RESUMO
The interaction of acute lymphoblastic leukemia (ALL) blasts with bone marrow (BM) stromal cells (BMSCs) has a positive impact on ALL resistance to chemotherapy. We investigated the modulation of a series of putative asparaginase-resistance/sensitivity genes in B-precursor ALL cells upon coculture with BMSCs. Coculture with stromal cells resulted in increased insulin-like growth factor (IGF)-binding protein 7 (IGFBP7) expression by ALL cells. Assays with IGFBP7 knockdown ALL and stromal cell lines, or with addition of recombinant rIGFBP7 (rIGFBP7) to the culture medium, showed that IGFBP7 acts as a positive regulator of ALL and stromal cells growth, and significantly enhances in-vitro resistance of ALL to asparaginase. In these assays, IGFBP7 function occurred mainly in an insulin- and stromal-dependent manner. ALL cells were found to contribute substantially to extracellular IGFBP7 levels in the conditioned coculture medium. Diagnostic BM plasma from children with ALL had higher levels of IGFBP7 than controls. IGFBP7, in an insulin/IGF-dependent manner, enhanced asparagine synthetase expression and asparagine secretion by BMSCs, thus providing a stromal-dependent mechanism by which IGFBP7 protects ALL cells against asparaginase in this coculture system. Importantly, higher IGFBP7 mRNA levels were associated with lower leukemia-free survival (Cox regression model, P=0.003) in precursor B-cell Ph(-) ALL patients (n=147) treated with a contemporary polychemotherapy protocol.
Assuntos
Asparaginase/farmacologia , Células da Medula Óssea/patologia , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/fisiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Células Estromais/patologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Técnicas de Cocultura , Meios de Cultivo Condicionados , Resistencia a Medicamentos Antineoplásicos , Feminino , Citometria de Fluxo , Técnicas de Silenciamento de Genes , Humanos , Lactente , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/genética , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/metabolismo , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , RNA Interferente Pequeno , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismoRESUMO
PURPOSE: To investigate the presence of human papillomavirus (HPV) DNA in tumour tissue from patients with unilateral retinoblastoma. METHODS: Samples of paraffin-embedded tumour tissue from 43 children with unilateral retinoblastoma were collected to investigate the presence of HPV DNA using polymerase chain reaction (PCR) and dot blot hybridization. RESULTS: Oncogenic HPV DNA types 16 and 35 were detected in 12 (27.9%) of 43 tumour specimens. A higher frequency of differentiated tumours (63.3%) was observed among the HPV-positive tumours. CONCLUSIONS: Future studies are necessary to demonstrate an association between HPV and sporadic retinoblastoma.
Assuntos
Papillomaviridae/isolamento & purificação , Neoplasias da Retina/virologia , Retinoblastoma/virologia , Pré-Escolar , DNA Viral/análise , Enucleação Ocular , Feminino , Humanos , Hibridização In Situ , Lactente , Masculino , Papillomaviridae/genética , Inclusão em Parafina , Reação em Cadeia da Polimerase , Neoplasias da Retina/patologia , Neoplasias da Retina/cirurgia , Retinoblastoma/patologia , Retinoblastoma/cirurgia , Proteínas Virais/análiseRESUMO
As the treatment of pediatric malignancies improves and survival increases, the diagnosis of acute abdomen in these patients also becomes more common. Nevertheless, the management of this condition is still controversial. The authors report their experience in treating 12 neutropenic children with acute abdomen. The charts of 12 neutropenic patients with a diagnosis of acute abdomen treated at Boldrini Children's Cancer Center in Campinas, Brazil, between 1991 and 1996, were reviewed. Therapeutic strategy included an initial period of bowel rest, general supportive measures, and broad-spectrum antibiotics while waiting for the neutrophil count to rise. Three patients recovered completely without surgery, 8 underwent late surgery without complications, and 1 died due to uncontrolled sepsis before surgery. The treatment of acute abdomen in neutropenic children remains controversial. As shown in the present series, an initial nonoperative approach with selective surgical indication appears to be safe and to yield good results. Supportive treatment, until the neutrophil count rises, followed by surgery, if necessary, appears to be a sound therapeutic approach for neutropenic children with acute abdomen.
Assuntos
Abdome Agudo/cirurgia , Neutropenia/cirurgia , Abdome Agudo/etiologia , Adolescente , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Criança , Pré-Escolar , Feminino , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/tratamento farmacológico , Humanos , Masculino , Neutropenia/etiologia , Resultado do TratamentoRESUMO
BACKGROUND: In order to evaluate the puberal development of girls treated by Acute Lymphocytic Leukaemia (ALL) a retrospective study was done at Campinas-SP, Brazil. MATERIAL AND METHODS: Forty two girls were treated by ALL with either 18 or 24 Grays of cranial irradiation. All patients were treated with chemotherapy including intrathecal methotrexate in similar dose regimens in either groups. RESULTS: The results showed lower mean ages at telarche, pubarche and menarche in the treated group, mainly in the group treated before five years old. No differences were observed in the 18 Grays or 24 Grays group. CONCLUSIONS: Our data suggest that girls treated by ALL have a precocious puberal development.
Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/radioterapia , Puberdade/efeitos dos fármacos , Puberdade/efeitos da radiação , Adolescente , Fatores Etários , Criança , Pré-Escolar , Feminino , Humanos , Modelos Lineares , Estudos RetrospectivosRESUMO
Objetivo. Com o objetivo de avaliar o desenvolvimento puberal após o tratamento de leucemia linfóide aguda (LLA) na infância, foi realizado um estudo retrospectivo, em meninas tratadas de janeiro de 1980 a janeiro de 1991, no Centro de Investigaçoes Hematológicas "Dr. Domingos A. Boldrini", em Campinas-SP. Casuística e Método. Foram selecionadas 42 meninas, tratadas antes da puberdade com quimioterapia sistêmica e intratecal e radioterapia cranial, utilizando doses de 18 a 24 Grays (Gy). Resultados. As idades médias da telarca, pubarca e menarca foram inferiores às do grupo-controle, embora com significância estatística apenas para a idade da telarca. Nao houve diferenças entre os grupos tratados com 18 ou 24Gy. As meninas tratadas antes dos cinco anos de idade apresentaram idade média da menarca estatisticamente inferior àquelas tratadas após cinco anos e em relaçao ao grupo-controle. Conclusao. Os resultados mostraram que o desenvolvimento puberbal em meninas tratadas de LLA na infância foi mais precoce que o de mininas saudáveis.
Assuntos
Pré-Escolar , Criança , Feminino , Humanos , Adolescente , Puberdade/efeitos dos fármacos , Puberdade/efeitos da radiação , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/radioterapia , Modelos Lineares , Estudos Retrospectivos , Fatores EtáriosRESUMO
BACKGROUND: The treatment of the acute lymphocytic leukaemia can determine impaired growth. SUBJECTS AND METHOD: All the patients had length measurements at the time of the beginning of the treatment and, at least, one year after the end of it. CONCLUSIONS: There was impaired growth after the treatment according to the dose regimens (18 or 24 Grays). No relation was observed related to the age at the diagnosis.
Assuntos
Irradiação Craniana/efeitos adversos , Crescimento/efeitos da radiação , Leucemia-Linfoma Linfoblástico de Células Precursoras/radioterapia , Fatores Etários , Estatura/efeitos da radiação , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Estudos RetrospectivosRESUMO
Objetivo. Determinar alteraçoes no crescimento após o tratamento de leucemia linfóide aguda em meninas. Pacientes e Métodos. Realizou-se estudo restrospectivo com 59 meninas que apresentavam medidas de estatura antes e com no mínimo um ano do tratamento, subdivididas de acordo com a dose de radioterapia cranial utilizada [18 ou 24 Grays Gy] e com a idade no início do tratamento (antes e após os cinco anos de idade). Resultados. Observou-se deficiência do crescimento com um, dois e mais de dois anos do tratamento. O crescimento foi mais afetado no grupo tratado com 24Gy, quando comparado com 18Gy. Nao houve diferenças com relaçao à idade no início do tratamento. Conclusoes. Houve retardo no crescimento após o tratamento, independentemente da idade em que foi realizado, mas dependente da dose de radioterapia cranial utilizada.
Assuntos
Criança , Pré-Escolar , Lactente , Feminino , Humanos , Irradiação Craniana/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/radioterapia , Crescimento/efeitos da radiação , Estatura/efeitos da radiação , Estudos Retrospectivos , Fatores EtáriosRESUMO
PURPOSE: Little clinical information about Hodgkin's disease in children is available from poor countries. The object of this study is to evaluate our data in Campinas, Brazil and hope "to make one dot on the geographic map of this disease more clear." PATIENTS AND METHODS: Between 1978 and 1988, 46 patients under the age of 17 years with biopsy-proven Hodgkin's Disease (HD) were referred for evaluation at Centro Boldrini in Campinas, São Paulo state, in Brazil. Thirty-seven of them were treated and followed-up only at this Center and are the subjects of this analysis. All the original histological slides were obtained, reviewed, and classified according to the Rye system. Staging procedures included exploratory laparotomy in 33 of 37 children, but none had lymphangiography. Treatment was individualized until January 1986 when the German protocol was adopted. RESULTS: Nineteen cases were classified as nodular sclerosis, 14 as mixed cellularity, and three as lymphocyte depleted. Mean age was 7 years; male/female ratio was 2:1. Fifty percent were advanced stages III and IV and 46% (17/37) had at least one of the systemic B symptoms. Mean follow-up was 81 months (range from 41 to 174 months). Five-year actuarial overall survival was 78%. Two children (5%) had acute myeloid leukemia at 25 and 49 months after diagnosis. CONCLUSIONS: Although distribution of histological subtypes of our cases is similar to other reports in developed countries, as well as percentage of advanced stages III/IV, our patients fared worse when compared to those reports. The reason for this continues to remain unclear but it does not seem to be related to histology subtypes.
Assuntos
Doença de Hodgkin , Adolescente , Brasil , Criança , Pré-Escolar , Feminino , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Humanos , Lactente , Masculino , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
The causes of high morbidity due to infection among children with sickle-cell disease (SD) are unknown. Immunlogical studies have focused on spleen function, on the alternative complement pathway, and recently on phagocytic activity. We evaluated Fc recptor-mediated phagocytic activity. We evaluated Fc receptor-mediated phagocytosis (sheep red cells opsonized with rabbit anti-E IgG, EA) and C3b receptor-mediated phagocytosis (zymosan particles incubated with fresh serum) in 27 children with SD. The control group consisted of 28 normal children matched by age and sex. The phagocytic indices obtained for cells from patients with SD were significantly lower than those for the controls (P < 0.001), both when EA and zymosan were used independent of whether the zymosan particles were incubated with patient serum or with a pool of normal sera. The results suggest the absence of abnormalities in the alternative complement pathway but do indicate an intrinsic cellular defect
Assuntos
Lactente , Pré-Escolar , Criança , Adolescente , Humanos , Anemia Falciforme/sangue , Monócitos/fisiologia , Fagocitose , Receptores de Complemento/fisiologia , Receptores Fc/fisiologiaRESUMO
The causes of high morbidity due to infection among children with sickle-cell disease (SD) are unknown. Immunological studies have focused on spleen function, on the alternative complement pathway, and recently on phagocytic activity. We evaluated Fc receptor-mediated phagocytosis (sheep red cells opsonized with rabbit anti-E IgG, EA) and C3b receptor-mediated phagocytosis (zymosan particles incubated with fresh serum) in 27 children with SD. The control group consisted of 28 normal children matched by age and sex. The phagocytic indices obtained for cells from patients with SD were significantly lower than those for the controls (P less than 0.001), both when EA and zymosan were used and independent of whether the zymosan particles were incubated with patient serum or with a pool of normal sera. The results suggest the absence of abnormalities in the alternative complement pathway but do indicate an intrinsic cellular defect.