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Biomedical subjects

W K Leung

Publications and source records attributed to W K Leung.

At least 19 recordsLinked to original sources
PubMed2006

Peroxisome proliferator-activated receptor-gamma Pro12Ala polymorphism, Helicobacter pylori infection and non-cardia gastric carcinoma in Chinese.

BACKGROUND: Peroxisome proliferator-activated receptor gamma inhibits the growth and induces apoptosis of gastric cancer cells. A common polymorphism at codon 12 of this gene (Pro12Ala) has been shown to confer protection against diabetes and colorectal cancer. AIM: To study the association between peroxisome proliferator-activated receptor gamma gene polymorphism, Helicobacter pylori infection and gastric cancer in Chinese. METHODS: One hundred and four consecutive patients with non-cardia gastric adenocarcinoma and 104 matched controls were examined. Peroxisome proliferator-activated receptor gamma Pro12Ala polymorphism was analysed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The frequency of peroxisome proliferator-activated receptor gamma G (Ala12) allele was significantly higher among cancer patients (19.2%) than in control (8.7%; OR 2.5, 95% CI 1.1-5.8). While H. pylori infection was more prevalent in gastric cancer patients (OR 3.0; 95% CI 1.6-5.7), the combination of peroxisome proliferator-activated receptor gamma G allele and H. pylori infection further increased the risk of gastric cancer (OR 12.8, 95% CI 3.2-50.5). The presence of the Ala12 did not increase the risk of gastric cancer in H. pylori-negative subjects. CONCLUSION: Our study suggests the potential association between peroxisome proliferator-activated receptor gamma polymorphism and H. pylori infection in the development of non-cardia gastric cancer.

Adenocarcinoma↗
PubMed2006

Ulcers and gastritis.

Explore the source record for details and available documents.

Endoscopy, Gastrointestinal↗
PubMed2006

Tooth loss in treated periodontitis patients responsible for their supportive care arrangements.

AIM: To identify risk indicators associated with tooth loss and periodontitis in treated patients responsible for arranging supportive periodontal care (SPC). MATERIALS AND METHODS: Ninety-seven Chinese subjects (34-77 years) who showed favourable responses to periodontal therapy provided in a teaching hospital 5-12 years previously were recalled. They were advised to seek regular SPC on discharge. Background information, general health status, smoking, oral hygiene habits, follow-up dental care, tooth loss, and periodontal parameters were investigated. Multiple regression analysis was performed. RESULTS: Two hundred and fifty-six teeth had been lost, 195 because of self-reported periodontal reasons. Up to 26.8% sites were with pockets > or =6 mm. Positive correlations were found between total/periodontal tooth loss and (i) smoking pack-years, (ii) time spent on oral hygiene, (iii) years since therapy's conclusion, (iv) age, and negative correlations with (v) inter-dental brush use, and (vi) education levels. Tooth loss by arch was correlated with wearing of removable partial denture in that arch. Percentage sites with pockets > or =6 mm were significantly negatively correlated with percentage sites without bleeding on probing. CONCLUSIONS: Smokers, more elderly patients, removable partial denture wearers, and patients with lower education levels or not using inter-dental brushes ought to be targeted for clinic-based SPC.

Adult↗
PubMed2005

Anti-proliferative and pro-apoptotic effects of herbal medicine on hepatic stellate cell.

Hepatic stellate cells (HSC) play a central role in hepatic fibrosis and compounds that promote apoptosis in HSC may have anti-fibrotic potentials. Herbal medicine has long been used in chronic liver disease but there is little scientific evidence for their actions. The present study investigated the effects of 14 commonly used herbs on cellular proliferation and apoptosis of a rat hepatic stellate cell line, HSC-T6 and the underlying mechanism of herb-induced apoptosis. HSC-T6 cell were incubated with herbal extracts and their proliferation was assessed by colorimetric assay. Apoptosis was measured and confirmed by flow cytometry, terminal transferase uridyl nick end labeling (TUNEL) assay and morphological features in hematoxylin and eosin staining. Apoptotic pathways involving Fas receptor and Bcl-2 family were investigated by Western blot. Five herbs, namely Angelica sinensis (AS), Carthamus tinctorius (CT), Ligusticum chuanxiong (LC), Salvia miltiorrhiza (SM) and Stephania tetrandra (ST) demonstrated both anti-proliferative and pro-apoptotic activities in HSC-T6. The highest potency was detected in SM and ST with 51.63 and 44.52% of HSC-T6 showing apoptotic changes, respectively. This was associated with upregulation of Fas and Bax and down-regulation of Bcl-xL in HSC. Fas ligand and Bcl2 expressions remained unchanged. The potential anti-fibrotic effect of herbal medicine warrants further evaluation.

Animals↗
PubMed2005

Potential diagnostic and prognostic values of detecting promoter hypermethylation in the serum of patients with gastric cancer.

While there is no reliable serum biomarker for the diagnosis and monitoring of patients with gastric cancer, we tested the potential diagnostic and prognostic values of detecting methylation changes in the serum of gastric cancer patients. DNA was extracted from the pretherapeutic serum of 60 patients with confirmed gastric adenocarcinoma and 22 age-matched noncancer controls. Promoter hypermethylation in 10 tumour-related genes (APC, E-cadherin, GSTP1, hMLH1, MGMT, p15, p16, SOCS1, TIMP3 and TGF-beta RII) was determined by quantitative methylation-specific PCR (MethyLight). Preferential methylation in the serum DNA of gastric cancer patients was noted in APC (17%), E-cadherin (13%), hMLH1 (41%) and TIMP3 (17%) genes. Moreover, patients with stages III/IV diseases tended to have higher concentrations of methylated APC (P = 0.08), TIMP3 (P = 0.005) and hMLH1 (P = 0.03) in the serum. In all, 33 cancers (55%) had methylation detected in the serum in at least one of these four markers, while three normal subjects had methylation detected in the serum (specificity 86%). The combined use of APC and E-cadherin methylation markers identified a subgroup of cancer patients with worse prognosis (median survival 3.3 vs 16.1 months, P = 0.006). These results suggest that the detection of DNA methylation in the serum may carry both diagnostic and therapeutic values in gastric cancer patients.

Adenocarcinoma↗
PubMed2005

Increasing incidence of colorectal cancer in Asia: implications for screening.

Many Asian countries, including China, Japan, South Korea, and Singapore, have experienced an increase of two to four times in the incidence of colorectal cancer during the past few decades. The rising trend in incidence and mortality from colorectal cancer is more striking in affluent than in poorer societies and differs substantially among ethnic groups. Although changes in dietary habits and lifestyle are believed to be the reasons underlying the increase, the interaction between these factors and genetic characteristics of the Asian populations might also have a pivotal role. Non-polypoidal (flat or depressed) lesions and colorectal neoplasms arising without preceding adenoma (de novo cancers) seem to be more common in Asian than in other populations. The absence of polypoid growth preceding malignancy has posed difficulties in screening for early colorectal cancer by radiological imaging or even endoscopic techniques. Although epidemiological data are scanty, most Asian populations are not aware of the growing problem of colorectal cancer. More work is needed to elucidate the magnitude of the problem in Asia.

Asia↗
PubMed2005

Diarrhoea and rash in a retired farmer.

An 83-year-old retired farmer developed invasive strongyloidiasis after using potent topical corticosteroids. Initial colonoscopy features mimicked ulcerative colitis, and the clinical course was complicated by bacterial septicaemia with Serratia and Enterococcus. He was treated successfully with oral ivermectin and antibiotics.

Aged↗
PubMed2004

Agreements among traditional Chinese medicine practitioners in the diagnosis and treatment of irritable bowel syndrome.

BACKGROUND: Traditional Chinese Medicine was frequently used by patients with irritable bowel syndrome. AIM: To evaluate the agreement on diagnoses and prescription of irritable bowel syndrome among Traditional Chinese Medicine practitioners. METHODS: Consecutive irritable bowel syndrome patients were interviewed independently by four Traditional Chinese Medicine practitioners. The study was divided into three phases: (i) blinded individual assessment, (ii) discussion to achieve consensus on diagnosis and treatment, (iii) individual assessment based on consensual diagnostic criteria. Patients with other causes of diarrhoea were recruited as controls in phase (iii). Percentage agreement and kappa-value in diagnosis, treatment principle and regime were determined. RESULTS: Thirty-nine irritable bowel syndrome patients were assessed in phase (i) whereas 65 irritable bowel syndrome patients and 17 non-irritable bowel syndrome controls were studied in phase (iii). The mean agreement rates in diagnosis, treatment principle and regimen were: 57, 58 and 52% for phase (i) and 80, 81 and 80% for phase (iii) (P = 0.002). Accordingly, there was significant improvement in the mean kappa-values in diagnosis (0.11-0.34, P = 0.015) and treatment principle (0.16-0.37, P = 0.002) but not in treatment regime. CONCLUSIONS: Variations in diagnosis and treatment principles do exist among Traditional Chinese Medicine practitioners. Concordant diagnosis can be reached by mutual understanding and converging opinion among Traditional Chinese Medicine practitioners.

Adult↗
PubMed2004

Constitutional activation of IL-6-mediated JAK/STAT pathway through hypermethylation of SOCS-1 in human gastric cancer cell line.

The interleukin-mediated Janus kinase (JAK)/STAT pathway plays a crucial role in carcinogenesis. Recently, increased STAT3 activity was found in hepatocellular carcinoma and multiple myeloma in which there was silencing of SOCS-1 (suppressor of cytokine signalling-1) by gene promoter hypermethylation. We investigated the expression level of interleukin-6 (IL-6) and SOCS-1 in gastric cancer cell lines. Expression of SOCS-1 correlated with IL-6 level in most of the cell lines, except for AGS cells in which SOCS-1 was absent despite a high level of IL-6 production. Methylation analysis by methylation-specific polymerase chain reaction and bisulphite sequencing revealed that CpG island of SOCS-1 was densely methylated in AGS cells. Demethylation treatment by 5'aza-deoxycytidine restored SOCS-1 expression and also suppressed constitutive STAT3 phosphorylation in AGS cells. Moreover, methylation of SOCS-1 was detected in 27.5% (11 of 40) of primary gastric tumours samples, 10% (one of 10) of adjacent noncancer tissues but not in any (zero of nine) normal gastric mucosa. Methylation of SOCS-1 also correlated with the loss of mRNA expression in some primary gastric cancers. In conclusion, this is the first report to demonstrate that hypermethylation of SOCS-1 led to gene silencing in gastric cancer cell line and primary tumour samples. Downregulation of SOCS-1 cooperates with IL-6 in the activation of JAK/STAT pathway in gastric cancer.

Carrier Proteins↗
PubMed2004

Oral health-related quality of life in southern Chinese following radiotherapy for nasopharyngeal carcinoma.

Although the complications of head and neck radiotherapy in the treatment of nasopharyngeal carcinoma (NPC) have been described, there is limited information on the effect of oral complications on oral health related quality of life. The aim of this study was to describe the psychosocial and functional impact of oral conditions in southern Chinese following radiotherapy for NPC. A cross-sectional study design was used with a sample of 109 subjects including NPC survivors, newly diagnosed NPC cases and a control group. Oral health related quality of life was assessed through the SF-36 and the Oral Health Impact Profile measures and a dry mouth measure. Data on socio-demographic variables and treatment seeking were also collected. The psychosocial and functional impact of oral conditions as revealed by the health status measures was significantly greater in NPC survivors than newly diagnosed NPC cases and controls. The oral specific and condition specific measures appeared to discriminate more effectively between groups than the generic measure. NPC survivors sought significantly more dental treatment than the other groups. The oral complications of radiotherapy for NPC, notably sequelae of salivary gland damage, have a significant negative effect on oral health related quality of life and result in an increased burden of dental care in the long-term.

Adult↗
PubMed2004

Impact of Sjögren's syndrome on oral health-related quality of life in southern Chinese.

The effect of oral symptoms of Sjögren's syndrome (SS) on health-related quality of life is presently uncertain. This study aimed to investigate oral health-related quality of life (OHRQOL) among southern Chinese people with SS. Twenty-six primary SS cases, 25 secondary cases and 29 matched controls took part in this cross-sectional study. Each participant completed a SF-36 questionnaire, the Oral Health Impact Profile and a dry mouth measure, assisted by a trained interviewer. Data on socio-demographic variables were also collected. The dry mouth measure revealed that people with primary and secondary SS had significant problems associated with subjective symptoms of dry mouth generally, and dry mouth when eating and speaking (P < 0.01). Sticky saliva and coughing were also problems in some primary SS cases. OHIP summary and sub-scale scores did not reveal differences in negative impacts between groups. Mean SF-36 sub-scale scores were significantly different between groups (P < 0.05). In physical function, role-physical and general health domains, primary and secondary SS sufferers had lower scores indicating poorer health. Oral symptoms of SS, notably xerostomia, had a negative effect on OHRQOL. Health-related quality of life in general was also impaired in SS sufferers. The OHIP did not appear to discriminate oral problems of concern to SS sufferers.

Adult↗
PubMed2004

Effect of peroxisome proliferator activated receptor gamma ligands on growth and gene expression profiles of gastric cancer cells.

BACKGROUND AND AIMS: Although peroxisome proliferator activated receptor gamma (PPARgamma) agonists have been implicated in differentiation and growth inhibition of cancer cells, the potential therapeutic and chemopreventive effects on gastric cancer are poorly defined. We examined the in vitro and in vivo effects of PPARgamma ligands on growth of gastric cancer, and the effect of PPARgamma activation on expression of cyclooxygenase 2 (COX-2) and cancer related genes. METHODS: Gastric cell lines (MKN28 and MKN45) were treated with two specific PPARgamma ligands: ciglitazone and 15-deoxy-Delta(12,)(14)-prostaglandin J(2). Cell growth was determined by bromodeoxyuridine incorporation assay and apoptosis was measured by DNA fragmentation. Expression of COX-2 was determined by western blot and real time quantitative polymerase chain reaction (PCR). Expression profiles of cancer related genes were screened with cDNA array. In vivo growth of implanted MKN45 cells in nude mice was monitored after oral treatment with rosiglitazone. RESULTS: PPARgamma ligands suppressed the in vitro growth of MKN45 cells in a dose dependent manner whereas prostacyclin, a PPARdelta agonist, had no growth inhibitory effect. Growth inhibition was more pronounced in MKN45 cells, which was accompanied by DNA fragmentation and downregulation of COX-2. Screening by cDNA microarray showed that PPARgamma ligand treatment was associated with upregulation of bad and p53, and downregulation of bcl-2, bcl-xl, and cyclin E1 in MKN45 cells, which was confirmed by quantitative real time PCR. In contrast, MKN28 cells with lower PPARgamma and COX-2 expression levels had lower growth inhibitory responses to PPARgamma ligands. Microarray experiments only showed induction of the bad gene in MKN28 cells. In vivo growth of MKN45 cells in nude mice was retarded by rosiglitazone. Mean tumour volume in rosiglitazone treated mice was significantly lower than controls at six weeks (p = 0.019) and seven weeks (p = 0.001) after treatment. CONCLUSIONS: PPARgamma ligands suppress both in vitro and in vivo growth of gastric cancer and may play a major role in cancer therapy and prevention.

Animals↗
PubMed2004

Chemoprevention of gastric cancer by celecoxib in rats.

BACKGROUND: Overexpression of cyclooxygenase 2 (COX-2) is frequently detected in gastric cancer and is believed to play a crucial role in gastric carcinogenesis. AIM: We examined the chemopreventive effect of a COX-2 inhibitor in an animal model of stomach carcinogenesis. METHODS: Eighty six male Wistar rats were divided into six different treatment groups: group A, water alone (n = 5); group B, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG 100 micro g/ml) (n = 16); group C, indomethacin (3 mg/kg/day) (n = 16); group D, celecoxib (5 mg/kg/day) (n = 17); group E, celecoxib (10 mg/kg/day) (n = 16); and group F, celecoxib (20 mg/kg/day) (n = 16). Group B-F animals were treated with 10% sodium chloride (in the initial six weeks) and MNNG in drinking water to induce adenocarcinoma in the stomach. All animals received treatment for 40 weeks, and were sacrificed after death or at 48 weeks. Gastric neoplasm was evaluated by histology. RESULTS: The incidences of gastric cancer were 0% in group A, 75% in group B, 68.8% in group C, 70.6% in group D, 18.8% in group E, and 31.3% in group F (p = 0.002, ANOVA). Compared with MNNG controls, treatment with celecoxib 10 mg/kg/day also showed lower tumour multiplicity (0.19 (0.40) v 1.00 (0.73); p = 0.004) and lower mean tumour volume (2.4 v 2805 mm(3); p = 0.02). Although tumours had significantly higher COX-2 expression than their adjacent normal tissues (p<0.02), there was no significant difference in COX-2 levels among tumours in the different treatment groups. The lowest tumour prostaglandin E(2) level was found in the indomethacin treated group, suggesting that the chemopreventive effect of celecoxib may be mediated by a COX independent pathway. CONCLUSION: While treatment with indomethacin had no significant effect on tumour development, treatment with celecoxib reduced gastric cancer incidence and growth in rats.

Analysis of Variance↗
PubMed2004

Factors predicting progression of gastric intestinal metaplasia: results of a randomised trial on Helicobacter pylori eradication.

BACKGROUND AND AIMS: Gastric intestinal metaplasia (IM) is generally considered to be a precancerous lesion in the gastric carcinogenesis cascade. This study identified the risk factors associated with progression of IM in a randomised control study. SUBJECTS AND METHODS: A total of 587 Helicobacter pylori infected subjects were randomised to receive a one week course of anti-Helicobacter therapy (omeprazole, amoxicillin, and clarithromycin (OAC)) or placebo. Subjects underwent endoscopy with biopsy at baseline and at five years. Severity of IM was graded according to the updated Sydney classification and progression was defined as worsening of IM scores at five years in either the antrum or corpus, or development of neoplasia. Backward stepwise multiple logistic regression was used to identify independent risk factors associated with IM progression. RESULTS: Of 435 subjects (220 in the OAC and 215 in the placebo group) available for analysis, 10 developed gastric cancer and three had dysplasia. Overall progression of IM was noted in 52.9% of subjects. Univariate analysis showed that persistent H pylori infection, age >45 years, male subjects, alcohol use, and drinking water from a well were significantly associated with IM progression. Duodenal ulcer and OAC treatment were associated with a reduced risk of histological progression. Progression of IM was more frequent in those with more extensive and more severe IM at baseline. With multiple logistic regression, duodenal ulcer (odds ratio (OR) 0.23 (95% confidence interval (CI) 0.09-0.58)) was found to be an independent protective factor against IM progression. Conversely, persistent H pylori infection (OR 2.13 (95% CI 1.41-3.24)), age >45 years (OR 1.92 (95% CI 1.18-3.11)), alcohol use (OR 1.67 (95% CI 1.07-2.62)), and drinking water from a well (OR 1.74 (95% CI 1.13-2.67)) were independent risk factors associated with IM progression. CONCLUSION: Eradication of H pylori is protective against progression of premalignant gastric lesions.

Aged↗
PubMed2004

Wireless capsule endoscopy in Chinese patients with suspected small bowel diseases.

OBJECTIVE: To evaluate the use of wireless capsule endoscopy in Chinese patients. DESIGN: Retrospective analysis. SETTING: University teaching hospital, Hong Kong. PATIENTS: Twenty-eight patients who had undergone wireless capsule endoscopy between December 2002 and December 2003. MAIN OUTCOME MEASURES: Diagnoses according to findings of capsule endoscopy and complications from the procedure. RESULTS: The mean age of the 28 patients (15 men and 13 women) was 60.0 (standard deviation, 18.3) years. The indications for capsule endoscopy were obscure gastro-intestinal bleeding (n=16), unexplained iron-deficiency anaemia (n=9), and recurrent abdominal pain (n=3). Half of the patients had abnormal endoscopy findings that may account for their presenting symptoms. The most common abnormality was angioectasia of the small bowel. Small bowel ulcers and erosions were also noted in three patients with obscure bleeding. In contrast, none of the patients with recurrent abdominal pain had abnormal capsule endoscopy. No complications arose from the procedure. CONCLUSIONS: Wireless capsule endoscopy is a safe and useful mode of investigation for the diagnosis of obscure gastro-intestinal bleeding in Chinese patients.

Abdominal Pain↗
PubMed2003

Absence of cyclin D2 expression is associated with promoter hypermethylation in gastric cancer.

Expression of cyclin D2 is absent in 30-70% of gastric cancers. We investigated the role of promoter hypermethylation in the transcriptional silencing of cyclin D2 in five gastric cell lines and 47 primary gastric carcinomas. CpG island methylation status of the cyclin D2 gene was studied by methylation-specific polymerase chain reaction and bisulphite sequencing. RNA and protein expression was analysed by reverse transcription-PCR and Western blot, respectively. Dense methylation of cyclin D2 was detected in three cell lines (KATOIII, AGS and NCI-N87), which also lacked cyclin D2 mRNA and protein expression. Bisulphite DNA sequencing revealed that loss of cyclin D2 expression was closely associated with the density of methylation in the promoter region. Treatment with DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine, restored the cyclin D2 expression level in methylated gastric cells. Among the 47 primary gastric cancers, cyclin D2 hypermethylation was detected in 23 (48.9%) cases. None of the 23 normal gastric biopsies from noncancer patients showed hypermethylation. Hypermethylation was associated with loss of mRNA (P&<0.001) and protein (P=0.006) expressions. Our study showed that cyclin D2 hypermethylation is associated with loss of cyclin D2 expression in a subset of gastric cancers, which may suggest an alternative gastric carcinogenesis pathway in the absence of cyclin D2 expression.

Blotting, Western↗
PubMed2003

Oral colonisation by aerobic and facultatively anaerobic Gram-negative rods and yeast in Tibetans living in Lhasa.

Sample groups of children (n=50) and adults (n=38) were selected from pools of 207 children, (11-13-year olds from two primary schools) and 94 adults (25-44-year olds from four governmental agencies) who were the subjects of an oral health survey among Tibetans living in Lhasa, Tibet Autonomous Region. Mean ages of the study groups of children (38% females) and adults (61% females) were 11.6+/-0.9 and 37.1+/-6.1 years, respectively. All had lived in Tibet since birth. Oral rinse samples were selective cultured to isolate, quantify and speciate aerobic and facultatively anaerobic Gram-negative rods (using the API 20E kit) and yeasts (using API 20C AUX and API ZYM kits). For children, the isolation rates for oral coliform bacteria and yeasts were 84 and 14%, respectively, for adults, the respective rates were 26 and 40%. The corresponding quantities of coliforms/yeasts for children and adults were 0.4+/-1.6 x 10(3)c.f.u./15.8+/-72.3 and 0.2+/-0.6 x 10(3)c.f.u./57.2+/-137.5c.f.u. per millilitre oral rinse, respectively. Aerobic and facultatively anaerobic Gram-negative rods and Stenotrophomonas maltophilia, a free-living saprophytic and ubiquitous bacterial species of wide geographic distribution, were significantly more frequently recovered from the children's oral rinses. The isolation rates of facultatively anaerobic Gram-negative rods in adults and yeasts in both groups were similar to those found in similar cohorts from southern China in earlier studies. Randomly amplified polymeric DNA analysis showed that the S. maltophilia spp. isolated from children were of several different clonal types and were school specific. This study shows that the colonisation rate of facultatively anaerobic Gram-negative rods in adults and yeasts in both groups are similar to those in populations living at lower altitudes, the native young, urban Tibetans appear to exhibit a high oral carriage rate of S. maltophilia spp.

Adolescent↗