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The JAK2/STAT5 signaling pathway as a potential therapeutic target in canine mastocytoma.


ABSTRACT: Mastocytoma are frequently diagnosed cutaneous neoplasms in dogs. In non-resectable mastocytoma patients, novel targeted drugs are often applied. The transcription factor STAT5 has been implicated in the survival of human neoplastic mast cells (MC). Our study evaluated the JAK2/STAT5 pathway as a novel target in canine mastocytoma.We employed inhibitors of JAK2 (R763, TG101348, AZD1480, ruxolitinib) and STAT5 (pimozide, piceatannol) and evaluated their effects on 2 mastocytoma cell lines, C2 and NI-1.Activated JAK2 and STAT5 were detected in both cell lines. The drugs applied were found to inhibit proliferation and survival in these cells with the following rank-order of potency: R763 > TG101348 > AZD1480 > pimozide > ruxolitinib > piceatannol. Moreover, synergistic anti-neoplastic effects were obtained by combining pimozide with KIT-targeting drugs (toceranib, masitinib, nilotinib, midostaurin) in NI-1 cells.The JAK2/STAT5 pathway is a novel potential target of therapy in canine mastocytoma.

SUBMITTER: Keller A 

PROVIDER: S-EPMC5824979 | biostudies-other | 2018 Mar

REPOSITORIES: biostudies-other

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The JAK2/STAT5 signaling pathway as a potential therapeutic target in canine mastocytoma.

Keller Alexandra A   Wingelhofer Bettina B   Peter Barbara B   Bauer Karin K   Berger Daniela D   Gamperl Susanne S   Reifinger Martin M   Cerny-Reiterer Sabine S   Moriggl Richard R   Willmann Michael M   Valent Peter P   Hadzijusufovic Emir E  

Veterinary and comparative oncology 20170411 1


<h4>Background</h4>Mastocytoma are frequently diagnosed cutaneous neoplasms in dogs. In non-resectable mastocytoma patients, novel targeted drugs are often applied. The transcription factor STAT5 has been implicated in the survival of human neoplastic mast cells (MC). Our study evaluated the JAK2/STAT5 pathway as a novel target in canine mastocytoma.<h4>Materials and methods</h4>We employed inhibitors of JAK2 (R763, TG101348, AZD1480, ruxolitinib) and STAT5 (pimozide, piceatannol) and evaluated  ...[more]

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