Sonic hedgehog signaling is active in human adrenal cortex development and deregulated in adrenocortical tumors.

BACKGROUND: The sonic hedgehog (SHH) pathway plays a key role in rodent adrenal cortex development and is involved in tumorigenesis in several human tissues, but data in human adrenal glands are limited. OBJECTIVES: The objectives of the study were to analyze the involvement of the SHH pathway in human adrenal development and tumorigenesis and the effects of SHH inhibition on an adrenocortical tumor (ACT) cell line. PATIENTS AND METHODS: Expression of SHH pathway components was evaluated by immunohistochemistry in 51 normal adrenals (33 fetal) and 34 ACTs (23 pediatric) and by quantitative PCR in 81 ACTs (61 pediatric) and 19 controls (10 pediatric). The effects of SHH pathway inhibition on gene expression and cell viability in the NCI-H295A adrenocortical tumor cell line after cyclopamine treatment were analyzed. RESULTS: SHH pathway proteins were present in fetal and postnatal normal adrenals and showed distinct patterns of spatiotemporal expression throughout development. Adult adrenocortical carcinomas presented with higher expression of PTCH1, SMO, GLI3, and SUFU compared with normal adult adrenal cortices. Conversely, pediatric ACTs showed lower mRNA expression of SHH, PTCH1, SMO, GLI1, and GLI3 compared with normal pediatric adrenal cortices. In vitro treatment with cyclopamine resulted in decreased GLI3, SFRP1, and CTNNB1 mRNA expression and ß-catenin staining as well as decreased cell viability. CONCLUSIONS: The SHH pathway is active in human fetal and postnatal adrenals, up-regulated in adult adrenocortical carcinomas, and down-regulated in pediatric ACTs. SHH pathway antagonism impaired cell viability. The SHH pathway is deregulated in ACTs and might provide a new target therapy to be explored.

Gonadal function in adolescent patients submitted to chemotherapy during childhood or during the pubertal period.

STUDY OBJECTIVE: To determine the presence of impaired gonadal function in adolescent patients submitted to chemotherapy during childhood or during the pubertal period. DESIGN: A case series study of 28 patients aged 12 to 19 years with menarche at least 2 years before the study. SETTING: Tertiary care public hospital. PARTICIPANTS: Group I: 14 adolescents previously submitted to chemotherapy during the prepubertal or peripubertal period and with remission of oncologic disease for at least 2 years; Group II: 14 normal adolescents with no previous oncologic disease and with regular menstrual cycles. INTERVENTIONS AND MAIN OUTCOME MEASURES: Pubertal development, menstrual cycles and serum levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were determined during the early follicular phase. RESULTS: There were no differences between the two groups in terms of age at appearance of secondary sexual characteristics or age at menarche. Menstrual irregularity was detected in 7 of the 14 patients in Group I, all 8 of whom presented oligomenorrhea. There were no differences in LH levels between the two groups (P = 0.55), although mean FSH levels were higher in Group I than in Group II (6.71 +/- 2.99 mIU/ml vs. 3.83 +/- 2.01 mIU/ml, P = 0.01). CONCLUSION: Although girls submitted to chemotherapy during the prepubertal or peripubertal period presented normal sexual development, the incidence of oligomenorrhea was higher than expected for their age, and FSH levels, although within normal limits, were higher than those seen in normally cycling girls.

Molecular profiling identifies prognostic subgroups of pediatric glioblastoma and shows increased YB-1 expression in tumors.

PURPOSE: Pediatric glioblastoma (pGBM) is a rare, but devastating brain tumor. In contrast to GBM in adults (aGBM), little is known about the mechanisms underlying its development. Our aim is to gain insight into the molecular pathways of pGBM. MATERIALS AND METHODS: Thirty-two pGBM and seven aGBM samples were investigated using biochemical and transcriptional profiling. Ras and Akt pathway activation was assessed through the phosphorylation of downstream effectors, and gene expression profiles were generated using the University Health Network Human 19K cDNA arrays. Results were validated using real-time polymerase chain reaction and immunohistochemistry and compared with existing data sets on aGBM. RESULTS: There are at least two subsets of pGBM. One subset, associated with Ras and Akt pathway activation, has very poor prognosis and exhibits increased expression of genes related to proliferation and to a neural stem-cell phenotype, similar to findings in aggressive aGBM. This subset was still molecularly distinguishable from aGBM after unsupervised and supervised analysis of expression profiles. A second subset, with better prognosis, is not associated with activation of Akt and Ras pathways, may originate from astroglial progenitors, and does not express gene signatures and markers shown to be associated with long-term survival in aGBM. Both subsets of pGBM show overexpression of Y-box-protein-1 that may help drive oncogenesis in this tumor. CONCLUSION: Our work, the first study of gene expression profiles in pGBM, provides valuable insight into active pathways and targets in a cancer with minimal survival, and suggests that these tumors cannot be understood exclusively through studies of aGBM.

Involvement of the bony orbit in infantile myofibromatosis.

Infantile myofibromatosis is a rare disorder of infancy that can provoke osteolytic lesions. A 15-day-old infant presented with three round, firm lesions located on the forehead, shoulder, and back. Excisional biopsy of the forehead lesion revealed that the tumor was composed of spindle cells resembling normal smooth muscle arranged in short fascicles. Immunohistochemical staining was positive for vimentin and actin. Five months later, the child presented with three new lesions, including one in the superolateral aspect of the left orbit. It is important to recognize the multicentric form of infantile myofibromatosis because, despite its aggressive clinical presentation, the disease is benign and usually does not require extensive surgery or chemotherapy.

Pancitopenia transitóoria induzida por parvovírus B19 em criança portadora de esferocitose hereditária / Transient pancytopenia induced by parvovirus B19 in a child with hereditary sherocytosis

Objetivo: Relatar a ocorrência de pancitopenia transitória, decorrente de infecção pelo parvovírus B19, em um paciente portador de anemia hemolíitica hereditária e comentar a importância do diagnóstico desta infecção. Métodos: Relato de caso clínico acompanhado pelos autores, diagnosticado sorologicamente e pelo método da reação em cadeia da polimerase (PCR), e revisão da literatura. Resultados: Menino de 12 anos, portador de esferocitose hereditária, apresentando quadro infeccioso inespecífico seguido de pancitopenia grave, transitória, com diagnóstico de infecção por parvovírus B19. Conclusões: O diagnóstico da infecção por parvovírus B19 é de particular importância em hematologia, principalmente quando estão presentes algumas condições mórbitas, entre elas as anemias hemolíticas hereditárias, sendo o método de PCR útil por permitir rapidez e boa sensibilidade no diagnóstico específico desta patologia