvolution and confocal immunofluorescence microscopy using an anMan-specific monoclonal antibody in non-growing, ascorbate-treated, and growing, untreated, wild-type mouse embryonic fibroblasts and hypoxia-exposed Alzheimer mouse Tg2576 fibroblasts and human U87 glioblastoma cells...
March 12, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28264987/nuclear-retention-of-the-lncrna-snhg1-by-doxorubicin-attenuates-hnrnpc-p53-protein-interactions
#7
Yuan Shen, Shanshan Liu, Jiao Fan, Yinghua Jin, Baolei Tian, Xiaofei Zheng, Hanjiang Fu
The protein p53 plays a crucial role in the regulation of cellular responses to diverse stresses. Thus, a major priority in cell biology is to define the mechanisms that regulate p53 activity in response to stresses or maintain it at basal levels under normal conditions. Moreover, further investigation is required to establish whether RNA participates in regulating p53's interaction with other proteins. Here, by conducting systematic experiments, we discovered a p53 interactor-hnRNPC-that directly binds to p53, destabilizes it, and prevents its activation under normal conditions...
March 6, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28248078/receptor-mediated-surface-charge-inversion-platform-based-on-porous-silicon-nanoparticles-for-efficient-cancer-cell-recognition-and-combination-therapy
#8
Feng Zhang, Alexandra Correia, Ermei Mäkilä, Wei Li, Jarno Salonen, Jouni J Hirvonen, Hongbo Zhang, Hélder A Santos
Negatively charged surface-modified drug delivery systems are promising for in vivo applications as they have more tendency to accumulate in tumor tissues. However, the inefficient cell uptake of these systems restricts their final therapeutic performance. Here, we have fabricated a receptor-mediated surface charge inversion nanoparticle made of undecylenic acid modified, thermally hydrocarbonized porous silicon (UnTHCPSi) nanoparticles core and sequentially modified with polyethylenimine (PEI), methotrexate (MTX), and DNA aptamer AS1411 (herein termed as UnTHCPSi-PEI-MTX@AS1411) for enhancing the cell uptake of nucleolin-positive cells...
March 22, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28202413/engineered-antibody-ch2-domains-binding-to-nucleolin-isolation-characterization-and-improvement-of-aggregation
#9
Dezhi Li, Rui Gong, Jun Zheng, Xihai Chen, Dimiter S Dimitrov, Qi Zhao
Smaller recombinant antibody fragments are now emerging as alternatives of conventional antibodies. Especially, immunoglobulin (Ig) constant CH2 domain and engineered CH2 with improved stability are promising as scaffolds for selection of specific binders to various antigens. We constructed a yeast display library based on an engineered human IgG1 CH2 scaffold with diversified loop regions. A group of CH2 binders were isolated from this yeast display library by panning against nucleolin, which is a tumor-associated antigen involved in cell proliferation, tumor cell growth and angiogenesis...
April 1, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28194553/acidic-domains-differentially-read-histone-h3-lysine-4-methylation-status-and-are-widely-present-in-chromatin-associated-proteins
#10
Meng Wu, Wei Wei, Jiwei Chen, Rong Cong, Tieliu Shi, Jiwen Li, Jiemin Wong, James X Du
Histone methylation is believed to provide binding sites for specific reader proteins, which translate histone code into biological function. Here we show that a family of acidic domain-containing proteins including nucleophosmin (NPM1), pp32, SET/TAF1β, nucleolin (NCL) and upstream binding factor (UBF) are novel H3K4me2-binding proteins. These proteins exhibit a unique pattern of interaction with methylated H3K4, as their binding is stimulated by H3K4me2 and inhibited by H3K4me1 and H3K4me3. These proteins contain one or more acidic domains consisting mainly of aspartic and/or glutamic residues that are necessary for preferential binding of H3K4me2...
February 13, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28153390/nucleolin-staining-may-aid-in-the-identification-of-circulating-prostate-cancer-cells
#11
Heather J Chalfin, James E Verdone, Emma E van der Toom, Stephanie Glavaris, Michael A Gorin, Kenneth J Pienta
INTRODUCTION: Circulating tumor cells (CTCs) have great potential as circulating biomarkers for solid malignancies. Currently available assays for CTC detection rely on epithelial markers with somewhat limited sensitivity and specificity. We found that the staining pattern of nucleolin, a common nucleolar protein in proliferative cells, separates CTCs from white blood cells (WBCs) in men with metastatic prostate cancer. PATIENTS AND METHODS: Whole peripheral blood from 3 men with metastatic prostate cancer was processed with the AccuCyte CTC system (RareCyte, Seattle, WA)...
January 4, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28149992/a-red-nir-fluorescent-dye-detecting-nuclear-dna-g-quadruplexes-in-vitro-analysis-and-cell-imaging
#12
F Doria, M Nadai, M Zuffo, R Perrone, M Freccero, S N Richter
Aggregation, red-NIR emission and light-up upon nucleic acid G-quadruplex binding have been investigated for a prototype core-extended naphthalene diimide, which is capable of fast cellular entry and nucleolar localization. Both high-level colocalization with an anti-G-quadruplex antibody and nucleolin displacement reveal that the compound targets and thus makes visible nuclear DNA G-quadruplexes.
February 2, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28131007/expression-of-the-cytoplasmic-nucleolin-for-post-transcriptional-regulation-of-macrophage-colony-stimulating-factor-mrna-in-ovarian-and-breast-cancer-cells
#13
Ho-Hyung Woo, Sang C Lee, Steven J Gibson, Setsuko K Chambers
The formation of the mRNP complex is a critical component of translational regulation and mRNA decay. Both the 5' and 3'UTRs of CSF-1 mRNA are involved in post-transcriptional regulation. In CSF-1 mRNA, a small hairpin loop structure is predicted to form at the extreme 5' end (2-21nt) of the 5'UTR. Nucleolin binds the hairpin loop structure in the 5'UTR of CSF-1 mRNA and enhances translation, while removal of this hairpin loop nucleolin binding element dramatically represses translation. Thus in CSF-1 mRNA, the hairpin loop nucleolin binding element is critical for translational regulation...
March 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28126548/smart-as1411-aptamer-conjugated-pegylated-pamam-dendrimer-for-the-superior-delivery-of-camptothecin-to-colon-adenocarcinoma-in-vitro-and-in-vivo
#14
Mona Alibolandi, Seyed Mohammad Taghdisi, Pouria Ramezani, Fazileh Hosseini Shamili, Sara Amel Farzad, Khalil Abnous, Mohammad Ramezani
In the current study camptothecin-loaded pegylated PAMAM dendrimer were synthesized and were functionalized with AS1411 anti-nucleolin aptamers for site-specific targeting against colorectal cancer cells which over expresses nucleolin receptors. The morphological properties and size dispersity of the prepared nanoparticles were evaluated using transmission electron microscope (TEM) and DLS. The drug-loading content and encapsulation efficiency were obtained 8.1% and 93.67% respectively. The in vitro release of camptothecin from the formulation was provided the sustained release of encapsulated camptothecin during 4days...
March 15, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28103300/expression-profiling-of-ribosome-biogenesis-factors-reveals-nucleolin-as-a-novel-potential-marker-to-predict-outcome-in-aml-patients
#15
Virginie Marcel, Frédéric Catez, Caroline M Berger, Emeline Perrial, Adriana Plesa, Xavier Thomas, Eve Mattei, Sandrine Hayette, Pierre Saintigny, Philippe Bouvet, Jean-Jacques Diaz, Charles Dumontet
Acute myeloid leukemia (AML) is a heterogeneous disease. Prognosis is mainly influenced by patient age at diagnosis and cytogenetic alterations, two of the main factors currently used in AML patient risk stratification. However, additional criteria are required to improve the current risk classification and better adapt patient care. In neoplastic cells, ribosome biogenesis is increased to sustain the high proliferation rate and ribosome composition is altered to modulate specific gene expression driving tumorigenesis...
2017: PloS One
https://www.readbyqxmd.com/read/28028501/aptamer-conjugated-magnetic-nanoparticles-as-targeted-magnetic-resonance-imaging-contrast-agent-for-breast-cancer
#16
Mohammad Keshtkar, Daryoush Shahbazi-Gahrouei, Seyyed Mehdi Khoshfetrat, Masoud A Mehrgardi, Mahmoud Aghaei
Early detection of breast cancer is the most effective way to improve the survival rate in women. Magnetic resonance imaging (MRI) offers high spatial resolution and good anatomic details, and its lower sensitivity can be improved by using targeted molecular imaging. In this study, AS1411 aptamer was conjugated to Fe3O4@Au nanoparticles for specific targeting of mouse mammary carcinoma (4T1) cells that overexpress nucleolin. In vitro cytotoxicity of aptamer-conjugated nanoparticles was assessed on 4T1 and HFFF-PI6 (control) cells...
October 2016: Journal of Medical Signals and Sensors
https://www.readbyqxmd.com/read/28024568/study-and-evaluation-of-nucleolin-targeted-delivery-of-magnetic-plga-peg-nanospheres-loaded-with-doxorubicin-to-c6-glioma-cells-compared-with-low-nucleolin-expressing-l929-cells
#17
Jafar Mosafer, Manouchehr Teymouri, Khalil Abnous, Mohsen Tafaghodi, Mohammad Ramezani
Magnetic nanoparticulate systems based on polymeric materials such as poly (lactic-co-glycolic acid) (PLGA(1)) are being studied for their potential applications in targeted therapy and imaging of malignant tumors. In the current study, superparamagnetic iron oxide nanocrystals (SPIONs(2)) and doxorubicin (Dox(3)) were entrapped in the PLGA-based nanoparticles via a modified multiple emulsion solvent evaporation method. Furthermore, SPIO/Dox-NPs(4) were conjugated to anti-nucleolin AS1411 aptamer (Apt(5)) and their targeting ability was investigated in high nucleolin-expressing C6 glioma cells compared to low nucleolin-expressing L929 cells...
March 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28012991/in-vitro-and-in-vivo-evaluation-of-anti-nucleolin-targeted-magnetic-plga-nanoparticles-loaded-with-doxorubicin-as-a-theranostic-agent-for-enhanced-targeted-cancer-imaging-and-therapy
#18
Jafar Mosafer, Khalil Abnous, Mohsen Tafaghodi, Ahad Mokhtarzadeh, Mohammad Ramezani
A superparamagnetic iron oxide nanoparticles (SPIONs)/doxorubicin (Dox) co-loaded poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles targeted with AS1411 aptamer (Apt) against murine C26 colon carcinoma cells is successfully developed via a modified multiple emulsion solvent evaporation method for theranostic purposes. The mean size of SPIO/Dox-NPs (NPs) was 130nm with a narrow particle size distribution and Dox loading of 3.0%. The SPIO loading of 16.0% and acceptable magnetic properties are obtained and analyzed using thermogravimetric and vibration simple magnetometer analysis, respectively...
April 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28007579/g-quadruplex-oligonucleotide-as1411-as-a-cancer-targeting-agent-uses-and-mechanisms
#19
REVIEW
Paula J Bates, Elsa M Reyes-Reyes, Mohammad T Malik, Emily M Murphy, Martin G O'Toole, John O Trent
BACKGROUND: AS1411 is a 26-mer G-rich DNA oligonucleotide that forms a variety of G-quadruplex structures. It was identified based on its cancer-selective antiproliferative activity and subsequently determined to be an aptamer to nucleolin, a multifunctional protein that preferentially binds quadruplex nucleic acids and which is present at high levels on the surface of cancer cells. AS1411 has exceptionally efficient cellular internalization compared to non-quadruplex DNA sequences. SCOPE OF REVIEW: Recent developments related to AS1411 will be examined, with a focus on its use for targeted delivery of therapeutic and imaging agents...
December 20, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27988470/precise-glioblastoma-targeting-by-as1411-aptamer-functionalized-poly-l-%C3%AE-glutamylglutamine-paclitaxel-nanoconjugates
#20
Zimiao Luo, Zhiqiang Yan, Kai Jin, Qiang Pang, Ting Jiang, Heng Lu, Xianping Liu, Zhiqing Pang, Lei Yu, Xinguo Jiang
Chemotherapy is still the main adjuvant strategy after surgery in glioblastoma therapy. As the main obstacles of chemotherapeutic drugs for glioblastoma treatment, the blood brain barrier (BBB) and non-specific delivery to non-tumor tissues greatly limit the accumulation of drugs into tumor tissues and simultaneously cause serious toxicity to nearby normal tissues which altogether compromised the chemotherapeutic effect. In the present study, we established an aptamer AS1411-functionalized poly (l-γ-glutamyl-glutamine)-paclitaxel (PGG-PTX) nanoconjugates drug delivery system (AS1411-PGG-PTX), providing an advantageous solution of combining the precisely active targeting and the optimized solubilization of paclitaxel...
December 7, 2016: Journal of Colloid and Interface Science
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