Efficacy and safety of adalimumab in comparison to infliximab for Crohn's disease: A systematic review and meta-analysis.

BACKGROUND: Adalimumab (ADA) and infliximab (IFX) are the cornerstones of the treatment of Crohn's disease (CD). It remains controversial whether there is a difference in the effectiveness and safety between IFX and ADA for CD. AIM: To perform a meta-analysis to compare the effectiveness and safety of ADA and IFX in CD. METHODS: PubMed, Embase, Cochrane Library, and Web of Science databases were searched. Cohort studies were considered for inclusion. The primary outcomes were induction of response and remission, maintenance of response and remission, and secondary loss of response. Adverse events were secondary outcomes. RESULTS: Fourteen cohort studies were included. There was no apparent difference between the two agents in the induction response [odds ratio (OR): 1.27, 95% confidence interval (CI): 0.93-1.74, P = 0.14] and remission (OR: 1.11, 95%CI: 0.78-1.57, P = 0.57), maintenance response (OR: 1.08, 95%CI: 0.76-1.53, P = 0.67) and remission (OR: 1.26, 95%CI: 0.87-1.82, P = 0.22), and secondary loss of response (OR: 1.01, 95%CI: 0.65-1.55, P = 0.97). Subgroup analysis revealed ADA and IFX had similar rates of response, remission, and loss of response either in anti-tumor necrosis factor-α naïve or non-naïve patients. Further, there was a similar result regardless of whether CD patients were treated with optimized therapy, including dose intensification, shortening interval, and combination immunomodulators. However, ADA had a fewer overall adverse events than IFX (OR: 0.62, 95%CI: 0.42-0.91, P = 0.02). CONCLUSION: ADA and IFX have similar clinical benefits for anti-tumor necrosis factor-α naïve or non-naïve CD patients. Overall adverse events rate is higher in patients in the IFX group.

Anti-Helicobacter pylori treatment can effectively improve the clinical remission rates of irritable bowel syndrome: a controlled clinical trial meta-analysis.

Here we used a meta-analysis of several clinical trials to determine whether anti-Helicobacter pylori therapy has any positive effect on IBS patients. Here we compared the effective clinical remission rates between IBS patients treated with anti-H. pylori therapy and those who were not. This data would provide more clinical evidence regarding the efficacy of novel treatments and intervention points for IBS patients. Relevant studies were identified using keyword searches on various electronic databases, including PubMed, Embase, the Cochrane Central Register of Controlled Trials, CNKI, and CBM. Keywords included "helicobacter pylori" and "irritable bowel syndrome" among others. The literature was screened using relatively strict inclusion and exclusion criteria and RevMan 5.3.5 and Stata 15.1 software were used for meta-analysis and to assess publication bias and sensitivity. A total of ten studies met all of the inclusion criteria; these included 655 IBS patients with H. pylori infection, of these, 385 patients were in the experimental group and 270 patients were in the control group. A random-effects model was used to pool the odds ratios (ORs) with a 95% confidence interval (CIs) and the combined OR was 2.87 (95% CI: 1.74-4.72), p<0.0001. These findings suggest that anti-H. pylori therapy can effectively improve the remission rates of H. pylori-positive IBS patients. H. pylori infection is known to correlate with the incidence of IBS. Anti-H. pylori treatment can effectively improve the clinical remission rates of IBS patients. Whether this means that IBS patients should be actively treated with anti-H. pylori compounds as a novel strategy to improve the remission rates needs to be evaluated in vivo.

Anti-Helicobacter pylori treatment can effectively improve the clinical remission rates of irritable bowel syndrome: a controlled clinical trial meta-analysis

Here we used a meta-analysis of several clinical trials to determine whether anti-Helicobacter pylori therapy has any positive effect on IBS patients. Here we compared the effective clinical remission rates between IBS patients treated with anti-H. pylori therapy and those who were not. This data would provide more clinical evidence regarding the efficacy of novel treatments and intervention points for IBS patients. Relevant studies were identified using keyword searches on various electronic databases, including PubMed, Embase, the Cochrane Central Register of Controlled Trials, CNKI, and CBM. Keywords included "helicobacter pylori" and "irritable bowel syndrome" among others. The literature was screened using relatively strict inclusion and exclusion criteria and RevMan 5.3.5 and Stata 15.1 software were used for meta-analysis and to assess publication bias and sensitivity. A total of ten studies met all of the inclusion criteria; these included 655 IBS patients with H. pylori infection, of these, 385 patients were in the experimental group and 270 patients were in the control group. A random-effects model was used to pool the odds ratios (ORs) with a 95% confidence interval (CIs) and the combined OR was 2.87 (95% CI: 1.74-4.72), p<0.0001. These findings suggest that anti-H. pylori therapy can effectively improve the remission rates of H. pylori-positive IBS patients. H. pylori infection is known to correlate with the incidence of IBS. Anti-H. pylori treatment can effectively improve the clinical remission rates of IBS patients. Whether this means that IBS patients should be actively treated with anti-H. pylori compounds as a novel strategy to improve the remission rates needs to be evaluated in vivo.

Preinduced intestinal HSP70 improves visceral hypersensitivity and abnormal intestinal motility in PI-IBS mouse model.

OBJECTIVE: To investigate the impact of the preinduced intestinal heat shock protein 70 (HSP70) on the visceral hypersensitivity and abnormal intestinal motility in a post-infectious irritable bowel syndrome (PI-IBS) mouse model. METHODS: Eighty-four female C57BL/6 mice were randomly assigned to four groups: control group (n = 21) and induction + PI-IBS group (n = 21), PI-IBS group (n = 21) and induction group (n = 21). The mice in PI-IBS group were infected in vivo with Trichinella spiralis by oral administration. The visceral hypersensitivity and intestinal motility were evaluated respectively with abdominal withdrawal reflex and colon transportation test. The intestinal HSP70 protein and mRNA level was measured by Western blot and real-time PCR. Meanwhile, the intestinal proinflammatory cytokines IL-10 and TNF-α level was detected by ELISA. RESULTS: Compared with their counterparts in PI-IBS group, the animals in the Induction + PI-IBS group show significantly increased intestinal level of HSP70 and obviously ameliorative clinical figures, including abdominal withdrawal reflex score, intestine transportation time and Bristol scores (P < 0.05). Meanwhile, the intestinal post-inflammatory cytokines remarkably changed, including increased IL-10 level and decreased TNF-α level (P < 0.05). CONCLUSIONS: Intestinal HSP70 may play a potential protective role through improving the imbalance between the intestinal post-inflammatory and anti-inflammatory cytokines in PI-IBS.

Preinduction of heat shock protein 70 protects mice against post-infection irritable bowel syndrome via NF-κB and NOS/NO signaling pathways.

This study aimed to investigate the protective effects of preinduction of heat shock protein 70 (HSP70) on Trichinella spiralis infection-induced post-infectious irritable bowel syndrome (PI-IBS) in mice. Trichinella spiralis infection significantly reduced HSP70 abundance, ileal villus height and crypt depth, expression of tight junctions, serum lysine and arginine concentrations, and ileal SCL7A6 and SCL7A7 mRNA levels, induced inflammatory response, and activated NF-κB signaling pathway. Meanwhile, the heat treatment upregulated HSP70 expression, and then reversed intestinal dysfunction and inflammatory response. Preinduction of HSP70 enhanced serum arginine and intestinal SCL7A7 expression and inhibited NF-κB activation compared with PI-IBS model. Treatment with pyrrolidine dithiocarbamate (PDTC, an NF-κB inhibitor) and N-nitro-L-arginine methyl ester hydrochloride (L-NAME, a nitric oxide synthase inhibitor, NOS) further demonstrated that preinduction of HSP70 might inhibit NF-κB and activated NOS/nitric oxide (NO) signaling pathways. In conclusion, preinduction of HSP70 by heat treatment may confer beneficial effects on Trichinella spiralis infection-induced PI-IBS in mice, and the protective effect of HSP70 may be associated with inhibition of NF-κB and stimulation of NOS/NO signaling pathways.

Changes of cytokine levels in a mouse model of post-infectious irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is a highly prevalent functional gastrointestinal disorder. Post-infectious IBS (PI-IBS) is caused by an acute gastrointestinal infection preceding the onset of symptoms. However, the pathophysiology of PI-IBS is not clear, and the purpose of this study was to investigate the probable immune mechanisms of PI-IBS. METHODS: C57BL/6 mice were randomly assigned to either an infection group or a control group. Mice in the infection group were infected with Trichinella spiralis to establish a model of PI-IBS (500 Trichinella), while control mice received only salt solution. Visceral sensitivity of colorectal distention in mice was evaluated by abdominal withdrawal reflex scores and intestinal inflammation was assessed using hematoxylin-eosin staining; at day 56 post-infection, the mRNA and protein levels of specific cytokines in the gut segments were detected using reverse-transcription polymerase chain reaction and enzyme-linked immunoabsorbent assay. RESULTS: Levels of interferon γ and interleukin (IL)-17 in the PI-IBS group were significantly increased in the duodenum and ileum, and IL-10 was decreased in the jejunum, ileum, and colon compared with control mice. However, the expression level of IL-1ß was not significantly different between the two groups. CONCLUSIONS: The present study suggests that the local low-grade inflammation and immune activation that are an important component of the pathophysiology of PI-IBS are primarily induced and maintained by specific cytokines.

Impact of the alterations in the interstitial cells of Cajal on intestinal motility in post-infection irritable bowel syndrome.

The interstitial cells of Cajal (ICC) are basic components of gastrointestinal motility. However, changes in ICC and their role in post­infection irritable bowel syndrome (PI­IBS) remain to be elucidated. To observe the impact of alterations in the ICC on intestinal motility in a PI­IBS mouse model, female C57BL\6 mice were infected by the oral administration of 400 Trichinella spiralis larvae. The abdominal withdrawal reflex, intestine transportation time (ITT), grain numbers, Bristol scores, wet/dry weights and the percentage water content of the mice feces every 2 h were used to assess changes in the intestinal motor function. The intestines were excised and sectioned for pathological and histochemical examination. These intestines were also used to quantify the protein and mRNA expression of c­kit. The C57BL\6 mouse can act as a PI­IBS model at day 56 post­infection. Compared with the control mice, the ITT was shorter, the grain numbers, Bristol scores, wet weights and water contents of the mice feces were higher and the dry weights were unchanged in the PI­IBS mice. The protein and mRNA expression levels of c­kit were upregulated in the entire PI­IBS mouse intestines. Following immunohistochemical staining, the increased number of c­kit­positive cells were detected predominantly in the submucosa and myenteron. These results suggested that the alterations of the ICC resulted in the changes of the intestinal motility patterns in the PI­IBS mouse models induced by Trichinella spiralis infection, which may be the main mechanism underlying intestinal motility disorders in PI­IBS.

Enhanced inhibitive effects of combination of rofecoxib and octreotide on the growth of human gastric cancer.

Our previous studies indicated that cyclooxygenase-2 inhibitor or octreotide could suppress the proliferation of gastric adenocarcinoma in vitro or in vivo. The present study was aimed to find whether rofecoxib combined with octreotide could enhance the inhibitive effects on the growth of gastric cancer. The effect of rofecoxib or octreotide on proliferation of gastric cancer cell line was determined by 3H-thymidine ribotide incorporation. The TdT-mediated dUTP nick end-labeling assay was used to detect the apopotosis. To determine their synergic antineoplastic effects, the interaction between rofecoxib and octreotide on SGC-7901 cell was evaluated by the median effect plot. After orthotopical implantion of xenografts of human gastric cancer in stomach, nude mice were given rofecoxib plus octreotide for 8 weeks. Cyclooxygenase-2 in gastric cancer tissues was measured by immunohistochemistry. Combination of rofecoxib and octreotide presented synergistic effect (combination index < 1) in the majority of responses. The inhibitory rate for xenografts in nude mice was 89.7% in rofecoxib group. Combination of rofecoxib and octreotide enhanced inhibitory rate to 98.8%. The combination greatly increased the apoptotic index (78.20% +/- 6.45%) of the xenografts as compared with that of using rofecoxib alone (46.60% +/- 3.42%); the difference was very significant (p < 0.001). Rofecoxib could inhibit the activity of cyclooxygenase-2 in the tissue of gastric adenocarcinomas of nude mice. Our results indicate that combination of rofecoxib and octreotide significantly enhances the antiproliferative effect in gastric adenocarcinoma, which might have potential therapeutic value.

[Effects of rofecoxib on angiogenesis of pancreatic cancer xenograft in nude mice].

BACKGROUND & OBJECTIVE: Angiogenesis plays a crucial role in invasive tumor growth. Overexpressed cyclooxygenases-2 (COX-2) may be related to increased angiogenesis in the rapidly progressed tumor. The purpose of the present study was to investigate the effects of the highly selective COX-2 inhibitor,rofecoxib on the growth of pancreatic cancer xenografts in nude mice in vivo as well as on tumor-associated angiogenesis. METHODS: BXPC-3 human pancreatic cancer cells overexpressing COX-2 was inoculated subcutaneously into nude mice. Rofecoxib (30 mg/kg) was administered orally to animals every day for eight weeks. The microvessel density was immunostained with factor VIII antibody. The expression of VEGF on BXPC-3 pancreatic cancer cell line was measured by immunocytochemistry in vitro. Gelatin zymography and RT-PCR technology were used to determine MMP-2 progelatinase and expression of MMP-2 mRNA. RESULTS: Rofecoxib significantly reduced the tumor volume with an inhibition rate of 87.7% as well as tumor weight with an inhibition rate of 73.64% for xenografts in nude mice. The density of microvessel was notably lower in xenografts treated with rofecoxib than in those without treatment (1.5+/-0.2 vs 4.7+/-1.5/200x; P< 0.05). Expression of VEGF protein, MMP-2 progelatinase and MMP-2 mRNA levels in the xenografts treated with rofecoxib were lower than those of control group. CONCLUSION: Antiangiogenesis is one of the mechanisms by which Rofecoxib suppresses pancreatic cancer proliferation.

[The effects of selective cyclooxygenase-2 inhibitors on the growth of gastric adenocarcinoma].

OBJECTIVE: This study was aimed to compare the effects of three kinds of selective cyclooxygenase-2 inhibitors (meloxicam, celecoxib, rofecoxib on the growth of gastric adenocarcinoma SGC7901 cell line, and to observe the effect of rofecoxib, on transplanted gastric cancer of nude mice in vivo. METHODS: The proliferation and apoptosis of SGC7901 cells were measured by 3H-thymidine incorporation into DNA and the TdT-mediated dUTP nick end-labeling assay (TUNEL) separately. The expression of PCNA and COX-2 of gastric adenocarcinoma cells were detected by immunocytochemistry. Human gastric adenocarcinoma SGC7901 cells were implanted orthotopically in the stomach of nude mice. Rofecoxib (30 mg.kg-1.d-1) was administrated i.g. for eight weeks. RESULTS: All the drugs potentially decreased 3H-thymidine incorporation into SGC7901 cells. The inhibition effects showed a dose-dependence manner. The median-response concentration was: 1.18 x 10(-7) mol/L (meloxicam), 1.68 x 10(-8) mol/L (celecoxib), 4.39 x 10(-9) mol/L (rofecoxib). After treatment with meloxicam, celecoxib, rofecoxib (1 x 10(-5) mol/L) for 24 hours, the apoptosis indices of SGC7901 cells were: 19.8% +/- 1.8%, 24.6% +/- 1.2% and 31.2% +/- 2.2%, respectively. The higher selective inhibition on COX-2, the higher apoptosis index (P < 0.01). Rofecoxib down-regulated the expression of COX-2 and PCNA of SGC7901 cell, both in vitro and in vivo. The inhibition rate for xenografts in situ in nude mice treated with rofecoxib was 93.9%. CONCLUSION: The higher selective inhibition on COX-2, the stronger inhibition on gastric adenocarcinoma cells. Rofecoxib may be one of the important medicines in the treatment of gastric adenocarcinoma.

[The combination of octreotide to rofecoxib enhanced the inhibitory effect on growth of human hepatocellular carcinoma].

OBJECTIVE: To know whether octreotide combined with rofecoxib would enhance the inhibitory effect on proliferation of hepatocellular carcinoma (HCC) in vitro and in vivo. METHODS: The proliferation of HCC SMMC 7721 cells were measured by incorporating (3)H-thymidine ribotide ((3)H-TdR) into DNA. The effect of octreotide combined with rofecoxib on proliferation of HCC cells was evaluated according to the median-response principle. SMMC-7721 cells were implanted orthotopically in the liver of nude mice. Nude mice were treated with either octreotide (100 micro g x kg(-1) x d(-1)) combined with rofecoxib (30 mg x kg(-1) x d(-1)) or rofecoxib (30 mg x kg(-1) x d(-1)) alone for 8 weeks. The volumes of implanted tumors were measured. RESULTS: The combination of octreotide and rofecoxib significantly inhibited (3)H-TdR incorporation of HCC cell line in culture in a dose-dependent manner (r = -0.997, P < 0.01). The combination indexes of octreotide and rofecoxib in the majority of effect range were less than 1. The inhibitory rate of xenograft in situ in the combined group (97.1%) was significantly higher than that in the rofecoxib group (73.2%). In addition, increased amount of fibroplasia was observed in the combined group as compared with that in control group. No severe side effect was observed in all the treatment groups. CONCLUSIONS: The inhibitory effect of octreotide combined with rofecoxib on HCC cell line was significantly greater than that of octreotide or rofecoxib alone in vitro. Octreotide combined with rofecoxib greatly enhanced the anti-growth effects on HCC in vivo when compared with rofecoxib alone. These synergic results may be of potential therapeutic benefit to those patients with non-resectable HCC.