2018
Somatic inactivating PTPRJ mutations and dysregulated pathways identified in canine malignant melanoma by integrated comparative genomic analysis
Hendricks W, Zismann V, Sivaprakasam K, Legendre C, Poorman K, Tembe W, Perdigones N, Kiefer J, Liang W, DeLuca V, Stark M, Ruhe A, Froman R, Duesbery N, Washington M, Aldrich J, Neff M, Huentelman M, Hayward N, Brown K, Thamm D, Post G, Khanna C, Davis B, Breen M, Sekulic A, Trent J. Somatic inactivating PTPRJ mutations and dysregulated pathways identified in canine malignant melanoma by integrated comparative genomic analysis. PLOS Genetics 2018, 14: e1007589. PMID: 30188888, PMCID: PMC6126841, DOI: 10.1371/journal.pgen.1007589.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell CycleCell ProliferationComparative Genomic HybridizationDNA Mutational AnalysisDog DiseasesDogsFemaleMaleMelanomaMutationProto-Oncogene Proteins B-rafProto-Oncogene Proteins p21(ras)Receptor-Like Protein Tyrosine Phosphatases, Class 3Signal TransductionSkin NeoplasmsTissue Array AnalysisConceptsLow point mutation ratePowerful comparative modelComparative genomic analysisCell cycle controlPoint mutation rateSingle nucleotide polymorphism arrayNucleotide polymorphism arrayWhole-genome sequencingArray comparative genomic hybridizationHuman melanomaComparative genomic hybridizationGenomic analysisRNA sequencingCycle controlGenome sequencingMutation rateGenomic landscapePolymorphism arrayCopy numberMutational landscapeMutational signaturesGenomic hybridizationRecurrent alterationsMulti-platform analysisMutations
2017
KTN0158, a Humanized Anti-KIT Monoclonal Antibody, Demonstrates Biologic Activity against both Normal and Malignant Canine Mast Cells
London CA, Gardner HL, Rippy S, Post G, La Perle K, Crew L, Lopresti-Morrow L, Garton AJ, McMahon G, LaVallee TM, Gedrich R. KTN0158, a Humanized Anti-KIT Monoclonal Antibody, Demonstrates Biologic Activity against both Normal and Malignant Canine Mast Cells. Clinical Cancer Research 2017, 23: 2565-2574. PMID: 27815356, PMCID: PMC5418113, DOI: 10.1158/1078-0432.ccr-16-2152.Peer-Reviewed Original ResearchConceptsMast cell tumorsSpontaneous mast cell tumoursMast cell numbersMast cell degranulationCutaneous mast cell numberKIT phosphorylationCell degranulationOpen-label clinical studyBiochemical adverse eventsAcceptable safety profileMetastatic lymph nodesPharmacokinetics/pharmacodynamics profileFuture clinical evaluationClin Cancer ResCell numberDose-dependent mannerObjective responseAdverse eventsLymph nodesMCT patientsClinical effectsClinical toxicityClinical benefitHuman clinical applicationsSafety profile
2003
Phase I dose-escalating study of SU11654, a small molecule receptor tyrosine kinase inhibitor, in dogs with spontaneous malignancies.
London CA, Hannah AL, Zadovoskaya R, Chien MB, Kollias-Baker C, Rosenberg M, Downing S, Post G, Boucher J, Shenoy N, Mendel DB, McMahon G, Cherrington JM. Phase I dose-escalating study of SU11654, a small molecule receptor tyrosine kinase inhibitor, in dogs with spontaneous malignancies. Clinical Cancer Research 2003, 9: 2755-68. PMID: 12855656.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsDog DiseasesDogsDose-Response Relationship, DrugEnzyme InhibitorsFemaleIndolesInhibitory Concentration 50MaleModels, ChemicalMutationNeoplasmsProto-Oncogene Proteins c-kitPyrrolesReceptor Protein-Tyrosine KinasesReceptors, Vascular Endothelial Growth FactorTime FactorsTomography, X-Ray ComputedConceptsReceptor tyrosine kinase inhibitorsTyrosine kinase inhibitorsGrowth factor receptorKinase inhibitorsSpontaneous malignanciesSpontaneous tumorsSmall molecule receptor tyrosine kinase inhibitorPhase I dose-escalating studyDose-escalating studyMeasurable objective responseSimilarities of canineVascular endothelial growth factor receptorStandard treatment regimensFactor receptorPhase I trialEndothelial growth factor receptorOverall response rateSoft tissue sarcomasPlatelet-derived growth factor receptorMast cell tumorsVariety of cancersStable diseaseObjective responseOral therapyProgressive disease