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01 februari 2023, Item does not contain fulltext, Background: Cannabinoids have been suggested to alleviate frequently experienced symptoms of reduced mental well-being such as anxiety and depression. Mental well-being is an important subdomain of health-related quality of life (HRQoL). Reducing symptoms and maintaining HRQoL are particularly important in malignant primary brain tumor patients, as treatment options are often noncurative and prognosis remains poor. These patients frequently report unprescribed cannabinoid use, presumably for symptom relieve. As studies on brain tumor patients specifically are lacking, we performed a meta-analysis of the current evidence on cannabinoid efficacy on HRQoL and mental well-being in oncological and neurological patients. Methods: We performed a systematic PubMed, PsychINFO, Embase, and Web of Science search according to PRISMA guidelines on August 2 and 3, 2021. We included randomized controlled trials (RCTs) that assessed the effects of tetrahydrocannabinol (THC) or cannabidiol (CBD) on general HRQoL and mental well-being. Pooled effect sizes were calculated using Hedges g. Risk of bias of included studies was assessed using Cochrane's Risk of Bias tool. Results: We included 17 studies: 4 in oncology and 13 in central nervous system (CNS) disease. Meta-analysis showed no effect of cannabinoids on general HRQoL (g=-0.02 confidence interval [95% CI -0.11 to 0.06]; p=0.57) or mental well-being (g=-0.02 [95% CI -0.16 to 0.13]; p=0.81). Conclusions: RCTs in patients with cancer or CNS disease showed no effect of cannabinoids on HRQoL or mental well-being. However, studies were clinically heterogeneous and since many glioma patients currently frequently use cannabinoids, future studies are necessary to evaluate its value in this specific population.

01 februari 2023, Item does not contain fulltext, Background: Cannabinoids have been suggested to alleviate frequently experienced symptoms of reduced mental well-being such as anxiety and depression. Mental well-being is an important subdomain of health-related quality of life (HRQoL). Reducing symptoms and maintaining HRQoL are particularly important in malignant primary brain tumor patients, as treatment options are often noncurative and prognosis remains poor. These patients frequently report unprescribed cannabinoid use, presumably for symptom relieve. As studies on brain tumor patients specifically are lacking, we performed a meta-analysis of the current evidence on cannabinoid efficacy on HRQoL and mental well-being in oncological and neurological patients. Methods: We performed a systematic PubMed, PsychINFO, Embase, and Web of Science search according to PRISMA guidelines on August 2 and 3, 2021. We included randomized controlled trials (RCTs) that assessed the effects of tetrahydrocannabinol (THC) or cannabidiol (CBD) on general HRQoL and mental well-being. Pooled effect sizes were calculated using Hedges g. Risk of bias of included studies was assessed using Cochrane's Risk of Bias tool. Results: We included 17 studies: 4 in oncology and 13 in central nervous system (CNS) disease. Meta-analysis showed no effect of cannabinoids on general HRQoL (g=-0.02 confidence interval [95% CI -0.11 to 0.06]; p=0.57) or mental well-being (g=-0.02 [95% CI -0.16 to 0.13]; p=0.81). Conclusions: RCTs in patients with cancer or CNS disease showed no effect of cannabinoids on HRQoL or mental well-being. However, studies were clinically heterogeneous and since many glioma patients currently frequently use cannabinoids, future studies are necessary to evaluate its value in this specific population.

04 april 2022, Item does not contain fulltext, People with gliomas need specialized neurosurgical, neuro-oncological, psycho-oncological, and neuropsychological care. The role of language and cognitive recovery and rehabilitation in patients’ well-being and resumption of work is crucial, but there are no clear guidelines for the ideal timing and character of assessments and interventions. The goal of the present work was to describe representative (neuro)psychological practices implemented after brain surgery in Europe.An online survey was addressed to professionals working with individuals after brain surgery. We inquired about the assessments and interventions and the involvement of caregivers. Additionally, we asked about recommendations for an ideal assessment and intervention plan.Thirty-eight European centers completed the survey. Thirty of them offered at least one postsurgical (neuro)psychological assessment, mainly for language and cognition, especially during the early recovery stage and at long term. Twenty-eight of the participating centers offered postsurgical therapies. Patients who stand the highest chances of being included in evaluation and therapy postsurgically are those who underwent awake brain surgery, harbored a low-grade glioma, or showed poor recovery. Nearly half of the respondents offer support programs to caregivers, and all teams recommend them. Treatments differed between those offered to individuals with low-grade glioma vs those with high-grade glioma. The figure of caregiver is not yet fully recognized in the recovery phase.We stress the need for more complete rehabilitation plans, including the emotional and health-related aspects of recovery. In respondents’ opinions, assessment and rehabilitation plans should also be individually tailored and goal-directed (eg, professional reinsertion).

Contains fulltext : 281792.pdf (Publisher’s version ) (Open Access), Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I-IV cancer patients and in half of 352 stage I-III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening.

Contains fulltext : 250278.pdf (Publisher’s version ) (Open Access), People with gliomas need specialized neurosurgical, neuro-oncological, psycho-oncological, and neuropsychological care. The role of language and cognitive recovery and rehabilitation in patients’ well-being and resumption of work is crucial, but there are no clear guidelines for the ideal timing and character of assessments and interventions. The goal of the present work was to describe representative (neuro)psychological practices implemented after brain surgery in Europe.An online survey was addressed to professionals working with individuals after brain surgery. We inquired about the assessments and interventions and the involvement of caregivers. Additionally, we asked about recommendations for an ideal assessment and intervention plan.Thirty-eight European centers completed the survey. Thirty of them offered at least one postsurgical (neuro)psychological assessment, mainly for language and cognition, especially during the early recovery stage and at long term. Twenty-eight of the participating centers offered postsurgical therapies. Patients who stand the highest chances of being included in evaluation and therapy postsurgically are those who underwent awake brain surgery, harbored a low-grade glioma, or showed poor recovery. Nearly half of the respondents offer support programs to caregivers, and all teams recommend them. Treatments differed between those offered to individuals with low-grade glioma vs those with high-grade glioma. The figure of caregiver is not yet fully recognized in the recovery phase.We stress the need for more complete rehabilitation plans, including the emotional and health-related aspects of recovery. In respondents’ opinions, assessment and rehabilitation plans should also be individually tailored and goal-directed (eg, professional reinsertion).

Contains fulltext : 250278.pdf (Publisher’s version ) (Open Access), People with gliomas need specialized neurosurgical, neuro-oncological, psycho-oncological, and neuropsychological care. The role of language and cognitive recovery and rehabilitation in patients’ well-being and resumption of work is crucial, but there are no clear guidelines for the ideal timing and character of assessments and interventions. The goal of the present work was to describe representative (neuro)psychological practices implemented after brain surgery in Europe.An online survey was addressed to professionals working with individuals after brain surgery. We inquired about the assessments and interventions and the involvement of caregivers. Additionally, we asked about recommendations for an ideal assessment and intervention plan.Thirty-eight European centers completed the survey. Thirty of them offered at least one postsurgical (neuro)psychological assessment, mainly for language and cognition, especially during the early recovery stage and at long term. Twenty-eight of the participating centers offered postsurgical therapies. Patients who stand the highest chances of being included in evaluation and therapy postsurgically are those who underwent awake brain surgery, harbored a low-grade glioma, or showed poor recovery. Nearly half of the respondents offer support programs to caregivers, and all teams recommend them. Treatments differed between those offered to individuals with low-grade glioma vs those with high-grade glioma. The figure of caregiver is not yet fully recognized in the recovery phase.We stress the need for more complete rehabilitation plans, including the emotional and health-related aspects of recovery. In respondents’ opinions, assessment and rehabilitation plans should also be individually tailored and goal-directed (eg, professional reinsertion).

Contains fulltext : 281792.pdf (Publisher’s version ) (Open Access), Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I-IV cancer patients and in half of 352 stage I-III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening.

Introduction: For decisions on glioblastoma surgery, the risk of complications and decline in performance is decisive. In this study, we determine the rate of complications and performance decline after resections and biopsies in a national quality registry, their risk factors and the risk-standardized variation between institutions. Methods: Data from all 3288 adults with first-time glioblastoma surgery at 13 hospitals were obtained from a prospective population-based Quality Registry Neuro Surgery in the Netherlands between 2013 and 2017. Patients were stratified by biopsies and resections. Complications were categorized as Clavien-Dindo grades II and higher. Performance decline was considered a deterioration of more than 10 Karnofsky points at 6 weeks. Risk factors were evaluated in multivariable logistic regression analysis. Patient-specific expected and observed complications and performance declines were summarized for institutions and analyzed in funnel plots. Results: For 2271 resections, the overall complication rate was 20 % and 16 % declined in performance. For 1017 biopsies, the overall complication rate was 11 % and 30 % declined in performance. Patient-related characteristics were significant risk factors for complications and performance decline, i.e. higher age, lower baseline Karnofsky, higher ASA classification, and the surgical procedure. Hospital characteristics, i.e. case volume, university affiliation and biopsy percentage, were not. In three institutes the observed complication rate was significantly less than expected. In one institute significantly more performance declines were observed than expected, and in one institute significantly less. Conclusions: Patient characteristics, but not case volume, were risk factors for complications and performance decline after glioblastoma surgery. After risk-standardization, hospitals varied in complications and performance declines.

Contains fulltext : 229052.pdf (publisher's version ) (Open Access), Tumor-educated platelets (TEPs) are potential biomarkers for cancer diagnostics. We employ TEP-derived RNA panels, determined by swarm intelligence, to detect and monitor glioblastoma. We assessed specificity by comparing the spliced RNA profile of TEPs from glioblastoma patients with multiple sclerosis and brain metastasis patients (validation series, n = 157; accuracy, 80%; AUC, 0.81 [95% CI, 0.74-0.89; p < 0.001]). Second, analysis of patients with glioblastoma versus asymptomatic healthy controls in an independent validation series (n = 347) provided a detection accuracy of 95% and AUC of 0.97 (95% CI, 0.95-0.99; p < 0.001). Finally, we developed the digitalSWARM algorithm to improve monitoring of glioblastoma progression and demonstrate that the TEP tumor scores of individual glioblastoma patients represent tumor behavior and could be used to distinguish false positive progression from true progression (validation series, n = 20; accuracy, 85%; AUC, 0.86 [95% CI, 0.70-1.00; p < 0.012]). In conclusion, TEPs have potential as a minimally invasive biosource for blood-based diagnostics and monitoring of glioblastoma patients.

Contains fulltext : 229052.pdf (publisher's version ) (Open Access), Tumor-educated platelets (TEPs) are potential biomarkers for cancer diagnostics. We employ TEP-derived RNA panels, determined by swarm intelligence, to detect and monitor glioblastoma. We assessed specificity by comparing the spliced RNA profile of TEPs from glioblastoma patients with multiple sclerosis and brain metastasis patients (validation series, n = 157; accuracy, 80%; AUC, 0.81 [95% CI, 0.74-0.89; p < 0.001]). Second, analysis of patients with glioblastoma versus asymptomatic healthy controls in an independent validation series (n = 347) provided a detection accuracy of 95% and AUC of 0.97 (95% CI, 0.95-0.99; p < 0.001). Finally, we developed the digitalSWARM algorithm to improve monitoring of glioblastoma progression and demonstrate that the TEP tumor scores of individual glioblastoma patients represent tumor behavior and could be used to distinguish false positive progression from true progression (validation series, n = 20; accuracy, 85%; AUC, 0.86 [95% CI, 0.70-1.00; p < 0.012]). In conclusion, TEPs have potential as a minimally invasive biosource for blood-based diagnostics and monitoring of glioblastoma patients.

Purpose: Standards for surgical decisions are unavailable, hence treatment decisions can be personalized, but also introduce variation in treatment and outcome. National registrations seek to monitor healthcare quality. The goal of the study is to measure between-hospital variation in risk-standardized survival outcome after glioblastoma surgery and to explore the association between survival and hospital characteristics in conjunction with patient-related risk factors. Methods: Data of 2,409 adults with first-time glioblastoma surgery at 14 hospitals were obtained from a comprehensive, prospective population-based Quality Registry Neuro Surgery in The Netherlands between 2011 and 2014. We compared the observed survival with patient-specific risk-standardized expected early (30-day) mortality and late (2-year) survival, based on age, performance, and treatment year. We analyzed funnel plots, logistic regression and proportional hazards models. Results: Overall 30-day mortality was 5.2% and overall 2-year survival was 13.5%. Median survival varied between 4.8 and 14.9 months among hospitals, and biopsy percentages ranged between 16 a

Contains fulltext : 195164.pdf (publisher's version ) (Open Access), Objective: Imaging studies in diffuse low-grade gliomas (DLGG) vary across centers. In order to establish a minimal core of imaging necessary for further investigations and clinical trials in the field of DLGG, we aimed to establish the status quo within specialized European centers. Methods: An online survey composed of 46 items was sent out to members of the European Low-Grade Glioma Network, the European Association of Neurosurgical Societies, the German Society of Neurosurgery and the Austrian Society of Neurosurgery. Results: A total of 128 fully completed surveys were received and analyzed. Most centers (n = 96, 75%) were academic and half of the centers (n = 64, 50%) adhered to a dedicated treatment program for DLGG. There were national differences regarding the sequences enclosed in MRI imaging and use of PET, however most included T1 (without and with contrast, 100%), T2 (100%) and TIRM or FLAIR (20, 98%). DWI is performed by 80% of centers and 61% of centers regularly performed PWI. Conclusion: A minimal core of imaging composed of T1 (w/wo contrast), T2, TIRM/FLAIR, PWI and DWI could be identified. All morphologic images should be obtained in a slice thickness of <= 3 mm. No common standard could be obtained regarding advanced MRI protocols and PET. Importance of the study: We believe that our study makes a significant contribution to the literature because we were able to determine similarities in numerous aspects of LGG imaging. Using the proposed "minimal core of imaging" in clinical routine will facilitate future cooperative studies.

Contains fulltext : 195164.pdf (publisher's version ) (Open Access), Objective: Imaging studies in diffuse low-grade gliomas (DLGG) vary across centers. In order to establish a minimal core of imaging necessary for further investigations and clinical trials in the field of DLGG, we aimed to establish the status quo within specialized European centers. Methods: An online survey composed of 46 items was sent out to members of the European Low-Grade Glioma Network, the European Association of Neurosurgical Societies, the German Society of Neurosurgery and the Austrian Society of Neurosurgery. Results: A total of 128 fully completed surveys were received and analyzed. Most centers (n = 96, 75%) were academic and half of the centers (n = 64, 50%) adhered to a dedicated treatment program for DLGG. There were national differences regarding the sequences enclosed in MRI imaging and use of PET, however most included T1 (without and with contrast, 100%), T2 (100%) and TIRM or FLAIR (20, 98%). DWI is performed by 80% of centers and 61% of centers regularly performed PWI. Conclusion: A minimal core of imaging composed of T1 (w/wo contrast), T2, TIRM/FLAIR, PWI and DWI could be identified. All morphologic images should be obtained in a slice thickness of <= 3 mm. No common standard could be obtained regarding advanced MRI protocols and PET. Importance of the study: We believe that our study makes a significant contribution to the literature because we were able to determine similarities in numerous aspects of LGG imaging. Using the proposed "minimal core of imaging" in clinical routine will facilitate future cooperative studies.

Contains fulltext : 195164.pdf (publisher's version ) (Open Access), Objective: Imaging studies in diffuse low-grade gliomas (DLGG) vary across centers. In order to establish a minimal core of imaging necessary for further investigations and clinical trials in the field of DLGG, we aimed to establish the status quo within specialized European centers. Methods: An online survey composed of 46 items was sent out to members of the European Low-Grade Glioma Network, the European Association of Neurosurgical Societies, the German Society of Neurosurgery and the Austrian Society of Neurosurgery. Results: A total of 128 fully completed surveys were received and analyzed. Most centers (n = 96, 75%) were academic and half of the centers (n = 64, 50%) adhered to a dedicated treatment program for DLGG. There were national differences regarding the sequences enclosed in MRI imaging and use of PET, however most included T1 (without and with contrast, 100%), T2 (100%) and TIRM or FLAIR (20, 98%). DWI is performed by 80% of centers and 61% of centers regularly performed PWI. Conclusion: A minimal core of imaging composed of T1 (w/wo contrast), T2, TIRM/FLAIR, PWI and DWI could be identified. All morphologic images should be obtained in a slice thickness of <= 3 mm. No common standard could be obtained regarding advanced MRI protocols and PET. Importance of the study: We believe that our study makes a significant contribution to the literature because we were able to determine similarities in numerous aspects of LGG imaging. Using the proposed "minimal core of imaging" in clinical routine will facilitate future cooperative studies.

Item does not contain fulltext, BACKGROUND: Glioma imaging, used for diagnostics, treatment planning, and follow-up, is currently based on standard magnetic resonance imaging (MRI) modalities (T1 contrast-enhancement for gadolinium-enhancing gliomas and T2 fluid-attenuated inversion recovery hyperintensity for nonenhancing gliomas). The diagnostic accuracy of these techniques for the delineation of gliomas is suboptimal. OBJECTIVE: To assess the diagnostic accuracy of advanced neuroimaging compared with standard MRI modalities for the detection of diffuse glioma infiltration within the brain. METHODS: A monocenter, prospective, diagnostic observational study in adult patients with a newly diagnosed, diffuse infiltrative glioma undergoing resective glioma surgery. Forty patients will be recruited in 3 years. Advanced neuroimaging will be added to the standard preoperative MRI. Serial neuronavigated biopsies in and around the glioma boundaries, obtained immediately preceding resective surgery, will provide histopathologic and molecular characteristics of the regions of interest, enabling comparison with quantitative measurements in the imaging modalities at the same biopsy sites. DISCUSSION: In this clinical study, we determine the diagnostic accuracy of advanced imaging in addition to standard MRI to delineate glioma. The results of our study can be valuable for the development of an improved standard imaging protocol for glioma treatment. EXPECTED OUTCOME: We hypothesize that a combination of positron emission tomography, MR spectroscopy, and standard MRI will have a superior accuracy for glioma delineation compared with standard MRI alone. In addition, we anticipate that advanced imaging will correlate with the histopathologic and molecular characteristics of glioma. ABBREVIATIONS: CHO, [11C-]CholineCRF, case report formsFET, [18F-]Fluoroethyl-tyrosineFLAIR, fluid-attenuated inversion recoveryMETC, Medical Ethical CommitteeMRS, magnetic resonance spectroscopyPET, positron emission tomographyVUmc

Contains fulltext : 171797.pdf (publisher's version ) (Open Access), In brain tumor surgery, recognition of tumor boundaries is key. However, intraoperative assessment of tumor boundaries by the neurosurgeon is difficult. Therefore, there is an urgent need for tools that provide the neurosurgeon with pathological information during the operation. We show that third harmonic generation (THG) microscopy provides label-free, real-time images of histopathological quality; increased cellularity, nuclear pleomorphism, and rarefaction of neuropil in fresh, unstained human brain tissue could be clearly recognized. We further demonstrate THG images taken with a GRIN objective, as a step toward in situ THG microendoscopy of tumor boundaries. THG imaging is thus a promising tool for optical biopsies.

Item does not contain fulltext, BACKGROUND: Glioma imaging, used for diagnostics, treatment planning, and follow-up, is currently based on standard magnetic resonance imaging (MRI) modalities (T1 contrast-enhancement for gadolinium-enhancing gliomas and T2 fluid-attenuated inversion recovery hyperintensity for nonenhancing gliomas). The diagnostic accuracy of these techniques for the delineation of gliomas is suboptimal. OBJECTIVE: To assess the diagnostic accuracy of advanced neuroimaging compared with standard MRI modalities for the detection of diffuse glioma infiltration within the brain. METHODS: A monocenter, prospective, diagnostic observational study in adult patients with a newly diagnosed, diffuse infiltrative glioma undergoing resective glioma surgery. Forty patients will be recruited in 3 years. Advanced neuroimaging will be added to the standard preoperative MRI. Serial neuronavigated biopsies in and around the glioma boundaries, obtained immediately preceding resective surgery, will provide histopathologic and molecular characteristics of the regions of interest, enabling comparison with quantitative measurements in the imaging modalities at the same biopsy sites. DISCUSSION: In this clinical study, we determine the diagnostic accuracy of advanced imaging in addition to standard MRI to delineate glioma. The results of our study can be valuable for the development of an improved standard imaging protocol for glioma treatment. EXPECTED OUTCOME: We hypothesize that a combination of positron emission tomography, MR spectroscopy, and standard MRI will have a superior accuracy for glioma delineation compared with standard MRI alone. In addition, we anticipate that advanced imaging will correlate with the histopathologic and molecular characteristics of glioma. ABBREVIATIONS: CHO, [11C-]CholineCRF, case report formsFET, [18F-]Fluoroethyl-tyrosineFLAIR, fluid-attenuated inversion recoveryMETC, Medical Ethical CommitteeMRS, magnetic resonance spectroscopyPET, positron emission tomographyVUmc

Contains fulltext : 171797.pdf (publisher's version ) (Open Access), In brain tumor surgery, recognition of tumor boundaries is key. However, intraoperative assessment of tumor boundaries by the neurosurgeon is difficult. Therefore, there is an urgent need for tools that provide the neurosurgeon with pathological information during the operation. We show that third harmonic generation (THG) microscopy provides label-free, real-time images of histopathological quality; increased cellularity, nuclear pleomorphism, and rarefaction of neuropil in fresh, unstained human brain tissue could be clearly recognized. We further demonstrate THG images taken with a GRIN objective, as a step toward in situ THG microendoscopy of tumor boundaries. THG imaging is thus a promising tool for optical biopsies.

Contains fulltext : 171797.pdf (publisher's version ) (Open Access), In brain tumor surgery, recognition of tumor boundaries is key. However, intraoperative assessment of tumor boundaries by the neurosurgeon is difficult. Therefore, there is an urgent need for tools that provide the neurosurgeon with pathological information during the operation. We show that third harmonic generation (THG) microscopy provides label-free, real-time images of histopathological quality; increased cellularity, nuclear pleomorphism, and rarefaction of neuropil in fresh, unstained human brain tissue could be clearly recognized. We further demonstrate THG images taken with a GRIN objective, as a step toward in situ THG microendoscopy of tumor boundaries. THG imaging is thus a promising tool for optical biopsies.

Contains fulltext : 88108.pdf (publisher's version ) (Closed access), Kinases execute pivotal cellular functions and are therefore widely investigated as potential targets in anticancer treatment. Here we analyze the kinase gene expression profiles of various tumor types and reveal the wee1 kinase to be overexpressed in glioblastomas. We demonstrate that WEE1 is a major regulator of the G(2) checkpoint in glioblastoma cells. Inhibition of WEE1 by siRNA or small molecular compound in cells exposed to DNA damaging agents results in abrogation of the G(2) arrest, premature termination of DNA repair, and cell death. Importantly, we show that the small-molecule inhibitor of WEE1 sensitizes glioblastoma to ionizing radiation in vivo. Our results suggest that inhibition of WEE1 kinase holds potential as a therapeutic approach in treatment of glioblastoma.

Contains fulltext : 88108.pdf (publisher's version ) (Closed access), Kinases execute pivotal cellular functions and are therefore widely investigated as potential targets in anticancer treatment. Here we analyze the kinase gene expression profiles of various tumor types and reveal the wee1 kinase to be overexpressed in glioblastomas. We demonstrate that WEE1 is a major regulator of the G(2) checkpoint in glioblastoma cells. Inhibition of WEE1 by siRNA or small molecular compound in cells exposed to DNA damaging agents results in abrogation of the G(2) arrest, premature termination of DNA repair, and cell death. Importantly, we show that the small-molecule inhibitor of WEE1 sensitizes glioblastoma to ionizing radiation in vivo. Our results suggest that inhibition of WEE1 kinase holds potential as a therapeutic approach in treatment of glioblastoma.

Item does not contain fulltext, Hangman's fractures are a rare finding in childhood. In case of suspected or proven child abuse, differentiation with a congenital defect of the posterior arch of C2 is essential. We present the case of a 5-month-old girl, who had a history of being physically abused by one of her caretakers. On the lateral view of the cervical spine, a defect of the posterior elements of C2 and an anterolisthesis of C2 on C3 was seen. CT scan showed a bilateral defect in the posterior elements of C2. No soft-tissue swelling of hematoma was noted. MRI showed a normal signal intensity of the intervertebral disc C2-C3. No haematoma was noted. Clinical examination revealed a slight head lag and local tenderness; there were no neurological deficits. This case shows that the differentiation between a congenital C2 arch defect and a hangman's fracture is precarious. In this case the findings on MRI and CT scan were interpreted as a congenital posterior arch defect (spondylolysis).

Item does not contain fulltext, Hangman's fractures are a rare finding in childhood. In case of suspected or proven child abuse, differentiation with a congenital defect of the posterior arch of C2 is essential. We present the case of a 5-month-old girl, who had a history of being physically abused by one of her caretakers. On the lateral view of the cervical spine, a defect of the posterior elements of C2 and an anterolisthesis of C2 on C3 was seen. CT scan showed a bilateral defect in the posterior elements of C2. No soft-tissue swelling of hematoma was noted. MRI showed a normal signal intensity of the intervertebral disc C2-C3. No haematoma was noted. Clinical examination revealed a slight head lag and local tenderness; there were no neurological deficits. This case shows that the differentiation between a congenital C2 arch defect and a hangman's fracture is precarious. In this case the findings on MRI and CT scan were interpreted as a congenital posterior arch defect (spondylolysis).

Item does not contain fulltext, Hangman's fractures are a rare finding in childhood. In case of suspected or proven child abuse, differentiation with a congenital defect of the posterior arch of C2 is essential. We present the case of a 5-month-old girl, who had a history of being physically abused by one of her caretakers. On the lateral view of the cervical spine, a defect of the posterior elements of C2 and an anterolisthesis of C2 on C3 was seen. CT scan showed a bilateral defect in the posterior elements of C2. No soft-tissue swelling of hematoma was noted. MRI showed a normal signal intensity of the intervertebral disc C2-C3. No haematoma was noted. Clinical examination revealed a slight head lag and local tenderness; there were no neurological deficits. This case shows that the differentiation between a congenital C2 arch defect and a hangman's fracture is precarious. In this case the findings on MRI and CT scan were interpreted as a congenital posterior arch defect (spondylolysis).