Low vaccination and infection rate of Omicron in patients with inflammatory bowel disease: a comparative study of three unique cohorts.

Background: The SARS-CoV-2 Omicron variant caused a large-scale outbreak of COVID-19 in Shanghai, China. Patients with inflammatory bowel disease (IBD) are at high risk of infection due to immunosuppressive interventions. We aimed to investigate the vaccination information of patients with IBD and update a vaccination guide based on a comparison of vaccination in asymptomatic carriers and healthy individuals. Methods: This retrospective study was conducted during an Omicron variant wave. We assessed the vaccination status in patients with IBD, asymptomatic carriers and healthy individuals. Factors with unvaccinated status and adverse events following vaccination were also determined in patients with IBD. Results: The vaccination rate was 51.2% in patients with IBD, 73.2% in asymptomatic carriers, and 96.1% in healthy individuals. Female sex (p = 0.012), Crohn's disease (p = 0.026), and disease behavior of B3 (p = 0.029) were factors that indicated a lower vaccination rate. A significantly higher proportion of healthy individuals had received one booster dose (76.8%) than asymptomatic carriers (43.4%) and patients with IBD (26.2%). Patients with IBD received vaccination without an increased risk of adverse events (p = 0.768). Conclusion: The vaccination rate of patients with IBD remains much lower than that of asymptomatic carriers and healthy individuals. The COVID-19 vaccine has been found to be safe among all three groups and patients with IBD are not more susceptible to adverse events.

CT enterography for evaluation of disease activity in patients with ileocolonic Crohn's disease.

BACKGROUND: CT enterography (CTE) is used routinely for assessment of activity and severity in Crohn's disease (CD), but there are few CTE scoring systems. The aim of this study was to develop a quantitative CTE scoring system for ileocolonic Crohn's disease activity. METHODS: Forty-nine CD patients with ileocolonic involvement were retrospectively included between March 2015 and May 2018. All patients underwent CTE and ileocolonoscopy. Mural hyperenhancement and mural thickening at CTE were scored quantitatively, while mural stratification, submucosal fat deposition, comb sign, perienteric fat hypertrophy and mesenteric fibrofatty proliferation were qualitative variables. A Tobit regression model was applied for assessing the association between Crohn's disease endoscopic index of severity (CDEIS) and CTE variables. RESULTS: A total of 280 intestinal segments were evaluated. Independent predictors for CDEIS were mural thickness (p < 0.001), mural stratification (p < 0.001) and comb sign (p = 0.002). In order to quantify disease activity based on CTE findings in each segment, a simplified CT enterography index of activity (CTEIA) was derived from logistic regression analysis. The formula was as follows: CTEIA (segment) = 2.1 mural thickness(mm) + 9.7 mural stratification + 5.2 comb sign. There was a high and significant correlation coefficient between CDEIS and CTEIA (r = 0.779, p < 0.001) for per-segment analysis. The model for the detection of ulcerative lesions in the colon and terminal ileum achieved an area under the receiver-operating curve of 0.901 using a cut-off point of 6.25. CONCLUSIONS: CTEIA is a new qualitative tool for evaluation of ileocolonic Crohn's disease, which need to be validated in further studies.

Drug therapy and monitoring for inflammatory bowel disease: a multinational questionnaire investigation in Asia.

BACKGROUND/AIMS: The incidence and prevalence of inflammatory bowel disease (IBD) is rising in Asia recently. The study aimed to obtain a comprehensive understanding of the current status of drug therapy and monitoring for IBD in Asia. METHODS: A questionnaire investigation on drug therapy and monitoring for IBD was conducted right before the 6th Annual Meeting of Asian Organization for Crohn's & Colitis. Questionnaires were provided to Asian physicians to fill out via emails between March and May 2018. RESULTS: In total, responses of 166 physicians from 129 medical centers were included for analysis. Among the surveyed regions, the most average number of IBD specialist gastroenterologists and nurses was 4.8 per center in Taiwan and 2.5 per center in Mainland China, respectively. 5-Aminosalicylic acid/sulfasalazine (99.4%) was the most preferred first-line choice for mild-moderate ulcerative colitis (UC), meanwhile corticosteroid (83.7%) was widely applied for severe UC. The first-line medication for Crohn's disease (CD) markedly varied as corticosteroid (68.1%) was the most favored in Mainland China, Japan, and South Korea, followed by infliximab (52.4%) and azathioprine (47.0%). Step-up strategy was preferred in mild-moderate UC (96.4%), while 51.8% of the physicians selected top-down treatment for CD. Only 25.9% and 17.5% of the physicians could test blood concentration of infliximab and antibody to infliximab in their hospitals, respectively. CONCLUSIONS: The current status of drug therapy and monitoring for IBD in Asia possesses commonalities as well as differences. Asian recommendations, IBD specialist teams and practice of therapeutic drug monitoring are required to improve IBD management in Asia.

Interleukin-26 Expression in Inflammatory Bowel Disease and Its Immunoregulatory Effects on Macrophages.

Background and Aim: Interleukin-26 (IL-26) has been implicated in several chronic inflammatory diseases. However, its role in inflammatory bowel disease (IBD) remains to be elucidated. We aimed to investigate IL-26 expression in IBD and its immunoregulatory effects on macrophages. Methods: We assessed IL-26 expression in the intestinal mucosa and blood samples of IBD patients and healthy controls (HC). The associations between the clinical characteristics of IBD and IL-26 expression levels in serum and peripheral blood mononuclear cells (PBMCs) were investigated. In addition, the transcriptional changes in THP-1 macrophages exposed to IL-26 were determined by RNA sequencing and validated with qRT-PCR, ELISA and western blots. Results: Compared with HC, in IBD patients, IL-26 expression levels were elevated in the inflamed intestinal mucosa, and reduced in serum and PBMCs. IL-26 mRNA levels in PBMCs, but not serum IL-26 levels, were inversely correlated with disease activity in IBD. Furthermore, IL-26 mRNA levels in PBMCs were significantly lower in patients with complicated Crohn's disease. A total of 1,303 differentially expressed protein-coding genes were identified between untreated and IL-26-treated macrophages. The up-regulated genes showed enrichment in some inflammatory and immune-related processes and pathways. Additionally, GSEA showed that neutrophil, monocyte, and lymphocyte chemotaxis was significantly enriched in IL-26-treated macrophages. Further validation revealed that IL-26 promotes the secretion of multiple inflammatory cytokines and chemokines and upregulates the expression of adhesion molecules, MMP-8, and MMP-9 while inhibiting MMP-1 in macrophages. Conclusion: Compared with HC, in IBD patients, IL-26 levels were elevated in the inflamed intestinal mucosa, and reduced in the peripheral blood. The transcriptional changes in macrophages exposed to IL-26 suggest that IL-26 may amplify the aberrant immune response in IBD by activating macrophages.

Relating the transcriptome and microbiome by paired terminal ileal Crohn disease.

Management of terminal ileal Crohn disease (CD) is difficult due to fibrotic prognosis and failure to achieve mucosal healing. A limited number of synchronous analyses have been conducted on the transcriptome and microbiome in unpaired terminal ileum tissues. Therefore, our study focused on the transcriptome and mucosal microbiome in terminal ileal tissues of patients with CD with the aim of determining the role of cross-talk between the microbiome and transcriptome in the pathogenesis of terminal ileal CD. Mucosa-attached microbial communities were significantly associated with segmental inflammation status. Interaction-related transcription factors (TFs) are the panel nodes for cross-talk between the gene patterns and microbiome for terminal ileal CD. The transcriptome and microbiome in terminal ileal CD can be differently related to the local inflammatory status, and specific differentially expressed genes may be targeted for mucosal healing. TFs connect gene patterns with the microbiome by reflecting environmental stimuli and signals from microbiota.

miR-27a induced by colon cancer cells in HLECs promotes lymphangiogenesis by targeting SMAD4.

AIM: Metastasis of tumor cells occurs through lymphatic vessels, blood vessels and transcoelomic spreading. Growing evidence from in vivo and in vitro studies has indicated that tumor lymphangiogenesis facilitates metastasis. However, the regulation of lymphangiogenesis in colon cancer remains unclear. The aims of this study were to identify key miRNAs in colon cancer lymphangiogenesis and to investigate its target and mechanism. METHODS: miRNA microarray analysis was conducted to identify miRNAs in human lymphatic endothelial cells (HLECs) that were regulated by co-cultured human colon cancer cells. Gain- and loss-of-function studies were performed to determine the function of miR-27a, a top hint, on lymphangiogenesis and migration in HLECs. Furthermore, bioinformatics prediction and experimental validation were performed to identify miR-27a target genes in lymphangiogenesis. RESULTS: We found that expression of miR-27a in HLECs was induced by co-culturing with colon cancer cells. Over-expression of miR-27a in HLECs enhanced lymphatic tube formation and migration, whereas inhibition of miR-27a reduced lymphatic tube formation and migration. Luciferase reporter assays showed that miR-27a directly targeted SMAD4, a pivotal component of the TGF-ß pathway. In addition, gain-of-function and loss-of-function experiments showed that SMAD4 negatively regulated the length of lymphatic vessels formed by HLECs and migration. CONCLUSIONS: Our data indicated that colon cancer cell induced the expression of miR-27a in HLECs, which promoted lymphangiogenesis by targeting SMAD4. Our finding implicated miR-27a as a potential target for new anticancer therapies in colon cancer.

Role of Raf-kinase inhibitor protein in colorectal cancer and its regulation by hydroxycamptothecine.

BACKGROUND: Recently accumulated evidence suggests that Raf kinase inhibitor protein (RKIP) participates in regulation of many signaling pathways and plays an important role in tumorigenesis and tumor metastasis. However, studies investigating the role of RKIP in colorectal cancer have not been reported. The aim of this study was to investigate the role of RKIP on colorectal cancer cell differentiation, progression and its correlation with chemosensitivity. RESULTS: Immunohistochemical analysis revealed that RKIP expression was higher in non-neoplastic colorectal tissue (NCRCT) and colorectal cancer tissue (CRCT) than that in metastatic lymph node tissue (MLNT) (P <0.05). P-ERK protein expression was higher in MLNT and CRCT than that in NCRCT (P = 0.02). Immunocytochemical analysis further revealed that RKIP expression was higher in the well differentiated cell line SW1116 as compared to that in the poorly differentiated cell line LoVo. Matrigel invasive assay demonstrated that the inhibition of RKIP by short hairpin RNA (shRNA) 271 transfection significantly increased the number of migrated cells (90.67 ± 4.04 vs. 37.33 ± 2.51, P <0.05), whereas over-expression of RKIP by PEBP-1 plasmid transfection significantly suppressed the number of migrated cells (79.24 ± 5.18 vs. 154.33 ± 7.25, P <0.05). Meanwhile, down-regulation of RKIP induced an increase in the cell survival rate by inhibiting apoptosis induced by hydroxycamptothecine. CONCLUSIONS: RKIP was also found to be associated with cell differentiation, with a higher activity in well differentiated colorectal cancer cells than in poorly differentiated ones. The upregulated expression of RKIP in colorectal cancer cells inhibited cell invasion and metastasis, while downregulation of RKIP reduced chemosensitivity by inhibiting apoptosis induced by HCPT.

Incidence, prevalence, and temporal trends of microscopic colitis: a systematic review and meta-analysis.

OBJECTIVES: A systematic review and meta-analysis was conducted to provide an accurate estimate of the incidence rate of microscopic colitis (MC) and to assess the association between medication use and the risk of MC. METHODS: We searched Medline, Embase, and Institute for Scientific Information (ISI) Web of Science up to 26 September 2014 to identify published epidemiological studies of MC. The pooled incidence rate, female-to-male incidence rate ratio, age at diagnosis, prevalence, as well as odds ratios (ORs) of MC in association with medication use were calculated using a fixed-effects model or a random-effects model. RESULTS: Of the 1,972 citations retrieved, 25 studies were included. Pooled incidence rate of collagenous colitis (CC) was 4.14 (95% confidence interval (CI) 2.89-5.40) per 100,000 person-years and 4.85 (95% CI, 3.45-6.25) for lymphocytic colitis (LC). The female-to-male incidence rate ratios were 3.05 (95% CI 2.92-3.19) for CC and 1.92 (95% CI 1.53-2.31) for LC. The median age at diagnosis for CC was 64.9 (range, 57.03-72.78) years, similar to LC (median 62.18, range 53.99-70.38). Furthermore, the incidence rate of MC increased with rising age. A steadily increasing trend of incidence rate for both CC and LC was observed before 2000; however, the incidence rate since then has become stable in the United States, Sweden, and Spain. An increased risk of MC was associated with the use of proton pump inhibitors (PPIs) and selective serotonin reuptake inhibitors (SSRIs) (OR 2.68, 95% CI 1.73-4.17 and OR 2.41, 95% CI 1.64-3.53, respectively). CONCLUSIONS: MC is a common disease process. Female gender, increased age, and the use of PPIs and SSRIs are associated with a significantly increased risk of developing MC. Further work is needed to evaluate reported data from developing countries and to elucidate the biologic mechanisms behind the risk factors for MC.

Optimal b value of diffusion-weighted imaging on a 3.0T magnetic resonance scanner in Crohn's disease.

AIM: To determine the optimal b value of diffusion-weighted imaging for detecting active inflammation in Crohn's disease. METHODS: Thirty-one patients clinically diagnosed with active Crohn's disease were referred for magnetic resonance examination. All patients were scanned on a 3.0T magnetic resonance scanner using the same protocol involving four different b values (800, 1500, 2000 and 2500 s/mm(2)). The diagnostic effect of diffusion-weighted imaging was evaluated and compared with endoscopic findings. The diffusion-weighted image quality of four b value groups was evaluated and apparent diffusion coefficient was measured for both normal and inflammatory intestinal segments. RESULTS: The contrast-to-noise ratio and signal-to-noise ratio were not satisfied when b value 2000 or 2500 s/mm(2) was adopted (36.52 ± 14.95 vs 34.78 ± 24.83, P > 0.05; 53.58 ± 23.45 vs 47.58 ± 29.67, P > 0.05). The qualitative image quality was not enough to meet diagnostic requirement. No matter which b value was chosen, the apparent diffusion coefficient of inflammatory intestinal segments was significantly lower than that of normal intestinal segments (1.38 ± 0.28 vs 2.00 ± 0.38, P < 0.01; 1.09 ± 0.20 vs 1.50 ± 0.28, P < 0.01; 0.95 ± 0.19 vs 1.34 ± 0.28, P < 0.01; 0.88 ± 0.14 vs 1.20 ± 0.21, P < 0.01). The lesion detection rate (90.32%), diagnostic sensitivity (81.18%) and specificity (95.10%) would be appropriate when b value 1500 s/mm(2) was adopted. CONCLUSION: High b value is suitable for intestinal DW examination on a high field MR scanner.

Nicotinamide phosphoribosyl transferase (Nampt) is a target of microRNA-26b in colorectal cancer cells.

A number of cancers show increased expression of Nicotinamide phosphoribosyl transferase (Nampt). However, the mechanism through which Nampt is upregulated is unclear. In our study, we found that the Nampt-specific chemical inhibitor FK866 significantly inhibited cell survival and reduced nicotinamide adenine dinucleotide (NAD) levels in LoVo and SW480 cell lines. Bioinformatics analyses suggested that miR-26b targets Nampt mRNA. We identified Nampt as a new target of miR-26b and demonstrated that miR-26b inhibits Nampt expression at the protein and mRNA levels by binding to the Nampt 3'-UTR. Moreover, we found that miR-26b was down regulated in cancer tissues relative to that in adjacent normal tissues in 18 colorectal cancer patients. A statistically significant inverse correlation between miR-26b and Nampt expression was observed in samples from colorectal cancer patients and in 5 colorectal cell lines (HT-29, SW480, SW1116, LoVo, and HCT116). In addition, over expression of miR-26b strongly inhibited LoVo cell survival and invasion, an effect partially abrogated by the addition of NAD. In conclusion, this study demonstrated that the NAD-salvaging biosynthesis pathway involving Nampt might play a role in colorectal cancer cell survival. MiR-26b may serve as a tumor suppressor by targeting Nampt.

18F-FDG-PET evaluation of pathological tumour response to neoadjuvant therapy in patients with NSCLC.

OBJECTIVES: The ability to identify potential responders to neoadjuvant treatment may improve patient selection or surgery and may help in the development of response criteria suitable for routine monitoring of response. The aim of this study was to evaluate the value of PET in predicting the pathological tumour response of non-small-cell lung cancer (NSCLC) to neoadjuvant therapy using a meta-analysis. METHODS: All available published studies investigating the value of PET in predicting the pathological response of NSCLC to neoadjuvant therapy were collected. Pooled sensitivity and specificity data were obtained using statistical software. Subgroup analysis was performed to explore the sources of heterogeneity. RESULTS: A total of 13 studies comprising 414 patients with NSCLC were included in the meta-analysis. Pooled sensitivity, specificity, positive predictive value and negative predictive value for PET-predicted response was 83% [95% confidence interval (CI); 76-89%], 84% (95% CI; 79-88%), 74% (95% CI; 67-81%) and 91% (95% CI; 87-94%), respectively. Significant heterogeneity (P<0.05) was observed. On the basis of our subgroup analyses, methodological quality could be responsible for this heterogeneity in our metaregression. The predictive value of PET in NSCLC patients with pathological response (considered the gold standard) was significantly higher than that of computed tomography (P<0.05). CONCLUSION: PET scanning has an important role in predicting nonresponders to neoadjuvant therapy in cases of NSCLC, and the predictive value of PET for evaluating pathologically documented responses is superior to that of computed tomography. However, additional evaluations using prospective clinical trials will be required to assess the clinical benefit of this strategy.

18F-FDG-PET evaluation of treatment response to neo-adjuvant therapy in patients with locally advanced rectal cancer: a meta-analysis.

The purpose of this meta-analysis was to evaluate the utility of positron emission tomography (PET) using fluor-18-deoxyglucose (FDG) to predict the response of rectal cancer to neo-adjuvant therapy. All previously published studies on the role of FDG-PET in predicting the response of rectal cancer to neo-adjuvant therapy were collected. Pooled sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated using statistical software. A total of 28 studies, comprising 1,204 patients with rectal cancer, were included in the meta-analysis. Pooled sensitivity, specificity, PPV and NPV for FDG-PET predicting the response to therapy was 78% [95% confidence interval (CI): 75-82%], 66% (95% CI: 62-69%), 70% (95% CI; 66-73%) and 75% (95% CI: 71-0.79%), respectively. The included studies were of a relatively high methodological quality according to the QUADAS (quality assessment of studies of diagnostic accuracy included in systematic reviews) criteria. Based on the subgroup analyses, there was no significant difference between the response index, the standardized uptake value and the visual response score in predicting the therapy response. However, the accuracy of the group that underwent PET scanning during therapy showed significantly higher values (sensitivity 86% and specificity 80%) than the group that was scanned after completion of the therapy. Therefore, FDG-PET is valuable for predicting the response of rectal carcinoma to neo-adjuvant therapy, and early evaluation of response during the therapy may be more promising. However, additional studies using prospective clinical trials will be required to assess the clinical benefit of this strategy.

The efficacy and safety of selective leukocytapheresis in the treatment of ulcerative colitis: a meta-analysis.

PURPOSE: The use of selective leukocytapheresis for the treatment of ulcerative colitis (UC) has been evaluated in several open and controlled trials, with varying outcomes. A meta-analysis was performed to better assess the efficacy and safety of selective leukocytapheresis as supplemental therapy compared with conventional pharmacotherapy in patients with UC. METHODS: All randomized trials comparing selective leukocytapheresis supplementation with conventional pharmacotherapy were included from electronic databases and reference lists. A meta-analysis that pooled the outcome effects of leukocytapheresis and pharmacotherapy was performed. A fixed effect model or random effect model was selected depending on the heterogeneity test of the trials. RESULTS: Nine randomized controlled trials met the inclusion criteria contributing a total of 686 participants. Compared with conventional pharmacotherapy, leukocytapheresis supplementation presented a significant benefit in promoting a response rate (OR, 2.88, 95% CI: 1.60-5.18) and remission rate (OR, 2.04; 95% CI, 1.36-3.07) together with significant higher steroid-sparing effects (OR, 10.49; 95% CI, 3.44-31.93) in patients with active moderate-to-severe UC by intention-to-treat analysis. Leukocytapheresis was more effective in maintaining clinical remission for asymptomatic UC patients than conventional therapy (OR, 8.14; 95% CI, 2.22-29.90). The incidence of mild-moderate adverse effects was much less frequent in the leukocytapheresis groups than conventional pharmacotherapy groups (OR, 0.16; 95% CI, 0.04-0.60). Few severe adverse events were observed. CONCLUSIONS: Current data indicate that leukocytapheresis supplementation may be more efficacious on improving response and remission rates and tapering corticosteroid dosage with excellent tolerability and safety than conventional pharmacotherapy in patients with UC. In addition, more high-quality randomized controlled trials are required to confirm the higher efficacy of leukocytapheresis in patients with UC.

[Epigallocatechin gallate induces apoptosis in human hepatocellular carcinoma HepG2 cells via TGF/Smad signaling pathway].

OBJECTIVE: To investigate the cytotoxic effect of epigallocatechin gallate (EGCG) on human hepatocellular carcinoma cell line HepG2 cells and corresponding changes of TGF-beta1-Smad pathway. METHODS: The cytotoxic effect of EGCG on HepG2 cells was determined by MTT assay. Cell cycle and apoptosis rate were detected by flow cytometry. RT-PCR and luciferase assay were used to verify whether TGF-beta1-Smad signaling pathway is intact in HepG2. The mRNA expression of Smad 2, Smad3, Smad4 and Smad7 was detected by real-time PCR. RESULTS: EGCG induced apoptosis in the HepG2 cells in a time- and concentration-dependent manner. The proportion of G(1) phase cells was increased gradually as the concentration increased. However, the percentage of cells in S phase was decreased gradually. Annexin V/PI assay demonstrated that early apoptosis increased as the concentration increased, and late apoptosis also increased, when treated with high-concentration EGCG. The intact TGF-beta1-Smad pathway was verified by luciferase assay and RT-PCR. There was no significant effect of EGCG on mRNA level of Smad 2, Smad 3, and Smad 4 in HepG2 cells, but downregulated mRNA level of Smad 7. CONCLUSION: EGCG can reduce apoptosis in human hepatocellular carcinoma cell line HepG2 cells. The activation of TGF-beta1-Smad signaling pathway may be involved in its cytotoxicity mechanisms.

Diagnostic value of FDG-PET in recurrent colorectal carcinoma: a meta-analysis.

Accurate detection of recurrent colorectal carcinoma remains a diagnostic challenge. The purposes of this study were to evaluate the diagnostic value of Positron emission tomography (PET) using fluor-18-deoxyglucose (FDG) in recurrent colorectal carcinoma with a meta-analysis. All the published studies in English relating the diagnostic value of FDG-PET in the detection of recurrent colorectal carcinoma were collected. Methodological quality of the included studies was evaluated. Pooled sensitivity, specificity and diagnostic odds ratio and SROC (summary receiver operating characteristic curves) were obtained by the statistical software. Twenty-seven studies were included in the meta-analysis. The pooled sensitivity and specificity for FDG-PET detecting distant metastasis or whole body involvement in recurrent colorectal carcinoma were 0.91 (95% CI 0.88-0.92) and 0.83 (95% CI 0.79-0.87), respectively. The pooled sensitivity and specificity for FDG-PET detecting hepatic metastasis were 0.97 (95% CI 0.95-0.98) and 0.98 (95% CI 0.97-0.99). The pooled sensitivity and specificity for pelvic metastasis or local regional recurrence were 0.94 (95% CI 0.91-0.97) and 0.94 (95% CI 0.92-0.96). FDG-PET is valuable for the assessment of recurrent colorectal carcinoma.

[Selective cyclooxygenase-2 inhibitors for the prevention of colorectal adenomas: a meta-analysis].

OBJECTIVE: To determine the validity and safety of selective cyclooxygenase (COX)-2 inhibitors for the prevention of colorectal adenomas. METHODS: The relevant data were retrieved from Medline (1966 to 2006), OVID (1996 to January 2007), EMBASE (1980 to January 2007), Chinese Cochrane Centre databases (up to January 2007) and Chinese Biological Medicine Disk (CBM disk, 1997 to 2007). Methodological quality assessment was based on the Cochrane Reviewers' Handbook and Jadad's Score Scale. Statistical software RevMan4.2 was used for meta-analysis. RESULTS: Six randomized clinical trials (5708 patients) were included in the study. Compared with placebo, selective COX-2 inhibitors lowered the detection rates of both adenomas and advanced adenomas (RR: 0.70, 95% CI: 0.55 - 0.88, P = 0.0003 and RR: 0.69, 95% CI: 0.53 - 0.89, P = 0.005). No significant difference was observed in the number of adverse events between patients taking selective COX-2 inhibitors and those taking placebo (RR: 1.07, 95% CI: 0.98 - 1.17, P = 0.11). Compared with placebo, selective COX-2 inhibitors increased the risk of cardiovascular events (RR: 1.21, 95% CI: 1.09 - 1.33, P = 0.0002). CONCLUSION: Selective COX-2 inhibitors can induce sufficient regression of colorectal adenomatous polyps and thus be used for chemoprevention of colorectal neoplasms. However, because of the potential cardiovascular events, it is not routinely recommended for this indication.

Apoptotic effect of Epigallocatechin-3-gallate on the human gastric cancer cell line MKN45 via activation of the mitochondrial pathway.

AIM: To investigate whether Epigallocatechin-3-gallate (EGCG) can induce apoptosis of the gastric cancer cell line MKN45 and its apoptotic pathway. METHODS: To determine this, apoptotic rates of MKN45 cells after EGCG treatment with or without caspase-3 inhibitor were evaluated by Annexin V-FITC + PI staining The influence of EGCG on the activity of caspase-3 in the MKN45 cells was determined by ELISA. By Rhodamine123 staining, the membrane potential change of the mitochondrion was also investigated, and mRNAs and protein expression of the bcl-2 family were analyzed by RT-PCR and Western blot. RESULTS: EGCG can induce apoptosis of MKN45 cells in time- and dose-dependent manner. Eight hours after EGCG treatment, the activity of caspase-3 in the MKN45 increased, especially 12 h after treatment. The mitochondrial membrane potential was significantly weakened 4 h after EGCG insult. The mRNA and protein expression levels of pro-apoptotic members, such as Bax, Bid and Bad, were upregulated gradually as treated time increased. Moreover, the mRNA and protein expression levels of anti-apoptotic members, such as Bcl-xL and Bcl-2, were inhibited. CONCLUSION: These data support that EGCG can induce apoptosis of the human gastric cancer cell line MKN45, and the effect is in a time- and dose-dependent manner. The apoptotic pathway triggered by EGCG in MKN45 is mitochondrial-dependent.