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.

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.

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.

[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 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.