| 1. |
- Andrae, Johanna, et al.
(författare)
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Platelet-derived growth factor-B and -C and active alpha-receptors in medulloblastoma cells.
- 2002
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Ingår i: Biochemical and biophysical research communications. - 0006-291X .- 1090-2104. ; 296:3, s. 604-11
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Tidskriftsartikel (refereegranskat)abstract
- The malignant childhood brain tumor medulloblastoma belongs to the group of primitive neuroectodermal tumours (PNETs). Medulloblastomas are thought to arise from remnants of the transient external germinal layer in the cerebellum. Proliferation, differentiation, and motility of cells in the central nervous system are regulated by growth factors, e.g., platelet-derived growth factor (PDGF). Recently, it was shown that higher level of PDGF alpha-receptor expression is characteristic of metastatic medulloblastomas. We have investigated five medulloblastoma/PNET cell lines and found that the PDGF alpha-receptor is actively signalling in most of them, an activity most likely driven by endogenously produced PDGF-C. PDGF-C is normally present in cells of the developing external germinal layer and our results are consistent with the idea that medulloblastomas are derived from such cells undergoing early neuronal differentiation. Moreover, the expression of PDGF and its receptors was associated with neuronal characteristics, but not with high levels of c-myc expression in the medullablastoma cells.
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| 2. |
- Babateen, Omar, et al.
(författare)
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Etomidate, propofol and diazepam potentiate GABA-evoked GABAA currents in a cell line derived from Human glioblastoma
- 2015
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Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 0014-2999 .- 1879-0712. ; 748, s. 101-107
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Tidskriftsartikel (refereegranskat)abstract
- GABAA receptors are pentameric chloride ion channels that are opened by GABA. We have screened a cell line derived from human glioblastoma, U3047MG, for expression of GABAA receptor subunit isoforms and formation of functional ion channels. We identified GABAA receptors subunit α2, α3, α5, β1, β2, β3, δ, γ3, π, and θ mRNAs in the U3047MG cell line. Whole-cell GABA-activated currents were recorded and the half-maximal concentration (EC50) for the GABA-activated current was 36μM. The currents were activated by THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) and enhanced by the benzodiazepine diazepam (1μM) and the general anesthetics etomidate and propofol (50μM). In line with the expressed GABAA receptors containing at least the α3β3θ subunits, the receptors were highly sensitive to etomidate (EC50=55nM). Immunocytochemistry identified expression of the α3 and β3 subunit proteins. Our results show that the GABAA receptors in the glial cell line are functional and are modulated by classical GABAA receptor drugs. We propose that the U3047MG cell line may be used as a model system to study GABAA receptors function and pharmacology in glial cells.
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| 3. |
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| 4. |
- Ballagi, A E, et al.
(författare)
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Platelet-derived growth factor receptor expression after neural grafting in a rat model of Parkinson's disease
- 1994
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Ingår i: Cell Transplantation. - 0963-6897 .- 1555-3892. ; 3:6, s. 453-460
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Tidskriftsartikel (refereegranskat)abstract
- Platelet-derived growth factor (PDGF) has trophic effect on dopaminergic neurons in vitro. We have previously shown dynamic changes in the expression of PDGF in embryonic mesencephalic grafts and surrounding host striatal tissue following intracerebral transplantation in a rat model of Parkinson's disease. In this study the expression of the PDGF receptors was examined in the same model using immunohistochemistry. Most ventral mesencephalic (VM) cells from E13-E15 rat embryos possessed both PDGF alpha- and beta-receptors before implantation. Double immunofluorescence staining revealed that about 10% of the cells also expressed tyrosine hydroxylase (TH). The PDGF alpha-receptor was detectable in the graft up to 1 wk after transplantation but had disappeared at 3 wk. In the host tissue, scattered glial cells were positive for the alpha-receptor but the expression was unchanged following transplantation. The beta-receptor expression almost completely disappeared from the grafted tissue by 4 h following transplantation, and only a few cells of the host striatum showed immunoreactivity. However, after 3 wk beta-receptor positive cells were again detectable in the graft. These cells appeared to be endothelial cells as identified by an antibody against von Willebrand's factor. Our data suggest that PDGF might act locally on embryonic dopaminergic cells in an autocrine or juxtacrine manner before and shortly after transplantation, and on surrounding glial cells in a paracrine manner after transplantation. Furthermore, PDGF-BB might influence neovascularization in the graft.
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| 5. |
- Berntsson, Shala, et al.
(författare)
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11c-methionine PET combined with advanced MRI for the preoperative evaluation of suspected diffuse low-grade gliomas
- 2012
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Ingår i: Neuro-Oncology. - : Oxford University Press (OUP). - 1522-8517 .- 1523-5866. ; 14:suppl 3, s. iii11-iii12
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- PURPOSE: To evaluate positron emission tomography (PET) with the tracer 11C-methionine (MET) combined with perfusion- and diffusion MRI (pMRI and dMRI) for the preoperative evaluation of patients with suspected diffuse low-grade gliomas (DLGG).MATERIALS AND METHODS: In this prospective study with institutional review board approval, 25 patients with suspected DLGG in cortical structures (n=24) were examined with 11C-methionine PET (MET PET), pMRI and dMRI. The hot spot (HS) in the tumor, i.e. the area with highest MET uptake, was used as a reference region for evaluating maximum relative cerebral blood volume (rCBVmax) and minimum apparent diffusion coefficient values (ADCmin) by MRI. The concordance between MET PET, pMRI and dMRI, as single parameters and combined, was assessed with respect to histological tumor diagnosis, which was available for 18 patients.RESULTS: In all but one patient tumor diagnosis was confirmed. The region showing highest rCBVmax corresponded with the HS region identified by MET PET in all cases, and a positive correlation between MET uptake and rCBVmax was found (Spearman: r=0.67, P < 0.0001). The concordance between MET uptake and rCBVmax in predicting malignancy grade of gliomas was 67%. MET uptake in the HS was inversely correlated with ADCmin values measured in this region (Spearman: r=-0.54, p < 0.005).CONCLUSION: MET PET combined with advanced MRI facilitates the identification of specific regions of interest for histological tumor diagnosis and thereby provides a powerful tool in the preoperative evaluation of DLGG.
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| 6. |
- Berntsson, Shala Ghaderi, et al.
(författare)
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Analysis of DNA repair gene polymorphisms and survival in low-grade and anaplastic gliomas
- 2011
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Ingår i: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 105:3, s. 531-538
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to explore the variation in DNA repair genes in adults with WHO grade II and III gliomas and their relationship to patient survival. We analysed a total of 1,458 tagging single-nucleotide polymorphisms (SNPs) that were selected to cover DNA repair genes, in 81 grade II and grade III gliomas samples, collected in Sweden and Denmark. The statistically significant genetic variants from the first dataset (P < 0.05) were taken forward for confirmation in a second dataset of 72 grade II and III gliomas from northern UK. In this dataset, eight gene variants mapping to five different DNA repair genes (ATM, NEIL1, NEIL2, ERCC6 and RPA4) which were associated with survival. Finally, these eight genetic variants were adjusted for treatment, malignancy grade, patient age and gender, leaving one variant, rs4253079, mapped to ERCC6, with a significant association to survival (OR 0.184, 95% CI 0.054-0.63, P = 0.007). We suggest a possible novel association between rs4253079 and survival in this group of patients with low-grade and anaplastic gliomas that needs confirmation in larger datasets.
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| 7. |
- Berntsson, Shala G., 1964-, et al.
(författare)
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Glioma-related seizures in relation to histopathological subtypes: a report from the glioma international case-control study.
- 2018
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Ingår i: Journal of neurology. - : Springer Science and Business Media LLC. - 1432-1459 .- 0340-5354. ; 265:6, s. 1432-1442
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to evaluate the distribution of glioma-related seizures and seizure control at the time of tumor diagnosis with respect to tumor histologic subtypes, tumor treatment and patient characteristics, and to compare seizure history preceding tumor diagnosis (or study enrollment) between glioma patients and healthy controls.The Glioma International Case Control study (GICC) risk factor questionnaire collected information on demographics, past medical/medication history, and occupational history. Cases from eight centers were also asked detailed questions on seizures in relation to glioma diagnosis; cases (n=4533) and controls (n=4171) were also asked about seizures less than 2years from diagnosis and previous seizure history more than 2years prior to tumor diagnosis, including childhood seizures.Low-grade gliomas (LGGs), particularly oligodendrogliomas/oligoastrocytomas, had the highest proportion of glioma-related seizures. Patients with low-grade astrocytoma demonstrated the most medically refractory seizures. A total of 83% of patients were using only one antiepileptic drug (AED), which was levetiracetam in 71% of cases. Gross total resection was strongly associated with reduced seizure frequency (p<0.009). No significant difference was found between glioma cases and controls in terms of seizure occurring more than 2 years before diagnosis or during childhood.Our study showed that glioma-related seizures were most common in low-grade gliomas. Gross total resection was associated with lower seizure frequency. Additionally, having a history of childhood seizures is not a risk factor ***for developing glioma-related seizures or glioma.
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| 8. |
- Berntsson, Shala Ghaderi, et al.
(författare)
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Perfusion and diffusion MRI combined with (11)C-methionine PET in the preoperative evaluation of suspected adult low-grade gliomas
- 2013
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Ingår i: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 114:2, s. 241-249
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Tidskriftsartikel (refereegranskat)abstract
- Perfusion and diffusion magnetic resonance imaging (pMRI, dMRI) are valuable diagnostic tools for assessing brain tumors in the clinical setting. The aim of this study was to determine the correlation of pMRI and dMRI with (11)C-methionine positron emission tomography (MET PET) in suspected low-grade gliomas (LGG) prior to surgery. Twenty-four adults with suspected LGG were enrolled in an observational study and examined by MET PET, pMRI and dMRI. Histological tumor diagnosis was confirmed in 23/24 patients (18 gliomas grade II, 5 gliomas grade III). The maximum relative cerebral blood volume (rCBVmax) and the minimum mean diffusivity (MDmin) were measured in tumor areas with highest MET uptake (hotspot) on PET by using automated co-registration of MRI and PET scans. A clearly defined hotspot on PET was present in all 23 tumors. Regions with rCBVmax corresponded with hotspot regions in all tumors, regions with MDmin corresponded with hotspot regions in 20/23 tumors. The correlation between rCBVmax (r = 0.19, P = 0.38) and MDmin (r = -0.41, P = 0.053) with MET uptake in the hotspot was not statistically significant. Taken into account the difficulties of measuring perfusion abnormalities in non-enhancing gliomas, this study demonstrates that co-registered MET PET and pMRI facilitates the identification of regions with rCBVmax. Furthermore, the lack of a clear positive correlation between tumor metabolism in terms of MET uptake and tumor vascularity measured as rCBVmax suggests that combined pMRI/PET provides complementary baseline imaging data in these tumors.
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| 9. |
- Berntsson, Shala Ghaderi, 1964-
(författare)
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Towards Novel Biomarkers for Low-grade Glioma
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Gliomas are common primary brain tumours that occur as low-grade (LGG) and high-grade gliomas (HGG). Typically occurring in younger adults, LGG has an indolent course with a median survival of 5-10 years, but carries an inherent potential for transforming into HGG. The thesis focused on LGG in adults, with the aim of identifying prognostic biomarkers for LGG.Paper I. Epileptic seizures are common symptoms in LGG. In a retrospective study, the correlation between 11C-methionine (MET) uptake, measured by Positron Emission Tomography (PET), and seizure activity was assessed in 101 patients with LGG. Although there was no correlation between MET uptake and seizure activity, survival was longer in patients who were seizure-free before surgery.Paper II. This finding prompted the search for common genetic pathways for both tumour and seizure development and a review of genetic polymorphisms in focal epilepsy and glioma risk. Cell cycle and immune response genes affecting both glioma and seizure risk were identified, and genes involved in synaptic transmission presented potential candidates for future studies.Paper III. The transcription factor PROX1 plays a pivotal role in normal development and carcinogenesis of various organs. The prognostic value of PROX1, together with established clinical and molecular prognostic factors for survival, was retrospectively assessed in 116 patients with LGG. High PROX1 expression in the tumour was associated with shorter survival.Paper IV. DNA repair enzymes, such as ERCC6, are crucial for maintaining genomic stability in glioma response to radiotherapy. An association between the polymorphism rs4253079, mapped to ERCC6, and longer survival in patients with LGG and HGG was identified.Paper V. As LGG typically presented as non-contrast enhancing tumours on morphological MRI (magnetic resonance imaging), the value of combined MET PET with physiological MRI for preoperative diagnosis was assessed in a prospective study of 32 patients with suspected LGG. Representative tumour areas were identified through a combination of perfusion-MRI with MET PET, which can be used as a baseline investigation for follow-up over time.Conclusions: The parameters seizure-freedom before surgery, the polymorphism rs4253079 in ERCC6 and low PROX1 expression in the tumor were identified as favorable prognostic biomarkers.
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| 10. |
- Berntsson, Shala, et al.
(författare)
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Tumor-associated epilepsy and glioma : are there common genetic pathways?
- 2009
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 48:7, s. 955-963
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Forskningsöversikt (refereegranskat)abstract
- Background. Patients with glioma exhibit a great variability in clinical symptoms apart from variations in response to therapy and survival. Many patients present with epileptic seizures at disease onset, especially in case of low-grade gliomas, but not all have seizures. A large proportion of patients develop refractory seizures. It is likely that the variability in epileptic symptoms cannot exclusively be explained by tumor-related factors, but rather reflects complex interaction between tumor-related, environmental and hereditary factors. Material and methods. No data exist on susceptibility genes associated with epileptic symptoms in patients with glioma. However, an increasing number of candidate genes have been proposed for other focal epilepsies such as temporal lobe epilepsy. Some of the susceptibility candidate genes associated with focal epilepsy may contribute to epileptic symptoms also in patients with glioma. Results. This review presents an update on studies on genetic polymorphisms and focal epilepsy and brings forward putative candidate genes for tumor-associated epilepsy, based on the assumption that common etiological pathways may exist for glioma development and glioma-associated seizures. Conclusion. Genes involved in the immune response, in synaptic transmission and in cell cycle control are discussed that may play a role in the pathogenesis of tumor growth as well as epileptic symptoms in patients with gliomas.
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| 11. |
- Carstam, Louise, et al.
(författare)
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Long-term follow up of patients with WHO grade 2 oligodendroglioma
- 2023
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Ingår i: Journal of Neuro-Oncology. - 0167-594X .- 1573-7373. ; 165, s. 65-74
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Since the introduction of the molecular definition of oligodendrogliomas based on isocitrate dehydrogenase (IDH)-status and the 1p19q-codeletion, it has become increasingly evident how this glioma entity differs much from other diffuse lower grade gliomas and stands out with longer survival and often better responsiveness to adjuvant therapy. Therefore, apart from using a molecular oligodendroglioma definition, an extended follow-up time is necessary to understand the nature of this slow growing, yet malignant condition. The aim of this study was to describe the long-term course of the oligodendroglioma disease in a population-based setting and to determine which factors affect outcome in terms of survival.Methods All adults with WHO-grade 2 oligodendrogliomas with known 1p19q-codeletion from five Scandinavian neurosurgical centers and with a follow-up time exceeding 5 years, were analyzed regarding survival and factors potentially affecting survival.Results 126 patients diagnosed between 1998 and 2016 were identified. The median follow-up was 12.0 years, and the median survival was 17.8 years (95% CI 16.0-19.6).Factors associated with shorter survival in multivariable analysis were age (HR 1.05 per year; CI 1.02-1.08, p < 0.001), tumor diameter (HR 1.05 per millimeter; CI 1.02-1.08, p < 0.001) and poor preoperative functional status (KPS < 80) (HR 4.47; CI 1.70-11.78, p = 0.002). In our material, surgical strategy was not associated with survival.Conclusion Individuals with molecularly defined oligodendrogliomas demonstrate long survival, also in a population-based setting. This is important to consider for optimal timing of therapies that may cause long-term side effects. Advanced age, large tumors and poor function before surgery are predictors of shorter survival.
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| 12. |
- Carstam, Louise, et al.
(författare)
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Neurosurgical patterns of care for diffuse low-grade gliomas in Sweden between 2005 and 2015
- 2018
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Ingår i: Neuro-Oncology Practice. - : Oxford University Press. - 2054-2577 .- 2054-2585. ; 6:2, s. 124-133
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Tidskriftsartikel (refereegranskat)abstract
- Background: In the last decade, increasing evidence has evolved for early and maximal safe resection of diffuse low-grade gliomas (LGGs) regarding survival. However, changes in clinical practice are known to occur slowly and we do not know if the scientific evidence has yet resulted in changes in neurosurgical patterns of care.Methods: The Swedish Brain Tumor Registry was used to identify all patients with a first-time histopathological diagnosis of LGG between 2005 and 2015. For analysis of surgical treatment patterns, we subdivided assessed time periods into 2005-2008, 2009-2012, and 2013-2015. Population-based data on patient and disease characteristics, surgical management, and outcomes were extracted.Results: A total of 548 patients with diffuse World Health Organization grade II gliomas were identified: 142 diagnosed during 2005-2008, 244 during 2009-2012, and 162 during 2013-2015. Resection as opposed to biopsy was performed in 64.3% during 2005-2008, 74.2% during 2009-2012, and 74.1% during 2013-2015 (P = .08). There was no difference among the 3 periods regarding overall survival (P = .11). However, post hoc analysis of data from the 4 (out of 6) centers that covered all 3 time periods demonstrated a resection rate of 64.3% during 2005-2008, 77.4% during 2009-2012, and 75.4% during 2013-2015 (P = .02) and longer survival of patients diagnosed 2009 and onward (P = .04).Conclusion: In this nationwide, population-based study we observed a shift over time in favor of LGG resection. Further, a positive correlation between the more active surgical strategy and longer survival is shown, although no causality can be claimed because of possible confounding factors.
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| 13. |
- Carstam, Louise, et al.
(författare)
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Socioeconomic factors affect treatment delivery for patients with low grade glioma : a Swedish population-based study
- 2020
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Ingår i: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 146:2, s. 329-337
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Despite aspirations to achieve equality in healthcare we know that socioeconomic differences exist and may affect treatment and patient outcome, also in serious diseases such as cancer. We investigated disparities in neurosurgical care and outcome for patients with low-grade glioma (LGG).METHODS: In this nationwide registry-based study, patients who had undergone surgery for LGG during 2005-2015 were identified (n = 547) through the Swedish Brain Tumor Registry. We linked data to multiple national registries with individual level data on income, education and comorbidity and analyzed the association of disease characteristics, surgical management and outcome, with levels of income, education and sex.RESULTS: Patients with either low income, low education or female gender showed worse pre-operative performance status. Patients with low income or education also had more comorbidities and those with low education endured longer waiting times for surgery. Median time from radiological imaging to surgery was 51 days (Q1-3 27-191) for patients with low education, compared to 32 days (Q1-3 20-80) for patients with high education (p = 0.006). Differences in waiting time over educational levels remained significant after stratification for age, comorbidity, preoperative performance status, and tumor size. Overall survival was better for patients with high income or high education, but income- and education-related survival differences were not significant after adjustment for age and comorbidity. The type of surgical procedure or complications did not differ over socioeconomic groups or sex.CONCLUSION: The neurosurgical care for LGG in Sweden, a society with universal healthcare, displays differences that can be related to socioeconomic factors.
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| 14. |
- Carstam, Louise, et al.
(författare)
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WHO Grade Loses Its Prognostic Value in Molecularly Defined Diffuse Lower-Grade Gliomas.
- 2021
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Ingår i: Frontiers in Oncology. - : Frontiers Media S.A.. - 2234-943X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: While molecular insights to diffuse lower-grade glioma (dLGG) have improved the basis for prognostication, most established clinical prognostic factors come from the pre-molecular era. For instance, WHO grade as a predictor for survival in dLGG with isocitrate dehydrogenase (IDH) mutation has recently been questioned. We studied the prognostic role of WHO grade in molecularly defined subgroups and evaluated earlier used prognostic factors in the current molecular setting.Material and Methods: A total of 253 adults with morphological dLGG, consecutively included between 2007 and 2018, were assessed. IDH mutations, codeletion of chromosomal arms 1p/19q, and cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) deletions were analyzed.Results: There was no survival benefit for patients with WHO grade 2 over grade 3 IDH-mut dLGG after exclusion of tumors with known CDKN2A/B homozygous deletion (n=157) (log-rank p=0.97). This was true also after stratification for oncological postoperative treatment and when astrocytomas and oligodendrogliomas were analyzed separately. In IDH-mut astrocytomas, residual tumor volume after surgery was an independent prognostic factor for survival (HR 1.02; 95% CI 1.01-1.03; p=0.003), but not in oligodendrogliomas (HR 1.02; 95% CI 1.00-1.03; p=0.15). Preoperative tumor size was an independent predictor in both astrocytomas (HR 1.03; 95% CI 1.00-1.05; p=0.02) and oligodendrogliomas (HR 1.05; 95% CI 1.01-1.09; p=0.01). Age was not a significant prognostic factor in multivariable analyses (astrocytomas p=0.64, oligodendrogliomas p=0.08).Conclusion: Our findings suggest that WHO grade is not a robust prognostic factor in molecularly well-defined dLGG. Preoperative tumor size remained a prognostic factor in both IDH-mut astrocytomas and oligodendrogliomas in our cohort, whereas residual tumor volume predicted prognosis in IDH-mut astrocytomas only. The age cutoffs for determining high risk in patients with IDH-mut dLGG from the pre-molecular era are not supported by our results.
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| 15. |
- Corell, Alba, et al.
(författare)
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Age and surgical outcome of low-grade glioma in Sweden.
- 2018
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Ingår i: Acta neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 138:4, s. 359-368
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Tidskriftsartikel (refereegranskat)abstract
- Low-grade gliomas (LGG) are slow-growing primary brain tumors that typically affect young adults. Advanced age is widely recognized as a poor prognostic factor in LGG. The impact of age on postoperative outcome in this patient group has not been systemically studied.We performed a nationwide register-based study with data from the Swedish Brain Tumor Registry (SBTR) for all adults diagnosed with a supratentorial LGG (WHO grade II astrocytoma, oligoastrocytoma, or oligodendroglioma) during 2005-2015. Patient- and tumor-related characteristics, postoperative complications, and survival were compared between three different age groups (18-39years, 40-59years, and ≥60years).We identified 548 patients; 204 patients (37.2%) aged 18-39years, 227 patients (41.4%) aged 40-59years, and 117 patients (21.4%) ≥60years of age. Unfavorable preoperative prognostic factors (eg, functional status and neurological deficit) were more common with increased age (P<.001). In addition, overall survival was significantly impaired in those 60years and above (P<.001). We observed a clear dose-response for age with separation of survival curves at 50years. Biopsy was more common in patients ≥60years (P<.001). Subgroup analysis of patients with resection revealed a higher amount of postoperative neurological deficits in older patients (P=.029).In general, older patients with LGG have several unfavorable prognostic factors compared with younger patients but seem to tolerate surgery in a comparable fashion. However, more neurological deficits were observed following resections in elderly. Our data further support a cutoff at 50years rather than 40years for selection of high-risk patients.
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| 16. |
- Corell, Alba, et al.
(författare)
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Stemness and clinical features in relation to the subventricular zone in diffuse lower-grade glioma : an exploratory study
- 2022
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Ingår i: Neuro-Oncology Advances. - : Oxford University Press. - 2632-2498. ; 4:1
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Tidskriftsartikel (refereegranskat)abstract
- Background The subventricular zone (SVZ) of the human brain is a site of adult stem cell proliferation and a microenvironment for neural stem cells (NSCs). It has been suggested that NSCs in the SVZ are potential cells of origin containing driver mutations of glioblastoma, but their role in the origin of diffuse lower-grade gliomas (dLGGs) is not much studied. Methods We included 188 patients >= 18 years with IDH-mutated dLGG (WHO grades 2-3) histologically diagnosed between 2007 and 2020. Tissue microarrays of tumor samples for patients between 2007 and 2016 were used for immunodetection of Nestin, SOX2, SOX9, KLF4, NANOG, CD133 cMYC, and Ki67. DNA methylation profile was used for stemness index (mDNAsi). Tumor contact with the SVZ was assessed and the distance was computed. Results Overall, 70.2% of the dLGG had SVZ contact. Tumors with SVZ contact were larger (102.4 vs 30.9 mL, P < .01), the patients were older (44.3 vs 40.4 years, P = .04) and more often had symptoms related to increased intracranial pressure (31.8% vs 7.1%, P < .01). The expression of SOX2, SOX9, Nestin, and Ki67 showed intersample variability, but no difference was found between tumors with or without SVZ contact, nor with the actual distance to the SVZ. mDNAsi was similar between groups (P = .42). Conclusions We found no statistical relationship between proximity with the SVZ and mDNAsi or expression of SOX2, SOX9, Nestin, and Ki67 in IDH-mutated dLGG. Our data suggest that the potential impact of SVZ on IDH-mutated dLGG is probably not associated with a more stemness-like tumor profile.
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| 17. |
- Corell, Alba, et al.
(författare)
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The clinical significance of the T2-FLAIR mismatch sign in grade II and III gliomas: a population-based study.
- 2020
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Ingår i: BMC cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- The T2-FLAIR mismatch sign is an imaging finding highly suggestive of isocitrate dehydrogenase mutated (IDH-mut) 1p19q non-codeleted (non-codel) gliomas (astrocytomas). In previous studies, it has shown excellent specificity but limited sensitivity for IDH-mut astrocytomas. Whether the mismatch sign is a marker of a clinically relevant subtype of IDH-mut astrocytomas is unknown.We included histopathologically verified supratentorial lower-grade gliomas (LGG) WHO grade II-III retrospectively during the period 2010-2016. In the period 2017-2018, patients with suspected LGG radiologically were prospectively included, and in this cohort other diagnoses than glioma could occur. Clinical, radiological and molecular data were collected. For clinical evaluation we included all patients with IDH-mut astrocytomas. In the 2010-2016 cohort DNA methylation analysis with Infinium MethylationEPIC BeadChip (Illumina) was performed for patients withan IDH-mut astrocytomawith available tissue. We aimed to examine the association of the T2-FLAIRmismatch sign with clinical factors and outcomes. Additionally, we evaluated the diagnostic reliability of the mismatch sign and its relation to methylation profiles.Out of 215 patients with LGG, 135 had known IDH-mutation and 1p19q codeletion status. Fifty patients hadan IDH-mut astrocytoma and 12 of these (24.0%) showed a mismatch sign. The sensitivity and specificity of the mismatch sign for IDH-mut detection were 26.4 and 97.6%, respectively. There were no differences between patients withan IDH-mut astrocytoma with or without mismatch sign when grouped according to T2-FLAIR mismatch sign with respect to baseline characteristics, clinical outcomes and methylation profiles. The overall interrater agreement between neuroradiologist and clinical neurosurgeons for the T2-FLAIR mismatch sign was significant when all 215 MRI examination assessed (κ=0.77, p<0.001, N=215).The T2-FLAIR mismatch sign in patients withan IDH-mut astrocytoma is not associated with clinical presentation or outcome. It seems unlikely that the IDH-mut astrocytomas with mismatch sign represent a specific subentity. Finally, we have validated that the T2-FLAIR mismatch sign is a reliable and specific marker of IDH-mut astrocytomas.
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| 18. |
- Danfors, Torsten, et al.
(författare)
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Epileptic seizures and survival in early disease of grade 2 gliomas
- 2009
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Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 16:7, s. 823-831
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Tidskriftsartikel (refereegranskat)abstract
- Background and purposeThe aims of this study were (i) to determine the correlation between seizure activity and the metabolic rate of the tumour measured by 11Cmethionine PET (MET PET) in patients with grade 2 gliomas, and (ii) to assess the prognostic impact of early seizure manifestations on patient survival.MethodsIn this retrospective review, early seizure manifestations were studied in 101 patients with supratentorial grade 2 gliomas subjected to MET PET as part of the pretreatment tumour investigation. Seizure manifestations as a variable was then used in multivariate survival analyses, together with established prognostic factors for this patient group.ResultsOf all 101 cases, 88 patients had seizures at tumour presentation. Fortyseven were seizure free at the early stage of the disease, whereas 54 had recurrent seizures. Patients with seizures at tumour presentation had a more favourable outcome before and after (P = 0.006) adjustment for conventional prognostic factors. However, for those who continued to have seizures early in the disease, the outcome was worse (P = 0.003). We found no significant correlation between MET PET and the seizure manifestations of the patients.ConclusionThe presence and termination of early seizure manifestations may be favourable prognostic factors in patients with low-grade gliomas.
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| 19. |
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| 20. |
- Dénes, Anna, et al.
(författare)
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The clinical value of proneural, classical and mesenchymal protein signatures in WHO 2021 adult-type diffuse lower-grade gliomas.
- 2023
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 18:5
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Tidskriftsartikel (refereegranskat)abstract
- Accumulating evidence shows that mesenchymal transition of glioblastomas is associated with a more aggressive course of disease and therapy resistance. In WHO2021-defined adult-type diffuse gliomas of lower grade (dLGG), the transition of the tumor phenotype over time, has not been studied. Most efforts to correlate proneural, classical or mesenchymal phenotype with outcome in dLGG were made prior to the WHO 2021 classification. Here, we set out to investigate if phenotype predicted survival and tumor recurrence in a clinical cohort of dLGGs, re-classified according to the 2021 WHO criteria.Using a TMA-based approach with five immunohistochemical markers (EGFR, p53, MERTK, CD44 and OLIG2), we investigated 183 primary and 49 recurrent tumors derived from patients with previously diagnosed dLGG. Of the 49 relapses, nine tumors recurred a second time, and one a third time.In total, 71.0% of all tumors could be subtyped. Proneural was most dominant in IDH-mut tumors (78.5%), mesenchymal more common among IDH-wt tumors (63.6%). There was a significant difference in survival between classical, proneural and mesenchymal phenotypes in the total cohort (p<0.001), but not after molecular stratification (IDH-mut: p = 0.220, IDH-wt: p = 0.623). Upon recurrence, proneural was retained in 66.7% of the proneural IDH-mut dLGGs (n = 21), whereas IDH-wt tumors (n = 10) mainly retained or gained mesenchymal phenotype. No significant difference in survival was found between IDH-mut gliomas remaining proneural and those shifting to mesenchymal phenotype (p = 0.347).Subtyping into classical, proneural and mesenchymal phenotypes by five immunohistochemical markers, was possible for the majority of tumors, but protein signatures did not correlate with patient survival in our WHO2021-stratified cohort. At recurrence, IDH-mut tumors mainly retained proneural, while IDH-wt tumors mostly retained or gained mesenchymal signatures. This phenotypic shift, associated with increased aggressiveness in glioblastoma, did not affect survival. Group sizes were, however, too small to draw any firm conclusions.
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- Ehrstedt, Christoffer
(författare)
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Glioneuronal tumours in childhood : Clinical picture, long-term outcome and possible new treatments
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Glioneuronal tumours are a subgroup of low-grade tumours of the central nervous system (CNS), often causing epilepsy. Overall survival is excellent, but data regarding long-term seizure outcome and late effects are scarce.Aims: The overall aim was to gather data about pre- and postsurgical factors of importance and long-term outcomes to improve standards of care. Another aim was to explore the expression of somatostatin receptor (SSTR) subtypes and mTOR pathway markers.Methods: This thesis, based on four population-based studies with both retrospective and cross-sectional parts, was performed through a long-term follow-up of a Swedish cohort of children with glioneuronal tumours in the Uppsala-Örebro health region. Patients were identified from the National Brain Tumour Registry and the National Epilepsy Surgery Registry. Various methods were used: reviews of hospital medical records, patient interviews, health-related quality of life (HRQoL) assessments with generic (Short Form 36version2) and disease specific (Quality of Life in Epilepsy-31) questionnaires, neuropsychological evaluations with Wechsler Intelligence Scale for Children-IV or Wechsler Adult Intelligence Test-IV and Reys Complex Figure Test and evaluation for possible depression with Hospital Anxiety Depression Scale. Immunohistochemical analyses for SSTR subtypes 1, 2a, 3 and 5 and mTOR pathway components ezrin-radixin-moesin and pS6 were performed on tumour specimens.Results: Glioneuronal tumours seem to be more frequent than previously reported, accounting for 13.5% of all childhood CNS tumours. They often cause medically refractory epilepsy resulting in cognitive impairment. Neurosurgery was often delayed; mean time from symptom debut to lesionectomy was 4.6 years. Long-term seizure freedom was achieved in 84% of patients who had a gross total resection (GTR) and is important for long-term cognitive restitution, HRQoL, educational and vocational outcomes. SSTR2a and SSTR3 expression was a frequent finding in glioneuronal tumours. Signs of mTOR pathway activation were abundant in ganglioglioma.Conclusions: A safe GTR should be striven for and considered a first-line treatment. Long-term clinical follow-up should be offered to all patients and for those with an inoperable tumour/tumour remnant causing tumour growth and/or medically refractory epilepsy, somatostatin analogues and/or mTOR inhibitors might represent a therapeutic alternative worth exploring further.
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- Ek, Lena, 1961-, et al.
(författare)
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Analysis of Cognitive Dysfunction in Patients with Low-Grade Glioma
- 2005
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Ingår i: Journal of clinical psychology in medical settings. - : Springer. - 1068-9583 .- 1573-3572. ; 12:2, s. 165-173
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Tidskriftsartikel (refereegranskat)abstract
- All living adults with histopatologically proven diagnosis of low-grade glioma in a Swedish county were identified with help of the Regional Cancer Register, half of them (n = 24) participated in a neuropsychological evaluation. A considerable variation was found in cognitive function within this group of patients, ranging from good ability to severe disturbance. Different patterns of cognitive dysfunction emerged resulting in three subgroups; patients with severe, mild, and minimal selective dysfunction. The patients with severe disturbance had a global dysfunction covering most assessed cognitive domains. Slow information-processing speed was obvious in the subgroups with both severe and mild dysfunction. Cognitive problems present in the best performing group seemed related to tumor localization. Cognitive function in the whole sample was related to histopathological diagnosis of the tumor, as well as to educational level of the patients. The nonworking patients had significantly poorer performance than the working patients.
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