Browsing by Author "Xu, X"

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    Antiviral inhibitory capacity of CD8+ T cells predicts the rate of CD4+ T-cell decline in HIV-1 infection.
    (J Infect Dis, 2012-08-15) Yang, H; Wu, H; Hancock, G; Clutton, G; Sande, N; Xu, X; Yan, H; Huang, X; Angus, B; Kuldanek, K; Fidler, S; Denny, TN; Birks, J; McMichael, A; Dorrell, L
    BACKGROUND: Rare human immunodeficiency virus type 1 (HIV-1)-infected individuals who maintain control of viremia without therapy show potent CD8+ T-cell-mediated suppression of viral replication in vitro. Whether this is a determinant of the rate of disease progression in viremic individuals is unknown. METHODS: We measured CD8+ T-cell-mediated inhibition of a heterologous HIV-1 isolate in 50 HIV-1-seropositive adults with diverse progression rates. Linear mixed models were used to determine whether CD8+ T-cell function could explain variation in the rate of CD4+ T-cell decline. RESULTS: There was a significant interaction between CD8+ T-cell antiviral activity in vitro and the rate of CD4+ T-cell decline in chronically infected individuals (P < .0001). In a second prospective analysis of recently infected subjects followed for up to 3 years, CD8+ T-cell antiviral activity strongly predicted subsequent CD4+ T-cell decline (P < .0001) and explained up to 73% of the interindividual variation in the CD4+ T-cell slope. In addition, it was inversely associated with viral load set point (r = -0.68 and P = .002). CONCLUSIONS: The antiviral inhibitory capacity of CD8+ T cells is highly predictive of CD4+ T-cell loss in early HIV-1 infection. It has potential as a benchmark of effective immunity in vaccine evaluation.
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    Evidence that SOX2 overexpression is oncogenic in the lung.
    (PLoS One, 2010-06-10) Lu, Y; Futtner, C; Rock, JR; Xu, X; Whitworth, W; Hogan, BL; Onaitis, MW
    BACKGROUND: SOX2 (Sry-box 2) is required to maintain a variety of stem cells, is overexpressed in some solid tumors, and is expressed in epithelial cells of the lung. METHODOLOGY/PRINCIPAL FINDINGS: We show that SOX2 is overexpressed in human squamous cell lung tumors and some adenocarcinomas. We have generated mouse models in which Sox2 is upregulated in epithelial cells of the lung during development and in the adult. In both cases, overexpression leads to extensive hyperplasia. In the terminal bronchioles, a trachea-like pseudostratified epithelium develops with p63-positive cells underlying columnar cells. Over 12-34 weeks, about half of the mice expressing the highest levels of Sox2 develop carcinoma. These tumors resemble adenocarcinoma but express the squamous marker, Trp63 (p63). CONCLUSIONS: These findings demonstrate that Sox2 overexpression both induces a proximal phenotype in the distal airways/alveoli and leads to cancer.
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    Genetic variants in the folate metabolic pathway genes predict melanoma-specific survival.
    (The British journal of dermatology, 2020-01-18) Dai, W; Liu, H; Liu, Y; Xu, X; Qian, D; Luo, S; Cho, E; Zhu, D; Amos, CI; Fang, S; Lee, JE; Li, X; Nan, H; Li, C; Wei, Q
    BACKGROUND:Folate metabolism plays an important role in DNA methylation and nucleic acid synthesis and thus may function as a regulatory factor in cancer development. Genome-wide association studies (GWAS) have identified some single-nucleotide polymorphisms (SNPs) associated with cutaneous melanoma-specific survival (CMSS), but no SNPs were found in genes involved in the folate metabolic pathway. OBJECTIVE:To examine associations between SNPs in folate metabolic pathway genes and CMSS. METHODS:We comprehensively evaluated 2,645 (422 genotyped and 2,223 imputed) common SNPs in folate metabolic pathway genes from a published GWAS of 858 patients from The University of Texas M.D. Anderson Cancer Center and performed the validation in another GWAS of 409 patients from the Nurses' Health Study and Health Professionals Follow-up Study, in which 95/858 (11.1%) and 48/409 (11.5%) patients died of cutaneous melanoma, respectively. RESULTS:We identified two independent SNPs (MTHFD1 rs1950902 G>A and ALPL rs10917006 C>T) to be associated with CMSS in both datasets, and their meta-analysis yielded an allelic hazards ratio of 1.75 (95% confidence interval=1.32-2.32, P=9.96×10-5 ) and 2.05 (1.39-3.01, P=2.84×10-4 ), respectively. The genotype-phenotype correlation analyses provided additional support for biologic plausibility of these two variants' roles in tumour progression, suggesting that variation in SNP-related mRNA expression levels is likely to be the mechanism underlying the observed associations with CMSS. CONCLUSION:Two possibly functional genetic variants, MTHFD1 rs1950902 and ALPL rs10917006, were likely to be independently or jointly associated with CMSS, which may add to personalized treatment in the future, once further validated.
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    ItemOpen Access
    The antiviral inhibitory capacity of CD8+T cells predicts the rate of CD4+cell decline in HIV-1 infection
    (HIV MEDICINE, 2012-04) Yang, H; Wu, H; Hancock, G; Clutton, G; Sande, N; Xu, X; Yan, H-P; Huang, X; Angus, B; Kuldanek, K; Fidler, S; Denny, T; Birks, J; McMichael, A; Dorrell, L