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https://www.readbyqxmd.com/read/28526811/proteomic-analysis-of-cerebrospinal-fluid-from-children-with-central-nervous-system-tumors-identifies-candidate-proteins-relating-to-tumor-metastatic-spread
#1
Filippo Spreafico, Italia Bongarzone, Sara Pizzamiglio, Ruben Magni, Elena Taverna, Maida De Bortoli, Chiara M Ciniselli, Elena Barzanò, Veronica Biassoni, Alessandra Luchini, Lance A Liotta, Weidong Zhou, Michele Signore, Paolo Verderio, Maura Massimino
Central nervous system (CNS) tumors are the most common solid tumors in childhood. Since the sensitivity of combined cerebrospinal fluid (CSF) cytology and radiological neuroimaging in detecting meningeal metastases remains relatively low, we sought to characterize the CSF proteome of patients with CSF tumors to identify biomarkers predictive of metastatic spread. CSF samples from 27 children with brain tumors and 13 controls (extra-CNS non-Hodgkin lymphoma) were processed using core-shell hydrogel nanoparticles, and analyzed with reverse-phase liquid chromatography/electrospray tandem mass spectrometry (LC-MS/MS)...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28502001/clustering-and-network-analysis-of-reverse-phase-protein-array-data
#2
Adam Byron
Molecular profiling of proteins and phosphoproteins using a reverse phase protein array (RPPA) platform, with a panel of target-specific antibodies, enables the parallel, quantitative proteomic analysis of many biological samples in a microarray format. Hence, RPPA analysis can generate a high volume of multidimensional data that must be effectively interrogated and interpreted. A range of computational techniques for data mining can be applied to detect and explore data structure and to form functional predictions from large datasets...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28502000/reverse-phase-protein-microarrays
#3
Elisa Baldelli, Valerie Calvert, Alex Hodge, Amy VanMeter, Emanuel F Petricoin, Mariaelena Pierobon
While genes and RNA encode information about cellular status, proteins are considered the engine of the cellular machine, as they are the effective elements that drive all cellular functions including proliferation, migration, differentiation, and apoptosis. Consequently, investigations of the cellular protein network are considered a fundamental tool for understanding cellular functions.Alteration of the cellular homeostasis driven by elaborate intra- and extracellular interactions has become one of the most studied fields in the era of personalized medicine and targeted therapy...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28491035/proteomic-analysis-reveals-autophagy-as-pro-survival-pathway-elicited-by-long-term-exposure-with-5-azacitidine-in-high-risk-myelodysplasia
#4
Alessandra Romano, Cesarina Giallongo, Piera La Cava, Nunziatina L Parrinello, Antonella Chiechi, Calogero Vetro, Daniele Tibullo, Francesco Di Raimondo, Lance A Liotta, Virginia Espina, Giuseppe A Palumbo
Azacytidine (5-AZA) is the standard first-choice treatment for high-risk myelodysplasia (MDS) patients. However, the clinical outcome for those patients who interrupt treatment or whose disease failed to respond is very poor. In order to identify the cellular pathways that are modified by long-term exposure to 5-AZA, we evaluated key proteins associated with the autophagy pathway by reverse-phase microarray (RPPA). Comparing bone marrow mononucleated cells (BMMCs) obtained from 20 newly-diagnosed patients and after four 5-AZA cycles we found an increased autophagy signaling...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28476872/integrative-analysis-identifies-a-novel-axl-pi3-kinase-pd-l1-signaling-axis-associated-with-radiation-resistance-in-head-and-neck-cancer
#5
Heath D Skinner, Uma Giri, Liang P Yang, Manish Kumar, Ying Liu, Michael D Story, Curtis R Pickering, Lauren A Byers, Michelle D Williams, Jing Wang, Li Shen, Suk Y Yoo, You Hong Fan, David P Molkentine, Beth M Beadle, Raymond E Meyn, Jeffrey N Myers, John V Heymach
Purpose: The primary cause of death due to head and neck squamous cell carcinoma (HNSCC) is local treatment failure. The goal of this study was to examine this phenomenon using an unbiased approach.Experimental Design: We utilized human papilloma virus (HPV)-negative cell lines rendered radiation-resistant (RR) via repeated exposure to radiation, a panel of HPV-negative HNSCC cell lines and three cohorts of HPV-negative HNSCC tumors (n = 68, 97, and 114) from patients treated with radiotherapy and subjected to genomic, transcriptomic, and proteomic analysis...
May 5, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28446508/enrichment-of-pik3-akt-mtor-pathway-activation-in-hepatic-metastases-from-breast-cancer
#6
Mariaelena Pierobon, Corrine Ramos, Shukmei Wong, K Alex Hodge, Jessica Aldrich, Sara A Byron, Stephen P Anthony, Nicholas J Robert, Donald W Northfelt, Mohammad Jahanzeb, Linda Vocila, Julia D Wulfkuhle, Guido Gambara, Rosa Isela Gallagher, Bryant Dunetz, Nicholas Hoke, Ting Dong, David W Craig, Massimo Cristofanilli, Brian Leyland Jones, Lance Liotta, Joyce A O'Shaughnessy, John D Carpten, Emanuel F Petricoin
Purpose: Little is known about the molecular signatures associated with specific metastatic sites in breast cancer. Using comprehensive multi-omic molecular profiling, we assessed whether alterations or activation of the PI3K-AKT-mTOR pathway is associated with specific sites of breast cancer metastasis. <p>Experimental Design: NGS-based whole exome sequencing was coupled with Reverse Phase Protein Microarray (RPPA) functional signaling network analysis to explore the PI3K-AKT-mTOR axis in 32 pretreated breast cancer metastases...
April 26, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28442428/rapamycin-modulation-of-p70-s6-kinase-signaling-inhibits-rift-valley-fever-virus-pathogenesis
#7
Todd M Bell, Virginia Espina, Svetlana Senina, Caitlin Woodson, Ashwini Brahms, Brian Carey, Shih-Chao Lin, Lindsay Lundberg, Chelsea Pinkham, Alan Baer, Claudius Mueller, Elizabeth A Chlipala, Faye Sharman, Cynthia de la Fuente, Lance Liotta, Kylene Kehn-Hall
Despite over 60 years of research on antiviral drugs, very few are FDA approved to treat acute viral infections. Rift Valley fever virus (RVFV), an arthropod borne virus that causes hemorrhagic fever in severe cases, currently lacks effective treatments. Existing as obligate intracellular parasites, viruses have evolved to manipulate host cell signaling pathways to meet their replication needs. Specifically, translation modulation is often necessary for viruses to establish infection in their host. Here we demonstrated phosphorylation of p70 S6 kinase, S6 ribosomal protein, and eIF4G following RVFV infection in vitro through western blot analysis and in a mouse model of infection through reverse phase protein microarrays (RPPA)...
April 23, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28440122/effects-of-low-dose-ionizing-radiation-on-dna-damage-caused-pathways-by-reverse-phase-protein-array-and-bayesian-networks
#8
Dong-Chul Kim, Mingon Kang, Ashis Biswas, Chin-Rang Yang, Xiaoyu Wang, Jean X Gao
Ionizing radiation (IR) causing damages to Deoxyribonucleic acid (DNA) constitutes a broad range of base damage and double strand break, and thereby, it induces the operation of relevant signaling pathways such as DNA repair, cell cycle control, and cell apoptosis. The goal of this paper is to study how the exposure to low dose radiation affects the human body by observing the signaling pathway associated with Ataxia Telangiectasia mutated (ATM) using Reverse-Phase Protein Array (RPPA) and isogenic human Ataxia Telangiectasia (A-T) cells under different amounts and durations of IR exposure...
April 2017: Journal of Bioinformatics and Computational Biology
https://www.readbyqxmd.com/read/28389531/chk1-targeted-therapy-to-deplete-dna-replication-stressed-p53-deficient-hyperdiploid-colorectal-cancer-stem-cells
#9
Gwenola Manic, Michele Signore, Antonella Sistigu, Giorgio Russo, Francesca Corradi, Silvia Siteni, Martina Musella, Sara Vitale, Maria Laura De Angelis, Matteo Pallocca, Carla Azzurra Amoreo, Francesca Sperati, Simone Di Franco, Sabina Barresi, Eleonora Policicchio, Gabriele De Luca, Francesca De Nicola, Marcella Mottolese, Ann Zeuner, Maurizio Fanciulli, Giorgio Stassi, Marcello Maugeri-Saccà, Marta Baiocchi, Marco Tartaglia, Ilio Vitale, Ruggero De Maria
OBJECTIVE: Cancer stem cells (CSCs) are responsible for tumour formation and spreading, and their targeting is required for tumour eradication. There are limited therapeutic options for advanced colorectal cancer (CRC), particularly for tumours carrying RAS-activating mutations. The aim of this study was to identify novel CSC-targeting strategies. DESIGN: To discover potential therapeutics to be clinically investigated as single agent, we performed a screening with a panel of FDA-approved or investigational drugs on primary CRC cells enriched for CSCs (CRC-SCs) isolated from 27 patients...
April 7, 2017: Gut
https://www.readbyqxmd.com/read/28376174/role-of-yap1-as-a-marker-of-sensitivity-to-dual-akt-and-p70s6k-inhibition-in-ovarian-and-uterine-malignancies
#10
Rebecca A Previs, Guillermo N Armaiz-Pena, Cristina Ivan, Heather J Dalton, Rajesha Rupaimoole, Jean M Hansen, Yasmin Lyons, Jie Huang, Monika Haemmerle, Michael J Wagner, Kshipra M Gharpure, Archana S Nagaraja, Justyna Filant, Michael H McGuire, Kyunghee Noh, Piotr L Dorniak, Sarah L Linesch, Lingegowda S Mangala, Sunila Pradeep, Sherry Y Wu, Anil K Sood
Background: The PI3K/AKT/P70S6K pathway is an attractive therapeutic target in ovarian and uterine malignancies because of its high rate of deregulation and key roles in tumor growth. Here, we examined the biological effects of MSC2363318A, which is a novel inhibitor of AKT1, AKT3, and P70S6K. Methods: Orthotopic murine models of ovarian and uterine cancer were utilized to study the effect of MSC2363318A on survival and regression. For each cell line, 10 mice were treated in each of the experimental arms tested...
July 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28294973/fusion-guided-hypothesis-development-leads-to-the-identification-of-n%C3%A2-n%C3%A2-dimethyladenosine-a-marine-derived-akt-pathway-inhibitor
#11
Rachel M Vaden, Nathaniel W Oswald, Malia B Potts, John B MacMillan, Michael A White
Chemicals found in nature have evolved over geological time scales to productively interact with biological molecules, and thus represent an effective resource for pharmaceutical development. Marine-derived bacteria are rich sources of chemically diverse, bioactive secondary metabolites, but harnessing this diversity for biomedical benefit is limited by challenges associated with natural product purification and determination of biochemical mechanism. Using Functional Signature Ontology (FUSION), we report the parallel isolation and characterization of a marine-derived natural product, N⁶,N⁶-dimethyladenosine, that robustly inhibits AKT signaling in a variety of non-small cell lung cancer cell lines...
March 15, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28255027/akt-activation-mediates-acquired-resistance-to-fibroblast-growth-factor-receptor-inhibitor-bgj398
#12
Jharna Datta, Senthilkumar Damodaran, Hannah Parks, Cristina Ocrainiciuc, Jharna Miya, Lianbo Yu, Elijah P Gardner, Eric Samorodnitsky, Michele R Wing, Darshna Bhatt, John Hays, Julie W Reeser, Sameek Roychowdhury
Activation of FGFR signaling through mutations, amplifications, or fusions involving FGFR1, 2, 3, or 4 is seen in multiple tumors, including lung, bladder, and cholangiocarcinoma. Currently, several clinical trials are evaluating the role of novel FGFR inhibitors in solid tumors. As we move forward with FGFR inhibitors clinically, we anticipate the emergence of resistance with treatment. Consequently, we sought to study the mechanism(s) of acquired resistance to FGFR inhibitors using annotated cancer cell lines...
April 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28254151/role-of-cyclooxygenase-2-pathway-in-creating-an-immunosuppressive-microenvironment-and-in-initiation-and-progression-of-wilms-tumor
#13
Paramahamsa Maturu, Devin Jones, E Cristy Ruteshouser, Qianghua Hu, Joseph M Reynolds, John Hicks, Nagireddy Putluri, Suhendan Ekmekcioglu, Elizabeth A Grimm, Chen Dong, Willem W Overwijk
Wilms' tumors (WT), which accountfor 6% of all childhood cancers, arise from dysregulated differentiation of nephrogenic progenitor cells from embryonic kidneys. Though there is an improvement in the prognosis of WT, still 10% of patients with WT die due to recurrence. Thus more effective treatment approaches are necessary. We previously characterized the inflammatory microenvironment in human WT and observed the robust expression of COX-2. The aim of this study was to extend our studies to analyze the role of COX-2 pathway components in WT progression using a mouse model of WT...
March 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28216608/expression-of-iron-related-proteins-differentiate-non-cancerous-and-cancerous-breast-tumors
#14
Sara Pizzamiglio, Maida De Bortoli, Elena Taverna, Michele Signore, Silvia Veneroni, William Chi-Shing Cho, Rosaria Orlandi, Paolo Verderio, Italia Bongarzone
We have previously reported hepcidin and ferritin increases in the plasma of breast cancer patients, but not in patients with benign breast disease. We hypothesized that these differences in systemic iron homeostasis may reflect alterations in different iron-related proteins also play a key biochemical and regulatory role in breast cancer. Thus, here we explored the expression of a bundle of molecules involved in both iron homeostasis and tumorigenesis in tissue samples. Enzyme-linked immunosorbent assay (ELISA) or reverse-phase protein array (RPPA), were used to measure the expression of 20 proteins linked to iron processes in 24 non-cancerous, and 56 cancerous, breast tumors...
February 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28185526/low-expression-of-ash2l-protein-correlates-with-a-favorable-outcome-in-acute-myeloid-leukemia
#15
Jill S Butler, Yi Hua Qiu, Nianxiang Zhang, Suk-Young Yoo, Kevin R Coombes, Sharon Y R Dent, Steven M Kornblau
ASH2L encodes a trithorax group protein that is a core component of all characterized mammalian histone H3K4 methyltransferase complexes, including mixed lineage leukemia (MLL) complexes. ASH2L protein levels in primary leukemia patient samples have not yet been defined. We analyzed ASH2L protein expression in 511 primary AML patient samples using reverse phase protein array (RPPA) technology. We discovered that ASH2L expression is significantly increased in a subset of patients carrying fms-related tyrosine kinase 3 (FLT3) mutations...
May 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28183315/pyruvate-kinase-m2-and-the-mitochondrial-atpase-inhibitory-factor-1-provide-novel-biomarkers-of-dermatomyositis-a-metabolic-link-to-oncogenesis
#16
Fulvio Santacatterina, María Sánchez-Aragó, Marc Catalán-García, Glòria Garrabou, Cristina Nuñez de Arenas, Josep M Grau, Francesc Cardellach, José M Cuezva
BACKGROUND: Metabolic alterations play a role in the development of inflammatory myopathies (IMs). Herein, we have investigated through a multiplex assay whether proteins of energy metabolism could provide biomarkers of IMs. METHODS: A cohort of thirty-two muscle biopsies and forty plasma samples comprising polymyositis (PM), dermatomyositis (DM) and sporadic inclusion body myositis (sIBM) and control donors was interrogated with monoclonal antibodies against proteins of energy metabolism using reverse phase protein microarrays (RPPA)...
February 10, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28157711/the-repurposed-anthelmintic-mebendazole-in-combination-with-trametinib-suppresses-refractory-nrasq61k-melanoma
#17
Cynthia M Simbulan-Rosenthal, Sivanesan Dakshanamurthy, Anirudh Gaur, You-Shin Chen, Hong-Bin Fang, Maryam Abdussamad, Hengbo Zhou, John Zapas, Valerie Calvert, Emanuel F Petricoin, Michael B Atkins, Stephen W Byers, Dean S Rosenthal
Structure-based drug repositioning in addition to random chemical screening is now a viable route to rapid drug development. Proteochemometric computational methods coupled with kinase assays showed that mebendazole (MBZ) binds and inhibits kinases important in cancer, especially both BRAFWT and BRAFV600E. We find that MBZ synergizes with the MEK inhibitor trametinib to inhibit growth of BRAFWT-NRASQ61K melanoma cells in culture and in xenografts, and markedly decreased MEK and ERK phosphorylation. Reverse Phase Protein Array (RPPA) and immunoblot analyses show that both trametinib and MBZ inhibit the MAPK pathway, and cluster analysis revealed a protein cluster showing strong MBZ+trametinib - inhibited phosphorylation of MEK and ERK within 10 minutes, and its direct and indirect downstream targets related to stress response and translation, including ElK1 and RSKs within 30 minutes...
February 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28003305/co-occurring-mutations-of-tumor-suppressor-genes-lats2-and-nf2-in-malignant-pleural-mesothelioma
#18
Robin Tranchant, Lisa Quetel, Anne Tallet, Clément Meiller, Annie Renier, Leanne de Koning, Aurélien de Reyniès, Francoise Le Pimpec Barthes, Jessica Zucman-Rossi, Marie-Claude Jaurand, Didier Jean
PURPOSE: To better define MPM heterogeneity and identify molecular subtypes of malignant pleural mesothelioma (MPM), we focus on the tumor suppressor gene LATS2, a member of the Hippo signaling pathway, which plays a key role in mesothelial carcinogenesis. EXPERIMENTAL DESIGN: Sixty-one MPM primary cultures established in our laboratory were screened for mutations in LATS2. Gene inactivation was modeled using siRNAs. Gene and protein expressions were analyzed by quantitative RT-PCR, western blot and RPPA...
December 21, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27933927/three-dimensionally-functionalized-reverse-phase-glycoprotein-array-for-cancer-biomarker-discovery-and-validation
#19
Li Pan, Hillary Andaluz Aguilar, Linna Wang, Anton Iliuk, W Andy Tao
Glycoproteins have vast structural diversity that plays an important role in many biological processes and have great potential as disease biomarkers. Here, we report a novel functionalized reverse phase protein array (RPPA), termed polymer-based reverse phase glycoprotein array (polyGPA), to capture and profile glycoproteomes specifically, and validate glycoproteins. Nitrocellulose membrane functionalized with globular hydroxyaminodendrimers was used to covalently capture preoxidized glycans on glycoproteins from complex protein samples such as biofluids...
November 30, 2016: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/27883284/novel-biomarkers-of-nasopharyngeal-carcinoma-metastasis-risk-identified-by-reverse-phase-protein-array-based-tumor-profiling-with-consideration-of-plasma-epstein-barr-virus-dna-load
#20
Tao Xu, Bojin Su, Peiyu Huang, Weihong Wei, Yanming Deng, Vasudha Sehgal, Donghui Wang, Jun Jiang, Guoyi Zhang, Anfei Li, Huiling Yang, Francois X Claret
PURPOSE: In patients with Epstein-Barr virus (EBV) associated nasopharyngeal carcinoma (NPC), intertumor heterogeneity causes interpatient heterogeneity in the risk of distant metastasis. We aimed to identify novel biomarkers of metastasis risk using reverse phase protein array (RPPA) profiling of NPC patients at risk for metastasis and considering plasma EBV DNA load. EXPERIMENTAL DESIGN: A total of 98 patients with NPC with and without metastasis after treatment, matched with respect to clinical parameters, are enrolled...
May 2017: Proteomics. Clinical Applications
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