{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T06:33:58Z","timestamp":1791182038663,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2012,5,15]],"date-time":"2012-05-15T00:00:00Z","timestamp":1337040000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2012,7]]},"abstract":"Abstract<\/jats:title>Background<\/jats:title>Advanced mast cell (MC<\/jats:styled-content>) disorders are characterized by uncontrolled growth of neoplastic MC<\/jats:styled-content> in various organs, mediator\u2010related symptoms, and a poor prognosis. Kit<\/jats:italic><\/jats:styled-content> mutations supposedly contribute to abnormal growth and drug resistance in these patients.<\/jats:p><\/jats:sec>Methods<\/jats:title>We established a novel canine mastocytoma cell line, NI<\/jats:styled-content>\u20101, from a patient suffering from MC<\/jats:styled-content> leukemia.<\/jats:p><\/jats:sec>Results<\/jats:title>NI<\/jats:styled-content>\u20101 cells were found to form mastocytoma lesions in NOD<\/jats:styled-content>\/SCID IL<\/jats:styled-content>\u20102R<\/jats:styled-content>gammanull<\/jats:sup> mice and to harbor several homozygous Kit<\/jats:italic><\/jats:styled-content> mutations, including missense mutations at nucleotides 107(C<\/jats:styled-content>\u2192T<\/jats:styled-content>) and 1187(A<\/jats:styled-content>\u2192G<\/jats:styled-content>), a 12\u2010bp duplication (nucleotide 1263), and a 12\u2010bp deletion (nucleotide 1550). NI<\/jats:styled-content>\u20101 cells expressed several MC<\/jats:styled-content> differentiation antigens, including tryptase, K<\/jats:styled-content>it, and a functional I<\/jats:styled-content>gE<\/jats:styled-content> receptor. Compared to the C<\/jats:styled-content>2 mastocytoma cell line harboring a Kit<\/jats:italic><\/jats:styled-content> exon 11 mutation, NI<\/jats:styled-content>\u20101 cells were found to be less responsive against the K<\/jats:styled-content>it tyrosine kinase inhibitors (TKI<\/jats:styled-content>) masitinib and imatinib, but were even more sensitive against proliferation\u2010inhibitory effects of the mammalian target of rapamycin (mTOR<\/jats:styled-content>) blocker RAD<\/jats:styled-content>001 and PI<\/jats:styled-content>3\u2010kinase\/mTOR<\/jats:styled-content> blocker NVP<\/jats:styled-content>\u2010BEZ<\/jats:styled-content>235. The K<\/jats:styled-content>it\u2010targeting multikinase inhibitors PK<\/jats:styled-content>C412 and dasatinib were also found to override TKI<\/jats:styled-content> resistance in NI<\/jats:styled-content>\u20101 cells, and produced growth inhibition with reasonable IC<\/jats:styled-content>50<\/jats:sub> values (<0.1\u00a0\u03bcM).<\/jats:p><\/jats:sec>Conclusion<\/jats:title>NI<\/jats:styled-content>\u20101 may serve as a useful tool to investigate I<\/jats:styled-content>gE<\/jats:styled-content>\u2010dependent reactions and mechanisms of abnormal growth and drug resistance in neoplastic MC<\/jats:styled-content> in advanced mastocytosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1398-9995.2012.02833.x","type":"journal-article","created":{"date-parts":[[2012,5,15]],"date-time":"2012-05-15T12:05:20Z","timestamp":1337083520000},"page":"858-868","source":"Crossref","is-referenced-by-count":22,"title":["NI<\/scp>\u20101: a novel canine mastocytoma model for studying drug resistance and I<\/scp>gER<\/scp>\u2010dependent mast cell activation"],"prefix":"10.1111","volume":"67","author":[{"given":"E.","family":"Hadzijusufovic","sequence":"first","affiliation":[{"name":"Department for Companion Animals and Horses Clinic for Internal Medicine and Infectious Diseases University of Veterinary Medicine Vienna Vienna Austria"},{"name":"Division of Hematology & Hemostaseology Department of Internal Medicine I Medical University of Vienna Vienna Austria"},{"name":"Ludwig Boltzmann Cluster Oncology Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Peter","sequence":"additional","affiliation":[{"name":"Department for Companion Animals and Horses Clinic for Internal Medicine and Infectious Diseases University of Veterinary Medicine Vienna Vienna Austria"},{"name":"Division of Hematology & Hemostaseology Department of Internal Medicine I Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Herrmann","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Cluster Oncology Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"R\u00fclicke","sequence":"additional","affiliation":[{"name":"Institute of Laboratory Animal Science University of Veterinary Medicine Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Cerny\u2010Reiterer","sequence":"additional","affiliation":[{"name":"Division of Hematology & Hemostaseology Department of Internal Medicine I Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Schuch","sequence":"additional","affiliation":[{"name":"Institute of Immunology Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Kenner","sequence":"additional","affiliation":[{"name":"Clinical Institute of Pathology Medical University of Vienna Vienna Austria"},{"name":"Ludwig Boltzmann Institute for Cancer Research Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Thaiwong","sequence":"additional","affiliation":[{"name":"Comparative Medicine and Integrative Biology Program Michigan State University East Lansing MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Yuzbasiyan\u2010Gurkan","sequence":"additional","affiliation":[{"name":"Comparative Medicine and Integrative Biology Program Michigan State University East Lansing MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. 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