Ontology type: schema:ScholarlyArticle Open Access: True
2015-12
AUTHORSFadzai Chinyengetere, David J. Sekula, Yun Lu, Andrew J. Giustini, Aarti Sanglikar, Masanori Kawakami, Tian Ma, Sandra S. Burkett, Burton L. Eisenberg, Wendy A. Wells, Paul J. Hoopes, Elizabeth G. Demicco, Alexander J Lazar, Keila E. Torres, Vincent Memoli, Sarah J. Freemantle, Ethan Dmitrovsky
ABSTRACTBACKGROUND: USP18 (ubiquitin-specific protease 18) removes ubiquitin-like modifier interferon stimulated gene 15 (ISG15) from conjugated proteins. USP18 null mice in a FVB/N background develop tumors as early as 2 months of age. These tumors are leiomyosarcomas and thus represent a new murine model for this disease. METHODS: Heterozygous USP18 +/- FVB/N mice were bred to generate wild-type, heterozygous and homozygous cohorts. Tumors were characterized immunohistochemically and two cell lines were derived from independent tumors. Cell lines were karyotyped and their responses to restoration of USP18 activity assessed. Drug testing and tumorigenic assays were also performed. USP18 immunohistochemical staining in a large series of human leiomyosacomas was examined. RESULTS: USP18 -/- FVB/N mice spontaneously develop tumors predominantly on the back of the neck with most tumors evident between 6-12 months (80 % penetrance). Immunohistochemical characterization of the tumors confirmed they were leiomyosarcomas, which originate from smooth muscle. Restoration of USP18 activity in sarcoma-derived cell lines did not reduce anchorage dependent or independent growth or xenograft tumor formation demonstrating that these cells no longer require USP18 suppression for tumorigenesis. Karyotyping revealed that both tumor-derived cell lines were aneuploid with extra copies of chromosomes 3 and 15. Chromosome 15 contains the Myc locus and MYC is also amplified in human leiomyosarcomas. MYC protein levels were elevated in both murine leiomyosarcoma cell lines. Stabilized P53 protein was detected in a subset of these murine tumors, another feature of human leiomyosarcomas. Immunohistochemical analyses of USP18 in human leiomyosarcomas revealed a range of staining intensities with the highest USP18 expression in normal vascular smooth muscle. USP18 tissue array analysis of primary leiomyosarcomas from 89 patients with a clinical database revealed cases with reduced USP18 levels had a significantly decreased time to metastasis (P = 0.0441). CONCLUSIONS: USP18 null mice develop leiomyosarcoma recapitulating key features of clinical leiomyosarcomas and patients with reduced-USP18 tumor levels have an unfavorable outcome. USP18 null mice and the derived cell lines represent clinically-relevant models of leiomyosarcoma and can provide insights into both leiomyosarcoma biology and therapy. More... »
PAGES886
http://scigraph.springernature.com/pub.10.1186/s12885-015-1883-8
DOIhttp://dx.doi.org/10.1186/s12885-015-1883-8
DIMENSIONShttps://app.dimensions.ai/details/publication/pub.1013611698
PUBMEDhttps://www.ncbi.nlm.nih.gov/pubmed/26555296
JSON-LD is the canonical representation for SciGraph data.
TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT
[
{
"@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json",
"about": [
{
"id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1112",
"inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/",
"name": "Oncology and Carcinogenesis",
"type": "DefinedTerm"
},
{
"id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11",
"inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/",
"name": "Medical and Health Sciences",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Animals",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Carcinogenesis",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Disease Models, Animal",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Female",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Gene Expression Regulation, Neoplastic",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Humans",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Leiomyosarcoma",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Mice",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Mice, Knockout",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Neoplasm Metastasis",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Tumor Suppressor Protein p53",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Ubiquitin Thiolesterase",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Uterine Neoplasms",
"type": "DefinedTerm"
}
],
"author": [
{
"affiliation": {
"alternateName": "Dartmouth\u2013Hitchcock Medical Center",
"id": "https://www.grid.ac/institutes/grid.413480.a",
"name": [
"Department of Pharmacology and Toxicology, Dartmouth, Hanover, NH, USA",
"Geisel School of Medicine, Dartmouth, Hanover, NH, USA",
"Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA"
],
"type": "Organization"
},
"familyName": "Chinyengetere",
"givenName": "Fadzai",
"id": "sg:person.0655652004.41",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0655652004.41"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Dartmouth\u2013Hitchcock Medical Center",
"id": "https://www.grid.ac/institutes/grid.413480.a",
"name": [
"Department of Pharmacology and Toxicology, Dartmouth, Hanover, NH, USA",
"Geisel School of Medicine, Dartmouth, Hanover, NH, USA",
"Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA"
],
"type": "Organization"
},
"familyName": "Sekula",
"givenName": "David J.",
"id": "sg:person.01366335121.38",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01366335121.38"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Dartmouth\u2013Hitchcock Medical Center",
"id": "https://www.grid.ac/institutes/grid.413480.a",
"name": [
"Department of Pharmacology and Toxicology, Dartmouth, Hanover, NH, USA",
"Geisel School of Medicine, Dartmouth, Hanover, NH, USA",
"Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA"
],
"type": "Organization"
},
"familyName": "Lu",
"givenName": "Yun",
"id": "sg:person.01064337730.26",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01064337730.26"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Dartmouth College",
"id": "https://www.grid.ac/institutes/grid.254880.3",
"name": [
"Geisel School of Medicine, Dartmouth, Hanover, NH, USA",
"Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA",
"Thayer School of Engineering, Dartmouth College, Hanover, NH, USA"
],
"type": "Organization"
},
"familyName": "Giustini",
"givenName": "Andrew J.",
"id": "sg:person.01356422125.17",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01356422125.17"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Dartmouth\u2013Hitchcock Medical Center",
"id": "https://www.grid.ac/institutes/grid.413480.a",
"name": [
"Norris Cotton Cancer Center, Lebanon, NH, USA"
],
"type": "Organization"
},
"familyName": "Sanglikar",
"givenName": "Aarti",
"id": "sg:person.01127301327.52",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01127301327.52"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Dartmouth\u2013Hitchcock Medical Center",
"id": "https://www.grid.ac/institutes/grid.413480.a",
"name": [
"Department of Pharmacology and Toxicology, Dartmouth, Hanover, NH, USA",
"Geisel School of Medicine, Dartmouth, Hanover, NH, USA",
"Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA"
],
"type": "Organization"
},
"familyName": "Kawakami",
"givenName": "Masanori",
"id": "sg:person.01170472433.11",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01170472433.11"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Dartmouth\u2013Hitchcock Medical Center",
"id": "https://www.grid.ac/institutes/grid.413480.a",
"name": [
"Department of Pharmacology and Toxicology, Dartmouth, Hanover, NH, USA",
"Geisel School of Medicine, Dartmouth, Hanover, NH, USA",
"Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA"
],
"type": "Organization"
},
"familyName": "Ma",
"givenName": "Tian",
"id": "sg:person.01177331565.50",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01177331565.50"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "National Cancer Institute",
"id": "https://www.grid.ac/institutes/grid.48336.3a",
"name": [
"Comparative Molecular Cytogenetics Core, Mouse Cancer Genetics Program, National Cancer Institute, Frederick, MD, USA"
],
"type": "Organization"
},
"familyName": "Burkett",
"givenName": "Sandra S.",
"id": "sg:person.0725563137.75",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0725563137.75"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Dartmouth\u2013Hitchcock Medical Center",
"id": "https://www.grid.ac/institutes/grid.413480.a",
"name": [
"Department of Surgery, Dartmouth, Hanover, NH, USA",
"Norris Cotton Cancer Center, Lebanon, NH, USA",
"Geisel School of Medicine, Dartmouth, Hanover, NH, USA",
"Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA"
],
"type": "Organization"
},
"familyName": "Eisenberg",
"givenName": "Burton L.",
"id": "sg:person.01255365721.64",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01255365721.64"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Dartmouth\u2013Hitchcock Medical Center",
"id": "https://www.grid.ac/institutes/grid.413480.a",
"name": [
"Department of Pathology, Dartmouth, Hanover, NH, USA",
"Norris Cotton Cancer Center, Lebanon, NH, USA",
"Geisel School of Medicine, Dartmouth, Hanover, NH, USA",
"Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA"
],
"type": "Organization"
},
"familyName": "Wells",
"givenName": "Wendy A.",
"id": "sg:person.07710316737.56",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.07710316737.56"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Dartmouth College",
"id": "https://www.grid.ac/institutes/grid.254880.3",
"name": [
"Department of Surgery, Dartmouth, Hanover, NH, USA",
"Norris Cotton Cancer Center, Lebanon, NH, USA",
"Geisel School of Medicine, Dartmouth, Hanover, NH, USA",
"Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA",
"Thayer School of Engineering, Dartmouth College, Hanover, NH, USA"
],
"type": "Organization"
},
"familyName": "Hoopes",
"givenName": "Paul J.",
"id": "sg:person.01334022143.81",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01334022143.81"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Mount Sinai Hospital",
"id": "https://www.grid.ac/institutes/grid.416167.3",
"name": [
"Department of Pathology, The Mount Sinai Hospital, New York, NY, USA"
],
"type": "Organization"
},
"familyName": "Demicco",
"givenName": "Elizabeth G.",
"id": "sg:person.0751521705.20",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0751521705.20"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "The University of Texas MD Anderson Cancer Center",
"id": "https://www.grid.ac/institutes/grid.240145.6",
"name": [
"Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA",
"Sarcoma Research Center, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"
],
"type": "Organization"
},
"familyName": "Lazar",
"givenName": "Alexander J",
"id": "sg:person.010255222337.53",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010255222337.53"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "The University of Texas MD Anderson Cancer Center",
"id": "https://www.grid.ac/institutes/grid.240145.6",
"name": [
"Sarcoma Research Center, The University of Texas MD Anderson Cancer Center, Houston, TX, USA",
"Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"
],
"type": "Organization"
},
"familyName": "Torres",
"givenName": "Keila E.",
"id": "sg:person.01017635105.71",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01017635105.71"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Dartmouth\u2013Hitchcock Medical Center",
"id": "https://www.grid.ac/institutes/grid.413480.a",
"name": [
"Department of Pathology, Dartmouth, Hanover, NH, USA",
"Norris Cotton Cancer Center, Lebanon, NH, USA",
"Geisel School of Medicine, Dartmouth, Hanover, NH, USA",
"Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA"
],
"type": "Organization"
},
"familyName": "Memoli",
"givenName": "Vincent",
"id": "sg:person.01153312054.97",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01153312054.97"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Dartmouth\u2013Hitchcock Medical Center",
"id": "https://www.grid.ac/institutes/grid.413480.a",
"name": [
"Department of Pharmacology and Toxicology, Dartmouth, Hanover, NH, USA",
"Geisel School of Medicine, Dartmouth, Hanover, NH, USA",
"Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA"
],
"type": "Organization"
},
"familyName": "Freemantle",
"givenName": "Sarah J.",
"id": "sg:person.01201045354.53",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01201045354.53"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Dartmouth\u2013Hitchcock Medical Center",
"id": "https://www.grid.ac/institutes/grid.413480.a",
"name": [
"Department of Pharmacology and Toxicology, Dartmouth, Hanover, NH, USA",
"Department of Medicine, Dartmouth, Hanover, NH, USA",
"Norris Cotton Cancer Center, Lebanon, NH, USA",
"Geisel School of Medicine, Dartmouth, Hanover, NH, USA",
"Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA",
"Present address: MD Anderson Cancer Center, 77030-4009, Houston, TX, USA"
],
"type": "Organization"
},
"familyName": "Dmitrovsky",
"givenName": "Ethan",
"id": "sg:person.01217700533.52",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01217700533.52"
],
"type": "Person"
}
],
"citation": [
{
"id": "https://doi.org/10.1158/1078-0432.ccr-10-2050",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1000820989"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/279523a0",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1002789585",
"https://doi.org/10.1038/279523a0"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/279523a0",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1002789585",
"https://doi.org/10.1038/279523a0"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1093/annonc/mdp415",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1003513538"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/s0165-4608(98)00119-8",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1003578353"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nrc1168",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1006265436",
"https://doi.org/10.1038/nrc1168"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nrc1168",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1006265436",
"https://doi.org/10.1038/nrc1168"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1097/00000478-199406000-00003",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1006390254"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1097/00000478-199406000-00003",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1006390254"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1111/his.12466",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1006684522"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/sj.onc.1203527",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1007050008",
"https://doi.org/10.1038/sj.onc.1203527"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/sj.onc.1203527",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1007050008",
"https://doi.org/10.1038/sj.onc.1203527"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1073/pnas.1412881112",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1010232587"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1161/01.cir.0000118462.22970.be",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1011008137"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/s0002-9440(10)63122-7",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1011637738"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1242/dmm.005223",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1011980815"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.4103/0976-9668.107316",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1013434176"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.4103/0976-9668.107316",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1013434176"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/j.cancergencyto.2006.11.011",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1014128458"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1200/jco.2006.09.7717",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1014449747"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1093/annonc/mds253",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1015073140"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/modpathol.2009.113",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1020674161",
"https://doi.org/10.1038/modpathol.2009.113"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/modpathol.2009.113",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1020674161",
"https://doi.org/10.1038/modpathol.2009.113"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1073/pnas.1121629109",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1024026172"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1371/journal.pone.0008534",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1026258032"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1074/jbc.m109078200",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1026258542"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nrc3087",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1026938278",
"https://doi.org/10.1038/nrc3087"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/356215a0",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1027559823",
"https://doi.org/10.1038/356215a0"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1158/1078-0432.ccr-08-1355",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1027850470"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1101/gad.1010202",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1031153745"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1158/0008-5472.can-10-1100",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1031925372"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1158/1535-7163.mct-12-0248",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1033810804"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1101/gad.1056303",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1037276160"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1002/emmm.201201864",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1037733506"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.4049/jimmunol.1000890",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1041772302"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nm1560",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1043717288",
"https://doi.org/10.1038/nm1560"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/j.yexcr.2012.12.021",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1045034850"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1006/geno.1994.1575",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1046056206"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nature13801",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1047285735",
"https://doi.org/10.1038/nature13801"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1002/1097-0142(20010515)91:10<1914::aid-cncr1214>3.0.co;2-3",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1048869679"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.2353/ajpath.2010.100104",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1048907716"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nrclinonc.2012.113",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1049357800",
"https://doi.org/10.1038/nrclinonc.2012.113"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1091/mbc.e08-08-0880",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1051073329"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1007/s00256-009-0855-y",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1051701635",
"https://doi.org/10.1007/s00256-009-0855-y"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/sj.bjc.6605198",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1052108984",
"https://doi.org/10.1038/sj.bjc.6605198"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/sj.bjc.6605198",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1052108984",
"https://doi.org/10.1038/sj.bjc.6605198"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1200/jco.2003.02.026",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1064203377"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1200/jco.1999.17.1.150",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1074511220"
],
"type": "CreativeWork"
},
{
"id": "https://app.dimensions.ai/details/publication/pub.1075298780",
"type": "CreativeWork"
},
{
"id": "https://app.dimensions.ai/details/publication/pub.1075969576",
"type": "CreativeWork"
},
{
"id": "https://app.dimensions.ai/details/publication/pub.1083005211",
"type": "CreativeWork"
}
],
"datePublished": "2015-12",
"datePublishedReg": "2015-12-01",
"description": "BACKGROUND: USP18 (ubiquitin-specific protease 18) removes ubiquitin-like modifier interferon stimulated gene 15 (ISG15) from conjugated proteins. USP18 null mice in a FVB/N background develop tumors as early as 2 months of age. These tumors are leiomyosarcomas and thus represent a new murine model for this disease.\nMETHODS: Heterozygous USP18 +/- FVB/N mice were bred to generate wild-type, heterozygous and homozygous cohorts. Tumors were characterized immunohistochemically and two cell lines were derived from independent tumors. Cell lines were karyotyped and their responses to restoration of USP18 activity assessed. Drug testing and tumorigenic assays were also performed. USP18 immunohistochemical staining in a large series of human leiomyosacomas was examined.\nRESULTS: USP18 -/- FVB/N mice spontaneously develop tumors predominantly on the back of the neck with most tumors evident between 6-12 months (80 % penetrance). Immunohistochemical characterization of the tumors confirmed they were leiomyosarcomas, which originate from smooth muscle. Restoration of USP18 activity in sarcoma-derived cell lines did not reduce anchorage dependent or independent growth or xenograft tumor formation demonstrating that these cells no longer require USP18 suppression for tumorigenesis. Karyotyping revealed that both tumor-derived cell lines were aneuploid with extra copies of chromosomes 3 and 15. Chromosome 15 contains the Myc locus and MYC is also amplified in human leiomyosarcomas. MYC protein levels were elevated in both murine leiomyosarcoma cell lines. Stabilized P53 protein was detected in a subset of these murine tumors, another feature of human leiomyosarcomas. Immunohistochemical analyses of USP18 in human leiomyosarcomas revealed a range of staining intensities with the highest USP18 expression in normal vascular smooth muscle. USP18 tissue array analysis of primary leiomyosarcomas from 89 patients with a clinical database revealed cases with reduced USP18 levels had a significantly decreased time to metastasis (P\u2009=\u20090.0441).\nCONCLUSIONS: USP18 null mice develop leiomyosarcoma recapitulating key features of clinical leiomyosarcomas and patients with reduced-USP18 tumor levels have an unfavorable outcome. USP18 null mice and the derived cell lines represent clinically-relevant models of leiomyosarcoma and can provide insights into both leiomyosarcoma biology and therapy.",
"genre": "research_article",
"id": "sg:pub.10.1186/s12885-015-1883-8",
"inLanguage": [
"en"
],
"isAccessibleForFree": true,
"isFundedItemOf": [
{
"id": "sg:grant.3933033",
"type": "MonetaryGrant"
},
{
"id": "sg:grant.2475039",
"type": "MonetaryGrant"
},
{
"id": "sg:grant.2411261",
"type": "MonetaryGrant"
},
{
"id": "sg:grant.2471849",
"type": "MonetaryGrant"
},
{
"id": "sg:grant.2438839",
"type": "MonetaryGrant"
}
],
"isPartOf": [
{
"id": "sg:journal.1024632",
"issn": [
"1471-2407"
],
"name": "BMC Cancer",
"type": "Periodical"
},
{
"issueNumber": "1",
"type": "PublicationIssue"
},
{
"type": "PublicationVolume",
"volumeNumber": "15"
}
],
"name": "Mice null for the deubiquitinase USP18 spontaneously develop leiomyosarcomas",
"pagination": "886",
"productId": [
{
"name": "readcube_id",
"type": "PropertyValue",
"value": [
"40d7d8ca452ae20a872c28267495fb23436398919f4339786e8deae0f8ef6322"
]
},
{
"name": "pubmed_id",
"type": "PropertyValue",
"value": [
"26555296"
]
},
{
"name": "nlm_unique_id",
"type": "PropertyValue",
"value": [
"100967800"
]
},
{
"name": "doi",
"type": "PropertyValue",
"value": [
"10.1186/s12885-015-1883-8"
]
},
{
"name": "dimensions_id",
"type": "PropertyValue",
"value": [
"pub.1013611698"
]
}
],
"sameAs": [
"https://doi.org/10.1186/s12885-015-1883-8",
"https://app.dimensions.ai/details/publication/pub.1013611698"
],
"sdDataset": "articles",
"sdDatePublished": "2019-04-10T22:31",
"sdLicense": "https://scigraph.springernature.com/explorer/license/",
"sdPublisher": {
"name": "Springer Nature - SN SciGraph project",
"type": "Organization"
},
"sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000001_0000000264/records_8690_00000511.jsonl",
"type": "ScholarlyArticle",
"url": "http://link.springer.com/10.1186%2Fs12885-015-1883-8"
}
]Download the RDF metadata as: json-ld nt turtle xml License info
JSON-LD is a popular format for linked data which is fully compatible with JSON.
curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1186/s12885-015-1883-8'
N-Triples is a line-based linked data format ideal for batch operations.
curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1186/s12885-015-1883-8'
Turtle is a human-readable linked data format.
curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1186/s12885-015-1883-8'
RDF/XML is a standard XML format for linked data.
curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1186/s12885-015-1883-8'
This table displays all metadata directly associated to this object as RDF triples.
407 TRIPLES
21 PREDICATES
86 URIs
34 LITERALS
22 BLANK NODES