student profile: Dr Laura Setyo


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Thesis work

Thesis title: c-Met, c-KIT and FLK-1 Expression in transitional cell carcinoma of the urinary bladder: prognostic and therapeutic implications

Supervisors: Rachael GRAY , Mark KROCKENBERGER

Thesis abstract:

Invasive transitional cell carcinoma (TCC) is the most common form of urinary bladder cancer[1] and most dogs ultimately die of the disease.
Because canine TCC shares many characteristics with human TCC, canine TCC is believed to be a an appropriate model.[2] A substantive comparative study on tumorigenic molecules expressed by canine and human TCC is anticipated as an important development toward understanding the mechanism.[3]
Tyrosine kinases are proteins that phosphorylate other proteins on tyrosine residues. Evidence suggests that in both human and veterinary patients, tyrosine kinases are often abnormally activated in malignant tumours.[4, 5] Examples of receptor tyrosine kinases include Kit, Met and VEGFR2, all of which are known to be dysregulated in particular forms of cancer.[6, 7] Toceranib phosphate (Palladia®; Pfizer Animal Health, Madison, NJ, USA) is an oral oxindole receptor tyrosine kinase inhibitor that blocks the activity of VEGFR2, PDGFRα,/β, FLT-3, KIT and CSFR1.[11]
By comparing expression of Flk-1, c-MET and c-KIT in canine TCC with pathological and clinical outcomes, the feasibility of using protein expression as diagnostic and clinical markers for predicting prognosis of canine TCC was investigated retrospectively.

References
1. Mutsaers, A.J., W.R. Widmer, and D.W. Knapp, Canine transitional cell carcinoma. J Vet Intern Med, 2003. 17(2): p. 136-44.
2. Knapp, D.W., et al., Urinary bladder cancer in dogs, a naturally occurring model for cancer biology and drug development. Ilar j, 2014. 55(1): p. 100-18.
3. Hanazono, K., et al., Epidermal growth factor receptor expression in canine transitional cell carcinoma. J Vet Med Sci, 2015. 77(1): p. 1-6.
4. Shchemelinin, I., L. Sefc, and E. Necas, Protein kinases, their function and implication in cancer and other diseases. Folia Biol (Praha), 2006. 52(3): p. 81-100.
5. London, C.A., Tyrosine Kinase Inhibitors in Veterinary Medicine. Topics in Companion Animal Medicine, 2009. 24(3): p. 106-112.
6. Cheng, H.L., et al., Co-expression of RON and MET is a prognostic indicator for patients with transitional-cell carcinoma of the bladder. Br J Cancer, 2005. 92(10): p. 1906-14.
7. Cheng, H.L., et al., Overexpression of c-met as a prognostic indicator for transitional cell carcinoma of the urinary bladder: a comparison with p53 nuclear accumulation. J Clin Oncol, 2002. 20(6): p. 1544-50.
8. Fieten, H., et al., Expression of hepatocyte growth factor and the proto-oncogenic receptor c-Met in canine osteosarcoma. Vet Pathol, 2009. 46(5): p. 869-77.
9. Liao, A.T., et al., A novel small molecule Met inhibitor, PF2362376, exhibits biological activity against osteosarcoma. Vet Comp Oncol, 2007. 5(3): p. 177-96.
10. Liao, A.T., M. McMahon, and C. London, Characterization, expression and function of c-Met in canine spontaneous cancers. Vet Comp Oncol, 2005. 3(2): p. 61-72.
11. Urie, B.K., et al., Evaluation of expression and function of vascular endothelial growth factor receptor 2, platelet derived growth factor receptors-alpha and -beta, KIT, and RET in canine apocrine gland anal sac adenocarcinoma and thyroid carcinoma. BMC Veterinary Research, 2012. 8(1): p. 67.

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