RESUMEN
Immunotherapy combined with targeted therapy can benefit the survival of patients with unresectable hepatocellular carcinoma. Atezolizumab combined with bevacizumab has achieved remarkable efficacy in patients with advanced hepatocellular carcinoma, but the efficacy of conversion therapy in patients with unresectable hepatocellular carcinoma still needs more evidences. The authors report the clinical efficacy of a case of unresectable hepatocellular carcinoma with hepatitis B virus related liver cirrhosis who was treated with immunotherapy plus targeted therapy combined with local treatment. Results show a good effect in patient without tumor recurrence after postoperative 9 months.
RESUMEN
AIM: To investigate the effects of alanyl - glutamine ( Ala -Gln) on expression of iNOS and TNF- α in injured intestinal mucosa induced by oral tacrolimus (FK506). METHODS: Twenty -four BALB/c mice were randomized to receive orally 0.2 mL of normal saline solution ( group Ⅰ ), 0.2 mL of FK506 in a dose of 0.1 mg/kg ( group Ⅱ ) or 1.0 mg/kg (group Ⅲ), and orally high -dose FK506 (0.2 mL, 1.0 mg/kg) plus intraperitoneal injection of Ala -Gln (0.5 g/kg )(group Ⅳ ),respectively. Damages of intestinal mucosa were determined by pathological examination.Intestinal mucosal permeability was analysed by FITC - dextran fluorescence assay. Expression of iNOS and TNF - α in intestine was detected by RT - PCR and Western blotting. RESULTS: Severe damage on the villi and increased intestinal permeability were observed in high - dose FK506 treated mice according to scanning electron microscopy and FITC - dextran flux respectively. The erosion and increased intestinal permeability were significantly alleviated by Ala - Gln treatment. Transcription of iNOS mRNA and TNF - α mRNA, which was up - regulated in high - dose FK506 treated group,was also markedly down- regulated in mice combined with Ala- Gln- treatment. A significantly increased expression of iNOS and TNF - α protein was found in the high - dose FK506 treated mice, while small amounts of these proteins were identified in the Ala - Gln - treated group. CONCLUSION: FK506 could induce a significant impairment of intestinal mucosa morphologically, which might be associated with up - regulated expression of iNOS and TNF - α in small intestinal mucosa. Subsequently, the intestinal permeability is increased. Ala - Gln has a strong protective effect on FK506 - induced intestinal barrier dysfunction, probably relates to the down - regulation of iNOS and TNF - α expression.
RESUMEN
AIM: To investigate the effects of alanyl-glutamine (Ala-Gln) on expression of iNOS and TNF-? in injured intestinal mucosa induced by oral tacrolimus(FK506). METHODS: Twenty-four BALB/c mice were randomized to receive orally 0.2 mL of normal saline solution ( groupⅠ), 0.2 mL of FK506 in a dose of 0.1 mg/kg (groupⅡ) or 1.0 mg/kg (groupⅢ), and orally high-dose FK506 (0.2 mL, 1.0 mg/kg) plus intraperitoneal injection of Ala-Gln (0.5 g/kg )(groupⅣ),respectively. Damages of intestinal mucosa were determined by pathological examination. Intestinal mucosal permeability was analysed by FITC-dextran fluorescence assay. Expression of iNOS and TNF-? in intestine was detected by RT-PCR and Western blotting.RESULTS: Severe damage on the villi and increased intestinal permeability were observed in high-dose FK506 treated mice according to scanning electron microscopy and FITC-dextran flux respectively. The erosion and increased intestinal permeability were significantly alleviated by Ala-Gln treatment. Transcription of iNOS mRNA and TNF-? mRNA, which was up-regulated in high-dose FK506 treated group, was also markedly down-regulated in mice combined with Ala-Gln-treatment. A significantly increased expression of iNOS and TNF-? protein was found in the high-dose FK506 treated mice, while small amounts of these proteins were identified in the Ala-Gln-treated group.CONCLUSION: FK506 could induce a significant impairment of intestinal mucosa morphologically, which might be associated with up-regulated expression of iNOS and TNF-? in small intestinal mucosa. Subsequently, the intestinal permeability is increased. Ala-Gln has a strong protective effect on FK506-induced intestinal barrier dysfunction, probably relates to the down-regulation of iNOS and TNF-? expression.