Associations Between Obesity and the Effectiveness of Anti-Tumor Necrosis Factor-α Agents in Inflammatory Bowel Disease Patients: A Literature Review and Meta-analysis.

Background: A total of 15% to 40% of adult inflammatory bowel disease (IBD) patients are obese. The influence of obesity on anti-tumor necrosis factor-α (anti-TNF-α) treatment in IBD patients is not consistent. Objective: To determine the association between obesity and the efficacy of anti-TNF treatment in IBD patients. Methods: We performed a systematic search from January 1990 through November 2019 on MEDLINE, Web of Science, Google Scholar, ClinicalTrials.gov, and Cochrane library. We included randomized controlled trials and observational cohort studies that investigated the outcome of anti-TNF treatment in IBD patients with stratification according to body mass index or body weight. The odds ratio (OR) and its 95% CI were calculated. Results: In this pooled meta-analysis, we observed that obesity increased the odds of failure of anti-TNF therapy (OR = 1.195; 95% CI = 1.034-1.380; P = 0.015; I2 = 47.8%). After performing subgroup analyses, obesity was associated with higher odds of anti-TNF treatment failure in ulcerative colitis (UC) patients (OR = 1.413; 95% CI = 1.008-1.980; P = 0.045; I2 = 20.0%) but not in Crohn's disease patients (OR = 1.099; 95% CI = 0.928-1.300). Obesity significantly increased the odds of treatment failure of both dose-fixed and weight-based anti-TNF agents (OR = 1.121, 95% CI = 1.027-1.224, P = 0.011, and OR = 1.449, 95% CI = 1.006-2.087, P = 0.046, respectively). Conclusion and Relevance: In our meta-analysis, obesity was associated with the inferior response of anti-TNF treatments in UC patients. Clinicians should be aware that obese UC patients may require higher doses in anti-TNF treatment.

Creeping fat in patients with ileo-colonic Crohn's disease correlates with disease activity and severity of inflammation: A preliminary study using energy spectral computed tomography.

OBJECTIVE: To investigate the relationship between creeping fat and inflammatory activity as well as the prognosis of ileo-colonic Crohn's disease (CD), based on a quantitative analysis of energy spectral computed tomography (CT). METHODS: A total of 40 patients with CD and 40 with other gastrointestinal diseases who underwent an energy spectral CT scanning between March 2014 and March 2015 were retrospectively enrolled. The endoscopic severity of CD was evaluated by the simple endoscopic score for Crohn's disease (SES-CD). The slope of the Hounsfield unit (HU) curve (λHU ) was measured and calculated on energy spectral CT images. Visceral and subcutaneous fat areas were also measured. The relationship between the quantitative data of creeping fat as well as the fat area and CD inflammation were analyzed. RESULTS: The λHU of creeping fat in patients with CD increased with the severity of intestinal inflammation (moderate/severe vs mild: -0.17 ± -0.68 vs -0.49 ± -0.61, P < 0.01). Moreover, the λHU of creeping fat around the intestinal segments without lesions in CD was significantly larger than that in the controls (-1.19 ± -0.56 vs - 1.42 ± -0.45, P < 0.01). The λHU was more accurate for detecting inflammatory lesions in CD than for calculating visceral fat. It was significantly correlated with SES-CD (r = 0.66, P < 0.01) and moderately correlated with the Harvey-Bradshaw index (r = 0.414, P < 0.01). CONCLUSION: The quantitative analysis of creeping fat using energy spectral CT is an effective method in inflammatory evaluation in patients with CD.

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.

High suppressor of cytokine signaling-3 expression impairs STAT3-dependent protective effects of interleukin-22 in ulcerative colitis in remission.

BACKGROUND: High SOCS3 expression in intestinal epithelial cells (IECs) of patients with ulcerative colitis (UC) in remission reflects the shorter time to relapse. We investigated whether high SOCS3 increased risk for relapse through violating STAT3-dependent protective effects of interleukin (IL)-22 during UC remission. METHODS: Expression of IL-22 and c-Myc in UC remission mucosa was analyzed by immunohistochemistry. Effects of IL-22 on migration and proliferation of IEC cell lines with enforced SOCS3 expression were assessed with wounding assay and CCK-8 assay, respectively. Influence of STAT3 interference and SOCS3 overexpression on IL-22-regulated expression of antimicrobial peptide and proliferation-related molecules, including DMBT1, c-Myc, Survivin, Bcl-2, and Bcl-xL, were performed with quantitative real-time polymerase chain reaction or Western blot. RESULTS: Patients with UC in remission showed significantly more IL-22-positive immune cells, but no difference of epithelial c-Myc levels, in mucosa compared with healthy controls. Overexpression of SOCS3 nearly abolished IL-22-induced activation of STAT3. By inhibiting STAT3 signaling, SOCS3 influenced IL-22-induced expression of DMBT1, c-Myc, Survivin, and Bcl-2 as well as proliferation and migration processes in cultured IEC cell line. CONCLUSIONS: SOCS3 overexpression impairs IL-22-mediated epithelial homeostasis and mucosal wound healing, which could be the mechanism for high SOCS3 IEC expression contributed early relapse of mucosal inflammation. Prevention of SOCS3 expression or enhancement of IL-22/STAT3 signaling in IEC seems to be rational therapeutic strategies for UC remission maintenance.

Prevalence and factors related to hepatitis B and C infection in inflammatory bowel disease patients in China: a retrospective study.

OBJECTIVES: The objectives of this retrospective study were to assess the prevalence of HBV and HCV infection in Chinese IBD patients, identify potential risk factors of the infection in this population, and discuss the prevalence of HBV and HCV in the general Chinese population. METHODS: A total of 714 IBD patients who had been investigated for HBV and/or HCV infection were consecutively enrolled in the study. Clinical and laboratory data on IBD and hepatitis infection were collected. A control group of 22,373 healthy individuals was also included in the study. RESULTS: Present and past HBV infection was found in 40.62% of IBD patients (ulcerative colitis: HBsAg+, 5.68%; anti-HBc+, 41.64%; Crohn's disease: HBsAg+, 5.29%; anti-HBc+, 39.80%;), and 27.58% of the non-IBD group (HBsAg+, 5.52%; anti-HBc+, 27.58% [P = 0.00]). HCV infection was found in 0.42% of IBD patients and 0.36% of the non-IBD group (P=0.80). One hundred and fifty-four of the IBD patients (21.57%) had been effectively vaccinated for HBV. In a multivariate analysis, age, family history of hepatitis B, and IBD-related admission were significantly related to HBV infection in IBD patients. Potential risk factors for HCV were not analyzed due to the limited number of HCV-positive patients in the study. CONCLUSIONS: Prevalence of HBV infection in IBD patients was higher than that in the non-IBD patients, whereas prevalence of HCV infection was similar to that of the non-IBD group. Effective vaccination for HBV was present in only a small proportion of IBD patients.

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.

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.

Efficacy and safety of adalimumab in Crohn's disease: meta-analysis of placebo-controlled trials.

OBJECTIVE: To evaluate the efficacy and safety of adalimumab in inducing and maintaining remission of Crohn's disease. METHODS: Electronic databases were searched. Placebo-controlled trials of adalimumab used in patients with Crohn's disease were included. Data were analyzed with Review Manager 4.2. RESULTS: Four studies enrolling 1402 patients were confirmed as meeting our criteria. Remission rates of inducing and maintaining remission in patients with Crohn's disease were higher for adalimumab than placebo (P<0.05). Adalimumab significantly improves the quality of life in patients with Crohn's disease. No significant difference in total adverse events was found in maintaining remission. Moreover, there were significantly less serious adverse events from taking adalimumab than from taking the placebo in long-term treatment. Patients with increased baseline C-reactive protein may benefit more from adalimumab therapy than those without. CONCLUSIONS: Adalimumab is effective and safe in Crohn's disease. However, studies of a larger number of patients are still required for better assessing the safety profile of adalimumab.

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.

Meta-analysis: the efficacy and safety of monoclonal antibody targeted to epidermal growth factor receptor in the treatment of patients with metastatic colorectal cancer.

OBJECTIVE: To evaluate systematically the efficacy and safety of anti-epidermal growth factor receptor (EGFR) monoclonal antibody added to a chemotherapeutic regimen in the treatment of patients with metastatic colorectal cancer (mCRC). METHODS: Eligible articles were identified by searching electronic databases. All randomized trials comparing the arm with an anti-EGFR monoclonal antibody to the arm without an anti-EGFR monoclonal antibody during the treatment of mCRC were included. A statistical analysis was performed with Review Manager 4.2.8. RESULTS: Seven randomized trials (n = 4186) were identified. The pooled response rates were 25.4% and 17.6% by intention-to-treat analyses for patients with or without an anti-EGFR monoclonal antibody, respectively, the OR was 3.36 (95% CI 1.42-7.95); the incidence of grades 3-4 adverse events were 71.2% and 54.3% for two groups, respectively, the OR was 2.23 (95% CI 1.74-2.86). The incidence of diarrhea, skin toxicity, hypomagnesemia was 62.3% versus 55.7%; 79.3% versus 19.7%; 27.2% versus 5.6%; and the summary OR was 1.36 (95% CI 1.03-1.80); 33.47 (95% CI 14.81-75.61); 6.73 (95% CI 3.84-11.82), respectively. CONCLUSION: Our results confirmed that monoclonal antibody targeted to EGFR could be effective in increasing response rates and could be a key therapeutic agent in the optimal treatment of mCRC, despite a moderate increase in grades 3-4 adverse events.