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  1. Article ; Online: Refining the Intraoperative Identification of Suspected High-Grade Glioma Using a Surgical Fluorescence Biomarker

    Colin Watts / Alimu Dayimu / Tomasz Matys / Keyoumars Ashkan / Stephen Price / Michael D. Jenkinson / Gail Doughton / Claire Mather / Gemma Young / Wendi Qian / Kathreena M. Kurian

    Journal of Personalized Medicine, Vol 13, Iss 514, p

    GALA BIDD Study Report

    2023  Volume 514

    Abstract: Background. Improving intraoperative accuracy with a validated surgical biomarker is important because identifying high-grade areas within a glioma will aid neurosurgical decision-making and sampling. Methods. We designed a multicentre, prospective ... ...

    Abstract Background. Improving intraoperative accuracy with a validated surgical biomarker is important because identifying high-grade areas within a glioma will aid neurosurgical decision-making and sampling. Methods. We designed a multicentre, prospective surgical cohort study (GALA-BIDD) to validate the presence of visible fluorescence as a pragmatic intraoperative surgical biomarker of suspected high-grade disease within a tumour mass in patients undergoing 5-aminolevulinic acid (5-ALA) fluorescence-guided cytoreductive surgery. Results. A total of 106 patients with a suspected high-grade glioma or malignant transformation of a low-grade glioma were enrolled. Among the 99 patients who received 5-ALA, 89 patients were eligible to assess the correlation of fluorescence with diagnosis as per protocol. Of these 89, 81 patients had visible fluorescence at surgery, and 8 patients had no fluorescence. A total of 80 out of 81 fluorescent patients were diagnosed as high-grade gliomas on postoperative central review with 1 low-grade glioma case. Among the eight patients given 5-ALA who did not show any visible fluorescence, none were high-grade gliomas, and all were low-grade gliomas. Of the seven patients suspected radiologically of malignant transformation of low-grade gliomas and with visible fluorescence at surgery, six were diagnosed with high-grade gliomas, and one had no tissue collected. Conclusion. In patients where there is clinical suspicion, visible 5-ALA fluorescence has clinical utility as an intraoperative surgical biomarker of high-grade gliomas and can aid surgical decision-making and sampling. Further studies assessing the use of 5-ALA to assess malignant transformation in all diffuse gliomas may be valuable.
    Keywords 5ALA ; intraoperative biomarker ; fluorescence ; Medicine ; R
    Subject code 610 ; 616
    Language English
    Publishing date 2023-03-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: GATA-4, a potential novel therapeutic target for high-grade meningioma, regulates miR-497, a potential novel circulating biomarker for high-grade meningioma

    Caterina Negroni / David A. Hilton / Emanuela Ercolano / Claire L. Adams / Kathreena M. Kurian / Daniele Baiz / C.Oliver Hanemann

    EBioMedicine, Vol 59, Iss , Pp 102941- (2020)

    2020  

    Abstract: Background: Meningiomas are the most common primary intracranial tumours. They are classified as grade I, II, and III based on their histopathological features. While most meningiomas can be managed by surgery alone, adjuvant treatment may be required in ...

    Abstract Background: Meningiomas are the most common primary intracranial tumours. They are classified as grade I, II, and III based on their histopathological features. While most meningiomas can be managed by surgery alone, adjuvant treatment may be required in case of recurrent, or high-grade tumours. To date, chemotherapy has proven ineffective in meningioma patients, reinforcing the need for novel therapeutic targets and molecular biomarkers. Methods: Using meningioma tissues and in vitro models, we investigated microRNA levels in meningioma samples of different grades, as well as their regulation. Based on this, we also investigated candidate miRNAs expression in serum, and their potential as biomarkers. Findings: We found that miR-497~195 cluster expression in meningioma decreases with increasing malignancy grade, and that Cyclin D1 overexpression correlated with downregulation of the miR-497~195 cluster. GATA binding protein 4, a transcription factor upregulated in malignant meningioma, caused increased cell viability by controlling the expression of the miR-497~195 cluster, resulting in increased Cyclin D1 expression. Accordingly, GATA-4 inhibition via the small-molecule inhibitor NSC140905 restored miR-497~195 cluster expression, resulting in decreased viability, and Cyclin D1 downregulation. Analysis of the miR-497~195 cluster expression in serum exosomes derived from high-grade meningioma patients, revealed lower levels of miR-497 compared to those of benign origin. Interpretation: Our data suggest that GATA-4 could be a novel potential therapeutic target, and miR-497 could serve as a potential non-invasive biomarker for high-grade meningioma.
    Keywords MeningiomaGATA-4ExosomesmiRNAmiR-497Liquid biopsies ; Medicine ; R ; Medicine (General) ; R5-920
    Subject code 570
    Language English
    Publishing date 2020-09-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: The usefulness of symptoms alone or combined for general practitioners in considering the diagnosis of a brain tumour

    Yoav Ben-Shlomo / Paul M Brennan / Robin Grant / Mio Ozawa / Karolis Zienius / Kathreena M Kurian

    BMJ Open, Vol 9, Iss

    a case-control study using the clinical practice research database (CPRD) (2000-2014)

    2019  Volume 8

    Abstract: ObjectivesTo evaluate the utility of different symptoms, alone or combined, presented to primary care for an adult brain tumour diagnosis.Design and settingMatched case-control study, using the data from Clinical Practice Research Datalink (2000–2014) ... ...

    Abstract ObjectivesTo evaluate the utility of different symptoms, alone or combined, presented to primary care for an adult brain tumour diagnosis.Design and settingMatched case-control study, using the data from Clinical Practice Research Datalink (2000–2014) from primary care consultations in the UK.MethodAll presentations within 6 months of the index diagnosis date (cases) or equivalent (controls) were coded into 32 symptom groups. Sensitivity, specificity, positive predictive values (PPVs) and positive likelihood ratios were calculated for symptoms and combinations of symptoms with headache and cognitive features. Diagnostic odds ratios were calculated using conditional logistic regression, adjusted for age group, sex and Charlson comorbidity. Stratified analyses were performed for age group, sex and whether the tumour was of primary or secondary origin.ResultsWe included 8,184 cases and 28,110 controls. Seizure had the highest PPV of 1.6% (95% CI 1.4% to 1.7%) followed by weakness 1.5% (1.3 to 1.7) and confusion 1.4% (1.3 to 1.5). Combining headache with other symptoms increased the PPV. For example, headache plus combined cognitive symptoms PPV 7.2% (6.0 to 8.6); plus weakness 4.4% (3.2 to 6.2), compared with headache alone PPV 0.1%. The diagnostic ORs were generally larger for patients <70 years; this was most marked for confusion, seizure and visual symptoms.ConclusionWe found seizure, weakness and confusion had relatively higher predictive values than many other symptoms. Headache on its own was a weak predictor but this was enhanced when combined with other symptoms especially in younger patients. Clinicians need to actively search for other neurological symptoms such as cognitive problems.
    Keywords Medicine ; R
    Subject code 150
    Language English
    Publishing date 2019-08-01T00:00:00Z
    Publisher BMJ Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Transcriptome-wide Mendelian randomization study prioritising novel tissue-dependent genes for glioma susceptibility

    Jamie W. Robinson / Richard M. Martin / Spiridon Tsavachidis / Amy E. Howell / Caroline L. Relton / Georgina N. Armstrong / Melissa Bondy / Jie Zheng / Kathreena M. Kurian

    Scientific Reports, Vol 11, Iss 1, Pp 1-

    2021  Volume 10

    Abstract: Abstract Genome-wide association studies (GWAS) have discovered 27 loci associated with glioma risk. Whether these loci are causally implicated in glioma risk, and how risk differs across tissues, has yet to be systematically explored. We integrated ... ...

    Abstract Abstract Genome-wide association studies (GWAS) have discovered 27 loci associated with glioma risk. Whether these loci are causally implicated in glioma risk, and how risk differs across tissues, has yet to be systematically explored. We integrated multi-tissue expression quantitative trait loci (eQTLs) and glioma GWAS data using a combined Mendelian randomisation (MR) and colocalisation approach. We investigated how genetically predicted gene expression affects risk across tissue type (brain, estimated effective n = 1194 and whole blood, n = 31,684) and glioma subtype (all glioma (7400 cases, 8257 controls) glioblastoma (GBM, 3112 cases) and non-GBM gliomas (2411 cases)). We also leveraged tissue-specific eQTLs collected from 13 brain tissues (n = 114 to 209). The MR and colocalisation results suggested that genetically predicted increased gene expression of 12 genes were associated with glioma, GBM and/or non-GBM risk, three of which are novel glioma susceptibility genes (RETREG2/FAM134A, FAM178B and MVB12B/FAM125B). The effect of gene expression appears to be relatively consistent across glioma subtype diagnoses. Examining how risk differed across 13 brain tissues highlighted five candidate tissues (cerebellum, cortex, and the putamen, nucleus accumbens and caudate basal ganglia) and four previously implicated genes (JAK1, STMN3, PICK1 and EGFR). These analyses identified robust causal evidence for 12 genes and glioma risk, three of which are novel. The correlation of MR estimates in brain and blood are consistently low which suggested that tissue specificity needs to be carefully considered for glioma. Our results have implicated genes yet to be associated with glioma susceptibility and provided insight into putatively causal pathways for glioma risk.
    Keywords Medicine ; R ; Science ; Q
    Subject code 616
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Fibulin-2

    Agbolahan A. Sofela / David A. Hilton / Sylwia Ammoun / Daniele Baiz / Claire L. Adams / Emanuela Ercolano / Michael D. Jenkinson / Kathreena M. Kurian / Mario Teo / Peter C. Whitfield / Felix Sahm / C. Oliver Hanemann

    International Journal of Molecular Sciences, Vol 22, Iss 2, p

    A Novel Biomarker for Differentiating Grade II from Grade I Meningiomas

    2021  Volume 560

    Abstract: There is an unmet need for the identification of biomarkers to aid in the diagnosis, clinical management, prognosis and follow-up of meningiomas. There is currently no consensus on the optimum management of WHO grade II meningiomas. In this study, we ... ...

    Abstract There is an unmet need for the identification of biomarkers to aid in the diagnosis, clinical management, prognosis and follow-up of meningiomas. There is currently no consensus on the optimum management of WHO grade II meningiomas. In this study, we identified the calcium binding extracellular matrix glycoprotein, Fibulin-2, via mass-spectrometry-based proteomics, assessed its expression in grade I and II meningiomas and explored its potential as a grade II biomarker. A total of 87 grade I and 91 grade II different meningioma cells, tissue and plasma samples were used for the various experimental techniques employed to assess Fibulin-2 expression. The tumours were reviewed and classified according to the 2016 edition of the Classification of the Tumours of the central nervous system (CNS). Mass spectrometry proteomic analysis identified Fibulin-2 as a differentially expressed protein between grade I and II meningioma cell cultures. Fibulin-2 levels were further evaluated in meningioma cells using Western blotting and Real-time Quantitative Polymerase Chain Reaction (RT-qPCR); in meningioma tissues via immunohistochemistry and RT-qPCR; and in plasma via Enzyme-Linked Immunosorbent Assay (ELISA). Proteomic analyses ( p < 0.05), Western blotting ( p < 0.05) and RT-qPCR ( p < 0.01) confirmed significantly higher Fibulin-2 (FBLN2) expression levels in grade II meningiomas compared to grade I. Fibulin-2 blood plasma levels were also significantly higher in grade II meningioma patients compared to grade I patients. This study suggests that elevated Fibulin-2 might be a novel grade II meningioma biomarker, when differentiating them from the grade I tumours. The trend of Fibulin-2 expression observed in plasma may serve as a useful non-invasive biomarker.
    Keywords meningioma ; atypical ; benign ; biomarker ; plasma ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 610
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Retrospective Case-Control Study of Apolipoprotein J/Clusterin Protein Expression in Early Liveborn Neonatal Deaths with and without Pontosubicular Necrosis

    Kathreena M. Kurian / Declan McGuone

    Pathology Research International, Vol

    2012  Volume 2012

    Keywords Pathology ; RB1-214 ; Medicine ; R ; DOAJ:Pathology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
    Language English
    Publishing date 2012-01-01T00:00:00Z
    Publisher Hindawi Publishing Corporation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: A Rapid Robust Method for Subgrouping Non-NF2 Meningiomas According to Genotype and Detection of Lower Levels of M2 Macrophages in AKT1 E17K Mutated Tumours

    Claire L. Adams / Emanuela Ercolano / Sara Ferluga / Agbolahan Sofela / Foram Dave / Caterina Negroni / Kathreena M. Kurian / David A. Hilton / C. Oliver Hanemann

    International Journal of Molecular Sciences, Vol 21, Iss 4, p

    2020  Volume 1273

    Abstract: The majority of meningiomas are grade I, but some grade I tumours are clinically more aggressive. Recent advances in the genetic study of meningiomas has allowed investigation into the influence of genetics on the tumour microenvironment, which is ... ...

    Abstract The majority of meningiomas are grade I, but some grade I tumours are clinically more aggressive. Recent advances in the genetic study of meningiomas has allowed investigation into the influence of genetics on the tumour microenvironment, which is important for tumorigenesis. We have established that the endpoint genotyping method Kompetitive Allele Specific PCR (KASP™) is a fast, reliable method for the screening of meningioma samples into different non-NF2 mutational groups using a standard real-time PCR instrument. This genotyping method and four-colour flow cytometry has enabled us to assess the variability in the largest immune cell infiltrate population, M2 macrophages (CD45 + HLA-DR + CD14 + CD163 + ) in 42 meningioma samples, and to suggest that underlying genetics is relevant. Further immunohistochemistry analysis comparing AKT1 E17K mutants to WHO grade I NF2-negative samples showed significantly lower levels of CD163-positive activated M2 macrophages in meningiomas with mutated AKT1 E17K, signifying a more immunosuppressive tumour microenvironment in NF2 meningiomas. Our data suggested that underlying tumour genetics play a part in the development of the immune composition of the tumour microenvironment. Stratifying meningiomas by mutational status and correlating this with their cellular composition will aid in the development of new immunotherapies for patients.
    Keywords meningioma ; m2 macrophage ; genotype ; akt1 e17k ; nf2 ; non-nf2 ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 333
    Language English
    Publishing date 2020-02-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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