ABSTRACT
BACKGROUND: Testicular germ cell tumors (TGCTs), a group of heterogeneous neoplasms, are the most frequent tumors of teenagers and young men, with the incidence rising worldwide. High cure rates can be achieved through cisplatin (CDDP)-based treatment, but approximately 10% of patients present refractory disease and virtually no treatment alternatives. Here, we explored new strategies to treat CDDP-resistant. METHODS: In vitro TGCT CDDP-resistance model was established and differential mRNA expression profiles were evaluated using NanoString technology. Then, TGCT cell lines were treated with four potential drugs (PCNA-I1, ML323, T2AA, and MG-132) to overcome CDDP-resistance. RESULTS: We found several differentially expressed genes related to DNA repair and cell cycle regulation on CDDP-resistant cell line (NTERA-2R) compared to parental cell line (NTERA-2P), and the proteasome inhibitor MG-132 demonstrated cytotoxic activity in all cell lines evaluated, even at a nanomolar range. MG-132 also enhanced cell lines' sensitivity to CDDP, increasing apoptosis in both NTERA-2P and NTERA-2R. CONCLUSIONS: MG-132 emerges as a potential new drug to treat CDDP-resistant TGCT. Targeted therapy based on molecular mechanism insights may contribute to overcome acquired chemotherapy CDDP-resistance.
Subject(s)
Antineoplastic Agents , Neoplasms, Germ Cell and Embryonal , Adolescent , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cisplatin/pharmacology , Cisplatin/therapeutic use , Drug Resistance, Neoplasm/genetics , Humans , Male , Neoplasms, Germ Cell and Embryonal/drug therapy , Neoplasms, Germ Cell and Embryonal/genetics , Testicular NeoplasmsABSTRACT
Objetivo Verificar a influência da dislipidemia no surgimento e agravamento de cardiopatias em adultos na cidade de Barretos-SP. Métodos Foi efetuado um estudo exploratório, através de pesquisa bibliográfica e levantamento de dados de prontuários do Ambulatório Médico de Especialidades de Barretos (AME) e Hospital São Jorge, ambos situados no município de Barretos, e retrospectivo, referentes ao período entre fevereiro de 2015 a agosto de 2015. Resultados Foram analisados os dados de 86 pacientes, sendo 37 homens (43,02%) e 49 mulheres (56,97%). A faixa etária variou de 31 a 88 anos (média de 59,10 anos de idade). Dentre o total de pacientes, 19 (22,09%) apresentaram dislipidemia, 13 (15,11%) cardiopatia, 45 (52,32%) dislipidemia associada a cardiopatia e nove (10,46%) não apresentaram nenhuma alteração. Conclusões Conforme os resultados obtidos no presente estudo, bem como o que foi descrito na literatura, confirmou-se que a dislipidemia pode ser avaliada como um significativo fator de risco para as cardiopatias, sendo capaz de influenciar o surgimento e o agravamento dessas patologias na população. Descritores: Cardiopatias; Fatores de risco
Objective To investigate the effect of dyslipidemia in the emergence and worsening of heart disease in the population. Methods We performed an exploratory study through literature search and data collection outpatient Barretos Medical Specialties (AME) and St. George Hospital, both located in the city of Barretos, and retrospective, covering the period from February 2015 to August 2015. Results We analyzed data from 86 patients, 37 men (43.02%) and 49 women (56.97%). The age range was 31-88 years (mean 59.10 years old). Among the total patients, 19 (22.09%) had dyslipidemia, 13 (15.11%) disease, 45 (52.32%) dyslipidemia associated with heart disease and nine (10.46%) showed no change. Conclusion According to the results obtained in this study, as well as what was described in the literature, it was confirmed that dyslipidemia can be assessed as a significant risk factor for heart disease, being able to influence the emergence and worsening of these diseases in population. Descriptors: Cardiac disorders; Risk factors
