↓ Direkt till sidans innehåll
↓ Direkt till sidans sekundära innehåll (sidomenyn)

Träfflista för sökning "L773:1573 7373 "

Sökning: L773:1573 7373

Resultat 1-50 av 70

Sortera/gruppera träfflistan

Sortering: Träffar per sida:

Numrering	Referens	Omslagsbild	Hitta
1.	Alexandru, O, et al. (författare) Helianthin induces antiproliferative effect on human glioblastoma cells in vitro 2011 Ingår i: Journal of neuro-oncology. - : Springer Science and Business Media LLC. - 1573-7373 .- 0167-594X. ; 102:1, s. 9-18 Tidskriftsartikel (refereegranskat)
2.	Antonsson, Malin, 1986, et al. (författare) Pre-operative language ability in patients with presumed low-grade glioma 2018 Ingår i: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 137:1, s. 93-102 Tidskriftsartikel (refereegranskat)abstract In patients with low-grade glioma (LGG), language deficits are usually only found and investigated after surgery. Deficits may be present before surgery but to date, studies have yielded varying results regarding the extent of this problem and in what language domains deficits may occur. This study therefore aims to explore the language ability of patients who have recently received a presumptive diagnosis of low-grade glioma, and also to see whether they reported any changes in their language ability before receiving treatment. Twenty-three patients were tested using a comprehensive test battery that consisted of standard aphasia tests and tests of lexical retrieval and high-level language functions. The patients were also asked whether they had noticed any change in their use of language or ability to communicate. The test scores were compared to a matched reference group and to clinical norms. The presumed LGG group performed significantly worse than the reference group on two tests of lexical retrieval. Since five patients after surgery were discovered to have a high-grade glioma, a separate analysis excluding them were performed. These analyses revealed comparable results; however one test of word fluency was no longer significant. Individually, the majority exhibited normal or nearly normal language ability and only a few reported subjective changes in language or ability to communicate. This study shows that patients who have been diagnosed with LGG generally show mild or no language deficits on either objective or subjective assessment.
3.	Bartek, J, et al. (författare) Receipt of brachytherapy is an independent predictor of survival in glioblastoma in the Surveillance, Epidemiology, and End Results database 2019 Ingår i: Journal of neuro-oncology. - : Springer Science and Business Media LLC. - 1573-7373 .- 0167-594X. ; 145:1, s. 75-83 Tidskriftsartikel (refereegranskat)
4.	Bartek Jr., Jiri, et al. (författare) Short-term outcome following surgery for rare brain tumor entities in adults : a Swedish nation-wide registry-based study and comparison with SEER database 2020 Ingår i: Journal of Neuro-Oncology. - : Springer. - 0167-594X .- 1573-7373. ; 148:2, s. 281-290 Tidskriftsartikel (refereegranskat)abstract Objective: To investigate outcomes after surgery for rare brain tumors using the Swedish Brain Tumor Registry (SBTR).Methods: This is a nationwide study of patient in the SBTR, validated in the Surveillance, Epidemiology, and End Results (SEER) registries. We included all adults diagnosed 2009-2015 with a rare brain tumor entity (n = 216), defined as ependymoma (EP, n = 64), subependymoma (SUBEP, n = 21), ganglioglioma (GGL, n = 54), pilocytic astrocytoma (PA, n = 56) and primitive neuroectodermal tumor (PNET, n = 21). We analyzed symptomatology, tumor characteristics and outcomes.Results: Mean age was 38.3 +/- 17.2 years in GGL, 36.2 +/- 16.9 in PA, 37.0 +/- 19.1 in PNET, 51.7 +/- 16.3 in EP and 49.8 +/- 14.3 in SUBEP. The most common symptom was focal deficit (39.6-71.4%), and this symptom was most common in GGL patients with 64.2% of GGL presenting with seizures. Most patients had no or little restriction in activity before surgery (Performance Status 0-1), although up to 15.0% of PNET patients had a performance status of 4. Gross total resection was achieved in most (> 50%) tumor categories. Incidence of new deficits was 11.1-34.4%. In terms of postoperative complications, 0-4.8% had a hematoma of any kind, 1.9-15.6% an infection, 0-7.8% a venous thromboembolism and 3.7-10.9% experienced a complication requiring reoperation. There were 3 deaths within 30-days of surgery, and a 1-year mortality of 0-14.3%.Conclusion: We have provided benchmarks for the current symptomatology, tumor characteristics and outcomes after surgery for rare brain tumors as collected by the SBTR and validated our results in an independent registry. These results may aid in clinical decision making and advising patients.
5.	Bergenheim, A Tommy, et al. (författare) Metabolic manipulation of glioblastoma in vivo by retrograde microdialysis of L-2, 4 diaminobutyric acid (DAB). 2006 Ingår i: J Neurooncol. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 80:3, s. 285-293 Tidskriftsartikel (refereegranskat)
6.	Bergqvist, Jenny, et al. (författare) The effects of clinical and sociodemographic factors on survival, resource use and lead times in patients with high-grade gliomas : a population-based register study 2018 Ingår i: Journal of Neuro-Oncology. - : Springer. - 0167-594X .- 1573-7373. ; 139:3, s. 599-608 Tidskriftsartikel (refereegranskat)abstract Background: Previous studies indicate an effect of sociodemographic factors on risk for being diagnosed with, as well as on survival of cancer in general. Our primary aim was to analyse sociodemographic factors, resource use and lead times in health care after diagnosis with high grade malignant glioma (HGG) in a large population based cohort.Methods: A register-based study using several unique high-coverage registries. All patients over the age of 18 diagnosed with HGG in the Swedish Stockholm-Gotland region between 2001 and 2013 (n=1149) were included.Results: In multivariable cox proportional hazard model of survival, older age, male sex and high tumour grade were associated with worse survival. No significant differences could be seen related to country of birth. A high disposable income was associated with better survival and fewer occasions of pre-diagnostic inpatient care. Older age and comorbidities were correlated with a significantly increased number of outpatient visits the year before HGG diagnosis. In addition, male sex, being born outside Sweden was associated to a higher number of outpatient visits the year after diagnosis in multivariable analysis. Leadtime from diagnosis (first suspicion on brain scan) to surgery showed that the oldest patients, patients with comorbidity and patients born outside Europe had to wait longer for surgery.Conclusions: Sociodemographic factors like education, income and country of birth have impact on care processes both before and after the diagnosis HGG. This needs to be acknowledged in addition to important clinical factors like age, comorbidity and tumour grade, in order to accomplish more equal cancer care.
7.	Berntsson, Shala Ghaderi, et al. (författare) Analysis of DNA repair gene polymorphisms and survival in low-grade and anaplastic gliomas 2011 Ingår i: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 105:3, s. 531-538 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.
8.	Berntsson, Shala Ghaderi, et al. (författare) Perfusion and diffusion MRI combined with (11)C-methionine PET in the preoperative evaluation of suspected adult low-grade gliomas 2013 Ingår i: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 114:2, s. 241-249 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.
9.	Boman, Krister K, et al. (författare) Disability, body image and sports/physical activity in adult survivors of childhood CNS tumors: population-based outcomes from a cohort study. 2013 Ingår i: Journal of neuro-oncology. - : Springer Science and Business Media LLC. - 1573-7373 .- 0167-594X. ; 112:1, s. 99-106 Tidskriftsartikel (refereegranskat)abstract Childhood CNS tumor survivors risk health and functional impairments that threaten normal psychological development and self-perception. This study investigated the extent to which health and functional ability predict adult survivors' body image (BI) and self-confidence regarding sports and physical activity. The study cohort covered 708 eligible ≥18year old CNS tumor survivors, and data from 528 (75%) were analyzed. Disability was estimated using the Health Utilities Index™ Mark2/3, a multidimensional self-report instrument. Physical self-confidence in terms of BI and sports/physical activity-related self-confidence (SPAS) were assessed using the BI and the Sports/Athletics modules of a standardized self-report assessment scale. In adjusted regression models, global health and functional status (GHFS) predicted BI (B=0.94, 95% CI 0.69-1.19) and SPAS (B=0.79, 95% CI 0.55-1.04). Emotion and pain, and to a lesser degree cognition, speech and vision disability, were associated with poorer BI and SPAS. Gender, sub-diagnosis, and time since diagnosis influenced the relationship between health status and physical self-confidence outcomes. Females had poorer GHFS, BI and SPAS than males. Decreased health and functional ability following childhood CNS cancer intrudes on physical self-confidence, with females being at heightened risk for both disability and negative self-confidence. Identified disability and gender-related risk calls for a follow-up plan that integrates treatment of psychological sequelae in lifetime monitoring of childhood CNS tumor survivors to restore and protect self-image and self-confidence, essential mental health correlates. An expanded plan should recognize the need for such services, optimizing life-long quality of survival for CNS tumor survivors.
10.	Bø, Hans Kristian, et al. (författare) Intra-rater variability in low-grade glioma segmentation. 2017 Ingår i: Journal of neuro-oncology. - : Springer Science and Business Media LLC. - 1573-7373 .- 0167-594X. ; 131:2, s. 393-402 Tidskriftsartikel (refereegranskat)abstract Assessment of size and growth are key radiological factors in low-grade gliomas (LGGs), both for prognostication and treatment evaluation, but the reliability of LGG-segmentation is scarcely studied. With a diffuse and invasive growth pattern, usually without contrast enhancement, these tumors can be difficult to delineate. The aim of this study was to investigate the intra-observer variability in LGG-segmentation for a radiologist without prior segmentation experience. Pre-operative 3D FLAIR images of 23 LGGs were segmented three times in the software 3D Slicer. Tumor volumes were calculated, together with the absolute and relative difference between the segmentations. To quantify the intra-rater variability, we used the Jaccard coefficient comparing both two (J2) and three (J3) segmentations as well as the Hausdorff Distance (HD). The variability measured with J2 improved significantly between the two last segmentations compared to the two first, going from 0.87 to 0.90 (p=0.04). Between the last two segmentations, larger tumors showed a tendency towards smaller relative volume difference (p=0.07), while tumors with well-defined borders had significantly less variability measured with both J2 (p=0.04) and HD (p<0.01). We found no significant relationship between variability and histological sub-types or Apparent Diffusion Coefficients (ADC). We found that the intra-rater variability can be considerable in serial LGG-segmentation, but the variability seems to decrease with experience and higher grade of border conspicuity. Our findings highlight that some criteria defining tumor borders and progression in 3D volumetric segmentation is needed, if moving from 2D to 3D assessment of size and growth of LGGs.
11.	Capala, J, et al. (författare) Boron neutron capture therapy for glioblastoma multiforme : Clinical studies in Sweden 2003 Ingår i: Journal of Neuro-Oncology. - 1573-7373. ; 62:1, s. 135-144 Tidskriftsartikel (refereegranskat)abstract A boron neutron capture therapy (BNCT) facility has been constructed at Studsvik, Sweden. It includes two filter/moderator configurations. One of the resulting neutron beams has been optimized for clinical irradiations with a filter/moderator system that allows easy variation of the neutron spectrum from the thermal to the epithermal energy range. The other beam has been designed to produce a large uniform field of thermal neutrons for radio-biological research. Scientific operations of the Studsvik BNCT project are overseen by the Scientific Advisory Board comprised of representatives of major universities in Sweden. Furthermore, special task groups for clinical and preclinical studies have been formed to facilitate collaboration with academia. The clinical Phase II trials for glioblastoma are sponsored by the Swedish National Neuro-Oncology Group and, presently, involve a protocol for BNCT treatment of glioblastoma patients who have not received any therapy other than surgery. In this protocol, p-boronophenylalanine (BPA), administered as a 6-h intravenous infusion, is used as the boron delivery agent. As of January 2002, 17 patients were treated. The 6-h infusion of 900 mg BPA/kg body weight was shown to be safe and resulted in the average blood-boron concentration of 24 μg/g (range: 15-32 μg/g) at the time of irradiation (approximately 2-3 h post-infusion). Peak and average weighted radiation doses to the brain were in the ranges of 8.0-15.5 Gy(W) and 3.3-6.1 Gy(W), respectively. So far, no severe BNCT-related acute toxicities have been observed. Due to the short follow-up time, it is too early to evaluate the efficacy of these studies.
12.	Carapancea, M, et al. (författare) Dual targeting of IGF-1R and PDGFR inhibits proliferation in high-grade gliomas cells and induces radiosensitivity in JNK-1 expressing cells 2007 Ingår i: Journal of neuro-oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 85:3, s. 245-254 Tidskriftsartikel (refereegranskat)
13.	Carapancea, M, et al. (författare) Growth factor receptors signaling in glioblastoma cells: therapeutic implications 2009 Ingår i: Journal of neuro-oncology. - : Springer Science and Business Media LLC. - 1573-7373 .- 0167-594X. ; 92:2, s. 137-147 Tidskriftsartikel (refereegranskat)
14.	Carlsson, Jörgen, et al. (författare) Planning for intracavitary anti-EGFR radionuclide therapy of gliomas : Literature review and data on EGFR expression 2006 Ingår i: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 77:1, s. 33-45 Tidskriftsartikel (refereegranskat)abstract Targeting with radionuclide labelled substances that bind specifically to the epidermal growth factor receptor, EGFR, is considered for intracavitary therapy of EGFR-positive glioblastoma multiforme, GBM. Relevant literature is reviewed and examples of EGFR expression in GBM are given. The therapeutical efforts made so far using intracavitary anti-tenascin radionuclide therapy of GBM have given limited effects, probably due to low radiation doses to the migrating glioma cells in the brain. Low radiation doses might be due to limited penetration of the targeting agents or heterogeneity in the expression of the target structure. In this article we focus on the possibilities to target EGFR on the tumour cells instead of an extracellular matrix component. There seems to be a lack of knowledge on the degree of intratumoral variation of EGFR expression in GBM, although the expression seemed rather homogeneous over large areas in most of the examples (n=16) presented from our laboratory. The observed homogeneity was surprising considering the genomic instability and heterogeneity that generally characterises highly malignant tumours. However, overexpression of EGFR is, at least in primary GBMs, one of the steps in the development of malignancy, and tumour cells that lose or downregulate EGFR will probably be outgrown in an expanding tumour cell population. Thus, loss of EGFR expression might not be the critical factor for successful intracavitary radionuclide therapy. Instead, it is likely that the penetration properties of the targeting agents are critical, and detailed studies on this are urgent.
15.	Carstam, Louise, et al. (författare) Long-term follow up of patients with WHO grade 2 oligodendroglioma 2023 Ingår i: Journal of Neuro-Oncology. - 0167-594X .- 1573-7373. ; 165, s. 65-74 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.
16.	Carstam, Louise, et al. (författare) Seizures in patients with IDH-mutated lower grade gliomas. 2022 Ingår i: Journal of neuro-oncology. - : Springer Science and Business Media LLC. - 1573-7373 .- 0167-594X. ; 160, s. 403-411 Tidskriftsartikel (refereegranskat)abstract Most patients with Lower Grade Gliomas (LGG) present with epileptic seizures. Since the advent of molecular diagnostics, more homogenous sub-entities have emerged, including the isocitrate dehydrogenase-mutated (IDH-mutated) astrocytomasand 1p19q-codeleted oligodendrogliomas. We aimed to describe the occurrence of seizures in patients with molecularly defined LGG pre- and postoperatively and to analyze factors affecting seizure status postoperatively.A population-based cohort of 130 adult patients with IDH-mutated WHO grade 2 or 3 astrocytomas and oligodendrogliomas was assessed pertaining to seizure burden before and after surgery.Fifty-four (79.4%) patients with astrocytoma and 45 (72.6%) patients with oligodendroglioma had a history of seizures before surgery. At 12months postoperatively, 51/67 (76.1%) patients with astrocytoma and 47/62 (75.8%) patients with oligodendrogliomas were seizure free. In a multivariable logistic regression analysis, lower extent of resection (EOR) (OR 0.98; 95% CI 0.97-1.00, p=0.01) and insular tumor location (OR 5.02; 95% CI 1.01-24.87, p=0.048) were associated with presence of seizures within 1 year postoperatively in the entire LGG cohort. In sub-entities, EOR was in a similar manner associated with seizures postoperatively in astrocytomas (OR 0.98; 95% CI 0.96-0.99, p<0.01) but not in oligodendrogliomas (p=0.34).Our results are well in line with data published for non-molecularly defined LGG with a large proportion of patients being seizure free at 1 year postoperative. Better seizure outcome was observed with increased EOR in astrocytomas, but this association was absent in oligodendrogliomas.
17.	Carstam, Louise, et al. (författare) Socioeconomic factors affect treatment delivery for patients with low grade glioma : a Swedish population-based study 2020 Ingår i: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 146:2, s. 329-337 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.
18.	Dahlin, Anna M., 1979-, et al. (författare) A genome-wide association study on medulloblastoma 2020 Ingår i: Journal of Neuro-Oncology. - : Springer. - 0167-594X .- 1573-7373. ; 147:2, s. 309-315 Tidskriftsartikel (refereegranskat)abstract Introduction: Medulloblastoma is a malignant embryonal tumor of the cerebellum that occurs predominantly in children. To find germline genetic variants associated with medulloblastoma risk, we conducted a genome-wide association study (GWAS) including 244 medulloblastoma cases and 247 control subjects from Sweden and Denmark.Methods: Genotyping was performed using Illumina BeadChips, and untyped variants were imputed using IMPUTE2.Results: Fifty-nine variants in 11 loci were associated with increased medulloblastoma risk (p < 1 × 10–5), but none were statistically significant after adjusting for multiple testing (p < 5 × 10–8). Thirteen of these variants were genotyped, whereas 46 were imputed. Genotyped variants were further investigated in a validation study comprising 249 medulloblastoma cases and 629 control subjects. In the validation study, rs78021424 (18p11.23, PTPRM) was associated with medulloblastoma risk with OR in the same direction as in the discovery cohort (ORT = 1.59, pvalidation = 0.02). We also selected seven medulloblastoma predisposition genes for investigation using a candidate gene approach: APC, BRCA2, PALB2, PTCH1, SUFU, TP53, and GPR161. The strongest evidence for association was found for rs201458864 (PALB2, ORT = 3.76, p = 3.2 × 10–4) and rs79036813 (PTCH1, ORA = 0.42, p = 2.6 × 10–3).Conclusion: The results of this study, including a novel potential medulloblastoma risk loci at 18p11.23, are suggestive but need further validation in independent cohorts.
19.	Dahlin, Anna M., et al. (författare) CCND2, CTNNB1, DDX3X, GLI2, SMARCA4, MYC, MYCN, PTCH1, TP53, and MLL2 gene variants and risk of childhood medulloblastoma 2015 Ingår i: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 125:1, s. 75-78 Tidskriftsartikel (refereegranskat)abstract Recent studies have described a number of genes that are frequently altered in medulloblastoma tumors and that have putative key roles in the development of the disease. We hypothesized that common germline genetic variations in these genes may be associated with medulloblastoma development. Based on recent publications, we selected 10 genes that were frequently altered in medulloblastoma: CCND2, CTNNB1, DDX3X, GLI2, SMARCA4, MYC, MYCN, PTCH1, TP53, and MLL2 (now renamed as KMT2D). Common genetic variants (single nucleotide polymorphisms) annotating these genes (n = 221) were genotyped in germline DNA (neonatal dried blood spot samples) from 243 childhood medulloblastoma cases and 247 control subjects from Sweden and Denmark. Eight genetic variants annotating three genes in the sonic hedgehog signaling pathway; CCND2, PTCH1, and GLI2, were found to be associated with the risk of medulloblastoma (P (combined) < 0.05). The findings were however not statistically significant following correction for multiple testing by the very stringent Bonferroni method. The results do not support our hypothesis that common germline genetic variants in the ten studied genes are associated with the risk of developing medulloblastoma.
20.	Dahlström Wester, Maria, et al. (författare) Accumulation of boron in human malignant glioma cells in vitro is cell type dependent 2004 Ingår i: Journal of Neuro-Oncology. - 0167-594X .- 1573-7373. ; 68:3, s. 199-205 Tidskriftsartikel (refereegranskat)abstract It has been shown that human malignant glioma tumours consist of several subpopulations of tumour cells. Due to heterogeneity and different degrees of vascularisation cell subpopulations possess varying resistance to chemo- or radiation therapy. Therefore, therapy is dependent on the ability to specifically target a tumour cell. Boron neutron capture therapy (BNCT) is a bimodal method, in radiation therapy, taking advantage of the ability of the stable isotope boron-10 to capture neutrons. It results in disintegration products depositing large amounts of energy within a short length, approximately one cell diameter. Thereby, selective irradiation of a target cell may be accomplished if a sufficient amount of boron has been accumulated and hence the cell-associated boron concentration is of critical importance. The accumulation of boron, boronophenylalanine (BPA), was investigated in two human glioma cell subpopulations and a human fibroblast cell line in vitro. The cells were incubated at low boron concentrations (0-5 microg B/ml). Oil filtration was then used for separation of extracellular and cell-associated boron. Inductively coupled plasma atomic emission spectroscopy (ICP-AES) was used for boron determination. Significant (P < 0.05) differences in accumulation ratio (relation between cell-associated and extracellular boron concentration) between human malignant glioma cell lines were found. Human fibroblasts, used to represent normal cells, showed a growth-dependent uptake and a lower accumulation ratio than the glioma cells. Our findings indicate that BPA concentration, incubation time and differences in boron uptake between cell subpopulations should be considered in BNCT.
21.	Fisher, JL, et al. (författare) Comorbid conditions associated with glioblastoma 2014 Ingår i: Journal of neuro-oncology. - : Springer Science and Business Media LLC. - 1573-7373 .- 0167-594X. ; 116:3, s. 585-591 Tidskriftsartikel (refereegranskat)
22.	Freyschlag, Christian F, et al. (författare) Imaging practice in low-grade gliomas among European specialized centers and proposal for a minimum core of imaging. 2018 Ingår i: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 139:3, s. 699-711 Tidskriftsartikel (refereegranskat)abstract 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.
23.	Gatsinzi, Tom, 1982-, et al. (författare) Sensitization to TRAIL-induced apoptosis in human neuroblastoma SK-N-AS cells by NF-kappa B inhibitors is dependent on reactive oxygen species (ROS) 2011 Ingår i: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 104:2, s. 459-472 Tidskriftsartikel (refereegranskat)abstract Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to induce apoptosis in a variety of cancer cell lines with almost no toxicity toward normal cells. However, many neuroblastoma cells acquire resistance to TRAIL by mechanisms that are poorly understood. The objective of this study was to investigate involvement of the transcription factor NF-kappa B in the resistance of human neuroblastoma SK-N-AS cells to TRAIL-induced apoptosis. We used five compounds previously reported to inhibit NF-kappa B activity. SN50, curcumin, oridonin, and pyrrolidine dithiocarbamate (PDTC) all sensitized cells to TRAIL-induced apoptosis. In contrast, N-alpha-tosyl-l-phenylalanyl chloromethyl ketone (TPCK) did not affect sensitivity to TRAIL, although reporter gene assay clearly showed inhibition of NF-kappa B activity. In addition, neither curcumin nor oridonin had any inhibitory effect on NF-kappa B activity at concentrations at which sensitization to TRAIL was observed. Instead, the free radical scavenger N-acetyl-l-cysteine (NAC) completely blocked the effect on TRAIL-induced apoptosis caused by curcumin, oridonin, and PDTC. Furthermore, exposure of SK-N-AS cells to H(2)O(2) could mimic the TRAIL-sensitizing effect of other agents. In conclusion, our results suggest that sensitization of neuroblastoma SK-N-AS cells to TRAIL-induced apoptosis is correlated with induction of reactive oxygen species (ROS) rather than inhibition of NF-kappa B.
24.	Gatsinzi, Tom, 1982-, et al. (författare) TRAIL resistance in human neuroblastoma SK-N-AS cells is dependent on protein kinase C and involves inhibition of caspase-3 proteolytic processing 2012 Ingår i: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 109:3, s. 503-512 Tidskriftsartikel (refereegranskat)abstract Neuroblastoma is the most common solid extracranial cancer form in childhood with an etiology that is mostly unknown. Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been proposed as a promising future anticancer drug candidate, highly malignant neuroblastoma has been reported to acquire TRAIL resistance by mechanisms that are poorly understood. Here, we show by western blot analysis, and live cell imaging using anchored FRET sensors, that the resistance to TRAIL-induced apoptosis in human neuroblastoma SK-N-AS cells depends on an incomplete processing of procaspase-3, generating an immature and catalytically inactive 21 kDa fragment. We have previously shown that the naturally occurring compound curcumin can sensitize SK-N-AS cells to TRAIL. In the present study, we show that curcumin also has a similar effect on human neuroblastoma SHEP1 cells. Furthermore, we show that curcumin and TRAIL co-treatment induces complete maturation and activation of caspase-3 in both cell lines. The mechanisms behind this effect seem to be dependent on protein kinase C (PKC), since inhibition of PKC using bisindolylmaleimide XI, could also sensitize these cells to TRAIL through a similar effect on caspase-3 activation. Moreover, TRAIL co-treatment with bisindolylmaleimide XI or curcumin resulted in down-regulation of X-linked inhibitor of apoptosis protein. In conclusion, our study shows that PKC can be involved in TRAIL resistance in human neuroblastoma cells by preventing caspase-3 maturation.
25.	Gehrke, A. K., et al. (författare) Neurocognitive deficits following primary brain tumor treatment: systematic review of a decade of comparative studies 2013 Ingår i: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 115:2, s. 135-142 Tidskriftsartikel (refereegranskat)abstract There has been an increase in the prevalence of adults diagnosed with and treated for primary brain tumors. Cognitive deficits are a common long-term effect in brain tumor survivors. The objective of this paper is to examine whether these deficits are specific to those diagnosed with and treated for a primary brain tumor. A systematic review of the medical literature from 2002 to 2012 was conducted to investigate neurocognitive deficits in brain tumor survivors (post-primary treatment) compared to healthy controls. Four studies were identified that met all inclusion criteria. Gliomas were the most common form of tumor included. Neuropsychological evaluation identified cognitive deficits in brain tumor survivors on tests of working memory, cognitive control and flexibility, cognitive processing speed, visual searching, planning and foresight, and general attention. While age, education, and gender can influence cognitive function, the present review indicates that deficits exist beyond those accounted for by these factors. Many primary brain tumor survivors are involved in roles (e.g., employee, parent, spouse/partner, student) that require optimal performance of these cognitive skills. Future research should evaluate brain tumor survivors on functional challenges resulting from these cognitive sequelae and develop effective ways to mitigate them.
26.	Georgakis, MK, et al. (författare) Clinical, neuroimaging and histopathological features of gliomatosis cerebri: a systematic review based on synthesis of published individual patient data 2018 Ingår i: Journal of neuro-oncology. - : Springer Science and Business Media LLC. - 1573-7373 .- 0167-594X. ; 140:2, s. 467-475 Tidskriftsartikel (refereegranskat)
27.	Ghasimi, Soma, et al. (författare) Genetic risk variants in the CDKN2A/B, RTEL1 and EGFR genes are associated with somatic biomarkers in glioma 2016 Ingår i: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 127:3, s. 483-492 Tidskriftsartikel (refereegranskat)abstract During the last years, genome wide association studies have discovered common germline genetic variants associated with specific glioma subtypes. We aimed to study the association between these germline risk variants and tumor phenotypes, including copy number aberrations and protein expression. A total of 91 glioma patients were included. Thirteen well known genetic risk variants in TERT, EGFR, CCDC26, CDKN2A, CDKN2B, PHLDB1, TP53, and RTEL1 were selected for investigation of possible correlations with the glioma somatic markers: EGFR amplification, 1p/19q codeletion and protein expression of p53, Ki-67, and mutated IDH1. The CDKN2A/B risk variant, rs4977756, and the CDKN2B risk variant, rs1412829 were inversely associated (p = 0.049 and p = 0.002, respectively) with absence of a mutated IDH1, i.e., the majority of patients homozygous for the risk allele showed no or low expression of mutated IDH1. The RTEL1 risk variant, rs6010620 was associated (p = 0.013) with not having 1p/19q codeletion, i.e., the majority of patients homozygous for the risk allele did not show 1p/19q codeletion. In addition, the EGFR risk variant rs17172430 and the CDKN2B risk variant rs1412829, both showed a trend for association (p = 0.055 and p = 0.051, respectively) with increased EGFR copy number, i.e., the majority of patients homozygote for the risk alleles showed chromosomal gain or amplification of EGFR. Our findings indicate that CDKN2A/B risk genotypes are associated with primary glioblastoma without IDH mutation, and that there is an inverse association between RTEL1 risk genotypes and 1p/19q codeletion, suggesting that these genetic variants have a molecular impact on the genesis of high graded brain tumors. Further experimental studies are needed to delineate the functional mechanism of the association between genotype and somatic genetic aberrations.
28.	Ghasimi, Soma, et al. (författare) Immunohistochemical analysis of LRIG proteins in meningiomas: correlation between estrogen receptor status and LRIG expression 2012 Ingår i: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 108:3, s. 435-441 Tidskriftsartikel (refereegranskat)abstract The leucine-rich repeats and immunoglobulin-like domains (LRIG) protein family is comprised of three integral membrane proteins: LRIG1, LRIG2, and LRIG3. LRIG1 is a negative regulator of growth factor signaling. The expression and subcellular localization of LRIG proteins have prognostic implications in primary brain tumors, such as oligodendrogliomas and astrocytomas. The expression of LRIG proteins has not previously been studied in meningiomas. In this study, the expression of LRIG1, LRIG2, and LRIG3 was analyzed in 409 meningiomas by immunohistochemistry, and potential associations between LRIG protein expression and tumor grade, gender, progesterone receptor status, and estrogen receptor (ER) status were investigated. The LRIG proteins were most often expressed in the cytoplasm, though LRIG1 also showed prominent nuclear expression. Cytoplasmic expression of LRIG1 and LRIG2 correlated with histological subtypes of meningiomas (p = 0.038 and 0.013, respectively). Nuclear and cytoplasmic expression of LRIG1 was correlated with ER status (p = 0.003 and 0.004, respectively), as was cytoplasmic expression of LRIG2 (p = 0.006). This study is the first to examine the expression of LRIG proteins in meningiomas, and it shows a correlation between ER status and the expression of LRIG1 and LRIG2, which suggests a possible role for LRIG proteins in meningioma pathogenesis.
29.	Hagiwara, Akifumi, et al. (författare) Incidence, molecular characteristics, and imaging features of "clinically-defined pseudoprogression" in newly diagnosed glioblastoma treated with chemoradiation 2022 Ingår i: Journal of Neuro-Oncology. - : Springer. - 0167-594X .- 1573-7373. ; 159, s. 509-518 Tidskriftsartikel (refereegranskat)abstract Purpose: Pseudoprogression (PsP) remains an elusive and clinically important, yet ill-defined, phenomena that, generally, involves a period of early radiographic progression (enhancement) followed by a period of radiographic stability or regression. In the current study, we utilized data from the control arm of a phase III clinical trial in newly-diagnosed glioblastoma to explore imaging characteristics of “clinically-defined PsP”, or early radiographic progression (PFS < 6 months from chemoradiation) followed by a long post-progression residual overall survival (ROS > 12 months).Methods: One hundred sixty-nine patients with newly-diagnosed GBM from the control arm of the AVAglio trial (NCT00943826) who presented with early radiographic progressive disease (PD) (< 6 months) were included. Clinical characteristics, topographical patterns, and radiomic features were compared between newly-diagnosed GBM exhibiting early PD and early death (< 12-month ROS, “true PD”) with those exhibiting early PD and a long residual survival (> 12-month ROS, “clinically-defined PsP”).Results: “Clinically-defined PsP” occurred to 38.5% of patients with early PD, and was more associated with MGMT methylation (P = 0.02), younger age (P = 0.003), better neurological performance (P = 0.01), and lower contrast-enhancing tumor volume (P = 0.002) at baseline. GBM showing “true PD” occurred more frequently in the right internal capsule, thalamus, lentiform nucleus, and temporal lobe than those with “clinical PsP”. Radiomic analysis predicted “clinical PsP” with > 70% accuracy on the validation dataset.Conclusion: Patients with early PD that eventually exhibit “clinically-defined PsP” have distinct clinical, molecular, and MRI characteristics. This information may be useful for treating clinicians to better understand the potential risks and outcome in patients exhibiting early radiographic changes following chemoradiation.
30.	Henriksson, Roger, et al. (författare) High-grade astrocytoma treated concomitantly with estramustine and radiotherapy. 2006 Ingår i: Journal of neuro-oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 78:3, s. 321-6 Tidskriftsartikel (refereegranskat)abstract Experimental and early clinical investigations have demonstrated encouraging results for estramustine in the treatment of malignant glioma. The present study is an open randomized clinical trial comparing estramustine phosphate (Estracyt) in addition to radiotherapy with radiotherapy alone as first line treatment of astrocytoma grade III and IV. The 140 patients included were in a good clinical condition with a median age of 55 years (range 22-87). Estramustine was given orally, 280 mg twice daily, as soon as the diagnosis was established, during and after the radiotherapy for a period of in total 3 months. Radiotherapy was delivered on weekdays 2 Gy daily up to 56 Gy. Eighteen patients were excluded due to misclassification, leaving 122 patients eligible for evaluation. Overall the treatment was well tolerated. Mild or moderate nausea was the most common side effect of estramustine. The minimum follow-up time was 5.2 years for the surviving patients. For astrocytoma grade III the median survival time was 10.6 (1.3-92.7) months for the radiotherapy only group and 17.3 (0.4-96.9+) months for the estramustine + radiotherapy group. In grade IV the corresponding median survival time was 12.3 (2.1-89.2) and 10.3 (0.3-91.7+) months, respectively. Median time to progress for radiotherapy only and radiotherapy and estramustin group in grade III tumours was 6.5 and 10.1 months, respectively. In grade IV tumours the corresponding figures were 5.1 and 3.3 months, respectively. Although there was a tendency for improved survival in grade III, no statistical significant differences were found between the treatment groups. No differences between the two treatment groups were evident with respect to quality of life according to the EORTC QLQ-protocol. In conclusion, this first randomized study did not demonstrate any significant improvement of using estramustine in addition to conventional radiotherapy, however, a trend for a positive response for the estramustine group was found in patients with grade III glioma.
31.	Henriksson, Roger, et al. (författare) Impact of therapy on quality of life, neurocognitive function and their correlates in glioblastoma multiforme : a review 2011 Ingår i: Journal of Neuro-Oncology. - Boston : Nijhoff. - 0167-594X .- 1573-7373. ; 104:3, s. 639-646 Forskningsöversikt (refereegranskat)abstract The maintenance of quality of life (QoL) in patients with high-grade glioma is an important endpoint during treatment, particularly in those with glioblastoma multiforme (GBM) given its dismal prognosis despite limited advances in standard therapy. It has proven difficult to identify new therapies that extend survival in patients with recurrent GBM, so one of the primary aims of new therapies is to reduce morbidity, restore or preserve neurologic functions, and the capacity to perform daily activities. Apart from temozolomide, cytotoxic chemotherapeutic agents do not appear to significantly impact response or survival, but produce toxicity that is likely to negatively impact QoL. New biological agents, such as bevacizumab, can induce a clinically meaningful proportion of durable responses among patients with recurrent GBM with an acceptable safety profile. Emerging evidence suggests that bevacizumab produces an improvement or preservation of neurocognitive function in GBM patients, suggestive of QoL improvement, in most poor-prognosis patients who would otherwise be expected to show a sudden and rapid deterioration in QoL.
32.	Huang, Wuqing, et al. (författare) Mortality patterns in long-term survivors of childhood or adolescent central nervous system tumour in Sweden 2019 Ingår i: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 1573-7373 .- 0167-594X. ; 145:3, s. 541-549 Tidskriftsartikel (refereegranskat)abstract PURPOSE: A growing number of young patients with central nervous system (CNS) tumour survived for more than five years. However, these long-term survivors might be at risk of multiple late effects thus leading to a higher risk of late mortality. We aimed to explore the risk of late mortality and the pattern of mortality among long-term survivors of childhood or adolescent CNS tumour.METHODS: We identified 5-year survivors with childhood or adolescent CNS tumour before age 20 years through the Swedish Cancer Registry. Five controls were randomly matched for each patient to generate the reference group. We retrieved information about death via Cause of Death Register. We calculated the absolute excess risk (AER) of death and the hazard ratio (HR) of death using Cox proportional hazard model.RESULTS: Long-term survivors with CNS tumour suffered a significant higher risk of overall mortality (HR 6.56, 95% CI 5.71-7.53; AER 5.89, 95% CI 5.03-6.87). The mortality rate declined with the increasing survival time, but it was still higher even after 30 years of follow-up. Malignant neoplasms contributed mostly to late mortality with an AER of 3.75 (95% CI 2.95-4.75). Female survivors, survivors diagnosed at a younger age and survivors with medulloblastoma were particularly strongly associated with a higher risk of death.CONCLUSIONS: Long-term survivors of childhood and adolescent CNS tumours are at a higher risk of late mortality, and the risk of death is affected by gender, age at diagnosis and types of CNS tumour.
33.	Indira Chandran, Vineesh, et al. (författare) Global extracellular vesicle proteomic signature defines U87-MG glioma cell hypoxic status with potential implications for non-invasive diagnostics 2019 Ingår i: Journal of Neuro-Oncology. - : SPRINGER. - 0167-594X .- 1573-7373. ; 144:3, s. 477-488 Tidskriftsartikel (refereegranskat)abstract Purpose Glioblastoma multiforme (GBM) is the most common and lethal of primary malignant brain tumors. Hypoxia constitutes a major determining factor for the poor prognosis of high-grade glioma patients, and is known to contribute to the development of treatment resistance. Therefore, new strategies to comprehensively profile and monitor the hypoxic status of gliomas are of high clinical relevance. Here, we have explored how the proteome of secreted extracellular vesicles (EVs) at the global level may reflect hypoxic glioma cells. Methods We have employed shotgun proteomics and label free quantification to profile EVs isolated from human high-grade glioma U87-MG cells cultured at normoxia or hypoxia. Parallel reaction monitoring was used to quantify the identified, hypoxia-associated EV proteins. To determine the potential biological significance of hypoxia-associated proteins, the cumulative Z score of identified EV proteins was compared with GBM subtypes from HGCC and TCGA databases. Results In total, 2928 proteins were identified in EVs, out of which 1654 proteins overlapped with the ExoCarta EV-specific database. We found 1034 proteins in EVs that were unique to the hypoxic status of U87-MG cells. We subsequently identified an EV protein signature, "HYPSIGNATURE", encompassing nine proteins that strongly represented the hypoxic situation and exhibited close proximity to the mesenchymal GBM subtype. Conclusions We propose, for the first time, an EV protein signature that could comprehensively reflect the hypoxic status of high-grade glioma cells. The presented data provide proof-of-concept for targeted proteomic profiling of glioma derived EVs, which should motivate future studies exploring its utility in non-invasive diagnosis and monitoring of brain tumor patients.
34.	Jain, R, et al. (författare) Treatment induced necrosis versus recurrent/ progressive brain tumor: Going beyond the bondaries of conventional morphologic imaging. 2010 Ingår i: Journal of Neuro-Oncology. - 1573-7373. ; 100:1, s. 17-29 Tidskriftsartikel (refereegranskat)
35.	Jakola, Asgeir Store, et al. (författare) Spatial distribution of malignant transformation in patients with low-grade glioma. 2020 Ingår i: Journal of neuro-oncology. - : Springer Science and Business Media LLC. - 1573-7373 .- 0167-594X. ; 146, s. 373-380 Tidskriftsartikel (refereegranskat)abstract Malignant transformation represents the natural evolution of diffuse low-grade gliomas (LGG). This is a catastrophic event, causing neurocognitive symptoms, intensified treatment and premature death. However, little is known concerning the spatial distribution of malignant transformation in patients with LGG.Patients histopathological diagnosed with LGG and subsequent radiological malignant transformation were identified from two different institutions. We evaluated the spatial distribution of malignant transformation with (1) visual inspection and (2) segmentations of longitudinal tumor volumes. In (1) a radiological transformation site<2cm from the tumor on precedingMRI was defined local transformation. In (2) overlap with pretreatment volume after importation into a common space was defined as local transformation. With a centroid model we explored if there were particular patterns of transformations within relevant subgroups.We included 43 patients in the clinical evaluation, and 36 patients had MRIs scans available for longitudinal segmentations. Prior to malignant transformation, residual radiological tumor volumes were>10ml in 93% of patients. The transformation site was considered local in 91% of patients by clinical assessment. Patients treated with radiotherapy prior to transformation had somewhat lower rate of local transformations (83%). Based upon the segmentations, the transformation was local in 92%. We did not observe any particular pattern of transformations in examined molecular subgroups.Malignant transformation occurs locally and within the T2w hyperintensities in most patients. Although LGG is an infiltrating disease, this data conceptually strengthens the role of loco-regional treatments in patients with LGG.
36.	Jeibmann, Astrid, et al. (författare) Involvement of CD9 and PDGFR in migration is evolutionarily conserved from Drosophila glia to human glioma 2015 Ingår i: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 124:3, s. 373-383 Tidskriftsartikel (refereegranskat)abstract Platelet-derived growth factor receptor (PDGFR) signaling plays an important role in the biology of malignant gliomas. To investigate mechanisms modulating PDGFR signaling in gliomagenesis, we employed a Drosophila glioma model and genetic screen to identify genes interacting with Pvr, the fly homolog of PDGFRs. Glial expression of constitutively activated Pvr (lambda Pvr) led to glial over migration and lethality at late larval stage. Among 3316 dsRNA strains crossed against the tester strain, 128 genes shifted lethality to pupal stage, including tetraspanin 2A (tsp2A). In a second step knockdown of all Drosophila tetraspanins was investigated. Of all tetraspanin dsRNA strains only knockdown of tsp2A partially rescued the Pvr-induced phenotype. Human CD9 (TSPAN29/MRP-1), a close homolog of tsp2A, was found to be expressed in glioma cell lines A172 and U343MG as well as in the majority of glioblastoma samples (16/22, 73 %). Furthermore, in situ proximity ligation assay revealed close association of CD9 with PDGFR alpha and beta. In U343MG cells, knockdown of CD9 blocked PDGF-BB stimulated migration. In conclusion, modulation of PDGFR signaling by CD9 is evolutionarily conserved from Drosophila glia to human glioma and plays a role in glia migration.
37.	Järvelä, Sally, et al. (författare) Antioxidant enzymes in oligodendroglial brain tumors : association with proliferation, apoptotic activity and survival 2006 Ingår i: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 77:2, s. 131-40 Tidskriftsartikel (refereegranskat)abstract Purpose of the study was to investigate the relationship between antioxidant enzyme expression and clinicopathological features in oligodendroglial tumors. The expression of antioxidant enzymes and related proteins (AOEs), manganese superoxide dismutase (MnSOD), thioredoxin (Trx), thioredoxin reductase (TrxR) and gammaglutamylcysteine synthetase catalytic and regulatory subunits (GLCL-C and GLCL-R), was studied in 85 oligodendroglial tumors. The material included 71 primary (43 grade II and 28 grade III) and 14 recurrent (6 grade II and 8 grade III) tumors. Fifty-seven cases were pure oligodendrogliomas and 28 were mixed oligoastrocytomas. Immunoreactivity for MnSOD was found in 89%, Trx in 29%, TrxR in 76%, GLCL-C in 70% and GLCL-R in 68% of cases. Increased Trx expression was associated with higher tumor grade, cell proliferation and apoptosis (P=0.006, P=0.001 and P=0.003, Mann-Whitney test). Pure oligodendrogliomas showed more intense staining than oligoastrocytomas, especially for MnSOD (P=0.002, Mann-Whitney test). In the total series Trx was associated with poor prognosis in univariate survival analysis (P=0.0343, log-rank test) and furthermore in Cox multivariate analysis (P=0.009) along with age (P=0.002). The results suggest that the expression of Trx has a correlation to patient outcome and that there may be some association between AOEs, like MnSOD and Trx, and clinicopathological features of oligodendrogliomas.
38.	Järvelä, Sally, et al. (författare) Decreased expression of antioxidant enzymes is associated with aggressive features in ependymomas 2008 Ingår i: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 90:3, s. 283-291 Tidskriftsartikel (refereegranskat)abstract The purpose of this study was to investigate the relationship between antioxidant enzyme expression and clinicopathological features in 67 ependymal tumors. We included into the analysis antioxidant enzymes (AOEs) and related proteins, such as, manganese superoxide dismutase (MnSOD), gammaglutamylcysteine synthetase catalytic and regulatory subunits (GLCL-C and GLCL-R), thioredoxin (Trx) and thioredoxin reductase (TrxR). Their expression was studied in 46 primary (10 grade I, 30 grade II and 6 grade III) and 21 recurrent (3 grade I, 12 grade II and 6 grade III) tumors. Immunoreactivity for MnSOD was found in 87%, GLCL-C in 74%, GLCL-R in 89%, Trx in 72%, TrxR in 54%, of primary tumors. Lower GLCL-C and GLCL-R expression was associated with higher tumor grade (P = 0.047 and 0.049, respectively). MnSOD, GLCL-C and TrxR expressions were significantly higher in tumors located in the spinal cord compared to those in the brain (P = 0.044, 0.046 and 0.004, respectively). In the primary tumors Trx-positivity was found to correlate significantly with patient survival. In univariate survival analysis patients whose tumors did not express Trx had shorter survival (P = 0.045) and there was even more significant association (P = 0.011) when only adults were included in the analysis (in the total material median follow-up time of Trx-positive tumors was 9.7 years and of Trx-negative 5.4 years). The results indicate that AOEs have several biological functions in ependymal tumors. Trx had important prognostic value: all adults with Trx-positive tumors were alive at follow-up (median 7.8 years).
39.	Kiuru, Anne, et al. (författare) XRCC1 and XRCC3 variants and risk of glioma and meningioma 2008 Ingår i: Journal of Neuro-Oncology. - : Springer. - 0167-594X .- 1573-7373. ; 88, s. 135-142 Tidskriftsartikel (refereegranskat)abstract Several single nucleotide polymorphisms (SNPs) affecting DNA repair capacity and modifying cancer susceptibility have been described. We evaluated the association of SNPs Arg194Trp, Arg280His, and Arg399Gln in the X-ray cross-complementing group 1 (XRCC1) and Thr241Met in the X-ray cross-complementing group 3 (XRCC3) DNA repair genes with the risk of brain tumors. The Caucasian study population consisted of 701 glioma (including 320 glioblastoma) cases, 524 meningioma cases, and 1,560 controls in a prospective population-based case-control study conducted in Denmark, Finland, Sweden, and the UK. The studied SNPs were not significantly associated with the risk of brain tumors. The highest odds ratios (ORs) for the associations were observed between the homozygous variant genotype XRCC1 Gln399Gln and the risk of glioma (OR = 1.32; 95% confidence interval, CI, 0.97-1.81), glioblastoma (OR = 1.48; 95% CI, 0.98-2.24), and meningioma (OR = 1.34; 95% CI, 0.96-1.86). However, in pair-wise comparisons a few SNP combinations were associated with the risk of brain tumors: Among others, carriers of both homozygous variant genotypes, i.e., XRCC1 Gln399Gln and XRCC3 Met241Met, were associated with a three-fold increased risk of glioma (OR = 3.18; 95% CI, 1.26-8.04) and meningioma (OR = 2.99; 95% CI, 1.16-7.72). In conclusion, no significant association with brain tumors was found for any of the polymorphisms, when examined one by one. Our results indicated possible associations between combinations of XRCC1 and XRCC3 SNPs and the risk of brain tumors.
40.	Kristiansen, Ingela, et al. (författare) Clinical characteristics, long-term complications and health related quality of life (HRQoL) in children and young adults treated for low-grade astrocytoma in the posterior fossa in childhood 2019 Ingår i: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 142:1, s. 203-210 Tidskriftsartikel (refereegranskat)abstract Pilocytic astrocytoma is the most common brain tumour in childhood but knowledge concerning its long-term outcome is sparse. The aim of the study was to investigate if children treated for low-grade pilocytic astrocytoma in the posterior fossa had complications affecting physical and psychological health, cognitive functions, learning difficulties and HRQoL.A descriptive single-centre study, where 22 children and young adults out of 27 eligible patients (81%) treated for pilocytic astrocytoma, with a mean follow-up time of 12.4 years (5-19 years) participated (14 adults, two by telephone interviews and eight children). The study included a review of medical records, an interview, neurological investigation, screening tools for psychiatric symptoms (Beck Depression and Anxiety Inventories and Beck Youth Inventory Scales) and HRQoL measures (RAND-36).Motor complications were most common, reported in 12 patients and mainly affecting fine-motor skills. Seven patients reported cognitive difficulties affecting performance in school. Educational support was given in the period immediately after treatment but not after primary school. None had elevated levels of psychiatric symptoms and the level of HRQoL as well as their psychosocial and educational situation was in correspondence with Swedish norms. The HRQoL score for vitality (VT) almost reached statistical significance.The long-term functional outcome for children treated for low-grade astrocytoma is favourable. However, some patients report neurological complications and learning difficulties, which are unmet in school. Therefore, there is a need to identify those who need more thorough medical and cognitive follow-up programmes including interventions in school.
41.	Källén, Kristina, et al. (författare) 201Thallium SPECT and 1H-MRS compared with MRI in chemotherapy monitoring of high-grade malignant astrocytomas 2000 Ingår i: Journal of Neuro-Oncology. - 1573-7373. ; 46:2, s. 173-185 Tidskriftsartikel (refereegranskat)abstract PURPOSE: To compare chemotherapy treatment monitoring in astrocytoma by 201thallium single photon emission computed tomography (SPECT) and photon magnetic resonance spectroscopy (1H-MRS) with magnetic resonance imaging (MRI), and to evaluate the influence of morphological tumor changes on cerebral 201thallium uptake and metabolic changes in 1H-MRS. MATERIALS AND METHODS: Six patients with highly malignant astrocytomas were followed with quantitative 201thallium SPECT, MRI, and 1H-MRS during chemotherapy. Maximum follow-up included six examinations per patient by either method during 18 months. Criteria were set for: (1) regression (> or = 25% tumor reduction), (2) status quo (< 25% reduction and < 25% increase), and (3) progression of disease (> or = 25% tumor increase). Results were compared with the clinical state of disease. Changes of tumor volume, contrast enhancement, necrosis, hemorrhage and edema on MRI were compared to changes in 201thallium uptake volumes and 1H-MRS metabolite ratios. RESULTS: Six patients were followed with a total of twenty-four examinations with 201thallium SPECT, MRI and 1H-MRS, respectively, between February 1997 and October 1998. Five patients developed clinical progression of disease, 4 out of 5 cases showed SPECT progression, 4 out of 5 cases MRI progression, and 1 out of 2 interpretable cases 1H-MRS progression at final assessment before clinical deterioration. During the phase of clinically stable disease; (A) the criterion for regression or status quo was met in 10 out of 13 assessments with SPECT, 11 out of 13 with MRI, and 8 out of 9 interpretable 1H-MRS; (B) the criterion for progression was met in 3 out of 13 with SPECT, 2 out of 13 with MRI, and 1 out of 9 interpretable 1H-MRS. The accuracy of SPECT, MRI, and 1H-MRS in identifying changes of tumor burden concordant with patients' clinical course was 78%, 83%, and 82%, respectively. SPECT regression was associated with MRI decrease of tumor size, contrast enhancement, edema and hemorrhage. SPECT progression was associated with MRI increase of the same parameters and the increase of necrosis. 1H-MRS regression was associated with decrease of edema. 1H-MRS progression was associated with increase of tumor size, hemorrhage, and increase or decrease of contrast enhancement. CONCLUSIONS: Both 201thallium SPECT and 1H-MRS evaluation showed sensitivity for detection of astrocytoma progression. We did not find a higher accuracy of SPECT or MRS than of MRI in astrocytoma chemotherapy monitoring. Treatment induced MRI changes were associated with 201thallium uptake variations. 1H-MRS was difficult to apply for astrocytoma treatment monitoring. Improvements regarding size of measurement area such as multivoxel MRS and fat suppression pulses appeared desirable, and also the use of functional techniques with superior resolution such as dual isotope SPECT. However, our results suggest that 201thallium SPECT and 1H-MRS can provide additional information to MRI for chemotherapy efficacy evaluation in selected cases.
42.	Lobon-Iglesias, M. J., et al. (författare) Diffuse intrinsic pontine gliomas (DIPG) at recurrence : is there a window to test new therapies in some patients? 2018 Ingår i: Journal of Neuro-Oncology. - : SPRINGER. - 0167-594X .- 1573-7373. ; 137:1, s. 111-118 Tidskriftsartikel (refereegranskat)abstract Children with diffuse intrinsic pontine glioma (DIPG) need new and more efficient treatments. They can be developed at relapse or at diagnosis, but therefore they must be combined with radiotherapy. Survival of children after recurrence and its predictors were studied to inform the possibility to design early phase clinical trials for DIPG at this stage. Among 142 DIPG patients treated between 1998 and 2014, 114 had biopsy-proven DIPG with histone H3 status available for 83. We defined as long survivors' patients who survived more than 3 months after relapse which corresponds to the minimal life expectancy requested for phase I/II trials. Factors influencing post-relapse survival were accordingly compared between short and long-term survivors after relapse. Fifty-seven percent of patients were considered long survivors and 70% of them had a Lansky Play Scale (LPS) above 50% at relapse. Patients who became steroids-independent after initial treatment for at least 2 months had better survival after relapse (3.7 versus 2.6 months, p = 0.001). LPS above 50% at relapse was correlated with better survival after relapse (3.8 versus 1.8 months, p < 0.001). Patients with H3.1 mutation survived longer after relapse (4.9 versus 2.7 months, p = 0.007). Patients who received a second radiotherapy at the time of relapse had an improved survival (7.5 versus 4 months, p = 0.001). In the two-way ANOVA analysis, steroid-independence and LPS predicted survival best and the type of histone H3 (H3.1 or H3.3) mutated did not improve prediction. Survival of many DIPG patients after relapse over 3 months would make possible to propose specific trials for this condition. Steroid-independence, H3 mutation status and LPS should be considered to predict eligibility.
43.	Malmer, Beatrice, et al. (författare) Genetic variation in p53 and ATM haplotypes and risk of glioma and meningioma. 2007 Ingår i: J Neurooncol. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 82:3, s. 229-237 Tidskriftsartikel (refereegranskat)
44.	Mirian, C, et al. (författare) The importance of considering competing risks in recurrence analysis of intracranial meningioma 2024 Ingår i: Journal of neuro-oncology. - 1573-7373. ; 166:3, s. 503-511 Tidskriftsartikel (refereegranskat)
45.	Nord, Helena, et al. (författare) Novel amplifications in pediatric medulloblastoma identified by genome-wide copy number profiling 2012 Ingår i: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 107:1, s. 37-49 Tidskriftsartikel (refereegranskat)abstract Medulloblastoma (MB) is a WHO grade IV, invasive embryonal CNS tumor that mainly affects children. The aggressiveness and response to therapy can vary considerably between cases, and despite treatment, ~30% of patients die within 2 years from diagnosis. Furthermore, the majority of survivors suffer long-term side-effects due to severe management modalities. Several distinct morphological features have been associated with differences in biological behavior, but improved molecular-based criteria that better reflect the underlying tumor biology are in great demand. In this study, we profiled a series of 25 MB with a 32K BAC array covering 99% of the current assembly of the human genome for the identification of genetic copy number alterations possibly important in MB. Previously known aberrations as well as several novel focally amplified loci could be identified. As expected, the most frequently observed alteration was the combination of 17p loss and 17q gain, which was detected in both high- and standard-risk patients. We also defined minimal overlapping regions of aberrations, including 16 regions of gain and 18 regions of loss in various chromosomes. A few noteworthy narrow amplified loci were identified on autosomes 1 (38.89-41.97 and 84.89-90.76 Mb), 3 (27.64-28.20 and 35.80-43.50 Mb), and 8 (119.66-139.79 Mb), aberrations that were verified with an alternative platform (Illumina 610Q chips). Gene expression levels were also established for these samples using Affymetrix U133Plus2.0 arrays. Several interesting genes encompassed within the amplified regions and presenting with transcript upregulation were identified. These data contribute to the characterization of this malignant childhood brain tumor and confirm its genetic heterogeneity.
46.	Näslund, Olivia, et al. (författare) Incidence, management, and outcome of incidental meningioma: what has happened in 10 years? 2023 Ingår i: Journal of Neuro-Oncology. - 0167-594X .- 1573-7373. Tidskriftsartikel (refereegranskat)abstract Purpose: The aim of this study was to study the use of brain scanning, and the subsequent findings of presumed incidental meningioma in two time periods, and to study differences in follow-up, treatment, and outcome. Methods: Records of all performed CT and MRI of the brain during two time periods were retrospectively reviewed in search of patients with presumed incidental meningioma. These patients were further analyzed using medical health records, with the purpose to study clinical handling and outcome during a 3 year follow up. Results: An identical number of unique patients underwent brain imaging during the two time periods (n = 22 259 vs. 22 013). In 2018–2019, 25% more incidental meningiomas were diagnosed compared to 2008–2009 (n = 161 vs. 129, p = 0.052). MRI was used more often in 2018–2019 (26.1 vs. 12.4%, p = 0.004), and the use of contrast enhancement, irrespective of modality, also increased (26.8 vs. 12.2%, p < 0.001). In the most recent cohort, patients were older (median 79 years vs. 73 years, p = 0.03). Indications showed a significant increase of cancer without known metastases among scanned patients. 29.5 and 35.4% of patients in the cohorts were deceased 3 years after diagnosis for causes unrelated to their meningioma. Conclusions: Despite the same number of unique patients undergoing brain scans in the time periods, there was a trend towards more patients diagnosed with an incidental asymptomatic meningioma in the more recent years. This difference may be attributed to more contrast enhanced scans and more scans among the elderly but needs to be further studied. Patients in the cohort from 2018 to 2019 more often had non-metastatic cancer, with their cause of scan screening for metastases. There was no significant difference in management decision at diagnosis, but within 3 years of follow up significantly more patients in the latter cohort had been re-scanned. Almost a third of all patients were deceased within 3 years after diagnosis, due to causes other than their meningioma.
47.	Olsson, Ann, et al. (författare) Survival of glioma patients in relation to mobile phone use in Denmark, Finland and Sweden 2019 Ingår i: Journal of Neuro-Oncology. - : Springer. - 0167-594X .- 1573-7373. ; 141:1, s. 139-149 Tidskriftsartikel (refereegranskat)abstract Purpose: Gliomas are the most common cancer of the brain, with a poor prognosis in particular for glioblastoma. In 2014, a study suggested reduced survival in relation to latency of mobile phone use among glioblastoma patients. A joint epidemiological/experimental project to study effects of RF-EMF on tumor development and progression was established. The current analysis relates to the epidemiological part and addresses whether pre-diagnostic mobile phone use was associated with survival among glioma patients.Methods: Glioma cases (n = 806) previously enrolled in a collaborative population-based case–control study in Denmark, Finland and Sweden were followed up for survival. Vital status, date of death, date of emigration, or date last known to be alive was obtained based on registry linkages with a unique personal ID in each country. Cox regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) stratified by country. Covariates investigated were sex, age, education, histology, treatment, anatomic location and marital status.Results: No indication of reduced survival among glioblastoma patients was observed for various measures of mobile phone use (ever regular use, time since start of regular use, cumulative call time overall or in the last 12 months) relative to no or non-regular use. All significant associations suggested better survival for mobile phone users. Results were similar for high-grade and low-grade gliomas.Conclusions: We found no evidence of reduced survival among glioma patients in relation to previous mobile phone use.
48.	Persson, Annette, et al. (författare) Cell type- and region- dependent coxsackie adenovirus receptor expression in the central nervous system. 2006 Ingår i: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 1573-7373 .- 0167-594X. ; 78:1, s. 1-6 Tidskriftsartikel (refereegranskat)abstract Model systems have shown that adenoviral vector mediated transient gene expression can potentially be applied for the treatment of brain tumours, neurodegenerative diseases and brain injuries. Most studies utilized adenovirus serotype 5 (Ad5) based vectors, which as adhesion molecules require the coxsackie adenovirus receptor (CAR) as a critical determinant for cellular infection. In this report, we have systematically characterized CAR expression in the adult human central nervous system (CNS) by using immunohistochemistry. A total of 85 specimens from various CNS regions were investigated for CAR expression in a cell type-dependent context. The most marked staining positivity was found in the choroid plexus and the pituitary gland. The neocortex had scattered positive neurons, while the white matter was mainly negative. We need to consider the possible adverse effects and the possible damage caused by adenoviral gene therapy if the virus-vector also binds to normal brain cells.
49.	Persson, Oscar, et al. (författare) Distribution, cellular localization, and therapeutic potential of the tumor-associated antigen Ku70/80 in glioblastoma multiforme. 2010 Ingår i: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 1573-7373 .- 0167-594X. ; 97, s. 207-215 Tidskriftsartikel (refereegranskat)abstract Antibodies specifically targeting tumor-associated antigens have proved to be important tools in the treatment of human cancer. A desirable target antigen should be unique to tumor cells, abundantly expressed, and readily available for antibody binding. The Ku70/80 DNA-repair protein is expressed in the nucleus of most cells; it is, however, also present on the cell surface of tumor cell lines, and antibodies binding Ku70/80 at the cell surface were recently shown to internalize into tumor cells. To evaluate the potential of Ku70/80-antigen as a therapeutic target for immunotoxins in glioblastoma multiforme, we investigated binding and localization of Ku70/80-specific antibodies in tissue samples from glioblastomas and normal human brains, and in glioma cell cultures. Furthermore, the internalization and drug-delivery capacity were evaluated by use of immunotoxicity studies. We demonstrate that Ku70/80 is localized on the cell plasma membrane of glioma cell lines, and is specifically present in human glioblastoma tissue. Antibodies bound to the Ku70/80 antigen on the cell surface of glioma cells were found to internalize via endocytosis, and shown to efficiently deliver toxins into glioblastoma cells. The data further imply that different antibodies directed against Ku70/80 possess different abilities to target the antigen, in relation to its presentation on the cell surface or intracellular localization. We conclude that Ku70/80 antigen is uniquely presented on the plasma membrane in glioblastomas, and that antibodies specific against the antigen have the capacity to selectively bind, internalize, and deliver toxins into tumor cells. These results imply that Ku70/80 is a potential target for immunotherapy of glioblastoma multiforme.
50.	Persson, Oscar, et al. (författare) Microarray analysis of gliomas reveals chromosomal position-associated gene expression patterns and identifies potential immunotherapy targets. 2007 Ingår i: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 1573-7373 .- 0167-594X. ; 85:J1, s. 11-24 Tidskriftsartikel (refereegranskat)abstract Gliomas are among the most aggressive malignant tumors and the most refractory to therapy, in part due to the propensity for malignant cells to disseminate diffusely throughout the brain. Here, we have used 27 K cDNA microarrays to investigate global gene expression changes between normal brain and high-grade glioma (glioblastoma multiforme) to try and better understand gliomagenesis and to identify new therapeutic targets. We have also included smaller groups of grade II and grade III tumors of mixed astrocytic and oligodendroglial origin as comparison. We found that the expression of hundreds of genes was significantly correlated to each group, and employed a naive Bayesian classifier with leave-one-out cross-validation to accurately classify the samples. We developed a novel algorithm to analyze the gene expression data from the perspective of chromosomal position, and identified distinct regions of the genome that displayed coordinated expression patterns that correlated significantly to tumor grade. The regions identified corresponded to previously known genetic copy number changes in glioma (e.g. 10q23, 10q25, 7q, 7p) as well as regions not previously associated significantly with glioma (e.g. 1p13, 6p22). Furthermore, to enrich for more suitable targets for therapy, we took a bioinformatics approach and annotated our signatures with two published datasets that identified membrane/secreted genes from cytosolic genes. The resulting focused list of 31 genes included interesting novel potential targets as well as several proteins already being investigated for immunotherapy (e.g. CD44 and tenascin-C). Software for the chromosome analysis was developed and is freely available at http://base.thep.lu.se.

Skapa referenser, mejla, bekava och länka

Länka till träfflistan

Resultat 1-50 av 70

Avgränsa träffmängd

Typ av publikation: tidskriftsartikel (69); forskningsöversikt (1)

Typ av innehåll: refereegranskat (69); övrigt vetenskapligt/konstnärligt (1)

Författare/redaktör: Jakola, Asgeir Store (14); Henriksson, Roger (12); Smits, Anja (8); Andersson, Ulrika (6); Bergenheim, A Tommy (6); Solheim, Ole (6); visa fler...; Brännström, Thomas (5); Wibom, Carl (5); Johansen, Christoffe ... (4); Feychting, Maria (4); Melin, Beatrice S. (4); Carstam, Louise (4); Rydenhag, Bertil, 19 ... (4); Bergström, Per (4); Salford, Leif (3); Englund, Elisabet (3); Alexandru, O (3); Dricu, A (3); Melin, Beatrice (3); Auvinen, Anssi (3); Widegren, Bengt (3); Gulati, Sasha (3); Henriksson, R (2); Kalimo, Hannu (2); Schüz, Joachim (2); Alafuzoff, Irina (2); Lannering, Birgitta, ... (2); Iverfeldt, Kerstin (2); Lewensohn, R. (2); Corell, Alba (2); Siesjö, Peter (2); Bartek, J (2); Dragutescu, L (2); Tataranu, L (2); Ciubotaru, V (2); Carapancea, M (2); Backlund, ML (2); Hougaard, David M. (2); Malmer, Beatrice (2); Sjöström, Sara (2); Kiuru, Anne (2); Lönn, Stefan (2); Hjalmars, Ulf (2); Dahlin, Anna M., 197 ... (2); Blomquist, Erik (2); Zetterling, Maria (2); Visse, Edward (2); Thurin, Erik (2); Sjåvik, Kristin (2); Berntsson, Shala Gha ... (2); visa färre...

Lärosäte: Umeå universitet (21); Uppsala universitet (21); Karolinska Institutet (21); Göteborgs universitet (20); Lunds universitet (11); Linköpings universitet (4); visa fler...; Stockholms universitet (2); Jönköping University (1); visa färre...

Språk: Engelska (70)

Forskningsämne (UKÄ/SCB): Medicin och hälsovetenskap (50); Naturvetenskap (1); Samhällsvetenskap (1)

År

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

LIBRIS.kb.se

Stäng

Kopiera och spara länken för att återkomma till aktuell vy