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https://www.readbyqxmd.com/read/28069519/denaturing-fixatives-are-compatible-with-the-nanostring-ncounter-%C3%A2-platform-and-the-prosigna-%C3%A2-assay
#1
Roman Rouzier, Aurelie Roulot, Arthur H Jeiranian, Namratha Ram, Jean Marc Guinebretiere, Anne Vincent Salomon, David Gentien
The objective of this study was to establish that the denaturing fixative, formalin and acetic acid (AFA), is equivalent to neutral-buffered formalin (NBF) on the nCounter system using the Prosigna assay. Twenty-five previously resected tumors from breast cancer patients were apportioned and fixed with either NBF or AFA prior to embedding in paraffin. Differentially fixed and paraffin embedded tissue pairs were sectioned and pathological review was performed according to the Prosigna assay protocol. RNA was isolated using the Prosigna assay kit and analyzed using the NanoString nCounter Dx Analysis system...
January 6, 2017: New Biotechnology
https://www.readbyqxmd.com/read/28068403/normalisation-against-circadian-and-age-related-disturbances-enables-robust-detection-of-gene-expression-changes-in-liver-of-aged-mice
#2
Sara S Fonseca Costa, Daniel Wegmann, Jürgen A Ripperger
The expression of some genes is affected by age. To detect such age-related changes, their expression levels are related to constant marker genes. However, transcriptional noise increasing with advancing age renders difficult the identification of real age-related changes because it may affect the marker genes as well. Here, we report a selection procedure for genes appropriate to normalise the mouse liver transcriptome under various conditions including age. These genes were chosen from an initial set of 16 candidate genes defined based on a RNA-sequencing experiment and published literature...
2017: PloS One
https://www.readbyqxmd.com/read/28053879/lysozyme-association-with-circulating-rna-extracellular-vesicles-and-chronic-stress
#3
Sarah K Abey, Yuana Yuana, Paule V Joseph, Natnael D Kenea, Nicolaas H Fourie, LeeAnne B Sherwin, Gregory E Gonye, Paul A Smyser, Erin S Stempinski, Christina M Boulineaux, Kristen R Weaver, Christopher K E Bleck, Wendy A Henderson
BACKGROUND: Stress has demonstrated effects on inflammation though underlying cell-cell communication mechanisms remain unclear. We hypothesize that circulating RNAs and extracellular vesicles (EVs) in patients with chronic stress contain signals with functional roles in cell repair. METHODS: Blood transcriptome from patients with Irritable Bowel Syndrome versus controls were compared to identify signaling pathways and effectors. Plasma EVs were isolated (size-exclusion chromatography) and characterized for effectors' presence (immunogold labelling-electron microscopy)...
June 2017: BBA Clinical
https://www.readbyqxmd.com/read/28052655/genetic-alterations-and-their-clinical-implications-in-high-recurrence-risk-papillary-thyroid-cancer
#4
Min-Young Lee, Bo Mi Ku, Hae Su Kim, Ji Yun Lee, Sung Hee Lim, Jong-Mu Sun, Se-Hoon Lee, Keunchil Park, Young Lyun Oh, Mineui Hong, Han-Sin Jeong, Young-Ik Son, Chung-Hwan Baek, Myung-Ju Ahn
Purpose: Papillary thyroid carcinomas (PTCs) frequently involve genetic alterations. The objective of this study was to investigate genetic alterations and further explore the relationships between these genetic alterations and clinicopathological characteristics in a high-recurrence risk (node positive, N1) PTC group. Materials and Methods: Tumor tissue blocks were obtained from 240 surgically resected patients with histologically confirmed stage III/IV (pT3/4 or N1) PTCs...
December 26, 2016: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28030841/vamorolone-a-dissociative-steroidal-compound-reduces-pro-inflammatory-cytokine-expression-in-glioma-cells-and-increases-activity-and-survival-in-a-murine-model-of-cortical-tumor
#5
Elizabeth Wells, Madhuri Kambhampati, Jesse M Damsker, Heather Gordish-Dressman, Sridevi Yadavilli, Oren J Becher, Jamila Gittens, Mojca Stampar, Roger J Packer, Javad Nazarian
Corticosteroids, such as dexamethasone, are routinely used as palliative care in neuro-oncology for their anti-inflammatory benefits, however many patients experience dose limiting side effects caused by glucocorticoid response element (GRE)-mediated transcription. The purpose of this study was to use a murine model to investigate a new steroid alternative, vamorolone, which promises to reduce side effects through dissociating GRE-mediated transcription and NF-κB -mediated anti-inflammatory actions. To compare vamorolone to dexamethasone in reducing pro-inflammatory signals in vitro, murine glioma cells were treated with dexamethasone, vamorolone or vehicle control...
December 21, 2016: Oncotarget
https://www.readbyqxmd.com/read/28017967/duvelisib-treatment-is-associated-with-altered-expression-of-apoptotic-regulators-that-helps-in-sensitization-of-chronic-lymphocytic-leukemia-cells-to-venetoclax-abt-199
#6
V M Patel, K Balakrishnan, M Douglas, T Tibbitts, E Y Xu, J L Kutok, M Ayers, A Sarkar, R Guerrieri, W G Wierda, S O'Brien, N Jain, H M Stern, V Gandhi
Duvelisib, an oral dual inhibitor of PI3K-δ and PI3K-γ, is in phase III trials for the treatment of chronic lymphocytic leukemia (CLL) and indolent non-Hodgkin's lymphoma (iNHL). In CLL, duvelisib monotherapy is associated with high iwCLL and nodal response rates, but complete remissions are rare. To characterize the molecular effect of duvelisib, we obtained samples from CLL patients on the duvelisib phase I trial. Gene-expression studies (RNA seq, Nanostring, Affymetrix array, and real time RT-PCR) demonstrated increased expression of BCL2 along with several BH3-only pro-apoptotic genes...
December 26, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28007920/role-of-il-32-in-hiv-reactivation-and-its-link-to-hiv-hsv-coinfection
#7
Pedro M M Mesquita, Paula Preston-Hurlburt, Marla J Keller, Nalini Vudattu, Lilia Espinoza, Michelle Altrich, Kathryn Anastos, Kevan C Herold, Betsy C Herold
BACKGROUND: HSV-2 exacerbates HIV by unclear mechanisms. These studies tested the impact of HSV-2 on systemic T cell populations and HIV reservoirs. METHODS: Peripheral blood mononuclear cells from HIV-infected women on antiretroviral therapy who were HSV-2 seropositive or seronegative (HIV(+)/HSV-2(+) or HIV(+)/HSV-2(-)) and HIV-uninfected controls were analyzed by flow cytometry. HIV cell-associated (CA)-DNA and RNA were quantified in the absence or presence of activating stimuli, recombinant IL-32γ, and a RUNX1 inhibitor...
December 22, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27994652/to-excavate-biomarkers-predictive-of-the-response-for-capecitabine-plus-rad001-through-nanostring-based-multigene-assay-in-advanced-gastric-cancer-patients
#8
Hansang Lee, Jeeyun Lee, Insuk Sohn, Se Hoon Park, Joon Oh Park, Young Suk Park, Kyoung-Mee Kim, Won Ki Kang, Seung Tae Kim
Comprehensive characterization of individual patients' tumour is important to realize personalized medicine. Here, we investigate to identify subsets that benefit from capecitabine plus RAD001 in advanced gastric cancer (GC) patients by comprehensive high-throughput genomic analysis (nCounter assay). Archival tumour tissue blocks, if possible, were collected at phase II trial of capecitabine plus RAD001 in 47 refractory GC patients (at clinicaltrials.gov NCT#01099527). A total of 42 formalin-fixed, paraffin-embedded (FFPE) tumour samples were available for nanostring based-multigene Assay...
2016: Journal of Cancer
https://www.readbyqxmd.com/read/27994651/massive-parallel-sequencing-and-digital-gene-expression-analysis-reveals-potential-mechanisms-to-overcome-therapy-resistance-in-pulmonary-neuroendocrine-tumors
#9
Robert Fred Henry Walter, Claudia Vollbrecht, Daniel Christoph, Robert Werner, Jan Schmeller, Elena Flom, Georgia Trakada, Aggeliki Rapti, Vasilis Adamidis, Wolfgang Hohenforst-Schmidt, Jens Kollmeier, Thomas Mairinger, Jeremias Wohlschlaeger, Paul Zarogoulidis, Konstantinos Porpodis, Kurt Werner Schmidt, Fabian Dominik Mairinger
Background: Lung cancer is the leading cause of cancer-related deaths worldwide. 25% show neuroendocrine differentiation (typical/atypical carcinoids, large-/small-cell neuroendocrine carcinomas). Carcinoids present with long survival rates, but metastatic carcinoids correlate with decreased survival and are commonly insensitive to standard chemotherapy or radiation. Therefore, novel therapeutic strategies are urgently needed. Material and methods: 70 representative tumor specimens were used for next-generation sequencing analysis of 14 genes related to therapy response...
2016: Journal of Cancer
https://www.readbyqxmd.com/read/27993815/differential-gene-expression-profiling-of-matched-primary-renal-cell-carcinoma-and-metastases-reveals-upregulation-of-extracellular-matrix-genes
#10
T H Ho, D J Serie, M Parasramka, J C Cheville, B M Bot, W Tan, L Wang, R W Joseph, T Hilton, B C Leibovich, A S Parker, J E Eckel-Passow
BACKGROUND: The majority of renal cell carcinoma (RCC) studies analyze primary tumors, and the corresponding results are extrapolated to metastatic RCC tumors. However, it is unknown if gene expression profiles from primary RCC tumors differs from patient-matched metastatic tumors. Thus, we sought to identify differentially expressed genes between patient-matched primary and metastatic RCC tumors in order to understand the molecular mechanisms underlying the development of RCC metastases...
December 19, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27993329/an-mrna-gene-expression-based-signature-to-identify-fgfr1-amplified-estrogen-receptor-positive-breast-tumors
#11
Jingqin Luo, Shuzhen Liu, Samuel Leung, Alejandro A Gru, Yu Tao, Jeremy Hoog, Julie Ho, Sherri R Davies, D Craig Allred, Andrea L Salavaggione, Jacqueline Snider, Elaine R Mardis, Torsten O Nielsen, Matthew J Ellis
Fibroblast growth factor receptor 1 (FGFR1) amplification drives poor prognosis and is an emerging therapeutic target. We sought to construct a multigene mRNA expression signature to efficiently identify FGFR1-amplified estrogen receptor-positive (ER(+)) breast tumors. Five independent breast tumor series were analyzed. Genes discriminative for FGFR1 amplification were screened transcriptome-wide by receiver operating characteristic analyses. The METABRIC series was leveraged to construct/evaluate four approaches to signature composition...
January 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/27991924/cooperation-among-heterogeneous-prostate-cancer-cells-in-the-bone-metastatic-niche
#12
K Shahriari, F Shen, A Worrede-Mahdi, Q Liu, Y Gong, F U Garcia, A Fatatis
The growth of disseminated tumor cells into metastatic lesions depends on the establishment of a favorable microenvironment in the stroma of the target organs. Here we show that mice treated with anakinra, an antagonist of the interleukin (IL)-1β receptor (IL-1R), or harboring a targeted deletion of IL-1R are significantly less prone to develop bone tumors when inoculated in the arterial circulation with human prostate cancer (PCa) cells expressing IL-1β. Interestingly, human mesenchymal stem cells exposed in vitro to medium conditioned by IL-1β-expressing cancer cells responded by upregulating S100A4, a marker of cancer-associated fibroblasts (CAFs), and this effect was blocked by anakinra...
December 19, 2016: Oncogene
https://www.readbyqxmd.com/read/27991575/efficient-derivation-of-extraembryonic-endoderm-stem-cell-lines-from-mouse-postimplantation-embryos
#13
Jiangwei Lin, Mona Khan, Bolek Zapiec, Peter Mombaerts
Various types of stem cell lines have been derived from preimplantation or postimplantation mouse embryos: embryonic stem cell lines, epiblast stem cell lines, and trophoblast stem cell lines. It is not known if extraembryonic endoderm stem (XEN) cell lines can be derived from postimplantation mouse embryos. Here, we report the derivation of 77 XEN cell lines from 85 postimplantation embryos at embryonic day E5.5 or E6.5, in parallel to the derivation of 41 XEN lines from 69 preimplantation embryos at the blastocyst stage...
December 19, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27975007/embryonic-stem-cell-like-population-in-dupuytren-s-disease
#14
Sabrina P Koh, Nicholas On, Helen D Brasch, Alice M Chibnall, James R Armstrong, Paul F Davis, Swee T Tan, Tinte Itinteang
BACKGROUND: Recent research has identified mesenchymal stem cells (MSCs) within Dupuytren's disease (DD) tissue and they have been proposed to give rise to the myofibroblasts, implicated in the progression of this condition. The aim of this study was to identify and characterize the primitive population that might be upstream of the MSC population, within DD. METHODS: Formalin-fixed paraffin-embedded 4-µm-thick sections of DD cords and nodules obtained from 6 patients underwent 3,3-diaminobenzidine and immunofluorescent immunohistochemical staining for embryonic stem cell (ESC) markers OCT4, NANOG, SOX2, pSTAT3, and SALL4 and endothelial markers CD34 and ERG...
November 2016: Plastic and Reconstructive Surgery. Global Open
https://www.readbyqxmd.com/read/27918555/gene-expression-profiling-of-anti-ctla4-treated-metastatic-melanoma-in-patients-with-treatment-induced-autoimmunity
#15
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
#16
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...
January 2017: 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
#17
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
#18
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...
December 2016: EBioMedicine
https://www.readbyqxmd.com/read/27894339/the-identification-of-human-pituitary-adenoma-initiating-cells
#19
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
#20
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...
February 2017: Acta Paediatrica
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