tbuckley/cabot-search huggingface dataset:
Expression of metabotropic glutamate receptors in human prostate cancers and its potential signaling through prostate specific membrane antigen
Authors: Michael Aleman, Aaron Milbank, Kelley M. Harsch, Nick Detore, Eric Klein, Warren Heston
Journal: Cancer Research (2004)

5188  Introduction and Objectives: Prostate Specific Membrane Antigen, PSMA, is a protein that is expressed in the normal human prostate and is markedly increased in prostate cancer. Our laboratory identified that PSMA has enzymatic activity as a glutamate carboxypeptidase, releasing glutamate from polygammaglutamated folate and N-acetylaspartylglutamate. Because PSMA generates glutamate outside of the cell, we considered that glutamate might be involved further in cell signaling. In gene array analysis of the commonly used prostate cancer line, LNCaP, we observed expression of metabotropic glutamate receptor-2 (mGluR2). We therefore explored the presence of metabotropic glutamate receptors in prostate cancer cells and report here on our initial findings. Materials and Methods: RT-PCR analysis of mGluR was performed as described (J Neurochem 84:1288-1295, 2003). Western analysis of protein expression was performed using antibodies against mGluR2/3 from Calbiochem and Sigma. Measurements of cell growth were performed using a MTS colorimetric assay with LNCaP, C4-2, MDA PCA 2b, CWR22, PC-3 and Du-145 cells which were grown in a glutamate free medium and dialyzed fetal bovine serum with the addition of either glutamate, highly selective metabotropic glutamate receptor agonist or antagonists (TOCRIS). Results: LNCaP cells displayed mGluR2 receptors by gene array analysis. We used RT-PCR to further confirm the expression of mGluR2 receptors. To verify that the RNA message was resulting in the expression of mGluR2 protein, we used three different antibodies, which recognize mGluR2/3 metabotropic receptors by western analysis. All three antibodies recognized a protein of the size reported for mGluR2, 100-110kD. Most of the established prostate cell lines were found to express mGluR2 by western analysis. We observed that the selective mGluR2 agonist (2R, 4R)-APDC decreased cell growth relative to the non-treated control by over 50% in glutamate free media in LNCaP cells. Conclusions: PSMA is a glutamate carboxypeptidase that releases glutamate. The presence of a G protein coupled glutamate metabotropic receptor system suggests that PSMA generated glutamate signaling may provide a non-androgen target for regulating prostate growth. Supported in part from Grant DK/CA47650.
Abstract 4849: GenomeSpace: An environment for frictionless bioinformatics
Authors: Michael M. Reich
Journal: Cancer Research (2015)

Abstract Over the past several years, cancer genome characterization initiatives such as The Cancer Genome Atlas and the International Cancer Genome Consortium have produced an explosion of genomic data. These efforts, together with the proliferation of repositories for small-molecule screens and large-scale data production efforts to discover the breadth of genomic variation in humans, offer a new era of potential for the understanding of the basic mechanisms of cancer and identification of novel treatments. Comprehensive analysis of these datasets requires the coordinated use of Web-based applications and data repositories, desktop analysis tools and visualizers, and single-purpose algorithms. However, the effort required to transfer data between tools, convert between data formats, and manage results often prevents researchers from utilizing the wealth of methods available to them. Many integrative genomics and translational “bench to bedside” discoveries are possible with combinations of existing tools, but the necessary transitions between them puts them out of the reach of most researchers. GenomeSpace, http://www.genomespace.org, is an environment that brings together diverse computational tools, enabling scientists without programming skills to easily combine their capabilities. It aims to offer a common space to create, manipulate and share an ever-growing range of genomic analysis tools. GenomeSpace features support for cloud-based data storage and analysis, multi-tool analytic workflows, automatic conversion of data formats, and ease of connecting new tools to the environment. A set of six “GenomeSpace-enabled” seed tools developed by collaborating organizations provides a comprehensive platform for the analysis of cancer data: Cytoscape (UCSD), Galaxy (Penn State University), GenePattern (Broad Institute), Genomica (Weitzmann Institute), Integrative Genomics Viewer (Broad Institute), and the UCSC Genome Browser (UCSC). Its open architecture has driven its adoption by a number of additional tools, including the Cancer Cell Line Encyclopedia, Multiple Myeloma Genomics Portal, Project Achilles Portal, ArrayExpress, and Cistrome, with new tools and resources being released regularly. We show how researchers can use GenomeSpace to effortlessly combine the capabilities of all of these tools in several cancer research scenarios. Citation Format: Michael M. Reich. GenomeSpace: An environment for frictionless bioinformatics. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4849. doi:10.1158/1538-7445.AM2015-4849
A major role for ferroptosis in <i>Mycobacterium tuberculosis</i>–induced cell death and tissue necrosis
Authors: Eduardo P. Amaral, Diego L. Costa, Sivaranjani Namasivayam, Nicolas Riteau, Olena Kamenyeva, Lara Mittereder, Katrin D. Mayer-Barber, Bruno B. Andrade, Alan Sher
Journal: The Journal of Experimental Medicine (2019)

Necrotic cell death during Mycobacterium tuberculosis (Mtb) infection is considered host detrimental since it facilitates mycobacterial spread. Ferroptosis is a type of regulated necrosis induced by accumulation of free iron and toxic lipid peroxides. We observed that Mtb-induced macrophage necrosis is associated with reduced levels of glutathione and glutathione peroxidase-4 (Gpx4), along with increased free iron, mitochondrial superoxide, and lipid peroxidation, all of which are important hallmarks of ferroptosis. Moreover, necrotic cell death in Mtb-infected macrophage cultures was suppressed by ferrostatin-1 (Fer-1), a well-characterized ferroptosis inhibitor, as well as by iron chelation. Additional experiments in vivo revealed that pulmonary necrosis in acutely infected mice is associated with reduced Gpx4 expression as well as increased lipid peroxidation and is likewise suppressed by Fer-1 treatment. Importantly, Fer-1–treated infected animals also exhibited marked reductions in bacterial load. Together, these findings implicate ferroptosis as a major mechanism of necrosis in Mtb infection and as a target for host-directed therapy of tuberculosis.
Cirmtuzumab Blocks Production of Proinflammatory Factors By Inhibiting Wnt5a/ROR1 Induced Activation of NF-Kappa B in Chronic Lymphocytic Leukemia
Authors: Yun Chen, Michael Y. Choi, Liguang Chen, Jian Yu, Ling Zhang, Emanuela M. Ghia, Elsa Sanchez-Lopez, George F. Widhopf II, Karen Messer, Laura Z. Rassenti, Catriona Jamieson, Thomas J. Kipps
Journal: Blood (2018)
A Multi-Drug Tolerant Phenotype Is Induced By Diverse Microenvironmental Agonists in Chronic Lymphocytic Leukemia and Mantle Cell Lymphoma
Authors: Kallesh D. Jayappa, Konrad J. Cios, Vicki L. Gordon, Puja C. Arora, Timothy P. Bender, Michael E. Williams, Craig A. Portell, Michael J. Weber
Journal: Blood (2018)
Executive Summary: Heart Disease and Stroke Statistics—2013 Update
Authors: Alan S. Go, Dariush Mozaffarian, Véronique L. Roger, Emelia J. Benjamin, Jarett D. Berry, William B. Borden, Dawn M. Bravata, Shifan Dai, Earl S. Ford, Caroline S. Fox, Sheila Franco, Heather J. Fullerton, Cathleen Gillespie, Susan M. Hailpern, John A. Heit, Virginia J. Howard, Mark D. Huffman, Brett M. Kissela, Steven J. Kittner, Daniel T. Lackland, Judith H. Lichtman, Lynda D. Lisabeth, David Magid, Gregory M. Marcus, Ariane Marelli, David B. Matchar, Darren K. McGuire, Emile R. Mohler, Claudia S. Moy, Michael E. Mussolino, Graham Nichol, Nina P. Paynter, Pamela J. Schreiner, Paul D. Sorlie, Joel Stein, Tanya N. Turan, Salim S. Virani, Nathan D. Wong, Daniel Woo, Melanie B. Turner
Journal: Circulation (2013)
Bacterial Adhesion on Soft Materials: Passive Physicochemical Interactions or Active Bacterial Mechanosensing?
Authors: Hervé Straub, Claudio M. Bigger, Jules Valentin, Dominik Abt, Xiao‐Hua Qin, Leo Eberl, Katharina Maniura‐Weber, Qun Ren
Journal: Advanced Healthcare Materials (2019)

Abstract The influence of mechanical stiffness of biomaterials on bacterial adhesion is only sparsely studied and the mechanism behind this influence remains unclear. Here, bacterial adhesion on polydimethylsiloxane (PDMS) samples, having four different degrees of stiffness with Young's modulus ranging from 0.06 to 4.52 MPa, is investigated. Escherichia coli and Pseudomonas aeruginosa are found to adhere in greater numbers on soft PDMS (7‐ and 27‐fold increase, respectively) than on stiff PDMS, whereas Staphylococcus aureus adheres in similar numbers on the four tested surfaces. To determine whether the observed adhesion behavior is caused by bacteria‐specific mechanisms, abiotic polystyrene (PS) beads are employed as bacteria substitutes. Carboxylate‐modified PS (PS‐COOH) beads exhibit the same adhesion pattern as E. coli and P. aeruginosa with four times more adhered beads on soft PDMS than on stiff PDMS. In contrast, amine‐modified PS (PS‐NH 2 ) beads adhere in similar numbers on all tested samples, reminiscent of S. aureus adhesion. This work demonstrates for the first time that the intrinsic physicochemical properties associated with PDMS substrates of different stiffness strongly influence bacterial adhesion and challenge the previously reported theory on active bacterial mechanosensing, which provides new insights into the design of antifouling surfaces.
Impact of estimation versus direct measurement of predonation glomerular filtration rate on the eligibility of potential living kidney donors
Authors: François Gaillard, Marie Courbebaisse, Nassim Kamar, Lionel Rostaing, Lola Jacquemont, Maryvonne Hourmant, Arnaud Del Bello, Lionel Couzi, Pierre Merville, Paolo Malvezzi, Benedicte Janbon, Bruno Moulin, Nicolas Maillard, Laurence Dubourg, Sandrine Lemoine, Cyril Garrouste, Hans Pottel, Christophe Legendre, Pierre Delanaye, Christophe Mariat
Journal: Kidney International (2019)
Dupilumab provides important clinical benefits to patients with atopic dermatitis who do not achieve clear or almost clear skin according to the Investigator's Global Assessment: a pooled analysis of data from two phase <scp>III</scp> trials
Authors: J.I. Silverberg, E.L. Simpson, M. Ardeleanu, D. Thaçi, S. Barbarot, J. Bagel, Z. Chen, L. Eckert, J. Chao, A. Korotzer, E. Rizova, A.B. Rossi, Y. Lu, N.M.H. Graham, T. Hultsch, G. Pirozzi, B. Akinlade
Journal: British Journal of Dermatology (2019)

In the U.S.A., an Investigator's Global Assessment (IGA) score of ≤ 1 (clear or almost clear skin) has been the standard measure in regulatory outcomes for registration clinical trials in atopic dermatitis (AD), including those supporting the recent approval of dupilumab. To evaluate the treatment effect of dupilumab in patients with IGA > 1 at the end of treatment, using other validated outcome measures for AD signs, symptoms and quality of life. LIBERTY AD SOLO 1 and 2 were two 16‐week, randomized, double‐blind trials enrolling adult patients with moderate‐to‐severe AD (IGA ≥ 3) inadequately controlled with topical treatment. We performed a post hoc analysis in patients receiving dupilumab 300 mg every 2 weeks (q2w) or placebo. Outcome measures in patients with IGA > 1 included Eczema Area and Severity Index (EASI), pruritus numerical rating scale (NRS), affected body surface area (BSA), Patient‐Oriented Eczema Measure (POEM) and Dermatology Life Quality Index (DLQI). The trials were registered at ClinicalTrials.gov: NCT02277743 and NCT02277769. At week 16, 278 of 449 dupilumab q2w‐treated patients (median age 36·0 years) and 396 of 443 placebo‐treated patients had IGA > 1. Among patients with IGA > 1 at week 16, dupilumab significantly improved several outcome measures compared with placebo: EASI (−48·9% vs. −11·3%, P < 0·001), pruritus NRS (−35·2% vs. −9·1%, P < 0·001), affected BSA (−23·1% vs. −4·5%, P < 0·001), POEM score ≥ 4‐point improvement (57·4% vs. 21·0%, P < 0·001) and DLQI score ≥ 4‐point improvement (59·3% vs. 24·4%, P < 0·001). In patients with IGA > 1 at week 16, dupilumab induced statistically significant benefits in multiple validated outcome measures compared with placebo. The IGA ≤ 1 end point significantly underestimates clinically relevant dupilumab treatment effects.
Pentoxifylline prevents TNF production and activation of coagulation induced by OKT3 in vitro but not in vivo
Authors: D. Abramowicz, O. Pradier, L. Schandene, A. Crusiaux, L. D. P. uw, J. L. Vanherweghem, P. Capel, P. Kinnaert, P. Vereerstraeten, M. Goldman
Journal: Journal of the American Society of Nephrology (1993)
Asthma: moving toward a global children's charter
Authors: Warren Lenney, Yuichi Adachi, Andrew Bush, Gilberto B Fischer, Jianguo Hong, Anders Ostrem, Soren Pedersen, Peter D Sly, Stanley J Szefler, Raj Tilak, Heather J Zar, Yuichi Adachi, Lara J Akinbami, Kathryn V Blake, Andrew Bush, Michael Cabana, Lisa C Cicutto, Adnan Custovic, Iolo Doull, Gilberto B Fischer, Dominic A Fitzgerald, Monica Fletcher, Jonathan Grigg, Jianguo Hong, Rod Hughes, Christina Keen, David A Leather, Rob F Lemanske, Warren Lenney, Louis Garcia-Marcos, Donna J Mazyck, Anders Ostrem, Soren Pedersen, Bruce K Rubin, Aziz Sheikh, Kunling Shen, Peter Sly, Renato T Stein, James W Stout, Padmaja Subbarao, Stanley J Szefler, Raj Tilak, Tonya Winders, Sian Williams, Heather J Zar
Journal: The Lancet Respiratory Medicine (2019)
L'endoscopie digestive pratiquée en France en 2006: résultats globaux d'une enquête prospective nationale de la Société Française d'Endoscopie Digestive (SFED)
Authors: JM Canard, L Palazzo, JC Letard, JP Arpurt, C Boustiere, J Boyer, J Cassigneul, P Dalbies, J Escourrou, G Gay, R Laugier, B Napoleon, T Ponchon, B Richard Molard, D Sautereau, G Tucat, B Vedrenne
Journal: Endoscopy (2008)

But: Quantifier prospectivement la pratique de l'endoscopie digestive réalisée en France en 2006 et suivre son évolution depuis la première enquête réalisée en 1998.
Retraction: Steering CAR T Cells into Solid Tumors. N Engl J Med 2019;380:289-91.
Authors: Marion H Brown, Michael L Dustin
Journal: New England Journal of Medicine (2019)

To the Editor: Because the authors of the Nature article entitled “A Homing System Targets Therapeutic T Cells to Brain Cancer”1 have retracted it owing to issues with figure presentation and underlying data, we hereby wish to retract our commentary on that article, entitled “Steering CAR T Cells into Solid Tumors.”2 . . .
Degradation of endogenous proteins and generation of a null-like phenotype in zebrafish using Trim-Away technology
Authors: Xiao Chen, Mi Liu, Hongyan Lou, Yiyi Lu, Meng-Tao Zhou, Rongying Ou, Yunsheng Xu, Kai-Fu Tang
Journal: Genome biology (2019)

Trim-Away is a recent technique to rapidly deplete a protein from any cell type. Guided by antibodies, TRIM21 selects proteins for destruction. However, the applicability of this method in model organisms has not been investigated. Here, we show that Trim-Away can degrade proteins in zebrafish embryos. Trim-Away depletes proteins faster than morpholinos, which enables analysis of protein function during early embryogenesis. Furthermore, Trim-Away can be applied to evaluate the role of maternally contributed proteins in zebrafish embryos. Our findings indicate that Trim-Away is a powerful tool to perform functional analysis of proteins during zebrafish development.
Abstract P3-09-01: Withdrawn
Authors: M Pollán, V Lope, A Castelló, A Mena-Bravo, P Amiano, N Aragonés, T Fernández-Villa, M Guevara, T Dierssen, G Fernández-Tardón, G Castaño-Vinyals, R Marcos-Grajera, V Moreno, D Salas-Trejo, M Díaz-Santos, M Kogevinas, B Pérez-Gómez, F Priego-Capote
Journal: Cancer Research (2018)

Abstract This abstract was withdrawn by the authors.
Phosphoproteome and gene expression profiling of ALK inhibition in neuroblastoma cell lines reveals conserved oncogenic pathways
Authors: G. Umapathy, J. Van den Eynden, D. Cervantes-Madrid, J. Szydzik, J. Guan, R.H. Palmer, B. Hallberg
Journal: Annals of Oncology (2019)

Background: Anaplastic lymphoma kinase (ALK) is a tyrosine kinase receptor that is a clinical target of major interest in cancer. Mutations and rearrangements in ALK trigger the activation of the encoded receptor and its downstream signaling pathways. ALK mutations have been identified in both familial and sporadic neuroblastoma cases as well as in 30 to 40% of relapses, which makes ALK a bona fide target in neuroblastoma therapy. Tyrosine kinase inhibitors (TKIs) that target ALK are currently in clinical use for the treatment of patients with ALK-positive non–small cell lung cancer. However, monotherapy with the ALK inhibitor crizotinib has been less encouraging in neuroblastoma patients with ALK alterations, raising the question of whether combinatorial therapy would be more effective. Methods: In this study, we established both phosphoproteomic and gene expression profiles of ALK activity in neuroblastoma cells exposed to first- and third-generation ALK TKIs, to identify the underlying molecular mechanisms and identify relevant biomarkers, signaling networks, and new therapeutic targets. Results: The phosphoproteomic analysis identified several conserved oncogenic downstream signaling pathways of ALK, similar to those involved in insulin receptor (INSR)/tropomyosin receptor kinase (TRK) and fibroblast growth factor receptor (FGFR) signaling. In addition, signaling events involved in feedback and cross-talk were identified, including modulation of DUSP (dual-specificity phosphatase) family phosphatases. Furthermore, from analysis of the RNA-seq data, several transcription factors were predicted and validated as responsive to ALK signaling, including members of the FOXO (forkhead box O) and ETS (E26 transformation-specific or E-twenty-six) transcription factor families. Conclusions: Although neuroblastoma is a complex heterogeneous disease, this in-depth investigation of downstream targets of ALK signaling offers future avenues to pursue to inhibit ALK-driven neuroblastoma. Legal entity responsible for the study: Bengt Hallberg. Funding: Barncancerfonden. Disclosure: All authors have declared no conflicts of interest.
Comparison of the Effects of Glucagon-Like Peptide Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors for Prevention of Major Adverse Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus
Authors: Thomas A. Zelniker, Stephen D. Wiviott, Itamar Raz, KyungAh Im, Erica L. Goodrich, Remo H.M. Furtado, Marc P. Bonaca, Ofri Mosenzon, Eri T. Kato, Avivit Cahn, Deepak L. Bhatt, Lawrence A. Leiter, Darren K. McGuire, John P.H. Wilding, Marc S. Sabatine
Journal: Circulation (2019)

Background: Glucagon-like peptide 1 receptor agonists (GLP1-RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) have emerged as 2 new classes of antihyperglycemic agents that also reduce cardiovascular risk. The relative benefits in patients with and without established atherosclerotic cardiovascular disease for different outcomes with these classes of drugs remain undefined. Methods: We performed a systematic review and trial-level meta-analysis of GLP1-RA and SGLT2i cardiovascular outcomes trials using the PubMed and EMBASE databases (Excerpta Medica Database). The primary outcomes were the composite of myocardial infarction, stroke, and cardiovascular death (MACE); hospitalization for heart failure; and progression of kidney disease. Results: In total, data from 8 trials and 77 242 patients, 42 920 (55.6%) in GLP1-RA trials, and 34 322 (44.4%) in SGLT2i trials, were included. Both drug classes reduced MACE in a similar magnitude with GLP1-RA reducing the risk by 12% (hazard ratio [HR], 0.88; 95% CI, 0.84–0.94; P &lt;0.001) and SGLT2i by 11% (HR, 0.89; 95% CI, 0.83–0.96; P =0.001). For both drug classes, this treatment effect was restricted to a 14% reduction in those with established atherosclerotic cardiovascular disease (HR, 0.86; 95% CI, 0.80–0.93; P =0.002), whereas no effect was seen in patients without established atherosclerotic cardiovascular disease (HR, 1.01; 95% CI, 0.87–1.19; P =0.81; P interaction, 0.028). SGLT2i reduced hospitalization for heart failure by 31% (HR, 0.69; 95% CI, 0.61–0.79; P &lt;0.001), whereas GLP1-RA did not have a significant effect (HR, 0.93; 95% CI, 0.83–1.04; P =0.20). Both GLP1-RA (HR, 0.82; 95% CI, 0.75–0.89; P &lt;0.001) and SGLT2i (HR, 0.62; 95% CI, 0.58–0.67; P &lt;0.001) reduced the risk of progression of kidney disease including macroalbuminuria, but only SGLT2i reduced the risk of worsening estimated glomerular filtration rate, end-stage kidney disease, or renal death (HR, 0.55; 95% CI, 0.48–0.64; P &lt;0.001). Conclusions: In trials reported to date, GLP1-RA and SGLT2i reduce atherosclerotic MACE to a similar degree in patients with established atherosclerotic cardiovascular disease, whereas SGLT2i have a more marked effect on preventing hospitalization for heart failure and progression of kidney disease. Their distinct clinical benefit profiles should be considered in the decision-making process when treating patients with type 2 diabetes mellitus.
A Nonjunctional, Nonsyndromic Case of Junctional Epidermolysis Bullosa With Renal and Respiratory Involvement
Authors: Eran Cohen-Barak, Nada Danial-Farran, Morad Khayat, Elana Chervinsky, Judith M. Nevet, Michael Ziv, Stavit A. Shalev
Journal: JAMA Dermatology (2019)

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