[Show abstract][Hide abstract] ABSTRACT: The angiographic findings and prognosis of patients with complete atrioventricular block (AVB) complicating acute inferior myocardial infarction (MI) remain unclear.
The clinical and angiographic findings of 70 consecutive patients with complete AVB were compared with those of 319 patients with inferior MI without AVB (control group) admitted within the same study period.
Patients with complete AVB were older (68 +/- 12 vs 63 +/- 13 years; P = 0.004) and clustered with clinical features indicative of larger infarct size, such as right ventricular infarction, cardiogenic shock, or low left ventricular ejection fraction (LVEF). The onset of the complete AVB was observed within 24 hours in 62 (88.6%), preceded by second-degree AVB in 26 (37.1%) and the escape QRS complex was wide in 8 (11.4%) patients. In patients with complete AVB, a dominant right coronary artery occlusion was found in >95% of cases and in-hospital mortality was increased (27.1% vs 10.7%; P = 0.000), especially in those with widen QRS escape rhythm (75.0%). Reperfusion therapy had a positive impact on the natural course of complete AVB.
Complete AVB in acute inferior MI was associated with advanced age and larger infarct size. Complete AVB was virtually always caused by dominant right coronary artery occlusion. The in-hospital mortality was significantly higher, but improved by reperfusion therapy. No permanent pacemaker is performed at a mean follow-up of 47 months.
Annals of the Academy of Medicine, Singapore 03/2010; 39(3):185-90. · 1.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study aimed to determine the potential diagnostic value of migration-inhibitory factor (MIF) for gastric cancer in patients presenting with dyspepsia and its prognostic value for gastric cancer.
A cohort of 97 patients with histologically confirmed gastric adenocarcinoma and 222 patients with dyspepsia were recruited. Enzyme-linked immunosorbent assay was used to measure serum MIF and carcinoembryonic antigen (CEA).
The serum MIF concentrations were 6554.0 +/- 204.1 pg/mL and 1453.7 +/- 79.9 pg/mL, respectively, in gastric cancer patients and dyspeptic patients (P < .001). Serum MIF levels increased with the advancing gastric pathologies (P < .001). With the cutoff value of 3230 pg/mL, serum MIF had sensitivity, specificity, and accuracy of 83.5%, 92.3%, and 89.7%, respectively, in diagnosing gastric cancer, whereas the rates were 60.8%, 83.3%, and 76.5%, respectively, for serum CEA. Gastric cancer patients with serum MIF levels above 6600 pg/mL had a lower 5-year survival rate than those with serum MIF level below that level (P = .012). Higher serum CEA levels were also associated with poor survival. The prediction for 5-year survival was even better (P = .0001), using a combination of serum MIF and CEA.
Serum MIF level, which correlates with gastric MIF expression, is a better molecular marker than CEA in diagnosing gastric cancer in patients presenting with dyspepsia. A combination of serum MIF and CEA predicts 5-year survival better than the individual test.
Cancer 12/2009; 115(23):5441-9. DOI:10.1002/cncr.24609 · 4.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Upper endoscopy records from 1998 to 2003 were reviewed. The demographic data, endoscopic diagnosis, results of rapid urease test and the absence or presence of intestinal metaplasia (IM) in histology were reviewed, to evaluate the prevalence of IM and Helicobacter pylori (Hp) infection over time in Hong Kong.
Among 1805 endoscopies performed, 1751 had both rapid urease test and histology available. A significant drop in the prevalence of duodenal ulcers from 17.9% in 1998 to 9.8% in 2003 was found (P = 0.015). Prevalence of IM was 13.9%, 5.9% and 9.4% in Hp positive, Hp negative and overall respectively (P < 0.05). The prevalence of IM increased with age, and the patterns were similar amongst subjects in 1998-2000 and those in 2001-2003. There was progressive decrease in Hp prevalence from 58% in 1998 to 40% in 2001 (P = 0.014), but no further decrease was seen in 2002-3. There was no corresponding decrease in IM prevalence. Instead IM prevalence in 2002-2003 was significantly higher than the prevalence in previous few years (P = 0.04).
The prevalence of IM did not change in the period from 1998 to 2003 despite a drop in the prevalence of Hp infection since 1994.
Journal of Gastroenterology and Hepatology 05/2009; 24(5):896-9. DOI:10.1111/j.1440-1746.2009.05799.x · 3.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Chest pain is common and data regarding noncardiac chest pain (NCCP) in Asia are lacking.
To determine the differences in clinical presentations, psychologic impact, and quality of life between patients with NCCP and cardiac chest pain (CCP), and to identify any factors that impacted on these patients.
Consecutive patients undergoing coronary angiography for the evaluation of chest pain were recruited in Hong Kong and Wuhan, China. One hundred and forty patients with abnormal and 141 patients with normal angiography were included in the study. The validated gastroesophageal reflux disease questionnaire, the Hospital Anxiety-Depression Scale, and the 12-item Short Form Health Survey (SF-12) were used for assessment.
NCCP patients reported similar days-off work and impairment of their social life compared with those with CCP. No difference was found in the anxiety and depression scores between the 2 groups. NCCP patients with reflux symptoms had higher anxiety score (7.19 vs. 5.74, P=0.044), reported more interruption of their social life (26% vs. 5%, P<0.0001), and had taken more sick leaves (17% vs. 5%, P=0.018) compared with those without gastroesophageal reflux disease.
The quality of life and psychologic impact of patients with NCCP were as significant as those with CCP. NCCP patients with reflux symptoms were more anxious and were impaired in their productivity and social life.
[Show abstract][Hide abstract] ABSTRACT: Helicobacter pylori infection is a major cause of gastritis and gastric carcinoma. Aspirin has anti-inflammatory and antineoplastic activity. The aim of the present study was to determine the effects of aspirin on H. pylori-induced gastritis and the development of heterotopic proliferative glands.
H. pylori strain SS1 was inoculated into the stomachs of Mongolian gerbils. Two weeks after inoculation, the animals were fed with the powder diets containing 0 p.p.m. (n = 10), 150 p.p.m. (n = 10), or 500 p.p.m. (n = 10) aspirin. Mongolian gerbils were killed after 36 weeks of infection. Uninfected Mongolian gerbils (n = 10) were used as controls. Histologic changes, epithelial cell proliferation and apoptosis, and prostaglandin E(2) (PGE(2)) levels of gastric tissue were determined.
H. pylori infection induced gastric inflammation. Administration of aspirin did not change H. pylori-induced gastritis, but alleviated H. pylori-induced hyperplasia and the development of heterotopic proliferative glands. Administration of aspirin accelerated H. pylori-associated apoptosis but decreased H. pylori-associated cell proliferation. In addition, the increased gastric PGE(2) levels due to H. pylori infection were suppressed by treatment with aspirin, especially at the dose of 500 p.p.m.
Aspirin alleviates H. pylori-induced hyperplasia and the development of heterotopic proliferative glands. Moreover, aspirin increases H. pylori-induced apoptosis. We demonstrated the antineoplastic activities of aspirin in H. pylori-related gastric carcinogenesis.
[Show abstract][Hide abstract] ABSTRACT: Previous studies suggested that Chinese have a milder spectrum of gastro-oesophageal reflux disease and a lower dose of proton pump inhibitors (PPI) is sufficient for the control of symptoms as compared with the Western population.
To determine if 8 weeks of esomeprazole 20 mg daily would be adequate for both symptom resolution and oesophagitis healing in Chinese patients and the predictive factors for the response.
66 patients with oesophagitis were included. Oesophagitis severity was graded by Los Angeles (LA) classification. 61 patients underwent 24-hour ambulatory pH study at baseline. All were given esomeprazole 20 mg daily for 8 weeks. Symptom response and healing of oesophagitis was assessed at the end of the treatment period.
75.8% of the patients had complete reflux symptom resolution but only 48% had complete healing of the oesophagitis at endoscopy after 8 weeks of treatment. LA classification grading at baseline endoscopy (p < 0.0001) and total number acid reflux episodes on 24-hour pH monitoring prior to treatment (p = 0.007) were both good predictors of oesophagitis healing but not for symptom resolution.
Our results suggested that 8 weeks of lower dose PPI is not sufficient for oesophagitis healing. Symptom resolution with PPI does not predict oesophagitis healing in Chinese.
[Show abstract][Hide abstract] ABSTRACT: Clinical observation showed that there is family aggregation in constipated subjects, but formal data are lacking. This prompted us to conduct a formal family study in constipated subjects.
Constipated subjects (probands) were identified according to the Rome II and Chinese constipation questionnaire criteria, healthy subjects were chosen as controls. Living first-degree relatives (parents, siblings, and children) and spouses (as internal controls) from both groups were identified. The questionnaire on Rome II criteria was given to the relatives either through the index subjects or by mail. The questionnaire was received by mailing back or through the index subjects. Any nonresponders were chased.
There were 132 probands with constipation and 114 controls. The Rome II questionnaire was sent to a total of 677 relatives of the probands and 591 of the controls. Relatives were comparable in mean age, sex distribution, family size, and marital status in the two groups. Constipation prevalence was 16.4% in probands' relatives versus 9.1% in controls' relatives, i.e., 13% in the relatives from both proband and controls. Among the constipated relatives, 6.3%versus 9.3% of the relatives were spouses of the probands and controls (P = 0.5). Subjects with more family members having constipation will have higher risk of constipation: OR 2.02, CI 1.14-3.65, P = 0.0177 for at least one family member; OR 3.99, CI 1.86-9.23, P = 0.0006 for at least two family members.
Familial aggregation of constipation occurs, supporting a genetic or intrafamilial environment component.
The American Journal of Gastroenterology 02/2007; 102(1):149-52. DOI:10.1111/j.1572-0241.2006.00886.x · 10.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The c-Jun NH(2)-terminal kinase (JNK) is activated in several tumor cell lines. The aim of this study was to determine the effects of SP-600125, a specific JNK inhibitor, on the viability, apoptosis, cell cycle distribution of gastrointestinal cancer cells, and the potential anti-tumor mechanisms. Three gastric cancer cell lines, AGS, BCG-823 and MKN-45, and three colorectal cancer cell lines, SW1116, COLO205 and HT-29, were used. Cells were treated with SP-600125, and cell viability, apoptosis and cell cycle distribution, caspase-3 activity, expression of JNK and apoptosis related proteins were detected. SP-600125 inhibited cell proliferation by 10-80% for the different cell lines, and increased apoptosis by 1.5-4.5 folds for COLO205, BCG-823, MKN-45, AGS cells. Caspase-8 and caspase-3 were involved in the induction of apoptosis. SP-600125 caused G2/M cell cycle arrest and elevation of cyclin B1 and p27(kip). The differential response in cells to SP-600125 was associated with the basal level of phosphorylated JNK2. It is concluded that SP-600125 inhibits proliferation, induces apoptosis and causes cell cycle arrest in gastrointestinal cancer cells, indicating that JNK inhibitors have an anti-tumor effect and are potential therapeutic agents for cancers.
Cancer Letters 10/2006; 241(2):268-74. DOI:10.1016/j.canlet.2005.10.031 · 5.62 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the optimal strategy to treat dyspeptic patients in primary care.
Dyspeptic patients presenting to primary care outpatient clinics were randomly assigned to: (1) empirical endoscopy, (2) H pylori test-and-treat, and (3) empirical prokinetic treatment with cisapride. Early endoscopy was arranged if patients remained symptomatic after 2 wk. Symptom severity, quality-of-life (SF-36) as well as patient preference and satisfaction were assessed. All patients underwent endoscopy by wk 6. Patients were followed up for one year.
Two hundred and thirty four patients were recruited (163 female, mean age 49). 46% were H pylori positive. 26% of H pylori tested and 25% of empirical prokinetic patients showed no improvement at wk 2 follow-up and needed early endoscopy. 15% of patients receiving empirical cisapride responded well to treatment but peptic ulcer was the final diagnosis. Symptom resolution and quality-of-life were similar among the groups. Costs for the three strategies were HK dollar 4343, dollar 1771 and dollar 1750 per patient. 66% of the patients preferred to have early endoscopy.
The three strategies are equally effective. Empirical prokinetic treatment was the least expensive but peptic ulcers may be missed with this treatment. The H pylori test-and-treat was the most cost-effective option.
World Journal of Gastroenterology 09/2006; 12(31):5010-6. · 2.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cyclooxygenases (COXs) play important roles in inflammation and carcinogenesis. The present study aimed to determine the effects of COX-1 and COX-2 gene disruption on Helicobacter pylori-induced gastric inflammation.
Wild-type (WT), COX-1 and COX-2 heterozygous (COX-1+/- and COX-2+/-), and homozygous COX-deficient (COX-1-/- and COX-2-/-) mice were inoculated with H. pylori strain TN2 and killed after 24 weeks of infection. Uninfected WT and COX-deficient mice were used as controls. Levels of gastric mucosal inflammation, epithelial cell proliferation and apoptosis, and cytokine expression were determined.
COX deficiency facilitated H. pylori-induced gastritis. In the presence of H. pylori infection, apoptosis was increased in both WT and COX-deficient mice, whereas cell proliferation was increased in WT and COX-1-deficient, but not in COX-2-deficient, mice. Tumor necrosis factor (TNF)-alpha and interleukin-10 mRNA expression was elevated in H. pylori-infected mice, but only TNF-alpha mRNA expression was further increased by COX deficiency. Prostaglandin E2 levels were increased in infected WT and COX-2-deficient mice but were at very low levels in infected COX-1-deficient mice. Leukotriene (LT) B4 and LTC4 levels were increased to a similar extent in infected WT and COX-deficient mice.
COX deficiency enhances H. pylori-induced gastritis, probably via TNF-alpha expression. COX-2, but not COX-1, deficiency suppresses H. pylori-induced cell proliferation.
The Journal of Infectious Diseases 05/2006; 193(7):1037-46. DOI:10.1086/500984 · 6.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: X-linked inhibitor of apoptosis protein (XIAP)-associated factor 1 (XAF1) is a novel tumor suppressor and interferon (IFN)-stimulated gene. All-trans retinoic acid (ATRA) exerts an antiproliferative effect on tumor cells through up-regulation of IFN regulatory factor 1 (IRF-1) and the downstream IFN-stimulated genes. The aim of this study was to determine the effect and mechanism of ATRA on XAF1 expression and the role of XAF1 in ATRA-induced growth inhibition in colon cancer.
Gene expression is detected by reverse-transcription polymerase chain reaction and immunoblotting. The transcription activity of XAF1 promoter is examined by luciferase reporter assay. The activity of IFN regulatory factor binding element (IRF-E) is assessed by electrophoretic mobility shift assay and chromatin immunoprecipitation assay. Cell growth is evaluated by both in vitro and in vivo in nude mice xenografts.
IFN-alfa stimulates XAF1 promoter activity in the colon cancer cells Lovo and SW1116 dose-dependently. An IRF-1 binding element (IRF-E-XAF1) is found in the -30 to -38 nucleotide region upstream of the ATG initiator codon of the XAF1 gene. Site-directed mutagenesis of IRF-E-XAF1 abrogates native and IFN-induced promoter activity and binding capacity. ATRA induces XAF1 expression both in vitro and in vivo through interaction with IRF-E-XAF1. Overexpression of XAF1 increases cell susceptibility to ATRA-induced growth suppression both in vitro and in vivo. Furthermore, the effect of ATRA on XAF1 expression is independent of the promoter methylation and the subcellular distribution of XIAP.
XAF1 participates in ATRA-induced growth suppression through IRF-1-mediated transcriptional regulation.
[Show abstract][Hide abstract] ABSTRACT: Telomerase activation, which is observed in most human cancers, plays an important role in carcinogenesis. Human telomerase reverse transcriptase (hTERT) is a subunit of telomerase that is essential for telomerase activity. The aim of the study was to investigate whether nonsteroidal antiinflammatory drugs (NSAIDs) inhibit telomerase activity and hTERT.
Four colon carcinoma cell lines, HT-29, COLO205, CRL-2134, and SW1116, were used in the experiments. Polymerase chain reaction-based telomeric repeat amplification (TRAP) enzyme-linked immunosorbent assay (ELISA) was used to measure telomerase activity in the cells after treatment with aspirin, indomethacin, or SC-236 (a specific cyclooxygenase-2 [COX-2] inhibitor). Expression of hTERT mRNA and protein was detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, respectively. The dual luciferase reporter assay was performed to identify the potential cis-response elements to NSAIDs in the promoter region of hTERT.
Aspirin, indomethacin, and SC-236 inhibited telomerase activity in HT-29, COLO205, and CRL-2134 cell lines, but not in the SW1116 cell line. NSAIDs inhibited hTERT mRNA and protein expression through suppression of hTERT transcriptional activity. The hTERT promoter fragment -145 to -330 basepairs (bp) upstream of the ATG starting site was sufficient to respond to the NSAID-induced inhibitory effect and the inhibition was COX-2-independent.
NSAIDs inhibit telomerase activity at hTERT transcriptional, mRNA, and protein levels in colon carcinoma cells. The hTERT promoter fragment -145 to -330 bp may be the cis-response element to NSAIDs.
Cancer 03/2006; 106(6):1243-9. DOI:10.1002/cncr.21694 · 4.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Inhibition of cyclooxygenase-2 has been proposed to be a potential mechanism for the chemoprevention of gastrointestinal tumors by nonsteroidal anti-inflammatory drugs. This study investigates the mechanisms by which the cyclooxygenase-2 inhibitor SC236 induces apoptosis of gastric cancer cell lines and its downstream signaling pathway.
Two gastric cancer cell lines, AGS and MKN28, were treated with SC236 and assessed for cell growth and apoptosis. The involvement of mitogen-activated protein kinase and Akt kinase/protein kinase B (Akt/PKB) pathways and their downstream signalings were studied in the AGS cell line.
SC236 treatment induced apoptosis in gastric cancer cells and caused activation of p38 and stress-activated protein kinase/jun kinase, but down-regulated Akt/PKB. The specific p38 inhibitor SB203580 and the dominant-negative stress-activated protein kinase/jun kinase both failed, while the constitutively active form of Akt/PKB was able to block SC236-induced apoptosis. SC236-induced apoptosis was coupled with release of cytochrome c and activation of caspases.
One of the pathways involved in SC-236-induced apoptosis in gastric cancer cells is through downregulation of Akt and then release of cytochrome c.
[Show abstract][Hide abstract] ABSTRACT: The incidence of colorectal cancer (CRC) in Hong Kong is rising. The trend of colonoscopy demand is uncertain.
To investigate colonoscopy demand and practice in a Hong Kong regional hospital over the past nine years.
Colonoscopy data from 1st January 1997 to 31st August 2005 were retrieved and divided into two equal periods for comparison. Colonoscopy practice and findings between the two periods were compared.
There was no change in the number of endoscopists and colonoscopy sessions in the two periods. The number of colonoscopy done in the two periods was 2,681 and 2,871, respectively. The indications for screening of CRC/polyp (9.3 vs. 24.7%, p < 0.0001) and surveillance of CRC/polyp (4.7 vs. 10.9%, p < 0.0001) were increased, but decreased for diarrhea (18 vs. 10.2%, p < 0.0001) and per rectal bleeding (19 vs. 8.1%, p < 0.0001). The waiting time was lengthened from 2 to 4 weeks (p < 0.0001). The percentage of colonic adenomas (19.9 vs. 27.2%, p < 0.0001) was increased. A right-shift was observed in both CRC (37 vs. 50%, p = 0.018) and adenoma (21.6 vs. 38.1%, p < 0.0001).
The number of colonoscopies performed was governed by capacity partly through lengthening of waiting time to cope with demand. Ways to improve capacity for colonoscopies is needed.
[Show abstract][Hide abstract] ABSTRACT: Rabeprazole in combination with amoxicillin and metronidazole (RAM) has been shown to be an effective second-line treatment of Helicobacter pylori infection. The effects were compared of 7-day low-dose and high dose rabeprazole in RAM for the primary treatment of H. pylori infection in Chinese patients.
Helicobacter pylori-positive dyspeptic patients were randomized to receive either (i) rabeprazole 10 mg, amoxicillin 1000 mg and metronidazole 400 mg (RAM-10) or (ii) high-dose rabeprazole 20 mg, amoxicillin 1000 mg and metronidazole 400 mg (RAM-20), each given twice daily for 7 days. Helicobacter pylori eradication was confirmed by (13)c-urea breath test 5 weeks after stopping medications. side-effects of treatments were documented.
A total of 120 patients were eligible for analysis. By intention-to-treat and per-protocol analysis, the eradication rates were 83% and 86% in the RAM-10 group and 75% and 76% in the RAM-20 group, respectively (P = 0.26 and P = 0.17). Both regimens were well-tolerated and compliance was >98% in both groups.
Low-dose rabeprazole in combination with amoxicillin and metronidazole is an effective, economical and well-tolerated therapy for the treatment of H. pylori infection in Chinese population.
Journal of Gastroenterology and Hepatology 07/2005; 20(6):935-40. DOI:10.1111/j.1440-1746.2005.03889.x · 3.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Helicobacter pylori (H pylori) is associated with increased gastric inflammatory and epithelial expression of macrophage migration inhibitory factor (MIF) and gastric epithelial cell proliferation. This study aimed at determining whether H pylori directly stimulates release of MIF in monocytes, whether the cag pathogenicity island (PAI) is involved for this function, and whether MIF stimulated by H pylori increases gastric epithelial cell proliferation in vitro.
A cytotoxic wild-type H pylori strain (TN2), its three isogenic mutants (TN2Deltacag, TN2DeltacagA and TN2DeltacagE) were co-cultured with cells of a human monocyte cell line, THP-1, for 24 h at different organism/cell ratios. MIF in the supernatants was measured by an ELISA. Cells of a human gastric cancer cell line, MKN45, were then co-cultured with the supernatants, with and without monoclonal anti-MIF antibody for 24 h. The cells were further incubated for 12 h after addition of 3H-thymidine, and the levels of incorporation of 3H-thymidine were measured with a liquid scintillation counter.
The wild-type strain and the isogenic mutants, TN2DeltacagA and TN2 DeltacagE, increased MIF release at organism/cell ratios of 200/1 and 400/1, but not at the ratios of 50/1 and 100/1. However, the mutant TN2delta cag did not increase the release of MIF at any of the four ratios. 3H-thymidine readings for MKN-45 cells were significantly increased with supernatants derived from the wild-type strain and the mutants TN2DeltacagA and TN2DeltacagE, but not from the mutant TN2Deltacag. Moreover, in the presence of monoclonal anti-MIF antibody, the stimulatory effects of the wild-type strain on cell proliferation disappeared.
H pylori stimulates MIF release in monocytes, likely through its cag PAI, but not related to cagA or cagE. H pylori-stimulated monocyte culture supernatant increases gastric cell proliferation, which is blocked by anti-MIF antibody, suggesting that MIF plays an important role in H pylori-induced gastric epithelial cell proliferation.
World Journal of Gastroenterology 05/2005; 11(13):1946-50. DOI:10.3748/wjg.v11.i13.1946 · 2.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aspirin-induced apoptosis is one of the important mechanisms for its antitumour effect against gastric cancer. We aimed at investigating the involvement of bcl-2 family members in the apoptotic pathway in gastric cancer. Gastric cancer cell line AGS and MKN-45 were observed as to cell growth inhibition and induction of apoptosis in response to treatment with aspirin. Cell proliferation was measured by MTT assay. Apoptosis was determined by 4'-6-diamidino-2-phenylindole staining. Protein expression was determined by western blotting. We showed that aspirin activated caspase-8, caspase-9 and capase-3, cleaved and translocated Bid, induced a conformational change in and translocation of Bax and cytochrome c release. In addition, suppression of caspase-8 with the specific inhibitor z-IETD-fmk, as well as the pan-caspase inhibitor z-VAD-fmk, prevented Bid cleavage and subsequent apoptosis. The caspase inhibitors failed to abolish the effects on Bax activation. In conclusion, our results identify a role of caspase-8/Bid and activation of Bax as a novel mechanism for aspirin-induced apoptosis in gastric cancer.
[Show abstract][Hide abstract] ABSTRACT: Reactivation of survivin expression is involved in carcinogenesis and angiogenesis in colon cancer. Previous in vitro studies showed that mutation of the cysteine residue at position 84 (Cys84Ala) of survivin generates a dominant-negative mutant that triggers mitotic catastrophe and apoptosis. We investigated the therapeutic effect of the adeno-associated virus (AAV)-mediated survivin mutant (Cys84Ala) on colon cancer.
Survivin mutant (Cys84Ala) (Sur-Mut(Cys84Ala)) was cloned into the AAV expression vector pAM/CAG-WPRE.poly(A) to generate recombinant AAV-Sur-Mut(Cys84Ala) virus. Cell proliferation, apoptosis, mitotic catastrophe, and tumor growth were measured in vitro and in vivo.
Transduction of colon cancer cells with rAAV-Sur-Mut(Cys84Ala) inhibited cell proliferation and induced apoptosis and mitotic catastrophe in vitro. rAAV-Sur-Mut(Cys84Ala) sensitized colon cancer cells to chemotherapeutic drugs. Furthermore, expression of survivin mutant mediated by AAV inhibited tumorigenesis in colon cancer cells. Intratumoral injection of rAAV-Sur-Mut(Cys84Ala) significantly induced apoptosis and mitotic catastrophe and inhibited angiogenesis and tumor growth in a colon cancer xenograft model in vivo. No obvious cytotoxicity to other tissues was observed. More importantly, rAAV-Sur-Mut(Cys84Ala) expression strongly enhanced the antitumor activity of 5-Fluorouracil (5-FU), resulting in regression of established tumors.
Our results showed that rAAV-Sur-Mut(Cys84Ala) induced apoptosis and mitotic catastrophe and inhibited tumor angiogenesis and tumor growth. Thus, use of AAV-mediated survivin mutant (Cys84Ala) is a promising strategy in colon cancer gene therapy.
[Show abstract][Hide abstract] ABSTRACT: Population-based assessment of noncardiac chest pain (NCCP) is lacking. The aim of this study was to evaluate the prevalence, psychosocial factors and health seeking behaviour of NCCP in southern Chinese.
A total of 2 209 ethnic Hong Kong Chinese households were recruited to participate in a telephone survey to study the epidemiology of NCCP using the Rose angina questionnaire, a validated gastroesophageal reflux disease (GERD) questionnaire and the hospital anxiety-depression scale. NCCP was defined as non-exertional chest pain according to the Rose angina questionnaire and had not been diagnosed as ischaemic heart diseases by a physician.
Chest pain over the past year was present in 454 subjects (20.6%, 95% CI 19-22), while NCCP was present in 307 subjects (13.9%, 95% CI 13-15). GERD was present in 51% of subjects with NCCP and 34% had consulted a physician for chest pain. Subjects with NCCP had a significantly higher anxiety (P<0.001) and depression score (P=0.007), and required more days off (P=0.021) than subjects with no chest pain. By multiple logistic regression analysis, female gender (OR 1.9, 95% CI 1.1-3.2), presence of GERD (OR 2.8, 95% CI 1.6-4.8), and social life being affected by NCCP (OR 6.9, 95% CI 3.3-15.9) were independent factors associated with health seeking behaviour in southern Chinese with NCCP.
NCCP is a common problem in southern Chinese and associated with anxiety and depression. Female gender, GERD and social life affected by chest pain were associated with health care utilization in subjects with NCCP.
World Journal of Gastroenterology 03/2004; 10(5):707-12. · 2.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The role of gastric acid suppression in preventing the recurrence of ulcer complications after the eradication of Helicobacter pylori infection in patients taking long-term low-dose aspirin is uncertain.
We enrolled 123 patients who had ulcer complications after using low-dose aspirin continuously for more than one month and who had H. pylori infection. After the ulcers had healed and the H. pylori infection was eradicated, the patients were randomly assigned to treatment with 30 mg of lansoprazole daily or placebo, in addition to 100 mg of aspirin daily, for 12 months. The primary end point was the recurrence of ulcer complications.
During a median follow-up of 12 months, 9 of the 61 patients in the placebo group (14.8 percent), as compared with 1 of the 62 patients in the lansoprazole group (1.6 percent), had a recurrence of ulcer complications (adjusted hazard ratio, 9.6; 95 percent confidence interval, 1.2 to 76.1). Of these 10 patients, 4 had evidence of a recurrence of H. pylori infection and 2 had taken nonsteroidal antiinflammatory drugs before the onset of complications. Patients in the lansoprazole group were significantly less likely to have a recurrence of ulcer complications than patients in the placebo group (P=0.008). There was no significant difference in mortality between the two groups.
In patients who had ulcer complications related to the long-term use of low-dose aspirin, treatment with lansoprazole in addition to the eradication of H. pylori infection significantly reduced the rate of recurrence of ulcer complications.
New England Journal of Medicine 07/2002; 346(26):2033-8. DOI:10.1056/NEJMoa012877 · 55.87 Impact Factor