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Reverse-phase protein array

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https://www.readbyqxmd.com/read/29335317/reduced-n-type-ca2-channels-in-atrioventricular-ganglion-neurons-are-involved-in-ventricular-arrhythmogenesis
#1
Dongze Zhang, Huiyin Tu, Liang Cao, Hong Zheng, Robert L Muelleman, Michael C Wadman, Yu-Long Li
BACKGROUND: Attenuated cardiac vagal activity is associated with ventricular arrhythmogenesis and related mortality in patients with chronic heart failure. Our recent study has shown that expression of N-type Ca2+ channel α-subunits (Cav2.2-α) and N-type Ca2+ currents are reduced in intracardiac ganglion neurons from rats with chronic heart failure. Rat intracardiac ganglia are divided into the atrioventricular ganglion (AVG) and sinoatrial ganglion. Ventricular myocardium receives projection of neuronal terminals only from the AVG...
January 15, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29300112/zoledronic-acid-overcomes-chemoresistance-by-sensitizing-cancer-stem-cells-to-apoptosis
#2
H Rouhrazi, N Turgan, G Oktem
Unlike low tumorigenic bulk tumor cells (non-CSCs), cancer stem cells (CSCs) are a subset of tumor cells that can self-renew and differentiate into different cancer subtypes. CSCs are considered responsible for tumor recurrence, distant metastasis, angiogenesis, and drug or radiation resistance. CSCs also are resistant to apoptosis. Zoledronic acid (ZA) is a third generation bisphosphonate that reduces cell proliferation and exhibits anti-tumor effects by inducing cell death in some malignancies; however, the effects of ZA on CSCs are unclear...
January 4, 2018: Biotechnic & Histochemistry: Official Publication of the Biological Stain Commission
https://www.readbyqxmd.com/read/29291005/proteomic-profiling-of-endometrioid-endometrial-cancer-reveals-differential-expression-of-hormone-receptors-and-mapk-signaling-proteins-in-obese-versus-non-obese-patients
#3
Karen Klepsland Mauland, Zhenlin Ju, Ingvild Løberg Tangen, Anna Berg, Karl-Henning Kalland, Anne Margrete Øyan, Line Bjørge, Shannon N Westin, Camilla Krakstad, Jone Trovik, Gordon B Mills, Erling A Hoivik, Henrica Maria Johanna Werner
Endometrial cancer development is strongly linked to obesity, but knowledge regarding the influence of excess weight on endometrial tumor signaling pathways remains scarce. We therefore analyzed reverse phase protein array (RPPA) data for obesity-related protein expression patterns, using one training (n=272) and two test cohorts (n=68; n=178) of well-annotated samples from women treated for endometrioid endometrial cancer. Gene expression profiling and immunohistochemistry were used for cross-platform validation...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228656/increased-pdgfr-beta-and-vegfr-2-protein-levels-are-associated-with-resistance-to-platinum-based-chemotherapy-and-adverse-outcome-of-ovarian-cancer-patients
#4
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...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29186355/global-proteomics-profiling-improves-drug-sensitivity-prediction-results-from-a-multi-omics-pan-cancer-modeling-approach
#5
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/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
#6
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
#7
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/29141913/multiplexed-biomarker-panels-discriminate-zika-and-dengue-virus-infection-in-humans
#8
Guang Song, Hee-Sool Rho, Jianbo Pan, Pedro Ramos, Ki-Jun Yoon, Freddy A Medina, Emily M Lee, Daniel J Eichinger, Guo-Li Ming, Jorge L Muñoz-Jordan, Hengli Tang, Ignacio Pino, Hongjun Song, Jiang Qian, Heng Zhu
Zika virus (ZIKV) and dengue virus (DENV) are closely related flaviviruses that cause widespread, acute febrile illnesses, notably microcephaly for fetuses of infected pregnant women. Detecting the viral cause of these illnesses is paramount to determine risks to patients, counsel pregnant women, and help fight outbreaks. A combined diagnostic algorithm for ZIKV and DENV requires Reverse transcription polymerase chain reaction (RT-PCR) and IgM antibody detection. RT-PCR differentiates between DENV and ZIKV infections during the acute phases of infection, but differentiation based on IgM antibodies is currently nearly impossible in endemic areas...
November 15, 2017: Molecular & Cellular Proteomics: MCP
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
#9
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/29136399/proteinaceous-sperm-motility-inhibitory-factor-from-the-female-indian-garden-lizard-calotes-versicolor
#10
Goutham Shankar, Shubhashree Uppangala, Satish K Adiga, Belinda Willard, Bhadravathi K C Sagar, Ruth S K Titus, Gopal K Marathe
Female sperm storage is an intriguing adaptation exhibited by a wide array of both vertebrates and invertebrates. The mechanisms underlying female sperm storage have remained elusive. Using the Indian garden lizard Calotes versicolor as a model organism, we investigated the role of low and high molecular weight factors in this phenomenon. Previously, we demonstrated three distinct phases of the reproductive cycle in this animal with live, motile spermatozoa recovered from the uterovaginal region during the reproductive phase...
November 15, 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/29101238/glucocorticoid-resistance-is-reverted-by-lck-inhibition-in-pediatric-t-cell-acute-lymphoblastic-leukemia
#11
Valentina Serafin, Giorgia Capuzzo, Gloria Milani, Sonia Anna Minuzzo, Marica Pinazza, Roberta Bortolozzi, Silvia Bresolin, Elena Porcù, Chiara Frasson, Stefano Indraccolo, Giuseppe Basso, Benedetta Accordi
Pediatric T-acute lymphoblastic leukemia (T-ALL) patients often display resistance to glucocorticoid (GC) treatment. These patients, classified as Prednisone Poor Responders (PPR), have poorer outcome compared to the other pediatric T-ALL patients receiving a high-risk adapted therapy. Since glucocorticoids are administered to ALL patients during all the different phases of therapy, GC resistance represents an important challenge to be addressed in order to improve the outcome for these patients. Mechanisms underlying resistance are not yet fully unraveled, thus our research focused on the identification of deregulated signaling pathways to point out new targeted approaches...
November 3, 2017: Blood
https://www.readbyqxmd.com/read/29099493/pharmacodynamics-and-proteomic-analysis-of-acalabrutinib-therapy-similarity-of-on-target-effects-to-ibrutinib-and-rationale-for-combination-therapy
#12
V K Patel, B Lamothe, M L Ayres, J Gay, J Cheung, K Balakrishnan, C Ivan, J Morse, M Nelson, M J Keating, W G Wierda, J R Marszalek, V Gandhi
Acalabrutinib, a highly selective Bruton's tyrosine kinase inhibitor, is associated with high overall response rates and durable remission in previously treated chronic lymphocytic leukemia (CLL), however, complete remissions were limited. To elucidate on-target and pharmacodynamic effects of acalabrutinib, we evaluated several laboratory endpoints, including proteomic changes, chemokine modulation, and impact on cell migration. Pharmacological profiling of samples from acalabrutinib-treated CLL patients was used to identify strategies for achieving deeper responses, and to identify additive/synergistic combination regimens...
November 3, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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
#13
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
#14
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
#15
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
#16
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/29040674/evaluation-of-apoptotic-and-autophagic-related-protein-expressions-before-and-after-ivm-of-fresh-slow-frozen-and-vitrified-pre-pubertal-mouse-testicular-tissue
#17
L Dumont, F Chalmel, A Oblette, B Berby, A Rives, V Duchesne, C Rondanino, N Rives
STUDY QUESTION: Do freezing and in vitro culture procedures enhance the expression of proteins involved in apoptotic or autophagic pathways in murine pre-pubertal testicular tissue? SUMMARY ANSWER: IVM strongly modified apoptosis- and autophagy-related relative protein levels in mice testicular tissue whereas the impact of cryopreservation procedures was minimal at the end of the culture. WHAT IS KNOWN ALREADY: In vitro spermatogenesis remains a challenging technical issue as it imposes to find a very close balance between survival and death of germ cell natural precursors (i...
November 1, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/29030353/rad50-expression-is-associated-with-poor-clinical-outcomes-after-radiotherapy-for-resected-non-small-cell-lung-cancer
#18
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/29024937/protein-biomarkers-predictive-for-response-to-anti-egfr-treatment-in-ras-wild-type-metastatic-colorectal-carcinoma
#19
Astrid Lièvre, Bérèngere Ouine, Jim Canet, Aurélie Cartier, Yael Amar, Wulfran Cacheux, Odette Mariani, Rosine Guimbaud, Janick Selves, Thierry Lecomte, Serge Guyetant, Ivan Bieche, Frédérique Berger, Leanne de Koning
BACKGROUND: Metastatic colorectal cancer (mCRC) patients with mutant KRAS or NRAS are ineligible for anti-epidermal growth factor receptor (anti-EGFR) therapy, as RAS mutations activate downstream pathways independently of EGFR and induce primary resistance. However, even among RAS wild-type (WT) patients, only a fraction responds to anti-EGFR therapy, suggesting that other mechanisms of resistance exist. We hypothesise that different (epi)genetic alterations can lead to primary anti-EGFR resistance and that the crucial end point is the activation of protein signalling pathways...
October 12, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29020998/proteomic-profiling-of-breast-cancer-metabolism-identifies-shmt2-and-asct2-as-prognostic-factors
#20
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
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