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https://www.readbyqxmd.com/read/27918555/gene-expression-profiling-of-anti-ctla4-treated-metastatic-melanoma-in-patients-with-treatment-induced-autoimmunity
#1
Scott C Bresler, Le Min, Scott J Rodig, Andrew C Walls, Shuyun Xu, Songmei Geng, F Stephen Hodi, George F Murphy, Christine G Lian
Ipilimumab (IPI) is a monoclonal antibody that targets the inhibitory CTLA4 receptor of T cells, enhancing T-cell-driven antitumor responses. IPI therapy in metastatic melanoma results in significant improvement in disease-free and overall survival, although after initial responses disease progression generally ensues. Identification of specific responses in tissue where melanoma tumor cells are subjected to IPI-driven immune attack may reveal mechanisms of treatment efficacy or resistance, permitting refinement of targeted therapeutic approaches...
December 5, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27917695/nanostring-a-novel-digital-color-coded-barcode-technology-current-and-future-applications-in-molecular-diagnostics
#2
Hin-Fung Tsang, Vivian Weiwen Xue, Su-Pin Koh, Ya-Ming Chiu, Lawrence Po-Wah Ng, Sze-Chuen Cesar Wong
Formalin-fixed, paraffin-embedded (FFPE) tissue sample is a gold mine of resources for molecular diagnosis and retrospective clinical studies. Although molecular technologies have expanded the range of mutations identified in FFPE samples, the applications of existing technologies are limited by the low nucleic acids yield and poor extraction quality. As a result, the routine clinical applications of molecular diagnosis using FFPE samples has been associated with many practical challenges. NanoString technologies utilize a novel digital color-coded barcode technology based on direct multiplexed measurement of gene expression and offer high levels of precision and sensitivity...
December 3, 2016: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/27917296/stat1-associated-intratumoural-th1-immunity-predicts-chemotherapy-resistance-in-high-grade-serous-ovarian-cancer
#3
Katrina K Au, Cécile Le Page, Runhan Ren, Liliane Meunier, Isabelle Clément, Kathrin Tyrishkin, Nichole Peterson, Jennifer Kendall-Dupont, Timothy Childs, Julie-Ann Francis, Charles H Graham, Andrew W Craig, Jeremy A Squire, Anne-Marie Mes-Masson, Madhuri Koti
High-grade serous ovarian carcinoma (HGSC) accounts for 70% of all epithelial ovarian cancers but clinical management is challenged by a lack of accurate prognostic and predictive biomarkers of chemotherapy response. This study evaluated the role of Signal Transducer and Activator of Transcription 1 (STAT1) as an independent prognostic and predictive biomarker and its correlation with intratumoural CD8(+) T cells in a second independent biomarker validation study. Tumour STAT1 expression and intratumoural CD8(+) T cell infiltration were assessed by immunohistochemistry as a multicentre validation study conducted on 734 chemotherapy-naïve HGSCs...
October 2016: Journal of Pathology. Clinical Research
https://www.readbyqxmd.com/read/27913155/early-molecular-stratification-of-high-risk-primary-biliary-cholangitis
#4
Claire Hardie, Kile Green, Laura Jopson, Ben Millar, Barbara Innes, Sarah Pagan, Dina Tiniakos, Jessica Dyson, Muzlifah Haniffa, Venetia Bigley, David E Jones, John Brain, Lucy J Walker
High-risk primary biliary cholangitis (PBC), defined by inadequate response at one year to Ursodeoxycholic acid (UDCA), is associated with disease progression and liver transplantation. Stratifying high-risk patients early would facilitate improved approaches to care. Using long-term follow-up data to define risk at presentation, 6 high-risk PBC patients and 8 low-risk patients were identified from biopsy, transplant and biochemical archival records. Formalin-fixed paraffin-embedded (FFPE) liver biopsies taken at presentation were graded (Scheuer and Nakanuma scoring) and gene expression analysed using the NanoString® nCounter PanCancer Immunity 770-gene panel...
November 21, 2016: EBioMedicine
https://www.readbyqxmd.com/read/27894339/the-identification-of-human-pituitary-adenoma-initiating-cells
#5
Branavan Manoranjan, Sujeivan Mahendram, Saleh A Almenawer, Chitra Venugopal, Nicole McFarlane, Robin Hallett, Thusyanth Vijayakumar, Almunder Algird, Naresh K Murty, Doron D Sommer, John P Provias, Kesava Reddy, Sheila K Singh
Classified as benign central nervous system (CNS) tumors, pituitary adenomas account for 10% of diagnosed intracranial neoplasms. Although surgery is often curative, patients with invasive macroadenomas continue to experience significant morbidity and are prone to tumor recurrence. Given the identification of human brain tumor-initiating cells (TICs) that initiate and maintain tumor growth while promoting disease progression and relapse in multiple CNS tumors, we investigated whether TICs also drive the growth of human pituitary adenomas...
November 28, 2016: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/27889920/neuropeptide-y-receptor-1-is-expressed-by-b-and-t-lymphocytes-and-mast-cells-in-infantile-haemangiomas
#6
Elysia M S Tan, Max G Blackwell, Jonathan C Dunne, Reginald Marsh, Swee T Tan, Tinte Itinteang
AIM: We investigated the expression of neuropeptide Y (NPY), NPY receptor 1 (NPYR1) and NPY receptor 2 (NPYR2) in infantile haemangiomas (IHs). METHODS: Immunohistochemical (IHC) staining was performed on proliferating IHs from six patients aged 4-13 (mean 8.7) months and involuted IHs from six patients aged 5-59 (mean 18.7) years, for the expression of NPY, NPYR1 and NPYR2. Protein and messenger ribonucleic acid expression corresponding to these proteins was investigated by Western blotting and NanoString analysis, respectively...
November 27, 2016: Acta Paediatrica
https://www.readbyqxmd.com/read/27872814/transcriptional-profiles-of-wnv-neurovirulence-in-a-genetically-diverse-collaborative-cross-population
#7
Richard Green, Courtney Wilkins, Sunil Thomas, Aimee Sekine, Renee C Ireton, Martin T Ferris, Duncan M Hendrick, Kathleen Voss, Fernando Pardo-Manuel de Villena, Ralph S Baric, Mark T Heise, Michael Gale
West Nile Virus (WNV) is a mosquito-transmitted virus from the Flaviviridae family that causes fever in 1 in 5 infected people. WNV can also become neuro-invasive and cross the blood-brain barrier leading to severe neurological symptoms in a subset of WNV infected individuals [1]. WNV neuro-invasion is believed to be influenced by a number of factors including host genetics. In order to explore these effects and recapitulate the complex immune genetic differences among individuals, we studied gene expression following WNV infection in the Collaborative Cross (CC) model...
December 2016: Genomics Data
https://www.readbyqxmd.com/read/27852037/placental-immune-editing-switch-pies-learning-about-immunomodulatory-pathways-from-a-unique-case-report
#8
Miguel H Bronchud, Francesc Tresserra, Wenjie Xu, Sarah Warren, Maite Cusido, Bernat Zantop, Ana Claudia Zenclussen, Alessandra Cesano
The hypothesis of this work is that, in order to escape the natural immune surveillance mechanisms, cancer cells and the surrounding microenvironment might express ectopically genes that are physiologically present in the placenta to mediate fetal immune-tolerance. These natural "placental immune-editing switch" mechanisms (PIES) may represent the result of millions of years of mammalian evolution developed to allow materno-fetal tolerance. Here, we introduce genes of the immune regulatory pathways that are either similarly over- or under-expressed in tumor vs normal tissue...
November 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27843766/identifying-protective-host-gene-expression-signatures-within-the-spleen-during-west-nile-virus-infection-in-the-collaborative-cross-model
#9
Richard Green, Courtney Wilkins, Sunil Thomas, Aimee Sekine, Renee C Ireton, Martin T Ferris, Duncan M Hendrick, Kathleen Voss, Fernando Pardo-Manuel de Villena, Ralph Baric, Mark Heise, Michael Gale
Flaviviruses are hematophagous arthropod-viruses that pose global challenges to human health. Like Zika virus, West Nile Virus (WNV) is a flavivirus for which no approved vaccine exists [1]. The role host genetics play in early detection and response to WNV still remains largely unexplained. In order to capture the impact of genetic variation on innate immune responses, we studied gene expression following WNV infection using the collaborative cross (CC). The CC is a mouse genetics resource composed of hundreds of independently bred, octo-parental recombinant inbred mouse lines [2]...
December 2016: Genomics Data
https://www.readbyqxmd.com/read/27843583/nanostring-expression-profiling-identifies-candidate-biomarkers-of-rad001-response-in-metastatic-gastric-cancer
#10
Kakoli Das, Xiu Bin Chan, David Epstein, Bin Tean Teh, Kyoung-Mee Kim, Seung Tae Kim, Se Hoon Park, Won Ki Kang, Steve Rozen, Jeeyun Lee, Patrick Tan
BACKGROUND: Gene expression profiling has contributed greatly to cancer research. However, expression-driven biomarker discovery in metastatic gastric cancer (mGC) remains unclear. A gene expression profile predicting RAD001 response in refractory GC was explored in this study. METHODS: Total RNA isolated from 54 tumour specimens from patients with mGC, prior to RAD001 treatment, was analysed via the NanoString nCounter gene expression assay. This assay targeted 477 genes representing 10 different GC-related oncogenic signalling and molecular subtype-specific expression signatures...
2016: ESMO Open
https://www.readbyqxmd.com/read/27835874/malignant-pleural-mesothelioma-and-mesothelial-hyperplasia-a-new-molecular-tool-for-the-differential-diagnosis
#11
Rossella Bruno, Greta Alì, Riccardo Giannini, Agnese Proietti, Marco Lucchi, Antonio Chella, Franca Melfi, Alfredo Mussi, Gabriella Fontanini
Malignant pleural mesothelioma (MPM) is a rare asbestos related cancer, aggressive and unresponsive to therapies. Histological examination of pleural lesions is the gold standard of MPM diagnosis, although it is sometimes hard to discriminate the epithelioid type of MPM from benign mesothelial hyperplasia (MH).This work aims to define a new molecular tool for the differential diagnosis of MPM, using the expression profile of 117 genes deregulated in this tumour.The gene expression analysis was performed by nanoString System on tumour tissues from 36 epithelioid MPM and 17 MH patients, and on 14 mesothelial pleural samples analysed in a blind way...
November 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27825137/fgfr-signaling-maintains-a-drug-persistent-cell-population-following-epithelial-mesenchymal-transition
#12
Wells S Brown, Saeed Salehin Akhand, Michael K Wendt
An emerging characteristic of drug resistance in cancer is the induction of epithelial-mesenchymal transition (EMT). However, the mechanisms of EMT-mediated drug resistance remain poorly defined. Therefore, we conducted long-term treatments of human epidermal growth factor receptor-2 (Her2)-transformed breast cancer cells with either the EGFR/Her2 kinase inhibitor, Lapatinib or TGF-β, a known physiological inducer of EMT. Both of these treatment regimes resulted in robust EMT phenotypes, but upon withdrawal a subpopulation of TGF-β induced cells readily underwent mesenchymal-epithelial transition, where as Lapatinib-induced cells failed to reestablish an epithelial population...
November 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27825118/amplification-of-muc1-in-prostate-cancer-metastasis-and-crpc-development
#13
Nicholas Wong, Pierre Major, Anil Kapoor, Fengxiang Wei, Judy Yan, Tariq Aziz, Mingxing Zheng, Dulitha Jayasekera, Jean-Claude Cutz, Mathilda Jing Chow, Damu Tang
Evidence supports the upregulation of MUC1 in prostate cancer (PC). However, this has not been thoroughly investigated. We report here an association of MUC1 upregulation with PC metastasis and the development of castration resistant PC (CRPC). MUC1 expression was specifically increased in DU145 cell-derived PC stem-like cells (PCSLCs) in comparison to their non-PCSLCs counterparts. While immunohistochemistry staining of 34 primary PCs revealed variability in MUC1 expression, Nanostring technology demonstrated elevated MUC1 mRNA levels in 4 of 7 PCs compared to their normal matched tissues...
November 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27821489/a-transcriptional-signature-identifies-lkb1-functional-status-as-a-novel-determinant-of-mek-sensitivity-in-lung-adenocarcinoma
#14
Jacob M Kaufman, Tadaaki Yamada, Kyungho Park, Cynthia D Timmers, Joseph M Amann, David P Carbone
LKB1 is a commonly mutated tumor suppressor in non-small cell lung cancer (NSCLC) that exerts complex effects on signal transduction and transcriptional regulation. To better understand the downstream impact of loss of functional LKB1, we developed a transcriptional fingerprint assay representing this phenotype. This assay was predictive of LKB1 functional loss in cell lines and clinical specimens, even those without detected sequence alterations in the gene. In silico screening of drug sensitivity data identified putative LKB1-selective drug candidates, revealing novel associations not apparent from analysis of LKB1 mutations alone...
November 7, 2016: Cancer Research
https://www.readbyqxmd.com/read/27815082/translating-a-prognostic-dna-genomic-classifier-into-the-clinic-retrospective-validation-in-563-localized-prostate-tumors
#15
Emilie Lalonde, Rached Alkallas, Melvin Lee Kiang Chua, Michael Fraser, Syed Haider, Alice Meng, Junyan Zheng, Cindy Q Yao, Valerie Picard, Michele Orain, Helène Hovington, Jure Murgic, Alejandro Berlin, Louis Lacombe, Alain Bergeron, Yves Fradet, Bernard Têtu, Johan Lindberg, Lars Egevad, Henrik Grönberg, Helen Ross-Adams, Alastair D Lamb, Silvia Halim, Mark J Dunning, David E Neal, Melania Pintilie, Theodorus van der Kwast, Robert G Bristow, Paul C Boutros
BACKGROUND: Localized prostate cancer is clinically heterogeneous, despite clinical risk groups that represent relative prostate cancer-specific mortality. We previously developed a 100-locus DNA classifier capable of substratifying patients at risk of biochemical relapse within clinical risk groups. OBJECTIVE: The 100-locus genomic classifier was refined to 31 functional loci and tested with standard clinical variables for the ability to predict biochemical recurrence (BCR) and metastasis...
November 1, 2016: European Urology
https://www.readbyqxmd.com/read/27812182/liver-monocytes-and-kupffer-cells-remain-transcriptionally-distinct-during-chronic-viral-infection
#16
Martijn D B van de Garde, Dowty Movita, Marieke van der Heide, Florence Herschke, Sandra De Jonghe, Lucio Gama, Andre Boonstra, Thomas Vanwolleghem
Due to the scarcity of immunocompetent animal models for chronic viral hepatitis, little is known about the role of the innate intrahepatic immune system during viral replication in the liver. These insights are however fundamental for the understanding of the inappropriate adaptive immune responses during the chronic phase of the infection. We apply the Lymphocytic Choriomenigitis Virus (LCMV) clone 13 mouse model to examine chronic virus-host interactions of Kupffer cells (KC) and infiltrating monocytes (IM) in an infected liver...
2016: PloS One
https://www.readbyqxmd.com/read/27802451/microrna-193b-3p-as-a-predictive-biomarker-of-chronic-kidney-disease-in-patients-undergoing-radical-nephrectomy-for-renal-cell-carcinoma
#17
Francesco Trevisani, Michele Ghidini, Alessandro Larcher, Andrea Lampis, Hazel Lote, Paolo Manunta, Maria Teresa Sciarrone Alibrandi, Laura Zagato, Lorena Citterio, Giacomo Dell'Antonio, Cristina Carenzi, Giovambattista Capasso, Massimo Rugge, Paolo Rigotti, Roberto Bertini, Luciano Cascione, Alberto Briganti, Andrea Salonia, Fabio Benigni, Chiara Braconi, Matteo Fassan, Jens Claus Hahne, Francesco Montorsi, Nicola Valeri
BACKGROUND: A significant proportion of patients undergoing radical nephrectomy (RN) for clear-cell renal cell carcinoma (RCC) develop chronic kidney disease (CKD) within a few years following surgery. Chronic kidney disease has important health, social and economic impact and no predictive biomarkers are currently available. MicroRNAs (miRs) are small non-coding RNAs implicated in several pathological processes. METHODS: Primary objective of our study was to define miRs whose deregulation is predictive of CKD in patients treated with RN...
November 22, 2016: British Journal of Cancer
https://www.readbyqxmd.com/read/27802291/actb-cdkn1b-gapdh-grb2-rhoa-and-sdcbp-were-identified-as-reference-genes-in-neuroendocrine-lung-cancer-via-the-ncounter-technology
#18
Robert Fred Henry Walter, Robert Werner, Claudia Vollbrecht, Thomas Hager, Elena Flom, Daniel Christian Christoph, Jan Schmeller, Kurt Werner Schmid, Jeremias Wohlschlaeger, Fabian Dominik Mairinger
BACKGROUND: Neuroendocrine lung cancer (NELC) represents 25% of all lung cancer cases and large patient collectives exist as formalin-fixed, paraffin-embedded (FFPE) tissue only. FFPE is controversially discussed as source for molecular biological analyses and reference genes for NELC are poorly establishes. MATERIAL AND METHODS: Forty-three representative FFPE-specimens were used for mRNA expression analysis using the digital nCounter technology (NanoString). Based on recent literature, a total of 91 mRNA targets were investigated as potential tumor markers or reference genes...
2016: PloS One
https://www.readbyqxmd.com/read/27797936/il-6-and-pd-l1-antibody-blockade-combination-therapy-reduces-tumour-progression-in-murine-models-of-pancreatic-cancer
#19
Thomas A Mace, Reena Shakya, Jason R Pitarresi, Benjamin Swanson, Christopher W McQuinn, Shannon Loftus, Emily Nordquist, Zobeida Cruz-Monserrate, Lianbo Yu, Gregory Young, Xiaoling Zhong, Teresa A Zimmers, Michael C Ostrowski, Thomas Ludwig, Mark Bloomston, Tanios Bekaii-Saab, Gregory B Lesinski
OBJECTIVE: Limited efficacy of immune checkpoint inhibitors in pancreatic ductal adenocarcinoma (PDAC) has prompted investigation into combination therapy. We hypothesised that interleukin 6 (IL-6) blockade would modulate immunological features of PDAC and enhance the efficacy of anti-programmed death-1-ligand 1 (PD-L1) checkpoint inhibitor therapy. DESIGN: Transcription profiles and IL-6 secretion from primary patient-derived pancreatic stellate cells (PSCs) were analyzed via Nanostring and immunohistochemistry, respectively...
October 21, 2016: Gut
https://www.readbyqxmd.com/read/27794124/intrinsic-subtype-and-therapeutic-response-among-her2-positive-breaty-st-tumors-from-the-ncctg-alliance-n9831-trial
#20
Edith A Perez, Karla V Ballman, Afshin Mashadi-Hossein, Kathleen S Tenner, Jennifer M Kachergus, Nadine Norton, Brian M Necela, Jennifer M Carr, Sean Ferree, Charles M Perou, Frederick Baehner, Maggie Chon U Cheang, E Aubrey Thompson
BACKGROUND: Genomic data from human epidermal growth factor receptor 2-positive (HER2+) tumors were analyzed to assess the association between intrinsic subtype and clinical outcome in a large, well-annotated patient cohort. METHODS: Samples from the NCCTG (Alliance) N9831 trial were analyzed using the Prosigna algorithm on the NanoString platform to define intrinsic subtype, risk of recurrence scores, and risk categories for 1392 HER2+ tumors. Subtypes were evaluated for recurrence-free survival (RFS) using Kaplan-Meier and Cox model analysis following adjuvant chemotherapy (n = 484) or chemotherapy plus trastuzumab (n = 908)...
February 2017: Journal of the National Cancer Institute
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