Serum lactate as a potential biomarker of malignancy in primary adult brain tumours

AbstractSolid tumours are less oxygenated than normal tissues. This is called tumour hypoxia and leads to resistance to radiotherapy and chemotherapy. The molecular mechanisms underlying such resistance have been investigated in a range of tumour types, including the adult brain tumours glioblastoma, yet little is known for paediatric brain tumours. Medulloblastoma (MB) is the most common malignant brain tumour in children. Here we used a common MB cell line (D283-MED), to investigate the mechanisms of chemo and radio-resistance in MB, comparing to another MB cell line (MEB-Med8A) and to a widely used glioblastoma cell line (U87MG). In D283-MED and U87MG, chronic hypoxia (5 days), but not acute hypoxia (24 h) induced resistance to etoposide and X-ray irradiation. This acquired resistance upon chronic hypoxia was much less pronounced in MEB-Med8A cells. Using a transcriptomic approach in D283-MED cells, we found a large transcriptional remodelling upon long term hypoxia, in particular the expression of a number of genes involved in detection and repair of double strand breaks (DSB) was altered. The levels of Nibrin (NBN) and MRE11, members of the MRN complex (MRE11/Rad50/NBN) responsible for DSB recognition, were significantly down-regulated. This was associated with a reduction of Ataxia Telangiectasia Mutated (ATM) activation by etoposide, indicating a profound dampening of the DNA damage signalling in hypoxic conditions. As a consequence, p53 activation by etoposide was reduced, and cell survival enhanced. Whilst U87MG shared the same dampened p53 activity, upon chemotherapeutic drug treatment in chronic hypoxic conditions, these cells used a different mechanism, independent of the DNA damage pathway. Together our results demonstrate a new mechanism explaining hypoxia-induced resistance involving the alteration of the response to DSB, but also highlight the cell type to cell type diversity and the necessity to take into account the differing tumour genetic make-up when considering re-sensitisation therapeutic protocols.

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26: Automated Machine-Learning Radiotherapy Planning for Pediatric and Adult Brain Tumours

Radiotherapy and Oncology ◽

10.1016/s0167-8140(20)30918-x ◽

2020 ◽

Vol 150 ◽

pp. S15

Author(s):

Grace Tsui ◽

Derek Tsang ◽

Chris McIntosh ◽

Tom Purdie ◽

Mohammad Khandwala ◽

...

Keyword(s):

Machine Learning ◽

Brain Tumours ◽

Adult Brain ◽

Radiotherapy Planning ◽

Automated Machine Learning

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A cytogenetic study of 68 childhood and adult brain tumours

Cancer Genetics and Cytogenetics ◽

10.1016/0165-4608(91)90534-2 ◽

1991 ◽

Vol 52 (2) ◽

pp. 250

Author(s):

L.R. Adam ◽

J.D. Edwards ◽

E.V. Davison ◽

E. Jaros ◽

Perry ◽

...

Keyword(s):

Brain Tumours ◽

Cytogenetic Study ◽

Adult Brain

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Methylation array profiling of adult brain tumours: diagnostic outcomes in a large, single centre

Acta Neuropathologica Communications ◽

10.1186/s40478-019-0668-8 ◽

2019 ◽

Vol 7 (1) ◽

Cited By ~ 22

Author(s):

Zane Jaunmuktane ◽

David Capper ◽

David T. W. Jones ◽

Daniel Schrimpf ◽

Martin Sill ◽

...

Keyword(s):

Brain Tumours ◽

Adult Brain ◽

Single Centre ◽

Methylation Array ◽

Diagnostic Outcomes

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Functional neurological disorders in patients with brain tumours

Neuro-Oncology ◽

10.1093/neuonc/noab195.026 ◽

2021 ◽

Vol 23 (Supplement_4) ◽

pp. iv12-iv12

Author(s):

Charmaine Toh ◽

Dorothy Joe ◽

Katia Cikurel ◽

Julia Johnson ◽

Francesco Vergani ◽

...

Keyword(s):

Brain Tumour ◽

Neurological Disorders ◽

Neurological Disorder ◽

Brain Tumours ◽

Neurological Symptoms ◽

Adult Brain ◽

Case Review ◽

Functional Neurological Symptoms ◽

Functional Neurological Disorders ◽

Functional Neurological Disorder

Abstract Aims Signs and symptoms that develop in people with brain tumours are often attributed to their tumour. The prevalence and management of functional neurological symptoms in brain tumour patients have received little attention. This is surprising because functional neurological symptoms complicate management greatly and misdiagnosis can lead to inappropriate treatment and iatrogenic side-effects. Therefore, we investigated the presentation, diagnosis and management of functional neurological disorders (FND) in patients who had a brain or meningeal tumour. Method A retrospective case review was performed from 2017 - 2021 to identify adult brain tumour patients who developed a functional neurological disorder that caused significant disability necessitating expedited investigations. All patients attended a regional neuro-oncology centre. We recorded type of brain tumour and diagnostic investigations. The onset of functional symptoms was divided into three time windows: before tumour diagnosis, after diagnosis and before treatment or after tumour treatment. A neuropsychological review looked for evidence of previous adverse life events. Therapeutic interventions for functional neurological disorder and their outcomes were documented. The case review was combined with a systematic review of the literature to identify the published presentations of functional neurological disorder in the adult brain tumour population. MEDLINE, EMBASE and PsycINFO databases were searched for studies published between January 1980 and February 2021. Results Six patients (5 female, 1 male) were identified from the case review with a median age of 41 (range 29 - 56) years old. Four patients had non-epileptic attack disorder, which was diagnosed with videotelemetry of habitual attacks. One patient had a functional hemiparesis with normal central motor conduction time. One patient had a functional speech disorder with normal EEG. Half of these patients had functional neurological symptoms prior to surgery/oncological treatment. Five patients (83%) were referred for further neuropsychiatric or psychological evaluation. A history of significant psychological trauma prior to the brain tumour diagnosis was elicited in four (66%) patients. Conclusion Patients with either a brain or meningeal tumour may develop functional neurological symptoms. Our findings suggest the possibility that diagnosis of a brain tumour may precipitate a debilitating functional neurological disorder. The neurobiological basis for functional neurological disorders is being actively investigated. There are suggestions in the literature that some brain diseases increase the risk of developing a functional neurological disorder. Further work is needed to determine whether this is true for patients with brain tumours. Increased awareness of functional neurological disorders will improve management. Withdrawal of unnecessary treatment, such as anticonvulsant drugs, reduces the risk of iatrogenic side effects. Initiation of multi-disciplinary care pathways, e.g. physiotherapy, speech and language therapy and psychological treatments, promotes recovery. Collectively, these interventions improve our patients’ quality of life.

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