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Reverse phase protein array

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https://www.readbyqxmd.com/read/28651964/protein-network-construction-using-reverse-phase-protein-array-data
#1
Rency S Varghese, Yiming Zuo, Yi Zhao, Yong-Wei Zhang, Sandra A Jablonski, Mariaelena Pierobon, Emanuel F Petricoin, Habtom W Ressom, Louis M Weiner
In this paper, we introduce a novel computational method for constructing protein networks based on reverse phase protein array (RPPA) data to identify complex patterns in protein signaling. The method is applied to phosphoproteomic profiles of basal expression and activation/phosphorylation of 76 key signaling proteins in three breast cancer cell lines (MCF7, LCC1, and LCC9). Temporal RPPA data are acquired at 48h, 96h, and 144h after knocking down four genes in separate experiments. These genes are selected from a previous study as important determinants for breast cancer survival...
June 23, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28648142/overcoming-intratumoural-heterogeneity-for-reproducible-molecular-risk-stratification-a-case-study-in-advanced-kidney-cancer
#2
Alexander L R Lubbock, Grant D Stewart, Fiach C O'Mahony, Alexander Laird, Peter Mullen, Marie O'Donnell, Thomas Powles, David J Harrison, Ian M Overton
BACKGROUND: Metastatic clear cell renal cell cancer (mccRCC) portends a poor prognosis and urgently requires better clinical tools for prognostication as well as for prediction of response to treatment. Considerable investment in molecular risk stratification has sought to overcome the performance ceiling encountered by methods restricted to traditional clinical parameters. However, replication of results has proven challenging, and intratumoural heterogeneity (ITH) may confound attempts at tissue-based stratification...
June 26, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28647089/reverse-phase-protein-arrays-elucidate-mechanisms-of-action-and-phenotypic-response-in-2d-and-3d-models
#3
REVIEW
Michael Pawlak, Neil O Carragher
The development of new 2D and 3D phenotypic screening assays combined with high-throughput genomic and proteomic technologies are well placed to advance a new era of molecular pathway informed Phenotypic Drug Discovery. We describe the application of Reverse Phase Protein Array (RPPA) technology to elucidate the mechanism-of-action of small molecules at the post-translational pathway level. We propose that profiling of phenotypic hits and lead molecules in increasingly more complex 3D in vitro and ex vivo models at the post-translational pathway network level represents an effective strategy to both triage and progress the preclinical development of phenotypic screening hits...
March 2017: Drug Discovery Today. Technologies
https://www.readbyqxmd.com/read/28634413/topical-fibronectin-improves-wound-healing-of-irradiated-skin
#4
Maxwell B Johnson, Brandon Pang, Daniel J Gardner, Solmaz Niknam-Benia, Vinaya Soundarajan, Athanasios Bramos, David P Perrault, Kian Banks, Gene K Lee, Regina Y Baker, Gene H Kim, Sunju Lee, Yang Chai, Mei Chen, Wei Li, Lawrence Kwong, Young-Kwon Hong, Alex K Wong
Wound healing is significantly delayed in irradiated skin. To better understand global changes in protein expression after radiation, we utilized a reverse phase protein array (RPPA) to identify significant changes in paired samples of normal and irradiated human skin. Of the 210 proteins studied, fibronectin was the most significantly and consistently downregulated in radiation-damaged skin. Using a murine model, we confirmed that radiation leads to decreased fibronectin expression in the skin as well as delayed wound healing...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28627414/role-of-akt-hyperactivation-and-the-potential-of-akt-targeted-therapy-in-diffuse-large-b-cell-lymphoma
#5
Jinfen Wang, Zijun Y Xu-Monette, Kausar J Jabbar, Qi Shen, Ganiraju C Manyam, Alexandar Tzankov, Carlo Visco, Jing Wang, Santiago Montes-Moreno, Karen Dybkær, Wayne Tam, Govind Bhagat, Eric D Hsi, J Han van Krieken, Maurilio Ponzoni, Andrés J M Ferreri, Shi Wang, Michael B Møller, Miguel A Piris, L Jeffrey Medeiros, Yong Li, Lan V Pham, Ken H Young
AKT signaling is important for proliferation and survival of tumor cells. The clinical significance of AKT activation in diffuse large B-cell lymphoma (DLBCL) is not well analyzed. Here, we assessed expression of phosphorylated AKT (p-AKT) in 522 DLBCL patients. We found high levels of p-AKT nuclear expression, observed in 24.3% of the study cohort, were associated with significantly worse progression-free survival and Myc and Bcl-2 overexpression. However, multivariate analysis indicated that AKT hyperactivation was not an independent factor...
June 13, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28624201/broad-spectrum-inhibition-of-respiratory-virus-infection-by-microrna-mimics-targeting-p38-mapk-signaling
#6
Jana L McCaskill, Sarah Ressel, Andreas Alber, Jane Redford, Ultan F Power, Jürgen Schwarze, Bernadette M Dutia, Amy H Buck
The majority of antiviral therapeutics target conserved viral proteins, however, this approach confers selective pressure on the virus and increases the probability of antiviral drug resistance. An alternative therapeutic strategy is to target the host-encoded factors that are required for virus infection, thus minimizing the opportunity for viral mutations that escape drug activity. MicroRNAs (miRNAs) are small noncoding RNAs that play diverse roles in normal and disease biology, and they generally operate through the post-transcriptional regulation of mRNA targets...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28622685/increased-pdgfr-beta-and-vegfr-2-protein-levels-are-associated-with-resistance-to-platinum-based-chemotherapy-and-adverse-outcome-of-ovarian-cancer-patients
#7
Stefanie Avril, Yasemin Dincer, Katharina Malinowsky, Claudia Wolff, Sibylle Gündisch, Alexander Hapfelmeier, Melanie Boxberg, Holger Bronger, Karl-Friedrich Becker, Barbara Schmalfeldt
Despite frequent initial response rates of epithelial ovarian cancer to platinum-based chemotherapy the majority of patients develop drug resistance. Our aim was to evaluate differential expression of signaling-pathway proteins in platinum-sensitive versus platinum-resistant primary epithelial ovarian cancer specimens to identify predictive biomarkers for treatment response.192 patients were studied comprising of independent training (n = 89) and validation (n = 103) cohorts. Full-length proteins were extracted from paraffin-embedded samples including multiple regions per tumor to account for intratumoral heterogeneity...
June 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28621158/signaling-pathway-profiling-using-reverse-phase-protein-array-and-its-clinical-applications
#8
Mari Masuda, Tesshi Yamada
Increased accessibility to next-generation sequencing within the last decade has led to a paradigm shift in cancer treatment from one-size-fits-all medicine to precision medicine providing therapeutic strategies tailored to the requirements of individual patients. However, the effect of even the most successful agent yet tested is only transient, and durable efficacy has yet to be achieved. Genome- and transcriptome-based approaches cannot fully predict the diversity of protein expression patterns or post-translational modifications that directly contribute to cancer pathogenesis and physiology...
June 16, 2017: Expert Review of Proteomics
https://www.readbyqxmd.com/read/28599981/p90rsk-blockade-inhibits-dual-braf-and-mek-inhibitor-resistant-melanoma-by-targeting-protein-synthesis
#9
Nicholas Theodosakis, Goran Micevic, Casey G Langdon, Alessandra Ventura, Robert Means, David F Stern, Marcus W Bosenberg
Despite improvements in survival in metastatic melanoma with combined BRAF and MEK inhibitor treatment, the overwhelming majority of patients eventually acquire resistance to both agents. Consequently, new targets for therapy in resistant tumors are currently being evaluated. Previous studies have identified p90RSK family kinases as key factors for growth and proliferation, as well as protein synthesis via assembly of the m(7)-GTP cap-dependent translation complex. We sought to evaluate inhibitors of p90RSK family members: BI-D1870 and BRD7389, for their ability to inhibit both proliferation and protein synthesis in patient-derived melanoma cell lines with acquired resistance to combined treatment with the BRAF inhibitor vemurafenib and MEK inhibitor selumetinib...
June 6, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28537612/proline-rich-antimicrobial-peptides-targeting-protein-synthesis
#10
Michael Graf, Mario Mardirossian, Fabian Nguyen, A Carolin Seefeldt, Gilles Guichard, Marco Scocchi, C Axel Innis, Daniel N Wilson
Covering: up to 2017The innate immune system employs a broad array of antimicrobial peptides (AMPs) to attack invading microorganisms. While most AMPs act by permeabilizing the bacterial membrane, specific subclasses of AMPs have been identified that pass through membranes and inhibit bacterial growth by targeting fundamental intracellular processes. One such subclass is the proline-rich antimicrobial peptides (PrAMPs) that bind to the ribosome and interfere with the process of protein synthesis. A diverse range of PrAMPs have been identified in insects, such as bees, wasps and beetles, and crustaceans, such as crabs, as well as in mammals, such as cows, sheep, goats and pigs...
May 24, 2017: Natural Product Reports
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
#11
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/28521850/differential-gene-expression-in-porcine-oviduct-during-the-oestrous-cycle
#12
O S Acuña, M Avilés, R López-Úbeda, A Guillén-Martínez, C Soriano-Úbeda, A Torrecillas, P Coy, M J Izquierdo-Rico
The oviduct undergoes changes under the influence of steroid hormones during the oestrous cycle. However, the molecular mechanisms underlying oviductal regulation are not fully understood. The aim of the present study was to identify the gene expression profile of the porcine oviduct in different stages of the cycle using microarray technology. A systematic study was performed on animals at four different stage: prepubertal gilts, and sows in the preovulatory, postovulatory and luteal phase of the oestrous cycle...
May 19, 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28502001/clustering-and-network-analysis-of-reverse-phase-protein-array-data
#13
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/28468774/synergy-between-androgen-receptor-antagonism-and-inhibition-of-mtor-and-her2-in-breast-cancer
#14
Michael A Gordon, Nicholas C D'Amato, Haihua Gu, Beatrice Babbs, Julia Wulfkuhle, Emanuel F Petricoin, Isela Gallagher, Ting Dong, Kathleen Torkko, Bolin Liu, Anthony Elias, Jennifer K Richer
The androgen receptor (AR) is widely expressed in breast cancer, and evidence suggests dependence on AR signaling for growth and survival. AR antagonists such as enzalutamide and seviteronel have shown success in preclinical models and clinical trials of prostate cancer and are currently being evaluated in breast cancer. Reciprocal regulation between AR and the HER2/PI3K/mTOR pathway may contribute to resistance to HER2- and mTOR-targeted therapies; thus, dual inhibition of these pathways may synergistically inhibit breast cancer growth...
May 3, 2017: Molecular Cancer Therapeutics
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
#15
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/28377578/role-of-cytochrome-p450-cyp-1a-in-hyperoxic-lung-injury-analysis-of-the-transcriptome-and-proteome
#16
Krithika Lingappan, Suman Maity, Weiwu Jiang, Lihua Wang, Xanthi Couroucli, Alex Veith, Guodong Zhou, Cristian Coarfa, Bhagavatula Moorthy
Hyperoxia contributes to lung injury in experimental animals and diseases such as acute respiratory distress syndrome in humans. Cytochrome P450 (CYP)1A enzymes are protective against hyperoxic lung injury (HLI). The molecular pathways and differences in gene expression that modulate these protective effects remain largely unknown. Our objective was to characterize genotype specific differences in the transcriptome and proteome of acute hyperoxic lung injury using the omics platforms: microarray and Reverse Phase Proteomic Array...
April 4, 2017: Scientific Reports
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
#17
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/28376145/next-generation-cdk2-9-inhibitors-and-anaphase-catastrophe-in-lung-cancer
#18
Masanori Kawakami, Lisa Maria Mustachio, Jaime Rodriguez-Canales, Barbara Mino, Jason Roszik, Pan Tong, Jing Wang, J Jack Lee, Ja Hye Myung, John V Heymach, Faye M Johnson, Seungpyo Hong, Lin Zheng, Shanhu Hu, Pamela Andrea Villalobos, Carmen Behrens, Ignacio Wistuba, Sarah Freemantle, Xi Liu, Ethan Dmitrovsky
Background: The first generation CDK2/7/9 inhibitor seliciclib (CYC202) causes multipolar anaphase and apoptosis in lung cancer cells with supernumerary centrosomes (known as anaphase catastrophe). We investigated a new and potent CDK2/9 inhibitor, CCT68127 (Cyclacel). Methods: CCT68127 was studied in lung cancer cells (three murine and five human) and control murine pulmonary epithelial and human immortalized bronchial epithelial cells. Robotic CCT68127 cell-based proliferation screens were used...
June 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28356166/integrative-clustering-reveals-a-novel-split-in-the-luminal-a-subtype-of-breast-cancer-with-impact-on-outcome
#19
Miriam Ragle Aure, Valeria Vitelli, Sandra Jernström, Surendra Kumar, Marit Krohn, Eldri U Due, Tonje Husby Haukaas, Suvi-Katri Leivonen, Hans Kristian Moen Vollan, Torben Lüders, Einar Rødland, Charles J Vaske, Wei Zhao, Elen K Møller, Silje Nord, Guro F Giskeødegård, Tone Frost Bathen, Carlos Caldas, Trine Tramm, Jan Alsner, Jens Overgaard, Jürgen Geisler, Ida R K Bukholm, Bjørn Naume, Ellen Schlichting, Torill Sauer, Gordon B Mills, Rolf Kåresen, Gunhild M Mælandsmo, Ole Christian Lingjærde, Arnoldo Frigessi, Vessela N Kristensen, Anne-Lise Børresen-Dale, Kristine K Sahlberg
BACKGROUND: Breast cancer is a heterogeneous disease at the clinical and molecular level. In this study we integrate classifications extracted from five different molecular levels in order to identify integrated subtypes. METHODS: Tumor tissue from 425 patients with primary breast cancer from the Oslo2 study was cut and blended, and divided into fractions for DNA, RNA and protein isolation and metabolomics, allowing the acquisition of representative and comparable molecular data...
March 29, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28352657/randomized-placebo-controlled-window-trial-of-egfr-src-or-combined-blockade-in-head-and-neck-cancer
#20
Julie E Bauman, Umamaheswar Duvvuri, William E Gooding, Tanya J Rath, Neil D Gross, John Song, Antonio Jimeno, Wendell G Yarbrough, Faye M Johnson, Lin Wang, Simion Chiosea, Malabika Sen, Jason Kass, Jonas T Johnson, Robert L Ferris, Seungwon Kim, Fred R Hirsch, Kimberly Ellison, John T Flaherty, Gordon B Mills, Jennifer R Grandis
BACKGROUND. EGFR and Src family kinases are upregulated in head and neck squamous cell carcinoma (HNSCC). EGFR interacts with Src to activate STAT3 signaling, and dual EGFR-Src targeting is synergistic in HNSCC preclinical models. pSrc overexpression predicted resistance to the EGFR inhibitor, erlotinib, in a prior window trial. We conducted a 4-arm window trial to identify biomarkers associated with response to EGFR and/or Src inhibition. METHODS. Patients with operable stage II-IVa HNSCC were randomized to 7-21 days of neoadjuvant erlotinib, the Src inhibitor dasatinib, the combination of both, or placebo...
March 23, 2017: JCI Insight
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