Osteopontin predicts radiotherapy response of glioblastoma patients : new role in DNA damage repair
Henry, Aurélie ; ; Leroi, Natacha et al
Conference (2016, March 22)
- Introduction: Glioblastoma (GBM) is the most aggressive and common solid human brain tumor. Because of GBM heterogeneity, location and aggressiveness, none of the available treatment is curative. These ... [more ▼]
- Introduction: Glioblastoma (GBM) is the most aggressive and common solid human brain tumor. Because of GBM heterogeneity, location and aggressiveness, none of the available treatment is curative. These treatments include maximal surgical resection, radiotherapy and concomitant or adjuvant chemotherapy with Temozolomide. However, the prognosis of adult patients with GBM remains poor and the survival outcome after treatment does not exceed 15 months. GBM-composing cells have developed many strategies to counteract these current therapies. Among the wide hallmarks acquired to survive, high osteopontin (OPN) expression correlates with lower overall and disease-free/relapse-free survival in all tumors combined, as well in brain cancer. Our recent study (Lamour V and Henry A, IJC 2015) has demonstrated the role of OPN in the tumorigenicity of glioblastoma cells and its importance in the maintenance of the stem characters. In the continuation of this work, our recent studies focused on the potential role of OPN in the resistance of GBM cells to radiotherapy and its potential implication in the initiation of Double Strand Breaks (DSBs) repair mechanisms. - Aims: In the context of this study, different GBM cell lines (U251-MG, U87-MG and U87 Viii) were used to assess the role of OPN in the initiation of the DSBs repair mechanism after an exposure to gamma-irradiation. - Methods and results: We performed the transient transfection of different GBM cell lines (U251-MG, U87-MG and U87-MG overexpressing EGFR VIII) with siRNAs specifically directed against OPN. After irradiation, all these OPN-depleted cells consistently showed a lower induction of γ–H2AX compared to control (irrelevant siRNA) as evidenced by western blot and immunofluorescence techniques. Thereafter, clonogenic assays allowed to prove that the survival of OPN-depleted cells was affected after an exposure to irradiation. To assess the importance of OPN expression in the response to radiotherapy, an heterotopic xenograft model was used. In brief, IPTG-inducible U87 shOPN clones were injected subcutaneously in NOD-SCID mice and were allowed to form a tumor. When average tumor volume reached a predetermined size range, mice were treated (or not) with IPTG by intraperitoneal injection during five days. At the end of the treatment, tumors were selectively exposed to gamma-irradiation by using a small animal irradiator X-RAD 225Cx (Precision X-Ray Inc., North Branford, CT). One week later, mice were sacrificed and tumors were measured. In this pilot study, we observed that mice in which the tumor was depleted in OPN displayed a slight regression in the tumor growth compared to mice that received radiotherapy alone (no IPTG), where the tumor volume remained constant. - Conclusions: Taken together, these preliminary data meet the fact that OPN is important in the response of GBM to radiotherapy. The in vitro results converge to the fact that OPN might be implicated in the initiation of the DSBs repair following irradiation. Currently, we would like to investigate this hypothesis in vivo but also to check the effect of OPN depletion combined to radiotherapy on the survival of mice in an orthotopic xenograft model. [less ▲]Detailed reference viewed: 25 (13 ULg)
Age and WHO Performance Score are major clinical prognostic factors in glioblastoma
Lambert, Jérémy ; Scholtes, Félix ; MARTIN, Didier
Conference (2015, March 21)
In glioblastoma patients with similar prognostic factors—like age, performance status and extent of surgical resection—clinical evolution is still variable. In addition, the benefit of resection of ... [more ▼]
In glioblastoma patients with similar prognostic factors—like age, performance status and extent of surgical resection—clinical evolution is still variable. In addition, the benefit of resection of recurrent tumours is uncertain. In this study, prognostic subgroups are established on a clinical basis and the benefit of surgery for recurrence is compared between them. Recursive partitioning analysis on EORTC sample 26981 (n=239) identified clinical factors influencing Progression-Free Survival (PFS), in order to create prognostic subgroups, whose PFS and survival after recurrence were compared using Kaplan-Meier curves and log-rank tests. Results were validated on a sample from Liège University Hospital (n=92). WHO Performance Status (WHO-PS) and age at first intervention (“age”) defined 4 subgroups. PFS was shorter in WHO-PS 2–3 than WHO PS 0–1 patients. In both groups, age was the second classifying factor (cut-off: 47.5y for WHO-PS 0–1, 60.5y for WHO-PS 2–3). The 4 subgroups had significantly different median PFS (77.5, 144, 234.5 and 346.5 days) and median overall survival (126, 330, 476 and 675 days). Survival after recurrence was correlated with PFS, and recurrence resection was associated with longer survival, regardless of the prognostic subgroup. Clinical prognostic glioblastoma subgroups with distinct PFS exist and can be defined by WHO-PS and age. This classification can be used as a clinical basis to identify molecular patterns associated with prognosis. In addition, in all subgroups, this retrospective analysis suggests a benefit of surgical resection when feasible. [less ▲]Detailed reference viewed: 58 (5 ULg)
Identification de sous-groupes de glioblastome sur base de critères cliniques
Lambert, Jérémy ; Scholtes, Félix ; MARTIN, Didier
Poster (2014, December)
Glioblastoma has terrible outcomes, but the disease evolution varies a lot between patients. We used a sample of 239 patients (EORTC 26981) and a validation sample of 93 patients (CHU Liège) to class ... [more ▼]
Glioblastoma has terrible outcomes, but the disease evolution varies a lot between patients. We used a sample of 239 patients (EORTC 26981) and a validation sample of 93 patients (CHU Liège) to class patients in groups with the same risk of recurrence. 4 distinct subgroups were created using recursive partitioning analysis. In the future, genetic profile will be compared between these groups to find markers of aggressiveness. Moreover, survival after recurrence is closely related to subgroups, and a surgical resection of the recurrence shows positive effect in each subgroup. [less ▲]Detailed reference viewed: 36 (2 ULg)
Facteurs de mauvais pronostic d’une lomboradiculalgie opérée par (micro) discectomie
Demoulin, Christophe ; ; DEFAWEUX, Michel et al
in Revue du Rhumatisme (2014, December), 81SDetailed reference viewed: 82 (14 ULg)
Polymethylmethacrylate (PMMA) augmentation of the pedicle screws in patients with fractures of osteoporotic bone. About our experience.
HENROTEAUX, Adrienne ; RACARU, Tudor ; Martin, Didier et al
Conference (2014, March 29)Detailed reference viewed: 56 (2 ULg)
Intraoperative MRI versus standard neuron- avigation for the neurosurgical treatment of glioblastoma: a randomized controlled trial.
; Scholtes, Félix ; et al
in Surgical Neurology (2014), 5Detailed reference viewed: 36 (6 ULg)
Head Trauma and Distal Anterior Cerebral Artery Aneurysm: Potential Role of an Adhesion to the Falx
Scholtes, Félix ; HENROTEAUX, Adrienne ; OTTO, Bernard et al
in Journal of Neurological Surgery. Part A, Central European Neurosurgery (2014), [Epub ahead of print]Detailed reference viewed: 47 (14 ULg)
Glioblastoma metastases:case report and literature review
REUTER, Gilles ; Lombard, Arnaud ; SCHOLTES, Félix et al
Poster (2013, March 30)Detailed reference viewed: 46 (15 ULg)
Malformations vasculaires du système nerveux central : que faire quand on en trouve ?
SCHOLTES, Félix ; MARTIN, Didier
Scientific conference (2013, January 16)Detailed reference viewed: 31 (4 ULg)
La hernie discale lombaire paralysante : une urgence chirurgicale ? Réflexion à propos d'une série de 24 patients et des données de la littérature.
DUBUISSON, Annie ; ; SCHOLTES, Félix et al
in Neuro-Chirurgie (2013), 59(2), 64-8
BACKGROUND AND PURPOSE: Paralysing lumbar disc herniation (LDH): what and when to do? Few studies have analyzed the optimal timing of surgery in case of paralysing LDH. METHODS: Twenty-four charts were ... [more ▼]
BACKGROUND AND PURPOSE: Paralysing lumbar disc herniation (LDH): what and when to do? Few studies have analyzed the optimal timing of surgery in case of paralysing LDH. METHODS: Twenty-four charts were retrospectively reviewed of patients suffering of LDH with severe motor deficit. RESULTS: There were 16 men and eight women. Mean age was 45.1 years. Seventeen patients suffered of lumbar pain, 15 of radicular pain and all of a severe motor deficit, implying mostly the ankle flexion (17 patients). LDH was most frequently located at L4/L5 or L5/S1 level. Surgery was proposed to all patients at the end of the consultation. Nine patients were operated within 48 hours. The mean interval between onset of motor deficit and operation was 20 days. The statistical analysis did not reveal any significant difference among different prognostic factors between the 17 patients with good motor recovery and the seven patients with poor motor recovery. In particular the operative delay did not appear to influence the degree of motor recovery. Literature review on paralysing LDH provides five published series since 1996, including 28 to 116 patients. Two series, including the single prospective one, conclude that the degree of recovery of motor function is inversely related to the degree and duration of motor deficit. CONCLUSIONS: Our retrospective series of 24 operated paralysing LDH did not reveal any prognostic factor for motor recovery. There is no evidence based medicine data in the literature about the optimal timing of decompressive surgery. A relative consensus exists among spine surgeons for paralysing LDH: since operative indication is obvious, surgery should be done as soon as possible. [less ▲]Detailed reference viewed: 181 (29 ULg)
Posterior cerebral artery duplication and plasty of the right third cranial nerve
SALADO, Anne-Laure ; SCHOLTES, Félix ; OTTO, Bernard et al
Conference (2012, March 10)Detailed reference viewed: 56 (8 ULg)
Multifocal choroid plexus papilloma: a case report.
; Scholtes, Félix ; Robe, Pierre et al
in Clinical neuropathology (2012), 31(6), 430-4
BACKGROUND: Multiple choroid plexus papillomas (CPPs) are rare. Usually, they correspond to villous hypertrophy or metastasis occurring during cerebrospinal dissemination. Multiple CPPs have rarely been ... [more ▼]
BACKGROUND: Multiple choroid plexus papillomas (CPPs) are rare. Usually, they correspond to villous hypertrophy or metastasis occurring during cerebrospinal dissemination. Multiple CPPs have rarely been reported as synchronous tumors. CASE REPORT: Three synchronous CPPs were resected in a 59-year-old female 6 years after their first imaging description. Pathology showed mucus-producing CPP in all 3, 1 of the 3 presenting some signs of atypia. No p53 or hSNF5/INI1 mutation, or signs of polyoma viruses infection were found. CONCLUSION: Although no clear cause for the multifocality was found, the simultaneous presence of the three tumors and their benign histology suggest that they were synchronous and not metastatic. The issue of differentiating synchronous CPPs from metastatic CPP is discussed. [less ▲]Detailed reference viewed: 41 (5 ULg)
Les anévrismes de très petite dimension : clip ou coil.
; SCHOLTES, Félix ;
in Neuro-Chirurgie (2012), 58(2-3), 156-9
INTRODUCTION: It is not unusual for very small aneurysms (</=3mm) to be responsible for subarachnoid haemorrhage. In addition, modern imaging has increased diagnosis of those that are asymptomatic ... [more ▼]
INTRODUCTION: It is not unusual for very small aneurysms (</=3mm) to be responsible for subarachnoid haemorrhage. In addition, modern imaging has increased diagnosis of those that are asymptomatic. Because of their spatial configuration and thin and fragile walls, very small aneurysms can be a sizeable challenge for both open surgical and endovascular treatment. Based on recent literature data, the present manuscript reviews treatment indications and the choice of treatment strategy to occlude these particular aneurysms. METHODS: Literature review concerning surgical and endovascular treatment of very small aneurysms (</=3mm). Arterial dissections and blister aneurysms were excluded. RESULTS: We found no study that systematically and specifically assessed surgical treatment of very small aneurysms. Investigations of endovascular treatment are almost exclusively retrospective, usually evaluating a small number of patients, and are limited by selection bias. Despite often contradictory results, it appears that very small aneurysms carry a higher risk of rupture during endovascular procedures and higher ensuing mortality, as compared to larger aneurysms. The use of more flexible coils and additional endovascular tools appears to reduce this risk. There is no study comparing surgical to endovascular treatment. CONCLUSION: Very small aneurysms carry higher treatment risks than larger aneurysms. A prospective randomised trial is justified for those very small aneurysms for which treatment is indicated. [less ▲]Detailed reference viewed: 17 (2 ULg)
Solitary fibrous tumour of the vagus nerve.
; SCHOLTES, Félix
in British journal of neurosurgery (2012), 26(2), 293-5
We describe the complete removal of a foramen magnum solitary fibrous tumour in a 36-year-old woman. It originated on a caudal vagus nerve rootlet, classically described as the 'cranial' accessory nerve ... [more ▼]
We describe the complete removal of a foramen magnum solitary fibrous tumour in a 36-year-old woman. It originated on a caudal vagus nerve rootlet, classically described as the 'cranial' accessory nerve root. This ninth case of immunohistologically confirmed cranial or spinal nerve SFT is the first of the vagus nerve. [less ▲]Detailed reference viewed: 44 (0 ULg)