2021-03-262021-02-24OLIVEIRA, Danilo Gabriel de.. Estabelecimento de linhagem celular de carcinoma pulmonar resistente à Cisplatina: impacto sobre heterogeneidade e instabilidade cromossômica.. 2021. 96f. Dissertação (Mestrado em Biociências Aplicada à Saúde) - Universidade Federal de Alfenas, Alfenas/MG, 2021.https://repositorio.unifal-mg.edu.br/handle/123456789/1785Cancer is one of the biggest public health problems and a major cause of death worldwide. Among the different types of cancer, lung cancer represents the second most common type of cancer in men and women (not counting non- melanoma skin cancer) and, in Brazil, it represents about 13% of all new cancer cases. Chemotherapy remains one of the main treatment methods to try to control the progress of the disease, with cisplatin as its main chemotherapic agent. However, a major clinical challenge is chemoresistance, which reduces the chances of therapeutic success, allowing the exploration of new drug alternatives. In order to understand this tumor mechanism, developers of cisplatin-resistant lung adenocarcinoma cell line, using in vitro analysis, focusing on analyses of chromosomal instability mechanisms (CIN) that could contribute to the resistant phenotype. After 3 sequential treatments at the dosage of 30 μM with cisplatin, the resistant strain A549-R30 had its chemoresistance confirmed through viability and clonogenic capacity tests, in addition to the visible morphological changes during the maintenance of cells in culture. The cell line A549-R30 also showed greater migration capacity through the wound healing assay in the 48h and 72h times. Interestingly, it was noted that the amount of NIC biomarkers present in A549-R30 cells was the lowest in the parental cell A549-P. Finally, a cytogenetic evaluation corroborates a high tumor heterogeneity of A549-P cells and a greater number of non-clonal chromosomal alterations (NCCAs) when compared to A549-R30 cells (12 vs 6 NCCAs, respectively); and showed that, after the cisplatin treatment cycles, the modal chromosomal number increased in the resistant cells A549-R30 and some karyotypic alterations of the parental lineage were selected . All of this suggests that the chemoresistance process is closely linked to the level of CIN, as well as the mechanisms for maintaining this instability and, consequently, the development of a process of selection and karyotype evolution, which determine advantageous genomic profiles for the resistant tumor cell.application/pdfAcesso Abertohttp://creativecommons.org/licenses/by-nc-nd/4.0/Carcinoma Pulmonar de Células não PequenasDiaminodicloroplatinaInstabilidade CromossômicaResistência a Medicamentos AntineoplásicosCIENCIAS DA SAUDEDissertaçãoGamero, Angel Mauricio Castro