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| Author(s): |
Daniel Soares Sanches
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Medicina Veterinária e Zootecnia (FMVZ/SBD) |
| Defense date: | 2013-04-02 |
| Examining board members: |
Maria Lucia Zaidan Dagli;
Bruno Cogliati;
Maria Aparecida Azevedo Koike Folgueira;
Heidge Fukumasu;
Thomas Prates Ong
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| Advisor: | Maria Lucia Zaidan Dagli |
| Abstract | |
Osteosarcoma is the most common type of bone cancer in dogs and humans. Due to the fact that canine osteosarcoma is similar to human osteosarcoma in its high occurrence rate, biological behavior, clinical signs and molecular characteristics, this naturally occurring canine disease represents an important model for the study of osteosarcoma in humans. Studies regarding the development of the osteoblast phenotype into terminally differentiated osteocytes provide an understanding of the neoplastic transformation in bone cancer. For this reason, further studies of bone differentiation may lead to the discovery of bone-tumorspecific markers used for disease detection and prognosis, and the development of drugtargeted therapies. The focus of this study is the process of induced bone differentiation after treatment with three different drugs that have a potential anti-neoplastic activity against osteosarcoma. Two osteosarcoma cell lines in three-dimensional culture were evaluated after being treated with Arctigenin, Genistein, and Trichostatin-A. Initially, we performed the establishment and characterization of a novel canine osteosarcoma cell line. Then the work on the evaluation of differentiation markers by different techniques has been initiated. Studies were also used for cell viability, proliferation assays and induced cell death, as well as invasion. The results showed that all three treatments were able to induce partial differentiation in osteosarcoma cell lines, since the heterogeneity of the data collected, as well as the partial expression of markers of late transition osteoblast / osteocyte. Associated with this it was found that there is reduced cell viability, but without acting directly connected to caspase3. It is further noticed that even with differences between strains, the active principles were able to inhibit the invasiveness in Transwell assay. The conclusion is thus that the partial differentiation inducing compounds used, but with important antineoplastic effect. Together, these results highlight the importance of the process of differentiation, tumorigenesis and differentiation therapy. (AU) | |