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Sequential Orbitrap Secondary Ion Mass Spectrometry and Liquid Extraction Surface Analysis-Tandem Mass Spectrometry-Based Metabolomics for Prediction of Brain Tumor Relapse from Sample-Limited Primary Tissue Archives (2021)
Journal Article
Meurs, J., Scurr, D. J., Lourdusamy, A., Storer, L. C., Grundy, R. G., Alexander, M. R., …Kim, D. (2021). Sequential Orbitrap Secondary Ion Mass Spectrometry and Liquid Extraction Surface Analysis-Tandem Mass Spectrometry-Based Metabolomics for Prediction of Brain Tumor Relapse from Sample-Limited Primary Tissue Archives. Analytical Chemistry, 93(18), 6947-6954. https://doi.org/10.1021/acs.analchem.0c05087

We present here a novel surface mass spectrometry strategy to perform untargeted metabolite profiling of formalin-fixed paraffin-embedded pediatric ependymoma archives. Sequential Orbitrap secondary ion mass spectrometry (3D OrbiSIMS) and liquid extr... Read More about Sequential Orbitrap Secondary Ion Mass Spectrometry and Liquid Extraction Surface Analysis-Tandem Mass Spectrometry-Based Metabolomics for Prediction of Brain Tumor Relapse from Sample-Limited Primary Tissue Archives.

Integrated Metabolomics and Transcriptomics Using an Optimised Dual Extraction Process to Study Human Brain Cancer Cells and Tissues (2021)
Journal Article
Rahman, R., Woodward, A., Pandele, A., Abdelrazig, S., Ortori, C., Khan, I., …Kim, D. (2021). Integrated Metabolomics and Transcriptomics Using an Optimised Dual Extraction Process to Study Human Brain Cancer Cells and Tissues. Metabolites, 11(4), Article 240. https://doi.org/10.3390/metabo11040240

The integration of untargeted metabolomics and transcriptomics from the same population of cells or tissue enhances the confidence in the identified metabolic pathways and understanding of the enzyme–metabolite relationship. Here, we optimised a simu... Read More about Integrated Metabolomics and Transcriptomics Using an Optimised Dual Extraction Process to Study Human Brain Cancer Cells and Tissues.

Assessment of Cannabidiol and ?9-Tetrahydrocannabiol in Mouse Models of Medulloblastoma and Ependymoma (2021)
Journal Article
Andradas, C., Byrne, J., Kuchibhotla, M., Ancliffe, M., Jones, A. C., Carline, B., …Endersby, R. (2021). Assessment of Cannabidiol and ∆9-Tetrahydrocannabiol in Mouse Models of Medulloblastoma and Ependymoma. Cancers, 13, Article 330. https://doi.org/10.3390/cancers13020330

Children with medulloblastoma and ependymoma are treated with a multidisciplinary approach that incorporates surgery, radiotherapy, and chemotherapy; however, overall survival rates for patients with high-risk disease remain unsatisfactory. Data indi... Read More about Assessment of Cannabidiol and ?9-Tetrahydrocannabiol in Mouse Models of Medulloblastoma and Ependymoma.

Epen-23. A computational analysis of the tumour immune microenvironment in paediatric ependymoma (2020)
Journal Article
Ritzmann, T., Lourdusamy, A., Jackson, A., Storer, L., Donson, A., Griesinger, A., …Grundy, R. (2020). Epen-23. A computational analysis of the tumour immune microenvironment in paediatric ependymoma. Neuro-Oncology, 22(Supplement 3), iii312. https://doi.org/10.1093/neuonc/noaa222.160

Ependymoma is the third commonest childhood brain tumour. Relapse is frequent, often fatal and current therapeutic strategies are inadequate. Previous ependymoma research describes an immunosuppressive environment with T-cell exhaustion, indicating a... Read More about Epen-23. A computational analysis of the tumour immune microenvironment in paediatric ependymoma.

Epen-22. Single-cell RNA sequencing identifies upregulation of IKZF1 in PFA2 myeloid subpopulation driving an anti-tumor phenotype (2020)
Journal Article
Griesinger, A., Prince, E., Donson, A., Riemondy, K., Ritzman, T., Harris, F., …Foreman, N. (2020). Epen-22. Single-cell RNA sequencing identifies upregulation of IKZF1 in PFA2 myeloid subpopulation driving an anti-tumor phenotype. Neuro-Oncology, 22(Supplement 3), iii312. https://doi.org/10.1093/neuonc/noaa222.159

We have previously shown immune gene phenotype variations between posterior fossa ependymoma subgroups. PFA1 tumors chronically secrete IL-6, which pushes the infiltrating myeloid cells to an immune suppressive function. In contrast, PFA2 tumors have... Read More about Epen-22. Single-cell RNA sequencing identifies upregulation of IKZF1 in PFA2 myeloid subpopulation driving an anti-tumor phenotype.

TBIO-14. Characterisation of the arginine pathway enzymes in paediatric brain tumours to determine susceptibility to therapeutic arginine depletion (2020)
Journal Article
Bishop, E., Dimitrova, M., Storer, L., Grundy, R., & Dandapani, M. (2020). TBIO-14. Characterisation of the arginine pathway enzymes in paediatric brain tumours to determine susceptibility to therapeutic arginine depletion. Neuro-Oncology, 22(Issue Supplement_3), iii469. https://doi.org/10.1093/neuonc/noaa222.841

INTRODUCTION Extracellular arginine dependency (auxotrophy) is increasingly being recognised in several tumours. This is due to the inability of cancer cells to recycle or synthesise intracellular arginine through the urea cycle pathway compared to... Read More about TBIO-14. Characterisation of the arginine pathway enzymes in paediatric brain tumours to determine susceptibility to therapeutic arginine depletion.

Metabolism based isolation of invasive glioblastoma cells with specific gene signatures and tumorigenic potential (2020)
Journal Article
Smith, S. J., Rowlinson, J., Estevez-Cebrero, M., Onion, D., Ritchie, A., Clarke, P., …Rahman, R. (2020). Metabolism based isolation of invasive glioblastoma cells with specific gene signatures and tumorigenic potential. Neuro-Oncology Advances, 2(1), Article vdaa087. https://doi.org/10.1093/noajnl/vdaa087

Background Glioblastoma (GBM) is a highly aggressive brain tumor with rapid subclonal diversification, harboring molecular abnormalities that vary temporo-spatially, a contributor to therapy resistance. Fluorescence guided neurosurgical resection ut... Read More about Metabolism based isolation of invasive glioblastoma cells with specific gene signatures and tumorigenic potential.

Thioredoxin system protein expression is associated with poor clinical outcome in adult and paediatric gliomas and medulloblastomas (2020)
Journal Article
Martin, S., Yao, A., Storr, S. J., Al-Hadyan, K., Rahman, R., Smith, S., …Paine, S. (2020). Thioredoxin system protein expression is associated with poor clinical outcome in adult and paediatric gliomas and medulloblastomas. Molecular Neurobiology, 57(7), 2889–2901. https://doi.org/10.1007/s12035-020-01928-z

The thioredoxin (Trx) system is an important enzyme family that regulates cellular redox homeostasis. Protein expression of Trx system family members has been assessed in various cancers and linked to various clinicopathological variables, disease pr... Read More about Thioredoxin system protein expression is associated with poor clinical outcome in adult and paediatric gliomas and medulloblastomas.

Distinguishing between paediatric brain tumour types using multi-parametric magnetic resonance imaging and machine learning: A multi-site study (2020)
Journal Article
Grist, J. T., Withey, S., MacPherson, L., Oates, A., Powell, S., Novak, J., …Peet, A. C. (2020). Distinguishing between paediatric brain tumour types using multi-parametric magnetic resonance imaging and machine learning: A multi-site study. NeuroImage: Clinical, 25, Article 102172. https://doi.org/10.1016/j.nicl.2020.102172

The imaging and subsequent accurate diagnosis of paediatric brain tumours presents a radiological challenge, with magnetic resonance imaging playing a key role in providing tumour specific imaging information. Diffusion weighted and perfusion imaging... Read More about Distinguishing between paediatric brain tumour types using multi-parametric magnetic resonance imaging and machine learning: A multi-site study.

Pineoblastoma segregates into molecular sub-groups with distinct clinico-pathologic features: a Rare Brain Tumor Consortium registry study (2019)
Journal Article
Li, B. K., Vasiljevic, A., Dufour, C., Yao, F., Ho, B. L. B., Lu, M., …Jouvet, A. (2020). Pineoblastoma segregates into molecular sub-groups with distinct clinico-pathologic features: a Rare Brain Tumor Consortium registry study. Acta Neuropathologica, 139(2), 223–241. https://doi.org/10.1007/s00401-019-02111-y

Pineoblastomas (PBs) are rare, aggressive pediatric brain tumors of the pineal gland with modest overall survival despite intensive therapy. We sought to define the clinical and molecular spectra of PB to inform new treatment approaches for this orph... Read More about Pineoblastoma segregates into molecular sub-groups with distinct clinico-pathologic features: a Rare Brain Tumor Consortium registry study.

In search of effective therapies to overcome resistance to Temozolomide in brain tumours (2019)
Journal Article
Grundy, R., Bouzinab, K., Summers, H., Zhang, J., Stevens, M. F. G., Moody, C. J., …Bradshaw, T. D. (2019). In search of effective therapies to overcome resistance to Temozolomide in brain tumours. Cancer Drug Resistance, 2(4), 1018-1031. https://doi.org/10.20517/cdr.2019.64

Glioblastoma multiforme is the most common and lethal brain tumour-type. The current standard of care includes Temozolomide (TMZ) chemotherapy. However, inherent and acquired resistance to TMZ thwart successful treatment. The direct repair protein me... Read More about In search of effective therapies to overcome resistance to Temozolomide in brain tumours.

A role for ABCB1 in prognosis, invasion and drug resistance in ependymoma (2019)
Journal Article
Sabnis, D. H., Storer, L. C. D., Liu, J., Jackson, H. K., Kilday, J. P., Grundy, R. G., …Coyle, B. (2019). A role for ABCB1 in prognosis, invasion and drug resistance in ependymoma. Scientific Reports, 9(1), 1-9. https://doi.org/10.1038/s41598-019-46700-z

© 2019, The Author(s). Three of the hallmarks of poor prognosis in paediatric ependymoma are drug resistance, local invasion and recurrence. We hypothesised that these hallmarks were due to the presence of a sub-population of cancer stem cells expres... Read More about A role for ABCB1 in prognosis, invasion and drug resistance in ependymoma.

A C19MC-LIN28A-MYCN Oncogenic Circuit Driven by Hijacked Super-enhancers Is a Distinct Therapeutic Vulnerability in ETMRs: A Lethal Brain Tumor (2019)
Journal Article
Sin-Chan, P., Mumal, I., Suwal, T., Ho, B., Fan, X., Singh, I., …Huang, A. (2019). A C19MC-LIN28A-MYCN Oncogenic Circuit Driven by Hijacked Super-enhancers Is a Distinct Therapeutic Vulnerability in ETMRs: A Lethal Brain Tumor. Cancer Cell, 36(1), 51-67.e7. https://doi.org/10.1016/j.ccell.2019.06.002

© 2019 Elsevier Inc. Embryonal tumors with multilayered rosettes (ETMRs) are highly lethal infant brain cancers with characteristic amplification of Chr19q13.41 miRNA cluster (C19MC) and enrichment of pluripotency factor LIN28A. Here we investigated... Read More about A C19MC-LIN28A-MYCN Oncogenic Circuit Driven by Hijacked Super-enhancers Is a Distinct Therapeutic Vulnerability in ETMRs: A Lethal Brain Tumor.

Switching from linear to macrocyclic gadolinium‐based contrast agents halts the relative T 1 ‐Weighted signal increase in deep gray matter of children with brain tumors: A retrospective study (2019)
Journal Article
Rowe, S. K., Rodriguez, D., Cohen, E., Grundy, R., Morgan, P. S., Jaspan, T., & Dineen, R. A. (2019). Switching from linear to macrocyclic gadolinium‐based contrast agents halts the relative T 1 ‐Weighted signal increase in deep gray matter of children with brain tumors: A retrospective study. Journal of Magnetic Resonance Imaging, https://doi.org/10.1002/jmri.26831

Background Studies have shown signal intensity (SI) changes in the brains of children exposed to repeated doses of a gadolinium‐based contrast agent (GBCA). Hypothesis The trajectory of changes in relative dentate nucleus (DN) and globus pal... Read More about Switching from linear to macrocyclic gadolinium‐based contrast agents halts the relative T 1 ‐Weighted signal increase in deep gray matter of children with brain tumors: A retrospective study.

Overall survival in malignant glioma is significantly prolonged by neurosurgical delivery of etoposide and temozolomide from a thermo-responsive biodegradable paste (2019)
Journal Article
Smith, S. J., Tyler, B., Gould, T. W., Veal, G. J., Gorelick, N. L., Rowlinson, J., …Rahman, R. (2019). Overall survival in malignant glioma is significantly prolonged by neurosurgical delivery of etoposide and temozolomide from a thermo-responsive biodegradable paste. Clinical Cancer Research, 25(16), 5094-5106. https://doi.org/10.1158/1078-0432.ccr-18-3850

Purpose: High-grade glioma (HGG) treatment is limited by the inability of otherwise potentially efficacious drugs to penetrate the blood brain barrier. We evaluate the unique intra-cavity delivery mode and translational potential of a blend of poly(D... Read More about Overall survival in malignant glioma is significantly prolonged by neurosurgical delivery of etoposide and temozolomide from a thermo-responsive biodegradable paste.

The European Society of Paediatric Oncology Ependymoma-II program Core-Plus model: Development and initial implementation of a cognitive test protocol for an international brain tumour trial (2019)
Journal Article
Thomas, S., Reynolds, D., Morrall, M., Limond, J., Chevignard, M., Calaminus, G., …Grundy, R. (2019). The European Society of Paediatric Oncology Ependymoma-II program Core-Plus model: Development and initial implementation of a cognitive test protocol for an international brain tumour trial. European Journal of Paediatric Neurology, 23(4), 560-570. https://doi.org/10.1016/j.ejpn.2019.05.009

© 2019 European Paediatric Neurology Society It is increasingly accepted that survival alone is an inadequate measure of the success of childhood brain tumour treatments. Consequently, there is growing emphasis on capturing quality of survival. Epend... Read More about The European Society of Paediatric Oncology Ependymoma-II program Core-Plus model: Development and initial implementation of a cognitive test protocol for an international brain tumour trial.

Outcomes of non-anaplastic stage III and ‘inoperable’ Wilms tumour treated in the UKW3 trial (2018)
Journal Article
Irtan, S., Messahel, B., Moroz, V., Taylor, R. E., Grundy, R., Kelsey, A., …Pritchard-Jones, K. (2019). Outcomes of non-anaplastic stage III and ‘inoperable’ Wilms tumour treated in the UKW3 trial. Radiotherapy and Oncology, 131, 1-7. https://doi.org/10.1016/j.radonc.2018.10.026

© 2018 Background and purpose: To describe the outcome of patients with stage III Wilms tumours (WT) treated in the UKW3 trial. Material and methods: Patients with a pathologically confirmed stage III non-anaplastic WT at nephrectomy (Group A) or wit... Read More about Outcomes of non-anaplastic stage III and ‘inoperable’ Wilms tumour treated in the UKW3 trial.

Limitations of current in vitro models for testing the clinical potential of epigenetic inhibitors for treatment of pediatric ependymoma (2018)
Journal Article
Rogers, H. A., Chapman, R., Kings, H., Allard, J., Barron-Hastings, J., Pajtler, K. W., …Grundy, R. G. (2018). Limitations of current in vitro models for testing the clinical potential of epigenetic inhibitors for treatment of pediatric ependymoma. Oncotarget, 9(92), 36530-36541. https://doi.org/10.18632/oncotarget.26370

Background: Epigenetic modifications have been shown to play an important role in the classification and pathogenesis of the pediatric brain tumor ependymoma, suggesting they are a potential therapeutic target. Results: Agents targeting epigenetic... Read More about Limitations of current in vitro models for testing the clinical potential of epigenetic inhibitors for treatment of pediatric ependymoma.