RESUMO
PURPOSE: Wilms tumor gene 1 (WT1), a zinc-finger transcription factor essential for testis development and function, along with other genes, was investigated for their role in the pathogenesis of testicular germ cell tumors (TGCT). METHODS: In total, 284 TGCT and 100 control samples were investigated, including qPCR for WT1 expression and BRAF mutation, p53 immunohistochemistry detection, and massively parallel amplicon sequencing. RESULTS: WT1 was significantly (p < 0.0001) under-expressed in TGCT, with an increased ratio of exon 5-lacking isoforms, reaching low levels in chemo-naïve relapsed TGCT patients vs. high levels in chemotherapy-pretreated relapsed patients. BRAF V600E mutation was identified in 1% of patients only. p53 protein was lowly expressed in TGCT metastases compared to the matched primary tumors. Of 9 selected TGCT-linked genes, RAS/BRAF and WT1 mutations were frequent while significant TP53 and KIT variants were not detected (p = 0.0003). CONCLUSIONS: WT1 has been identified as a novel factor involved in TGCT pathogenesis, with a potential prognostic impact. Distinct biologic nature of the two types of relapses occurring in TGCT has been demonstrated. Differential mutation rate of the key TGCT-related genes has been documented.
Assuntos
Biomarcadores Tumorais/genética , Genes ras , Mutação , Neoplasias Embrionárias de Células Germinativas/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas c-kit/genética , Neoplasias Testiculares/genética , Proteína Supressora de Tumor p53/genética , Proteínas WT1/genética , Linhagem Celular Tumoral , Análise Mutacional de DNA/métodos , Regulação para Baixo , Estudos de Viabilidade , Predisposição Genética para Doença , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imuno-Histoquímica , Masculino , Neoplasias Embrionárias de Células Germinativas/enzimologia , Neoplasias Embrionárias de Células Germinativas/patologia , Fenótipo , Estudos Prospectivos , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Neoplasias Testiculares/enzimologia , Neoplasias Testiculares/patologiaRESUMO
The suspicion of phimosis is more frequent than it's real occurrence. The diagnosis of phimosis is often used for another nonobstructive conditions of prepuce--conglutination or tight prepuce. The early operation is necessary just in cases of real phimosis, whereas conservative approach is recommended in cases of conglutination and tight prepuce. Physiological development can bring spontaneous improvement in these children. In boys with persisting tight prepuce operation is indicated.
Assuntos
Fimose/cirurgia , Pré-Escolar , Humanos , Lactente , Masculino , Métodos , Fimose/diagnósticoRESUMO
The authors defined a uniform classification of abnormal positions of the testes. They recommend also a uniform therapeutic procedure: after the first year of life treatment with human chorionic gonadotropin in one or two curves, if orchiopexy fails.
Assuntos
Criptorquidismo/terapia , Testículo/patologia , Humanos , Lactente , MasculinoRESUMO
The standard of care of children and adolescents with chronic renal failure and chronic renal insufficiency in the CSR does not correspond to the european average so far. Dialysis- treatment, contrary to treatment of adults, was started at the beginning of the eighties. The reason was that equipment for dialysis was not readily available. At presents the basic prerequisites have been created for dialysis and transplantation in the mentioned age groups. Rapid improvement will be helped also by organizational provisions the concept of which outlined in the paper.
