References of "Robe, Pierre"
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See detailCXCL12 mediates glioblastoma resistance to radiotherapy in the subventricular zone.
Goffart, Nicolas ULg; Lombard, Arnaud; Lallemand, François ULg et al

in Neuro-Oncology (2017), 19(1), 66-77

BACKGROUND: Patients with glioblastoma (GBM) have an overall median survival of 15 months despite multimodal therapy. These catastrophic survival rates are to be correlated to systematic relapses that ... [more ▼]

BACKGROUND: Patients with glioblastoma (GBM) have an overall median survival of 15 months despite multimodal therapy. These catastrophic survival rates are to be correlated to systematic relapses that might arise from remaining glioblastoma stem cells (GSCs) left behind after surgery. In this line, it has recently been demonstrated that GSCs are able to escape the tumor mass and preferentially colonize the adult subventricular zone (SVZ). At a distance from the initial tumor site, these GSCs might therefore represent a high-quality model of clinical resilience to therapy and cancer relapses as they specifically retain tumor-initiating abilities. METHOD: While relying on recent findings that have validated the existence of GSCs in the human SVZ, we questioned the role of the SVZ niche as a potential GSC reservoir involved in therapeutic failure. RESULTS: Our results demonstrate that (i) GSCs located in the SVZ are specifically resistant to radiation in vivo, (ii) these cells display enhanced mesenchymal roots that are known to be associated with cancer radioresistance, (iii) these mesenchymal traits are specifically upregulated by CXCL12 (stromal cell-derived factor-1) both in vitro and in the SVZ environment, (iv) the amount of SVZ-released CXCL12 mediates GBM resistance to radiation in vitro, and (v) interferes with the CXCL12/CXCR4 signalling system, allowing weakening of the tumor mesenchymal roots and radiosensitizing SVZ-nested GBM cells. CONCLUSION: Together, these data provide evidence on how the adult SVZ environment, through the release of CXCL12, supports GBM therapeutic failure and potential tumor relapse. [less ▲]

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See detailMolecular-Based Recursive Partitioning Analysis Model for Glioblastoma in the Temozolomide Era: A Correlative Analysis Based on NRG Oncology RTOG 0525.
Bell, Erica Hlavin; Pugh, Stephanie L.; McElroy, Joseph P. et al

in JAMA Oncology (2017)

Importance: There is a need for a more refined, molecularly based classification model for glioblastoma (GBM) in the temozolomide era. Objective: To refine the existing clinically based recursive ... [more ▼]

Importance: There is a need for a more refined, molecularly based classification model for glioblastoma (GBM) in the temozolomide era. Objective: To refine the existing clinically based recursive partitioning analysis (RPA) model by incorporating molecular variables. Design, Setting, and Participants: NRG Oncology RTOG 0525 specimens (n = 452) were analyzed for protein biomarkers representing key pathways in GBM by a quantitative molecular microscopy-based approach with semiquantitative immunohistochemical validation. Prognostic significance of each protein was examined by single-marker and multimarker Cox regression analyses. To reclassify the prognostic risk groups, significant protein biomarkers on single-marker analysis were incorporated into an RPA model consisting of the same clinical variables (age, Karnofsky Performance Status, extent of resection, and neurologic function) as the existing RTOG RPA. The new RPA model (NRG-GBM-RPA) was confirmed using traditional immunohistochemistry in an independent data set (n = 176). Main Outcomes and Measures: Overall survival (OS). Results: In 452 specimens, MGMT (hazard ratio [HR], 1.81; 95% CI, 1.37-2.39; P < .001), survivin (HR, 1.36; 95% CI, 1.04-1.76; P = .02), c-Met (HR, 1.53; 95% CI, 1.06-2.23; P = .02), pmTOR (HR, 0.76; 95% CI, 0.60-0.97; P = .03), and Ki-67 (HR, 1.40; 95% CI, 1.10-1.78; P = .007) protein levels were found to be significant on single-marker multivariate analysis of OS. To refine the existing RPA, significant protein biomarkers together with clinical variables (age, Karnofsky Performance Status, extent of resection, and neurological function) were incorporated into a new model. Of 166 patients used for the new NRG-GBM-RPA model, 97 (58.4%) were male (mean [SD] age, 55.7 [12.0] years). Higher MGMT protein level was significantly associated with decreased MGMT promoter methylation and vice versa (1425.1 for methylated vs 1828.0 for unmethylated; P < .001). Furthermore, MGMT protein expression (HR, 1.84; 95% CI, 1.38-2.43; P < .001) had greater prognostic value for OS compared with MGMT promoter methylation (HR, 1.77; 95% CI, 1.28-2.44; P < .001). The refined NRG-GBM-RPA consisting of MGMT protein, c-Met protein, and age revealed greater separation of OS prognostic classes compared with the existing clinically based RPA model and MGMT promoter methylation in NRG Oncology RTOG 0525. The prognostic significance of the NRG-GBM-RPA was subsequently confirmed in an independent data set (n = 176). Conclusions and Relevance: This new NRG-GBM-RPA model improves outcome stratification over both the current RTOG RPA model and MGMT promoter methylation, respectively, for patients with GBM treated with radiation and temozolomide and was biologically validated in an independent data set. The revised RPA has the potential to contribute to improving the accurate assessment of prognostic groups in patients with GBM treated with radiation and temozolomide and to influence clinical decision making. Trial Registration: clinicaltrials.gov Identifier: NCT00304031. [less ▲]

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See detailInvolvement of Ikbζ in glioblastomas and its potential implication in radioresistance
Dubois, Nadège ULg; Willems, Marie; Kroonen, Jérôme et al

Poster (2016, November 29)

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See detailInvolvement of Ikbζ in glioblastomas and its potential implication in radioresistance
Dubois, Nadège; Willems, Marie; Kroonen, Jérôme et al

Poster (2016, September 09)

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See detailIkappaBzeta: an emerging player in cancer.
Willems, Marie; Dubois, Nadege; Musumeci, Lucia ULg et al

in Oncotarget (2016), 7(40), 66310-66322

IkappaBzeta, an atypical member of the nuclear IkappaB family of proteins, is expressed at low levels in most resting cells, but is induced upon stimulation of Toll-like/IL-1 receptors through an IRAK1 ... [more ▼]

IkappaBzeta, an atypical member of the nuclear IkappaB family of proteins, is expressed at low levels in most resting cells, but is induced upon stimulation of Toll-like/IL-1 receptors through an IRAK1/IRAK4/NFkappaB-dependent pathway. Like its homolog Bcl3, IkappaBzeta can regulate the transcription of a set of inflamatory genes through its association with the p50 or p52 subunits of NF-kappaB. Long studied as a key component of the immune response, IkappaBzeta emerges as an important regulator of inflammation, cell proliferation and survival. As a result, growing evidence support the role of this transcription factor in the pathogenesis number of human hematological and solid malignancies. [less ▲]

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See detailResponse to: "Prognostic relevance of epilepsy at presentation in lower-grade gliomas".
Berendsen, Sharon; Snijders, Tom J.; Robe, Pierre ULg

in Neuro-Oncology (2016), 18(9), 1327-8

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See detail214 Fractal Structure in Volumetric Contrast Enhancement of Malignant Gliomas Correlates With Oxidative Metabolic Pathway Gene Expression.
Miller, Kai; Berendsen, Sharon; Seute, Tatjana et al

in Neurosurgery (2016), 63 Suppl 1

INTRODUCTION: Fractal structure is found throughout many processes in nature, and often arises from sets of simple rules. We examined the contrast enhancement pattern in glioblastoma brain tumor MRIs for ... [more ▼]

INTRODUCTION: Fractal structure is found throughout many processes in nature, and often arises from sets of simple rules. We examined the contrast enhancement pattern in glioblastoma brain tumor MRIs for evidence of fractal structure, which might then be compared with expression of specific gene sets obtained from surgical specimens of each tumor. METHODS: Volumetric T1 postcontrast imaging was obtained in 39 patients prior to surgical resection of pathology-confirmed glioblastoma lesions. For each tumor, we calculated the fractal dimension (Minkowski Bouligand dimension) using a box-counting (cubic scaling) approach. RNA expression microarray data from resected tissue were explored by gene set enrichment analysis (GSEA). RESULTS: We found robust evidence for fractal structure in the contrast enhancement pattern, with an average fractal dimension of 2.17 +/- 0.10, with a visually apparent split at 2.10. GSEA analysis showed a definitive association between this split in fractal dimension and 6 gene sets (of 4080), all 6 of which are linked to mitochondrial respiration/ATP production pathways. CONCLUSION: There is fractal structure in the volumetric enhancement pattern of glioblastoma tumors, with dimension approximately 2.15. Variation in this fractal dimension, and therefore the complexity of contrast enhancement it reflects, is specifically associated with genetic correlates of a shift to glycolytic metabolism in tumor cells. Drugs that shift glioblastoma to oxidative metabolism have recently been identified as independent therapeutic agents as well as sensitizing agents for irradiation. Therefore, a radiogenomic marker of glucose metabolism, such as this fractal structure in enhancement, might help to guide individualized therapy. [less ▲]

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See detailConstitutive activation of casein kinase 2 in glioblastomas: Absence of class restriction and broad therapeutic potential.
Dubois, Nadege; Willems, Marie; Nguyen-Khac, Minh-Tuan et al

in International Journal of Oncology (2016), 48(6), 2445-52

Casein kinase II contributes to the growth and survival of malignant gliomas and attracts increasing attention as a therapeutic target in these tumors. Several reports have suggested that this strategy ... [more ▼]

Casein kinase II contributes to the growth and survival of malignant gliomas and attracts increasing attention as a therapeutic target in these tumors. Several reports have suggested that this strategy might be most relevant for specific subgroups of patients, namely Verhaak's classical and TP53 wild-type tumors. Using kinase assays and microarray genetic profiling in a series of 27 proprietary fresh frozen surgical glioma samples, we showed that constitutive CK2 kinase activation is not restricted to tumors that present increased copy numbers or mRNA expression of its catalytic or regulatory subunits, and can result from a functional activation by various cytokines from the glioma microenvironment. Using corresponding primary tumor and human astrocyte cell cultures as well as glioma cell lines, we confirmed that CK2 inhibition is selectively toxic to malignant glial tumors, without any restriction to tumor class or to TP53 status. We finally showed that while the contribution of CK2 to the constitutive NF-kappaB hyperactivation in malignant gliomas is at best moderate, a delayed activation of NF-kappaB may associate with the therapeutic resistance of glioma cells to CK2 inhibition. [less ▲]

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See detailInvolvement of Ikbζ in glioblastomas and its potential implication in radioresistance
Dubois, Nadège ULg; Willems, Marie; Kroonen, Jérôme et al

Poster (2016)

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See detailAmide proton transfer (APT) imaging of brain tumors at 7 T: The role of tissue water T -Relaxation properties.
Khlebnikov, Vitaliy; Polders, Daniel; Hendrikse, Jeroen et al

in Magnetic resonance in medicine (2016)

PURPOSE: To provide insight into the effect of water T1 relaxation (T1wat ) on amide proton transfer (APT) contrast in tumors. Three different metrics of APT contrast-magnetization transfer ratio (MTRRex ... [more ▼]

PURPOSE: To provide insight into the effect of water T1 relaxation (T1wat ) on amide proton transfer (APT) contrast in tumors. Three different metrics of APT contrast-magnetization transfer ratio (MTRRex ), relaxation-compensated MTRRex (AREX), and traditional asymmetry (MTRasym )-were compared in normal and tumor tissues in a variety of intracranial tumors at 7 Tesla (T). METHODS: Six consented intracranial tumor patients were scanned using a low-power, three-dimensional (3D) APT imaging sequence. MTRRex and MTRasym were calculated in the region of 3 to 4 ppm. AREX was calculated by T1wat correction of MTRRex . Tumor tissue masks, which classify different tumor tissues, were drawn by an experienced neuroradiologist. ROI-averaged tumor tissue analysis was done for MTRRex , AREX, and MTRasym . RESULTS: MTRRex and MTRasym were slightly elevated in tumor-associated structures. Both metrics were positively correlated to T1wat . The correlation coefficient (R) was determined to be 0.88 (P < 0.05) and 0.92 (P << 0.05) for MTRRex and MTRasym , respectively. After T1wat correction (R = -0.21, P = 0.69), no difference between normal and tumor tissues was found for AREX. CONCLUSIONS: The strong correlation of MTRRex and MTRasym with T1wat and the absence thereof in AREX suggests that much of APT contrast in tumors for the low-power, 3D-acquisition scheme at 7 T originates from the inherent tissue water T1 -relaxation properties. Magn Reson Med, 2016. (c) 2016 Wiley Periodicals, Inc. [less ▲]

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See detailPrognostic relevance of epilepsy at presentation in glioblastoma patients.
Berendsen, Sharon; Varkila, Meri; Kroonen, Jerome et al

in Neuro-oncology (2016)

BACKGROUND: Epileptogenic glioblastomas are thought to convey a favorable prognosis, either due to early diagnosis or potential antitumor effects of antiepileptic drugs. We investigated the relationship ... [more ▼]

BACKGROUND: Epileptogenic glioblastomas are thought to convey a favorable prognosis, either due to early diagnosis or potential antitumor effects of antiepileptic drugs. We investigated the relationship between survival and epilepsy at presentation, early diagnosis, and antiepileptic drug therapy in glioblastoma patients. METHODS: Multivariable Cox regression was applied to survival data of 647 consecutive patients diagnosed with de novo glioblastoma between 2005 and 2013 in order to investigate the association between epilepsy and survival in glioblastoma patients. In addition, we quantified the association between survival and valproic acid (VPA) treatment. RESULTS: Epilepsy correlated positively with survival (HR: 0.75 (95% CI: 0.61-0.92), P < .01). This effect is independent of age, sex, performance status, type of surgery, adjuvant therapy, tumor location, and tumor volume, suggesting that this positive correlation cannot be attributed solely to early diagnosis. For patients who presented with epilepsy, the use of the antiepileptic drug VPA did not associate with survival when compared with patients who did not receive VPA treatment. CONCLUSION: Epilepsy is an independent prognostic factor for longer survival in glioblastoma patients. This prognostic effect is not solely explained by early diagnosis, and survival is not associated with VPA treatment. [less ▲]

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See detailSHIP2 controls plasma membrane PI(4,5)P2 thereby participating in the control of cell migration in 1321 N1 glioblastoma.
Edimo, William S Elong; Ghosh, Somadri; Derua, Rita et al

in Journal of cell science (2016)

Phosphoinositides, particularly PI(3,4,5)P3, and PI(4,5)P2, are recognized by SHIP2 a member of the inositol polyphosphate 5-phosphatase family. SHIP2 dephosphorylates PI(3,4,5)P3 to form PI(3,4)P2; the ... [more ▼]

Phosphoinositides, particularly PI(3,4,5)P3, and PI(4,5)P2, are recognized by SHIP2 a member of the inositol polyphosphate 5-phosphatase family. SHIP2 dephosphorylates PI(3,4,5)P3 to form PI(3,4)P2; the latter interacts with specific target proteins (e.g. lamellipodin). Although the SHIP2 preferred substrate is PI(3,4,5)P3, PI(4,5)P2 could also be dephosphorylated to PI4P. Through depletion of SHIP2 in a glioblastoma cell line 1321 N1 cells, we show that SHIP2 inhibits cell migration. In different glioblastoma cell lines and primary cultures, SHIP2 staining at the plasma membrane partly overlaps with PI(4,5)P2 immunoreactivity. PI(4,5)P2 was upregulated in SHIP2-deficient N1 cells as compared to control cells; in contrast, PI4P was very much decreased in SHIP2-deficient cells. Therefore, SHIP2 controls both PI(3,4,5)P3 and PI(4,5)P2 levels in intact cells. In N1 cells, the PI(4,5)P2 binding protein myosin-1c was identified as a new interactor of SHIP2. Regulation of PI(4,5)P2 and PI4P content by SHIP2 controls N1 cell migration through the organization of focal adhesions. Thus, our results reveal a novel role of SHIP2 in the control of PI(4,5)P2, PI4P and cell migration in PTEN-deficient glioblastoma N1 cells. [less ▲]

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See detailHigh Resolution postontrast time of flight MR angiography of intracranial perforators at 7.0 Tesla
Harteveld, A; de Cocker, L; Dieleman, N et al

in PLoS ONE (2015)

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See detailGlioblastoma-derived extracellular vesicles induce tumor-supportive phenotypes in monocytic cells
de Vrij, Jeroen; Maas, Sybren; Kwappenberg, Kitty et al

in International Journal of Cancer = Journal International du Cancer (2015), 137

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See detailPI3 kinase mutations and mutational load as poor prognostic markers in diffuse glioma patients.
Draaisma, Kaspar; Wijnenga, Maarten M. J.; Weenink, Bas et al

in Acta neuropathologica communications (2015), 3(1), 88

INTRODUCTION: Recent advances in molecular diagnostics allow diffuse gliomas to be classified based on their genetic changes into distinct prognostic subtypes. However, a systematic analysis of all ... [more ▼]

INTRODUCTION: Recent advances in molecular diagnostics allow diffuse gliomas to be classified based on their genetic changes into distinct prognostic subtypes. However, a systematic analysis of all molecular markers has thus far not been performed; most classification schemes use a predefined and select set of genes/molecular markers. Here, we have analysed the TCGA dataset (combined glioblastoma (GBM) and lower grade glioma (LGG) datasets) to identify all prognostic genetic markers in diffuse gliomas in order to generate a comprehensive classification scheme. RESULTS: Of the molecular markers investigated (all genes mutated at a population frequency >1.7 % and frequent chromosomal imbalances) in the entire glioma dataset, 57 were significantly associated with overall survival. Of these, IDH1 or IDH2 mutations are associated with lowest hazard ratio, which confirms IDH as the most important prognostic marker in diffuse gliomas. Subsequent subgroup analysis largely confirms many of the currently used molecular classification schemes for diffuse gliomas (ATRX or TP53 mutations, 1p19q codeletion). Our analysis also identified PI3-kinase mutations as markers of poor prognosis in IDH-mutated + ATRX/TP53 mutated diffuse gliomas, median survival 3.7 v. 6.3 years (P = 0.02, Hazard rate (HR) 2.93, 95 % confidence interval (CI) 1.16 - 7.38). PI3-kinase mutations were also prognostic in two independent datasets. In our analysis, no additional molecular markers were identified that further refine the molecular classification of diffuse gliomas. Interestingly, these molecular classifiers do not fully explain the variability in survival observed for diffuse glioma patients. We demonstrate that tumor grade remains an important prognostic factor for overall survival in diffuse gliomas, even within molecular glioma subtypes. Tumor grade was correlated with the mutational load (the number of non-silent mutations) of the tumor: grade II diffuse gliomas harbour fewer genetic changes than grade III or IV, even within defined molecular subtypes (e.g. ATRX mutated diffuse gliomas). CONCLUSION: We have identified PI3K mutations as novel prognostic markers in gliomas. We also demonstrate that the mutational load is associated with tumor grade. The increase in mutational load may partially explain the increased aggressiveness of higher grade diffuse gliomas when a subset of the affected genes actively contributes to gliomagenesis and/or progression. [less ▲]

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See detailLocus coeruleus syndrome as a complication of tectal surgery.
Kronenburg, Annick; Spliet, Wim G.; Broekman, Marike et al

in BMJ case reports (2015), 2015

We describe a case of a 48-year-old woman who underwent a resection of a tectal pilocytic astrocytoma complicated by a sequence of fluctuating consciousness, psychosis with complex hallucinations and ... [more ▼]

We describe a case of a 48-year-old woman who underwent a resection of a tectal pilocytic astrocytoma complicated by a sequence of fluctuating consciousness, psychosis with complex hallucinations and lasting sleeping disturbances in which she vividly acts out her dreams. Based on the clinical and anatomical evidence of this case, we propose the term locus coeruleus syndrome to describe this association of iatrogenic symptoms. Along with those of the locus coeruleus, lesions of the dorsal raphe nucleus, ventral tegmentum, substantia nigra pars compacta, the superior colliculus and other peduncular lesions (such as peduncular hallucinosis) are involved in the regulation of sleep-wake/arousal, behaviour, sleeping disorders and rapid eye movement atonia. However, iatrogenic lesion of the locus coeruleus could explain the complications on all levels in our patient. [less ▲]

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See detailThe use of (18)F-FDG PET to differentiate progressive disease from treatment induced necrosis in high grade glioma.
Dankbaar, J. W.; Snijders, T. J.; Robe, Pierre ULg et al

in Journal of neuro-oncology (2015), 125(1), 167-75

In the follow-up of patients treated for high grade glioma, differentiation between progressive disease (PD) and treatment-induced necrosis (TIN) is challenging. The purpose of this study is to evaluate ... [more ▼]

In the follow-up of patients treated for high grade glioma, differentiation between progressive disease (PD) and treatment-induced necrosis (TIN) is challenging. The purpose of this study is to evaluate the diagnostic accuracy of FDG PET for the differentiation between TIN and PD after high grade glioma treatment. We retrospectively identified patients between January 2011 and July 2013 that met the following criteria: age >18; glioma grade 3 or 4; treatment with radiotherapy or chemoradiotherapy; new or progressive enhancement on post treatment MRI; FDG PET within 4 weeks of MRI. Absolute and relative (to contralateral white matter) values of SUVmax and SUVpeak were determined in new enhancing lesions on MRI. The outcome of PD or TIN was determined by neurosurgical biopsy/resection, follow-up MRI, or clinical deterioration. The association between FDG PET and outcome was analyzed with univariate logistic regression and ROC analysis for: all lesions, lesions >10, >15, and >20 mm. We included 30 patients (5 grade 3 and 25 grade 4), with 39 enhancing lesions on MRI. Twenty-nine lesions represented PD and 10 TIN. Absolute and relative values of SUVmax and SUVpeak showed no significant differences between PD and TIN. ROC analysis showed highest AUCs for relative SUVpeak in all lesion sizes. Relative SUVpeak for lesions >20 mm showed reasonable discriminative properties [AUC 0.69 (0.41-0.96)]. FDG PET has reasonable discriminative properties for differentiation of PD from TIN in high grade gliomas larger than 20 mm. Overall diagnostic performance is insufficient to guide clinical decision-making. [less ▲]

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See detailConnexin 30 expression inhibits growth of human malignant gliomas but protects them against radiation therapy.
Artesi, Maria ULg; Kroonen, Jerome; Bredel, Markus et al

in Neuro-oncology (2014)

BACKGROUND: Glioblastomas remain ominous tumors that almost invariably escape treatment. Connexins are a family of transmembrane, gap junction-forming proteins, some members of which were reported to act ... [more ▼]

BACKGROUND: Glioblastomas remain ominous tumors that almost invariably escape treatment. Connexins are a family of transmembrane, gap junction-forming proteins, some members of which were reported to act as tumor suppressors and to modulate cellular metabolism in response to cytotoxic stress. METHODS: We analyzed the copy number and expression of the connexin (Cx)30 gene gap junction beta-6 (GJB6), as well as of its protein immunoreactivity in several public and proprietary repositories of glioblastomas, and their influence on patient survival. We evaluated the effect of the expression of this gap junction protein on the growth, DNA repair and energy metabolism, and treatment resistance of these tumors. RESULTS: The GJB6 gene was deleted in 25.8% of 751 analyzed tumors and mutated in 15.8% of 158 tumors. Cx30 immunoreactivity was absent in 28.9% of 145 tumors. Restoration of Cx30 expression in human glioblastoma cells reduced their growth in vitro and as xenografts in the striatum of immunodeficient mice. Cx30 immunoreactivity was, however, found to adversely affect survival in 2 independent retrospective cohorts of glioblastoma patients. Cx30 was found in clonogenic assays to protect glioblastoma cells against radiation-induced mortality and to decrease radiation-induced DNA damage. This radioprotection correlated with a heat shock protein 90-dependent mitochondrial translocation of Cx30 following radiation and an improved ATP production following this genotoxic stress. CONCLUSION: These results underline the complex relationship between potential tumor suppressors and treatment resistance in glioblastomas and single out GJB6/Cx30 as a potential biomarker and target for therapeutic intervention in these tumors. [less ▲]

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See detailChanging incidence and improved survival of gliomas.
Ho, Vincent K. Y.; Reijneveld, Jaap C.; Enting, Roelien H. et al

in European journal of cancer (Oxford, England : 1990) (2014), 50(13), 2309-18

BACKGROUND: Tumours of the central nervous system (CNS) represent a relatively rare but serious health burden. This study provides insight into the incidence and survival patterns of gliomas in the ... [more ▼]

BACKGROUND: Tumours of the central nervous system (CNS) represent a relatively rare but serious health burden. This study provides insight into the incidence and survival patterns of gliomas in the Netherlands diagnosed in adult patients during the time period 1989-2010, with a focus on glioblastoma and low-grade gliomas. METHODS: Data on 21,085 gliomas (excluding grade I tumours) were obtained from the Netherlands Cancer Registry, including tumours of the CNS without pathological confirmation. We calculated the age-standardised incidence rates and the estimated annual percentage change (EAPC) for all glioma subtypes. Crude and relative survival rates were estimated using information on the vital status obtained from the Dutch Municipal Personal Records Database. RESULTS: Incidence of gliomas in adults increased over time, from 4.9 per 100,000 in 1989 to 5.9 in 2010 (EAPC 0.7%, p<0.001). Two thirds were astrocytoma, 10% oligodendroglioma/oligoastrocytoma, 3% ependymoma and 21% were unspecified. Within the group of astrocytic tumours, the proportion of glioblastoma rose, while the proportion of anaplastic and unspecified astrocytoma decreased. Unspecified neoplasms also decreased, but this was significant only after 2005. Over the course of the study period, glioblastoma patients more often received multimodality treatment with chemotherapy concomitant and adjuvant to radiotherapy. The crude two-year survival rate of glioblastoma patients improved significantly, from 5% in the time period 1989-1994 to 15% in 2006-2010, with median survival increasing from 5.5 to 9months. The incidence of low-grade gliomas did not change over time. Survival rates for low-grade oligodendroglial and mixed tumours show a modest improvement. CONCLUSIONS: The incidence rate for the total group of gliomas slightly increased, with a decrease of anaplastic and unspecified tumours and an increase of glioblastoma. Following the introduction of combined chemoradiation, two-year survival rates for glioblastoma significantly improved. Survival improved for low-grade gliomas except for low-grade astrocytic tumours. [less ▲]

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See detailPrognosis and therapy of tumor-related versus non-tumor-related status epilepticus: a systematic review and meta-analysis.
Arik, Yunus; Leijten, Frans Ss; Seute, Tatjana et al

in BMC neurology (2014), 14

BACKGROUND: Status epilepticus (SE) is a medical emergency with high mortality rates. Of all SE's, 7% are caused by a brain tumor. Clinical guidelines on the management of SE do not make a distinction ... [more ▼]

BACKGROUND: Status epilepticus (SE) is a medical emergency with high mortality rates. Of all SE's, 7% are caused by a brain tumor. Clinical guidelines on the management of SE do not make a distinction between tumor-related SE and SE due to other causes. However, pathophysiological research points towards specific mechanisms of epilepsy in brain tumors. We investigated whether clinical features support a distinct profile of tumor-related SE by looking at measures of severity and response to treatment. METHODS: Systematic review of the literature and meta-analysis of studies on adult SE that report separate data for tumor-related SE and non-tumor-related SE on the following outcomes: short-term mortality, long-term morbidity, duration of SE, and efficacy of anticonvulsant intervention. RESULTS: Fourteen studies on outcome of SE were included. Tumor-related SE was associated with higher mortality than non-tumor-related SE (17.2% versus 11.2%, RR 1.53, 95%-CI 1.24-1.90). After exclusion of patients with hypoxic-ischemic encephalopathy (a group with a known poor prognosis) from the non-tumor-group, the difference in mortality increased (17.2% versus 6.6%; RR 2.78, 95%-CI 2.21 - 3.47). Regarding long-term morbidity and duration of SE there were insufficient data. We did not find studies that systematically compared effects of therapy for SE between tumor- and non-tumor-related SE. CONCLUSIONS: Based on - mostly retrospective - available studies, short-term mortality seems higher in tumor-related SE than in SE due to other causes. Further studies on the outcome and efficacy of different therapeutic regimens in tumor-related SE are needed, to clarify whether tumor-related SE should be regarded as a distinct clinical entity. [less ▲]

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