DOCSLIB.ORG

Patient Derived BTIC Lines %CD70+ Cells BT241 94 MBT190 69

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Patient Derived BTIC Lines %CD70+ Cells BT241 94 MBT190 69 A B BT956_CC JSRP1JSRP1 TSIX FAM166A ZACN RPL21 AMN Patient MMP3CXCR5 EDN2 APOA1 GRIN3B XIST %CD70+ 5 PP2D1 HIST1H4I TMEM184A APCDD1LRIPK4 HCRTR1 LHFPL5 TFPI2EPHA1 DKK1 CD70 MRAP derived BTIC TWIST2 WDR38 TH ALDH3A1 MAP3K15 cells lines MYCN MET BT241 94 TERT EGFR TP53 MBT190 69 CCND1 CDK4 CCNE1 ATRX SOX2 CDKN1A CDK6 PTEN MDM2 NF1 50 PDGFRA − MBT225 68 PROM1 CDKN2A BT618 46 10 − MBT173 41 log2( Our Sample / Median TCGA Expr ) Expr Median TCGA / Sample log2( Our CSF3RELAVL4ADGRL4NOTCH2NLNOTCH2NLBCANRGS18NRXN1LRRTM4RGPD4RGPD6RGPD6WNT7AFAM107A SERF1AGAPTC7PCDHA1 PIK3CGKCND2GIMAP6VIPR2ST18FOCADITIH5PTERPRF1LY V E 1 VWFACVRL1ARL11SMOC1RASGRF1SV2B GALR1 PTPRT ANKRD44LRRC3B HPGDSADCY2IRX1TXNDC5UBDADGRF5LHFPL3LRRC61 APBB1IPMS4A6A RNASE2GCOM1ACSM5CNTNAP4SPN AQP4 SLC52A3PWP2PWP2CLDN5CSF2RBSPRY3SPN BT972 11.3 FCGR3APTPN7 MMRN1IBSP MYCT1 TSPYL5KLHL9TEK FOLH1FOLH1ZBTB16 CELF6 ARHGEF15 CELF5SIGLEC14FPR1MYT1OLIG1GPR34ITM2A SELL AMIGO3 ETNPPLEMCNSPOCK3 TREM1 GIMAP7HACD4WDFY4MGMT SLCO1A2 FAM20A IFI30 SRXN1 SLC6A1ATRIPLTFP2RY13 HAPLN1 TUSC1 AS3MT TEN1ZNF177NCANGPR4 GUSBP11TLR7VSIG4UTYZFY CDH10 PI16NXPH1 CAAP1AKAP2 PIRT NLGN4YEIF1AYUSP9Y 15 MOG PIK3R2 CMC4 BRINP3 SCN3A APLNR SLX1B SMIM11ASMIM11A DCXSLX1B − HBB NDN LRRC55 OMGOMG DDX3Y SB2b 4 MFRPLMO3 BOLA2 BOLA2CD99 ALOX5AP HBA2 CD93 SCHIP1 OLIG2 BT566 3 12345 6 78 9 10 11 12 13 15 16 17 18 19 20 22 X GBM4 72 Chromosome GBM8 70 BT698_CC BT698 65 JSRP1JSRP1 RN1 35 ZACN TSIX LCN2 FAM166A POU2F3 RPL21 AMN PLA2G3 PP2D1 CXCR5 CD70 XIST MBT103 35 5 OPRD1 MYCNOS LHFPL5 TMEM213 HCRTR1 HIST1H4IBMP5 EPHA1MAPK15 BEST1COL2A1 WNT10A AKR1B10 SLC18A2 GRIN3B MRAPRIPK4 CSAG3 MBT121 12 MYCN BT458 9 TERT MET PROM1 CDK4 BT428 5 CDK6 CCND1 SOX2 TP53NF1 ATRX CDKN1A PTEN MDM2 50 PDGFRA CCNE1 − EGFR BT954 4 CDKN2A WK1 3 MGMT 10 − BT799 2.2 FCGR1B RASGRF1 GPR34 PLA2G5S1PR1FCGR1ARGS18PTPRCTNR LRRTM1RGPD4DPP10CX3CR1CCRL2ITIH4 CDS1SERF1AGAPTSERPINB9TXNDC5LY86MOG CDKN2BGDAPALM2 LYSYT13MS4A7 V E 1 RPH3AARL11RNASE4 ATP6V0CCYBACCL4CD300LFGALR1BCKDHASIGLEC8LILRB2PTPRTCTSZ SASH3 ADGRL4SLC6A17BCANCD48NTSR2GPR17CYTIPLRRC3BHHATLCCR5CADM2HCLS1KLHL6HPGDSPCDH10LIX1 UBDSOGA3MYO1G FAM225BMRC1ZNF488EMX2 GCOM1ACSM5CNTNAP4SPNDPEP1 COX7A1MAGSIGLEC14SIGLEC7ADAMTS5NCAM2CSF2RBSPRY3SPN log2( Our Sample / Median TCGA Expr ) Expr Median TCGA / Sample log2( Our CD84PTPN7 MSTN RASGEF1BMMRN1CD14 GPR37GIMAP7HACD4SYKH2AFY2FOLH1FOLH1ZBTB16HSPB2VWF CELF6 PLVAPAPOC1LILRA2LILRB4SRXN1 ANOS1 GBM123 1.5 TNFAIP8L2CD53TSTD1RGS1 GALNT15SLC6A1AMIGO3ALDH1L1ETNPPLEMCNSPOCK3ESM1EMB NRSN1FGD2ENPP5 GRM3GIMAP8EPHB6MSR1FAM135BSLAMTAP WDFY4LUZP2MFRPCD163 SHISA9BOLA2 HAMPSIGLEC9CYYR1ERG BOLA2 GRIK3 MNDA ST6GAL2 P2RY13SNCAHAPLN1 GGTA1PLRRTM3MS4A6ACLEC7ADCNALOX5APRNASE1 HBA1 TEN1VAV1HAPLN4FPR3THBDGUSBP11NCF4TLR7 UTYZFY IGSF21C1QA TREM2 LHFPL3CLEC5AGIMAP5 AKAP2 FOLR2SLCO1C1 CLEC14A PRKCBIRF8PIRT CHST9PIK3R2TYROBP SAMSN1CLDN5CYBBVSIG4NLGN4YEIF1AYUSP9YCMC4 15 CCR1 C1QCC1QBHEYLFCGR3A GIMAP6DOCK8 MS4A4A RNASE6 SLX1B EVI2B SLC24A3SMIM11ASMIM11A SLX1B − FYB GIMAP4 OLR1 SMOC1 AQP4MRO KLHL9APBB1IPHBB FPR1 DDX3Y MBT63 1.3 ADORA3 AIF1 LMO3 TSPAN7 HBA2 CD93 SCHIP1 MBT27 1 CD99 20 − BT935 <1 12345 6 78 9 10 11 12 13 15 16 17 18 19 20 22 X BT594 0.5 Chromosome BT459 <1 BT618_CC BT778 <1 ZACN JSRP1JSRP1 TSIX AMN NSC195 1.8 PP2D1 HIST1H4I FAM166A RPL21 GRIN3B DKK1 BEST1CXCR5 5 PRDM13FEZF1 SLC39A5 HOXB8 XIST HCRTR1DCDC2B GPR39 AKR1B10 ATP12A MRAP PITX2 TFPI2EPHA1FOXH1 KRT16KLHL14CD70 NSC201FT 8.5 Astrocytes 1.2 MET MGMT TERT CDKN1A CDK6 CCND1 SOX2 MDM2 TP53 CCNE1 CDK4 NF1 ATRX 50 − PDGFRA EGFR MYCN CDKN2A PROM1 10 − GALNT15CCK SLC16A10KBTBD11 PRF1 SHANK2CACNA2D4 RASGRF1SULT1A3EIF3CLCDH1 CD300LFSYT4FXYD7 CLDN5MAGED4BSULT1A3 GABRDPADI2ELAVL4NOTCH2NLNOTCH2NLSLC6A17RGS18 RGPD6RGPD6DPP10WNT7ACCRL2ALDH1L1 GAPT WBSCR17PIK3CGGFRA2MSR1ST18CDKN2BRASGEF1ACSNK2A3SLC1A2PTPN5IL10RANCKAP1LDCNRFX4ARL11SMOC1 SV2BACSM5CNTNAP4DPEP1HP CD300ACA10 LILRB2PTPRTHCKNKAIN4OSMZNF674RAI2BEX5GLUD2SPRY3 RUNX3LAPTM5 CD48 ARHGAP15TFCP2L1CYTIPCCR5KLHL6HPGDSBASP1ECSCRPACSIN1UBDCARD11CNTNAP2GIMAP1CSMD1SLAKLHL9SUSD3PTGS1STAMBPL1MS4A6AMS4A7SLCO2B1VWF FLT1RNASE2GCOM1HBA2FA2HCYBAEIF4A1CCL3ST8SIA3ATCAYPLVAPCHST8IFI30SIGLEC14SIGLEC7SLC52A3SIRPB2BMP7MYT1CSF2RBKIAA2022PGAM4RP2 log2( Our Sample / Median TCGA Expr ) Expr Median TCGA / Sample log2( Our GSTM5CD84PTPN7FMOD KIF1ACX3CR1TM4SF18 TREM1AIF1MYCT1GTF2IP1TFECCTHRC1TSPYL5LY6HHACD4ANKRD22ADIRFPTENFOLH1FOLH1ZBTB16 RNASE1 CELF6 LYL1 LILRA2CD33KLK6 ADORA3S100A8ATP1A2 NHEJ1AMIGO3 SPOCK3ENPP6ESM1TXNDC5FGD2SMOC2GIMAP8MTAP SORCS3AS3MT PDE1BGALNT4 GPR65 TMC8SLC14A1FXYD1HAMPSIGLEC9HIF3ASIGLEC1CYYR1 VSIG4 CD53FCGR3AMNDA ST6GAL2SLC6A11P2RY13 HAPLN1 PI16 GIMAP5MLLT3 GPR183PRKCH ATP6V0CHBA1 HAPLN4NCANIGLON5LILRB1PPP1R16BTHBDGUSBP11TLR7 UTYZFY C1QCC1QAGRIK3FCGR1B ZNF518B SERPINB9CPLX2MOG TMEM176BCLEC5A AKAP2 FOLR2IL18LPAR5CD163 CLEC14A RAP1GAP2IRF8 PIK3R2SIGLEC8 SIK1KRBOX4NLGN4YEIF1AYUSP9YCMC4 15 C1QB TMEFF1 FAM181A NAPSB S100A9RCSD1 CD86 LY86 GIMAP6 ALOX5 TMEM132EKCNJ16ABI3 MAGSLC24A3SMIM11ASMIM11AMFNGFUNDC1 − PTPRC SERPINB1ADGRF5 GIMAP4 SYKAPBB1IPATAD1 OLR1 LILRB4 SASH3DDX3Y SERF1A SOGA3TMEM176A MFRP BOLA2 BCKDHAFPR1LAIR1SRXN1 GPR34NDPBOLA2 TREM2 ALOX5AP TYROBPCD93 ITM2A RGS1 SCHIP1 HBB MAOB CD99 20 − 12345 6 78 9 10 11 12 13 15 16 17 18 19 20 22 X Chromosome A B CD70neg 15000 100 shGFP * CD70pos shCD70 80 10000 60 * 40 * 25 5000 20 15 % CD70 population 10 5 Flourescence intensity (A.U.) intensity Flourescence 0 0 BT698 BT428 BT458 BT241 GBM8 GBM4 C GBM4 D 150 GBM4 100 shGFP ** ) shCD70 2 100 * 50 50 Percent Survival Tumor area (mm 0 0 0 50 100 150 Days Elapsed shGFP shCD70 A MOSERLE_IFNA_RESPONSE PID_IL1_PATHWAY REACTOME_ANTIVIRAL_MECHANISM_BY_IFN_STIMULATED_GENES PID_IL1_PATHWAY HALLMARK_INTERFERON_ALPHA_RESPONSE IL1-MEDIATED SIGNALING EVENTS CD70-dependent activation ISG15 ANTIVIRAL MECHANISM ANTIVIRAL MECHANISM BY IFN-STIMULATED GENES HALLMARK_HYPOXIA HALLMARK_EPITHELIAL_MESENCHYMAL_TRANSITION BMI1_DN_MEL18_DN.V1_UP CD70-dependent repression MEL18_DN.V1_UP ESC_V6.5_UP_EARLY.V1_DN MENSE_HYPOXIA_UP ELVIDGE_HYPOXIA_UP ELVIDGE_HIF1A_TARGETS_DN -3 -2 -1 0 1 2 3 NES score B Geranylgeranylation ATM Pathway Resolution of D-loop Structures Folate Metabolism Hypoxia Cell cycle Epigenetic Modifications HIF1A Pathway TLR Cascade UV Response Protein degradation and antigen processing TRAF6-mediated NF KB Signaling Protein sumoylation and uiquitinylation IFN Signaling UV Response Complement Cascade mRNA Translation EGF Signaling HIF1A/HIP2A Signaling H3K27ME3 Activity PKA Signaling Collagen Processing CK1 Pathway EMT Process mRNA decay Cancer Cell Metastasis Apoptosis Cell Junction STAT3 Target Response TCA Cycle A B C ConCAR ConCAR BT241 CD70CAR CD70CAR 150 25000 200 **** 20000 **** **** 150 100 15000 (pg/mL) (pg/mL) 100 α γ 10000 50 ** ns IFN- **** TNF- Median MFI (A.U) 50 5000 0 0 0 BT935 GBM4 GBM8 BT935 GBM4 GBM8 4°C, 2h 37°C, 2h D GBM8 100 ConCAR 80 CD70CAR * * 60 * 40 % Cell lysis Cell % 20 0 0:1 1:1 2:1 3:1 4:1 -20 E:T Ratio A B 1010 ConCAR 100 109 CD70CAR ConCAR 8 10 CD70CAR 107 50 106 CAR Injection Total flux(p/s) Total Percentsurvival *** 105 104 0 0 20 40 60 80 100 120 140 0 50 100 150 Days post-tumor injection Days post-tumor injection C 60 ConCAR CD70CAR ) 2 40 20 Tumor area (mm 5 mm 0 ConCAR CD70CAR A CD27 in CD45+CD3+ pop. 100 CD8+ in CD45+CD3+ pop. 80 60 40 %CD27+ Cells %CD27+ 20 Respective of parental gating) parental of Respective ( 0 MBT155MBT162MBT163MBT168MBT189MBT190MBT191 MBT155MBT162MBT163MBT168MBT189MBT190MBT191 B Experimental setup %CD3+ %CD3+/CD27+ T cells alone 84 78 T cells + BT241 crAAVS1 (supernatant) 76 78 T cells + BT241 crCD70-A (supernatant) 76 78 T cells + BT241 crCD70-B (supernatant) 78 78 T cells + BT241 crAAVS1 (cells) 77 43 T cells + BT241 crCD70-A (cells) 77 79 T cells + BT241 crCD70-B (cells) 80 76 T cells T cells + BT241 crAAVS1 T cells + BT241 crCD70-A.
Load more

Recommended publications
  • A Fratricide-Resistant Allogeneic CAR T
    Investigation of ALLO-316: A Fratricide- Resistant Allogeneic CAR T Targeting CD70 As a Potential Therapy for the Treatment of AML Surabhi Srinivasan, Nguyen Tan, Hsin-Yuan Cheng, Yi Zhang, Silvia Tacheva-Grigorova, Tom Van Blarcom, Cesar Sommer, Duy Nguyen , Barbra Sasu, and Siler Panowski 1 Disclosures • Full-time employee of Allogene Therapeutics • Equity interest in Allogene Therapeutics ALLO-316 (CD70) utilizes TALEN® gene-editing technology pioneered and owned by Cellectis. Allogene has an exclusive license to the Cellectis technology for allogeneic products directed at this target and holds all global development and commercial rights for this investigational candidate. 22 CONFIDENTIAL Disclaimers This presentation is not intended for product promotion. All information is related to investigational therapies not available for commercial use. The safety and efficacy of the therapies have not been established for FDA approval. Forward-Looking Statements To the extent statements contained in this Presentation are not descriptions of historical facts regarding Allogene Therapeutics, Inc. (“Allogene,” “we,” “us,” or “our”), they are forward-looking statements reflecting management’s current beliefs and expectations. Forward-looking statements are subject to known and unknown risks, uncertainties, and other factors that may cause our or our industry’s actual results, levels or activity, performance, or achievements to be materially different from those anticipated by such statements. You can identify forward-looking statements by words such as “anticipate,” “believe,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “will,” “would” or the negative of those terms, and similar expressions that convey uncertainty of future events or outcomes. Forward-looking statements contained in this Presentation include, but are not limited to, statements regarding: the ability to progress the clinical development of allogeneic CAR T (AlloCAR T™) therapies and the potential benefits of AlloCAR T™ therapy, including ALLO-316.
    [Show full text]
  • The Orphan Receptor GPR17 Is Unresponsive to Uracil Nucleotides and Cysteinyl Leukotrienes S
    Supplemental material to this article can be found at: http://molpharm.aspetjournals.org/content/suppl/2017/03/02/mol.116.107904.DC1 1521-0111/91/5/518–532$25.00 https://doi.org/10.1124/mol.116.107904 MOLECULAR PHARMACOLOGY Mol Pharmacol 91:518–532, May 2017 Copyright ª 2017 by The American Society for Pharmacology and Experimental Therapeutics The Orphan Receptor GPR17 Is Unresponsive to Uracil Nucleotides and Cysteinyl Leukotrienes s Katharina Simon, Nicole Merten, Ralf Schröder, Stephanie Hennen, Philip Preis, Nina-Katharina Schmitt, Lucas Peters, Ramona Schrage,1 Celine Vermeiren, Michel Gillard, Klaus Mohr, Jesus Gomeza, and Evi Kostenis Molecular, Cellular and Pharmacobiology Section, Institute of Pharmaceutical Biology (K.S., N.M., Ral.S., S.H., P.P., N.-K.S, L.P., J.G., E.K.), Research Training Group 1873 (K.S., E.K.), Pharmacology and Toxicology Section, Institute of Pharmacy (Ram.S., K.M.), University of Bonn, Bonn, Germany; UCB Pharma, CNS Research, Braine l’Alleud, Belgium (C.V., M.G.). Downloaded from Received December 16, 2016; accepted March 1, 2017 ABSTRACT Pairing orphan G protein–coupled receptors (GPCRs) with their using eight distinct functional assay platforms based on label- cognate endogenous ligands is expected to have a major im- free pathway-unbiased biosensor technologies, as well as molpharm.aspetjournals.org pact on our understanding of GPCR biology. It follows that the canonical second-messenger or biochemical assays. Appraisal reproducibility of orphan receptor ligand pairs should be of of GPR17 activity can be accomplished with neither the coapplica- fundamental importance to guide meaningful investigations into tion of both ligand classes nor the exogenous transfection of partner the pharmacology and function of individual receptors.
    [Show full text]
  • Edinburgh Research Explorer
    Edinburgh Research Explorer International Union of Basic and Clinical Pharmacology. LXXXVIII. G protein-coupled receptor list Citation for published version: Davenport, AP, Alexander, SPH, Sharman, JL, Pawson, AJ, Benson, HE, Monaghan, AE, Liew, WC, Mpamhanga, CP, Bonner, TI, Neubig, RR, Pin, JP, Spedding, M & Harmar, AJ 2013, 'International Union of Basic and Clinical Pharmacology. LXXXVIII. G protein-coupled receptor list: recommendations for new pairings with cognate ligands', Pharmacological reviews, vol. 65, no. 3, pp. 967-86. https://doi.org/10.1124/pr.112.007179 Digital Object Identifier (DOI): 10.1124/pr.112.007179 Link: Link to publication record in Edinburgh Research Explorer Document Version: Publisher's PDF, also known as Version of record Published In: Pharmacological reviews Publisher Rights Statement: U.S. Government work not protected by U.S. copyright General rights Copyright for the publications made accessible via the Edinburgh Research Explorer is retained by the author(s) and / or other copyright owners and it is a condition of accessing these publications that users recognise and abide by the legal requirements associated with these rights. Take down policy The University of Edinburgh has made every reasonable effort to ensure that Edinburgh Research Explorer content complies with UK legislation. If you believe that the public display of this file breaches copyright please contact [email protected] providing details, and we will remove access to the work immediately and investigate your claim. Download date: 02. Oct. 2021 1521-0081/65/3/967–986$25.00 http://dx.doi.org/10.1124/pr.112.007179 PHARMACOLOGICAL REVIEWS Pharmacol Rev 65:967–986, July 2013 U.S.
    [Show full text]
  • 0.5) in Stat3∆/∆ Compared with Stat3flox/Flox
    Supplemental Table 2 Genes down-regulated (<0.5) in Stat3∆/∆ compared with Stat3flox/flox Probe ID Gene Symbol Gene Description Entrez gene ID 1460599_at Ermp1 endoplasmic reticulum metallopeptidase 1 226090 1460463_at H60c histocompatibility 60c 670558 1460431_at Gcnt1 glucosaminyl (N-acetyl) transferase 1, core 2 14537 1459979_x_at Zfp68 zinc finger protein 68 24135 1459747_at --- --- --- 1459608_at --- --- --- 1459168_at --- --- --- 1458718_at --- --- --- 1458618_at --- --- --- 1458466_at Ctsa cathepsin A 19025 1458345_s_at Colec11 collectin sub-family member 11 71693 1458046_at --- --- --- 1457769_at H60a histocompatibility 60a 15101 1457680_a_at Tmem69 transmembrane protein 69 230657 1457644_s_at Cxcl1 chemokine (C-X-C motif) ligand 1 14825 1457639_at Atp6v1h ATPase, H+ transporting, lysosomal V1 subunit H 108664 1457260_at 5730409E04Rik RIKEN cDNA 5730409E04Rik gene 230757 1457070_at --- --- --- 1456893_at --- --- --- 1456823_at Gm70 predicted gene 70 210762 1456671_at Tbrg3 transforming growth factor beta regulated gene 3 21378 1456211_at Nlrp10 NLR family, pyrin domain containing 10 244202 1455881_at Ier5l immediate early response 5-like 72500 1455576_at Rinl Ras and Rab interactor-like 320435 1455304_at Unc13c unc-13 homolog C (C. elegans) 208898 1455241_at BC037703 cDNA sequence BC037703 242125 1454866_s_at Clic6 chloride intracellular channel 6 209195 1453906_at Med13l mediator complex subunit 13-like 76199 1453522_at 6530401N04Rik RIKEN cDNA 6530401N04 gene 328092 1453354_at Gm11602 predicted gene 11602 100380944 1453234_at
    [Show full text]
  • Transcriptomic Analysis of Native Versus Cultured Human and Mouse Dorsal Root Ganglia Focused on Pharmacological Targets Short
    bioRxiv preprint doi: https://doi.org/10.1101/766865; this version posted September 12, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-ND 4.0 International license. Transcriptomic analysis of native versus cultured human and mouse dorsal root ganglia focused on pharmacological targets Short title: Comparative transcriptomics of acutely dissected versus cultured DRGs Andi Wangzhou1, Lisa A. McIlvried2, Candler Paige1, Paulino Barragan-Iglesias1, Carolyn A. Guzman1, Gregory Dussor1, Pradipta R. Ray1,#, Robert W. Gereau IV2, # and Theodore J. Price1, # 1The University of Texas at Dallas, School of Behavioral and Brain Sciences and Center for Advanced Pain Studies, 800 W Campbell Rd. Richardson, TX, 75080, USA 2Washington University Pain Center and Department of Anesthesiology, Washington University School of Medicine # corresponding authors [email protected], [email protected] and [email protected] Funding: NIH grants T32DA007261 (LM); NS065926 and NS102161 (TJP); NS106953 and NS042595 (RWG). The authors declare no conflicts of interest Author Contributions Conceived of the Project: PRR, RWG IV and TJP Performed Experiments: AW, LAM, CP, PB-I Supervised Experiments: GD, RWG IV, TJP Analyzed Data: AW, LAM, CP, CAG, PRR Supervised Bioinformatics Analysis: PRR Drew Figures: AW, PRR Wrote and Edited Manuscript: AW, LAM, CP, GD, PRR, RWG IV, TJP All authors approved the final version of the manuscript. 1 bioRxiv preprint doi: https://doi.org/10.1101/766865; this version posted September 12, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.
    [Show full text]
  • Targeting Lysophosphatidic Acid in Cancer: the Issues in Moving from Bench to Bedside
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by IUPUIScholarWorks cancers Review Targeting Lysophosphatidic Acid in Cancer: The Issues in Moving from Bench to Bedside Yan Xu Department of Obstetrics and Gynecology, Indiana University School of Medicine, 950 W. Walnut Street R2-E380, Indianapolis, IN 46202, USA; [email protected]; Tel.: +1-317-274-3972 Received: 28 August 2019; Accepted: 8 October 2019; Published: 10 October 2019 Abstract: Since the clear demonstration of lysophosphatidic acid (LPA)’s pathological roles in cancer in the mid-1990s, more than 1000 papers relating LPA to various types of cancer were published. Through these studies, LPA was established as a target for cancer. Although LPA-related inhibitors entered clinical trials for fibrosis, the concept of targeting LPA is yet to be moved to clinical cancer treatment. The major challenges that we are facing in moving LPA application from bench to bedside include the intrinsic and complicated metabolic, functional, and signaling properties of LPA, as well as technical issues, which are discussed in this review. Potential strategies and perspectives to improve the translational progress are suggested. Despite these challenges, we are optimistic that LPA blockage, particularly in combination with other agents, is on the horizon to be incorporated into clinical applications. Keywords: Autotaxin (ATX); ovarian cancer (OC); cancer stem cell (CSC); electrospray ionization tandem mass spectrometry (ESI-MS/MS); G-protein coupled receptor (GPCR); lipid phosphate phosphatase enzymes (LPPs); lysophosphatidic acid (LPA); phospholipase A2 enzymes (PLA2s); nuclear receptor peroxisome proliferator-activated receptor (PPAR); sphingosine-1 phosphate (S1P) 1.
    [Show full text]
  • Bioinformatics Identification of CCL8/21 As Potential Prognostic
    Bioscience Reports (2020) 40 BSR20202042 https://doi.org/10.1042/BSR20202042 Research Article Bioinformatics identification of CCL8/21 as potential prognostic biomarkers in breast cancer microenvironment 1,* 2,* 3 4 5 1 Bowen Chen , Shuyuan Zhang ,QiuyuLi, Shiting Wu ,HanHe and Jinbo Huang Downloaded from http://portlandpress.com/bioscirep/article-pdf/40/11/BSR20202042/897847/bsr-2020-2042.pdf by guest on 28 September 2021 1Department of Breast Disease, Maoming People’s Hospital, Maoming 525000, China; 2Department of Clinical Laboratory, Maoming People’s Hospital, Maoming 525000, China; 3Department of Emergency, Maoming People’s Hospital, Maoming 525000, China; 4Department of Oncology, Maoming People’s Hospital, Maoming 525000, China; 5Department of Medical Imaging, Maoming People’s Hospital, Maoming 525000, China Correspondence: Shuyuan Zhang ([email protected]) Background: Breast cancer (BC) is the most common malignancy among females world- wide. The tumor microenvironment usually prevents effective lymphocyte activation and infiltration, and suppresses infiltrating effector cells, leading to a failure of the host toreject the tumor. CC chemokines play a significant role in inflammation and infection. Methods: In our study, we analyzed the expression and survival data of CC chemokines in patients with BC using several bioinformatics analyses tools. Results: The mRNA expression of CCL2/3/4/5/7/8/11/17/19/20/22 was remark- ably increased while CCL14/21/23/28 was significantly down-regulated in BC tis- sues compared with normal tissues. Methylation could down-regulate expression of CCL2/5/15/17/19/20/22/23/24/25/26/27 in BC. Low expression of CCL3/4/23 was found to be associated with drug resistance in BC.
    [Show full text]
  • Uva-DARE (Digital Academic Repository)
    UvA-DARE (Digital Academic Repository) Balancing effector lymphocyte formation via CD27-CD70 interactions Arens, R. Publication date 2003 Link to publication Citation for published version (APA): Arens, R. (2003). Balancing effector lymphocyte formation via CD27-CD70 interactions. General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: https://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. UvA-DARE is a service provided by the library of the University of Amsterdam (https://dare.uva.nl) Download date:27 Sep 2021 Chapter 3 Constitutive CD27/CD70 interaction induces expansion of effector-type T cells and results in IFNy-mediated B cell depletion Ramon Arens*, Kiki Tesselaar*, Paul A. Baars, Gijs M.W. van Schijndel, Jenny Hendriks, Steven T. Pals, Paul Krimpenfort, Jannie Borst, Marinus H.J. van Oers, and René A.W. van Lier 'These authors contributed equally to this work Immunity 15, 801-812 (2001) Chapter 3 Constitutive CD27/CD70 interaction induces expansion of effector-type T cells and results in IFNy-mediated B cell depletion Ramon Arens123#, Kiki Tesselaar23", Paul A.
    [Show full text]
  • Supplementary Table 1: Adhesion Genes Data Set
    Supplementary Table 1: Adhesion genes data set PROBE Entrez Gene ID Celera Gene ID Gene_Symbol Gene_Name 160832 1 hCG201364.3 A1BG alpha-1-B glycoprotein 223658 1 hCG201364.3 A1BG alpha-1-B glycoprotein 212988 102 hCG40040.3 ADAM10 ADAM metallopeptidase domain 10 133411 4185 hCG28232.2 ADAM11 ADAM metallopeptidase domain 11 110695 8038 hCG40937.4 ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha) 195222 8038 hCG40937.4 ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha) 165344 8751 hCG20021.3 ADAM15 ADAM metallopeptidase domain 15 (metargidin) 189065 6868 null ADAM17 ADAM metallopeptidase domain 17 (tumor necrosis factor, alpha, converting enzyme) 108119 8728 hCG15398.4 ADAM19 ADAM metallopeptidase domain 19 (meltrin beta) 117763 8748 hCG20675.3 ADAM20 ADAM metallopeptidase domain 20 126448 8747 hCG1785634.2 ADAM21 ADAM metallopeptidase domain 21 208981 8747 hCG1785634.2|hCG2042897 ADAM21 ADAM metallopeptidase domain 21 180903 53616 hCG17212.4 ADAM22 ADAM metallopeptidase domain 22 177272 8745 hCG1811623.1 ADAM23 ADAM metallopeptidase domain 23 102384 10863 hCG1818505.1 ADAM28 ADAM metallopeptidase domain 28 119968 11086 hCG1786734.2 ADAM29 ADAM metallopeptidase domain 29 205542 11085 hCG1997196.1 ADAM30 ADAM metallopeptidase domain 30 148417 80332 hCG39255.4 ADAM33 ADAM metallopeptidase domain 33 140492 8756 hCG1789002.2 ADAM7 ADAM metallopeptidase domain 7 122603 101 hCG1816947.1 ADAM8 ADAM metallopeptidase domain 8 183965 8754 hCG1996391 ADAM9 ADAM metallopeptidase domain 9 (meltrin gamma) 129974 27299 hCG15447.3 ADAMDEC1 ADAM-like,
    [Show full text]
  • G-Protein-Coupled Receptor Gpr17 Regulates Oligodendrocyte
    www.nature.com/scientificreports OPEN G-Protein-Coupled Receptor Gpr17 Regulates Oligodendrocyte Diferentiation in Response Received: 11 May 2017 Accepted: 2 October 2017 to Lysolecithin-Induced Published: xx xx xxxx Demyelination Changqing Lu1,2, Lihua Dong2, Hui Zhou3, Qianmei Li3, Guojiao Huang3, Shu jun Bai3 & Linchuan Liao1 Oligodendrocytes are the myelin-producing cells of the central nervous system (CNS). A variety of brain disorders from “classical” demyelinating diseases, such as multiple sclerosis, stroke, schizophrenia, depression, Down syndrome and autism, are shown myelination defects. Oligodendrocyte myelination is regulated by a complex interplay of intrinsic, epigenetic and extrinsic factors. Gpr17 (G protein- coupled receptor 17) is a G protein-coupled receptor, and has been identifed to be a regulator for oligodendrocyte development. Here, we demonstrate that the absence of Gpr17 enhances remyelination in vivo with a toxin-induced model whereby focal demyelinated lesions are generated in spinal cord white matter of adult mice by localized injection of LPC(L-a-lysophosphatidylcholine). The increased expression of the activated form of Erk1/2 (phospho-Erk1/2) in lesion areas suggested the potential role of Erk1/2 activity on the Gpr17-dependent modulation of myelination. The absence of Gpr17 enhances remyelination is correlate with the activated Erk1/2 (phospho-Erk1/2).Being a membrane receptor, Gpr17 represents an ideal druggable target to be exploited for innovative regenerative approaches to acute and chronic CNS diseases. Oligodendrocytes are the myelin-producing cells of the central nervous system (CNS), and as such, wrap layers of lipid-dense insulating myelin around axons1. Mature oligodendrocytes have also been shown to provide met- abolic support to axons through transport systems within myelin, which may help prevent neurodegeneration2.
    [Show full text]
  • Sialic Acids and Their Influence on Human NK Cell Function
    cells Review Sialic Acids and Their Influence on Human NK Cell Function Philip Rosenstock * and Thomas Kaufmann Institute for Physiological Chemistry, Martin-Luther-University Halle-Wittenberg, Hollystr. 1, D-06114 Halle/Saale, Germany; [email protected] * Correspondence: [email protected] Abstract: Sialic acids are sugars with a nine-carbon backbone, present on the surface of all cells in humans, including immune cells and their target cells, with various functions. Natural Killer (NK) cells are cells of the innate immune system, capable of killing virus-infected and tumor cells. Sialic acids can influence the interaction of NK cells with potential targets in several ways. Different NK cell receptors can bind sialic acids, leading to NK cell inhibition or activation. Moreover, NK cells have sialic acids on their surface, which can regulate receptor abundance and activity. This review is focused on how sialic acids on NK cells and their target cells are involved in NK cell function. Keywords: sialic acids; sialylation; NK cells; Siglecs; NCAM; CD56; sialyltransferases; NKp44; Nkp46; NKG2D 1. Introduction 1.1. Sialic Acids N-Acetylneuraminic acid (Neu5Ac) is the most common sialic acid in the human organism and also the precursor for all other sialic acid derivatives. The biosynthesis of Neu5Ac begins in the cytosol with uridine diphosphate-N-acetylglucosamine (UDP- Citation: Rosenstock, P.; Kaufmann, GlcNAc) as its starting component [1]. It is important to understand that sialic acid T. Sialic Acids and Their Influence on formation is strongly linked to glycolysis, since it results in the production of fructose-6- Human NK Cell Function. Cells 2021, phosphate (F6P) and phosphoenolpyruvate (PEP).
    [Show full text]
  • CD Markers Are Routinely Used for the Immunophenotyping of Cells
    ptglab.com 1 CD MARKER ANTIBODIES www.ptglab.com Introduction The cluster of differentiation (abbreviated as CD) is a protocol used for the identification and investigation of cell surface molecules. So-called CD markers are routinely used for the immunophenotyping of cells. Despite this use, they are not limited to roles in the immune system and perform a variety of roles in cell differentiation, adhesion, migration, blood clotting, gamete fertilization, amino acid transport and apoptosis, among many others. As such, Proteintech’s mini catalog featuring its antibodies targeting CD markers is applicable to a wide range of research disciplines. PRODUCT FOCUS PECAM1 Platelet endothelial cell adhesion of blood vessels – making up a large portion molecule-1 (PECAM1), also known as cluster of its intracellular junctions. PECAM-1 is also CD Number of differentiation 31 (CD31), is a member of present on the surface of hematopoietic the immunoglobulin gene superfamily of cell cells and immune cells including platelets, CD31 adhesion molecules. It is highly expressed monocytes, neutrophils, natural killer cells, on the surface of the endothelium – the thin megakaryocytes and some types of T-cell. Catalog Number layer of endothelial cells lining the interior 11256-1-AP Type Rabbit Polyclonal Applications ELISA, FC, IF, IHC, IP, WB 16 Publications Immunohistochemical of paraffin-embedded Figure 1: Immunofluorescence staining human hepatocirrhosis using PECAM1, CD31 of PECAM1 (11256-1-AP), Alexa 488 goat antibody (11265-1-AP) at a dilution of 1:50 anti-rabbit (green), and smooth muscle KD/KO Validated (40x objective). alpha-actin (red), courtesy of Nicola Smart. PECAM1: Customer Testimonial Nicola Smart, a cardiovascular researcher “As you can see [the immunostaining] is and a group leader at the University of extremely clean and specific [and] displays Oxford, has said of the PECAM1 antibody strong intercellular junction expression, (11265-1-AP) that it “worked beautifully as expected for a cell adhesion molecule.” on every occasion I’ve tried it.” Proteintech thanks Dr.
    [Show full text]