Evaluation of the efficacy of 5-azacytidine and trichostatin-A in canine and human hemangiosarcoma cell lines

• Grant number: 13/16423-8
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: November 01, 2013
• End date: December 31, 2017
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Pathology
• Principal Investigator: Maria Lucia Zaidan Dagli
• Grantee: Karen Batschinski
• Host Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Hemangiosarcoma (HSA) is a fatal cancer in both humans and dogs. In humans, HSA behaves and has lesions with similar distributions to canine HSA. In both species, metastases are commonly seen and adjuvant chemotherapy provides only a modest benefit. There are many important mutated tumor supressor genes related to the pathogenesis of human, canine, and murine HSA. Identification of new tumor-specific targets and the extensive study of canine HSA biology are critical for the development of more effective therapeutics against this devastating cancer. It has been shown that 5- azacytidine, a drug found to have a hypomethylating effect, and trichostatin A, which promotes acetylation, have the potential to revert the phenotype associated with the development and progression of cancer. The aim of this current project is to evaluate the effect of 5-azacytidine and trichostatin A on canine HSA cell lines DEN-HSA and SB-HSA, and also on a human HSA cell line ISO-HSA, with the focus on the decrease of cell viability, apoptosis, changes in the cell cycle progression and epigenetic alterations related to the acetylation of histones. We will also assess cytotoxicity, proliferation, invasion, and metastases. Furthermore, we will evaluate the effects of 5-azacytidine and trichostatin A in comparison to and in combination with doxorubicin, the chemotherapy of choice for HSA. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

BATSCHINSKI, KAREN; NOBRE, ALESSANDRA; VARGAS-MENDEZ, ERNESTO; TEDARDI, V, MARCELLO; CIRILLO, JULIANA; CESTARI, GREICE; UBUKATA, RODRIGO; DAGLI, MARIA LUCIA Z.. Canine visceral hemangiosarcoma treated with surgery alone or surgery and doxorubicin: 37 cases (2005-2014). CANADIAN VETERINARY JOURNAL-REVUE VETERINAIRE CANADIENNE, v. 59, n. 9, p. 967-972, SEP 2018. (13/16423-8)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

BATSCHINSKI, Karen. Visceral hemangiosarcoma in dogs: a retrospective study of 42 cases (2005-2014). 2017. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.