Biology subjects

Teesdale-Spittle, P.

Publications and source records attributed to Teesdale-Spittle, P..

2 recordsLinked to original sources

bioRxiv2023

BCL6 is a context-dependent mediator of the glioblastoma response to irradiation therapy

Glioblastoma is a rapidly fatal brain cancer with no cure. The resistance of glioblastoma tumours to available therapies means that more effective treatments are desperately needed. Previous research showed that the transcriptional repressor protein BCL6 is upregulated by chemo- and radiotherapy in glioblastoma and that inhibition of BCL6 enhances the effectiveness of these therapies. Therefore, BCL6 is a promising target to improve the efficacy of available treatments for glioblastoma. BCL6 is known as a transcriptional repressor in germinal centre B cells and is an oncogene in lymphoma, as well as in other cancers. However, previous research indicated that BCL6 induced by chemotherapy or irradiation in glioblastoma may not act as a transcriptional repressor. This study aimed to clarify the role of BCL6 in the response of glioblastoma to irradiation. The effect of BCL6 inhibition on the whole proteome response of glioblastoma cells to fractionated and acute irradiation treatment was investigated. Acute irradiation appeared to cause BCL6 to switch from a repressor of the DNA damage response to a promoter of stress response signalling. Rapid immunoprecipitation mass spectrometry of endogenous proteins enabled identification of proteins associated with BCL6 in untreated and irradiated glioblastoma cells. BCL6 associated with transcriptional coregulators in untreated glioblastoma and its association with the corepressor NCOR2 was validated using proximity ligation assays. However, the association of BCL6 with transcriptional regulatory proteins was lost in response to acute irradiation. This was accompanied by the irradiation-induced association of BCL6 with synaptic and plasma membrane proteins. Overall, these results reveal that the activity of BCL6 in glioblastoma therapy responses is context-dependent and may be mediated by the intensity of cellular stress.

cancer biology↗

bioRxiv2018

Predictive Modelling of The Dynamic Patterns of Thinkingin Attention-Deficit/Hyperactivity Disorder: DiagnosticAccuracy of Spatiotemporal Fractal Measures

BackgroundAttention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental condition characterized by executive function (EF) dynamics disturbances. Notwithstanding, current advances in translational neuroscience, no ADHD objective, clinically useful, diagnostic marker is available to date.\n\nObjectivesUsing a customized definition of EF and a new clinical paradigm, we performed a prospective diagnostic accuracy trial to assess the diagnostic value of several fractal measures from the thinking processes or inferences in a cohort of ADHD children and typically developing controls.\n\nMethodWe included children from age five to twelve diagnosed with a reference standard based on case history, physical and neurological examination, Conners 3rd Edition, and DSM-V. The index test consisted of a computer-based inference task with a set of eight different instances of the \"Battleships\" game to be solved. A consecutive series of 18 cases and 18 controls (n = 36) recruited at the primary paediatrics service from the Nelson Marlborough Health in New Zealand underwent the reference standard and the index test. Several fractal measures were obtained from the inference task to produce supervised classification models.\n\nResultsNotably, the summarized logistic regressions predicted probabilities from the eight games played by each children yielded a 100% classification accuracy, sensitivity and specificity in both a training and an independent testing/validating cohort.\n\nConclusionsFrom a translational vantage point the expeditious method and the robust results make this technique a promising candidate to develop a screening, diagnostic and monitoring system for ADHD, and may serve to assess other EF disturbances.

clinical trials↗