Rôle de l'adrénomédulline dans la néoangiogenèse et l'invasion tumorale

Les glioblastomes sont des tumeurs fatales du fait de leur agressivité et du manque de traitements efficaces. La prolifération accrue, le caractère invasif et la résistance à la mort cellulaire leur confèrent une croissance rapide et une invasion du parenchyme cérébral environnant, à l origine de leur systématique récidive. Exprimée par la composante tumorale en hypoxie mais également par la composante vasculaire, l AM participe de façon autocrine et paracrine au développement des glioblastomes en favorisant la croissance des cellules tumorales et l angiogenèse tumorale.Il a été montré que des anticorps polyclonaux dirigés contre les récepteurs de l AM inhibent in vitro la croissance, la migration et la formation de pseudo-capillaires des cellules endothéliales, suggérant une neutralisation par ces anticorps de certaines étapes de l angiogenèse. De même, il a été montré in vivo que ces anticorps inhibent la croissance tumorale en supprimant l angiogenèse et la croissance des cellules tumorales suggérant ainsi que les récepteurs de l AM constitueraient une bonne cible thérapeutique. Des anticorps capables de reconnaître et neutraliser à la fois l AM, les CLR, RAMP2 et RAMP3 agissant de la même manière sur la croissance tumorale et l angiogenèse représenteraient un bénéfice thérapeutique majeur. Des anticorps dirigés contre un peptide chimérique constitué de l enchainement de séquences peptidiques des protéines CLR, RAMP2, RAMP3 et du peptide AM sont en cours. Le traitement par ces anticorps diminue la croissance des cellules tumorales ainsi que leurs migration et invasion. Ces résultats très encourageants nous permettent pour le moment de valider la faisabilité du concept d anticorps développés à partir d un peptide chimérique pour neutraliser le système AM/AMR dans le but d envisager dans le futur une application thérapeutique.Glioblastoma are fatal tumors because of their aggressiveness and lack of effective treatments. The increased proliferation, the invasiveness and resistance to cell death gives them a rapid growth and invasion of brain parenchyma surrounding the origin of their systematic recurrence. Expressed by the tumoral component in hypoxia but also by the vascular component, the AM participate by an autocrine and paracrine way, the development of glioblastoma by promoting tumor ell growth and tumor angiogenesis.It was shown that polyclonal antibodies directed against the AM receptor inhibit in vitro growth, migration and the formation of pseudo-capillary of endothelial cells, suggesting neutralization by theses antibodies in certain stages of angiogenesis. Similarly, it has been shown in vivo that these antibodies inhibit tumor growth by suppressing angiogenesis and tumor cell growth, suggesting that the AM receptor would be a good therapeutic target. Antibodies that recognized and neutralized both the AM, the CLR, RAMP2 and RAMP3 acting the same way on tumor growth and angiogenesis represent a major therapeutic benefit. Antibodies against a chimeric peptide consisting of peptide sequence of CLR, RAMP2, RAMP3 and AM peptide are in progress. Treatment with these antibodies decreases the growth of tumor cells, their migration and invasion. These encouraging results allow us the time to validate the feasibility of the concept of antibodies developed from a chimeric peptide to neutralize the AM/AMR system in order to consider in the future therapeutic application.AIX-MARSEILLE2-Bib.electronique (130559901) / SudocSudocFranceF

Clinical course and progression-free survival of adult intracranial and spinal ependymoma patients

Ependymomas are rare CNS tumors. Previous studies describing the clinical course of ependymoma patients were restricted to small sample sizes, often with patients at a specific institution

Diagnosis and treatment of brain metastases from solid tumors: guidelines from the European Association of Neuro-Oncology (EANO)

The management of patients with brain metastases has become a major issue due to the increasing frequency and complexity of the diagnostic and therapeutic approaches. In 2014, the European Association of Neuro-Oncology (EANO) created a multidisciplinary Task Force to draw evidence-based guidelines for patients with brain metastases from solid tumors. Here, we present these guidelines, which provide a consensus review of evidence and recommendations for diagnosis by neuroimaging and neuropathology, staging, prognostic factors, and different treatment options. Specifically, we addressed options such as surgery, stereotactic radiosurgery/stereotactic fractionated radiotherapy, whole-brain radiotherapy, chemotherapy and targeted therapy (with particular attention to brain metastases from non-small cell lung cancer, melanoma and breast and renal cancer), and supportive care

Rôle de l'adrénomédulline dans la néoangiogenèse et l'invasion tumorale

Les glioblastomes sont des tumeurs fatales du fait de leur agressivité et du manque de traitements efficaces. La prolifération accrue, le caractère invasif et la résistance à la mort cellulaire leur confèrent une croissance rapide et une invasion du parenchyme cérébral environnant, à l’origine de leur systématique récidive. Exprimée par la composante tumorale en hypoxie mais également par la composante vasculaire, l’AM participe de façon autocrine et paracrine au développement des glioblastomes en favorisant la croissance des cellules tumorales et l’angiogenèse tumorale.Il a été montré que des anticorps polyclonaux dirigés contre les récepteurs de l’AM inhibent in vitro la croissance, la migration et la formation de pseudo-capillaires des cellules endothéliales, suggérant une neutralisation par ces anticorps de certaines étapes de l’angiogenèse. De même, il a été montré in vivo que ces anticorps inhibent la croissance tumorale en supprimant l’angiogenèse et la croissance des cellules tumorales suggérant ainsi que les récepteurs de l’AM constitueraient une bonne cible thérapeutique. Des anticorps capables de reconnaître et neutraliser à la fois l’AM, les CLR, RAMP2 et RAMP3 agissant de la même manière sur la croissance tumorale et l’angiogenèse représenteraient un bénéfice thérapeutique majeur. Des anticorps dirigés contre un peptide chimérique constitué de l’enchainement de séquences peptidiques des protéines CLR, RAMP2, RAMP3 et du peptide AM sont en cours. Le traitement par ces anticorps diminue la croissance des cellules tumorales ainsi que leurs migration et invasion. Ces résultats très encourageants nous permettent pour le moment de valider la faisabilité du concept d’anticorps développés à partir d’un peptide chimérique pour neutraliser le système AM/AMR dans le but d’envisager dans le futur une application thérapeutique.Glioblastoma are fatal tumors because of their aggressiveness and lack of effective treatments. The increased proliferation, the invasiveness and resistance to cell death gives them a rapid growth and invasion of brain parenchyma surrounding the origin of their systematic recurrence. Expressed by the tumoral component in hypoxia but also by the vascular component, the AM participate by an autocrine and paracrine way, the development of glioblastoma by promoting tumor ell growth and tumor angiogenesis.It was shown that polyclonal antibodies directed against the AM receptor inhibit in vitro growth, migration and the formation of pseudo-capillary of endothelial cells, suggesting neutralization by theses antibodies in certain stages of angiogenesis. Similarly, it has been shown in vivo that these antibodies inhibit tumor growth by suppressing angiogenesis and tumor cell growth, suggesting that the AM receptor would be a good therapeutic target. Antibodies that recognized and neutralized both the AM, the CLR, RAMP2 and RAMP3 acting the same way on tumor growth and angiogenesis represent a major therapeutic benefit. Antibodies against a chimeric peptide consisting of peptide sequence of CLR, RAMP2, RAMP3 and AM peptide are in progress. Treatment with these antibodies decreases the growth of tumor cells, their migration and invasion. These encouraging results allow us the time to validate the feasibility of the concept of antibodies developed from a chimeric peptide to neutralize the AM/AMR system in order to consider in the future therapeutic application

Prise en charge thérapeutique des méningiomes du sinus caverneux (évaluation comparative des traitements par radiochirurgie Gamma Knife et radiothérapie conventionnelle fractionnée)

AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Successful Insular Glioma Removal in a Deaf Signer Patient During an Awake Craniotomy Procedure

International audienc

5-aminolevulinic acid–protoporphyrin IX fluorescence-guided surgery of high-grade gliomas : a systematic review

The current first-line treatment of malignant gliomas consists in surgical resection (if possible) as large as possible. The existing tools don’t permit to identify the limits of tumor infiltration, which goes beyond the zone of contrast enhancement on MRI. The fluorescence-guided malignant gliomas surgery was started 15 years ago and had become a standard of care in many countries. The technique is based on fluorescent molecule revelation using the filters, positioned within the surgical microscope. The fluorophore, protoporphyrin IX (PpIX), is converted in tumoral cells from 5-aminolevulinic acid (5-ALA), given orally before surgery. Many studies have shown that the ratio of gross total resections was higher if the fluorescence technique was used. The fluorescence signal intensity is correlated to the cell density and the PpIX concentration. The current method has a very high specificity but still lower sensibility, particularly regarding the zones with poor tumoral infiltration. This book reviews the principles of the technique and the results (extent of resection and survival)

Differential expression of miR200a-3p and miR21 in grade II–III and grade IV gliomas

International audienc

Comparative genomic analysis of primary tumors and paired brain metastases in lung cancer patients by whole exome sequencing: a pilot study

International audienceLung cancer brain metastases (BMs) are frequent and associated with poor prognosis despite a better knowledge of lung cancer biology and the development of targeted therapies. The inconstant intracranial response to systemic treatments is partially due to tumor heterogeneity between the primary lung tumor (PLT) and BMs. There is therefore a need for a better understanding of lung cancer BMs biology to improve treatment strategies for these patients. We conducted a study of whole exome sequencing of paired BM and PLT samples. The number of somatic variants and chromosomal alterations was higher in BM samples. We identified recurrent mutations in BMs not found in PLT. Phylogenic trees and lollipop plots were designed to describe their functional impact. Among the 13 genes mutated in ≥ 1 BM, 7 were previously described to be associated with invasion process, including 3 with recurrent mutations in functional domains which may be future targets for therapy. We provide with some insights about the mechanisms leading to BMs. We found recurrent mutations in BM samples in 13 genes. Among these genes, 7 were previously described to be associated with cancer and 3 of them (CCDC178, RUNX1T1, MUC2) were described to be associated with the metastatic process