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  • 1
    Online Resource
    Online Resource
    Recurrence of chest wall hydatid cyst disease involving the thoracic spine in an Australian patient
    Elsevier BV ; 2016
    In:  Journal of Clinical Neuroscience Vol. 30 ( 2016-08), p. 132-136
    Details
    In: Journal of Clinical Neuroscience, Elsevier BV, Vol. 30 ( 2016-08), p. 132-136
    Type of Medium: Online Resource
    ISSN: 0967-5868
    URL: Article
    DOI: 10.1016/j.jocn.2016.01.030
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2016
    detail.hit.zdb_id: 2009190-4
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  • 2
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    Targeting the Sphingolipid System as a Therapeutic Direction for Glioblastoma
    MDPI AG ; 2020
    In:  Cancers Vol. 12, No. 1 ( 2020-01-01), p. 111-
    Details
    In: Cancers, MDPI AG, Vol. 12, No. 1 ( 2020-01-01), p. 111-
    Abstract: Glioblastoma (GBM) is the most commonly diagnosed malignant brain tumor in adults. The prognosis for patients with GBM remains poor and largely unchanged over the last 30 years, due to the limitations of existing therapies. Thus, new therapeutic approaches are desperately required. Sphingolipids are highly enriched in the brain, forming the structural components of cell membranes, and are major lipid constituents of the myelin sheaths of nerve axons, as well as playing critical roles in cell signaling. Indeed, a number of sphingolipids elicit a variety of cellular responses involved in the development and progression of GBM. Here, we discuss the role of sphingolipids in the pathobiology of GBM, and how targeting sphingolipid metabolism has emerged as a promising approach for the treatment of GBM.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers12010111
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2527080-1
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  • 3
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    Necrobiotic xanthogranuloma with cutaneous and cerebral manifestations : Case report and review of the literature
    Journal of Neurosurgery Publishing Group (JNSPG) ; 2004
    In:  Journal of Neurosurgery Vol. 100, No. 6 ( 2004-06), p. 1111-1114
    Details
    In: Journal of Neurosurgery, Journal of Neurosurgery Publishing Group (JNSPG), Vol. 100, No. 6 ( 2004-06), p. 1111-1114
    Abstract: ✓ Necrobiotic xanthogranuloma (NXG) is a rare inflammatory histiocytic disease of the skin. Xanthogranuloma of the central nervous system is rare and few cases have been reported. To the authors' knowledge, there has been no previously reported case of NXG in which an intracranial lesion was found. This 52-year-old man, in whom NXG with all its cutaneous manifestations had been diagnosed, presented with three episodes of generalized tonic—clonic seizures. A contrast-enhanced computerized tomography scan of his brain revealed a bifrontal, dura-based mass lesion. The lesion was excised and reported to be an NXG that was similar, but not identical to the skin lesions. The patient was placed on a regimen of antiepileptic drug and chlorambucil after surgery.
    Type of Medium: Online Resource
    ISSN: 0022-3085
    URL: Article
    DOI: 10.3171/jns.2004.100.6.1111
    RVK:
    XA 10000
    RVK:
    XA 55270
    Language: Unknown
    Publisher: Journal of Neurosurgery Publishing Group (JNSPG)
    Publication Date: 2004
    detail.hit.zdb_id: 2026156-1
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  • 4
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    Rate of Resolution of Histologically Verified Intracranial Tuberculomas
    Ovid Technologies (Wolters Kluwer Health) ; 2003
    In:  Neurosurgery Vol. 53, No. 4 ( 2003-10), p. 873-879
    Details
    In: Neurosurgery, Ovid Technologies (Wolters Kluwer Health), Vol. 53, No. 4 ( 2003-10), p. 873-879
    Type of Medium: Online Resource
    ISSN: 0148-396X
    URL: Article
    DOI: 10.1227/01.NEU.0000083553.25421.6F
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2003
    detail.hit.zdb_id: 1491894-8
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  • 5
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    GD2-targeting CAR-T cells enhanced by transgenic IL-15 expression are an effective and clinically feasible therapy for glioblastoma
    BMJ ; 2022
    In:  Journal for ImmunoTherapy of Cancer Vol. 10, No. 9 ( 2022-09), p. e005187-
    Details
    In: Journal for ImmunoTherapy of Cancer, BMJ, Vol. 10, No. 9 ( 2022-09), p. e005187-
    Abstract: Aggressive primary brain tumors such as glioblastoma are uniquely challenging to treat. The intracranial location poses barriers to therapy, and the potential for severe toxicity. Effective treatments for primary brain tumors are limited, and 5-year survival rates remain poor. Immune checkpoint inhibitor therapy has transformed treatment of some other cancers but has yet to significantly benefit patients with glioblastoma. Early phase trials of chimeric antigen receptor (CAR) T-cell therapy in patients with glioblastoma have demonstrated that this approach is safe and feasible, but with limited evidence of its effectiveness. The choices of appropriate target antigens for CAR-T-cell therapy also remain limited. Methods We profiled an extensive biobank of patients’ biopsy tissues and patient-derived early passage glioma neural stem cell lines for GD2 expression using immunomicroscopy and flow cytometry. We then employed an approved clinical manufacturing process to make CAR- T cells from patients with peripheral blood of glioblastoma and diffuse midline glioma and characterized their phenotype and function in vitro. Finally, we tested intravenously administered CAR-T cells in an aggressive intracranial xenograft model of glioblastoma and used multicolor flow cytometry, multicolor whole-tissue immunofluorescence and next-generation RNA sequencing to uncover markers associated with effective tumor control. Results Here we show that the tumor-associated antigen GD2 is highly and consistently expressed in primary glioblastoma tissue removed at surgery. Moreover, despite patients with glioblastoma having perturbations in their immune system, highly functional GD2-specific CAR-T cells can be produced from their peripheral T cells using an approved clinical manufacturing process. Finally, after intravenous administration, GD2-CAR-T cells effectively infiltrated the brain and controlled tumor growth in an aggressive orthotopic xenograft model of glioblastoma. Tumor control was further improved using CAR-T cells manufactured with a clinical retroviral vector encoding an interleukin-15 transgene alongside the GD2-specific CAR. These CAR-T cells achieved a striking 50% complete response rate by bioluminescence imaging in established intracranial tumors. Conclusions Targeting GD2 using a clinically deployed CAR-T-cell therapy has a sound scientific and clinical rationale as a treatment for glioblastoma and other aggressive primary brain tumors.
    Type of Medium: Online Resource
    ISSN: 2051-1426
    URL: Article
    DOI: 10.1136/jitc-2022-005187
    Language: English
    Publisher: BMJ
    Publication Date: 2022
    detail.hit.zdb_id: 2719863-7
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  • 6
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    Endothelial, pericyte and tumor cell expression in glioblastoma identifies fibroblast activation protein (FAP) as an excellent target for immunotherapy
    Wiley ; 2020
    In:  Clinical & Translational Immunology Vol. 9, No. 10 ( 2020-01)
    Details
    In: Clinical & Translational Immunology, Wiley, Vol. 9, No. 10 ( 2020-01)
    Abstract: Targeted immunotherapies such as chimeric antigen receptor (CAR)‐T cells are emerging as attractive treatment options for glioblastoma, but rely on identification of a suitable tumor antigen. We validated a new target antigen for glioblastoma, fibroblast activation protein (FAP), by undertaking a detailed expression study of human samples. Methods Glioblastoma and normal tissues were assessed using immunostaining, supported by analyses of published transcriptomic datasets. Short‐term cultures of glioma neural stem (GNS) cells were compared to cultures of healthy astrocytes and neurons using flow cytometry. Glioblastoma tissues were dissociated and analysed by high‐parameter flow cytometry and single‐cell transcriptomics (scRNAseq). Results Compared to normal brain, FAP was overexpressed at the gene and protein level in a large percentage of glioblastoma tissues, with highest levels of expression associated with poorer prognosis. FAP was also overexpressed in several paediatric brain cancers. FAP was commonly expressed by cultured GNS cells but absent from normal neurons and astrocytes. Within glioblastoma tissues, the strongest expression of FAP was around blood vessels. In fact, almost every tumor vessel was highlighted by FAP expression, whereas normal tissue vessels and cultured endothelial cells (ECs) lacked expression. Single‐cell analyses of dissociated tumors facilitated a detailed characterisation of the main cellular components of the glioblastoma microenvironment and revealed that vessel‐localised FAP is because of expression on both ECs and pericytes. Conclusion Fibroblast activation protein is expressed by multiple cell types within glioblastoma, highlighting it as an ideal immunotherapy antigen to target destruction of both tumor cells and their supporting vascular network.
    Type of Medium: Online Resource
    ISSN: 2050-0068 , 2050-0068
    URL: Issue
    URL: Article
    DOI: 10.1002/cti2.v9.10
    DOI: 10.1002/cti2.1191
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2694482-0
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  • 7
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    Abstract PO-004: A deep convolutional neural network for segmentation of whole-slide pathology images in glioblastoma
    American Association for Cancer Research (AACR) ; 2021
    In:  Clinical Cancer Research Vol. 27, No. 5_Supplement ( 2021-03-01), p. PO-004-PO-004
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 27, No. 5_Supplement ( 2021-03-01), p. PO-004-PO-004
    Abstract: Glioblastoma is the most aggressive type of brain cancer with high-levels of intra- and inter-tumour heterogeneity that contribute to its rapid growth and invasion within the brain. Here, we have used a deep convolutional neural network (DCNN) as a semantic segmentation model to segment seven different tumour regions including leading-edge (LE), infiltrating tumour (IT), cellular tumour (CT), cellular tumour microvascular proliferation (CTmvp), cellular tumour pseudopalisading region around necrosis (CTpan), cellular tumour perinecrotic zones (CTpnz) and cellular tumour necrosis (CTne) in digitised glioblastoma histopathological slides from The Cancer Genome Atlas (TCGA). Analysis of segmentation results from tumour images together with matched RNA expression data identified genetic signatures that are specific to these different tumour regions. We found that spatially resolved gene signatures were strongly correlated with survival in patients with defined genetic mutations. Moreover, in silico cell ontology analysis and single-cell RNA sequencing data from resected glioblastoma tissue samples, showed that these tumour regions had different gene signatures, suggesting they are driven by different cell types in the tumour microenvironment. This points to a key role for interactions between microglia/pericytes/monocytes and tumour cells that occur in the IT and CTmvp regions, which may contribute to poor patient survival. Overall, this work identifies key histopathological features that are indicative of patient survival and detected spatially associated genetic signatures that mediate tumour-stroma interactions that should be investigated as new targets in glioblastoma. Citation Format: Amin Zadeh Shirazi, Mark D. McDonnell, Eric Fornaciari, Narjes Sadat Bagherian, Kaitlin G. Scheer, Michael S. Samuel, Mahdi Yaghoobi, Rebecca J. Ormsby, Santosh Poonnoose, Damon Tumes, Guillermo A. Gomez. A deep convolutional neural network for segmentation of whole-slide pathology images in glioblastoma [abstract]. In: Proceedings of the AACR Virtual Special Conference on Artificial Intelligence, Diagnosis, and Imaging; 2021 Jan 13-14. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(5_Suppl):Abstract nr PO-004.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1557-3265.ADI21-PO-004
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
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  • 8
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    SRRM4 Expands the Repertoire of Circular RNAs by Regulating Microexon Inclusion
    MDPI AG ; 2020
    In:  Cells Vol. 9, No. 11 ( 2020-11-16), p. 2488-
    Details
    In: Cells, MDPI AG, Vol. 9, No. 11 ( 2020-11-16), p. 2488-
    Abstract: High-throughput RNA sequencing (RNA-seq) and dedicated bioinformatics pipelines have synergized to identify an expansive repertoire of unique circular RNAs (circRNAs), exceeding 100,000 variants. While the vast majority of these circRNAs comprise canonical exonic and intronic sequences, microexons (MEs)—which occur in 30% of functional mRNA transcripts—have been entirely overlooked. CircRNAs which contain these known MEs (ME-circRNAs) could be identified with commonly utilized circRNA prediction pipelines, CIRCexplorer2 and CIRI2, but were not previously recognized as ME-circRNAs. In addition, when employing a bespoke bioinformatics pipeline for identifying RNA chimeras, called Hyb, we could also identify over 2000 ME-circRNAs which contain novel MEs at their backsplice junctions, that are uncalled by either CIRCexplorer2 or CIRI2. Analysis of circRNA-seq datasets from gliomas of varying clinical grades compared with matched control tissue has shown circRNAs have potential as prognostic markers for stratifying tumor from healthy tissue. Furthermore, the abundance of microexon-containing circRNAs (ME-circRNAs) between tumor and normal tissues is correlated with the expression of a splicing associated factor, Serine/arginine repetitive matrix 4 (SRRM4). Overexpressing SRRM4, known for regulating ME inclusion in mRNAs critical for neural differentiation, in human HEK293 cells resulted in the biogenesis of over 2000 novel ME-circRNAs, including ME-circEIF4G3, and changes in the abundance of many canonical circRNAs, including circSETDB2 and circLRBA. This shows SRRM4, in which its expression is correlated with poor prognosis in gliomas, acts as a bona fide circRNA biogenesis factor. Given the known roles of MEs and circRNAs in oncogenesis, the identification of these previously unrecognized ME-circRNAs further increases the complexity and functional purview of this non-coding RNA family.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    URL: Article
    DOI: 10.3390/cells9112488
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2661518-6
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  • 9
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    The O-Arm as an Additional Tool to Confirm Optimal Ventricular Tip Position—A Technical Note
    Elsevier BV ; 2022
    In:  World Neurosurgery Vol. 163 ( 2022-07), p. 68-70
    Details
    In: World Neurosurgery, Elsevier BV, Vol. 163 ( 2022-07), p. 68-70
    Type of Medium: Online Resource
    ISSN: 1878-8750
    URL: Article
    DOI: 10.1016/j.wneu.2022.04.053
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 2530041-6
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  • 10
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    Dose-Dependent Effects of Statins for Patients with Aneurysmal Subarachnoid Hemorrhage: Meta-Regression Analysis
    Elsevier BV ; 2018
    In:  World Neurosurgery Vol. 113 ( 2018-05), p. 153-162
    Details
    In: World Neurosurgery, Elsevier BV, Vol. 113 ( 2018-05), p. 153-162
    Type of Medium: Online Resource
    ISSN: 1878-8750
    URL: Article
    DOI: 10.1016/j.wneu.2018.01.184
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2018
    detail.hit.zdb_id: 2530041-6
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