Publications by authors named "Wing-Ki Chan"

6 Publications

  • Page 1 of 1

X-chromosome inactivation and PCDH19-associated epileptic encephalopathy: A novel PCDH19 variant in a Chinese family.

Clin Chim Acta 2021 Oct 28;521:285-288. Epub 2021 Jul 28.

Kowloon West Cluster Laboratory Genetic Service, Chemical Pathology Laboratory, Department of Pathology, Princess Margaret Hospital, Hong Kong Special Administrative Region, China. Electronic address:

Background: Developmental and epileptic encephalopathy 9 (DEE9, MIM #300088) is an early onset seizure disorder associated with cognitive impairment and behavioral disturbances. It is caused by mutation in protocadherin 19 with an unusual X-linked inheritance selectively involving heterozygous females or mosaic hemizygous males, while hemizygous males are unaffected. Cellular interference was the postulated mechanism underlying the unusual inheritance pattern.

Case Report: We report a Chinese girl who presented with severe treatment refractory seizures at 26 months of age and was found heterozygous for a novel likely pathogenic missense variant NM_001184880.2:c.488T>A p.(Val163Glu) in PCDH19. Her younger sister, who was also heterozygous for the variant, was asymptomatic with normal development at the time of reporting at 37 months of age. X-chromosome inactivation study by androgen receptor gene methylation assay in DNA from peripheral leukocytes was performed which demonstrated somewhat skewed X-chromosome inactivation in the proband and extremely skewed X-chromosome inactivation in the asymptomatic younger sibling.

Conclusion: PCDH19-related seizure disorder has incomplete penetrance and variable expressivity. Further studies are required to determine the potential role of X-chromosome inactivation on the phenotypic variability and patient outcomes. Liberal referral for PCDH19 testing among female patients with early-onset seizures should be considered to enhance case detection.
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http://dx.doi.org/10.1016/j.cca.2021.07.023DOI Listing
October 2021

A nuclear transport inhibitor that modulates the unfolded protein response and provides in vivo protection against lethal dengue virus infection.

J Infect Dis 2014 Dec 5;210(11):1780-91. Epub 2014 Jun 5.

Nuclear Signaling Laboratory, Department of Biochemistry and Molecular Biology, Monash University.

Background: Dengue virus (DENV) is estimated to cause 390 million infections each year, but there is no licensed vaccine or therapeutic currently available.

Methods: We describe a novel, high-throughput screen to identify compounds inhibiting the interaction between DENV nonstructural protein 5 and host nuclear transport proteins. We document the antiviral properties of a lead compound against all 4 serotypes of DENV, antibody-dependent enhanced (ADE) infection, and ex vivo and in vivo DENV infections. In addition, we use quantitative reverse-transcription polymerase chain reaction to examine cellular effects upon compound addition.

Results: We identify N-(4-hydroxyphenyl) retinamide (4-HPR) as effective in protecting against DENV-1-4 and DENV-1 ADE infections, with 50% effective concentrations in the low micromolar range. 4-HPR but not the closely related N-(4-methoxyphenyl) retinamide (4-MPR) could reduce viral RNA levels and titers when applied to an established infection. 4-HPR but not 4-MPR was found to specifically upregulate the protein kinase R-like endoplasmic reticulum kinase arm of the unfolded protein response. Strikingly, 4-HPR but not 4-MPR restricted infection in peripheral blood mononuclear cells and in a lethal ADE-infection mouse model.

Conclusions: 4-HPR is a novel antiviral that modulates the unfolded protein response, effective against DENV1-4 at concentrations achievable in the plasma in a clinical setting, and provides protection in a lethal mouse model.
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http://dx.doi.org/10.1093/infdis/jiu319DOI Listing
December 2014

Efficacy and safety of celgosivir in patients with dengue fever (CELADEN): a phase 1b, randomised, double-blind, placebo-controlled, proof-of-concept trial.

Lancet Infect Dis 2014 Aug 28;14(8):706-715. Epub 2014 May 28.

Program in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, Singapore, Singapore. Electronic address:

Background: Dengue infection is the most common mosquito-borne viral disease worldwide, but no suitable antiviral drugs are available. We tested the α-glucosidase inhibitor celgosivir as a treatment for acute dengue fever.

Methods: To establish eligibility for inclusion in a phase 1b, randomised, double-blind, placebo-controlled, proof-of-concept trial, individuals aged 21-65 years who had had a fever (≥38°C) for less than 48 h, met at least two criteria indicating probable dengue infection, and had a positive result on a dengue point-of-care test kit or PCR assay were referred for screening at a centre in Singapore between July 30, 2012, and March 4, 2013. Using a web-based system, we randomly assigned patients who met full inclusion criteria after screening (1:1; random permuted block length four) to celgosivir (initial 400 mg loading dose within 6 h of randomisation, followed by 200 mg every 12 h for a total of nine doses) or matched placebo. Patients and the entire study team were masked to group assignment. The primary endpoints were mean virological log reduction (VLR) from baseline for days 2, 3, and 4, and area under the fever curve (AUC) for a temperature above 37°C from 0 h to 96 h. Efficacy analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01619969.

Findings: We screened 69 patients and randomly assigned 50 (24 to celgosivir, 26 to placebo). Mean VLR was greater in the celgosivir group (-1·86, SD 1·07) than in the placebo group (-1·64, 0·75), but the difference was non-significant (-0·22, 90% CI -0·65 to 0·22; one-sided p=0·203). The mean AUC was also higher in the celgosivir group (54·92, SD 31·04) than in the placebo group (40·72, 18·69), but again the difference was non-significant (14·20, 90% CI 2·16-26·25; one-sided p=0·973). We noted similar incidences of adverse events between groups.

Interpretation: Although generally safe and well tolerated, celgosivir does not seem to reduce viral load or fever burden in patients with dengue.

Funding: STOP Dengue Translational Clinical Research.
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http://dx.doi.org/10.1016/S1473-3099(14)70730-3DOI Listing
August 2014

Effect of a prodrug of the green tea polyphenol (-)-epigallocatechin-3-gallate on the growth of androgen-independent prostate cancer in vivo.

Nutr Cancer 2008 ;60(4):483-91

Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, HKSAR, China.

Epigallocatechin-3-gallate (EGCG) is the major and most potent polyphenol compound of green tea that has been shown to have anticancer effects against various types of cancers. In this study, in addition to the EGCG compound, a synthetic derivative, the peracetate of EGCG (EGCG-P), was used to investigate the inhibitory effects on growth of androgen-independent prostate cancer in vivo. The advantage of EGCG-P is that it may act as a prodrug, leading to higher bioavailability than EGCG itself. The aim of our study was to compare the differences between EGCG and EGCG-P on their inhibitory effect on androgen-independent prostate cancer, CWR22R, xenograft model in nude mice. The mice were administrated daily with solvent dimethyl sulfoxide, EGCG, and EGCG-P separately through intraperitoneal injection for 20 days. Tumor volume and body weight of nude mice were recorded daily. Serum prostate-specific antigen (PSA) levels were also measured before and after the treatment. The effects of both EGCG and EGCG-P on tumor cell proliferation were assessed by immunohistochemical (IHC) method using antibodies against Ki-67 and proliferating cell nuclear antigen. The apoptotic effect was evaluated by IHC against B-cell non-Hodgkin lymphoma-2 and terminal deoxynucleotidyl transferase dUTP nick-end labeling assay by in situ apoptosis detection kit. Moreover, the potential suppression of angiogenesis by EGCG and EGCG-P on prostate cancer was examined by IHC against CD31. Our results revealed that treatment of EGCG and EGCG-P compounds suppressed the growth of CWR22R xenografts without causing any detectable side effects in nude mice. The suppression of growth of the tumor was correlated with the decrease of serum PSA level together with the reduction in tumor angiogenesis and an increase in apoptosis on prostate cancer cells. The results showed that treatment of EGCG and EGCG-P inhibited tumor growth and angiogenesis while promoting apoptosis of the prostate cancer cells in vivo. Our results suggest that EGCG-P may be a more stable and useful compound for increasing the therapeutic anticancer effects in androgen-independent prostate cancer.
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http://dx.doi.org/10.1080/01635580801947674DOI Listing
November 2008

Effect of a home exercise program based on tai chi in patients with end-stage renal disease.

Perit Dial Int 2003 Dec;23 Suppl 2:S99-S103

Renal Dialysis Unit and Physiotherapy Department, Alice Ho Miu Ling Nethersole Hospital, Hong Kong SAR, China.

Objective: Previous reports have documented the benefits of exercise on the well-being of renal patients. However, fewer than 50% of our end-stage renal disease (ESRD) patients engage in regular exercise. To promote exercise, we implemented a home-based exercise program. The aim of the program was to reduce barriers to exercise by helping patients to exercise at their convenience and without the need to travel. The effect of the program was evaluated 3 months after implementation.

Patients And Methods: Each study participant received a videotape that demonstrated 30 minutes of low-capacity aerobic exercise. Participants were advised to exercise by following the demonstration on the videotape. Encouragement was given over the telephone. Self-reports on practice were recorded in a log book that was also provided. The effect of the program was evaluated by comparing outcomes data before, and 3 months after, implementation of the program. Outcomes assessment included functional mobility (timed "Up & Go" test), muscle flexibility ("Sit & Reach" test), physical capacity ("Six-Minute Walk"), and quality of life [Kidney Disease Quality of Life Short Form (KDQOL-SF)].

Results: The program began with 72 participants. Over time, 39 dropped out. The remaining 33 participants included 11 men and 22 women with a mean age of 52.8 +/- 9.8 years. They exercised 3 - 7 times weekly. Significant improvements were observed in the timed "Up & Go" (p = 0.003) and "Sit & Reach" (p < 0.001) tests. Improvements in the "Six-Minute Walk" (p = 0.130) and in KDQOL-SF scores for emotional well-being (p = 0.456), pain (p = 0.100), burden of kidney disease (p = 0.061), and general health (p = 0.085) were statistically insignificant.

Conclusions: Physically, patients with ESRD benefit from home-based low-capacity aerobic exercise. A home-based program provides an alternative to outdoor and group exercise. In view of a high drop-out rate, intensive promotion and encouragement should be considered to achieve a positive outcome.
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December 2003

Comparison of clinical outcome and ease of handling in two double-bag systems in continuous ambulatory peritoneal dialysis: a prospective, randomized, controlled, multicenter study.

Am J Kidney Dis 2002 Aug;40(2):373-80

Department of Medicine, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, Hong Kong.

Background: We performed a prospective, randomized, controlled, multicenter study on the use of two double-bag disconnect systems: Stay-Safe (SS; Fresenius Deutschland GmbH2) and Ultrabag (UB; Baxter Healthcare, Deerfield, IL) to assess the ease of handling, peritonitis rate, exit-site infection rate, and clinical outcome.

Methods: We enrolled 110 new continuous ambulatory peritoneal dialysis (CAPD) patients; 55 patients were randomized to SS treatment, and 55 patients, to UB treatment.

Results: Patients using the UB and SS systems were followed up for 946 and 846 patient-months, respectively. There were 21 episodes of peritonitis in 18 patients in the UB group and 23 episodes in 18 patients in the SS group. No significant difference was observed in peritonitis rates between the two systems, which were 45 and 36.8 patient-months per episode for the UB and SS groups, respectively. At 12 months, 82.1% of patients in the UB group and 72.1% in the SS group were free of peritonitis; at 18 months, 71.1% and 62.2% were free of peritonitis for the UB and SS groups, respectively (P = 0.559). Gram-positive organisms accounted for 28.6% of infections in the UB group and 39.1% in the SS group. Exit-site infection rates were one episode per 21 patient-months versus 19.2 patient-months in the UB and SS groups, respectively (P = 0.743). Patients perceived SS as easier to handle in 4 of the 13 steps immediately post-CAPD training. However, there was no significant difference in rankings between the two systems after 1 month of adaptation. Median training periods were 4 and 5 days for the SS and UB groups, respectively (P = 0.640).

Conclusion: The two double-bag systems (UB and SS) have similar incidences of peritonitis and exit-site infection. Both systems showed comparably good clinical outcome. The SS system is easier to learn during the initial training period, but the difference is not significant after 1 month's adaptation.
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http://dx.doi.org/10.1053/ajkd.2002.34522DOI Listing
August 2002
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