Inhibition of Dll4 signalling inhibits tumour growth by deregulating angiogenesis
It is shown that Dll4-mediated Notch signalling has a unique role in regulating endothelial cell proliferation and differentiation, and is crucial during active vascularization, but less important for normal vessel maintenance.
Phase I dose-escalating study of SU11654, a small molecule receptor tyrosine kinase inhibitor, in dogs with spontaneous malignancies.
This study provides the first evidence that p.o. administered kinase inhibitors can exhibit activity against a variety of spontaneous malignancies in dogs, and it is likely that such agents will demonstrate comparable antineoplastic activity in people.
Prevalence and importance of internal tandem duplications in exons 11 and 12 of c-kit in mast cell tumors of dogs.
- S. Downing, May Chien, P. Kass, P. Moore, C. London
- Medicine, BiologyAmerican Journal of Veterinary Research
- 1 December 2002
Evidence is provided that ITDs in c-kit occur frequently in MCTs of dogs, providing an ideal naturally developing tumor in which to test the safety and efficacy of novel small-molecule kinase inhibitors such as imatinib mesylate.
Inhibition of constitutively active forms of mutant kit by multitargeted indolinone tyrosine kinase inhibitors.
3 indolinones (SU11652, SU11654, and SU11655) are effective RTK inhibitors capable of disrupting the function of all forms of mutant Kit and may be useful in the treatment of spontaneous cancers expressing Kit mutations.
Exon 15 BRAF mutations are uncommon in canine oral malignant melanomas
D canine oral malignant melanomas do not possess codon 599 BRAF mutations commonly identified in human cutaneous melanomas, and this finding supports the notion that melanomas arising from non-sun-exposed sites exhibit distinct mechanisms of molecular transformation.
Detection of c-kit Mutations in Canine Mast Cell Tumors using Fluorescent Polyacrylamide Gel Electrophoresis
- L. R. J. Cameron, R. Grahn, May Chien, L. Lyons, C. London
- BiologyJournal of Veterinary Diagnostic Investigation
- 1 March 2004
Fluorescent PAGE provides a more accurate, economical, and higher throughput method for the detection of c-kit mutations in canine MCTs.
Evaluation of dysregulation of the receptor tyrosine kinases Kit, Flt3, and Met in histiocytic sarcomas of dogs.
- R. Zavodovskaya, A. Liao, C. London
- Biology, MedicineAmerican Journal of Veterinary Research
- 31 March 2006
It is suggested that dysregulation of Kit/SCF, Flt3/Flt3L, and Met/HGF signaling pathways is unlikely to occur in histiocytic sarcomas of dogs and that inhibitors of the Kit, FlT3, and met pathways are unlikely to provide clinical benefit to dogs with histiocytes.
A Blueprint for Identifying Phenotypes and Drug Targets in Complex Disorders with Empirical Dynamics
PP2A Deficiency Enhances Carcinogenesis of Lgr5+ Intestinal Stem Cells Both in Organoids and In Vivo
A tumorigenesis model based on a combination of carcinogenesis and genetically engineered mouse models is developed and it is suggested that PP2A functions as a tumor suppressor in intestine carcinogenesis.
Use of kit internal tandem duplications to establish mast cell tumor clonality in 2 dogs.
- R. Zavodovskaya, May Chien, C. London
- Biology, MedicineJournal of Veterinary Internal Medicine
- 1 November 2004
It is demonstrated that similar to the situation in humans, specific somatic mutations identified in oncogenes found in canine neoplasms can be used to provide evidence of tumor clonality.