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https://www.readbyqxmd.com/read/29186355/global-proteomics-profiling-improves-drug-sensitivity-prediction-results-from-a-multi-omics-pan-cancer-modeling-approach
#1
Mehreen Ali, Suleiman A Khan, Krister Wennerberg, Tero Aittokallio
Motivation: Proteomics profiling is increasingly being used for molecular stratification of cancer patients and cell-line panels. However, systematic assessment of the predictive power of large-scale proteomic technologies across various drug classes and cancer types is currently lacking. To that end, we carried out the first pan-cancer, multi-omics comparative analysis of the relative performance of two proteomic technologies, targeted reverse phase protein array (RPPA) and global mass spectrometry (MS), in terms of their accuracy for predicting the sensitivity of cancer cells to both cytotoxic chemotherapeutics and molecularly-targeted anticancer compounds...
November 27, 2017: Bioinformatics
https://www.readbyqxmd.com/read/29167824/protein-activation-mapping-of-human-sun-protected-epidermis-after-an-acute-dose-of-erythemic-solar-simulated-light
#2
Janine G Einspahr, Clara Curiel-Lewandrowski, Valerie S Calvert, Steven P Stratton, David S Alberts, James Warneke, Chengcheng Hu, Kathylynn Saboda, Elisabeth L Wagener, Sally Dickinson, Zigang Dong, Ann M Bode, Emanuel F PetricoinIII
Ultraviolet radiation is an important etiologic factor in skin cancer and a better understanding of how solar stimulated light (SSL) affects signal transduction pathways in human skin which is needed in further understanding activated networks that could be targeted for skin cancer prevention. We utilized Reverse Phase Protein Microarray Analysis (RPPA), a powerful technology that allows for broad-scale and quantitative measurement of the activation/phosphorylation state of hundreds of key signaling proteins and protein pathways in sun-protected skin after an acute dose of two minimal erythema dose (MED) of SSL...
2017: NPJ Precision Oncology
https://www.readbyqxmd.com/read/29156708/a-preclinical-evaluation-of-the-mek-inhibitor-refametinib-in-her2-positive-breast-cancer-cell-lines-including-those-with-acquired-resistance-to-trastuzumab-or-lapatinib
#3
John O'Shea, Mattia Cremona, Clare Morgan, Malgorzata Milewska, Frankie Holmes, Virginia Espina, Lance Liotta, Joyce O'Shaughnessy, Sinead Toomey, Stephen F Madden, Aoife Carr, Naomi Elster, Bryan T Hennessy, Alex J Eustace
Purpose: The MEK/MAPK pathway is commonly activated in HER2-positive breast cancer, but little investigation of targeting this pathway has been undertaken. Here we present the results of an in vitro preclinical evaluation of refametinib, an allosteric MEK1/2 inhibitor, in HER2-positive breast cancer cell lines including models of acquired resistance to trastuzumab or lapatinib. Methods: A panel of HER2-positive breast cancer cells were profiled for mutational status and also for anti-proliferative response to refametinib alone and in combination with the PI3K inhibitor (PI3Ki) copanlisib and the HER2-targeted therapies trastuzumab and lapatinib...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29142297/5-aminolevulinic-acid-guided-sampling-of-glioblastoma-microenvironments-identifies-pro-survival-signaling-at-infiltrative-margins
#4
James L Ross, Lee A D Cooper, Jun Kong, David Gutman, Merete Williams, Carol Tucker-Burden, Myles R McCrary, Alexandros Bouras, Milota Kaluzova, William D Dunn, Duc Duong, Constantinos G Hadjipanayis, Daniel J Brat
Glioblastoma (GBM) contains diverse microenvironments with uneven distributions of oncogenic alterations and signaling networks. The diffusely infiltrative properties of GBM result in residual tumor at neurosurgical resection margins, representing the source of relapse in nearly all cases and suggesting that therapeutic efforts should be focused there. To identify signaling networks and potential druggable targets across tumor microenvironments (TMEs), we utilized 5-ALA fluorescence-guided neurosurgical resection and sampling, followed by proteomic analysis of specific TMEs...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29137348/reverse-phase-protein-array-rppa-combined-with-computational-analysis-to-unravel-relevant-prognostic-factors-in-non-small-cell-lung-cancer-nsclc-a-pilot-study
#5
Vienna Ludovini, Rita Chiari, Lorenzo Tomassoni, Chiara Antonini, Elisa Baldelli, Sara Baglivo, Annamaria Siggillino, Francesca Romana Tofanetti, Guido Bellezza, K Alex Hodge, Emanuel Petricoin, Mariaelena Pierobon, Lucio Crinò, Fortunato Bianconi
In this work high throughput technology and computational analysis were used to study two stage IV lung adenocarcinoma patients treated with standard chemotherapy with markedly different survival (128 months vs 6 months, respectively) and whose tumor samples exhibit a dissimilar protein activation pattern of the signal transduction. Tumor samples of the two patients were subjected to Reverse Phase Protein Microarray (RPPA) analysis to explore the expression/activation levels of 51 signaling proteins. We selected the most divergent proteins based on the ratio of their RPPA values in the two patients with short (s-OS) and long (l-OS) overall survival (OS) and tested them against a EGFR-IGF1R mathematical model...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29093017/a-population-of-heterogeneous-breast-cancer-patient-derived-xenografts-demonstrate-broad-activity-of-parp-inhibitor-in-brca1-2-wild-type-tumors
#6
Kurt W Evans, Erkan Yuca, Argun Akcakanat, Stephen M Scott, Natalia Paez Arango, Xiaofeng Zheng, Ken Chen, Coya Tapia, Emily Tarco, Agda K Eterovic, Dalliah M Black, Jennifer K Litton, Timothy A Yap, Debu Tripathy, Gordon B Mills, Funda Meric-Bernstam
Background: Breast cancer patients who do not respond to neoadjuvant therapy have a poor prognosis. There is a pressing need for novel targets and models for preclinical testing. Here we report characterization of breast cancer patient-derived xenografts (PDX) largely generated from residual tumors following neoadjuvant chemotherapy.Experimental Design: PDXs were derived from surgical samples of primary or locally recurrent tumors. Normal and tumor DNA sequencing, RNASeq, and reverse phase protein arrays (RPPA) were performed...
November 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29092939/explore-visualize-and-analyze-functional-cancer-proteomic-data-using-the-cancer-proteome-atlas
#7
Jun Li, Rehan Akbani, Wei Zhao, Yiling Lu, John N Weinstein, Gordon B Mills, Han Liang
Reverse-phase protein arrays (RPPA) represent a powerful functional proteomic approach to elucidate cancer-related molecular mechanisms and to develop novel cancer therapies. To facilitate community-based investigation of the large-scale protein expression data generated by this platform, we have developed a user-friendly, open-access bioinformatic resource, The Cancer Proteome Atlas (TCPA, http://tcpaportal.org), which contains two separate web applications. The first one focuses on RPPA data of patient tumors, which contains >8,000 samples of 32 cancer types from The Cancer Genome Atlas and other independent patient cohorts...
November 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/29079660/dual-mtor-kinases-mln0128-inhibitor-sensitizes-hr-her2-breast-cancer-patient-derived-xenografts-to-trastuzumab-or-fulvestrant
#8
Pei-Yin Hsu, Victoria Shang Wu, Noriko Kanaya, Karineh Petrossian, Hang-Kai Hsu, Duc Nguyen, Daniel Schmolze, Masaya Kai, Chun-Yu Liu, Hannah Lu, Peiguo Chu, Courtney A Vito, Laura Kruper, Joanne Mortimer, Shiuan Chen
PURPOSE: Therapeutic strategies against hormonal receptor-positive (HR+)/HER2+ breast cancers with poor response to trastuzumab need to be optimized. EXPERIMENTAL DESIGN: Two HR+/HER2+ patient-derived xenograft (PDX) models named as COH-SC1 and COH-SC31 were established to explore targeted therapies for HER2+ breast cancers. RNA sequencing and RPPA (reverse phase protein array) analyses were conducted to decipher molecular features of the two PDXs and define the therapeutic strategy of interest, validated by in vivo drug efficacy examination and in vitro cell proliferation analysis...
October 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29050296/reverse-phase-protein-array-identification-of-triple-negative-breast-cancer-subtypes-and-comparison-with-mrna-molecular-subtypes
#9
Hiroko Masuda, Yuan Qi, Shuying Liu, Naoki Hayashi, Takahiro Kogawa, Gabriel N Hortobagyi, Debu Tripathy, Naoto T Ueno
BACKGROUND: Reverse phase protein array (RPPA) analysis, allows investigation of potential targets at the functional protein level,. We identified TNBC subtypes at the protein level using RPPA and compared them with mRNA molecular subtypes (TNBCtype, TNBCtype-4, and PAM50) that is unique in its availability of both RPPA and mRNA analyses. METHODS: We classified the samples from 80 TNBC patients using both k-means and hierarchical consensus clustering analysis and performed Ingenuity Pathway Analysis...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29030353/rad50-expression-is-associated-with-poor-clinical-outcomes-after-radiotherapy-for-resected-non-small-cell-lung-cancer
#10
Yifan Wang, Jayanthi Gudikote, Uma Giri, Jun Yan, Weiye Deng, Rui Ye, Wen Jiang, Nan Li, Brian Hobbs, Jing Wang, Stephen G Swisher, Junya Fujimoto, Ignacio Ivan Wistuba, Ritsuko Komaki, John Heymach, Steven H Lin
PURPOSE: Although postoperative radiotherapy is often used to maintain local control after surgical resection and chemotherapy for locally advanced non-small cell lung cancer (NSCLC), both locoregional failure and distant metastasis remain problematic.  The mechanisms of therapeutic resistance remain poorly understood.    Experimental Design: We used reverse-phase protein arrays (RPPAs) to profile the baseline expression of 170 total and phosphorylated proteins in 70 NSCLC cell lines to categorize pathways that may contribute to radiation resistance...
October 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29020998/proteomic-profiling-of-breast-cancer-metabolism-identifies-shmt2-and-asct2-as-prognostic-factors
#11
Stephan Bernhardt, Michaela Bayerlová, Martina Vetter, Astrid Wachter, Devina Mitra, Volker Hanf, Tilmann Lantzsch, Christoph Uleer, Susanne Peschel, Jutta John, Jörg Buchmann, Edith Weigert, Karl-Friedrich Bürrig, Christoph Thomssen, Ulrike Korf, Tim Beissbarth, Stefan Wiemann, Eva Johanna Kantelhardt
BACKGROUND: Breast cancer tumors are known to be highly heterogeneous and differences in their metabolic phenotypes, especially at protein level, are less well-understood. Profiling of metabolism-related proteins harbors the potential to establish new patient stratification regimes and biomarkers promoting individualized therapy. In our study, we aimed to examine the relationship between metabolism-associated protein expression profiles and clinicopathological characteristics in a large cohort of breast cancer patients...
October 11, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28986799/protein-arrays-iii-reverse-phase-protein-arrays
#12
Yulin Yuan, Xia Hong, Zuan-Tao Lin, Hongting Wang, Mikala Heon, Tianfu Wu
The reverse-phase protein array (RPPA) is to use highly specific antibodies to interrogate pan or posttranslationally modified protein targets, such as phosphorylated proteins, particularly the proteins involved in cell signaling pathways. In this protocol we will cover the preparation of cell (or tissue) lysates, sample printing, antibody validation, antibody interrogation, signal amplification steps, imaging and data analysis. In this protocol, colorimetric catalyzed signal amplification (CSA) chemistry, fluorescence and near-infrared (NIR) based detection methods will be described...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28984208/unique-protein-expression-signatures-of-survival-time-in-kidney-renal-clear-cell-carcinoma-through-a-pan-cancer-screening
#13
Guangchun Han, Wei Zhao, Xiaofeng Song, Patrick Kwok-Shing Ng, Jose A Karam, Eric Jonasch, Gordon B Mills, Zhongming Zhao, Zhiyong Ding, Peilin Jia
BACKGROUND: In 2016, it is estimated that there will be 62,700 new cases of kidney cancer in the United States, and 14,240 patients will die from the disease. Because the incidence of kidney renal clear cell carcinoma (KIRC), the most common type of kidney cancer, is expected to continue to increase in the US, there is an urgent need to find effective diagnostic biomarkers for KIRC that could help earlier detection of and customized treatment strategies for the disease. Accordingly, in this study we systematically investigated KIRC's prognostic biomarkers for survival using the reverse phase protein array (RPPA) data and the high throughput sequencing data from The Cancer Genome Atlas (TCGA)...
October 3, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28955722/the-progestin-receptor-interactome-in-the-female-mouse-hypothalamus-interactions-with-synaptic-proteins-are-isoform-specific-and-ligand-dependent
#14
Kalpana D Acharya, Sabin A Nettles, Katherine J Sellers, Dana D Im, Moriah Harling, Cassandra Pattanayak, Didem Vardar-Ulu, Cheryl F Lichti, Shixia Huang, Dean P Edwards, Deepak P Srivastava, Larry Denner, Marc J Tetel
Progestins bind to the progestin receptor (PR) isoforms, PR-A and PR-B, in brain to influence development, female reproduction, anxiety, and stress. Hormone-activated PRs associate with multiple proteins to form functional complexes. In the present study, proteins from female mouse hypothalamus that associate with PR were isolated using affinity pull-down assays with glutathione S-transferase-tagged mouse PR-A and PR-B. Using complementary proteomics approaches, reverse phase protein array (RPPA) and mass spectrometry, we identified hypothalamic proteins that interact with PR in a ligand-dependent and isoform-specific manner and were confirmed by Western blot...
September 2017: ENeuro
https://www.readbyqxmd.com/read/28949454/a-pilot-study-exploring-the-molecular-architecture-of-the-tumor-microenvironment-in-human-prostate-cancer-using-laser-capture-microdissection-and-reverse-phase-protein-microarray
#15
(no author information available yet)
The cross-talk between tumor epithelium and surrounding stromal/immune microenvironment is essential to sustain tumor growth and progression and provides new opportunities for the development of targeted treatments focused on disrupting the tumor ecology. Identification of novel approaches to study these interactions is of primary importance. Using laser capture microdissection (LCM) coupled with reverse phase protein microarray (RPPA) based protein signaling activation mapping we explored the molecular interconnection between tumor epithelium and surrounding stromal microenvironment in 18 prostate cancer (PCa) specimens...
December 2016: Molecular Oncology
https://www.readbyqxmd.com/read/28936799/proteomic-features-of-colorectal-cancer-identify-tumor-subtypes-independent-of-oncogenic-mutations-and-independently-predict-relapse-free-survival
#16
Callisia N Clarke, Michael S Lee, Wei Wei, Ganiraju Manyam, Zhi-Qin Jiang, Yiling Lu, Jeffrey Morris, Bradley Broom, David Menter, Eduardo Vilar-Sanchez, Kanwal Raghav, Cathy Eng, George J Chang, Iris Simon, Rene Bernards, Michael Overman, Gordon B Mills, Dipen Maru, Scott Kopetz
BACKGROUND: The directed study of the functional proteome in colorectal cancer (CRC) has identified critical protein markers and signaling pathways; however, the prognostic relevance of many of these proteins remains unclear. METHODS: We determined the prognostic implications of the functional proteome in 263 CRC tumor samples from patients treated at MD Anderson Cancer Center (MDACC) and 462 patients from The Cancer Genome Atlas (TCGA) to identify patterns of protein expression that drive tumorigenesis...
December 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28886403/increased-mapk1-3-phosphorylation-in-luminal-breast-cancer-related-with-pik3ca-hotspot-mutations-and-prognosis
#17
Diana Ramirez-Ardila, A Mieke Timmermans, Jean A Helmijr, John W M Martens, Els M J J Berns, Maurice P H M Jansen
INTRODUCTION: While mutations in PIK3CA are most frequently (45%) detected in luminal breast cancer, downstream PI3K/AKT/mTOR pathway activation is predominantly observed in the basal subtype. The aim was to identify proteins activated in PIK3CA mutated luminal breast cancer and the clinical relevance of such a protein in breast cancer patients. MATERIALS AND METHODS: Expression levels of 171 signaling pathway (phospho-)proteins established by The Cancer Genome Atlas (TCGA) using reverse phase protein arrays (RPPA) were in silico examined in 361 breast cancers for their relation with PIK3CA status...
October 2017: Translational Oncology
https://www.readbyqxmd.com/read/28869900/integration-of-rna-seq-and-rppa-data-for-survival-time-prediction-in-cancer-patients
#18
Zerrin Isik, Muserref Ece Ercan
Integration of several types of patient data in a computational framework can accelerate the identification of more reliable biomarkers, especially for prognostic purposes. This study aims to identify biomarkers that can successfully predict the potential survival time of a cancer patient by integrating the transcriptomic (RNA-Seq), proteomic (RPPA), and protein-protein interaction (PPI) data. The proposed method -RPBioNet- employs a random walk-based algorithm that works on a PPI network to identify a limited number of protein biomarkers...
August 26, 2017: Computers in Biology and Medicine
https://www.readbyqxmd.com/read/28860008/a-signalome-screening-approach-in-the-autoinflammatory-disease-tnf-receptor-associated-periodic-syndrome-traps-highlights-the-anti-inflammatory-properties-of-drugs-for-repurposing
#19
Ian Todd, Ola H Negm, Jenna Reps, Paul Radford, Grazziela Figueredo, Elizabeth M McDermott, Elizabeth Drewe, Richard J Powell, Susan Bainbridge, Mohamed Hamed, Sharon Crouch, Jon Garibaldi, Steve St-Gallay, Lucy C Fairclough, Patrick J Tighe
TNF receptor associated periodic syndrome (TRAPS) is an autoinflammatory disease caused by mutations in TNF Receptor 1 (TNFR1). Current therapies for TRAPS are limited and do not target the pro-inflammatory signalling pathways that are central to the disease mechanism. Our aim was to identify drugs for repurposing as anti-inflammatories based on their ability to down-regulate molecules associated with inflammatory signalling pathways that are activated in TRAPS. This was achieved using rigorously optimized, high through-put cell culture and reverse phase protein microarray systems to screen compounds for their effects on the TRAPS-associated inflammatory signalome...
August 30, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28809001/reverse-phase-protein-arrays-and-drug-discovery
#20
Kenneth G Macleod, Bryan Serrels, Neil O Carragher
Reverse Phase Protein Arrays (RPPA) represent a sensitive antibody-based proteomic approach, which enables simultaneous quantification of the abundance of multiple proteins and posttranslational modifications across multiple samples. Here, we provide protocols for RPPA performed on two distinct protein-binding substrates associated with two most commonly used RPPA platform technologies. We compare and contrast the respective advantages and limitations of each platform within the context of drug discovery applications...
2017: Methods in Molecular Biology
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