Lay Wai Khin

National University of Singapore, Tumasik, Singapore

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Publications (7)29.72 Total impact

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    ABSTRACT: Histone deacetylases (HDACs) are enzymes involved in transcriptional repression. We aimed to examine the significance of HDAC1 and HDAC2 gene expression in the prediction of recurrence and survival in 156 patients with hepatocellular carcinoma (HCC) among a South East Asian population who underwent curative surgical resection in Singapore. We found that HDAC1 and HDAC2 were upregulated in the majority of HCC tissues. The presence of HDAC1 in tumor tissues was correlated with poor tumor differentiation. Notably, HDAC1 expression in adjacent non-tumor hepatic tissues was correlated with the presence of satellite nodules and multiple lesions, suggesting that HDAC1 upregulation within the field of HCC may contribute to tumor spread. Using competing risk regression analysis, we found that increased cancer-specific mortality was significantly associated with HDAC2 expression. Mortality was also increased with high HDAC1 expression. In the liver cancer cell lines, HEP3B, HEPG2, PLC5, and a colorectal cancer cell line, HCT116, the combined knockdown of HDAC1 and HDAC2 increased cell death and reduced cell proliferation as well as colony formation. In contrast, knockdown of either HDAC1 or HDAC2 alone had minimal effects on cell death and proliferation. Taken together, our study suggests that both HDAC1 and HDAC2 exert pro-survival effects in HCC cells, and the combination of isoform-specific HDAC inhibitors against both HDACs may be effective in targeting HCC to reduce mortality.
    Oncology Reports 09/2015; DOI:10.3892/or.2015.4263 · 2.30 Impact Factor
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    ABSTRACT: One of the well-studied epidemiological phenomena of anterior cruciate ligament (ACL) injuries is the 2- to 9-fold increase in the relative risk of ACL rupture in female athletes compared with male athletes. However, the influence of patient sex on the outcome after ACL reconstruction remains unclear, with some authors reporting inferior outcomes in females and others noting no significant difference. To provide a comprehensive systematic review and meta-analysis to examine the possible association between patient sex and the subjective and objective outcomes after ACL reconstruction. This study was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. All studies that reported clinical outcomes after ACL reconstruction in males and females independently were included in the review. A quantitative random-effects meta-analysis was performed to compare outcomes between sexes. For outcomes with considerable heterogeneity, meta-regression was used to identify potential moderators. Articles were evaluated qualitatively when quantitative data were not reported. A total of 135 publications were included in the review. Females had inferior outcomes in instrumented laxity (standardized mean difference [SMD], 0.24; 95% CI, 0.11-0.37), revision rate (relative risk [RR], 1.15; 95% CI, 1.02-1.28), Lysholm score (SMD, -0.33; 95% CI, -0.55 to -0.11), Tegner activity scale (SMD, -0.37; 95% CI, -0.49 to -0.24), and incidence of not returning to sports (RR, 1.12; 95% CI, 1.04-1.21), all of which were statistically significant. Other outcomes were comparable between sexes, including anterior drawer test, Lachman test, pivot-shift test, timed single-legged hop test, single-legged hop test, quadriceps testing, hamstring testing, extension loss, flexion loss, development of cyclops lesion, and International Knee Documentation Committee (IKDC) knee examination score. Females and males were equally likely to develop anterior knee pain and osteoarthritis after ACL reconstruction. The graft rupture and graft failure rates did not differ significantly between sexes. There were comparable or inferior results for females compared with males in all outcomes analyzed. No statistically significant sex difference was identified in most of the objective parameters. However, subjective and functional outcomes, including Lysholm score, Tegner activity scale, and ability to return to sports, have been shown to be poorer in females. © 2015 The Author(s).
    The American Journal of Sports Medicine 03/2015; DOI:10.1177/0363546515573008 · 4.36 Impact Factor
  • Linqi Yang · Bee-Choo Tai · Lay Wai Khin · Swee Chye Quek
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    ABSTRACT: Advances in interventional techniques now allow for transcatheter treatment of some ventricular septal defects (VSD), although there remain concerns about adverse events. We performed a systematic review to look at outcomes and complications associated with transcatheter closure of VSD. A PubMed search for series in English on device closure of VSD from 2003 to June 2012 was performed. We excluded small series that were included in multicenter studies and patients who had acquired VSD following myocardial infarction. The random effects model was used to obtain pooled estimates of success and complications. A total of 37 publications comprising 4,406 patients with VSD (perimembranous = 3,758, muscular = 419, intracristal = 47, doubly committed subarterial = 36, multiple = 16, postsurgical = 123, unclassified = 7) were included in this analysis. The age of patients ranged from 3 days to 84 years. The pooled estimate of successful device implantation was 96.6% (95% CI: 95.7-97.5). The most common complication is residual shunt (pooled estimated 25.5%; 95% CI: 18.9-32.1). Others included valvular defects (pooled estimate 4.9%; 95% CI: 3.4-6.4) and arrhythmias (pooled estimate 10.6%; 95% CI: 8.4-12.7). Our analysis suggests that transcatheter device closure of VSD is safe and yields good results. The limitations of this study are difficulties in analyzing different devices individually, and segregating the different VSD types. Further stratification by type of VSD, age of patients, and prevention of complications is needed before this can be recommended for routine treatment.
    Journal of Interventional Cardiology 04/2014; 27(3). DOI:10.1111/joic.12121 · 1.18 Impact Factor
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    ABSTRACT: Objectives: The underlying mechanism for amphotericin B-induced acute kidney injury (AKI) remains poorly understood and may be immunologically mediated. We assessed whether the development of nephrotoxicity is linked to a distinct cytokine profile in patients receiving amphotericin B deoxycholate (AmBD). Patients and methods: In 58 patients who received AmBD, circulating serum interleukin (IL)-6, IL-8 and IL-10 were measured at baseline, week 1 and week 2 of antifungal treatment and correlated to the development of renal impairment. The Cox proportional hazards model approach was adopted for analysis. Results: The P value was 0.026 for the overall effect of IL-6 on time to development of AKI. An increasing or non-receding IL-6 trend by week 1 of AmBD treatment (followed by a decreasing or non-receding IL-6 trend from week 1 to week 2) correlated with an increased likelihood of nephrotoxicity [hazard ratio (HR) 6.93, P value 0.005 and HR 3.46, P value 0.035, respectively]. Similarly, persistently increasing IL-8 levels were linked to a 3.84-fold increased likelihood of AKI. Conclusions: In patients receiving AmBD, persistence of an elevated pro-inflammatory cytokine milieu is associated with a predisposition to drug-related kidney injury.
    Journal of Antimicrobial Chemotherapy 04/2013; 68(7). DOI:10.1093/jac/dkt055 · 5.31 Impact Factor
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    ABSTRACT: Lymph node ratio (LNR, i.e. the ratio of the number of positive nodes to the total number of nodes excised) is reported to be superior to the absolute number of nodes involved (pN stage) in classifying patients at high versus low risk of death following breast cancer. The added prognostic value of LNR over pN in addition to other prognostic factors has never been assessed. All patients diagnosed with lymph node positive, non-metastatic invasive breast cancer at the National University Hospital (Singapore) and University of Malaya Medical Center (Kuala Lumpur) between 1990-2007 were included (n = 1589). Overall survival of the patients was estimated by the Kaplan Meier method for LNR [categorized as low (>0 and <0.2), intermediate (0.2-0.65) and high (>0.65-1)] and pN staging [pN1, pN2 and pN3]. Adjusted overall relative mortality risks associated with LNR and pN were calculated by Cox regression. The added prognostic value of LNR over pN was evaluated by comparing the discriminating capacity (as indicated by the c statistic) of two multivariate models, one including pN and one including LNR. LNR was superior to pN in categorizing mortality risks for women ≥60 years, those with ER negative or grade 3 tumors. In combination with other factors (i.e. age, treatment, grade, tumor size and receptor status), substituting pN by LNR did not result in better discrimination of women at high versus low risk of death, neither for the entire cohort (c statistic 0.72 [0.70-0.75] and 0.73 [0.71-0.76] respectively for pN versus LNR), nor for the subgroups mentioned above. In combination with other prognosticators, substitution of pN by LNR did not provide any added prognostic value for South East Asian breast cancer patients.
    PLoS ONE 09/2012; 7(9):e45809. DOI:10.1371/journal.pone.0045809 · 3.23 Impact Factor
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    ABSTRACT: The monitoring and prediction of treatment responses to invasive aspergillosis (IA) are difficult. We determined whether serum galactomannan index (GMI) trends early in the course of disease may be useful in predicting eventual clinical outcomes. For the subjects recruited into the multicenter Global Aspergillosis Study, serial GMIs were measured at baseline and at weeks 1, 2, and 4 following antifungal treatment. Clinical response and survival at 12 weeks were the outcome measures. GMI trends were analyzed by using the generalized estimation equation approach. GMI cutoffs were evaluated by using receiver-operating curve analyses incorporating pre- and posttest probabilities. Of the 202 study patients diagnosed with IA, 71 (35.1%) had a baseline GMI of ≥ 0.5. Week 1 GMI was significantly lower for the eventual responders to treatment at week 12 than for the nonresponders (GMIs of 0.62 ± 0.12 and 1.15 ± 0.22, respectively; P = 0.035). A GMI reduction of >35% between baseline and week 1 predicted a probability of a satisfactory clinical response. For IA patients with pretreatment GMIs of <0.5 (n = 131; 64.9%), GMI ought to remain low during treatment, and a rising absolute GMI to >0.5 at week 2 despite antifungal treatment heralded a poor clinical outcome. Here, every 0.1-unit increase in the GMI between baseline and week 2 increased the likelihood of an unsatisfactory clinical response by 21.6% (P = 0.018). In summary, clinical outcomes may be anticipated by charting early GMI trends during the first 2 weeks of antifungal therapy. These findings have significant implications for the management of IA.
    Journal of clinical microbiology 05/2012; 50(7):2330-6. DOI:10.1128/JCM.06513-11 · 3.99 Impact Factor
  • Cancer Research 04/2012; 72(8 Supplement):2460-2460. DOI:10.1158/1538-7445.AM2012-2460 · 9.33 Impact Factor