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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
#1
Tao Xu, Bojin Su, Peiyu Huang, Weihong Wei, Yanming Deng, Vasudha Sehgal, Donghui Wang, Jun Jiang, Guoyi Zhang, Anfei Li, Huiling Yang, François 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, were enrolled...
November 24, 2016: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/27861902/the-molecular-basis-of-breast-cancer-pathological-phenotypes
#2
Yujing J Heng, Susan C Lester, Gary M K Tse, Rachel E Factor, Kimberly H Allison, Laura C Collins, Yunn-Yi Chen, Kristin C Jensen, Nicole B Johnson, Jong Cheol Jeong, Rahi Punjabi, Sandra J Shin, Kamaljeet Singh, Gregor Krings, David A Eberhard, Puay Hoon Tan, Konstanty Korski, Frederic M Waldman, David A Gutman, Melinda Sanders, Jorge S Reis-Filho, Sydney R Flanagan, Deena M A Gendoo, Gregory M Chen, Benjamin Haibe-Kains, Giovanni Ciriello, Katherine A Hoadley, Charles M Perou, Andrew H Beck
The histopathological evaluation of morphological features in breast tumours provides prognostic information to guide therapy. Adjunct molecular analyses provide further diagnostic, prognostic and predictive information. However, there is limited knowledge of the molecular basis of morphological phenotypes in invasive breast cancer. This study integrated genomic, transcriptomic and protein data to provide a comprehensive molecular profiling of morphological features in breast cancer. Fifteen pathologists assessed 850 invasive breast cancer cases from The Cancer Genome Atlas (TCGA)...
November 14, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/27858266/reverse-phase-protein-arrays-enable-glioblastoma-molecular-subtyping
#3
Gregor Hutter, Martin Sailer, Tej Deepak Azad, André O von Bueren, Peter Nollau, Stephan Frank, Cristobal Tostado, Durga Sarvepalli, Arkasubhra Ghosh, Marie-Françoise Ritz, Jean-Louis Boulay, Luigi Mariani
In the present study we investigated the phosphorylation status of the 12 most important signaling cascades in glioblastomas. More than 60 tumor and control biopsies from tumor center and periphery (based on neuronavigation) were subjected to selective protein expression analysis using reverse-phase protein arrays (RPPA) incubated with antibodies against posttranslationally modified cancer pathway proteins. The ratio between phosphorylated (or modified) and non-phosphorylated protein was assessed. All samples were histopathologically validated and proteomic profiles correlated with clinical and survival data...
November 17, 2016: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/27825696/a-pilot-study-exploring-the-molecular-architecture-of-the-tumor-microenvironment-in-human-prostate-cancer-using-laser-capture-microdissection-and-reverse-phase-protein-microarray
#4
Elisa Pin, Steven Stratton, Claudio Belluco, Lance Liotta, Ray Nagle, K Alex Hodge, Jianghong Deng, Ting Dong, Elisa Baldelli, Emanuel Petricoin, Mariaelena Pierobon
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...
October 14, 2016: Molecular Oncology
https://www.readbyqxmd.com/read/27813428/how-may-targeted-proteomics-complement-genomic-data-in-breast-cancer
#5
Mathilde Guerin, Anthony Gonçalves, Yves Toiron, Emilie Baudelet, Stéphane Audebert, Jean-Baptiste Boyer, Jean-Paul Borg, Luc Camoin
Breast cancer (BC) is the most common female cancer in the world and was recently deconstructed in different molecular entities. Although most of the recent assays to characterize tumors at the molecular level are genomic-based, proteins are the actual executors of cellular functions and represent the vast majority of targets for anticancer drugs. Accumulated data has demonstrated an important level of quantitative and qualitative discrepancies between genomic/transcriptomic alterations and their protein counterparts, mostly related to the large number of post-translational modifications...
November 4, 2016: Expert Review of Proteomics
https://www.readbyqxmd.com/read/27751915/defining-the-na-h-exchanger-nhe1-interactome-in-triple-negative-breast-cancer-cells
#6
Schammim Ray Amith, Krista Marie Vincent, Jodi Marie Wilkinson, Lynne Marie Postovit, Larry Fliegel
Mounting evidence supports a major role for the Na(+)/H(+) exchanger NHE1 in cancer progression and metastasis. NHE1 is hyperactive at the onset of oncogenic transformation, resulting in intracellular alkalinization and extracellular microenvironmental acidification. These conditions promote invasion and facilitate metastasis. However, the signal pathways governing the regulation of exchanger activity are still unclear. This is especially important in the aggressively metastatic, triple-negative basal breast cancer subtype...
October 15, 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27663479/using-reverse-phase-protein-arrays-as-pharmacodynamic-assays-for-functional-proteomics-biomarker-discovery-and-drug-development-in-cancer
#7
REVIEW
Yiling Lu, Shiyun Ling, Apurva M Hegde, Lauren A Byers, Kevin Coombes, Gordon B Mills, Rehan Akbani
The majority of the targeted therapeutic agents in clinical use target proteins and protein function. Although DNA and RNA analyses have been used extensively to identify novel targets and patients likely to benefit from targeted therapies, these are indirect measures of the levels and functions of most therapeutic targets. More importantly, DNA and RNA analysis is ill-suited for determining the pharmacodynamic effects of target inhibition. Assessing changes in protein levels and function is the most efficient way to evaluate the mechanisms underlying sensitivity and resistance to targeted agents...
August 2016: Seminars in Oncology
https://www.readbyqxmd.com/read/27658583/hypoxia-promotes-chemoresistance-in-acute-lymphoblastic-leukemia-cell-lines-by-modulating-death-signaling-pathways
#8
C Petit, F Gouel, I Dubus, C Heuclin, K Roget, J P Vannier
BACKGROUND: Several studies show that bone marrow (BM) microenvironment and hypoxia condition can promote the survival of leukemic cells and induce resistance to anti-leukemic drugs. However, the molecular mechanism for chemoresistance by hypoxia is not fully understood. METHODS: In the present study, we investigated the effect of hypoxia on resistance to two therapies, methotrexate (MTX) and prednisolone (PRD), in two cell models for acute lymphoblastic leukemia (ALL)...
2016: BMC Cancer
https://www.readbyqxmd.com/read/27622568/reverse-phase-protein-arrays-for-compound-profiling
#9
Nathan Moerke, Mohammad Fallahi-Sichani
Reverse phase protein arrays (RPPAs), also called reverse phase lysate arrays (RPLAs), involve immobilizing cell or tissue lysates, in small spots, onto solid supports which are then probed with primary antibodies specific for proteins or post-translational modifications of interest. RPPA assays are well suited for large-scale, high-throughput measurement of protein and PTM levels in cells and tissues. RPPAs are affordable and highly multiplexable, as a large number of arrays can readily be produced in parallel and then probed separately with distinct primary antibodies...
2016: Current Protocols in Chemical Biology
https://www.readbyqxmd.com/read/27600857/mir-564-acts-as-a-dual-inhibitor-of-pi3k-and-mapk-signaling-networks-and-inhibits-proliferation-and-invasion-in-breast-cancer
#10
Merve Mutlu, Özge Saatci, Suhail A Ansari, Emre Yurdusev, Huma Shehwana, Özlen Konu, Umar Raza, Özgür Şahin
Dysregulation of PI3K and MAPK pathways promotes uncontrolled cell proliferation, apoptotic inhibition and metastasis. Individual targeting of these pathways using kinase inhibitors has largely been insufficient due to the existence of cross-talks between these parallel cascades. MicroRNAs are small non-coding RNAs targeting several genes simultaneously and controlling cancer-related processes. To identify miRNAs repressing both PI3K and MAPK pathways in breast cancer, we re-analyzed our previous miRNA mimic screen data with reverse phase protein array (RPPA) output, and identified miR-564 inhibiting both PI3K and MAPK pathways causing markedly decreased cell proliferation through G1 arrest...
September 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27579675/identification-of-igfbp2-and-igfbp3-as-compensatory-biomarkers-for-ca19-9-in-early-stage-pancreatic-cancer-using-a-combination-of-antibody-based-and-lc-ms-ms-based-proteomics
#11
Toshihiro Yoneyama, Sumio Ohtsuki, Kazufumi Honda, Makoto Kobayashi, Motoki Iwasaki, Yasuo Uchida, Takuji Okusaka, Shoji Nakamori, Masashi Shimahara, Takaaki Ueno, Akihiko Tsuchida, Naohiro Sata, Tatsuya Ioka, Yohichi Yasunami, Tomoo Kosuge, Takashi Kaneda, Takao Kato, Kazuhiro Yagihara, Shigeyuki Fujita, Wilber Huang, Tesshi Yamada, Masanori Tachikawa, Tetsuya Terasaki
Pancreatic cancer is one of the most lethal tumors, and reliable detection of early-stage pancreatic cancer and risk diseases for pancreatic cancer is essential to improve the prognosis. As 260 genes were previously reported to be upregulated in invasive ductal adenocarcinoma of pancreas (IDACP) cells, quantification of the corresponding proteins in plasma might be useful for IDACP diagnosis. Therefore, the purpose of the present study was to identify plasma biomarkers for early detection of IDACP by using two proteomics strategies: antibody-based proteomics and liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics...
2016: PloS One
https://www.readbyqxmd.com/read/27464795/clinical-and-biological-significance-of-rad51-expression-in-breast-cancer-a-key-dna-damage-response-protein
#12
Alaa Tarig Alshareeda, Ola H Negm, Mohammed A Aleskandarany, Andrew R Green, Christopher Nolan, Patrick J TigHhe, Srinivasan Madhusudan, Ian O Ellis, Emad A Rakha
Impaired DNA damage response (DDR) may play a fundamental role in the pathogenesis of breast cancer (BC). RAD51 is a key player in DNA double-strand break repair. In this study, we aimed to assess the biological and clinical significance of RAD51 expression with relevance to different molecular classes of BC and patients' outcome. The expression of RAD51 was assessed immunohistochemically in a well-characterised annotated series (n = 1184) of early-stage invasive BC with long-term follow-up. A subset of cases of BC from patients with known BRCA1 germline mutations was included as a control group...
August 2016: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/27372609/characterization-of-protein-expression-levels-with-label-free-detected-reverse-phase-protein-arrays
#13
Xuexue Guo, Yihong Deng, Chenggang Zhu, Junlong Cai, Xiangdong Zhu, James P Landry, Fengyun Zheng, Xunjia Cheng, Yiyan Fei
In reverse-phase protein arrays (RPPA), one immobilizes complex samples (e.g., cellular lysate, tissue lysate or serum etc.) on solid supports and performs parallel reactions of antibodies with immobilized protein targets from the complex samples. In this work, we describe a label-free detection of RPPA that enables quantification of RPPA data and thus facilitates comparison of studies performed on different samples and on different solid supports. We applied this detection platform to characterization of phosphoserine aminotransferase (PSAT) expression levels in Acanthamoeba lysates treated with artemether and the results were confirmed by Western blot studies...
September 15, 2016: Analytical Biochemistry
https://www.readbyqxmd.com/read/27342398/idelalisib-impacts-cell-growth-through-inhibiting-translation-regulatory-mechanisms-in-mantle-cell-lymphoma
#14
Qingshan Yang, Lisa S Chen, Min Jin Ha, Kim-Anh Do, Sattva S Neelapu, Varsha Gandhi
PURPOSE: PI3K is a critical node in the B-cell receptor pathway, which is responsible for survival and proliferation of B-cell malignancies. Idelalisib, a PI3Kδ-isoform-specific inhibitor, has been approved to treat B-cell malignancies. Although biological activity of the drug has been evaluated, molecular mechanisms and signaling pathway disruption leading to the biological effects of idelalisib are not yet well defined. Prior laboratory reports have identified transcription and translation as the primary events for attenuation of PI3Kα isoform...
June 24, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27312846/profiling-b-cell-chronic-lymphocytic-leukemia-by-reverse-phase-protein-array-focus-on-apoptotic-proteins
#15
Federica Frezzato, Benedetta Accordi, Valentina Trimarco, Cristina Gattazzo, Veronica Martini, Gloria Milani, Silvia Bresolin, Filippo Severin, Andrea Visentin, Giuseppe Basso, Gianpietro Semenzato, Livio Trentin
B cell chronic lymphocytic leukemia (CLL) is characterized by the accumulation of B lymphocytes from proliferative activity and apoptosis resistance. The increased awareness of the importance of B cell receptor signaling in CLL has raised new opportunities for targeted intervention. Herein, we describe a study performed with the high-throughput RPPA (reverse phase protein array) technique, which allowed us to simultaneously study different molecules in a large series of patients. We analyzed B lymphocytes from 57 patients with CLL and 11 healthy subjects...
June 16, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27305912/proteomic-modulation-in-breast-tumors-after-metformin-exposure-results-from-a-window-of-opportunity-trial
#16
K Kalinsky, T Zheng, H Hibshoosh, X Du, P Mundi, J Yang, S Refice, S M Feldman, B Taback, E Connolly, K D Crew, M A Maurer, D L Hershman
PURPOSE: Reverse Phase Protein Array (RPPA) is a high-throughput antibody-based technique to assess cellular protein activity. The goal of this study was to assess protein marker changes by RPPA in tumor tissue from a pre-surgical metformin trial in women with operable breast cancer (BC). METHODS: In an open-label trial, metformin 1500-mg PO daily was administered prior to resection in 35 non-diabetic patients with stage 0-III BC, body mass index ≥25 kg/m(2)...
June 15, 2016: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/27304907/naturally-inspired-peptide-leads-alanine-scanning-reveals-an-actin-targeting-thiazole-analogue-of-bisebromoamide
#17
Heather J Johnston, Sarah K Boys, Ashraff Makda, Neil O Carragher, Alison N Hulme
Systematic alanine scanning of the linear peptide bisebromoamide (BBA), isolated from a marine cyanobacterium, was enabled by solid-phase peptide synthesis of thiazole analogues. The analogues have comparable cytotoxicity (nanomolar) to that of BBA, and cellular morphology assays indicated that they target the actin cytoskeleton. Pathway inhibition in human colon tumour (HCT116) cells was explored by reverse phase protein array (RPPA) analysis, which showed a dose-dependent response in IRS-1 expression. Alanine scanning reveals a structural dependence to the cytotoxicity, actin targeting and pathway inhibition, and allows a new readily synthesised lead to be proposed...
September 2, 2016: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/27286453/ucn-01-enhances-cytotoxicity-of-irinotecan-in-colorectal-cancer-stem-like-cells-by-impairing-dna-damage-response
#18
Michele Signore, Mariachiara Buccarelli, Emanuela Pilozzi, Gabriele De Luca, Marianna Cappellari, Maurizio Fanciulli, Frauke Goeman, Elisa Melucci, Mauro Biffoni, Lucia Ricci-Vitiani
Colorectal cancer (CRC) is one of the most common and lethal cancers worldwide. Despite recent progress, the prognosis of advanced stage CRC remains poor, mainly because of cancer recurrence and metastasis. The high morbidity and mortality of CRC has been recently ascribed to a small population of tumor cells that hold the potential of tumor initiation, i.e. cancer stem cells (CSCs), which play a pivotal role in cancer recurrence and metastasis and are not eradicated by current therapy. We screened CRC-SCs in vitro with a library of protein kinase inhibitors and showed that CRC-SCs are resistant to specific inhibition of the major signaling pathways involved in cell survival and proliferation...
June 6, 2016: Oncotarget
https://www.readbyqxmd.com/read/27198223/pkc%C3%AE-and-hmgb1-antagonistically-control-hydrogen-peroxide-induced-poly-adp-ribose-formation
#19
Anneli Andersson, Andrej Bluwstein, Nitin Kumar, Federico Teloni, Jens Traenkle, Michael Baudis, Matthias Altmeyer, Michael O Hottiger
Harmful oxidation of proteins, lipids and nucleic acids is observed when reactive oxygen species (ROS) are produced excessively and/or the antioxidant capacity is reduced, causing 'oxidative stress'. Nuclear poly-ADP-ribose (PAR) formation is thought to be induced in response to oxidative DNA damage and to promote cell death under sustained oxidative stress conditions. However, what exactly triggers PAR induction in response to oxidative stress is incompletely understood. Using reverse phase protein array (RPPA) and in-depth analysis of key stress signaling components, we observed that PAR formation induced by H2O2 was mediated by the PLC/IP3R/Ca(2+)/PKCα signaling axis...
September 19, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27172895/high-intratumoral-stromal-content-defines-reactive-breast-cancer-as-a-low-risk-breast-cancer-subtype
#20
Jennifer B Dennison, Maria Shahmoradgoli, Wenbin Liu, Zhenlin Ju, Funda Meric-Bernstam, Charles M Perou, Aysegul A Sahin, Alana Welm, Steffi Oesterreich, Matthew J Sikora, Robert E Brown, Gordon B Mills
PURPOSE: The current study evaluated associative effects of breast cancer cells with the tumor microenvironment and its influence on tumor behavior. EXPERIMENTAL DESIGN: Formalin-fixed, paraffin-embedded tissue and matched protein lysates were evaluated from two independent breast cancer patient datasets (TCGA and MD Anderson). Reverse-phase protein arrays (RPPA) were utilized to create a proteomics signature to define breast tumor subtypes. Expression patterns of cell lines and normal breast tissues were utilized to determine markers that were differentially expressed in stroma and cancer cells...
October 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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