Macrophage Polarization States in the Tumor Microenvironment
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TNF-Α Promotes Colon Cancer Cell Migration and Invasion by Upregulating TROP-2
3820 ONCOLOGY LETTERS 15: 3820-3827, 2018 TNF-α promotes colon cancer cell migration and invasion by upregulating TROP-2 PENG ZHAO and ZHONGTAO ZHANG Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China Received March 3, 2017; Accepted October 24, 2017 DOI: 10.3892/ol.2018.7735 Abstract. High levels of tumor-associated calcium signal but did not significantly affect p38 and JNK phosphoryla- transduction protein (TROP)-2 have been demonstrated to tion levels. Treatment with a specific ERK1/2 inhibitor be strongly associated with tumor necrosis factor (TNF)-α suppressed the TNF-α-induced upregulation of TROP-2 and levels in colon cancer. In the present study, the effect of the TNF-α-induced colon cancer cell migration and inva- TNF-α on the regulation of TROP-2 expression and its effect sion. In conclusion, the present results demonstrated that in colon cancer cell migration and invasion were investigated low concentrations of TNF-α significantly enhanced colon in vitro. TROP-2 protein levels were evaluated in HCT-116 cancer cell migration and invasion by upregulating TROP-2 human colon cancer cells cultured with various concentra- via the ERK1/2 signaling pathway. tions of TNF-α using western blot analysis. Changes in the migratory and invasive potential of the cells were evaluated Introduction using a wound healing and transwell assay, respectively. Then, TROP-2 expression was downregulated in cells by use Colon cancer is a common malignant tumor of the digestive of siRNA, and TROP‑2 knockdown was confirmed at the tract, from which morbidity and mortality have been increasing mRNA and protein level by reverse transcription-quantitative in recent years. -
Environmental Influences on Endothelial Gene Expression
ENDOTHELIAL CELL GENE EXPRESSION John Matthew Jeff Herbert Supervisors: Prof. Roy Bicknell and Dr. Victoria Heath PhD thesis University of Birmingham August 2012 University of Birmingham Research Archive e-theses repository This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder. ABSTRACT Tumour angiogenesis is a vital process in the pathology of tumour development and metastasis. Targeting markers of tumour endothelium provide a means of targeted destruction of a tumours oxygen and nutrient supply via destruction of tumour vasculature, which in turn ultimately leads to beneficial consequences to patients. Although current anti -angiogenic and vascular targeting strategies help patients, more potently in combination with chemo therapy, there is still a need for more tumour endothelial marker discoveries as current treatments have cardiovascular and other side effects. For the first time, the analyses of in-vivo biotinylation of an embryonic system is performed to obtain putative vascular targets. Also for the first time, deep sequencing is applied to freshly isolated tumour and normal endothelial cells from lung, colon and bladder tissues for the identification of pan-vascular-targets. Integration of the proteomic, deep sequencing, public cDNA libraries and microarrays, delivers 5,892 putative vascular targets to the science community. -
Angiopoietin/Tek Interactions Regulate MMP-9 Expression and Retinal Neovascularization
0023-6837/03/8311-1637$03.00/0 LABORATORY INVESTIGATION Vol. 83, No. 11, p. 1637, 2003 Copyright © 2003 by The United States and Canadian Academy of Pathology, Inc. Printed in U.S.A. Angiopoietin/Tek Interactions Regulate MMP-9 Expression and Retinal Neovascularization Arup Das, William Fanslow, Douglas Cerretti, Erin Warren, Nicholas Talarico, and Paul McGuire Department of Surgery (AD, PM), Division of Ophthalmology, Cell Biology and Physiology (AD, EW, NT, PM), University of New Mexico School of Medicine, and New Mexico Veterans Health Care System (AD), Albuquerque, New Mexico; and Cancer Pharmacology Amgen Washington (WF, DC), Seattle, Washington SUMMARY: The objective of the study was to determine the role of the angiopoietins in the regulation of gelatinase expression during angiogenesis, and whether inhibition of the angiopoietin/Tek interaction in vivo can suppress the extent of retinal neovascularization. Retinal microvascular endothelial cells were treated with angiopoietins and examined for the production of gelatinases. The effects of inhibiting angiopoietin binding to the Tie-2 receptor was studied in newborn mice with experimentally induced retinal neovascularization. Animals were treated with an ip injection of the Tie-2 antagonist, muTek delta Fc, while oxygen-exposed mice treated with similar concentrations of murine IgG were used as controls. The effect of muTek delta Fc on the gelatinase expression in the retina was examined by real-time RT-PCR analysis. The stimulation of cultured retinal endothelial cells with Ang-1 and -2 resulted in the increased expression of matrix metalloproteinase (MMP)-9. Ang-2 expression was up-regulated in experimental animals during the period of angiogenesis and was the greatest on Day 17 (the time of maximal angiogenic response). -
PDGFR-Β+ Fibroblasts Deteriorate Survival in Human Solid Tumors: a Meta-Analysis
www.aging-us.com AGING 2021, Vol. 13, No. 10 Research Paper PDGFR-β+ fibroblasts deteriorate survival in human solid tumors: a meta-analysis Guoming Hu1,*, Liming Huang1,*, Kefang zhong1, Liwei Meng1, Feng Xu1, Shimin Wang2, Tao Zhang3,& 1Department of General Surgery (Breast and Thyroid Surgery), Shaoxing People’s Hospital, Shaoxing Hospital, Zhejiang University School of Medicine, Zhejiang 312000, China 2Department of Nephrology, Shaoxing People’s Hospital, Shaoxing Hospital, Zhejiang University School of Medicine, Zhejiang 312000, China 3Department of General Surgery III, Affiliated Hospital of Shaoxing University, Zhejiang 312000, China *Equal contribution Correspondence to: Tao Zhang, Guoming Hu; email: [email protected], https://orcid.org/0000-0001-7533-4900; [email protected] Keywords: tumor-infiltrating PDGFR-β+ fibroblasts, worse prognosis, solid tumor, meta-analysis Received: January 11, 2021 Accepted: April 2, 2021 Published: May 3, 2021 Copyright: © 2021 Hu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Fibroblasts are a highly heterogeneous population in tumor microenvironment. PDGFR-β+ fibroblasts, a subpopulation of activated fibroblasts, have proven to correlate with cancer progression through multiple of mechanisms including inducing angiogenesis and immune evasion. However, the prognostic role of these cells in solid tumors is still not conclusive. Herein, we carried out a meta-analysis including 24 published studies with 6752 patients searched from PubMed, Embase and EBSCO to better comprehend the value of such subpopulation in prognosis prediction for solid tumors. -
Appendix Table A.2.3.1 Full Table of All Chicken Proteins and Human Orthologs Pool Accession Human Human Protein Human Product Cell Angios Log2( Endo Gene Comp
Appendix table A.2.3.1 Full table of all chicken proteins and human orthologs Pool Accession Human Human Protein Human Product Cell AngioS log2( Endo Gene comp. core FC) Specific CIKL F1NWM6 KDR NP_002244 kinase insert domain receptor (a type III receptor tyrosine M 94 4 kinase) CWT Q8AYD0 CDH5 NP_001786 cadherin 5, type 2 (vascular endothelium) M 90 8.45 specific CWT Q8AYD0 CDH5 NP_001786 cadherin 5, type 2 (vascular endothelium) M 90 8.45 specific CIKL F1P1Y9 CDH5 NP_001786 cadherin 5, type 2 (vascular endothelium) M 90 8.45 specific CIKL F1P1Y9 CDH5 NP_001786 cadherin 5, type 2 (vascular endothelium) M 90 8.45 specific CIKL F1N871 FLT4 NP_891555 fms-related tyrosine kinase 4 M 86 -1.71 CWT O73739 EDNRA NP_001948 endothelin receptor type A M 81 -8 CIKL O73739 EDNRA NP_001948 endothelin receptor type A M 81 -8 CWT Q4ADW2 PROCR NP_006395 protein C receptor, endothelial M 80 -0.36 CIKL Q4ADW2 PROCR NP_006395 protein C receptor, endothelial M 80 -0.36 CIKL F1NFQ9 TEK NP_000450 TEK tyrosine kinase, endothelial M 77 7.3 specific CWT Q9DGN6 ECE1 NP_001106819 endothelin converting enzyme 1 M 74 -0.31 CIKL Q9DGN6 ECE1 NP_001106819 endothelin converting enzyme 1 M 74 -0.31 CWT F1NIF0 CA9 NP_001207 carbonic anhydrase IX I 74 CIKL F1NIF0 CA9 NP_001207 carbonic anhydrase IX I 74 CWT E1BZU7 AOC3 NP_003725 amine oxidase, copper containing 3 (vascular adhesion protein M 70 1) CIKL E1BZU7 AOC3 NP_003725 amine oxidase, copper containing 3 (vascular adhesion protein M 70 1) CWT O93419 COL18A1 NP_569712 collagen, type XVIII, alpha 1 E 70 -2.13 CIKL O93419 -
HCC and Cancer Mutated Genes Summarized in the Literature Gene Symbol Gene Name References*
HCC and cancer mutated genes summarized in the literature Gene symbol Gene name References* A2M Alpha-2-macroglobulin (4) ABL1 c-abl oncogene 1, receptor tyrosine kinase (4,5,22) ACBD7 Acyl-Coenzyme A binding domain containing 7 (23) ACTL6A Actin-like 6A (4,5) ACTL6B Actin-like 6B (4) ACVR1B Activin A receptor, type IB (21,22) ACVR2A Activin A receptor, type IIA (4,21) ADAM10 ADAM metallopeptidase domain 10 (5) ADAMTS9 ADAM metallopeptidase with thrombospondin type 1 motif, 9 (4) ADCY2 Adenylate cyclase 2 (brain) (26) AJUBA Ajuba LIM protein (21) AKAP9 A kinase (PRKA) anchor protein (yotiao) 9 (4) Akt AKT serine/threonine kinase (28) AKT1 v-akt murine thymoma viral oncogene homolog 1 (5,21,22) AKT2 v-akt murine thymoma viral oncogene homolog 2 (4) ALB Albumin (4) ALK Anaplastic lymphoma receptor tyrosine kinase (22) AMPH Amphiphysin (24) ANK3 Ankyrin 3, node of Ranvier (ankyrin G) (4) ANKRD12 Ankyrin repeat domain 12 (4) ANO1 Anoctamin 1, calcium activated chloride channel (4) APC Adenomatous polyposis coli (4,5,21,22,25,28) APOB Apolipoprotein B [including Ag(x) antigen] (4) AR Androgen receptor (5,21-23) ARAP1 ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 1 (4) ARHGAP35 Rho GTPase activating protein 35 (21) ARID1A AT rich interactive domain 1A (SWI-like) (4,5,21,22,24,25,27,28) ARID1B AT rich interactive domain 1B (SWI1-like) (4,5,22) ARID2 AT rich interactive domain 2 (ARID, RFX-like) (4,5,22,24,25,27,28) ARID4A AT rich interactive domain 4A (RBP1-like) (28) ARID5B AT rich interactive domain 5B (MRF1-like) (21) ASPM Asp (abnormal -
The Evolving Relationship of Wound Healing and Tumor Stroma
The evolving relationship of wound healing and tumor stroma Deshka S. Foster, … , Michael T. Longaker, Jeffrey A. Norton JCI Insight. 2018;3(18):e99911. https://doi.org/10.1172/jci.insight.99911. Review The stroma in solid tumors contains a variety of cellular phenotypes and signaling pathways associated with wound healing, leading to the concept that a tumor behaves as a wound that does not heal. Similarities between tumors and healing wounds include fibroblast recruitment and activation, extracellular matrix (ECM) component deposition, infiltration of immune cells, neovascularization, and cellular lineage plasticity. However, unlike a wound that heals, the edges of a tumor are constantly expanding. Cell migration occurs both inward and outward as the tumor proliferates and invades adjacent tissues, often disregarding organ boundaries. The focus of our review is cancer associated fibroblast (CAF) cellular heterogeneity and plasticity and the acellular matrix components that accompany these cells. We explore how similarities and differences between healing wounds and tumor stroma continue to evolve as research progresses, shedding light on possible therapeutic targets that can result in innovative stromal-based treatments for cancer. Find the latest version: https://jci.me/99911/pdf REVIEW The evolving relationship of wound healing and tumor stroma Deshka S. Foster,1,2 R. Ellen Jones,1 Ryan C. Ransom,1 Michael T. Longaker,1,2 and Jeffrey A. Norton1,2 1Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Division of Plastic and Reconstructive Surgery, and 2Department of Surgery, Stanford University School of Medicine, Stanford, California, USA. The stroma in solid tumors contains a variety of cellular phenotypes and signaling pathways associated with wound healing, leading to the concept that a tumor behaves as a wound that does not heal. -
Supplementary Table 1. in Vitro Side Effect Profiling Study for LDN/OSU-0212320. Neurotransmitter Related Steroids
Supplementary Table 1. In vitro side effect profiling study for LDN/OSU-0212320. Percent Inhibition Receptor 10 µM Neurotransmitter Related Adenosine, Non-selective 7.29% Adrenergic, Alpha 1, Non-selective 24.98% Adrenergic, Alpha 2, Non-selective 27.18% Adrenergic, Beta, Non-selective -20.94% Dopamine Transporter 8.69% Dopamine, D1 (h) 8.48% Dopamine, D2s (h) 4.06% GABA A, Agonist Site -16.15% GABA A, BDZ, alpha 1 site 12.73% GABA-B 13.60% Glutamate, AMPA Site (Ionotropic) 12.06% Glutamate, Kainate Site (Ionotropic) -1.03% Glutamate, NMDA Agonist Site (Ionotropic) 0.12% Glutamate, NMDA, Glycine (Stry-insens Site) 9.84% (Ionotropic) Glycine, Strychnine-sensitive 0.99% Histamine, H1 -5.54% Histamine, H2 16.54% Histamine, H3 4.80% Melatonin, Non-selective -5.54% Muscarinic, M1 (hr) -1.88% Muscarinic, M2 (h) 0.82% Muscarinic, Non-selective, Central 29.04% Muscarinic, Non-selective, Peripheral 0.29% Nicotinic, Neuronal (-BnTx insensitive) 7.85% Norepinephrine Transporter 2.87% Opioid, Non-selective -0.09% Opioid, Orphanin, ORL1 (h) 11.55% Serotonin Transporter -3.02% Serotonin, Non-selective 26.33% Sigma, Non-Selective 10.19% Steroids Estrogen 11.16% 1 Percent Inhibition Receptor 10 µM Testosterone (cytosolic) (h) 12.50% Ion Channels Calcium Channel, Type L (Dihydropyridine Site) 43.18% Calcium Channel, Type N 4.15% Potassium Channel, ATP-Sensitive -4.05% Potassium Channel, Ca2+ Act., VI 17.80% Potassium Channel, I(Kr) (hERG) (h) -6.44% Sodium, Site 2 -0.39% Second Messengers Nitric Oxide, NOS (Neuronal-Binding) -17.09% Prostaglandins Leukotriene, -
Current Strategies to Target Tumor-Associated-Macrophages to Improve Anti-Tumor Immune Responses
cells Review Current Strategies to Target Tumor-Associated-Macrophages to Improve Anti-Tumor Immune Responses Clément Anfray 1, Aldo Ummarino 2 , Fernando Torres Andón 1,3 and Paola Allavena 1,* 1 IRCCS Istituto Clinico Humanitas, Via A. Manzoni 56, 20089 Rozzano, Milan, Italy; [email protected] (C.A.); [email protected] (F.T.A.) 2 Humanitas University, Via Rita Levi Montalcini 4, 20090 Pieve Emanuele, Milan, Italy; [email protected] 3 Center for Research in Molecular Medicine & Chronic Diseases (CIMUS), Universidade, de Santiago de Compostela, Campus Vida, 15706 Santiago de Compostela, Spain * Correspondence: [email protected] Received: 4 December 2019; Accepted: 20 December 2019; Published: 23 December 2019 Abstract: Established evidence demonstrates that tumor-infiltrating myeloid cells promote rather than stop-cancer progression. Tumor-associated macrophages (TAMs) are abundantly present at tumor sites, and here they support cancer proliferation and distant spreading, as well as contribute to an immune-suppressive milieu. Their pro-tumor activities hamper the response of cancer patients to conventional therapies, such as chemotherapy or radiotherapy, and also to immunotherapies based on checkpoint inhibition. Active research frontlines of the last years have investigated novel therapeutic strategies aimed at depleting TAMs and/or at reprogramming their tumor-promoting effects, with the goal of re-establishing a favorable immunological anti-tumor response within the tumor tissue. In recent years, numerous clinical trials have included pharmacological strategies to target TAMs alone or in combination with other therapies. This review summarizes the past and current knowledge available on experimental tumor models and human clinical studies targeting TAMs for cancer treatment. -
Characterization of a Stem Cell Population Derived from Human Peripheral Blood and Its Therapeutic Potential in Brain Tumors
Characterization of a stem cell population derived from human peripheral blood and its therapeutic potential in brain tumors A thesis submitted to Imperial College London for the degree of Doctor of Philosophy in the Faculty of Medicine Catherine T. Flores, BSc, MSc Department of Haematology, Faculty of Medicine, Division of Investigative Science, Imperial College London, Hammersmith Hospital, London Supervisors Professor Myrtle Y Gordon Department of Haematology Faculty of Medicine Imperial College London Hammersmith Campus London W120NN Dr Deanna L Taylor Department of Neurosciences Faculty of Medicine Imperial College London Hammersmith Campus London W120NN 1 Abstract Adherent CD34 + cells are a stem cell enriched population with a high frequency of primitive stem cells that are genetically primed to differentiate into tissue-specific lineages. These cells make up the adherent CD34 + cells in peripheral blood which are the focus of this study. The first aim of this study was to transcriptionally characterize adherent CD34+ cells relative to non- adherent CD34 + cells using a whole human genome Affymetrix U133 plus 2 array. The subsequent analysis demonstrated transcriptional differences in genes which are involved in quiescence, cell cycle, homing and adhesion, which are likely to be relevant to the suitability of adherent CD34 + cells for clinical application. To verify the microarray analysis, a selection of representative transcripts was chosen and their relative expression was compared using real-time qPCR. To analyze further the stem cell characteristics of adherent CD34 + cells, the DNA replication timing kinetics of pluripotency-associated genes in bone marrow-derived adherent CD34+ cells, non-adherent CD34+ cells, and foetal mesenchymal stem cells were conducted and compared to those of embryonic stem (ES) cells. -
IL-10 Responsiveness and Anti-TNF Therapy in Inflammatory Bowel Disease
https://www.scientificarchives.com/journal/journal-of-cellular-immunology Journal of Cellular Immunology Short Communication IL-10 Responsiveness and Anti-TNF Therapy in Inflammatory Bowel Disease Felicia M. Bloemendaal1,2, Charlotte P. Peters1, Anje A. te Velde1,2, Cyriel Y. Ponsioen1, Gijs R. van den Brink1,2,3, Manon E. Wildenberg1,2#, Pim J. Koelink2#* 1Department of Gastroenterology and Hepatology, University of Amsterdam, Amsterdam, the Netherlands 2Tytgat Institute for Liver and Intestinal Research, Amsterdam UMC, location AMC, AG&M Amsterdam, University of Amsterdam, Amsterdam, the Netherlands 3Current address: Roche Innovation Center Basel, F. Hoffmann-La Roche AG, Basel, Switzerland #Contributed equally *Correspondence should be addressed to Pim J. Koelink; [email protected] Received date: December 05, 2020, Accepted date: January 28, 2021 Copyright: © 2021 Bloemendaal FM, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Keywords: IBD, IL-10, Anti-TNF, Macrophages, developing IBD [6]. Colitis While initially it was assumed that IL-10 suppressed inflammatory responses by directly affecting T-cells [7], Macrophages, IL-10 and Anti-TNF Therapy in further experimental studies pointed out a pivotal role for IBD IL-10 signaling within the myeloid compartment as the absence of IL-10 Rα in intestinal macrophages resulted Inflammatory bowel disease (IBD) is a multifactorial in spontaneous colitis [8,9]. Therefore, IL-10 signaling disease in which both genetic and environmental factors within macrophages plays a central role in the regulation play an important role, although the precise cause remains of intestinal mucosal homeostasis. -
AUSTRALIAN PATENT OFFICE (11) Application No. AU 199875933 B2
(12) PATENT (11) Application No. AU 199875933 B2 (19) AUSTRALIAN PATENT OFFICE (10) Patent No. 742342 (54) Title Nucleic acid arrays (51)7 International Patent Classification(s) C12Q001/68 C07H 021/04 C07H 021/02 C12P 019/34 (21) Application No: 199875933 (22) Application Date: 1998.05.21 (87) WIPO No: WO98/53103 (30) Priority Data (31) Number (32) Date (33) Country 08/859998 1997.05.21 US 09/053375 1998.03.31 US (43) Publication Date : 1998.12.11 (43) Publication Journal Date : 1999.02.04 (44) Accepted Journal Date : 2001.12.20 (71) Applicant(s) Clontech Laboratories, Inc. (72) Inventor(s) Alex Chenchik; George Jokhadze; Robert Bibilashvilli (74) Agent/Attorney F.B. RICE and CO.,139 Rathdowne Street,CARLTON VIC 3053 (56) Related Art PROC NATL ACAD SCI USA 93,10614-9 ANCEL BIOCHEM 216,299-304 CRENE 156,207-13 OPI DAtE 11/12/98 APPLN. ID 75933/98 AOJP DATE 04/02/99 PCT NUMBER PCT/US98/10561 IIIIIIIUIIIIIIIIIIIIIIIIIIIII AU9875933 .PCT) (51) International Patent Classification 6 ; (11) International Publication Number: WO 98/53103 C12Q 1/68, C12P 19/34, C07H 2UO2, Al 21/04 (43) International Publication Date: 26 November 1998 (26.11.98) (21) International Application Number: PCT/US98/10561 (81) Designated States: AL, AM, AT, AU, AZ, BA, BB, BG, BR, BY, CA, CH, CN, CU, CZ, DE, DK, EE, ES, FI, GB, GE, (22) International Filing Date: 21 May 1998 (21.05.98) GH, GM, GW, HU, ID, IL, IS, JP, KE, KG, KP, KR, KZ, LC, LK, LR, LS, LT, LU, LV, MD, MG, MK, MN, MW, MX, NO, NZ, PL, PT, RO, RU, SD, SE, SG, SI, SK, SL, (30) Priority Data: TJ, TM, TR, TT, UA, UG, US, UZ, VN, YU, ZW, ARIPO 08/859,998 21 May 1997 (21.05.97) US patent (GH, GM, KE, LS, MW, SD, SZ, UG, ZW), Eurasian 09/053,375 31 March 1998 (31.03.98) US patent (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), European patent (AT, BE, CH, CY, DE, DK, ES, Fl, FR, GB, GR, IE, IT, LU, MC, NL, PT, SE), OAPI patent (BF, BJ, CF, (71) Applicant (for all designated States except US): CLONTECH CG, CI, CM, GA, GN, ML, MR, NE, SN, TD, TG).