RESUMO
Osteosarcomas (OS) are the most common malignant bone tumors, and the identification of useful tumor biomarkers and target proteins is required to predict the clinical outcome of patients and therapeutic response as well as to develop novel therapeutic strategies. In our previous study, MAPK7 has been identified as a candidate oncogene, and a promising prognostic marker for OS. Sequential activation of protein kinases within the mitogen-activated protein kinase (MAPK) cascades is a common mechanism of signal transduction in many cellular processes. In this study, we investigated the behavior of MAPK7 gene in OS cell lines. Technical viability, proliferation, migration, invasion, and apoptosis were used to evaluate the function of the MAPK7 gene. We evaluated the behavior of the OS cells with MAPK7 gene silenced, not silenced, and exposed to the main chemotherapy drugs used in OS treatment. We found that silenced MAPK7 gene is effective at suppressing cell proliferation, inhibiting cell migration, and invasion. Furthermore, MAPK7 is an important activator of transcription factors and is the main expression modulator of other key genes in the MAPK pathway. In summary, our study suggests that MAPK7 might be a promising therapeutic target for OS. © 2015 Wiley Periodicals, Inc.
Assuntos
Neoplasias Ósseas/metabolismo , Proteína Quinase 7 Ativada por Mitógeno/genética , Proteína Quinase 7 Ativada por Mitógeno/metabolismo , Osteossarcoma/metabolismo , Apoptose , Neoplasias Ósseas/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Humanos , Invasividade Neoplásica , Osteossarcoma/genética , Regulação para CimaRESUMO
OBJETIVO: Dosar os marcadores tumorais antígeno carcinoembrionário (CEA), fragmento da citoqueratina 19 (CYFRA21-1) e antígeno glicosídico associado a tumor 15-3 (CA 15-3) em sangue e líquido pleural de portadores de derrames pleurais benignos e malignos, avaliando a sensibilidade de cada um deles nesses fluidos. MÉTODOS: Avaliamos prospectivamente 85 pacientes com derrame pleural. O estudo do líquido pleural obedeceu a critérios determinados pela literatura. A dosagem dos marcadores foi realizada por eletroquimioluminescência. A sensibilidade foi determinada sob a condição de que a especificidade fosse > 90 por cento. RESULTADOS: Foram diagnosticados 36 casos malignos (42,4 por cento), 30 benignos (35,3 por cento); em 19 pacientes (22,3 por cento), o diagnóstico foi inconclusivo. Nos casos malignos, os valores de CEA e CYFRA21-1 foram maiores no líquido pleural do que no sangue, fato não observado para o CA 15-3. Nos casos benignos, os valores do CYFRA21-1 foram maiores no líquido pleural do que no soro, enquanto que para o CEA e o CA 15-3, ocorreu o oposto. Todos os marcadores apresentaram diferença significativa entre os casos malignos e benignos, em líquido pleural e soro. Foi encontrada sensibilidade para CEA, CYFRA21-1 e CA 15-3 no líquido pleural de 69,4 por cento, 69,4 por cento e 66,7 por cento, respectivamente e quando associados, foi 80,6 por cento. No soro, a sensibilidade foi 57,1, 71,4 e 48,6 por cento para CEA, CYFRA21-1 e CA 15-3, respectivamente, e quando associados, foi 77 por cento. CONCLUSÃO: Os resultados sugerem que a utilização desses marcadores pode ser útil na diferenciação entre derrames pleurais malignos e benignos.
OBJECTIVE: To determine the levels of the tumor markers carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1) and carbohydrate antigen 15-3 (CA 15-3) in the blood and pleural fluid of patients with benign or malignant pleural effusion, evaluating the sensitivity of each marker in these fluids. METHODS: We prospectively evaluated 85 patients with pleural effusion. The study of the pleural fluid observed the criteria established in the literature. Levels of the markers were determined using electrochemiluminescence. The sensitivity was determined on the condition that the specificity was > 90 percent. RESULTS: Of the 85 cases, 36 (42.4 percent) were malignant, 30 (35.3 percent) were benign, and the results were inconclusive in 19 (22.3 percent). In the malignant cases, the CEA and CYFRA21-1 levels were higher in the pleural fluid than in the blood, which was not observed for CA 15-3. In the benign cases, the CYFRA21-1 levels were higher in the pleural fluid than in the blood, whereas the opposite was found for CEA and CA 15-3. There were significant differences between malignant and benign cases for all markers, in pleural fluid and blood. In the pleural fluid, the sensitivity of CEA, CYFRA21-1 and CA 15-3 was 69.4, 69.4 and 66.7 percent, respectively, and the combined sensitivity was 80.6 percent. In the blood, the sensitivity was 57.1 percent, 71.4 percent and 48.6 percent for CEA, CYFRA21-1 and CA 15-3, respectively, and the combined sensitivity was 77 percent. CONCLUSION: The results suggest that these markers might be useful in the differentiation between malignant and benign pleural effusion.