<i>In vitro</i> effects of the tyrosine kinase inhibitor, masitinib mesylate, on canine hemangiosarcoma cell lines

Lyles, Sarah E.; Milner, Rowan J.; Kow, Kelvin; Salute, Marc E.

doi:10.1111/j.1476-5829.2012.00335.x

Cited by 24 publications

(36 citation statements)

References 43 publications

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“…This is consistent with findings from an invitro study investigating canine hemangiosarcoma cells treated with masitinib, which reported a similar increased VEGF level in cell supernatant close to the IC 50 for masitinib, and concluded that this effect may serve as a surrogate biomarker for TKI activity in dogs [43]. For the POS, HMPOS, and COS31 cell lines that were not treated with masitinib, VEGF levels were 118, 961, and 1287 pg/ml, respectively.…”

Section: Discussionsupporting

confidence: 88%

Apoptotic effects of the tyrosine kinase inhibitor, masitinib mesylate, on canine osteosarcoma cells

et al. 2013

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Osteosarcoma (OSA) is the most common primary bone tumor in dogs and the guarded prognosis highlights the necessity to find new treatments. Masitinib mesylate is a highly selective tyrosine kinase inhibitor that predominantly targets c-Kit and PDGFR-α/β. This study evaluated the in-vitro activity of masitinib against three canine OSA cell lines after treatment with increasing concentrations of masitinib (0.1-50 µmol/l) at 24, 48, and 72 h. The IC50 values at 72 h for the three OSA cell lines (POS, HMPOS, and COS31) were determined to be 11.04, 7.09, and 9.74 µmol/l, respectively. In addition, increases in caspase-3/7 activity and transferase dUTP nick end labeling-positive cells indicated apoptotic cell death. Because increased levels of vascular endothelial growth factor are found in dogs with OSA, vascular endothelial growth factor in the supernatant was quantified. Overall, the study found that masitinib causes dose-time dependent OSA cell death in vitro through initiation of caspase-mediated apoptosis, which supports future OSA clinical trials.

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Section: Discussionsupporting

confidence: 88%

Apoptotic effects of the tyrosine kinase inhibitor, masitinib mesylate, on canine osteosarcoma cells

et al. 2013

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“…Multiple receptor tyrosine kinases are known to be expressed by HSA tumor cells including KIT, PDGFR, and VEGFR, although their contributions to tumor growth are not clear [17, 18, 20–23, 32]. The small molecule inhibitors imatinib, dasatinib, and masatinib have all shown activity against canine HSA cell lines in vitro, with evidence of direct effects on PDGFR family members [16, 19]. Furthermore, imatinib demonstrated activity against canine HSA mouse xenografts, supporting the role of PDGFR signaling on tumor biology in vitro [16].…”

Section: Discussionmentioning

confidence: 99%

“…Other cell signaling elements found to be expressed and activated include focal adhesion kinase (FAK), SRC, and several members of the mTOR pathway [24–26]. The small molecule masitinib which blocks function of KIT and PDGFR inhibited the proliferation and induce apoptosis in canine HSA cell lines in vitro, although drug concentrations necessary for this effect ranged from 8.5–10.6 uM [19]. This is higher than the Cmax achievable in healthy beagle dogs (1.3–1.5 uM) [27].…”

Section: Introductionmentioning

confidence: 99%

Maintenance therapy with toceranib following doxorubicin-based chemotherapy for canine splenic hemangiosarcoma

et al. 2015

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BackgroundSpenic hemangiosarcoma (HSA) in dogs treated with surgery alone is associated with short survival times, and the addition of doxorubicin (DOX) chemotherapy only modestly improves outcome. The purpose of this study was to evaluate the impact of toceranib administration on progression free survival in dogs with stage I or II HSA following splenectomy and single agent DOX chemotherapy. We hypothesized that dogs with splenic HSA treated with adjuvant DOX followed by toceranib would have prolonged disease-free interval (DFI) and overall survival time (OS) when compared to historical dogs treated with DOX-based chemotherapy alone.ResultsDogs with stage I or II splenic HSA were administered 5 cycles of single-agent DOX every 2 weeks beginning within 14 days of splenectomy. Dogs were restaged 2 weeks after completing DOX, and those without evidence of metastatic disease began toceranib therapy at 3.25 mg/kg every other day. Forty-three dogs were enrolled in this clinical trial. Seven dogs had evidence of metastatic disease either before or at re-staging, and an additional 3 dogs were found to have metastatic disease within 1 week of toceranib administration. Therefore 31 dogs went on to receive toceranib following completion of doxorubicin treatment. Twenty-five dogs that received toceranib developed metastatic disease. The median disease free interval for all dogs enrolled in this study (n = 43) was 138 days, and the median disease free interval for those dogs that went on to receive toceranib (n = 31) was 161 days. The median survival time for all dogs enrolled in this study was 169 days, and the median survival time for those dogs that went on to receive toceranib was 172 days.ConclusionsThe use of toceranib following DOX chemotherapy does not improve either disease free interval or overall survival in dogs with stage I or II HSA.

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“…In one study, dogs with hemangiosarcoma ( n = 17) were significantly more likely to have detectable concentrations of plasma VEGF compared to healthy dogs ( n = 17) [119], although the same group were not able to demonstrate a marked difference in VEGF concentration between body cavity effusions associated with malignant versus nonmalignant diseases [120]. VEGF is a target for some of the newly licensed tyrosine kinase inhibitors including masitinib mesylate (Masivet—AB Science) and it has recently been shown that masitinib causes a dose-dependent-cell death in canine haemangiosarcoma cell lines [121]—further implicating a role for VEGF in canine haemangiosarcoma.…”

Section: Hemangiosarcomamentioning

confidence: 99%

Breed-Predispositions to Cancer in Pedigree Dogs

Dobson

2013

ISRN Veterinary Science

252

278

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Cancer is a common problem in dogs and although all breeds of dog and crossbred dogs may be affected, it is notable that some breeds of pedigree dogs appear to be at increased risk of certain types of cancer suggesting underlying genetic predisposition to cancer susceptibility. Although the aetiology of most cancers is likely to be multifactorial, the limited genetic diversity seen in purebred dogs facilitates genetic linkage or association studies on relatively small populations as compared to humans, and by using newly developed resources, genome-wide association studies in dog breeds are proving to be a powerful tool for unravelling complex disorders. This paper will review the literature on canine breed susceptibility to histiocytic sarcoma, osteosarcoma, haemangiosarcoma, mast cell tumours, lymphoma, melanoma, and mammary tumours including the recent advances in knowledge through molecular genetic, cytogenetic, and genome wide association studies.

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In vitro effects of the tyrosine kinase inhibitor, masitinib mesylate, on canine hemangiosarcoma cell lines

Cited by 24 publications

References 43 publications

Apoptotic effects of the tyrosine kinase inhibitor, masitinib mesylate, on canine osteosarcoma cells

Apoptotic effects of the tyrosine kinase inhibitor, masitinib mesylate, on canine osteosarcoma cells

Maintenance therapy with toceranib following doxorubicin-based chemotherapy for canine splenic hemangiosarcoma

Breed-Predispositions to Cancer in Pedigree Dogs

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