ORCID Profile
0000-0003-1107-0365
Current Organisations
University of Oxford
,
Imperial College London
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Publisher: American Association for Cancer Research (AACR)
Date: 14-02-2013
DOI: 10.1158/1078-0432.CCR-12-2880
Abstract: Purpose: Endoscopic surveillance of Barrett's esophagus is problematic because dysplasia/early-stage neoplasia is frequently invisible and likely to be missed because of s ling bias. Molecular abnormalities may be more diffuse than dysplasia. The aim was therefore to test whether DNA methylation, especially on imprinted and X-chromosome genes, is able to detect dysplasia/early-stage neoplasia. Experimental design: 27K methylation arrays were used to find genes best able to differentiate between 22 Barrett's esophagus and 24 esophageal adenocarcinoma (EAC) s les. These were validated using pyrosequencing on a retrospective cohort (60 Barrett's esophagus, 36 dysplastic, and 90 EAC) and then in a prospective multicenter study (98 Barrett's esophagus patients, including 28 dysplastic and 9 early EAC) designed to utilize biomarkers to stratify patients according to their prevalent dysplasia/EAC status. Results: Genes (23%) on the array, including 7% of X-linked and 69% of imprinted genes, have shown statistically significant changes in methylation in EAC versus Barrett's esophagus (Wilcoxon P & 0.05). 6/7 selected candidate genes were successfully internally (Pearson's P & 0.01) and externally validated (ANOVA P & 0.001). Four genes (SLC22A18, PIGR, GJA12, and RIN2) showed the greatest area under curve (0.988) to distinguish between Barrett's esophagus and dysplasia/EAC in the retrospective cohort. This methylation panel was able to stratify patients from the prospective cohort into three risk groups based on the number of genes methylated (low risk: & genes, intermediate: 2, and high: & ). Conclusion: Widespread DNA methylation changes were observed in Barrett's carcinogenesis including ≈70% of known imprinted genes. A four-gene methylation panel stratified patients with Barrett's esophagus into three risk groups with potential clinical utility. Clin Cancer Res 19(4) 878–88. ©2012 AACR.
Publisher: Oxford University Press (OUP)
Date: 07-03-2019
DOI: 10.1093/CID/CIY1107
Abstract: Typhoid fever illnesses are responsible for more than 100 000 deaths worldwide each year. In Bangladesh, typhoid fever is endemic, with incidence rates between 292–395 per 100 000 people annually. While considerable effort has been made to improve access to clean water and sanitation services in the country, there is still a significant annual typhoid burden, which particularly affects children. A typhoid conjugate vaccine (Vi-TCV) was recently prequalified by the World Health Organization and recommended for use, and offers the potential to greatly reduce the typhoid burden in Bangladesh. This study is a double-blind, cluster-randomized, controlled trial of Vi-TCV in a geographically defined area in Dhaka, Bangladesh. At least 32 500 children from 9 months to & years of age will be vaccinated and followed for 2 years to assess the effectiveness and safety of Vi-TCV in a real-world setting. All cluster residents will also be followed to measure the indirect effect of Vi-TCV in this community. This protocol has been approved by the International Centre for Diarrhoeal Disease Research, Bangladesh a University of Oxford research review and both ethical review committees. Informed written consent and assent will be obtained before enrollment. Vi-TCV has been shown to be safe and effective in previous, smaller-scale studies. The results of this study will be shared through a series of peer-reviewed journal articles. The findings will also be disseminated to the local government, stakeholders within the community, and the population within which the study was conducted. This trial is the largest and only cluster-randomized control trial of Vi-TCV ever conducted, and will describe the effectiveness of Vi-TCV in an endemic population. The results of this trial may provide important evidence to support the introduction of TCVs in countries with a high burden of typhoid. ISRCTN11643110.
Publisher: Elsevier BV
Date: 03-2023
Publisher: Public Library of Science (PLoS)
Date: 26-12-2019
Publisher: Springer Science and Business Media LLC
Date: 13-10-2013
DOI: 10.1038/NG.2796
Publisher: BMJ
Date: 10-04-2015
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 Xinxue Liu.