Publications by authors named "Lucy Hamilton"

3 Publications

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Single-Cell Analyses of Prostate Cancer Liquid Biopsies Acquired by Apheresis.

Clin Cancer Res 2018 11 9;24(22):5635-5644. Epub 2018 Aug 9.

Division of Clinical Studies, The Institute of Cancer Research, London, United Kingdom.

Circulating tumor cells (CTCs) have clinical relevance, but their study has been limited by their low frequency. We evaluated liquid biopsies by apheresis to increase CTC yield from patients suffering from metastatic prostate cancer, allow precise gene copy-number calls, and study disease heterogeneity. Apheresis was well tolerated and allowed the separation of large numbers of CTCs; the average CTC yield from 7.5 mL of peripheral blood was 167 CTCs, whereas the average CTC yield per apheresis (mean volume: 59.5 mL) was 12,546 CTCs. Purified single CTCs could be isolated from apheresis product by FACS sorting; copy-number aberration (CNA) profiles of 185 single CTCs from 14 patients revealed the genomic landscape of lethal prostate cancer and identified complex intrapatient, intercell, genomic heterogeneity missed on bulk biopsy analyses. Apheresis facilitated the capture of large numbers of CTCs noninvasively with minimal morbidity and allowed the deconvolution of intrapatient heterogeneity and clonal evolution. .
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http://dx.doi.org/10.1158/1078-0432.CCR-18-0862DOI Listing
November 2018

Halting of Caspase Activity Protects Tau from MC1-Conformational Change and Aggregation.

J Alzheimers Dis 2016 10;54(4):1521-1538

Lilly Research Centre, Windlesham, Surrey, UK.

Intracellular neurofibrillary tangles (NFTs) are the hallmark of Alzheimer's disease and other tauopathies in which tau, a microtubule-associated protein, loses its ability to stabilize microtubules. Several post-translational modifications including phosphorylation and truncation increase tau's propensity to aggregate thus forming NFTs; however, the mechanisms underlying tau conformational change and aggregation still remain to be defined. Caspase activation and subsequent proteolytic cleavage of tau is thought to be a potential trigger of this disease-related pathological conformation. The aim of this work was to investigate the link between caspase activation and a disease-related conformational change of tau in a neuroblastoma cell-based model of spontaneous tau aggregation. We demonstrated that caspase induction initiates proteolytic cleavage of tau and generation of conformationally altered and aggregated tau recognized by the MC1 conformational antibody. Most importantly, these events were shown to be attenuated with caspase inhibitors. This implies that therapeutics aimed at inhibiting caspase-mediated tau cleavage may prove beneficial in slowing cleavage and aggregation, thus potentially halting tau pathology and disease progression.
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http://dx.doi.org/10.3233/JAD-150960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5088409PMC
October 2016

The effect of a specialist seating assessment clinic on the skin management of individuals with spinal cord injury.

J Tissue Viability 2003 Jul;13(3):122-5

National Spinal Injuries Centre, University of Oxford.

Objective: To evaluate the specialist seating clinic's effectiveness in improving skin management knowledge and independence, represented by the Needs Assessment Checklist (NAC).

Design: Longitudinal, between subjects design, with two intervention groups and one control.

Setting: Tertiary care, spinal cord injury centre (National Spinal Injuries Centre), Stoke Mandeville Hospital, United Kingdom.

Method: This study assessed the skin management ability of three groups. Group 1 consisted of individuals who had attended a specialist seating assessment (SSA) clinic before their first needs assessment, group 2 had attended SSA between their first and second needs assessment, and group 3 (control) had not attended at all. Patient skin management ability was assessed using the skin management subscale of the NAC, a measure of rehabilitation outcome, at two time points.

Results: Significant differences were identified between group 3 and group 1 at both the first (t = 2.36, degrees of freedom (df) = 37, p < 0.05) and second (t = 2.84, df = 37, p < 0.01) needs assessment. Significant improvements were also observed within each group between the first and second needs assessment time points in all seating assessment categories.

Conclusion: Skin management achievement scores were significantly higher for patients who had attended a SSA clinic before their first NAC (group 1) at both time points, supporting the use of SSA as a proactive intervention to improve patient independence, knowledge and awareness, and potentially reduce pressure ulcer incidence.
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http://dx.doi.org/10.1016/s0965-206x(03)80017-7DOI Listing
July 2003