RESUMO
BACKGROUND: Bax activation and intracellular redistribution as well as its prognostic significance during steroid-induced apoptosis of leukemic cells in childhood acute lymphoblastic leukemia (ALL) remain a matter of controversy. The purpose of this study was to assess time-resolved changes in Bax activation and its intracellular distribution as well as the percentage of apoptotic cells evaluated by PARP cleavage in response to prednisone treatment in childhood ALL. MATERIAL/METHODS: The study comprised 43 children with de novo ALL. Bax activation and PARP cleavage were measured by laser scanning cytometry in peripheral blood mononuclear cells collected prior to and 6 and 12 hours after prednisone administration. RESULTS: The mean pretreatment proportion of p89 PARP-positive cells was 3.5%. Six and twelf hours after prednisone administration it increased significantly (p<0.01) only in the group of good treatment responders. A significant rise (p<0.05) in cytoplasmic Bax expression was seen in the good responders as early as 6 hours after prednisone administration followed by a significant rise in Bax nuclear expression after 12 hours. At the same time points the mean percentage of apoptotic cells as well as Bax expression in the cytoplasm and nucleus remained unchanged in the group of poor responders. CONCLUSIONS: Increased Bax nuclear accumulation (and possibly also aggregation) together with increased PARP cleavage observed within 12 hours after prednisone oral administration were associated with and may predict good outcome in children with newly diagnosed ALL.
Assuntos
Núcleo Celular/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/enzimologia , Proteína X Associada a bcl-2/metabolismo , Adolescente , Criança , Pré-Escolar , Feminino , Fluoresceína-5-Isotiocianato , Fluorescência , Humanos , Lactente , Leucócitos Mononucleares/metabolismo , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Prednisona/uso terapêutico , Resultado do TratamentoRESUMO
Clear statement that pediatric neoplasms are really rare is not easy. Thus the incidence of rare tumours in children has not been defined so far. The paper efforts to assess the topic of rare tumours of childhood in the Polish population. Following two categories are proposed: tumours typical for adults, but possible in children (neoplasms of epithelial origin--mainly carcinomas, melanomas, carcinoids) and paediatric tumours consisting less than 10% of cases in corresponding clinical groups according to the ICCC classification. Data on 317 patients aged 0-18 years treated in centres associated in the Polish Paediatric Group for Solid Tumours (PPGST) were analysed. Classical adult malignancies were registered in 130 patients: carcinomas in 90 (mean age 12.6 +/- 4.5 years), melanomas in 25 (mean age 9.4 +/- 4.9) and carcinoids in 9 (mean age 14.5 +/- 1.2 years). Non epithelial neoplasms were registered in 187 patients (mean age 10.4 +/- 5.5). That group included rare tumours of soft tissue, CNS, bones and other organs. Treatments of certain groups were specified by separate therapeutic protocols within PPGST. Rare malignancies of adult-type among children under 18 years of age in Poland comprised 1.5% of all pediatric neoplasms. The incidence of adult-type neoplasms increased with age until 14 years. In patients over 15 years of age the number of registered cases decreased. It may suggest a first peak of incidence in early adolescence or an underestimation of number of patients with carcinoma aged over 15 years. In the analyzed group, the mean age of patients with carcinomas and other epithelial and unspecified tumours significantly exceeded the age of children with rare neoplasms of non-epithelial origin (12.1 +/- 4.7 vs 10.4 +/- 5.5 years; p<0.05). A very young age at diagnosis of malignant melanomas (mean 9.4 years) and numerous cases of carcinomas affecting the digestive tract (n=24; 27% of all carcinomas), especially those located in colorectal region (n=10), seem surprising. The preliminary analysis of the collected data on rare neoplasms in Poland encourage to undertake a prospective study, meant to link the epidemiology and characteristics of rare epithelial tumours in childhood with diagnostic and therapeutic suggestions for these types that are not coordinated within Polish Paediatric Group of Solid Tumours.
Assuntos
Neoplasias/epidemiologia , Doenças Raras/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Fatores Etários , Criança , Proteção da Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Neoplasias/diagnóstico , Polônia/epidemiologia , Doenças Raras/diagnóstico , Estudos Retrospectivos , Fatores de RiscoRESUMO
In our previous study the pattern of glutathione peroxidase (GPX) activity in the course of steroid-sensitive nephrotic syndrome (SSNS) in children suggested a defect in antioxidant defense. In the present report the serum selenium (Se) level, an essential component of GPX activity, was measured in a comparable group of children with SSNS at the same clinical stages at which GPX activity was determined in the previous study. Nephrotic children had normal serum Se levels during the edematous stage, at the end of prednisone treatment, and in remission. At the end of high-dose prednisone treatment, the serum Se level increased ( P<0.01) simultaneously with enhanced activity of GPX. These results suggest that children with SSNS have a persistent defect in the antioxidant defense at the important stage of hydrogen peroxide and fatty acid hydroperoxide decomposition. This defect is transiently alleviated by high-dose prednisone treatment.
Assuntos
Glutationa Peroxidase/metabolismo , Síndrome Nefrótica/sangue , Síndrome Nefrótica/enzimologia , Selênio/sangue , Adolescente , Antioxidantes/metabolismo , Criança , Pré-Escolar , Glucocorticoides/uso terapêutico , Humanos , Síndrome Nefrótica/tratamento farmacológico , Prednisolona/uso terapêuticoRESUMO
Although relationship between vesico-ureteric reflux, urinary tract infection and renal scarring is known, pathogenesis of the renal scarring is still unclear. Vesico-ureteric reflux and urinary tract infection remain in very close relationship, they may also occur separately. The factor promoting renal injury is also young age of a child. The aim of this paper was to analyse the influence of the selected factors, namely: degree of the vesico-ureteric reflux; child's age at reflux diagnosis time as well as the frequency of recurrences of urinary tract infections exerted on reflux nephropathy. In 45 children with diagnosed vesicoureteric reflux the intensity of renal scarring was estimated using planar scintigraphy with DMSA-Tc-99m and a questionnaire was prepared. The questionnaire included information as follows: age at which the diagnosis was established, degree of reflux at the time of diagnosis, treatment applied, frequency of urinary tract infections before and after having taking medical care of children. It was revealed that the degree of scarring correlated with degree of vesico-ureteric reflux of particular kidney. In the investigated group no correlations were found between intensity of renal scarring and both the age of establishing diagnosis and frequency of urinary tract infections before starting the treatment. Taking the obtained results into consideration it seems, that the degree of vesico-ureteric reflux estimated prior to treatment determines degree of renal injuries though, undoubtedly all factors being studied affect renal scarring.