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Nucleolin

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https://www.readbyqxmd.com/read/29352243/nucleolin-and-erbb2-inhibition-reduces-tumorigenicity-of-erbb2-positive-breast-cancer
#1
Eya Wolfson, Shira Solomon, Eran Schmukler, Yona Goldshmit, Ronit Pinkas-Kramarski
ErbB2, a member of the ErbB family of receptor tyrosine kinases, is an essential player in the cell's growth and proliferation signaling pathways. Amplification or overexpression of ErbB2 is observed in ∼30% of breast cancer patients, and often drives cellular transformation and cancer development. Recently, we have shown that ErbB2 interacts with the nuclear-cytoplasmic shuttling protein nucleolin, an interaction which enhances cell transformation in vitro, and increases mortality risk and disease progression rate in human breast cancer patients...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29339453/pgrmc1-localization-and-putative-function-in-the-nucleolus-of-bovine-granulosa-cells-and-oocytes
#2
Laura Terzaghi, Alberto Maria Luciano, Priscila C Dall Acqua, Silvia Modina, John J Peluso, Valentina Lodde
Progesterone Receptor Membrane Component-1 (PGRMC1) is a highly conserved multifunctional protein that is found in numerous systems, including reproductive system. Interestingly, PGRMC1 is expressed at several intracellular locations, including the nucleolus. The aim of this study is to investigate the functional relationship between PGRMC1 and nucleolus. Immunofluorescence experiments confirmed PGRMC1's nucleolar localization in cultured bovine granulosa cells (bGC) and oocytes. Additional experiments conducted on bGC revealed that PGRMC1 co-localizes with nucleolin (NCL), a major nucleolar protein...
January 16, 2018: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/29328377/feature-genes-in-metastatic-breast-cancer-identified-by-metade-and-svm-classifier-methods
#3
Youlin Tuo, Ning An, Ming Zhang
The aim of the present study was to investigate the feature genes in metastatic breast cancer samples. A total of 5 expression profiles of metastatic breast cancer samples were downloaded from the Gene Expression Omnibus database, which were then analyzed using the MetaQC and MetaDE packages in R language. The feature genes between metastasis and non‑metastasis samples were screened under the threshold of P<0.05. Based on the protein‑protein interactions (PPIs) in the Biological General Repository for Interaction Datasets, Human Protein Reference Database and Biomolecular Interaction Network Database, the PPI network of the feature genes was constructed...
January 9, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29328002/dexamethasone-mediated-oncogenicity-in-vitro-and-in-an-animal-model-of-glioblastoma
#4
Markus M Luedi, Sanjay K Singh, Jennifer C Mosley, Islam S A Hassan, Masumeh Hatami, Joy Gumin, Lukas Andereggen, Erik P Sulman, Frederick F Lang, Frank Stueber, Gregory N Fuller, Rivka R Colen, Pascal O Zinn
OBJECTIVE Dexamethasone, a known regulator of mesenchymal programming in glioblastoma (GBM), is routinely used to manage edema in GBM patients. Dexamethasone also activates the expression of genes, such as CEBPB, in GBM stem cells (GSCs). However, the drug's impact on invasion, proliferation, and angiogenesis in GBM remains unclear. To determine whether dexamethasone induces invasion, proliferation, and angiogenesis in GBM, the authors investigated the drug's impact in vitro, in vivo, and in clinical information derived from The Cancer Genome Atlas (TCGA) cohort...
January 12, 2018: Journal of Neurosurgery
https://www.readbyqxmd.com/read/29325460/targeted-delivery-of-melittin-to-cancer-cells-by-as1411-anti-nucleolin-aptamer
#5
Seyed Hossein Rajabnejad, Ahad Mokhtarzadeh, Khalil Abnous, Seyed Mohammad Taghdisi, Mohammad Ramezani, Bibi Marjan Razavi
Melittin, a small water-soluble cationic amphipathic α-helical linear peptide, consisted of 26 amino acids, is the honeybee venom major constituent. Several reports have proved the lytic and apoptotic effects of melittin in several cancerous cell lines. In this study, we aimed to fabricate an AS1411 aptamer-melittin to specifically deliver melittin to nucleolin positive cells (A549). Melittin was covalently attached to antinucleolin aptamer (AS1411) and its toxicity in A549 (Nucleolin positive) and L929 (Nucleolin negative) was studied using MTT and Annexin V flow cytometry methods...
January 12, 2018: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/29310244/a-dual-targeting-dna-tetrahedron-nanocarrier-for-breast-cancer-cell-imaging-and-drug-delivery
#6
Xiaoting Liu, Lina Wu, Lei Wang, Wei Jiang
To enhance efficacy of chemotherapy and achieve real-time imaging of cancer cells, it is crucial to develop nanocarriers with targeted drug delivery capacity and fluorescence property for cancer theranostics. Herein, a dual-targeting DNA tetrahedron nanocarrier (MUC1-Td-AS1411) was constructed for breast cancer cell imaging and targeted drug delivery. This nanocarrier consisted of three components: (i) DNA tetrahedron core for multivalent conjugation of function ligands and loading doxorubicin (Dox); (ii) activatable MUC1 aptamer probe (MUC1-probe), formed by the hybridization of MUC1 aptamer sequence with fluorophore extended from one vertex and complementary sequence with quencher, for targeting and imaging MUC1 protein on cytomembrane; (iii) AS1411 aptamer, which was hybridized to the overhang on three vertexes via prolonged sequence, for binding to nucleolin...
March 1, 2018: Talanta
https://www.readbyqxmd.com/read/29295891/a-peptidylic-inhibitor-for-neutralizing-expanded-cag-rna-induced-nucleolar-stress-in-polyglutamine-diseases
#7
Qian Zhang, Zhefan Stephen Chen, Ying An, Haizhen Liu, Yonghui Hou, Wen Li, Kwok-Fai Lau, Alex Koon, Jacky Ngo, Edwin Chan
Polyglutamine (polyQ) diseases are a set of progressive neurodegenerative disorders ascribed by the expression of both expanded CAG RNA and misfolded polyQ protein. We previously reported that the direct interaction between expanded CAG RNA and nucleolar protein nucleolin (NCL) leads to impediment of pre-ribosomal RNA (pre-rRNA) transcription, and eventually triggers nucleolar stress-induced apoptosis in polyQ diseases. Here, we report a 21-amino acid peptide, named beta-structured inhibitor for neurodegenerative disease (BIND), effectively suppresses expanded CAG RNA toxicity...
January 2, 2018: RNA
https://www.readbyqxmd.com/read/29291159/dual-radiosensitization-and-anti-stat3-anti-proliferative-strategy-based-on-delivery-of-gold-nanoparticle-oligonucleotide-nanoconstructs-to-head-and-neck-cancer-cells
#8
Surong Zhang, Suresh Gupta, Thomas J Fitzgerald, Alexei A Bogdanov
Constitutively activated signal transducer and activator of transcription 3 (STAT3) factor is an important therapeutic target in head and neck cancer (HNC). Despite early promising results, a reliable systemic delivery system for STAT3- targeted oligonucleotide (ODN) drugs is still needed for future clinical translation of anti-STAT3 therapies. We engineered and tested a novel ODN duplex/gold nanoparticle (AuNP)-based system carrying a therapeutic STAT3 decoy (STAT3d) payload. This strategy is two-pronged because of the additive STAT3 antagonism and radiosensitizing properties of AuNP...
2018: Nanotheranostics
https://www.readbyqxmd.com/read/29259342/non-structural-protein-1-of-h3n2-influenza-a-virus-induces-nucleolar-stress-via-interaction-with-nucleolin
#9
Yinxia Yan, Yongming Du, Gefei Wang, Kangsheng Li
The nucleolus is a stress sensor associated with cell cycle progression and a central hub for the replication of pathogenic RNA viruses. However, the role of nucleolus in influenza A virus infection has not been well studied. Here we show that the interaction between NS1 protein of influenza A/Shantou/602/06 (H3N2) and nucleolin, a ubiquitous protein of nucleolus repressed RNA Pol I-dependent transcription via establishing hyper-methylation in the UCE of rRNA gene promoter. NS1 expressed cells showed significant association of ribosomal proteins with MDM2, and p53 accumulation, suggesting induced nucleolar stress...
December 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29250957/nucleolin-targeting-as1411-aptamer-modified-graft-polymeric-micelle-with-dual-ph-redox-sensitivity-designed-to-enhance-tumor-therapy-through-the-codelivery-of-doxorubicin-tlr4-sirna-and-suppression-of-invasion
#10
Shudi Yang, Zhaoxiang Ren, Mengtian Chen, Ying Wang, Bengang You, Weiliang Chen, Chenxi Qu, Yang Liu, Xuenong Zhang
In this article, a novel graft polymeric micelle with targeting function ground on aptamer AS1411 was synthesized. The micelle was based on chitosan-ss-polyethylenimine-urocanic acid (CPU) with dual pH/redox sensitivity and targeting effects. This micelle was produced for codelivering Toll-like receptor 4 siRNA (TLR4-siRNA) and doxorubicin (Dox). In vitro investigation revealed the sustained gene and drug release from Dox-siRNA-loaded micelles under physiological conditions, and this codelivery nanosystem exhibited high dual pH/redox sensitivity, rapid intracellular drug release, and improved cytotoxicity against A549 cells in vitro...
December 18, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29250796/xiap-overexpression-promotes-bladder-cancer-invasion-in-vitro-and-lung-metastasis-in-vivo-via-enhancing-nucleolin-mediated-rho-gdi%C3%AE-mrna-stability
#11
Yonghui Yu, Honglei Jin, Jiheng Xu, Jiayan Gu, Xin Li, Qipeng Xie, Haishan Huang, Jingxia Li, Zhongxian Tian, Guosong Jiang, Caiyi Chen, Feng He, Xue-Ru Wu, Chuanshu Huang
Our recent studies demonstrate that X-linked inhibitor of apoptosis protein (XIAP) is essential for regulating colorectal cancer invasion. Here we discovered that RhoGDIβ was a key XIAP downstream effector mediating bladder cancer (BC) invasion in vitro and in vivo. We found that both XIAP and RhoGDIβ expressions were consistently elevated in BCs of N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-treated mice in comparison to bladder tissues from vehicle-treated mice and human BCs in comparison to the paired adjacent normal bladder tissues...
December 18, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29246300/the-bioactivity-of-d-l-isonucleoside-and-2-deoxyinosine-incorporated-aptamer-as1411s-including-dna-replication-microrna-expression
#12
Xinmeng Fan, Lidan Sun, Kunfeng Li, Xiantao Yang, Baobin Cai, Yanfen Zhang, Yuejie Zhu, Yuan Ma, Zhu Guan, Yun Wu, Lihe Zhang, Zhenjun Yang
In this study, chemical modification of 2'-deoxyinosine (2'-dI) and D-/L-isothymidine (D-/L-isoT) was performed on AS1411. They could promote the nucleotide-protein interaction by changing the local conformation. Twenty modified sequences were obtained, FCL-I and FCL-II showed the most noticeable activity improvement. They stabilized the G-quadruplex, remained highly resistant to serum degradation and specificity for nucleolin, further inhibited tumor cell growth, exhibited a stronger ability to influence the different phases of the tumor cell cycle, induced S-phase arrest, promoted the inhibition of DNA replication, and suppressed the unwound function of a large T antigen as powerful as AS1411...
December 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/29208488/multi-targeted-effects-of-g4-aptamers-and-their-antiproliferative-activity-against-cancer-cells
#13
Anna M Ogloblina, Alexandra N Khristich, Natalia Y Karpechenko, Svetlana E Semina, Gennady A Belitsky, Nina G Dolinnaya, Marianna G Yakubovskaya
We selected and investigated nine G-quadruplex (G4)-forming aptamers originally designed against different proteins involved in the regulation of cellular proliferation (STAT3, nucleolin, TOP1, SP1, VEGF, and SHP-2) and considered to be potential anticancer agents. We showed that under physiological conditions all the aptamers form stable G4s of different topology. G4 aptamers designed against STAT3, nucleolin and SP1 inhibit STAT3 transcriptional activity in human breast adenocarcinoma MCF-7 cells, and all the studied aptamers inhibit TOP1-mediated relaxation of supercoiled plasmid DNA...
December 2, 2017: Biochimie
https://www.readbyqxmd.com/read/29192701/aptamer-mediated-selective-delivery-of-a-cytotoxic-cationic-nhc-au-i-complex-to-cancer-cells
#14
Weijia Niu, I-Ting Teng, Xigao Chen, Weihong Tan, Adam S Veige
A novel cationic NHC-Au(i) complex was synthesized and studied for its antitumor activity. For all the cell lines tested, cationic NHC-Au(i) complex 2 shows much higher cytotoxicity than its neutral analogue 1. To achieve selective cancer cell targeting, complex 2 was covalently conjugated to aptamer AS1411, a DNA aptamer with strong binding affinity for nucleolin. The successful conjugation was confirmed by HPLC, gel electrophoresis, fluorescence spectroscopy and UV-Vis absorption. Conjugate AS1411-2 was then examined for its specific targeting and binding ability towards cancer cells over human normal cells using flow cytometry analysis and confocal microscopy...
December 1, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/29181974/atp-activatable-photosensitizer-enables-dual-fluorescence-imaging-and-targeted-photodynamic-therapy-of-tumor
#15
Yizhong Shen, Qian Tian, Yidan Sun, Jing-Juan Xu, Deju Ye, Hong-Yuan Chen
Targeted delivery of intracellular stimuli-activatable photosensitizers (PSs) into tumor cells to achieve selective imaging and on-demand photodynamic therapy (PDT) of tumors has provided a vital opportunity for precise cancer diagnosis and ther-apy. In this paper, we report a tumor targeting and adenosine triphosphate (ATP)-activatable nanophotosensitizer Apt-HyNP/BHQ2 by modifying hybrid micellar nanoparticles with both nucleolin-targeting aptamer AS1411 and quencher BHQ2-labeled ATP-binding aptamer BHQ2-ATP-apt...
November 28, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29168431/nucleolin-phosphorylation-regulates-parn-deadenylase-activity-during-cellular-stress-response
#16
Xiaokan Zhang, Shu Xiao, Rachele Dolce Rameau, Emral Devany, Zaineb Nadeem, Elif Caglar, Kenneth Ng, Frida Esther Kleiman, Anjana Saxena
Nucleolin (NCL) is an abundant stress-responsive, RNA-binding phosphoprotein that controls gene expression by regulating either mRNA stability and/or translation. NCL binds to the AU-rich element (ARE) in the 3'UTR of target mRNAs, mediates miRNA functions in the nearby target sequences, and regulates mRNA deadenylation. However, the mechanism by which NCL phosphorylation affects these functions and the identity of the deadenylase involved, remain largely unexplored. Earlier we demonstrated that NCL phosphorylation is vital for cell cycle progression and proliferation, whereas phosphorylation-deficient NCL at six consensus CK2 sites confers dominant-negative effect on proliferation by increasing p53 expression, possibly mimicking cellular DNA damage conditions...
November 23, 2017: RNA Biology
https://www.readbyqxmd.com/read/29164198/aptamer-modified-selenium-nanoparticles-for-dark-field-microscopy-imaging-of-nucleolin
#17
Meng Li Liu, Hong Yan Zou, Chun Mei Li, Rong Sheng Li, Cheng Zhi Huang
Selenium nanoparticles (SeNPs) with strong green scattering light serving as light scattering nanoprobes for dark-field microscopy imaging are developed for the first time. The SeNPs show good stability, excellent biocompatibility, and high light-producing power, and can precisely and specifically target cancer cells with overexpressed nucleolin (NCL) after modification with aptamers, revealing that the SeNPs can act as a good light scattering nanoprobe for bioimaging and biolabeling.
November 22, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/29163814/multivalent-cationic-pseudopeptide-polyplexes-as-a-tool-for-cancer-therapy
#18
Zoi Diamantopoulou, Maud-Emmanuelle Gilles, Maha Sader, Mélissande Cossutta, Benoit Vallée, Claire Houppe, Damien Habert, Blandine Brissault, Eric Leroy, Federica Maione, Enrico Giraudo, Damien Destouches, Jacques Penelle, José Courty, Ilaria Cascone
In this study, a novel anticancer reagent based on polyplexes nanoparticles was developed. These nanoparticles are obtained by mixing negatively charged polyelectrolytes with the antitumour cationically-charged pseudopeptide N6L. Using two in vivo experimental tumor pancreatic models based upon PANC-1 and mPDAC cells, we found that the antitumour activity of N6L is significantly raised via its incorporation in polyplexed nanoparticles. Study of the mechanism of action using affinity isolation and si-RNA experiments indicated that N6L-polyplexes are internalized through their interaction with nucleolin...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29141533/targeting-cancer-stem-cells-and-non-stem-cancer-cells-the-potential-of-lipid-based-nanoparticles
#19
Ana Filipa Cruz, Nuno Andre Fonseca, Vera Moura, Sergio Simoes, Joao Nuno Moreira
Background Cancer stem cells (CSCs) have been described as a relevant contributor to tumorigenicity, metastasis, tumor recurrence and drug resistance, making this cell population a relevant target in solid tumors. METHODS: This has stimulated the development of different therapeutic strategies often targeting surface markers (CD44, epithelial cell adhesion molecule (EpCAM), aldehyde dehydrogenase (ALDH) and nucleolin) and/or signaling pathways that are aberrantly activated and contribute to CSCs proliferation and survival...
November 14, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29123088/a-water-soluble-nucleolin-aptamer-paclitaxel-conjugate-for-tumor-specific-targeting-in-ovarian-cancer
#20
Fangfei Li, Jun Lu, Jin Liu, Chao Liang, Maolin Wang, Luyao Wang, Defang Li, Houzong Yao, Qiulong Zhang, Jia Wen, Zong-Kang Zhang, Jie Li, Quanxia Lv, Xiaojuan He, Baosheng Guo, Daogang Guan, Yuanyuan Yu, Lei Dang, Xiaohao Wu, Yongshu Li, Guofen Chen, Feng Jiang, Shiguo Sun, Bao-Ting Zhang, Aiping Lu, Ge Zhang
Paclitaxel (PTX) is among the most commonly used first-line drugs for cancer chemotherapy. However, its poor water solubility and indiscriminate distribution in normal tissues remain clinical challenges. Here we design and synthesize a highly water-soluble nucleolin aptamer-paclitaxel conjugate (NucA-PTX) that selectively delivers PTX to the tumor site. By connecting a tumor-targeting nucleolin aptamer (NucA) to the active hydroxyl group at 2' position of PTX via a cathepsin B sensitive dipeptide bond, NucA-PTX remains stable and inactive in the circulation...
November 9, 2017: Nature Communications
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