Wilms tumor (wt)1 gene expression in children with acute leukemia in Serbia

Acute leukemias constitute the most common malignancy in childhood, accounting for 25-35% of all cancer in children. They are divided into acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Genetic susceptibility is known to play a major role in childhood leukemias. Wilms tumor (WT)1 is a zinc finger transcription factor involved in regulating the process of cell differentiation; it has been implicated in a wide range of human neoplasms. WT1 overexpression in the bone marrow at diagnosis is reported to be an independent negative prognostic factor in adults and children with AML. The aim of the present investigation was to determine the expression of WT1 in the bone marrow of children with AML and ALL in Serbia and its possible impact on patient survival. We determined bone marrow WT1 expression levels by reverse -transcription polymerase chain reaction (RT-PCR) at diagnosis in 20 children with AML and 20 children with ALL (16 B-ALL and 4 T-ALL), as well as 15 age- and sex-matched controls who were evaluated for immune thrombocytopenic purpura (ITP). For children with AML, follow-up samples were also analyzed one month after treatment initiation and at variable later timepoints of control punctures. The results were normalized based on WT1 expression in controls. We found that children with AML had significantly higher WT1 expression at diagnosis (median SD: 139.42 244.03) than those with ALL (1.18 54.37; Mann -Whitney U=82; p lt 0.01) and ITP (0.76 1.01; U=32; p lt 0.01). Patients with T-ALL had higher WT1 expression than those with B-ALL, though significance was not reached due to subgroup size; differences between AML subgroups according to the French-American-British (FAB) classification were also below the level of significance, though a tendency toward higher values in M3 and M4 leukemias was notable. There was also a tendency toward higher values in 14 children with AML who were still alive after a median follow-up of 1.5 years (181.42 192.52) than in 6 who succumbed to the disease (104.29 354.87). All children with AML who had WT1 expression 1 month after diagnosis below the fourth quartile (10 of 10) were still alive, while only 2 of 5 with 1 -month WT1 expression in the fourth quartile survived (Fisher's exact test: p=0.0952). Taken together, our results support a role for WT1 in the diagnostic workup in children with acute leukemia, although it needs to be considered in view of a complex and indvidualized context

Elicitation effects of a synthetic 1,2,4,5-tetraoxane and a 2,5-diphenylthiophene in shoot cultures of two Nepeta species

The presented study aimed to investigate the elicitation possibility for the production of main secondary metabolites in Nepeta cataria L. and N. pannonica L. plants, by exposing them to synthetic compounds belonging to tetraoxanes and thiophenes group. The effect of DO63 (1,2,4,5-tetraoxane) and DOVF15 (2,5-diphenylthiophene) on the production of cis-trans-nepetalactone (NL) and rosmarinic acid (RA) in two Nepeta species, was investigated in shoots grown on the culture medium with the addition of synthetic compounds in the concentrations ranging from 0.1 to 2 mg L-1. The content of targeted metabolites in tested in vitro shoots depended on the type and concentration of applied synthetic compounds. Application of DO63 in the concentration range 0.1-1 mg L-1 affected only NL production in both Nepeta species resulting in its increased content, while production of RA was not influenced in the treated shoots. Addition of DOVF15 caused decreased RA content in N. pannonica shoots and an increase in N. cataria shoots, whereas NL production was not affected. The presented results reveal the possibility of DO63 and DOVF15 application for the elicitation of the main secondary metabolites production in species from the genus Nepeta

Improving the Diagnosis of Children with 22q11.2 Deletion Syndrome: A Single-center Experience from Serbia

Objective: The incidence of the 22q11.2 microdeletion among children who have at least two out of five major clinical criteria for 22q11.2 deletion syndrome. Design: Prospective study. Setting: University Children's Hospital in Belgrade, Serbia between 2005 and 2014. Participants: 57 patients with clinical characteristics of 22q11.2 deletion syndrome. Methods: Standard G-banding cytogenetic analysis was performed in all children, and the 22q11.2 genomic region was examined using fluorescence in situ hybridization (FISH). For patients with no deletion detected by FISH, multiplex ligation dependent probe amplification (MLPA) analysis was also done in order to detect cryptic deletions of this region and to analyze other genomic loci associated with phenotypes resembling the syndrome. A selected group of patients diagnosed to have 22q11.2 microdeletion by FISH underwent MLPA testing in order to characterize the size and position of deletion. Outcome Measure: The frequency of 22q11.2 microdeletion among children with at least two of the five major characteristics of 22q11.2 deletion syndrome (heart malformations, facial dysmorphism, T-cell immunodeficiency, palatal clefts and hypocalcemia/hypoparathyroid ism) Results: Typical 22q11.2 microdeletion was detected in 42.1% of patients; heart malformation were identified in all of them, facial dysmorphism in 79.2%, immunological problems in 63.6%, hypocalcemia in 62.5% and cleft palate in 8.3%. Conclusions: A higher detection rate compared to one-feature criterion is obtained when at least two major features of 22q11.2 deletion syndrome are taking into consideration. The criteria applied in this study could be considered by centers in low-income countries

The Impact of 22q11.2 Microdeletion on Cardiac Surgery Postoperative Outcome

22q11.2 microdeletion is the most common microdeletion in humans. The purpose of this study was to evaluate postoperative outcome in children with 22q11.2 microdeletion who had undergone complete surgical correction of a congenital heart defect. The study included 34 patients who underwent complete correction of conotruncal heart defects. Of these, 17 patients diagnosed with 22q11.2 microdeletion represent the investigated group. Another 17 patients without 22q11.2 microdeletion represent the control group. Investigated and control groups differ significantly for total length of stay in the hospital (average 37.35 and 14.12 days, respectively); length of postoperative stay in the intensive care unit (average 10.82 and 6.76 days, respectively); sepsis (eight and two patients, respectively); administration of antibiotics (15 and seven patients, respectively); duration of antibiotic therapy (average 17.65 and 14.59 days, respectively); occurrence of hypocalcemia (16 and 0 patients, respectively); and initiation of peroral nutrition during the postoperative course (average 10.29 and 3.88 days, respectively). No difference was found for duration of ventilatory support (average 6.12 and 4.24 days, respectively), administration of total parenteral nutrition, and postoperative mortality rate. The study results suggest that genotype of 22q11.2 microdeletion affects postoperative outcome after cardiac surgery. Possible targets for intervention in postoperative intensive care management are prevention and treatment of systemic infections, monitoring, and treatment of hypocalcemias, rational administration of antibiotics and careful planning of nutrition. Consequently, this could shorten patients' intensive care stay and overall duration of hospitalization