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.

Tuberculosis screening using IGRA and chest computed tomography in patients with inflammatory bowel disease: A retrospective study.

OBJECTIVES: To assess the prevalence and potential risk factors of latent tuberculosis infection (LTBI) in Chinese patients with inflammatory bowel disease (IBD) and to evaluate the role of chest computed tomography (CT) in the screening of LTBI. METHODS: A single-center retrospective study was conducted and all IBD patients who had been screened for LTBI by T-SPOT.TB between December 2011 and January 2016 were enrolled in the study. Both inpatient and outpatient records were collected and comprehensively reviewed. RESULTS: Altogether 534 IBD patients were included. The positivity rate of T-SPOT.TB was 18.0% overall, 31.9% in IBD unclassified, 22.5% in ulcerative colitis and 13.0% in Crohn's disease patients, respectively. Age, history of TB and the administration of immunosuppressants were significantly associated with T-SPOT.TB positivity. Among 123 patients who underwent serial testing, the conversion and reversion rate of T-SPOT.TB was 10.2% and 42.9%, respectively. Furthermore, 102 of 447 (22.8%) patients who underwent chest computed tomography (CT) were found with abnormal CT findings suggestive of LTBI. The concordance rate was 75% between the T-SPOT.TB and chest CT with a kappa value of 0.25 (95% CI 0.15-0.35). CONCLUSIONS: The prevalence of LTBI in IBD patients is high in China. Chest CT is recommended as an alternative to IGRA for screening LTBI of IBD patients before commencing immunosuppressive therapy in high-prevalence regions.

Intestinal tuberculosis and Crohn's disease: challenging differential diagnosis.

Along with epidemiological changes in tuberculosis (TB) and an increased incidence of Crohn's disease (CD), the differential diagnosis of intestinal TB (ITB) and CD is of vital importance and has become a clinical challenge because treatment based on misdiagnosis may lead to fatal outcomes. In this study, we reviewed the similarities and differences in clinical, endoscopic, radiological and histological features of these two diseases. Concomitant pulmonary TB, ascites, night sweats, involvement of fewer than four segments of the bowel, patulous ileocecal valve, transverse ulcers, scars or pseudopolyps strongly indicate ITB. Bloody stools, perianal signs, chronic diarrhea, extraintestinal manifestations, anorectal lesions, longitudinal ulcers and a cobblestone appearance are all suggestive of CD. Significant differences in the size, number, location and patterns of granulomas in ITB and CD with regard to their histopathologic features have been noted. Immune stain of cell surface markers is also helpful. Interferon-γ release assay and polymerase chain reaction analysis have achieved satisfactory sensitivity and specificity in the diagnosis of ITB. Computed tomography enterographic findings of segmental small bowel or left colon involvement, mural stratification, the comb sign and fibrofatty proliferation are significantly more common in CD, whereas mesenteric lymph node changes (calcification or central necrosis) and focal ileocecal lesions are more frequently seen in ITB. A diagnosis should be carefully established before the initiation of the therapy. In suspicious cases, short-term empirical anti-TB therapy is quite efficient to further confirm the diagnosis.

Organoids derived from digestive tract, liver, and pancreas.

Lgr5 marks stem cells in digestive epithelial tissues by lineage tracing, and in vitro ever-expansion of Lgr5 stem cells form organoids, which can be directed to differentiate into functional somatic cells. Organoids derived from gastrointestinal epithelium even recapitulate the morphologic features of their in vivo counterpart. Culture conditions are also modified to establish cancer organoids from individual patients. With great genetic stability during derivation and expansion, organoids retain either single mutation in patients with inherited disease or multiple mutations of cancer tissues. Together with efficient gene-editing protocol, organoids are emerging as powerful in vitro disease models.

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.

Computed tomography enterography versus balloon-assisted enteroscopy for evaluation of small bowel lesions in Crohn's disease.

BACKGROUND AND AIM: We aimed to assess the correlation between computed tomography enterography (CTE) and balloon-assisted enteroscopy on severity of small bowel lesions, and evaluated the accuracy of CTE parameters in assessing small intestine lesions in patients with Crohn's disease (CD). METHODS: We performed an observational study of a single-center cohort. Data were retrieved from our inpatient databases starting from October 2007. Correlations between computed tomography parameters (bowel wall thickness, mural enhancement, comb sign, extramural findings, and stricture), endoscopic and histological severity scores, CD Activity Index [CDAI], and C-reactive protein were assessed using Spearman's rank correlation. RESULTS: Seventy patients were included in this study. One hundred fifty-seven segments were examined. Bowel wall thickness (r = 0.6334, P < 0.0001), mural enhancement (r = 0.5477, P < 0.0001), comb sign (r = 0.5898, P < 0.0001), and extramural findings (r = 0.4754, P < 0.0001) were moderately correlated with the segmental Capsule Endoscopy CDAI. The segmental CTE score also moderately correlated with the segmental Capsule Endoscopy CDAI (r = 0.6714, P < 0.0001), while the total CTE score strongly correlated with the total Capsule Endoscopy CDAI (r = 0.7252, P < 0.0001). Both total CTE score (r = 0.5937, P < 0.0001) and total Capsule Endoscopy CDAI (r = 0.6364, P < 0.0001) correlated significantly with the Harvey-Bradshaw Index. Of five computed tomography parameters, bowel wall thickness have the best accuracy to detect small intestine lesions with an area under the receiver operating characteristic curve of 0.811 (P < 0.0001), with a sensitivity and specificity of 81.82% and 74.14%, respectively. CONCLUSION: CTE is a reliable technique for detecting small intestine lesions in patients with CD, also provides accurate information on small bowel CD severity and activity, with close agreement to inflammatory markers, CDAI, and histopathology.

Predictive and prognostic roles of BRAF mutation in patients with metastatic colorectal cancer treated with anti-epidermal growth factor receptor monoclonal antibodies: a meta-analysis.

OBJECTIVE: This study aimed to evaluate the predictive and prognostic roles of BRAF mutation in patients with metastatic colorectal cancer (mCRC) treated with anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (MoAbs). METHODS: Computer searches of the literature on BRAF mutation in mCRC patients were performed. Studies with objective response rate (ORR) to anti-EGFR MoAbs and/or overall survival (OS) and progression-free survival (PFS) with different BRAF gene expression in mCRC patients were eligible. RESULTS: A total of 19 studies including 2875 patients was enrolled in the meta-analysis. BRAF mutation was detected in 246 patients. The ORR was 18.4% (40/217) in mutant BRAF group and 41.7% (831/1993) in the wild-type BRAF group. The overall risk ratio (RR) for the ORR of BRAF mutation patients compared with wild-type BRAF patients was 0.58 (95% confidence intervals [CI] 0.35-0.94, P = 0.027). The median PFS of patients with BRAF mutation was significantly shorter than that of patients with wild-type BRAF (hazard ratio [HR] 2.98, 95% CI 2.07-4.27, P < 0.001) and the median OS of patients with BRAF mutation was also significantly shorter than that of those with wild-type BRAF (HR 2.85, 95% CI 2.31-3.52, P < 0.001). CONCLUSION: BRAF mutation is associated with poor response to anti-EGFR MoAbs and it is an adverse prognostic biomarker of the survival of patients with mCRC.

Gene expression of tumor necrosis factor receptor associated-factor (TRAF)-1 and TRAF-2 in inflammatory bowel disease.

OBJECTIVE: This study aimed to investigate the expression of tumor necrosis factor receptor-associated factor (TRAF)-1 and TRAF-2 in patients with inflammatory bowel disease (IBD). METHODS: Immunostaining, western blot and real-time polymerase chain reaction (PCR) were used to detect the expression of TRAF-1 and TRAF-2 in colonic mucosa of IBD patients and control. Furthermore, serum protein levels of TRAF-1 and TRAF-2 were measured by ELISA and the receiver operating characteristic (ROC) curve was used to determine their diagnostic value. RESULTS: The expression of TRAF-1 and TRAF-2 was significantly higher in inflamed and non-inflamed tissues of IBD patients than those in control (P < 0.05). Moreover, inflamed tissues had higher TRAF-1 and TRAF-2 expression than non-inflamed tissues (P < 0.05). Both TRAF-1 and TRAF-2 were shown to have a fair to excellent value in the differentiation of control and IBD patients with the area under the ROC curve (AUROC) of 0.680-1.000 (P < 0.001). CONCLUSION: The activation of TRAF-1 and TRAF-2 may be early events in the pathogenesis of IBD and their functions are not quite the same.

Safety and efficacy of calcium and magnesium infusions in the chemoprevention of oxaliplatin-induced sensory neuropathy in gastrointestinal cancers.

OBJECTIVE: To derive a more precise estimation on the safety and efficacy of calcium and magnesium (Ca and Mg) infusions in the prevention of oxaliplatin-induced sensory neuropathy. METHODS: A total of 16 studies including 1765 individuals were involved in this meta-analysis. Odds ratio (OR) and its 95% confidence interval (CI) were calculated. RESULTS: The difference in the incidence of oxaliplatin-induced neuropathy grade ≥ 1 was statistically significant between the Ca and Mg infusions treatment group and the untreated group (National Cancer Institute common toxicity criteria [NCI CTC]: OR 0.44, 95% CI 0.31-0.62, P = 0.000; oxaliplatin-specific scale [OSS]: OR 0.30, 95% CI 0.20-0.45, P = 0.000). Similar results were found in the incidences of oxaliplatin-induced neuropathy grade ≥ 2 (NCI CTC: OR 0.60, 95% CI 0.46-0.77, P = 0.000; OSS: OR 0.45, 95% CI 0.30-0.67, P = 0.000). However, we did not detect a trend of fewer oxaliplatin-induced neuropathy grade ≥ 3 incidences in the Ca and Mg infusions treatment group than the untreated group (NCI CTC: OR 0.67, 95% CI 0.44-1.01, P = 0.054; OSS: OR 0.66, 95% CI 0.34-1.29, P = 0.224). There was no difference in the response rate between the Ca and Mg treated group and the untreated group (OR 0.89, 95% CI 0.67-1.17, P = 0.391). CONCLUSION: Ca and Mg infusions do not alter the efficacy of oxaliplatin-based chemotherapy in gastrointestinal cancers, which may be reasonable to add them to lessen the incidence of neuropathy.

Increased JNK1 signaling pathway is responsible for ABCG2-mediated multidrug resistance in human colon cancer.

Multidrug resistance remains a major obstacle to effective chemotherapy of colon cancer. ABCG2, as a half-transporter of the G subfamily of ATP-binding cassette transporter genes (ABC transporters), is known to play a crucial role in multidrug resistance. However, the molecular mechanism of controlling ABCG2 expression in drug resistance of colon cancer is unclear and scarcely reported. In the present study, we systematically investigate the potential role of the c-Jun NH2-terminal kinase (JNK) signal pathway in ABCG2-induced multidrug resistance in colon cancer. In the hydroxycamptothecin (HCPT) resistant cell line SW1116/HCPT from human colon cancer cell line SW1116, ABCG2 is the major factor for multidrug resistance, other than well-studied ABCB1 or ABCC1. Our findings indicate that blocking the JNK pathway by pathway inhibitor SP600125 reduces the expression level and transport function of ABCG2 in drug-resistant cells SW116/HCPT. Notably, the experiments of small interfering RNA directed against JNK1 and JNK2 show that only silence of JNK1 gene has the equal effect as SP600125 on dephosphorylation of transcription factor c-Jun and the expression of ABCG2 protein, while the corresponding phenomena were not observed after silence of JNK2 gene. Meanwhile, SP600125 induces the apoptosis of SW116/HCPT cells by promoting the cleavage of PARP and suppressing the anti-apoptotic protein survivin and bcl-2, and increases the sensitivity of SW1116/HCPT to HCPT. Taken together, our work demonstrated that JNK1/c-jun signaling pathway was involved in ABCG2-mediated multidrug resistance in colon cancer cells. Definitely, inhibition of the JNK1/c-jun pathway is useful for reversing ABCG2-mediated drug resistance in HCPT-resistant colon cancer cells.

Once-daily versus multiple-daily mesalamine for patients with ulcerative colitis: a meta-analysis.

OBJECTIVE: To systematically review the efficacy and safety of once-daily (OD) mesalamine for the treatment of ulcerative colitis (UC) compared with multiple-daily (MD) mesalamine. METHODS: Electronic databases up to July 2011 were searched for related studies evaluating the efficacy of OD vs MD for treatment of UC. Only randomized controlled trials (RCTs) were considered eligible. Remission rates or relapse rates were analyzed using intention-to-treat (ITT) and per-protocol (PP) analysis. Pooled relative risk (RR) and 95% confidence interval (CI) were calculated. Publication bias was assessed with a funnel plot. RESULTS: Overall 10 RCTs including 9 full-text manuscripts and one abstract met the inclusion criteria. OD dosing of mesalamine was shown to be as effective as MD dosing for the maintenance of clinical remission in patients with quiescent UC (RR = 1.00, 95% CI 0.89-1.12) by ITT analysis. For active UC, a mild but significant benefit was achieved by OD dosing compared with MD dosing (RR = 0.80, 95% CI 0.64-0.99). Total adverse events were similar using OD and MD mesalamine in quiescent UC (RR = 1.06, 95% CI 0.93-1.20). Compliance with OD was slightly better than with MD (RR = 0.92, 95% CI 0.82-1.03). CONCLUSIONS: OD mesalamine is as effective and has a comparable safety profile as MD regimens for the maintenance treatment of UC, and is even more effective for inducing remission in active UC.

MicroRNA 506 regulates expression of PPAR alpha in hydroxycamptothecin-resistant human colon cancer cells.

Chemotherapeutic drug resistance remains a major obstacle to the successful treatment of colon cancer. Here, we show that 77 differentially expressed miRNAs were identified in SW1116/HCPT versus SW1116, and over-expressed miR-506 in SW1116/HCPT cells was validated. Then it was indicated that PPARα is a common target of miR-506 by using a luciferase reporter assay. Our results also demonstrated that cytotoxic ability of HCPT requires the concomitant presence of PPARα, and that loss of PPARα expression imparts resistance to HCPTs anti-tumor effects. All together, our studies indicate that miR-506 over-expression in established HCPT-resistant colon cancer cell line confers resistance to HCPT by inhibiting PPARα expression, then providing a rationale for the development of miRNA-based strategies for reversing resistance in HCPT-resistant colon cancer cells.

Factor V Leiden and thrombosis in patients with inflammatory bowel disease (IBD): a meta-analysis.

BACKGROUND: Testing for genetic risks of Factor V Leiden ( FVL ) in inflammatory bowel disease (IBD) patients with thromboembolism (TE) is common, but the safety and utility of such testing need review. AIM: The aim of the present study was to investigate whether the FVL polymorphisms would be one inherited prothrombotic risk factor that could significantly increase the risk of thrombosis in patients with IBD. METHODS: We performed an electronic databases search to identify published studies correlating the FVL mutations with four populations including one IBD group with TE complications, one control IBD group without TE complications, one control non-IBD group with TE complications and another healthy control (HC) group. Statistical analysis was performed with Review Manager (RevMan) 5.0. Sub-analysis/sensitivity analysis was also performed. RESULTS: We identified 112 titles and included 22 studies in this meta-analysis. The odds ratio (OR) of TE in IBD patients with FVL was higher as compared with IBD patients (OR: 4.00; 95%CI: 2.04, 7.87) and HC (OR: 3.19; 95%CI: 1.38, 7.36). There was a 1.25-fold (95%CI: 0.90-1.74) increase in incidence of FVL gene mutation in IBD patients compared with HC. The FVL mutations were not significantly different between IBD patients with thrombosis and non-IBD patients with thrombosis (OR: 0.79; 95%CI: 0.43, 1.47). CONCLUSION: FVL plays a role in IBD-TE, but to no greater extent than it does in the general population with TE.

Meta-analysis: circulating adiponectin levels and risk of colorectal cancer and adenoma.

OBJECTIVE: To provide a systematic review with a meta-analysis for addressing the association between circulating adiponectin levels and the risk of colorectal cancer and adenoma. METHODS: Multiple electronic sources including MEDLINE, EMBASE and the Science Citation Index Expanded databases were searched to identify relevant studies for this systematic review. All existing observational studies that examined the relationship between circulating adiponectin and colorectal cancer or adenoma were included. Weighted mean difference and 95% confidence intervals (CI) were estimated and pooled using meta-analysis methods. RESULTS: Overall 13 case control or nested case control studies met the inclusion criteria. A total of 6175 participants and 3015 cases of colorectal cancer and adenoma were included in this meta-analysis. The weighted mean difference (95% CI) were -1.084 µg/mL (-1.836, -0.331), P = 0.005 in colorectal cancer and -1.43 µg/mL (-2.231, -0.628), P = 0.000 in adenoma. In men, a 2% decreased risk of colorectal neoplasm for a 1 µg/mL increment in adiponectin levels was observed (OR = 0.98, 95% CI 0.96-0.99) whereas among women there is no evidence of such a trend (OR = 0.99, 95% CI 0.97-1.01). CONCLUSIONS: Patients with colorectal cancer and adenoma demonstrated markedly lower adiponectin values than controls, yet there was significant heterogeneity among studies. A negative dose response relationship between levels of adiponectin and the risk of colorectal neoplasm was observed in men.

Chemopreventive effect of epigallocatechin-3-gallate (EGCG) and folic acid on the N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastrointestinal cancer in rat model.

OBJECTIVE: To investigate the chemopreventive effect and mechanisms of epigallocatechin-3-gallate (EGCG) and folic acid on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastrointestinal cancer in rats, and to investigate and compare the combinatorial effects of EGCG and folic acid on the chemoprevention of gastrointestinal carcinogenesis. METHODS: A total of 159 healthy male Wistar rats were randomly divided into seven groups to have the MNNG in drink (group M), MNNG in drink and EGCG in the feed (group ME), MNNG in drink and folic acid in the feed (group MF), MNNG in drink and EGCG+folic acid in the feed (group MEF), EGCG in the feed (group E), folic acid in the feed (group F) or normal feed (group C), respectively. At 44 weeks, all the rats were killed and assessed for the presence of gastrointestinal tumor. The occurrence of cancer was evaluated by histology. Ki-67 in cancerous tissues and in situ apoptosis were determined by immunohistochemical staining or terminal deoxyribonucleotide transferase-mediated nick-end labeling (TUNEL) assay, respectively. RESULTS: The experiment was completed in 157 rats (98.74%). As compared with group M, the tumor incidence of group MEF decreased significantly (P=0.011). Ki-67 expression in cancerous tissues of group ME and MEF also decreased significantly (P=0.038, P=0.009), while apoptosis of group ME, MF and MEF increased significantly (P=0.000, P=0.003, P=0.000). CONCLUSION: EGCG combined with folic acid has an obvious chemopreventive effect on gastrointestinal carcinogenesis induced by MNNG in rats.

RNA interference (RNAi) of Ufd1 protein can sensitize a hydroxycamptothecin-resistant colon cancer cell line SW1116/HCPT to hydroxycamptothecin.

OBJECTIVE: To investigate whether RNA interference (RNAi) of the ubiquitin fusion-degradation 1-like protein (Ufd1) could sensitize hydroxycamptothecin (HCPT)-resistant colon cancer cell line SW1116/HCPT to the cytotoxic effect of HCPT. METHODS: SW1116/HCPT cells were transfected with plasmids containing Ufd1-specific small interfering RNA (siRNA) (Ufd1 knockdown cells) and non-specific siRNA (control cells). A drug sensitivity analysis, 3-(4,5)-dimethylthiahiazol (-z-y1)-3,5-di- phenytetrazoliumromide (MTT) assay was performed on Ufd1 knockdown cells and control cells. After treating the cells with HCPT, a caspase-3 and caspase-4 activity assay, flow cytometric analysis and Western blot for detecting phosphorylated c-Jun N-terminal kinase (p-JNK), phosphorylated protein kinases B (p-Akt), P53, ubiquitin, GADD 153 and Grp78/Bip were performed. RESULTS: According to the MTT assay, the survival rate of knockdown cells was significantly lower than that of the control cells (P < 0.01). Both caspase-3 and caspase-4 activity assay showed higher activation level in Ufd1 knockdown cells than that in the control cells (P < 0.01). A flow cytometric analysis revealed more severe S-phase arrest in the Ufd1 knockdown cells than that in the control cells (P < 0.05). The Western blot showed that increasing the concentration of HCPT resulted in a higher expression level of p-JNK, P53, ubiquitin, GADD 153 and Grp78/Bip in the Ufd1 knockdown cells than that in the control cells. CONCLUSION: Ufd1 plays a key role in HCPT resistance of SW1116/HCPT and RNAi of Ufd1 can sensitize SW1116/HCPT to the cytotoxic effect of HCPT via strengthening the activation of caspase-3 pathway and disturbing endoplasmic reticulum functions.

Comparison of immunochemical and guaiac-based fecal occult blood test in screening and surveillance for advanced colorectal neoplasms: a meta-analysis.

OBJECTIVE: To systematically evaluate whether immunochemical fecal occult blood tests (iFOBT) could improve clinical performance and test accuracy in screening and surveillance for advanced colorectal neoplasms. METHODS: Eligible articles were identified by searches of electronic databases. All randomized trials and diagnostic cohort trials directly comparing iFOBT with guaiac-based FOBT (gFOBT) were included. A statistical analysis was performed using RevMan 4.2.8. A sensitivity, specificity and summary receiver operating characteristic curve was performed using Meta Disc. RESULTS: We identified five randomized trials and 11 diagnostic cohort trials. In the randomized trials, the detection rates of advanced colorectal neoplasms with iFOBT or gFOBT were 2.23 percent and 1.24 percent, respectively. The pooled odds ratio (OR) was 1.50 (95% CI 0.94-2.39). In cohort trials, the advanced neoplasm detection rates of iFOBT or gFOBT were 1.44 percent and 0.50 percent (OR 1.99, 95% CI 1.24-3.19) in the average-risk screened population, and were 8.8 percent and 7.1 percent (OR 1.27, 95% CI 1.01-1.60) in diagnosed patients scheduled for colonoscopy. The sensitivity of iFOBT (0.67, 95% CI 0.61-0.73) was superior to that of gFOBT (0.54, 95% CI 0.48-0.60), as well as the specificities (0.85, 95% CI 0.83-0.87 vs 0.80, 95% CI 0.78-0.82) and positive predictive values (0.41 vs 0.29) in cohort trials of diagnosed patients. CONCLUSION: Our review suggests that iFOBT could perform better in increasing the detection rate of advanced colorectal neoplasm than gFOBT and possesses higher sensitivity and specificity in the surveillance of advanced colorectal neoplasm for patients.

[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.