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Sofia Romano, Vera Moura, Sérgio Simões, João Nuno Moreira, João Gonçalves
Nucleolin arises as a relevant target for cancer therapy, as it is overexpressed at the surface of cancer and angiogenic endothelial cells thus enabling a dual cellular targeting strategy. Immunotherapeutic strategies, albeit of proven therapeutic relevance, have been scarcely explored against this target. Therefore, this work aimed at engineering an anti-nucleolin VHH-based antibody capable of triggering anticancer immune responses. Herein, anti-nucleolin VHHs have been generated upon grafting F3 peptide-derived nucleolin-binding sequences onto a VHH CDR1 or CDR3...
May 10, 2018: Scientific Reports
Yuxiu Zou, Siqi Huang, Yixin Liao, Xupeng Zhu, Yiqin Chen, Long Chen, Fang Liu, Xiaoxiao Hu, Haijun Tu, Liang Zhang, Zhangkun Liu, Zhuo Chen, Weihong Tan
For cancer diagnosis, technologies must be capable of molecular recognition, and they must possess a built-in pattern recognition component for efficient imaging and discrimination of targeted cancer cells. Surface enhanced Raman scattering (SERS) tags based on plasmonically active nanoparticles hold promise for accurate and efficient cancer cell recognition, owing to ultra-narrow peak and sensitive optical properties. However, a complex fingerprint spectrum increases data analysis difficulty, making it necessary to develop multicolor SERS tags with a simple fingerprint spectrum...
March 14, 2018: Chemical Science
Dingfeng Li, Juan Zhang, Ming Wang, Xiaohui Li, Huarui Gong, Huiping Tang, Lin Chen, Lili Wan, Qiang Liu
The ribosome is indispensable for precisely controlling the capacity of protein synthesis. However, how translational machinery is coordinated to meet the translational demands remains elusive. Here, we identify a nucleolar-specific lncRNA (LoNA), its 5' portion binds and sequesters nucleolin to suppress rRNA transcription, and its snoRNA like 3' end recruits and diminishes fibrillarin activity to reduce rRNA methylation. Activity-dependent decrease of LoNA leads to elevated rRNA and ribosome levels, an increased proportion of polysomes, mRNA polysome loading, and protein translation...
April 30, 2018: Nature Communications
Juan Wang, Jiacai Wu, Xumei Li, Haowei Liu, Jianli Qin, Zhun Bai, Bixia Chi, Chen Xu
Identification of the specific protein target(s) of a drug is a critical step in unraveling its mechanisms of action (MOA) in many natural products. Curcumol, isolated from well known Chinese medicinal plant Curcuma zedoary, has been shown to possess multiple biological activities. It can inhibit nasopharyngeal carcinoma (NPC) proliferation and induce apoptosis, but its target protein(s) in NPC cells remains unclear. In this study, we employed a mass spectrometry-based chemical proteomics approach reveal the possible protein targets of curcumol in NPC cells...
April 20, 2018: Journal of Proteomics
Seyed Mohammad Taghdisi, Noor Mohammad Danesh, Mohammad Ramezani, Rezvan Yazdian-Robati, Khalil Abnous
Active targeting of nanostructures containing chemotherapeutic agents can improve cancer treatment. Here, a three-way junction pocket DNA nanostructure was developed for efficient doxorubicin (Dox) delivery into cancer cells. Three-way junction pocket DNA nanostructure is composed of three strands of AS1411 aptamer as both therapeutic aptamer and nucleolin targeting, the potential biomarker of prostate (PC-3 cells) and breast (4T1 cells) cancers. The properties of the Dox-loaded three-way junction pocket DNA nanostructure was characterized and verified to have several advantages, including high serum stability and pH-responsive property...
April 18, 2018: Molecular Pharmaceutics
Ana C Gregório, Manuela Lacerda, Paulo Figueiredo, Sérgio Simões, Sérgio Dias, João Nuno Moreira
A major challenge in the management of breast cancer disease has been the development of metastases. Finding new molecular targets and the design of targeted therapeutic approaches to improve the overall survival and quality of life of these patients is, therefore, of great importance. Nucleolin, which is overexpressed in cancer cells and tumor-associated blood vessels, have been implicated in various processes supporting tumorigenesis and angiogenesis. Additionally, its overexpression has been demonstrated in a variety of human neoplasias as an unfavorable prognostic factor, associated with a high risk of relapse and low overall survival...
May 2018: Critical Reviews in Oncology/hematology
Shuntaro Takahashi, Ki Tae Kim, Peter Podbevsek, Janez Plavec, Byeang Hyean Kim, Naoki Sugimoto
Oxidation is one of the frequent causes of DNA damage, especially to guanine bases. Guanine bases in the G-quadruplex (G4) are sensitive to damage by oxidation, resulting in transformation to 8-oxo-7,8-dihydroguanine (8-oxoG). Because the formation of G4 represses the expression of some cancer-related genes, the presence of 8-oxoG in a G4 sequence might affect G4 formation and induce cancer progression. Thus, oxidized-G4 formation must be controlled using a chemical approach. In the present study, we investigated the effect of introduction of 8-oxoG into a G4 sequence on the formation and function of the G4 structure...
April 2, 2018: Journal of the American Chemical Society
Leila Farzin, Mojtaba Shamsipur, Leila Samandari, Shahab Sheibani
Nucleolin is a multifunctional protein that is markedly overexpressed on the surface of most cancer cells. By taking advantage of the high affinity and specificity of the AS1411 aptamer for nucleolin, a signalling probe displacement electrochemical aptasensor was developed. The thiolated AS1411 aptamer was conjugated to hydroxyapatite nanorods (HApNRs) decorated with gold nanoparticles (AuNPs). To further increase the electrical conductivity of the interface, the ionic liquid 1-ethyl-3-methylimidazolium alanine with its high ion conductivity was placed on the electrode surface...
February 3, 2018: Mikrochimica Acta
Csaba Mahotka, Sanil Bhatia, Jutta Kollet, Edgar Grinstein
No abstract text is available yet for this article.
March 8, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Marco Terenzio, Sandip Koley, Nitzan Samra, Ida Rishal, Qian Zhao, Pabitra K Sahoo, Anatoly Urisman, Letizia Marvaldi, Juan A Oses-Prieto, Craig Forester, Cynthia Gomes, Ashley L Kalinski, Agostina Di Pizio, Ella Doron-Mandel, Rotem Ben-Tov Perry, Indrek Koppel, Jeffery L Twiss, Alma L Burlingame, Mike Fainzilber
How is protein synthesis initiated locally in neurons? We found that mTOR (mechanistic target of rapamycin) was activated and then up-regulated in injured axons, owing to local translation of mTOR messenger RNA (mRNA). This mRNA was transported into axons by the cell size-regulating RNA-binding protein nucleolin. Furthermore, mTOR controlled local translation in injured axons. This included regulation of its own translation and that of retrograde injury signaling molecules such as importin β1 and STAT3 (signal transducer and activator of transcription 3)...
March 23, 2018: Science
Tinchou Li, Mingcheng Lee, Fuming Tsai, Yunhsiang Chen, Yiyin Lin, Maoliang Chen
BACKGROUND: Based on accumulating evidence, the regulation of protein expression by antipsychotic drugs (APDs) might be closely related to the control of psychotic symptoms when these drugs are used to treat mental disorders. The low quantity of nuclear proteins in the cell hinders their detection because signal for rare proteins are masked in most proteomic detection systems. METHODS: Nuclear proteins fractionated from APD-treated B35 cells were labeled with iTRAQ and detected by LC/MS/MS to investigate APD-induced alterations in nuclear protein expression...
March 7, 2018: BMC Pharmacology & Toxicology
Jiang Zou, Nian Wang, Manting Liu, Yongping Bai, Hao Wang, Ke Liu, Huali Zhang, Xianzhong Xiao, Kangkai Wang
Hydroxysafflor Yellow A (HSYA), a most representative ingredient of Carthamus tinctorius L., had long been used in treating ischaemic cardiovascular diseases in China and exhibited prominently anticoagulant and pro-angiogenic activities, but the underlying mechanisms remained largely unknown. This study aimed to further elucidate the pro-angiogenic effect and mechanism of HSYA on ischaemic cardiac dysfunction. A C57 mouse model of acute myocardial infarction (AMI) was firstly established, and 25 mg/kg HSYA was intraperitoneally injected immediately after operation and given once, respectively, each morning and evening for 2 weeks...
May 2018: Journal of Cellular and Molecular Medicine
Annely Lorents, Pille Säälik, Ülo Langel, Margus Pooga
Proficient transport vectors called cell-penetrating peptides (CPPs) internalize into eukaryotic cells mostly via endocytic pathways and facilitate the uptake of various cargo molecules attached to them. However, some CPPs are able to induce disturbances in the plasma membrane and translocate through it seemingly in an energy-independent manner. For understanding this phenomenon, giant plasma membrane vesicles (GPMVs) derived from the cells are a beneficial model system, since GPMVs have a complex membrane composition comparable to the cells yet lack cellular energy-dependent mechanisms...
April 18, 2018: Bioconjugate Chemistry
Preethi Devanand, Yukiko Oya, Santhoshkumar Sundaramoorthy, Kye Yong Song, Tatsuro Watanabe, Yasuhito Kobayashi, Yoshihiko Shimizu, Soon Auck Hong, Masami Suganuma, In Kyoung Lim
To understand the regulation of Helicobacter pylori (H. pylori)-associated gastric carcinogenesis, we examined the effect of B-cell translocation gene 2 (BTG2) expression on the biological activity of Tipα, an oncoprotein secreted from H. pylori. BTG2, the human ortholog of mouse TIS21 (BTG2/TIS21 ), has been reported to be a primary response gene that is transiently expressed in response to various stimulations. Here, we report that BTG2 is constitutively expressed in the mucous epithelium and parietal cells of the gastric gland in the stomach...
February 23, 2018: Experimental & Molecular Medicine
Wei-Hai Chen, Sohn Yang Sung, Michael Fadeev, Alessandro Cecconello, Rachel Nechushtai, Itamar Willner
Amino-triphenyl dicarboxylate-bridged Zr4+ metal-organic framework nanoparticles (NMOFs), 100-130 nm, are modified with a nucleic acid complementary to the VEGF aptamer. The nucleic acid-functionalized NMOFs were loaded with the anti-cancer drug doxorubicin (or Rhodamine 6G as a drug model), and the loaded NMOFs were capped by hybridization with the VEGF aptamer that yielded VEGF-responsive duplex nucleic acid gates. In the presence of VEGF, a biomarker over-expressed in cancer cells, selective unlocking of the gates proceeds through the formation of VEGF/aptamer complexes, resulting in the release of the loads...
March 8, 2018: Nanoscale
Iva Ugrinova, Maria Petrova, Mounira Chalabi-Dchar, Philippe Bouvet
Discovered in 1973, nucleolin is one of the most abundant phosphoproteins of the nucleolus. The ability of nucleolin to be involved in many cellular processes is probably related to its structural organization and its capability to form many different interactions with other proteins. Many functions of nucleolin affect cellular processes involved in oncogenesis-for instance: in ribosome biogenesis; in DNA repair, remodeling, and genome stability; in cell division and cell survival; in chemokine and growth factor signaling pathways; in angiogenesis and lymphangiogenesis; in epithelial-mesenchymal transition; and in stemness...
2018: Advances in Protein Chemistry and Structural Biology
Kei Daizumoto, Tetsuro Yoshimaru, Yosuke Matsushita, Tomoya Fukawa, Hisanori Uehara, Masaya Ono, Masato Komatsu, Hiro-Omi Kanayama, Toyomasa Katagiri
The p53 and EGFR pathways are frequently altered in bladder cancer, yet their contributions to its progression remain elusive. Here we report that DEAD box polypeptide 31 (DDX31) plays a critical role in the multistep progression of muscle-invasive bladder cancer (MIBC) through its sequential interactions with mutant p53 (mutp53) and EGFR. In early MIBC cells, nuclear DDX31-bound mutp53/SP1 enhanced mutp53 transcriptional activation, leading to migration and invasion of MIBC. Cytoplasmic DDX31 also bound EGFR and phospho-nucleolin in advanced MIBC, leading to EGFR-Akt signaling activation...
May 1, 2018: Cancer Research
Suping Li, Qiao Jiang, Shaoli Liu, Yinlong Zhang, Yanhua Tian, Chen Song, Jing Wang, Yiguo Zou, Gregory J Anderson, Jing-Yan Han, Yung Chang, Yan Liu, Chen Zhang, Liang Chen, Guangbiao Zhou, Guangjun Nie, Hao Yan, Baoquan Ding, Yuliang Zhao
Nanoscale robots have potential as intelligent drug delivery systems that respond to molecular triggers. Using DNA origami we constructed an autonomous DNA robot programmed to transport payloads and present them specifically in tumors. Our nanorobot is functionalized on the outside with a DNA aptamer that binds nucleolin, a protein specifically expressed on tumor-associated endothelial cells, and the blood coagulation protease thrombin within its inner cavity. The nucleolin-targeting aptamer serves both as a targeting domain and as a molecular trigger for the mechanical opening of the DNA nanorobot...
March 2018: Nature Biotechnology
Xiaoling Yuan, Tao Hu, Hanwen He, Huan Qiu, Xuan Wu, Jingxian Chen, Minmin Wang, Cheng Chen, Shenghai Huang
BACKGROUND: Respiratory syncytial virus (RSV) infects the central nervous system, resulting in neurological symptoms. However, the precise underlying pathogenic mechanisms have not been elucidated. In the present study, the infectivity of RSV on N2a neuronal cells and the possible roles of Toll-like receptor 4 (TLR4) and nucleolin (C23) during RSV infection were investigated. METHODS: We compared two experimental groups (infected and non-infected) and monitored the RSV viral titers in the culture supernatant by a viral plaque assay...
February 10, 2018: Journal of Biomedical Science
Xiao-Ping Huang, Xiao Wang, Xiao-Lan Xie, Gao-Ping Zhang, Feng-Jiao Lv, Wen-Ting Weng, Fei Qiu, Zhao-Fa Li, Jun-Sheng Lin, Yong Diao
Kallistatin is a unique serine proteinase inhibitor and heparin-binding protein. A previous study conducted by our group indicated that kallistatin has antiangiogenic and antitumoral activities. In the present study, we report that kallistatin specifically binds to membrane surface-expressed nucleolin with high affinity. Antibody-mediated neutralization or siRNA-induced nucleolin knockdown results in loss of kallistatin suppression of endothelial cell proliferation and migration in vitro and tumor angiogenesis and growth in vivo ...
January 5, 2018: Oncotarget
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