60 LEARNING CURVE / Cancer Treatment
with self-renewal and survival. Much work remains to be completed. It is apparent that some or many properties of hemangiosarcoma are dependent on interactions between tumor cells and their local microenvironment. These interactions probably depend
on the microanatomy of the niche and the capability of the cells to alter the niche by recruitment or reprogramming of local stromal cells. Local or systemic microangiopathy may precede the dis- ease, but it also may be a consequence of the vascular disruption it creates. Plate- lets and platelet-derived factors, inflam- mation, and hypoxia are probably key drivers of the disease. Our ongoing studies include develop-
ment of innovative “home-grown” treat- ment modalities (Schappa et al. 2013) as well as genetic manipulation of tumors to highlight potential interventions that can be used to attack their environmen- tal niche and improve outcomes for dogs with this dreadful disease. n
References
1. Andersen NJ, Froman RE, Kitchell BE, et al. Clinical and molecular biology of angiosarcoma. In Derbel F, ed., Soft tissue tumors. New York: InTech, 2011, 149–174.
2. Appleby EC, Hayward AH, Douce G. German shepherds and splenic tumors. Vet Rec 1978;102:449.
3. Bergman PJ. Anticancer vaccines. Vet Clin N Am Small Anim Pract 2007;37:1111–1119;vi-ii.
4. Chao MP, Alizadeh AA, Tang C, et al. Anti-CD47 antibody synergizes with rituximab to promote phagocytosis and eradicate non-Hodgkin lymphoma. Cell 2010;142:699–713.
5. Clifford CA, Mackin AJ, Henry CJ. Treatment of canine hemangiosarcoma: 2000 and beyond. J Vet Intern Med 2000;14:479–485.
6. Dickerson EB, Thomas R, Fosmire SP, et al. Mutations of phosphatase and tensin homolog deleted from chromosome 10 in canine hemangiosarcoma. Vet Pathol 2005;42:618–632.
7. Fosmire SP, Dickerson EB, Scott AM, et al. Canine malignant hemangiosarcoma as a model of primitive angiogenic endothelium. Lab Invest 2004;84:562–572.
8. Frantz AM, Sarver AL, Ito D, et al. Molecular profiling reveals prognostically significant subtypes of canine lymphoma. Vet Pathol 2013; in press.
9. Lamerato-Kozicki AR, Helm KM, Jubala CM, et al. Canine hemangiosarcoma originates from hematopoietic precursors with potential for endothelial differentiation.
Trends magazine, April 2013
Exp Hematol 2006;34:870–878.
10. London CA, Malpas PB, Wood-Follis SL, et al. Multi- center, placebo-controlled, double-blind, randomized study of oral toceranib phosphate (SU11654), a receptor tyrosine kinase inhibitor, for the treatment of dogs with recurrent (either local or distant) mast cell tumor following surgical excision. Clin Cancer Res 2009;15:3856–3865.
11. Modiano JF, Breen M, Valli VE, et al. Predictive value of p16 or Rb inactivation in a model of naturally occurring canine non-Hodgkin’s lymphoma. Leukemia 2007;21:184–187.
12. Priester WA. Hepatic angiosarcomas in dogs: an excessive frequency as compared with man. J Natl Cancer Inst 1976;57:451–454.
13. Priester WA, McKay FW. The occurrence of tumors in domestic animals. Natl Cancer Inst Monogr 1980:1–210.
14. Prymak C, McKee LJ, Goldschmidt MH, et al. Epidemiologic, clinical, pathologic, and prognostic characteristics of splenic hemangiosarcoma and splenic hematoma in dogs: 217 cases (1985). J Am Vet Med Assoc 1988;193:706–712.
15. Schappa JT, Frantz AM, Gorden BH, et al. Hemangiosarcoma and its cancer stem cell subpopulation are effectively killed by a toxin targeted through epidermal growth factor and urokinase receptors. Intl J Cancer 2013; accepted for publication.
16. Scott MC, Sarver AL, Gavin KJ, et al. Molecular subtypes of osteosarcoma identified by reducing tumor heterogeneity through an interspecies comparative approach. Bone 2011;49:356–367.
17. Tamburini BA, Phang TL, Fosmire SP, et al. Gene expression profiling identifies inflammation and angiogenesis as distinguishing features of canine hemangiosarcoma. BMC Cancer 2010;10:619.
18. Tamburini BA, Trapp S, Phang TL, et al. Gene expression profiles of sporadic canine hemangiosarcoma are uniquely associated with breed. PLoS ONE 2009;4:e5549.
19. Valli VE, San Myint M, Barthel A, et al. Classification of canine malignant lymphomas according to the World Health Organization criteria. Vet Pathol 2011;48:198–211.
20. Withrow SJ, Powers BE, Straw RC, et al. Comparative aspects of osteosarcoma. Dog versus man. Clin Orthop 1991:159–168.
Jaime Modiano, VMD, PhD, holds the Alvin and June Perlman Endowed Chair as Professor of Oncology and Comparative Medicine, and as Director of the Animal Cancer Care and Research Program, the College of Veterinary Medicine, School of Medicine, and Masonic Cancer Center at the University of Minnesota, where he has been since 2007. He completed his veterinary training and PhD in Immunology through the Veterinary Medical Scientist Training Program at the University of Pennsylvania, followed by a residency in Veterinary Clinical Pathology at Colorado State University and a post-doctoral fellowship at the National Jewish Center for Immunology and Respiratory Medicine.
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