Inhibiting the proinflammatory cytokine tumor necrosis factor dramatically reduces gut inflammation and largely restores the gut barrier in Crohn's disease. Our data confirm the central role of TNF in gut barrier modulation in inflammatory conditions in vivo.
Short-term exposure to nicotine does not alter normal basal or NSAID-induced gut barrier function or transit. 51Cr-EDTA and the respective sugar markers correlate well in in vivo permeability testing in healthy humans. The radioactive test detects more NSAID-induced permeability increase than does the lactulose/mannitol ratio permeability test.
Several lines of evidence support immunotherapy in hepatocellular carcinoma (HCC). We have shown that intratumoral injections of the immune primer ilixadencel (pro-inflammatory allogeneic dendritic cells) are safe in renal-cell carcinoma. Here, we assessed ilixadencel as a single agent and combined with sorafenib in advanced HCC. Of 17 HCC patients enrolled, 12 patients received ilixadencel at the dose of 10 × 106 cells (six as monotherapy and six in combination with sorafenib), and five received ilixadencel at the dose of 20 × 106 cells as monotherapy. The primary objective was to evaluate tolerability. All patients had at least one adverse event, with 30% of such events considered as treatment-related, with one single treatment-related grade three event. The most common toxicity was grade 1 and 2 fever and chills. Eleven of 15 evaluable patients (73%) showed increased frequency of tumor-specific CD8+ T cells in peripheral blood. Overall one patient had a partial response (with ilixadencel as monotherapy), and five had stable disease as overall best response per mRECIST. The median time to progression was 5.5 months, and overall survival ranged from 1.6 to 21.4 months. Our study confirms the safety of ilixadencel as single agent or in combination with sorafenib and indicates tumor-specific immunological responses in advanced HCC.Clinical Trial Registration:
www.ClinicalTrials.gov, identifier: NCT01974661
Background:
Smoking modulates inflammatory bowel disease, protecting from ulcerative colitis on the one hand and worsening the course of Crohn’s disease on the other. This influence might occur through changes in intestinal permeability, because permeability is increased in most patients with Crohn’s disease.
Aim:
To study the influence of smoking on small intestinal permeability and its increase induced by indomethacin.
Methods:
50 smokers and 50 nonsmokers underwent a 51Cr‐EDTA basal permeability test and the same test after challenge with indomethacin 125 mg p.o.
Results:
Small intestinal permeability was the same in smokers (median 1.22%; IQR 1.00–1.58) and nonsmokers (1.24%; 0.94–1.66). Basal small intestinal permeability was lower in females (1.09%; 0.87–1.33) than in males (1.48%; 1.18–1.88). Indomethacin challenge increased permeability by 110% (71–141) in smokers, vs. 156% (78–220) in the nonsmokers (P=0.04).
Conclusion:
Smoking reduces the effect of NSAID on small intestinal permeability. It is therefore unlikely that the adverse effect of smoking on Crohn’s disease is related to its influence on intestinal permeability.
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