bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application of self-made rubber drainage strip in the operation of giant lipoma
Authors: Chen Qing , Shao Ping 
Published: October 2022

Abstract
Lipoma is a common benign soft-tissue tumor. Giant lipoma [1] is generally defined as more than 10 cm in length or more than 1000 g in weight. We report a 33-year-old patient with a giant lipoma in the left scapular region. We placed a self-made rubber drainage strip during the operation to control exudate, which is effective in improving incision effusion.
IDHwt Glioblastomas Show Opposing Resistance Mechanisms Across Patients in Response to Standard Treatment
Authors: Tanner Georgette , Finetti Martina A , Pollock Steven , Rippaus Nora , Bruns Alexander-Francisco , Hogg Catherine , Droop Alastair , Bruning-Richardson Anke , Care Mathew , Wilkinson Joseph , Jenkinson Michael , Brodbelt Andrew , Chakrabarty Aruna , Ismail Azzam , Short Susan , Stead Lucy 
Published: October 2022

Abstract

AIMS
Glioblastoma (GBM) is the most common primary malignant brain tumour in adults. Despite aggressive treatment, a resistant tumour recurs in practically all patients. We therefore aimed to better understand the mechanisms driving this treatment resistance through investigating changes in gene expression across pairs of primary and recurrent GBM tumours.

METHOD
We generated or acquired bulk tumour RNA sequencing data for primary and first recurrent tumours from 107 patients who received standard treatment. Differential expression analysis between primary and recurrent samples found that the most dysregulated genes were involved in neurodevelopment and neurodifferentiation. We therefore used a publicly available ChIP-seq database to identify DNA binding factors for which binding sites are enriched in the promotors of genes with the largest expression changes from primary to recurrent.

RESULTS
Jumonji and AT-Rich Interacting Domain 2 (JARID2) was the most strongly enriched for binding to promotors of dysregulated genes. 65 patients showed an up-regulation and 42 showed a down-regulation of genes bound by this protein. The same set of JARID2 bound genes were found to be dysregulated in each direction, and correlated with the largest source of variation between samples in their response to treatment. Further enrichment analyses indicated that ‘Up’ responders may resist treatment through reduced proliferation and increased interaction with the tumour microenvironment, whereas ‘Down’ responders instead rely on a shift to mesenchymal cell states.

CONCLUSION
These results indicate that GBM tumours can be split into two subtypes that transcriptionally reprogramme in different directions through treatment and may benefit from different treatment approaches.
Temozolomide Sensitivity of Malignant Glioma Cell Lines – A Systematic Review Assessing Consistencies Between In Vitro Studies
Authors: Poon Michael T C , Bruce Morgan , Simpson Joanne , Hannan Cathal , Brennan Paul 
Published: October 2022

Abstract

AIMS
Malignant glioma cell line models are integral to pre-clinical testing of novel potential therapies. Accurate prediction of likely efficacy in the clinic requires that these models are reliable and consistent. We assessed this by examining the reporting of experimental conditions and sensitivity to temozolomide in glioma cells lines.

METHOD
We searched Medline and Embase (Jan 1994-Jan 2021) for studies evaluating the effect of temozolomide monotherapy on cell viability of at least one malignant glioma cell line. Key data items included type of cell lines, temozolomide exposure duration in hours (hr), and cell viability measure (IC50).

RESULTS
We included 212 studies from 2789 non-duplicate records that reported 248 distinct cell lines. The commonest cell line was U87 (60.4%). Only 10.4% studies used a patient-derived cell line. The proportion of studies not reporting each experimental condition ranged from 8.0–27.4%, including base medium (8.0%), serum supplementation (9.9%) and number of replicates (27.4%). In studies reporting IC50, the median value for U87 at 24 h, 48 h and 72 h was 123.9 μM (IQR 75.3–277.7 μM), 223.1 μM (IQR 92.0–590.1 μM) and 230.0 μM (IQR 34.1–650.0 μM), respectively. The median IC50 at 72 h for patient-derived cell lines was 220 μM (IQR 81.1–800.0 μM).

CONCLUSION
Temozolomide sensitivity reported in comparable studies was not consistent between or within malignant glioma cell lines. Drug discovery science performed on these models cannot reliably inform clinical translation. A consensus model of reporting can maximise reproducibility and consistency among in vitro studies.
Comparative Analysis of the Histone H3 Mutant Protein Interactome Landscape in Paediatric High-Grade Gliomas
Authors: Haque Farhana 
Published: October 2022

Abstract

AIMS
There have been no significant improvements in the treatments for childhood and adolescent High-Grade Glioma (pHGG) and Diffuse Intrinsic Pontine Glioblastoma (DIPG), which have a very poor prognosis. These cancers harbour mutations affecting histone 3 (H3) proteins, 80% of DIPGs harbour histone H3.1 and H3.3 K27M somatic mutations whilst 30% of pHGGs exhibit H3.3 G34R or G34V mutations. Several studies have highlighted the epigenetic changes associated with these mutations, however their precise role in tumourigenesis is still unknown. We hypothesize that H3 mutations promote an aberrant interaction landscape and analysis of these interactome will highlight important pathophysiological consequences in these tumours.

METHOD
Two different affinity chromatographic proteomic analyses were performed using different recombinant H3 wild type (WT) and H3 mutant histone proteins (K27M, G34R and G34V) to purify their binding partners, from cell extracts of control and pHGG/DIPG patients cell lines. The purified samples were then subjected to Liquid Chromatography-Mass Spectrometry (LC-MS) to identify their co-bound partners.

RESULTS
The results have isolated unique and common differential interaction partners of the H3 mutants and with cellular proteins in comparison to H3 WT protein, in the pHGG tumour cells.

CONCLUSION
The role these altered protein interactions are being investigating in tumour initiation, progression and/or maintenance of H3 mutated pHGG/DIPG, with the aim to manipulate their function as alternate therapeutic intervention. Results of these analyses/experiments will be presented.
Neurosurgically-Applied Chemotherapy for Childhood Brain Tumours Arising in the Posterior Fossa Using a Biodegradable Paste
Authors: Moloney Cara , Mavromoustakos Menelaos , Alexander Cameron , Rahman Ruman 
Published: October 2022

Abstract

AIMS
This project aims to develop a local drug delivery system for treatment of childhood medulloblastoma (MB) and atypical teratoid/rhabdoid tumours (AT/RT), malignant brain neoplasms occurring in the posterior fossa for which prognoses remains poor. Our goal is to repurpose drug compounds reported as effective against MB and AT/RT, but which either cannot cross the blood-brain-barrier (BBB) or have not been assessed for localised delivery. We have developed a novel intra-cavity drug delivery system, consisting of polymer microparticles made from poly(DL-lactic-co-glycolic acid) and poly(ethylene glycol) (PLGA/PEG) which will be employed to release drugs over several weeks.

METHOD
Cell toxicity assays were undertaken using drugs of interest against an in vitro panel of relevant MB and AT/RT cell lines. PLGA/PEG paste incorporating the drugs were prepared and release kinetics assessed.

RESULTS
IC50 values of the drugs were assessed across all cell lines and a range of potencies were observed, with optimum conditions identified as dual treatments of PG545 (heparanse inhibitor) with CHIR99021 (glycogen synthase kinase-3 inhibitor) for MB and ribavirin (anti-viral) with CHIR99021 for AT/RT. Importantly, it was noted that the drugs retained their cytotoxicity following release from PLGA/PEG. Furthermore, release kinetics were finely tuned through careful control of the composition through addition of excipients and encapsulation of drugs in nanoparticles, and a library of formulations were prepared.

CONCLUSION
A local drug delivery system for MB and AT/RT has been developed and an optimum formulation, based upon in vitro cell assays and release kinetics, has been identified for in vivo efficacy studies in orthotopic models.
Surgical and Oncological Score to Estimate the Survival Benefit of Resection and Chemoradiotherapy in Elderly (≥70 Years) Glioblastoma Patients: A Preliminary Analysis Authors
Authors: Zorman Mark , Webb Philip , Nixon Mickaela , Sravanam Sanskrithi , Honeyman Susan , Nandhabalan Meera , Apostolopoulos Vasileios , Stacey Richard , Hobbs Claire , Plaha Puneet 
Published: October 2022

Abstract

AIMS
Elderly patients with glioblastoma are perceived to face a poor prognosis with perceptions surrounding older age and a relative lack of randomized data contributing. This study aimed to evaluate survival prognosticators in elderly glioblastoma patients to more accurately guide their treatment.

METHOD
The records of 169 elderly (≥70 years) patients with a new diagnosis of glioblastoma who had undergone neurosurgical intervention were retrospectively examined for patient sex, age, performance status, comorbidities, MGMT promoter methylation, surgical intervention and chemoradiation regime. The adjusted survival impact of these factors was determined using Cox proportional hazards model and used to devise a two-stage scoring system to estimate patient survival at the stage of surgical (Elderly Glioblastoma Surgical Score, EGSS) and oncological management (Elderly Glioblastoma Oncological Score, EGOS).

RESULTS
The median overall survival (mOS) of the cohort was 28.8 weeks. Gross-total and subtotal resection were associated with improved survival compared to biopsy alone (respective mOS 65.3 and 28.1 vs 15.7 weeks, p&lt;0.001). Hypofractionated radiotherapy (40Gy in 15 fractions) with Temozolomide was non-inferior to the Stupp protocol, p=0.72. Exploratory subgroup analysis revealed a significant benefit of Temozolomide-based approaches in MGMT-methylated patients as well as a trend towards improved survival in MGMT-unmethylated patients. Our EGSS and EGOS scores successfully estimated survival in this retrospective cohort with 65% and 73% accuracy.

CONCLUSION
Where appropriate and safe, elderly glioblastoma patients may benefit from surgical resection and combined chemoradiotherapy with Temozolomide. The proposed EGSS and EGOS scores take into account important prognostic factors to help guide which patients should receive such treatment.
Awake Craniotomy Is Well-tolerated in the Elderly: Our Early Experience
Authors: Khan Rosina , Okoh Magnus , Ogbu Ikenna , Chan Huan , Albanese Erminia 
Published: October 2022

Abstract

AIMS
Awake craniotomy for brain tumour resection aims to increase the extent of resection while minimising neurological deficit. The major concerns for patients during awake craniotomies include peri-operative discomfort/pain and anxiety for some patients. Older patients are generally not offered aggressive operative options due to longer lengths of hospital stay (LOS), expected higher rates of peri-operative morbidity/mortality, and poorer survival. However, increased extent of glioma resection is associated with greater overall and progression-free survival. Furthermore, previous studies have shown that awake craniotomies are well tolerated in elderly patients. This study aims to evaluate our experience in awake craniotomies for glioma resection in patients over 65 years old.

METHOD
Seventeen elderly patients who had undergone awake craniotomies at University Hospitals of North Midlands between 2015 and 2021 were included. Outcome measures included LOS, post-operative morbidity/mortality, and the difference between pre- and post-operative Hospital Anxiety and Depression scores (HADS).

RESULTS
There was an 11% operative mortality rate in our cohort. The average LOS was 5.7 days. The median pre- and post-operative score at 6 months was 1 indicating that there is no difference post-operatively. There was a positive net difference between pre- and post-operative anxiety/depression scores in our cohort.

CONCLUSION
Awake craniotomies are generally well tolerated among the elderly patients with unchanged post-operative performance status and improved HADS scores. These findings suggest that awake craniotomies should be offered to elderly patients if deemed appropriate.
Transcriptome-wide Mendelian Randomisation Using Expression, Protein and Splicing Quantitative Trait Loci to Identify Novel Drug Targets Associated With Risk of Gliomagenesis
Authors: Thornton Zak , Robinson Jamie , Kurian Kathreena 
Published: October 2022

Abstract

AIMS
To use two-sample Mendelian Randomisation to prioritise novel genes for drug targeting in glioma risk using expression, protein and splicing quantitative trait loci (eQTLs, pQTLs and sQTLs, respectively).

METHOD
We used genetic variants from GWAS to compare the effects of eQTLs, pQTLs and sQTLs on genetic liability to glioma risk (n=12,496). eQTL data was retrieved from the MetaBrain study of five different brain tissues (n=108 to 2,970). pQTL data was retrieved from the BrainQTL study of dorsolateral prefrontal cortex tissue (n = 330), and sQTL data was retrieved from Genotype-Tissue Expression (GTEx) Project (v8) of 13 brain tissues (n=114 to 209). SNPs which were trans-QTLs (&gt;1 Mb) due to risk of horizontal pleiotropy, and greater than GWAS significance (P &gt; 5 × 10-8) were excluded. Instruments were constructed using independent SNPs (r2 &lt; 0.001). Results underwent relevant sensitivity analysis; colocalisation and Steiger filtering.

RESULTS
We found 123 MR associations for 28 genes with genetically predicted altered expression, protein or splicing levels affected risk of glioma. These included genes recurrently associated with glioma risk such as TERT, RTEL1, CDKN2A/B and EGFR, and novel putative genes; BTN3A2, GALNT6, GMPPB and FAIM. Following sensitivity analyses, we found that 58 MR associations for 25 genes had robust evidence.

CONCLUSION
We identified four novel associations not previously found in GWAS; BTN3A2 (6p22.2), FAIM (3q22.3), GALNT6 (12q13.13) and GMPPB (3p21.31) are implicated in glioma risk and are also not located on a known glioma risk locus. Further analysis is required to identify the suitability of these genes for drug targeting in glioma.
Early Post-treatment Pseudo-continuous Arterial Spin Labelling Stratifies 12 Month Survival in Gliomas
Authors: Maguire Alice , Obasi Emeka , Markus Julia , Gupta Meetakshi , Kosmin Michael , Sokolska Magdalena , Hyare Harpreet 
Published: October 2022

Abstract

AIMS
Arterial spin labelling (ASL) is a non-invasive perfusion technique that uses endogenous contrast and is proving to be of value in paediatric neuro-oncology. ASL derived rCBV has been shown to correlate with Dynamic Susceptibility Contrast (DSC) -derived CBV and could be an alternative perfusion technique when DSC is not possible. The aim of the study was to investigate whether early post-treatment tumour ASL can stratify patient survival at 12 months.

METHOD
180 consecutive patients diagnosed with glioblastoma and undergoing treatment between 2017-2021 were imaged with an extended MRI protocol that included pseudo-continuous ASL (pCASL). Patients that were imaged with pCASL within 1-3 months of completing radiotherapy were identified retrospectively. Scanner generated Perfusion weighted images were inspected and regions of interest encompassing the tumour were generated and compared with a control region in the contra-lateral grey matter. Overall survival data was collated and a comparison of tumour ASL was assessed with t-test statistics between patients surviving &lt; and &gt;12 months.

RESULTS
43 patients were identified (23 male, median age 58 years, diagnoses: IDHwt-GBM 17, IDHmut-Astrocytoma 13, IDHmut 1p19q co-deleted Oligodendroglioma 13). Tumour ASL was 3.22 (± 2.1) in patients that survived less than 12 months compared to 1.64 (± 1.9) in patients that survived greater than 12 months, p=0.02).

CONCLUSION
Early post-treatment ASL can stratify patient survival at 12 months and show promise as an alternative to DSC perfusion in the prognostication of patients being treated for glioma.
The Role of miRNAs in Gliomas in Response to Hypoxia
Authors: Smith Louise , Chakraborty Sajib , Lourdusamy Anbarasu , McIntyre Alan , Smith Stuart 
Published: October 2022

Abstract

AIMS
Identifying significant miRNAs that are either under or overexpressed in hypoxia compared to normoxia in glioma cells. Further exploring the effect and role of hypoxia on miR-92a-3p and miR-149-5p in gliomas in apoptotic and cellular senescence pathways.

METHOD
A range of glioma cells were used for screening, including primary cell lines: GIN28 and GIN31; low-grade cell lines: LGG19 and LGG24; a paediatric cell line: SF188 and a commercially available glioblastoma cell line U87. These cells were cultured at both 1% (hypoxia) and 20% (normoxia) oxygen levels. Screening of miRNAs was achieved by quantitative polymerase chain reaction (qPCR) using miRNA specific primers. Knockdowns/in were achieved by transfecting with miR-92a-3p and miR-149-5p mimics and inhibitors. Caspase-glo assay was used to assess the effect of hypoxia on apoptosis.

RESULTS
A range of miRNAs were differentially expressed in hypoxia in a range of glioma cell lines. miRNA 92a-3p and miR-149-5p were found to be downregulated and upregulated respectively in primary gliomablastoma cells in hypoxia compared to normoxia. These particular miRNAs are also found to have multiple targets in apoptosis and cellular senescence.

CONCLUSION
The screening of 90 miRNAs among the different categories of gliomas highlighted multiple miRNAs that were significant in hypoxia compared to normoxia. Using primary cell lines have identified hypoxia-affected miRNAs in glioblastomas. This discovery will increase our knowledge and understanding of the hypoxia effect on miRNAs which may aid and direct targeted therapy to conquer hypoxia in glioblastomas.
Multifocal and Multicentric Glioblastomas: A 10 Year Single Centre Experience
Authors: Maye Helen , Mavrovounis Georgios , Roncaroli Federico , McBain Catherine , Bailey Matthew , D’Urso Pietro , Coope David , Leach John , Leggate James , Karabatsou Tina 
Published: October 2022

Abstract

AIMS
The aims of this study are to share our experience of a large series of multifocal/multicentric glioblastomas (mGBM) and analyse the clinical, histological/molecular and neuroimaging characteristics as well as the outcomes of the patients in order to inform and contribute to future patient care.

METHOD
We conducted a retrospective single centre study of all multifocal/multicentric glioblastomas treated at our institution over a 10 year period. Data was collected from electronic patient records including patient demographics, clinical presentation, diagnostic imaging, treatment plans and histopathology/molecular findings. Time to recurrence/progression and overall survival was assessed.

RESULTS
1158 glioblastomas were treated surgically over this time period of which 121 multifocal/multicentric tumours were identified (10.4%). The median age at diagnosis was 63 years with a slight male predominance (54.5%). Half of all patients (61/121) presented with focal neurological deficits. 69% of patients underwent a craniotomy for diagnosis/debulking of the larger enhancing component of the tumour whilst 31% underwent only a biopsy. The median time to recurrence/progression was 154 days. Median length of survival was 269 days. Those who underwent craniotomy had significantly prolonged survival compared to biopsy alone 301 vs 198 days (p= 0.027) as did those who had a near total resection 401 vs 269 for subtotal resection (P=0.006) and those &lt; 60 years (p=&lt; 0.001). 88% of patients were IDH1 wildtype. Radiotherapy and chemotherapy confer a significant survival advantage when compared with no further treatment (p&lt;0.001).

CONCLUSION
Near total resection of the larger enhancing component and post-operative chemo/radiotherapy can offer prolonged survival in patients with mGBM.
A Retrospective Review of the Management of Lung Cancer Patients Referred into the Regional Neuro-Oncology Pathway in Merseyside, United Kingdom
Authors: Heseltine Jonathan , Corte Ana , Kennedy Oliver , Sharples Harry , Brodbelt Andrew , Mehta Shaveta 
Published: October 2022

Abstract

AIMS
Brain metastases (BMs) are common in lung cancer and carry adverse prognostic significance. Such occurrences should be reviewed through a regional specialist neuro-oncology MDT. Our aim is to highlight which aspects of the pathway could be contributing to delays in the treatment of lung cancer patients with BMs.

METHOD
All lung cancer patients discussed at the Neuro-Oncology MDT in 2020 were identified. Details of the patient journey through the pathway from diagnosis to death were obtained from the Orion System, regional PACS system, regional neuro-oncology MDT notes and electronic case notes from Clatterbridge.

RESULTS
Full datasets were available for 100 patients discussed at the Neuro-Oncology MDT. 49 of these were patients presenting with BMs and lung cancer synchronously. Only 5 out of 13 (38%) of synchronous patients recommended for SRS received this treatment. 7 of 13 patients received a suboptimal treatment (best supportive care or whole-brain radiotherapy). Length of time from neuro-oncology MDT discussion to receiving SRS in the synchronous cohort was 47 versus 20.3 days in the asynchronous group. A review of all 13 cases found that 4 of the 7 cases of CNS-specific deterioration were potentially preventable. Further analysis of these cases revealed common themes of lengthy delays in histological sampling (9), delayed referral or discussion in the appropriate MDT (8) and not jointly referring to neuro-oncology and respiratory oncology (7).

CONCLUSION
Lung cancer patients with synchronous BMs receive SRS after full staging and biopsy. There is potential evidence of suboptimal outcomes due to inflexible MDT systems and delays for histology.
A Comparative Proteomic Analysis of the Cell Membrane of Histone 3 Mutated Paediatric High-Grade Gliomas in order to Identify Potential Immunotherapeutic Targets
Authors: Haque Farhana 
Published: October 2022

Abstract

AIMS
Improvements in the treatments for childhood and adolescent brain tumours, High-Grade Glioma (pHGG) and Diffuse Intrinsic Pontine Glioblastoma (DIPG), have not advanced much and they continue to carry a very poor prognosis. These brain tumours are now defined by mutations affecting histone 3 proteins, indeed 80% of DIPGs harbour histone H3.1 and H3.3 K27M somatic mutations whilst 30% of pHGGs exhibit H3.3 G34R or G34V mutations. We hypothesized that the histone 3 mutant tumours will have distinct mutation specific surfactome or cell surface proteins. We analysed the cell surface proteomics of H3.3 G34V and G34R mutated high-grade glioma in comparison to the H3 wild-type Glioma, to explore whether these proteins have the potential to be used as immunotherapeutic targets.

METHOD
We have at first isolated the cell membrane fractions from a range of patient cells carrying histone 3 mutations (G34R, G34V) relative to wild type histone 3. A comparative quantitative liquid chromatographic mass- spectrometry analyses of these cell surface membrane fractions were performed to identify specific targetable factors.

RESULTS
The results of these were analysed with the focus in identifying proteins that can be targeted for tumour specific immune modulation or immunotherapeutic intervention.

CONCLUSION
Results of these analyses will be presented.