Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
474
result(s) for
"Yu, Kelly J."
Sort by:
The new voices of science fiction
\"Your Future Is Bright! After all, your mother is a robot, your father has joined the alien hive mind, and your dinner will be counterfeit 3D-printed steak. Even though your worker bots have staged a mutiny, and your tour guide speaks only in memes, you can always sell your native language if you need some extra cash.\" -- From publisher's description.
Book
Whole-Exome Sequencing of Nasopharyngeal Carcinoma Families Reveals Novel Variants Potentially Involved in Nasopharyngeal Carcinoma
Genetic susceptibility is likely involved in nasopharyngeal carcinoma (NPC), a cancer caused by Epstein-Barr virus (EBV) infection. Understanding of genetic factors involved in NPC and how they contribute to EBV-induced carcinogenesis is limited. We conducted whole-exome capture/sequencing among 251 individuals from 97 multiplex families from Taiwan (205 affected, 21 obligate carriers, and 25 unaffected) using SeqCap EZ Human Exome Library v3.0 and Illumina HiSeq. Aligned sequences were filtered to identify likely-to-be-functional deleterious variants that co-segregated with disease. Ingenuity Pathway analysis was performed. Circulating magnesium levels were measured in 13 individuals in 2 families with NIPAL1 mutations and in 197 sporadic NPC cases and 237 controls. We identified variants in 12 genes likely involved in cancer pathogenesis, viral infection or immune responses to infection. These included genes postulated to be involved in magnesium transport (NIPAL1), EBV cell entry (ITGB6), modulation of EBV infection (BCL2L12, NEDD4L), telomere biology (CLPTM1L, BRD2, HNRNPU), modulation of cAMP signaling (RAPGEF3), DNA repair (PRKDC, MLH1), and Notch signaling (NOTCH1, DLL3). Pathway based analysis demonstrated enrichment for Notch signaling genes (p-value = 0.0006). Evaluation of individuals within NIPAL1 families suggested lower serum magnesium in NPC compared to unaffected members. A significant reduction in serum magnesium levels was observed among sporadic NPC cases compared to controls (7.1% NPC/1.7% controls below normal range; OR = 4.5; 95% CI = 1.4,14) and is consistent with findings demonstrating a role for magnesium channeling in T-cell responses to EBV. We identified novel genes associated with NPC that point to new areas of inquiry to better understand genetic factors that determine the fate of viral infections and/or otherwise predisposes to NPC.
Journal Article
Lowered Risk of Nasopharyngeal Carcinoma and Intake of Plant Vitamin, Fresh Fish, Green Tea and Coffee: A Case-Control Study in Taiwan
A case-control study was conducted to evaluate the role of adult diet on nasopharyngeal carcinoma (NPC) in Taiwan.
A total of 375 incident NPC cases and 327 controls matched to the cases on sex, age, and residence were recruited between July 1991 and December 1994. A structured questionnaire inquiring complete dietary history, socio-demographic characteristics, and other potential confounding factors was used in the personal interview. Unconditional logistic regression analysis was used to estimate multivariate-adjusted odds ratio (OR(adj)) with 95% confidence interval (CI) after accounting for known risk factors.
Fresh fish (OR(adj), 0.56; 95% CI, 0.38-0.83 for the highest vs. lowest tertile of intake), green tea (OR(adj), 0.61; 95% CI, 0.40-0.91 for drinking ≥1 times/week vs. never) and coffee (OR(adj), 0.56; 95% CI, 0.37-0.85 for drinking ≥0.5 times/week vs. never) were inversely associated with the NPC risk. No association with NPC risk was observed for the intake of meats, salted fish, fresh vegetables, fruits and milk. Intake of vitamin A from plant sources was associated with a decreased NPC risk (OR(adj), 0.62; 95% CI, 0.41-0.94 for the highest vs. lowest tertile).
The study findings suggest that certain adult dietary patterns might protect against the development of NPC.
Journal Article
Characterization of the humoral immune response to the EBV proteome in extranodal NK/T-cell lymphoma
Extranodal natural killer/T-cell lymphoma (NKTCL) is an aggressive malignancy that has been etiologically linked to Epstein-Barr virus (EBV) infection, with EBV gene transcripts identified in almost all cases. However, the humoral immune response to EBV in NKTCL patients has not been well characterized. We examined the antibody response to EBV in plasma samples from 51 NKTCL cases and 154 controls from Hong Kong and Taiwan who were part of the multi-center, hospital-based AsiaLymph case–control study. The EBV-directed serological response was characterized using a protein microarray that measured IgG and IgA antibodies against 202 protein sequences representing the entire EBV proteome. We analyzed 157 IgG antibodies and 127 IgA antibodies that fulfilled quality control requirements. Associations between EBV serology and NKTCL status were disproportionately observed for IgG rather than IgA antibodies. Nine anti-EBV IgG responses were significantly elevated in NKTCL cases compared with controls and had ORs
highest vs. lowest tertile
> 6.0 (Bonferroni-corrected
P
-values < 0.05). Among these nine elevated IgG responses in NKTCL patients, three IgG antibodies (all targeting EBNA3A) are novel and have not been observed for other EBV-associated tumors of B-cell or epithelial origin. IgG antibodies against EBNA1, which have consistently been elevated in other EBV-associated tumors, were not elevated in NKTCL cases. We characterize the antibody response against EBV for patients with NKTCL and identify IgG antibody responses against six distinct EBV proteins. Our findings suggest distinct serologic patterns of this NK/T-cell lymphoma compared with other EBV-associated tumors of B-cell or epithelial origin.
Journal Article
Assessing T-cell responses to Epstein-Barr virus in individuals at risk for nasopharyngeal carcinoma
Background
Elevated Epstein-Barr virus (EBV) antibody levels are associated with risk of nasopharyngeal carcinoma (NPC) and risk scores based on these antibodies can predict NPC risk with high accuracy. The immune mechanisms underlying this association remain unclear. We evaluated whether individuals with elevated EBV-NPC antibody risk scores had a reduced T-cell response to EBV proteins within a NPC multiplex family study in Taiwan.
Methods
In total, 79 cancer-free individuals from families with a history of NPC had blood tested for (i) EBV antibodies using a multiplex serology assay and (ii) T-cell responses to 7 EBV proteins (EBNA1, LMP1, LMP2, BZLF1, BRLF1, BARF1, gp350) using interferon-γ ELISPOT.
Results
Excluding individuals with low phytohemagglutinin proliferative responses, no statistically significant association was observed between lower EBV T-cell responses and higher EBV antibody-based NPC risk scores (
P
= 0.21). However, our findings did trend in the a-priori hypothesized direction, with lower EBV T-cell responses noted among those with higher EBV antibody-based NPC risk scores. Compared to individuals who responded to at least 3 EBV-specific T-cell peptide pools by ELISPOT, those who responded to 1–2 peptide pools had a 10% increased risk of having an EBV-NPC risk score above the median value (OR = 1.1; 95% CI = 0.3, 4.5) and those who responded to none had a 3-fold increased risk (OR = 3.0; 95% CI = 0.6, 17).
Conclusions
Our study is the first to evaluate whether high EBV antibody responses observed among individuals at risk of NPC are associated with reduced T-cell responses to EBV. Our findings suggest such an association but require replication in larger studies.
Journal Article
Evaluation of Human Leukocyte Antigen-A (HLA-A), Other Non-HLA Markers on Chromosome 6p21 and Risk of Nasopharyngeal Carcinoma
The association between human leukocyte antigen (HLA) genes (located in the Major Histocompatibility Complex [MHC] region of chromosome 6p21) and NPC has been known for some time. Recently, two genome-wide association studies (GWAS) conducted in Taiwan and China confirmed that the strongest evidence for NPC association was mapped to the MHC region. It is still unclear, however, whether these findings reflect direct associations with Human Leukocyte Antigen (HLA) genes and/or to other genes in this gene-rich region.
To better understand genetic associations for NPC within the MHC region of chromosome 6, we conducted an evaluation that pooled two previously conducted NPC case-control studies in Taiwan (N = 591 cases and N = 521 controls). PCR-based genotyping was performed for 12 significant SNPs identified within 6p21 in the Taiwan NPC GWAS and for the HLA-A gene (exons 2 and 3).
After confirming homogeneity between the two studies, pooled odds ratios (OR) and 95% confidence intervals (CI) were estimated by logistic regression. We found that HLA-A (p-trend = 0.0006) and rs29232 (within the GABBR1 gene; p-trend = 0.005) were independent risk factors for NPC after adjustment for age, gender, study and each other. NPC risk was highest among individuals who were homozygous for the HLA-A*0207 risk allele and carriers of the rs29232 risk allele (A).
Our study suggests that most of the SNPs significantly associated with NPC from GWAS reflect previously identified HLA-A associations. An independent effect of rs29232 (GABBR1), however, remained, suggesting that additional genes within this region might be associated with NPC risk.
Journal Article
Pancreatic cancer among solid organ transplant recipients in the United States
Introduction
Pancreatic cancer (PC) in solid organ transplant (SOT) recipients is not well studied. Some PC cases may be incidentally detected during hepatobiliary imaging.
Methods
We evaluated PC among 374,106 SOT recipients during 1995–2017 in the United States using linked data from the national transplant registry and multiple state/regional cancer registries. Standardized incidence ratios (SIRs) were used to compare PC risk in recipients to the general population. We used multivariate Poisson regression to identify independent risk factors for PC. We assessed survival after PC diagnosis using Kaplan–Meier curves and log-rank tests.
Results
SOT recipients had elevated incidence for PC compared with the general population (SIR 1.40, 95% CI 1.29–1.52), and this increase was strongest in liver recipients (1.65, 1.41–1.92). Among all recipients, PC incidence was especially increased for cases arising in the head of the pancreas (SIR 1.50, 95% CI 1.34–1.68) and for cases diagnosed at localized stage (1.85, 1.37–2.44). Among SOT recipients, factors independently associated with increased incidence were consistent with those in general population including male sex, older age, non-O blood type, and history of diabetes. Additionally, compared to other organ recipients, liver transplant recipients had higher PC incidence (adjusted incidence rate ratio 1.28; 95% CI 1.06–1.54). Overall survival after PC diagnosis was poor (median 4 months) and similar between liver and other organ transplant recipients (
p
= 0.08).
Conclusions
PC incidence is elevated among SOT recipients, and more commonly diagnosed in liver transplant recipients perhaps related to incidental detection. However, survival is poor even in liver recipients, arguing against routine PC screening.
Journal Article
Patterns of Interindividual Variability in the Antibody Repertoire Targeting Proteins Across the Epstein-Barr Virus Proteome
Little is known about variation in antibody responses targeting the full spectrum of Epstein-Barr virus (EBV) proteins and how such patterns inform disease risk.
We used a microarray to measure immunoglobulin G (IgG) and immunoglobulin A (IgA) antibody responses against 199 EBV protein sequences from 5 EBV strains recovered from 289 healthy adults from Taiwan. We described positivity patterns, estimated the correlation between antibodies, and investigated the associations between environmental and genetic risk factors and variations in antibody responses.
Healthy adults were more likely to mount IgG antibody responses to EBV proteins (median positivity frequency, 46.5% for IgG and 17.3% for IgA; P = 1.6 × 10-46, by the Wilcoxon rank sum test). Responses against glycoproteins were particularly prevalent. The correlations between antibody responses of the same class were higher than correlations across classes. The mucosal exposure to proteins involved in EBV reactivation (as determined by the IgA response) was associated with smoking (P = .002, by the sequence kernel association test-combined), and approximately one quarter of adults displayed antibody responses associated with EBV-related cancer risk.
These data comprehensively define the variability in human IgG and IgA antibody responses to the EBV proteome. Patterns observed can serve as the foundation for elucidating which individuals are at highest risk of EBV-associated clinical conditions and for identifying targets for effective immunodiagnostic tests.
Journal Article
Evaluation of Total and IgA-Specific Antibody Targeting Epstein-Barr Virus Glycoprotein 350 and Nasopharyngeal Carcinoma Risk
We previously reported that higher levels of antibody targeting Epstein-Barr virus (EBV) glycoprotein350 (gp350), an EBV vaccine candidate, were protective against nasopharyngeal carcinoma (NPC) in genetically high-risk families from Taiwan. The current study attempted to extend this association to a general population cohort.
We compared total and IgA-specific gp350 antibody levels in 35 incident NPC cases and 81 disease-free controls from the Cancer Screening Program in Taiwan (23943 individuals recruited 1991-1992). Luciferase immunoprecipitation assays quantified gp350 antibody.
Total EBVgp350 antibody levels were not higher in individuals who remained disease free compared to those who developed NPC (P = .11). This lack of a protective gp350 association persisted for cases diagnosed ≥5 years (odds ratio [OR] = 1.05; P = .91) and <5 years (OR = 1.85; P = .40) after blood draw. IgA-specific gp350 antibody levels were higher in cases than controls (OR = 7.03; P = .001). This increased risk was most pronounced for cases diagnosed <5 years after blood draw (OR = 11.7; P = .004).
Unlike our prior findings in those with a strong family history of NPC, total gp350 antibody levels were not protective against NPC development in this general population setting.
Journal Article
Association Between Antibodies That Bind Epstein-Barr Virus (EBV) gp350 and gH/gL and Shedding of EBV in Saliva From Nasopharyngeal Carcinoma Multiplex Family Members in Taiwan
Abstract
Elevated levels of Epstein-Barr virus (EBV) gp350 and gH/gL antibodies have been associated with a lower risk of developing nasopharyngeal carcinoma (NPC), although the evidence remains inconclusive and unexplained. We conducted a longitudinal study within a high-risk Taiwanese cohort, analyzing total immunoglobulin against EBV-gp350 and -gH/gL in blood and EBV DNA shedding in saliva. Contrary to our hypothesis—that elevated levels of antibodies previously shown to be associated with a lower NPC risk should result in a decrease in EBV shedding in saliva—higher anti-gp350 antibodies at baseline were significantly associated with detectable EBV DNA in saliva at follow-up (odds ratio [OR], 1.99 [95% confidence interval {CI}, 1.03–3.97]; P = .04). Higher anti-EBV-gH/gL antibodies at baseline were not significantly associated with risk of detectable EBV DNA at follow-up (OR, 0.69 [95% CI, .35–1.32]; P = .26). These findings underscore the complexity of virus–host interactions and emphasize the need for further investigations into their role in EBV-associated diseases.
Journal Article