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BackgroundAcute lymphoblastic leukemia is the most common malignant cancer in childhood. The signs and symptoms of childhood cancer are difficult to recognize, as it is not the first diagnosis to be considered for nonspecific complaints, leading to potential uncertainty in diagnosis. The aim of this study was to perform proteomic analysis of serum from pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL) to identify candidate biomarker proteins, for use in early diagnosis and evaluation of treatment.MethodsSerum samples were obtained from ten patients at the time of diagnosis (B-ALL group) and after induction therapy (AIT group). Sera from healthy children were used as controls (Control group). The samples were subjected to immunodepletion, affinity chromatography with α-d-galactose-binding lectin (from Artocarpus incisa seeds) immobilized on a SepharoseTM 4B gel, concentration, and digestion for subsequent analysis with nano-UPLC tandem nano-ESI-MSE. The program ExpressionE was used to quantify differences in protein expression between groups.ResultsA total of 96 proteins were identified. Leucine-rich alpha-2-glycoprotein 1 (LRG1), Clusterin (CLU), thrombin (F2), heparin cofactor II (SERPIND1), alpha-2-macroglobulin (A2M), alpha-2-antiplasmin (SERPINF2), Alpha-1 antitrypsin (SERPINA1), Complement factor B (CFB) and Complement C3 (C3) were identified as candidate biomarkers for early diagnosis of B-ALL, as they were upregulated in the B-ALL group relative to the control and AIT groups. Expression levels of the candidate biomarkers did not differ significantly between the AIT and control groups, providing further evidence that the candidate biomarkers are present only in the disease state, as all patients achieved complete remission after treatment.ConclusionA panel of protein biomarker candidates has been developed for pre-diagnosis of B-ALL and also provided information that would indicate a favorable response to treatment after induction therapy.

e There have recently been significant increases in the prevalence of systemic invasive fungal infections. However, the number of antifungal drugs on the market is limited in comparison to the number of available antibacterial drugs. This fact, coupled with the increased frequency of cross-resistance, makes it necessary to develop new therapeutic strategies. Combination drug therapies have become one of the most widely used and effective strategies to alleviate this problem. Amiodarone (AMD) is classically used for the treatment of atrial fibrillation and is the drug of choice for patients with arrhythmia. Recent studies have shown broad antifungal activity of the drug when administered in combination with fluconazole (FLC). In the present study, we induced resistance to fluconazole in six strains of Candida tropicalis and evaluated potential synergism between fluconazole and amiodarone. The evaluation of drug interaction was determined by calculating the fractional inhibitory concentration and by performing flow cytometry. We conclude that amiodarone, when administered in combination with fluconazole, exhibits activity against strains of C. tropicalis that are resistant to fluconazole, which most likely occurs via changes in the integrity of the yeast cell membrane and the generation of oxidative stress, mitochondrial dysfunction, and DNA damage that could lead to cell death by apoptosis.

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