4 results on '"Ian Dick"'
Search Results
2. Prognostic significance of pleural effusion exhausted CD8+ T cell subsets in non-small cell lung cancer and mesothelioma
- Author
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Linda Ye, Ian Dick, Peter Chiang, Tina Firth, Jenette Creaney, Bruce WS Robinson, and Alec Redwood
- Subjects
Cancer Research ,Oncology - Abstract
e21111 Background: Following repeated tumor antigen stimulation, T cells lose functional capacity and become exhausted. T cell exhaustion is a progressive change in phenotype. Early in the pathway, stem-like exhausted T cells (Texstem) retain proliferative and cytotoxic potential. However, they differentiate into terminally exhausted T cells (Texterm) that become epigenetically fixed in a suppressed state and lose much of their effector function. Malignant pleural effusion is a peri-tumoral microenvironment that could offer insight into anti-tumor immune responses. In this study we characterized exhausted CD8+ T cells, examined the prognostic significance of Texstem and Texterm levels in the pleural effusions of patients with non-small cell lung cancer (NSCLC) and validated our findings in a mesothelioma cohort. Methods: Pre-treatment malignant pleural effusions from 43 NSCLC (41 non-squamous and 2 squamous) and 50 mesothelioma patients were analyzed by flow cytometry. The percentages of Texstem (PD1midCD39- or PD1midCD39-CD28+) and Texterm (PD1hi CD39+) CD8+ T cells were correlated with overall survival (OS). Survival analysis was performed using Kaplan-Meier and multivariate Cox regression analysis adjusting for age, sex, histological and molecular subtypes, performance status, smoking history, comorbidities and the number of lines of systemic therapy. Results: The relative percentages of exhausted T cells within the CD8+ T cell compartment of pleural effusions from NSCLC and mesothelioma were similar (Table). In NSCLC patients, multivariate analysis demonstrated that the percentage of Texstem was an independent predictor of OS. The median OS for patients with high (above median) Texstem was significantly longer than those with low Texstem (9.9 vs 3.4 months, HR 0.398, p = 0.020). In addition, the ratio of Texstem to Texterm also showed a positive association with OS. Similarly, in mesothelioma patients, a greater percentage of Texstem was associated with longer OS in multivariate analysis (p = 0.049). The median OS for patients with high vs low Texstem was 33.5 vs 11.1 months (HR 0.302, 95% CI 0.129 – 0.705, p = 0.006). In addition, there was also a positive association between Texstem to Texterm ratio and OS. Conversely, Texterm CD8+ T cells did not impact OS in either cancer type. Conclusions: NSCLC and mesothelioma patients with greater abundance of pleural effusion stem-like exhausted CD8+ T cells exhibit better survival outcomes irrespective of patient and disease characteristics, supporting its role as a prognostic biomarker.[Table: see text]
- Published
- 2022
3. Uptake of severe acute respiratory syndrome coronavirus 2 spike protein mediated by angiotensin converting enzyme 2 and ganglioside in human cerebrovascular cells
- Author
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Conor McQuaid, Alexander Solorzano, Ian Dickerson, and Rashid Deane
- Subjects
brain endothelial cells ,brain pericytes ,brain vascular smooth muscle cells ,COVID-19 ,SARS-CoV-2 variants of interest and lipid raft ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
IntroductionThere is clinical evidence of neurological manifestations in coronavirus disease-19 (COVID-19). However, it is unclear whether differences in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/spike protein (SP) uptake by cells of the cerebrovasculature contribute to significant viral uptake to cause these symptoms.MethodsSince the initial step in viral invasion is binding/uptake, we used fluorescently labeled wild type and mutant SARS-CoV-2/SP to study this process. Three cerebrovascular cell types were used (endothelial cells, pericytes, and vascular smooth muscle cells), in vitro.ResultsThere was differential SARS-CoV-2/SP uptake by these cell types. Endothelial cells had the least uptake, which may limit SARS-CoV-2 uptake into brain from blood. Uptake was time and concentration dependent, and mediated by angiotensin converting enzyme 2 receptor (ACE2), and ganglioside (mono-sialotetrahexasylganglioside, GM1) that is predominantly expressed in the central nervous system and the cerebrovasculature. SARS-CoV-2/SPs with mutation sites, N501Y, E484K, and D614G, as seen in variants of interest, were also differentially taken up by these cell types. There was greater uptake compared to that of the wild type SARS-CoV-2/SP, but neutralization with anti-ACE2 or anti-GM1 antibodies was less effective.ConclusionThe data suggested that in addition to ACE2, gangliosides are also an important entry point of SARS-CoV-2/SP into these cells. Since SARS-CoV-2/SP binding/uptake is the initial step in the viral penetration into cells, a longer exposure and higher titer are required for significant uptake into the normal brain. Gangliosides, including GM1, could be an additional potential SARS-CoV-2 and therapeutic target at the cerebrovasculature.
- Published
- 2023
- Full Text
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4. Self-sampling to identify pathogens and inflammatory markers in patients with acute sore throat: Feasibility study
- Author
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Mark Lown, Elizabeth A. Miles, Helena L. Fisk, Kirsten A. Smith, Ingrid Muller, Emma Maund, Kirsty Rogers, Taeko Becque, Gail Hayward, Michael Moore, Paul Little, Margaret Glogowska, Alastair D. Hay, Beth Stuart, Efi Mantzourani, Chris Butler, Jennifer Bostock, Firoza Davies, Ian Dickerson, Natalie Thompson, and Nick Francis
- Subjects
sore throat diagnosis ,inflammatory markers ,swabs ,saliva ,infection ,Immunologic diseases. Allergy ,RC581-607 - Abstract
IntroductionSore throat is a common reason for overuse of antibiotics. The value of inflammatory or biomarkers in throat swab or saliva samples in predicting benefit from antibiotics is unknown.MethodsWe used the ‘person-based approach’ to develop an online tool to support self-swabbing and recruited adults and children with sore throats through participating general practices and social media. Participants took bacterial and viral swabs and a saliva sponge swab and passive drool sample. Bacterial swabs were cultured for streptococcus (Group A, B, C, F and G). The viral swab and saliva samples were tested using a routine respiratory panel PCR and Covid-19 PCR testing. We used remaining viral swab and saliva sample volume for biomarker analysis using a panel of 13 biomarkers.ResultsWe recruited 11 asymptomatic participants and 45 symptomatic participants. From 45 symptomatic participants, bacterial throat swab, viral throat swab, saliva sponge and saliva drool samples were returned by 41/45 (91.1%), 43/45 (95.6%), 43/45 (95.6%) and 43/45 (95.6%) participants respectively. Three saliva sponge and 6 saliva drool samples were of insufficient quantity. Two adult participants had positive bacterial swabs. Six participants had a virus detected from at least one sample (swab or saliva). All of the biomarkers assessed were detectable from all samples where there was sufficient volume for testing. For most biomarkers we found higher concentrations in the saliva samples. Due to low numbers, we were not able to compare biomarker concentrations in those who did and did not have a bacterial pathogen detected. We found no evidence of a difference between biomarker concentrations between the symptomatic and asymptomatic participants but the distributions were wide.ConclusionsWe have demonstrated that it is feasible for patients with sore throat to self-swab and provide saliva samples for pathogen and biomarker analysis. Typical bacterial and viral pathogens were detected but at low prevalence rates. Further work is needed to determine if measuring biomarkers using oropharyngeal samples can help to differentiate between viral and bacterial pathogens in patients classified as medium or high risk using clinical scores, in order to better guide antibiotic prescribing and reduce inappropriate prescriptions.
- Published
- 2022
- Full Text
- View/download PDF
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