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Sturm D.,German Cancer Research Center | Sturm D.,University of Heidelberg | Bender S.,German Cancer Research Center | Bender S.,University of Heidelberg | And 14 more authors.
Nature Reviews Cancer | Year: 2014

We have extended our understanding of the molecular biology that underlies adult glioblastoma over many years. By contrast, high-grade gliomas in children and adolescents have remained a relatively under-investigated disease. The latest large-scale genomic and epigenomic profiling studies have yielded an unprecedented abundance of novel data and provided deeper insights into gliomagenesis across all age groups, which has highlighted key distinctions but also some commonalities. As we are on the verge of dissecting glioblastomas into meaningful biological subgroups, this Review summarizes the hallmark genetic alterations that are associated with distinct epigenetic features and patient characteristics in both paediatric and adult disease, and examines the complex interplay between the glioblastoma genome and epigenome. © 2014 Macmillan Publishers Limited.

Grill J.,Gustave Roussy Cancer Institute | Grill J.,University Paris - Sud | Bergthold G.,University Paris - Sud | Ferreira C.,University Paris - Sud
Current Opinion in Oncology | Year: 2011

Purpose of Review: Ependymomas remain a therapeutic challenge in pediatric neuro-oncology. These tumors are chemoresistant and rather radioresistant and until recently little was known about their biology. Recent Findings: Histopathological grading of ependymomas according to the WHO classification is neither reproducible, nor correlated with outcome, especially in young children. Characterization of molecular abnormalities in ependymomas offers now a better understanding of their initiation and progression; different biological subtypes of tumors have been described and would need further validation. The identification of new prognostic biomarkers, such as tenascin-C overexpression or chromosome 1q gain, will considerably help patient stratification in future trials. Finally, the recent discovery of specific pathways involved in ependymomas oncogenesis, such as Notch-1or EPHB2 offers new perspectives for the development of targeted therapies. Summary: A comprehensive biological work-out including CGHarray and immunohistochemistry for specific biomarkers should now be recommended for the current management of pediatric ependymoma, especially in young children if radiotherapy has to be omitted in the first line of treatment. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Jacques G.,Gustave Roussy Cancer Institute | Cormac O.,Our Ladys Childrens Hospital
Handbook of Clinical Neurology | Year: 2013

Central nervous system tumors are the most frequent malignant tumor in children and the main cause of death in this age group after traffic accidents. The current estimates are that one adult in 2500 is a survivor of a brain tumor that occurred during childhood. These tumors are particularly heterogeneous in terms of histology/biology, treatment, and outcome. They share, however, a high risk of neurological and cognitive morbidity due to the disease itself and the treatment modalities (radiotherapy, surgery, and chemotherapy). Diagnosis is frequently delayed because symptoms are usually nonspecific at the beginning of the evolution. Posterior fossa is the most frequent site and the tumors present most frequently with signs of intracranial hypertension. Supratentorial tumors are more frequent in infants and in adolescents; seizures are not uncommon, especially for benign tumors. When adjuvant treatment is needed, radiotherapy is usually the mainstay apart from some histologies where chemotherapy may be sufficient: low-grade gliomas, desmoplastic medulloblastomas, malignant glial tumors in infants. Multidisciplinary care is best performed in tertiary care centers and should include early rehabilitation programs soon after surgery. © 2013 Elsevier B.V.

Bellesoeur A.,University of Paris Descartes | Carton E.,University of Paris Descartes | Mir O.,University of Paris Descartes | Mir O.,Gustave Roussy Cancer Institute | And 5 more authors.
Investigational New Drugs | Year: 2014

Sorafenib, a multi-kinase inhibitor that targets the VEGF, PDGF and BRAF pathways, has demonstrated significant clinical activity in metastatic differentiated thyroid cancer. However, all patients eventually experience disease progression with a median progression-free survival close to 10 months. Since sorafenib exposure is known to decrease over time, we hypothesized that dose adjustments aiming to restore adequate exposure could lead to further clinical activity. We report, as a proof of concept on a patient with radio-iodine resistant metastatic thyroid cancer, who experienced disease progression after an initial response to sorafenib (400 mg twice daily). Whereas the thyroglobulin-progression-free survival at standard doses was 6 months, iterative dose optimization led to a prolonged progression-free survival up to 41 months. Sorafenib doses were increased up to 1600 mg bid, in order to maintain clinical activity, and to restore active plasma concentration, since sorafenib exposure had decreased over the time. Toxicity was mild and manageable for more than 2 years. However, the patient eventually experienced grade 3 proteinuria leading to treatment discontinuation. This observation opens up new horizons for daily management of radioactive iodine-refractory differentiated thyroid cancer patients progressing under standard doses of sorafenib, and stress the need to monitor its plasma concentration. © 2014 Springer Science+Business Media.

Hay R.J.,Kings College | Baran R.,Nail Disease Center | Baran R.,Gustave Roussy Cancer Institute
Journal of the American Academy of Dermatology | Year: 2011

The classification of onychomycosis, infection of the nail apparatus caused by fungi, has changed over time with the recognition of new pathways of nail infection, new organisms, and new variations in the appearance of diseased infected nail. Taking into account published descriptions of nail morphology in fungal infection, the following forms of onychomycosis are recognized: distal and lateral subungual, superficial, endonyx, proximal subungual, mixed, totally dystrophic, and secondary onychomycosis. These can be subdivided, where appropriate, by color and pattern of nail plate change. The purpose of the revised classification is to provide a framework to assist selection of treatment, estimate prognosis, and evaluate new diagnostic methods. © 2010 by the American Academy of Dermatology, Inc.

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