Plasma Levels of Plasminogen Activator Inhibitor Type 1 and Vitronectin in Children With Cancer.

BACKGROUND: The plasminogen activator system controls intravascular fibrin deposition; besides, it also participates in a wide variety of physiologic and pathologic processes, including cancer. PROCEDURE: In this study, we examined the levels of plasminogen activator inhibitor 1 (PAI-1) and vitronectin in 32 newly diagnosed pediatric patients with malignancies, determined by enzyme-linked immunosorbent assay between January 2009 and January 2010 and compared them to 35 age-matched healthy children, using SPSS 16.0 software. RESULTS: The mean level of PAI-1 was 23.02 ± 15 (8.2-71.19) ng/mL and vitronectin was 83.10% ± 23.77% (12%-126%) in the tumor group. Thirty-five healthy children in the same age range were enrolled in the control group. The levels of PAI-1 and vitronectin were 23.63 ± 10.44 (11.67-58.85) ng/mL and 85% ± 20.85% (39%-126%), respectively. No significant difference was found between the 2 groups by independent sample t-test (P = .86 and P = .69). CONCLUSIONS: This is a preliminary study done in children with malignancies, investigating PAI-1 and vitronectin. Further study is needed, including larger trials and tumor tissue with histopathological examination as in adults.

Deregulated WNT signaling in childhood T-cell acute lymphoblastic leukemia.

WNT signaling has been implicated in the regulation of hematopoietic stem cells and plays an important role during T-cell development in thymus. Here we investigated WNT pathway activation in childhood T-cell acute lymphoblastic leukemia (T-ALL) patients. To evaluate the potential role of WNT signaling in T-cell leukomogenesis, we performed expression analysis of key components of WNT pathway. More than 85% of the childhood T-ALL patients showed upregulated ß-catenin expression at the protein level compared with normal human thymocytes. The impact of this upregulation was reflected in high expression of known target genes (AXIN2, c-MYC, TCF1 and LEF). Especially AXIN2, the universal target gene of WNT pathway, was upregulated at both mRNA and protein levels in ∼40% of the patients. When ß-CATENIN gene was silenced by small interfering RNA, the cancer cells showed higher rates of apoptosis. These results demonstrate that abnormal WNT signaling activation occurs in a significant fraction of human T-ALL cases independent of known T-ALL risk factors. We conclude that deregulated WNT signaling is a novel oncogenic event in childhood T-ALL.

Effects of malnutrition on oxidative burst functions and infection episodes in children with acute lymphoblastic leukemia.

INTRODUCTION: The aim of this study was to determine the effect of malnutrition on oxidative burst functions (OBF) of neutrophils in children with acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: Twenty-eight patients with ALL and thirty healthy controls were enrolled to the study. Thirteen patients with ALL were found to have malnutrition. While neutrophil OBF of ALL patients without malnutrition were studied both before induction chemotherapy and 3 months after, the same functions in ALL patients with malnutrition were studied both before induction chemotherapy and when the nutritional status improved. Control group were studied at admission and 3 months later. RESULTS: The OBF of ALL patients with and without malnutrition before induction chemotherapy were found to be significantly lower than the control group (P = 0.009), whereas the OBF were found to be similar in both patient groups with ALL (P = 0.27). The median infection episode rate and the duration of antibiotics therapy during the study period were similar in both patient groups with ALL. The repeated OBF of both patient groups with ALL were shown to increase to similar values with the control group in the third month of chemotherapy (P = 0.002). The median infection episode rate during the first month of chemotherapy was shown to decrease significantly during the third month of chemotherapy in both patient with ALL groups (P < 0.001). CONCLUSIONS: We have not been able to demonstrate an overt effect of malnutrition on OBF. However, our results still need to be verified via further larger scaled studies of OBF in leukemic children with and without malnutrition.

Urine endothelin-1 levels as a predictor of renal scarring in children with urinary tract infections.

AIMS: Endothelin-1 (ET-1) contributes to renal fibrogenesis in several manners such as increasing collagen synthesis in mesangium, decreasing extracellular matrix (ECM) degradation by mesangial cells and stimulating mesangial contraction. The aim of our study was to investigate whether urine level of ET-1 (uET-1) could represent a useful biomarker of renal scarring and if so, to determine the optimal cutoff level for uET-1 to predict a renal scar. METHODS: 44 children with renal scarring and 32 children without renal scarring were enrolled in the study. Urine ET-1 was measured by enzyme-linked immunosorbent assay. RESULTS: Mean uET-1 level was significantly higher in the scar group than in controls (2.75 ± 1.35 fmol/ml vs. 0.68 ± 0.41 fmol/ml, p = 0.001). The optimal cut-off level was 1.064 fmol/ml for uET-1 to predict renal scarring. Using this cut-off point, sensitivity and specificity were 97.73% and 93.91%, respectively. AUC was found 0.975 (95% CI 0.917 - 0.996) for uET-1. Mean urine Endothelin-1/Creatinine ratio (uET-1/Cr) was also significantly higher in the scar group than in the control group (4.04 ± 2.29 fmol/mg Cr vs. 1.09 ± 0.67 fmol/mg Cr, p = 0.0001). Using 1.67 fmol/mgCr as optimal cut-off level, sensitivity and specificity were 95.45% and 84.09%, respectively. AUC was 0.945 (95% CI 0.875 - 0.982) for uET-1/Cr. CONCLUSION: Our study suggests that both uET-1 and uET-1/Cr can be used for prediction of renal scarring in children with normal renal function. Measuring urine level of ET-1 can help us to avoid unnecessary DMSA studies if the patient's uET-1 level is found to be under the determined cut-off point.

Efficacy of FEIBA for acute bleeding and surgical haemostasis in haemophilia A patients with inhibitors: a multicentre registry in Turkey.

Long used in established industrialized nations to treat patients with haemophilia and inhibitors, factor eight inhibitor bypassing activity (FEIBA) has, in recent years, been introduced into more geographically diverse settings. Data are needed on how successfully FEIBA therapy has been implemented in new regions. To determine the efficacy and safety of FEIBA for the treatment of acute bleeding and surgical haemostasis in a newly industrialized country. A multicentre registry of haemophilia A patients with inhibitors receiving FEIBA treatment was established in Turkey. With a standardized case report form, data were collected retrospectively on: patient demographics; characteristics of acute bleeding episodes and surgical interventions; FEIBA regimen; and treatment outcomes. Thirty-seven patients received a total of 112 FEIBA treatment courses, 90 for acute bleeding and 22 for surgical haemostasis. The median FEIBA dose per infusion for acute bleeding was 50 IU kg(-1), and for surgery was 100 IU kg(-1). For both acute joint and muscle/soft tissue bleeding and in surgery, haemostasis was attained in a median of two FEIBA infusions. FEIBA was judged effective in 92% of treatment courses for acute bleeding, with a 95% confidence interval (CI) of 85-97%. Rates of haemostatic efficacy did not differ significantly between anatomical sites of acute bleeding. The haemostatic efficacy rate of FEIBA in surgery was 86% (CI, 65-97%). No thromboembolic complications or other adverse events occurred during any treatment course. FEIBA has been successfully integrated into clinical practice in Turkey, with rates of haemostatic efficacy comparable to those reported in countries with a longer history of FEIBA usage.