ABSTRACT
BACKGROUND/AIM: Although IL-6-mediated activation of the signal transduction and activator of transcription 3 (STAT3) axis is involved in inflammation and cancer, the role of STAT3 in Helicobacter-associated gastric inflammation and carcinogenesis is unclear. This study investigated the role of STAT3 in gastric inflammation and carcinogenesis and examined the molecular mechanism of Helicobacter-induced gastric phenotypes. METHODS: To evaluate the contribution of STAT3 to gastric inflammation and carcinogenesis, we used wild-type (WT) and gastric epithelial conditional Stat3-knockout (Stat3Δgec ) mice. Mice were infected with Helicobacter felis and euthanized at 18 months postinfection. Mouse gastric organoids were treated with recombinant IL-6 (rIL-6) or rIL-11 and a JAK inhibitor (JAKi) to assess the role of IL-6/STAT3 signaling in vitro. RESULTS: Inflammation and mucous metaplasia were more severe in WT mice than in Stat3Δgec mice. The epithelial cell proliferation rate and STAT3 activation were increased in WT mice. Application of rIL-6 and rIL-11 induced expression of intestinal metaplasia-associated genes, such as Tff2; this induction was suppressed by JAKi administration. CONCLUSIONS: Loss of STAT3 signaling in the gastric mucosa leads to decreased epithelial cell proliferation, atrophy, and metaplasia in the setting of Helicobacter infection. Therefore, activation of STAT3 signaling may play a key role in Helicobacter-associated gastric carcinogenesis.
ABSTRACT
Objective We evaluated the safety and efficacy of vonoprazan-based amoxicillin and clarithromycin 7-day triple therapy (VAC) in comparison to proton pump inhibitor (PPI)-based (PAC) as a first-line treatment and vonoprazan-based amoxicillin and metronidazole 7-day triple therapy (VAM) in comparison to PPI-based (PAM) as a second-line treatment for the eradication of Helicobacter pylori in Japan. Methods We performed a non-randomized, multi-center, parallel-group study to compare first-line VAC to PAC and second-line VAM to PAM. A pre-planned subgroup analysis on CAM resistance was also performed. Safety was evaluated with an adverse effects questionnaire (AEQ), which was completed by patients during therapy. Results The first-line eradication rates (ER) in the intention-to-treat (ITT) and per protocol (PP) analyses were 84.9% (95% CI: 81.9-87.6%, n=623) and 86.4% (83.5-89.1%, n=612), respectively, for VAC and 78.8% (75.3-82.0%, n=608) and 79.4% (76.0-82.6%, n=603), respectively, for PAC. The ER of VAC was higher than that of PAC in the ITT (p=0.0061) and PP analyses (p=0.0013). The ERs for VAC in patients with CAM-resistant and CAM-susceptible bacteria were 73.2% (59.7-84.2%, n=56) and 88.9% (83.4-93.1%, n=180), respectively. PAC was associated with higher AEQ scores for diarrhea, nausea, headache, and general malaise. In the second-line ITT and PP analyses VAM achieved ERs of 80.5% (74.6-85.6%, n=216) and 82.4% (76.6-87.3%, n=211), respectively, while PAM achieved ERs of 81.5% (74.2-87.4%, n=146) and 82.1% (74.8-87.9%, n=145), respectively. No significant differences were observed in the ITT (p=0.89) or PP (p=1.0) analyses. Conclusion The ER of first-line VAC was higher than that of PAC, but still <90%. No difference was observed between second-line VAM and PAM. Vonoprazan-based triple therapy was safe and well tolerated.
Subject(s)
Amoxicillin/therapeutic use , Anti-Bacterial Agents/therapeutic use , Clarithromycin/therapeutic use , Helicobacter Infections/drug therapy , Helicobacter pylori/drug effects , Proton Pump Inhibitors/therapeutic use , Pyrroles/therapeutic use , Sulfonamides/therapeutic use , Adult , Aged , Aged, 80 and over , Cohort Studies , Drug Therapy, Combination , Female , Humans , Japan , Male , Middle Aged , Prospective Studies , Young AdultABSTRACT
An 83-year-old male presented with distended abdomen. A computed tomography scan demonstrated pleural effusion, ascites, peritoneal thickness, and panniculitis. Multiple small white nodules of peritoneum were observed during a laparoscopy examination, and biopsy specimens revealed noncaseating granulomas. Gallium scintigram demonstrated an accumulation in the peritoneum and revealed a panda sign that has been described as an indication of sarcoidosis. Although sarcoidosis rarely induces peritonitis with ascites, peritoneal sarcoidosis was diagnosed and he began receiving steroid therapy. After primary steroid therapy, his ascites completely disappeared, and he has maintained a complete response with continuous low dose steroid therapy.
Subject(s)
Ascites/etiology , Peritonitis/complications , Sarcoidosis/complications , Aged, 80 and over , Humans , Male , Peritonitis/diagnostic imaging , Peritonitis/drug therapy , Sarcoidosis/diagnostic imaging , Sarcoidosis/drug therapy , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
A 52-year-old woman presented with recurrent, severe abdominal pain. Laboratory tests and imaging were insignificant, and treatment for functional dyspepsia was ineffective. The poorly localized, dull, and severe abdominal pain, associated with anorexia, nausea, and vomiting, was consistent with abdominal migraine. The symptoms were relieved by loxoprofen and lomerizine, which are used in the treatment of migraine. We herein report a case of abdominal migraine in a middle-aged woman. Abdominal migraine should be considered as a cause of abdominal pain as it might easily be relieved by appropriate treatment.