RESUMO
In this study, we target arginine auxotrophy of AML cell lines using human arginase I cobalt-PEG5000. HuArgI(Co)-PEG5000 was cytotoxic to all AML cell lines tested. Mononuclear cells and CD34(+) blasts were not sensitive demonstrating the selectivity of HuArgI(Co)-PEG5000-induced arginine deprivation. Addition of L-citrulline led to the rescue of five cell lines. The four cell lines that were not rescued by L-citrulline did not express argininosuccinate synthetase-1, indicating complete arginine auxotrophy. Inhibition of autophagy increased cell sensitivity to HuArgI(Co)-PEG5000 demonstrating the protective role of autophagy following arginine deprivation. We have shown that AML can be selectively targeted using HuArgI(Co)-PEG5000-induced arginine depletion.
Assuntos
Apoptose/efeitos dos fármacos , Arginase/metabolismo , Arginina/metabolismo , Autofagia , Leucemia Mieloide Aguda/patologia , Polietilenoglicóis/química , Proteínas Recombinantes/metabolismo , Argininossuccinato Sintase , Western Blotting , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Citometria de Fluxo , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/metabolismo , Células Tumorais CultivadasRESUMO
Apolipoprotein E (ApoE) has an important role in the metabolism of lipids through its major isoforms (ε2, ε3, ε4). In particular, ApoE ε4, has been considered as a major genetic risk factor for cardiovascular diseases (CVD). The aim of our study is to investigate the frequency of ApoE gene polymorphisms (rs 429358C>T, rs 7412C>T) and their relationship to lipid parameters in a group of Lebanese hypercholesterolemic subjects (22 males and 24 females, aged 25-80 years). Lipid profile, apolipoproteins A-I and B were determined using fasting serum samples; and molecular analysis of ApoE polymorphisms using blood in EDTA tubes. The distribution of the four ApoE genotypes detected in this study was: ε3/ε3 (73.9%), ε3/ε4 (17.4%), ε2/ε3 (6.5%), and ε2/ε4 (2.2%) resulting in allelic frequencies for ε2, ε3 and ε4 of 4.3%, 85.9% and 9.8%, respectively. No association was determined among any of the lipid parameters, gender and ApoE genotypes. Lipid parameters were not statistically different among various ApoE genotypes (p>0.05). ApoE ε2 frequency was found to be lower than that previously reported for healthy Lebanese (7.2%). CVD is one of the major leading causes of mortality in Lebanon with a reported prevalence of 12.2% in males and 7.7% in females, which incidentally agrees with our finding regarding ε4 allelic frequency of 13.6% in males and 6.3% in females. Consequently, larger prospective studies are recommended to highlight the correlation of ApoE polymorphisms to other biochemical and environmental factors involved in CVD.
Assuntos
Apolipoproteínas E/genética , Predisposição Genética para Doença/genética , Hipercolesterolemia/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Frequência do Gene , Genótipo , Humanos , Líbano , Lipídeos/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo GenéticoRESUMO
BACKGROUND: Asparaginase is an essential component of the chemotherapy regimens during the induction and intensification phases for acute lymphoblastic leukemia and lymphoblastic lymphoma. The administration of asparaginase can cause elevation of the triglyceride levels. CASE REPORT: This study reports the case of an adult patient presenting with acute pancreatitis secondary to severe hypertriglyceridemia after asparaginase treatment during the consolidation phase of lymphoblastic lymphoma. This condition was successfully treated with plasmapheresis. CONCLUSIONS: Our case demonstrates that plasmapheresis in severe cases of hypertriglyceridemia offers a safe and efficient treatment option for symptomatic patients.
