Targeted approaches to childhood cancer: progress in drug discovery and development.

INTRODUCTION: Cancer is a leading cause of death in childhood. Encouraging progress has been made in the treatment of childhood malignancies, but there is an unmet need for new drugs to improve survival and reduce treatment-associated toxicities. Drug development in paediatric oncology has specific requirements with regard to the patient population and the regulatory background and presents several unique challenges that need addressing. AREAS COVERED: This review discusses the current framework of paediatric oncology drug development and some of the specific challenges in pre-clinical and clinical research. The authors discuss the recent developments in the targeting of various signalling pathways. These pathways represent a selection of targets that have been identified by pre-clinical and clinical investigators to be highly relevant in paediatric malignancies. EXPERT OPINION: The development of targeted agents in paediatric oncology must be driven by knowledge of tumour biology. Predictive and pharmacodynamic biomarkers should be incorporated within paediatric early clinical trials wherever possible. Faster dose-escalation, limited numbers of cohorts and novel adaptive designs can help to make paediatric early clinical trials more efficient. Close collaboration between academic/clinical researchers, the pharmaceutical industry, regulatory bodies and parent groups are crucial in overcoming the challenges associated with paediatric oncology drug development.

Hemicerebellitis: Report of three paediatric cases and review of the literature.

Acute inflammation of a single cerebellar hemisphere (hemicerebellitis) is a rare disorder of unknown origin. The clinical presentation is mainly characterized by headache, ataxia, dysmetria, and vomiting. In addition, some children may develop severe intracranial hypertension. The neuroimaging of hemicerebellitis raises a challenging differential diagnosis, particularly with posterior fossa tumours. Although there is no standard treatment for hemicerebellitis, its outcome is usually favourable. However, ipsilateral hemicerebellar atrophy develops in up to half of cases, and a minority of children may show persisting fine motor and/or neurocognitive sequelae. In this article, we contribute with three new reports and review a total of 35 cases of hemicerebellitis.

Neurofibromatosis type 1 associated with moyamoya syndrome in children.

BACKGROUND: Vascular abnormalities in neurofibromatosis type 1 may arise anywhere in the cardiovascular system, and cerebrovascular involvement is the predominant feature of moyamoya syndrome. Because neurofibromatosis type 1 is a neurocutaneous disorder and routine follow-up with cranial MRI is not standard practice in asymptomatic children, accurate epidemiologic data are lacking. On follow-up, clinical and radiologic progression is often found in patients with moyamoya syndrome. METHODS: We performed a retrospective analysis on children with neurofibromatosis type 1 who had been diagnosed with moyamoya syndrome on cranial MRI. RESULTS: Of the 197 children diagnosed with neurofibromatosis type 1, 168 had undergone a cranial MRI, and four (2.3%) of them had moyamoya syndrome. At diagnosis, one child had headache and vomiting related to a right frontal hematoma and the other three children were asymptomatic, including one child with a previous history of renal arteriopathy. In two children moyamoya syndrome was unilateral. CONCLUSIONS: The association between moyamoya syndrome and neurofibromatosis type 1 is rare, but it poses a potential risk of clinicoradiologic progression. Targeted monitoring of children with neurofibromatosis type 1 ensures an early diagnosis of moyamoya syndrome.

Gorham-Stout disease and cerebrospinal fluid otorrhea.

OBJECTIVE AND IMPORTANCE: Gorham-Stout disease is a rare entity characterized by vascular proliferation causing local destruction of bone tissue. Owing to its low incidence and variable clinical presentation, the diagnosis requires a high degree of awareness by the clinician. CLINICAL PRESENTATION: We present the case of a 2-year-old boy diagnosed of Gorham-Stout syndrome with involvement of the temporal bone and secondary cerebrospinal fluid (CSF) leakage. INTERVENTION: Because of the CSF leakage, the patient required two surgical interventions. The second intervention included mastectomy and placement of a patch and a lumbar drainage device during 50 days, after which the leakage ceased. CONCLUSION: Gorham-Stout disease is a rare condition that can affect the skull base and even present with CSF leakage.

Acute glomerulonephritis associated with pneumonia: a review of three cases.

We evaluated the clinical presentation and prognosis of three children with acute glomerulonephritis (AGN) associated with pneumonia. The patient database of Niño Jesús Children's Hospital was analyzed retrospectively (1996-2007) for patients diagnosed at discharge with both pneumonia and AGN. Those with recent pharyngeal or cutaneous infection were excluded. Three patients (1.67, 4.25, and 5 years old, respectively) were selected. All of them had lobar pneumonia, developing both macrohematuria and proteinuria within 24 h after admission. Decreased glomerular filtration rate was found in one patient. Two children developed arterial hypertension and one a slight pleural effusion. Two children had low C3 levels, and one had both low C3 and C4 levels. A Streptococcus pneumoniae serotype 17F was isolated from the blood culture of one patient. On follow-up, all patients had normal blood pressure and renal function with microhematuria persisting long term. Our patients with pneumonia-associated AGN had a good prognosis for both pulmonary and renal involvement.

Fiebre mediterránea familiar / Familial Mediterrane an fever

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