ORCID Profile
0000-0001-7254-2333
Current Organisations
University of Birmingham
,
University Of Strathclyde
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Publisher: MDPI AG
Date: 15-04-2017
Publisher: Springer Science and Business Media LLC
Date: 11-02-2019
DOI: 10.1007/S00262-019-02307-X
Abstract: Adoptive cell therapy using autologous tumor-infiltrating lymphocytes (TIL) has shown significant clinical benefit, but is limited by toxicities due to a requirement for post-infusion interleukin-2 (IL-2), for which high dose is standard. To assess a modified TIL protocol using lower dose IL-2, we performed a single institution phase II protocol in unresectable, metastatic melanoma. The primary endpoint was response rate. Secondary endpoints were safety and assessment of immune correlates following TIL infusion. Twelve metastatic melanoma patients were treated with non-myeloablative lymphodepleting chemotherapy, TIL, and low-dose subcutaneous IL-2 (125,000 IU/kg/day, maximum 9-10 doses over 2 weeks). All but one patient had previously progressed after treatment with immune checkpoint inhibitors. No unexpected adverse events were observed, and patients received an average of 6.8 doses of IL-2. By RECIST v1.1, two patients experienced a partial response, one patient had an unconfirmed partial response, and six had stable disease. Biomarker assessment confirmed an increase in IL-15 levels following lymphodepleting chemotherapy as expected and a lack of peripheral regulatory T-cell expansion following protocol treatment. Interrogation of the TIL infusion product and monitoring of the peripheral blood following infusion suggested engraftment of TIL. In one responding patient, a population of T cells expressing a T-cell receptor Vβ chain that was dominant in the infusion product was present at a high percentage in peripheral blood more than 2 years after TIL infusion. This study shows that this protocol of low-dose IL-2 following adoptive cell transfer of TIL is feasible and clinically active. (ClinicalTrials.gov identifier NCT01883323.).
Publisher: Spandidos Publications
Date: 31-12-2015
DOI: 10.3892/OL.2015.4069
Publisher: Springer Science and Business Media LLC
Date: 12-10-2022
DOI: 10.1007/S00432-022-04391-6
Abstract: Extracellular vesicles (EV) secreted from cancer cells are present in various biological fluids, carrying distinctly different cellular components compared to normal cells, and have great potential to be used as markers for disease initiation, progression, and response to treatment. This under-utilised tool provides insights into a better understanding of prostate cancer. EV from serum and urine of healthy men and castration-resistant prostate cancer (CRPC) patients were isolated and characterised by transmission electron microscopy, particle size analysis, and western blot. Proteomic and cholesterol liquid chromatography-mass spectrometry (LC–MS) analyses were conducted. There was a successful enrichment of small EV/exosomes isolated from serum and urine. EV derived from biological fluids of CRPC patients had significant differences in composition when compared with those from healthy controls. Analysis of matched serum and urine s les from six prostate cancer patients revealed specific EV proteins common in both types of biological fluid for each patient. Some of the EV proteins identified from our analyses have potential to be used as CRPC markers. These markers may depict a pattern in cancer progression through non-invasive s le collection.
Publisher: Elsevier BV
Date: 08-2019
Abstract: Despite the completion of numerous phase II studies, a standard of care treatment has yet to be defined for metastatic uveal melanoma (mUM). To determine benchmarks of progression free survival (PFS) and overall survival (OS), we carried out a meta-analysis using in idual patient level trial data. In idual patient variables and survival outcomes were requested from 29 trials published from 2000 to 2016. Univariable and multivariable analysis were carried out for prognostic factors. The variability between trial arms and between therapeutic agents on PFS and OS was investigated. OS data were available for 912 patients. The median PFS was 3.3 months (95% CI 2.9-3.6) and 6-month PFS rate was 27% (95% CI 24-30). Univariable analysis showed male sex, elevated (i.e. > versus ≤ upper limit of normal) lactate dehydrogenase (LDH), elevated alkaline phosphatase (ALP) and diameter of the largest liver metastasis (≥3 cm versus <3 cm) to be substantially associated with shorter PFS. Multivariable analysis showed male sex, elevated LDH and elevated ALP were substantially associated with shorter PFS. The most substantial factors associated with 6-month PFS rate, on both univariable and multivariable analysis were elevated LDH and ALP. The median OS was 10.2 months (95% CI 9.5-11.0) and 1 year OS was 43% (95% CI 40-47). The most substantial prognostic factors for shorter OS by univariable and multivariable analysis were elevated LDH and elevated ALP. Patients treated with liver directed treatments had statistically significant longer PFS and OS. Benchmarks of 6-month PFS and 1-year OS rates were determined accounting for prognostic factors. These may be used to facilitate future trial design and stratification in mUM.
Publisher: Public Library of Science (PLoS)
Date: 02-02-2017
Publisher: Elsevier BV
Date: 10-2017
Abstract: Immune checkpoint inhibitor (ICI) monoclonal antibodies (mAbs) targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1) or its ligand (PD-L1) produce unique toxicity profiles. The objective of this review was to identify patterns and incidence of immune-related adverse events (irAE) based on tumour type and ICI class. Medline, EMBASE and COCHRANE databases were searched to identify prospective monotherapy trials of ICIs from 2003 to November 2015. Paired reviewers selected studies for inclusion and extracted data. Odds ratio (OR), χ2 tests and multivariable regression models were used to analyse for effect size and associations. We identified 48 trials (6938 patients), including 26 CTLA-4, 17 PD-1, 2 PD-L1 trials, and 3 studies tested both CTLA-4 and PD-1. Grade 3/4 irAE were more common with CTLA-4 mAbs compared with PD-1 (31% versus 10%). All grades colitis (OR 8.7, 95% CI 5.8-12.9), hypophysitis (OR 6.5, 95% CI 3.0-14.3) and rash (OR 2.0, 95% CI 1.8-2.3) were more frequent with CTLA-4 mAbs whereas pneumonitis (OR 6.4, 95% CI 3.2-12.7), hypothyroidism (OR 4.3, 95% CI 2.9-6.3), arthralgia (OR 3.5, 95% CI 2.6-4.8) and vitiligo (OR 3.5, 95% CI 2.3-5.3) were more common with PD-1 mAbs. Comparison of irAE from the three most studied tumour types in PD-1 mAbs trials [melanoma (n = 2048), non-small-cell lung cancer (n = 1030) and renal cell carcinoma (n = 573)] showed melanoma patients had a higher frequency of gastrointestinal and skin irAE and lower frequency of pneumonitis. CTLA-4 and PD-1 mAbs have distinct irAE profiles. Different immune microenvironments may drive histology-specific irAE patterns. Other tumour-dependent irAE profiles may be identified as data emerge from ICI trials.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2018
Publisher: Springer Science and Business Media LLC
Date: 04-10-2016
DOI: 10.1038/BJC.2016.308
Publisher: Springer Science and Business Media LLC
Date: 13-01-2016
Publisher: American Association for Cancer Research (AACR)
Date: 29-02-2016
DOI: 10.1158/2326-6066.CIR-15-0186
Abstract: Anti–PD-1 inhibitors have significant activity in metastatic melanoma. Responses often occur early and may be sustained. The optimal duration of treatment with these agents is unknown. Here, we report the case of a 51-year-old woman treated with pembrolizumab, as part of the Keynote-001 trial, as first-line treatment for metastatic disease. She experienced a complete response after 13.8 months of treatment with no adverse events. One month after the last drug infusion and 18 months from starting treatment, the patient presented with eosinophilic fasciitis. She then developed acute confusion and weakness, thought to be due to intracranial vasculitis. High-dose steroids were initiated with resolution of the fasciitis. Aspirin was commenced for presumed vasculitis with resolution of the neurologic symptoms. To our knowledge, there are no previous reports of eosinophilic fasciitis or cerebral vasculitis due to anti–PD-1 agents. This case demonstrates that toxicity may occur in association with pembrolizumab treatment after a prolonged period of treatment without toxicity. Future trials should explore the optimal duration of treatment with pembrolizumab. Cancer Immunol Res 4(3) 175–8. ©2016 AACR.
Publisher: MDPI AG
Date: 08-03-2022
DOI: 10.3390/JMSE10030388
Abstract: The decarbonisation of waterborne transport is arguably the biggest challenge faced by the maritime industry presently. By 2050, the International Maritime Organization (IMO) aims to reduce greenhouse gas emissions from the shipping industry by 50% compared to 2008, with a vision to phase out fossil fuels by the end of the century as a matter of urgency. To meet such targets, action must be taken immediately to address the barriers to adopt the various clean shipping options currently at different technological maturity levels. Green hydrogen as an alternative fuel presents an attractive solution to meet future targets from international bodies and is seen as a viable contributor within a future clean shipping vision. The cost of hydrogen fuel—in the short-term at least—is higher compared to conventional fuel therefore, energy-saving devices (ESDs) for ships are more important than ever, as implementation of rules and regulations restrict the use of fossil fuels while promoting zero-emission technology. However, existing and emerging ESDs in standalone/combination for traditional fossil fuel driven vessels have not been researched to assess their compatibility for hydrogen-powered ships, which present new challenges and considerations within their design and operation. Therefore, this review aims to bridge that gap by firstly identifying the new challenges that a hydrogen-powered propulsion system brings forth and then reviewing the quantitative energy saving capability and qualitive additional benefits of in idual existing and emerging ESDs in standalone and combination, with recommendations for the most applicable ESD combinations with hydrogen-powered waterborne transport presented to maximise energy saving and minimise the negative impact on the propulsion system components. In summary, the most compatible combination ESDs for hydrogen will depend largely on factors such as vessel types, routes, propulsion, operation, etc. However, the mitigation of load fluctuations commonly encountered during a vessels operation was viewed to be a primary area of interest as it can have a negative impact on hydrogen propulsion system components such as the fuel cell therefore, the ESD combination that can maximise energy savings as well as minimise the fluctuating loads experienced would be viewed as the most compatible with hydrogen-powered waterborne transport.
Publisher: Wiley
Date: 29-09-2016
DOI: 10.1002/CAM4.878
Publisher: Elsevier BV
Date: 05-2015
Publisher: BMJ
Date: 12-2014
Publisher: MDPI AG
Date: 08-2015
DOI: 10.3747/CO.22.2418
Abstract: The approval of ipilimumab [...]
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Yunxin Xu.