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https://www.readbyqxmd.com/read/29049978/targeting-eif4e-inhibits-growth-survival-and-angiogenesis-in-retinoblastoma-and-enhances-efficacy-of-chemotherapy
#1
Genguo Wang, Zhi Li, Zhuojun Li, Yi Huang, Xiaochun Mao, Chang Xu, Sha Cui
Although the eukaryotic translation initiation factor 4E (eIF4E) has been shown to be critically involved in the transformation and progression of various tumors, little is known about the role of eIF4E in retinoblastoma. In this work, we report that ribavirin, a pharmacologic inhibitor of eIF4E function, effectively targets retinoblastoma and angiogenesis. Ribavirin treatment dose-dependently blocked the growth and stimulated apoptosis in various retinoblastoma cell lines, with IC50 values that are within the clinically achievable range...
October 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29045428/the-role-of-pka-in-the-translational-response-to-heat-stress-in-saccharomyces-cerevisiae
#2
Carla E Barraza, Clara A Solari, Irina Marcovich, Christopher Kershaw, Fiorella Galello, Silvia Rossi, Mark P Ashe, Paula Portela
Cellular responses to stress stem from a variety of different mechanisms, including translation arrest and relocation of the translationally repressed mRNAs to ribonucleoprotein particles like stress granules (SGs) and processing bodies (PBs). Here, we examine the role of PKA in the S. cerevisiae heat shock response. Under mild heat stress Tpk3 aggregates and promotes aggregation of eIF4G, Pab1 and eIF4E, whereas severe heat stress leads to the formation of PBs and SGs that contain both Tpk2 and Tpk3 and a larger 48S translation initiation complex...
2017: PloS One
https://www.readbyqxmd.com/read/29042487/differential-response-of-glioma-stem-cells-to-arsenic-trioxide-therapy-is-regulated-by-mnk1-and-mrna-translation
#3
Jonathan B Bell, Frank Eckerdt, Harshil Dhruv, Darren Finlay, Sen Peng, Seungchan Kim, Barbara Kroczynska, Elspeth Beauchamp, Kristen Alley, Jessica Clymer, Stewart Goldman, Shi-Yuan Cheng, C David James, Ichiro Nakano, Craig Horbinski, Andrew P Mazar, Kristiina Vuori, Priya Kumthekar, Jeffery Raizer, Michael E Berens, Leonidas C Platanias
Mesenchymal (MES) and proneural (PN) are two distinct glioma stem cells (GSCs) populations that drive therapeutic resistance in glioblastoma (GBM). We screened a panel of 650 small molecules against patient-derived GBM cells to discover compounds targeting specific GBM subtypes. Arsenic trioxide (ATO), a FDA-approved drug that crosses the blood-brain barrier, was identified as a potent PN-specific compound in the initial screen and follow-up validation studies. Furthermore, MES and PN GSCs exhibited differential sensitivity to ATO...
October 17, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29038175/predictability-of-recurrence-using-immunohistochemistry-to-delineate-surgical-margins-in-mucosal-head-and-neck-squamous-cell-carcinoma-prism-hnscc-study-protocol-for-a-prospective-observational-and-bilateral-study-in-australia-and-india
#4
Sheela Joseph, Rajinikanth Janakiraman, Geeta Chacko, Rama Jayaraj, Mahiban Thomas, Meera Thomas, Sramana Mukhopadhyay
OBJECTIVES: Treatment failure and poor 5-year survival in mucosal head and neck squamous cell carcinoma (HNSCC) has remained unchanged for decades mainly due to advanced stage of presentation and high rates of recurrence. Incomplete surgical removal of the tumour, attributed to lack of reliable methods to delineate the surgical margins, is a major cause of disease recurrence. The predictability of recurrence using immunohistochemistry (IHC) to delineate surgical margins (PRISM) in mucosal HNSCC study aims to redefine margin status by identifying the true extent of the tumour at the molecular level by performing IHC with molecular markers, eukaryotic initiation factor, eIF4Eand tumour suppressor gene, p53, on the surgical margins and test the use of Lugol's iodine and fluorescence visualisation prior to the wide local excision...
October 15, 2017: BMJ Open
https://www.readbyqxmd.com/read/29035277/mnk1-2-inhibition-limits-oncogenicity-and-metastasis-of-kit-mutant-melanoma
#5
Yao Zhan, Jun Guo, William Yang, Christophe Goncalves, Tomasz Rzymski, Agnieszka Dreas, Eliza Żyłkiewicz, Maciej Mikulski, Krzysztof Brzózka, Aniela Golas, Yan Kong, Meng Ma, Fan Huang, Bonnie Huor, Qianyu Guo, Sabrina Daniela da Silva, Jose Torres, Yutian Cai, Ivan Topisirovic, Jie Su, Krikor Bijian, Moulay A Alaoui-Jamali, Sidong Huang, Fabrice Journe, Ghanem E Ghanem, Wilson H Miller, Sonia V Del Rincón
Melanoma can be stratified into unique subtypes based on distinct pathologies. The acral/mucosal melanoma subtype is characterized by aberrant and constitutive activation of the proto-oncogene receptor tyrosine kinase C-KIT, which drives tumorigenesis. Treatment of these melanoma patients with C-KIT inhibitors has proven challenging, prompting us to investigate the downstream effectors of the C-KIT receptor. We determined that C-KIT stimulates MAP kinase-interacting serine/threonine kinases 1 and 2 (MNK1/2), which phosphorylate eukaryotic translation initiation factor 4E (eIF4E) and render it oncogenic...
October 16, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28987382/arginine-methyltransferase-inhibitor-1-inhibits-gastric-cancer-by-downregulating-eif4e-and-targeting-prmt5
#6
Baolai Zhang, Su Zhang, Lijuan Zhu, Xue Chen, Yunfeng Zhao, Li Chao, Juanping Zhou, Xing Wang, Xinyang Zhang, Nengqian Ma
Arginine methylation is carried out by protein arginine methyltransferase (PRMTs) family. Arginine methyltransferase inhibitor 1 (AMI-1) is mainly used to inhibit type I PRMT activity in vitro. However, the effects of AMI-1 on type II PRMT5 activity and gastric cancer (GC) remain unclear. In this study, we provided the first evidence that AMI-1 significantly inhibited GC cell proliferation and migration while induced GC cell apoptosis, and reduced the expression of PRMT5, eukaryotic translation initiation factor 4E (eIF4E), symmetric dimethylation of histone 3 (H3R8me2s) and histone 4 (H4R3me2s)...
October 4, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28982715/capturing-the-asc1p-rack1-microenvironment-at-the-head-region-of-the-40s-ribosome-with-quantitative-bioid-in-yeast
#7
Nadine Opitz, Kerstin Schmitt, Verena Hofer-Pretz, Bettina Neumann, Heike Krebber, Gerhard H Braus, Oliver Valerius
The Asc1 protein of Saccharomyces cerevisiae is a scaffold protein at the head region of ribosomal 40S that links mRNA translation to cellular signaling. In this study, proteins that co-localize with Asc1p were identified with proximity-dependent Biotin IDentification (BioID), an in vivo labeling technique described here for the first time for yeast. Biotinylated Asc1p-birA*-proximal proteins were identified and quantitatively verified against controls applying SILAC and mass spectrometry. The mRNA-binding proteins Sro9p and Gis2p appeared together with Scp160p, each providing ribosomes with nuclear transcripts...
October 5, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28978144/targeting-the-pi3k-akt-mtor-signaling-pathway-as-an-effectively-radiosensitizing-strategy-for-treating-human-oral-squamous-cell-carcinoma-in-vitro-and-in-vivo
#8
Chih-Chia Yu, Shih-Kai Hung, Hon-Yi Lin, Wen-Yen Chiou, Moon-Sing Lee, Hui-Fen Liao, Hsien-Bin Huang, Hsu-Chueh Ho, Yu-Chieh Su
Radiation therapy (RT) is the current standard adjuvant approach for oral squamous cell carcinoma (OSCC) patients. Radioresistance is a major contributor to radiotherapy failure. In this study, we used patient-derived cells and a radiation-resistant cell line in vitro and in vivo for two purposes: evaluate the anti-tumor effects and understand the mechanisms in the dual PI3K/mTOR signaling pathway regulation of radiosensitization. Our findings indicate that in OML1-R cells, the radioresistance phenotype is associated with activation of the PI3K/AKT/mTOR signaling pathway...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28968974/cap-dependent-translational-control-of-oncolytic-measles-virus-infection-in-malignant-mesothelioma
#9
Blake A Jacobson, Ahad A Sadiq, Shaogeng Tang, Joe Jay-Dixon, Manish R Patel, Jeremy Drees, Brent S Sorenson, Stephen J Russell, Robert A Kratzke
Malignant mesothelioma has a poor prognosis for which there remains an urgent need for successful treatment approaches. Infection with the Edmonston vaccine strain (MV-Edm) derivative of measles virus results in lysis of cancer cells and has been tested in clinical trials for numerous tumor types including mesothelioma. Many factors play a role in MV-Edm tumor cell selectivity and cytopathic activity while also sparing non-cancerous cells. The MV-Edm receptor CD46 (cluster of differentiation 46) was demonstrated to be significantly higher in mesothelioma cells than in control cells...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28963881/selective-recruitment-of-nucleoporins-on-vaccinia-virus-factories-and-the-role-of-nup358-in-viral-infection
#10
Deepak Khuperkar, Ashish Kamble, Aditi Singh, Arya Ghate, Renuka Nawadkar, Arvind Sahu, Jomon Joseph
Vaccinia virus (VACV), a member of the Poxviridae family, uses cytoplasmic factories for its replication. Recent studies indicated that VACV infection requires a set of nucleoporins. However, how the nucleoporins contribute to viral life cycle remains unclear. Here, we report that the nucleoporins Nup62 and Nup358 localize to the cytoplasmic viral factories (VFs). Nup358 was targeted to the VFs at 6h post-infection (hpi), whereas Nup62, along with the previously reported translation factors such as eIF4E, eIF3η and G3BP1, was recruited to the VFs at 8 hpi...
September 27, 2017: Virology
https://www.readbyqxmd.com/read/28951222/dietary-pyridoxine-deficiency-reduced-growth-performance-and-impaired-intestinal-immune-function-associated-with-tor-and-nf-%C3%AE%C2%BAb-signalling-of-young-grass-carp-ctenopharyngodon-idella
#11
Xin Zheng, Lin Feng, Wei-Dan Jiang, Pei Wu, Yang Liu, Jun Jiang, Sheng-Yao Kuang, Ling Tang, Wu-Neng Tang, Yong-An Zhang, Xiao-Qiu Zhou
The objective of this study was to evaluate the effects of dietary pyridoxine (PN) deficiency on growth performance, intestinal immune function and the potential regulation mechanisms in young grass carp (Ctenopharyngodon idella). Fish were fed six diets containing graded levels of PN (0.12-7.48 mg/kg) for 70 days. After that, a challenge test was conducted by infection of Aeromonas hydrophila for 14 days. The results showed that compared with the optimal PN level, PN deficiency: (1) reduced the production of innate immune components such as lysozyme (LZ), acid phosphatase (ACP), complements and antimicrobial peptides and adaptive immune components such as immunoglobulins in three intestinal segments of young grass carp (P < 0...
September 23, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28934492/concerted-action-of-two-3-cap-independent-translation-enhancers-increases-the-competitive-strength-of-translated-viral-genomes
#12
Zhiyou Du, Olga M Alekhina, Konstantin S Vassilenko, Anne E Simon
Several families of plant viruses evolved cap-independent translation enhancers (3'CITE) in the 3' untranslated regions of their genomic (g)RNAs to compete with ongoing cap-dependent translation of cellular mRNAs. Umbravirus Pea enation mosaic virus (PEMV)2 is the only example where three 3'CITEs enhance translation: the eIF4E-binding Panicum mosaic virus-like translational enhancer (PTE) and ribosome-binding 3' T-shaped structure (TSS) have been found in viruses of different genera, while the ribosome-binding kl-TSS that provides a long-distance interaction with the 5' end is unique...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28918902/mtor-controls-mitochondrial-dynamics-and-cell-survival-via-mtfp1
#13
Masahiro Morita, Julien Prudent, Kaustuv Basu, Vanessa Goyon, Sakie Katsumura, Laura Hulea, Dana Pearl, Nadeem Siddiqui, Stefan Strack, Shawn McGuirk, Julie St-Pierre, Ola Larsson, Ivan Topisirovic, Hojatollah Vali, Heidi M McBride, John J Bergeron, Nahum Sonenberg
The mechanisms that link environmental and intracellular stimuli to mitochondrial functions, including fission/fusion, ATP production, metabolite biogenesis, and apoptosis, are not well understood. Here, we demonstrate that the nutrient-sensing mechanistic/mammalian target of rapamycin complex 1 (mTORC1) stimulates translation of mitochondrial fission process 1 (MTFP1) to control mitochondrial fission and apoptosis. Expression of MTFP1 is coupled to pro-fission phosphorylation and mitochondrial recruitment of the fission GTPase dynamin-related protein 1 (DRP1)...
September 21, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28916625/transcriptional-correlates-of-memory-maintenance-following-long-term-sensitization-of-aplysia-californica
#14
Catherine Conte, Samantha Herdegen, Saman Kamal, Jency Patel, Ushma Patel, Leticia Perez, Marissa Rivota, Robert J Calin-Jageman, Irina E Calin-Jageman
We characterized the transcriptional response accompanying maintenance of long-term sensitization (LTS) memory in the pleural ganglia of Aplysia californica using microarray (N = 8) and qPCR (N = 11 additional samples). We found that 24 h after memory induction there is strong regulation of 1198 transcripts (748 up and 450 down) in a pattern that is almost completely distinct from what is observed during memory encoding (1 h after training). There is widespread up-regulation of transcripts related to all levels of protein production, from transcription (e...
October 2017: Learning & Memory
https://www.readbyqxmd.com/read/28915586/hepatitis-c-virus-core-protein-targets-4e-bp1-expression-and-phosphorylation-and-potentiates-myc-induced-liver-carcinogenesis-in-transgenic-mice
#15
Cosette Abdallah, Charlène Lejamtel, Nassima Benzoubir, Serena Battaglia, Nazha Sidahmed-Adrar, Christophe Desterke, Matthieu Lemasson, Arielle R Rosenberg, Didier Samuel, Christian Bréchot, Delphine Pflieger, François Le Naour, Marie-Françoise Bourgeade
Hepatitis C virus (HCV) is a leading cause of liver diseases including the development of hepatocellular carcinoma (HCC). Particularly, core protein has been involved in HCV-related liver pathologies. However, the impact of HCV core on signaling pathways supporting the genesis of HCC remains largely elusive. To decipher the host cell signaling pathways involved in the oncogenic potential of HCV core, a global quantitative phosphoproteomic approach was carried out. This study shed light on novel differentially phosphorylated proteins, in particular several components involved in translation...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28913664/supplementation-of-enzyme-treated-soy-protein-saves-dietary-protein-and-promotes-digestive-and-absorptive-ability-referring-to-tor-signaling-in-juvenile-fish
#16
Weiwei Xiao, Weidan Jiang, Lin Feng, Yang Liu, Pei Wu, Jun Jiang, Yongan Zhang, Xiaoqiu Zhou
This study was conducted to evaluate the effect of enzyme-treated soy protein (ETSP) supplementation in the low-protein diet on growth performance, digestive and absorptive capacities, and related signaling molecules' gene expressions in juvenile Jian carp. The results showed that percent weight gain (PWG), specific growth rate (SGR), and feed intake (FI) were decreased by reducing dietary protein from 34 to 32% (P < 0.05). Supplying low-protein diet with optimal ETSP increased previously mentioned indices of juvenile Jian carp (P < 0...
December 2017: Fish Physiology and Biochemistry
https://www.readbyqxmd.com/read/28887716/inhibitory-effect-and-molecular-mechanism-of-mesenchymal-stem-cells-on-nsclc-cells
#17
Mengwu Pan, Lingling Hou, Jingsi Zhang, Diandian Zhao, Jilei Hua, Ziling Wang, Jinsheng He, Hong Jiang, Honggang Hu, Lishu Zhang
Non-small-cell lung cancer (NSCLC) is still the main threat of cancer-associated death. Current treatment of NSCLC has limited effectiveness, and unfortunately, the prognosis of NSCLC remains poor. Therefore, a novel strategy for cancer therapy is urgently needed. Stem cell therapy has significant potential for cancer treatment. Mesenchymal stem cells (MSCs) with capacity for self-renewal and differentiation into various cells types exhibit the feature of homing to tumor site and immunosuppression, have been explored as a new treatment for various cancers...
September 8, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28881737/galeterone-and-its-analogs-inhibit-mnk-eif4e-axis-synergize-with-gemcitabine-impede-pancreatic-cancer-cell-migration-invasion-and-proliferation-and-inhibit-tumor-growth-in-mice
#18
Andrew K Kwegyir-Afful, Francis N Murigi, Puranik Purushottamachar, Vidya P Ramamurthy, Marlena S Martin, Vincent C O Njar
Survival rate for pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC) is poor, with about 80% of patients presenting with the metastatic disease. Gemcitabine, the standard chemotherapeutic agent for locally advanced and metastatic PDAC has limited efficacy, attributed to innate/acquired resistance and activation of pro-survival pathways. The Mnk1/2-eIF4E and NF-κB signaling pathways are implicated in PDAC disease progression/metastasis and also associated with gemcitabine-induced resistance in PDAC...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881582/metformin-requires-4e-bps-to-induce-apoptosis-and-repress-translation-of-mcl-1-in-hepatocellular-carcinoma-cells
#19
Mamatha Bhat, Akiko Yanagiya, Tyson Graber, Nataliya Razumilava, Steve Bronk, Domenick Zammit, Yunhao Zhao, Chadi Zakaria, Peter Metrakos, Michael Pollak, Nahum Sonenberg, Gregory Gores, Maritza Jaramillo, Masahiro Morita, Tommy Alain
Metformin inhibits the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, which is frequently upregulated in hepatocellular carcinoma (HCC). Metformin has also been shown to induce apoptosis in this cancer. Here, we investigate whether metformin-induced apoptosis in HCC is mediated by the downstream mTORC1 effectors eukaryotic initiation factor 4E and (eIF4E)-binding proteins (4E-BPs). Further, we ask whether changes in 4E-BPs activity during metformin treatment negatively regulate translation of the anti-apoptotic myeloid cell leukemia 1 (Mcl-1) mRNA...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28878291/map-kinase-interacting-serine-threonine-kinase-2-promotes-proliferation-metastasis-and-predicts-poor-prognosis-in-non-small-cell-lung-cancer
#20
Zhihua Guo, Guilin Peng, Ermao Li, Shaoyan Xi, Yu Zhang, Yong Li, Xiaodong Lin, Guangqiu Li, Qinian Wu, Jianxing He
We hypothesized that MAP kinase-interacting serine/threonine kinase 2 (MNK2) may contribute to non-small cell lung cancer (NSCLC) development, and serve as a new therapeutic target. Immunohistochemical staining evaluated the correlation between MNK2 expression and clinicopathological features in 367 NSCLC cancer tissues. We determined the effects of MNK2 silencing in NSCLC cell lines in vitro and in vivo. RT-PCR and western blotting was used to examine the impact of MNK2 on ERK and AKT pathways. MNK2 was overexpressed in NSCLC cell lines and tumor tissues...
September 6, 2017: Scientific Reports
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