LIVIVO - Search results -

Search results

Result 1 - 10 of total 30

Search options

Article ; Online: Transcription Profile and Pathway Analysis of the Endocannabinoid Receptor Inverse Agonist AM630 in the Core and Infiltrative Boundary of Human Glioblastoma Cells

Gareth Williams / David Chambers / Ruman Rahman / Francisco Molina-Holgado

Molecules, Vol 27, Iss 2049, p

2022 Volume 2049

Abstract: Background: We have previously reported that the endocannabinoid receptor inverse agonist AM630 is a potent inhibitor of isocitrade dehydrogenase-1 wild-type glioblastoma (GBM) core tumour cell proliferation. To uncover the mechanism behind the anti- ... ...

Abstract	Background: We have previously reported that the endocannabinoid receptor inverse agonist AM630 is a potent inhibitor of isocitrade dehydrogenase-1 wild-type glioblastoma (GBM) core tumour cell proliferation. To uncover the mechanism behind the anti-tumour effects we have performed a transcriptional analysis of AM630 activity both in the tumour core cells (U87) and the invasive margin cells (GIN-8), the latter representing a better proxy of post-surgical residual disease. Results: The core and invasive margin cells exhibited markedly different gene expression profiles and only the core cells had high expression of a potential AM630 target, the CB1 receptor. Both cell types had moderate expression of the HTR2B serotonin receptor, a reported AM630 target. We found that the AM630 driven transcriptional response was substantially higher in the central cells than in the invasive margin cells, with the former driving the up regulation of immune response and the down regulation of cell cycle and metastatic pathways and correlating with transcriptional responses driven by established anti-neoplastics as well as serotonin receptor antagonists. Conclusion: Our results highlight the different gene sets involved in the core and invasive margin cell lines derived from GBM and an associated marked difference in responsiveness to AM630. Our findings identify AM630 as an anti-neoplastic drug in the context of the core cells, showing a high correlation with the activity of known antiproliferative drugs. However, we reveal a key set of similarities between the two cell lines that may inform therapeutic intervention.
Keywords	brain cancer ; glioblastoma ; CB2 cannabinoid receptor ; gene expression ; Organic chemistry ; QD241-441
Subject code	570
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Neurodegenerative Disease Associated Pathways in the Brains of Triple Transgenic Alzheimer’s Model Mice Are Reversed Following Two Weeks of Peripheral Administration of Fasudil

Richard Killick / Christina Elliott / Elena Ribe / Martin Broadstock / Clive Ballard / Dag Aarsland / Gareth Williams

International Journal of Molecular Sciences, Vol 24, Iss 11219, p

2023 Volume 11219

Abstract: The pan Rho-associated coiled-coil-containing protein kinase (ROCK) inhibitor fasudil acts as a vasodilator and has been used as a medication for post-cerebral stroke for the past 29 years in Japan and China. More recently, based on the involvement of ... ...

Abstract	The pan Rho-associated coiled-coil-containing protein kinase (ROCK) inhibitor fasudil acts as a vasodilator and has been used as a medication for post-cerebral stroke for the past 29 years in Japan and China. More recently, based on the involvement of ROCK inhibition in synaptic function, neuronal survival, and processes associated with neuroinflammation, it has been suggested that the drug may be repurposed for neurodegenerative diseases. Indeed, fasudil has demonstrated preclinical efficacy in many neurodegenerative disease models. To facilitate an understanding of the wider biological processes at play due to ROCK inhibition in the context of neurodegeneration, we performed a global gene expression analysis on the brains of Alzheimer’s disease model mice treated with fasudil via peripheral IP injection. We then performed a comparative analysis of the fasudil-driven transcriptional profile with profiles generated from a meta-analysis of multiple neurodegenerative diseases. Our results show that fasudil tends to drive gene expression in a reverse sense to that seen in brains with post-mortem neurodegenerative disease. The results are most striking in terms of pathway enrichment analysis, where pathways perturbed in Alzheimer’s and Parkinson’s diseases are overwhelmingly driven in the opposite direction by fasudil treatment. Thus, our results bolster the repurposing potential of fasudil by demonstrating an anti-neurodegenerative phenotype in a disease context and highlight the potential of in vivo transcriptional profiling of drug activity.
Keywords	Alzheimer’s disease ; Parkinson’s disease ; transcriptional profiling ; fasudil ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	570
Language	English
Publishing date	2023-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Book ; Online: Using the SARS Infection Transcriptional Signature to Identify Potential Treatments for Covid-19

Richard Killick / Clive Ballard / Patrick Doherty / Gareth Williams

2020

Abstract: Gene expression data associated with viral infection of human cell lines is harnessed to define a conserved viral response signature. Drugs that tend to drive gene expression in the direction of the cellular viral response are significantly enriched for ... ...

Abstract	Gene expression data associated with viral infection of human cell lines is harnessed to define a conserved viral response signature. Drugs that tend to drive gene expression in the direction of the cellular viral response are significantly enriched for those with established antiviral activity. Transcription therefore facilitates a simple and effective filtering of candidate drugs to be put forward for bioassay validation.
Keywords	Bioinformatics and Computational Biology ; gene expression arrays ; virues ; covid19
Publishing date	2020-05-20T09:40:42Z
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Utilisation of semiconductor sequencing for the detection of predictive biomarkers in glioblastoma.

Gareth Williams / Alexander Llewelyn / Robert Thatcher / Keeda-Marie Hardisty / Marco Loddo

PLoS ONE, Vol 17, Iss 3, p e

2022 Volume 0245817

Abstract: The standard treatment for glioblastoma involves a combination of surgery, radiation and chemotherapy but have limited impact on survival. The exponential increase in targeted agents directed at pivotal oncogenic pathways now provide new therapeutic ... ...

Abstract	The standard treatment for glioblastoma involves a combination of surgery, radiation and chemotherapy but have limited impact on survival. The exponential increase in targeted agents directed at pivotal oncogenic pathways now provide new therapeutic opportunities for this tumour type. However, lack of comprehensive precision oncology testing at diagnosis means such therapeutic opportunities are potentially overlooked. To investigate the role of semiconductor sequencing for detection of predictive biomarkers in routine glioblastoma samples we have undertaken analysis of test trending data generated by a clinically validated next generation sequencing platform designed to capture actionable genomic variants distributed across 505 genes. Analysis was performed across a cohort of 55 glioblastoma patients. Analysis of trending data has revealed a complex and rich actionable mutational landscape in which 166 actionable mutations were detected across 36 genes linked to 17 off label targeted therapy protocols and 111 clinical trials. The majority of patients harboured three or more actionable mutations affecting key cancer related regulatory networks including the PI3K/AKT/MTOR and RAS/RAF/MEK/MAPK signalling pathways, DNA-damage repair pathways and cell cycle checkpoints. Linkage with immunotherapy and PARP inhibitors was identified in 44% of glioblastoma patients as a consequence of alterations in DNA-damage repair genes. Taken together our data indicates that precision oncology testing utilising semiconductor sequencing can be used to identify a broad therapeutic armamentarium of targeted therapies and immunotherapies that can be potentially employed for the improved clinical management of glioblastoma patients.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Utilisation of semiconductor sequencing for detection of actionable fusions in solid tumours.

Marco Loddo / Keeda-Marie Hardisty / Alexander Llewelyn / Tiffany Haddow / Robert Thatcher / Gareth Williams

PLoS ONE, Vol 17, Iss 8, p e

2022 Volume 0246778

Abstract: Oncogenic fusions represent compelling druggable targets in solid tumours highlighted by the recent site agnostic FDA approval of larotrectinib for NTRK rearrangements. However screening for fusions in routinely processed tissue samples is constrained ... ...

Abstract	Oncogenic fusions represent compelling druggable targets in solid tumours highlighted by the recent site agnostic FDA approval of larotrectinib for NTRK rearrangements. However screening for fusions in routinely processed tissue samples is constrained due to degradation of nucleic acid as a result of formalin fixation., To investigate the clinical utility of semiconductor sequencing optimised for detection of actionable fusion transcripts in formalin fixed samples, we have undertaken an analysis of test trending data generated by a clinically validated next generation sequencing platform designed to capture 867 of the most clinically relevant druggable driver-partner oncogenic fusions. Here we show across a real-life cohort of 1112 patients with solid tumours that actionable fusions occur at high frequency (7.4%) with linkage to a wide range of targeted therapy protocols including seven fusion-drug matches with FDA/EMA approval and/or NCCN/ESMO recommendations and 80 clinical trials. The more prevalent actionable fusions identified were independent of tumour type in keeping with signalling via evolutionary conserved RAS/RAF/MEK/ERK, PI3K/AKT/MTOR, PLCy/PKC and JAK/STAT pathways. Taken together our data indicates that semiconductor sequencing for detection of actionable fusions can be integrated into routine diagnostic pathology workflows enabling the identification of personalised treatment options that have potential to improve clinical cancer management across many tumour types.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article: A stochastic approach to model chemical looping combustion

Schnellmann, Matthias A / Gareth Williams / John S. Dennis

Powder technology. 2019 Mar. 02,

2019

Abstract: A stochastic model is presented of two coupled fluidised-bed reactors with a steady circulation of particles between them. The particles undergo reaction in each fluidised bed. The model uniquely accounts for the full conversion history of particles as ... ...

Abstract	A stochastic model is presented of two coupled fluidised-bed reactors with a steady circulation of particles between them. The particles undergo reaction in each fluidised bed. The model uniquely accounts for the full conversion history of particles as they are circulated. Chemical looping combustion (CLC) is an example of such a process. We have previously used the model, in a general form, to understand the sensitivity of a CLC process to factors such as the nature of the gas-solid reactions or the residence time distribution of the particles in the reactors. To demonstrate that the stochastic model is also valuable for simulating and optimising specific configurations of CLC, it is applied in this paper to simulate CLC with methane as the fuel gas, conducted in a laboratory-scale circulating fluidised bed. Under the operating conditions of the circulating fluidised bed, it was found that the oxidation and reduction reactions were limited by the intrinsic chemical kinetics of the oxygen carrier particles. It was possible to conduct experiments in a packed bed reactor for reduction and a thermogravimetric analyser for oxidation where the reaction was also limited by the intrinsic chemical kinetics. This enabled a single particle model, for inclusion in the stochastic model, to be developed independently of the experiments in the circulating fluidised bed. The resulting stochastic model was able to simulate the performance of the circulating fluidised bed with reasonable accuracy.
Keywords	combustion ; fluidized beds ; fuels ; methane ; models ; oxygen ; powders ; reaction kinetics ; stochastic processes ; thermogravimetry
Language	English
Dates of publication	2019-0302
Size	p. .
Publishing place	Elsevier B.V.
Document type	Article
Note	Pre-press version
ISSN	0032-5910
DOI	10.1016/j.powtec.2019.03.004
Database	NAL-Catalogue (AGRICOLA)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Targeted repositioning identifies drugs that increase fibroblast growth factor 20 production and protect against 6-hydroxydopamine-induced nigral cell loss in rats

Edward J. R. Fletcher / Aran D. Jamieson / Gareth Williams / Patrick Doherty / Susan Duty

Scientific Reports, Vol 9, Iss 1, Pp 1-

2019 Volume 9

Abstract: Abstract Endogenous fibroblast growth factor 20 (FGF20) supports maintenance of dopaminergic neurones within the nigrostriatal pathway. Moreover, direct intracerebral infusion of FGF20 protects against nigrostriatal tract loss in the 6-hydroxydopamine ... ...

Abstract	Abstract Endogenous fibroblast growth factor 20 (FGF20) supports maintenance of dopaminergic neurones within the nigrostriatal pathway. Moreover, direct intracerebral infusion of FGF20 protects against nigrostriatal tract loss in the 6-hydroxydopamine lesion rat model of Parkinson’s disease. Increasing endogenous FGF20 production might provide a less-invasive, more translational way of providing such protection. Accordingly, we adopted a targeted repositioning approach to screen for candidate FDA-approved drugs with potential to enhance endogenous FGF20 production in brain. In silico interrogation of the Broad Institute’s Connectivity Map database (CMap), revealed 50 candidate drugs predicted to increase FGF20 transcription, 16 of which had profiles favourable for use in Parkinson’s disease. Of these, 11 drugs were found to significantly elevate FGF20 protein production in MCF-7 cells, between two- and four-fold. Four drugs were selected for examination in vivo. Following oral dosing in rats for 7 days, salbutamol and triflusal, but not dimethadione or trazodone, significantly elevated FGF20 levels in the nigrostriatal tract. Preliminary examination in the unilateral 6-hydroxydopamine-lesioned rat revealed a modest but significant protection against nigral cell loss with both drugs. Our data demonstrate the power of targeted repositioning as a method to identify existing drugs that may combat disease progression in Parkinson’s by boosting FGF20 levels.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2019-06-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: New N^C^N-coordinated Pd(ii) and Pt(ii) complexes of a tridentate N-heterocyclic carbene ligand featuring a 6-membered central ring: synthesis, structures and luminescence.

Moussa, Jamal / Haddouche, Kamel / Chamoreau, Lise-Marie / Amouri, Hani / Gareth Williams, J A

Dalton transactions (Cambridge, England : 2003)

2016 Volume 45, Issue 32, Page(s) 12644–12648

Abstract: We describe Pd(ii) and Pt(ii) complexes of an N^C^N-coordinating pincer-like ligand featuring two lateral pyridine rings and a 6-membered carbene core. Their crystal structures display 1-dimensional chains with short π-π and M(ii)M(ii) interactions. Such ...

Abstract	We describe Pd(ii) and Pt(ii) complexes of an N^C^N-coordinating pincer-like ligand featuring two lateral pyridine rings and a 6-membered carbene core. Their crystal structures display 1-dimensional chains with short π-π and M(ii)M(ii) interactions. Such interactions also impact on the photophysical properties, with the Pt(ii) complex being luminescent in the solid state at room temperature.
Language	English
Publishing date	2016-08-09
Publishing country	England
Document type	Journal Article
ZDB-ID	1472887-4
ISSN	1477-9234 ; 1364-5447 ; 0300-9246 ; 1477-9226
ISSN (online)	1477-9234 ; 1364-5447
ISSN	0300-9246 ; 1477-9226
DOI	10.1039/c6dt02415g
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: The UK Foundation Programme for newly qualified doctors

David Stephen Lawrence / Christopher Gareth Williams

Revista Brasileira de Medicina de Família e Comunidade, Vol 9, Iss

a SWOT analysis

2014 Volume 30

Abstract: Introduction: After completing a five year undergraduate degree, all newly qualified doctors in the United Kingdom undertake a two-year Foundation Programme which aims to provide them with the necessary experience, supervision and guidance to prepare ... ...

Abstract	Introduction: After completing a five year undergraduate degree, all newly qualified doctors in the United Kingdom undertake a two-year Foundation Programme which aims to provide them with the necessary experience, supervision and guidance to prepare them for a career in clinical medicine. Foundation Doctors are paid members of the team and undertake a variety of clinical rotations with supervision from senior colleagues, a process that is regulated by a UK Foundation Programme Office. Objective: This paper aims to provide a reflective analysis of this programme to greater inform the international audience. Methods: A critical reflective analysis utilising the SWOT format (Strength, Weaknesses, Opportunities and Threats), conducted by two Foundation Doctors working in the UK. Results and Discussion: We identified a well-established programme which enabled graduates to gain a broad range of clinical experience as a paid doctor but one with considerable variation at both individual and group level. Long-standing shortcomings of being a junior-doctor including long hours and excessive paperwork were still prevalent. We highlighted potential opportunities and threats within the current system, some of which were dependent upon larger political systems governing the NHS in the UK. Conclusion: The Foundation Programme is a robust approach to the training and development of early career doctors. Further research and a deeper international dialogue on the best-practice in this field is needed.
Keywords	Health Human Resource Training ; Physicians ; Junior ; Education ; Medical ; Great Britain ; Medicine (General) ; R5-920 ; Public aspects of medicine ; RA1-1270
Subject code	300
Language	English
Publishing date	2014-01-01T00:00:00Z
Publisher	Sociedade Brasileira de Medicina de Família e Comunidade
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article: Development of Suitable CuO-Based Materials Supported on Al2O3, MgAl2O4, and ZrO2 for Ca/Cu H2 Production Process

Díez-Martín, Laura / Andrew Scullard / Gareth Williams / Gemma Grasa / Ramón Murillo

Industrial & engineering chemistry process design and development. 2018 Feb. 28, v. 57, no. 8

2018

Abstract: Functional materials for the sorption enhanced reforming process for H2 production coupled to a Cu/CuO chemical loop have been synthesized. The performance of CuO-based materials supported on Al2O3, MgAl2O4, and ZrO2 and synthesized by different routes ... ...

Abstract	Functional materials for the sorption enhanced reforming process for H2 production coupled to a Cu/CuO chemical loop have been synthesized. The performance of CuO-based materials supported on Al2O3, MgAl2O4, and ZrO2 and synthesized by different routes has been analyzed. Highly stable materials supported on Al2O3 or MgAl2O4 synthesized by coprecipitation and mechanical mixing with sufficient Cu loads (around 65% wt) have been successfully developed. However, it has been found that coprecipitation under these conditions is not a suitable route for ZrO2. Spray-drying and deposition precipitation did not provide the best chemical features to the materials. As the Ca/Cu process is operated in fixed bed reactors, the best candidates were pelletized and their stability was again assessed. Pellets with high chemical and mechanical stability, high oxygen transport capacity, and good mechanical properties have been finally obtained by coprecipitation. The good homogeneity that provides this route would allow an easy scaling up.
Keywords	aluminum oxide ; calcium ; coprecipitation ; cupric oxide ; hydrogen ; hydrogen production ; mechanical properties ; mixing ; oxygen ; pellets ; process design ; sorption ; spray drying ; zirconium oxide
Language	English
Dates of publication	2018-0228
Size	p. 2890-2904.
Publishing place	American Chemical Society
Document type	Article
ZDB-ID	1484436-9
ISSN	1520-5045 ; 0888-5885
ISSN (online)	1520-5045
ISSN	0888-5885
DOI	10.1021/acs.iecr.7b05103
Database	NAL-Catalogue (AGRICOLA)

Order via subito

To top

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

Order via subito