Subject(s)
Esophageal Neoplasms/pathology , Hemangioma, Cavernous/pathology , Adult , Endoscopic Mucosal Resection , Endoscopy, Digestive System , Endosonography , Esophageal Neoplasms/diagnostic imaging , Esophageal Neoplasms/surgery , Hemangioma, Cavernous/diagnostic imaging , Hemangioma, Cavernous/surgery , Humans , Male , Tumor BurdenABSTRACT
Human tumorigenesis resembles embryogenesis by aberrant activation of several developmental pathways including Wnt/ß-catenin signaling. Norrin is an atypical ligand for Frizzled receptor that is preferentially expressed in the endothelium to promote retinal vascularization during development. However, its expression pattern and potential roles in human cancers remain unclear. Here we report that Norrin expression is elevated in the parenchymal cells, but not endothelial cells, in gastric cancer (GC). Moreover, Norrin is required for growth and invasion of GC cells and its expression status is associated with unfavorable outcomes. However, analysis of the TGCA database demonstrates that Norrin expression status is not correlated with key target genes of Wnt/ß-catenin signaling. Among several signaling pathways hyperactivated in cancer, Norrin-depleted GC cells also display down-regulated AKT signaling except the canonical Wnt/ß-catenin signaling. Consistently, small molecule-induced cytosolic activation of AKT partially rescues the proliferative and invasive capability of Norrin-depleted cells. Together, these findings suggest a novel role of Norrin in gastric tumorigenesis that could be exploited for adjuvant therapy against the deadly malignancy.
Subject(s)
Eye Proteins/metabolism , Nerve Tissue Proteins/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Stomach Neoplasms/metabolism , Adult , Aged , Carcinogenesis/metabolism , Carcinogenesis/pathology , Cell Line, Tumor , Cell Movement , Cell Proliferation , Eye Proteins/antagonists & inhibitors , Eye Proteins/genetics , Female , Humans , Male , Middle Aged , Neoplasm Invasiveness , Nerve Tissue Proteins/antagonists & inhibitors , Nerve Tissue Proteins/genetics , Prognosis , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA, Small Interfering/genetics , Signal Transduction , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , Wnt Signaling PathwayABSTRACT
Background\Aim: Quadruple daily administration of proton-pump inhibitor (PPI) therapy achieves potent acid inhibition, and combined with amoxicillin, with its pharmacodynamic and pharmacokinetic characteristics, may be efficient for Helicobacter pylori eradication. We compared the efficacy of two optimized high-dose dual therapies with a bismuth-containing quadruple regimen for treating H. pylori infection. Rabeprazole dosages for H. pylori eradication were also evaluated. PATIENTS AND METHODS: Treatment-naive and H. pylori-positive subjects were recruited and randomly apportioned to three treatment groups: Group A (n = 87), rabeprazole 10 mg plus amoxicillin 750 mg (4 times/day for 14 days); Group B (n = 87), rabeprazole 20 mg plus amoxicillin 750 mg (4 times/day for 14 days); and Group C (n = 89), bismuth-containing quadruple regimen consisting of rabeprazole 20 mg, bismuth 220 mg, amoxicillin 1000 mg, and clarithromycin 500 mg (2 times/day for 14 days). Four weeks after treatment discontinuation, patients were examined for H. pylori infection by 13C-urea breath test. The rates of adverse effects, compliance, and eradication were evaluated. RESULTS: Eradication rates in groups A, B, and C were 78.1, 81.6, and 84.3%, respectively, based on intention-to-treat analysis, or 79.1, 83.5, and 86.2%, according to per-protocol analysis. Rates of adverse events and compliance of the three groups were similar. CONCLUSION: For treating H. pylori infection, optimized high-dose amoxicillin-PPI dual therapies failed to achieve high cure rates in China and held no advantage over a bismuth-containing quadruple regimen.
Subject(s)
Amoxicillin/pharmacokinetics , Helicobacter Infections/drug therapy , Helicobacter pylori/drug effects , Proton Pump Inhibitors/pharmacokinetics , Rabeprazole/pharmacokinetics , Adult , Amoxicillin/administration & dosage , Amoxicillin/pharmacology , Anti-Bacterial Agents/administration & dosage , Bismuth/administration & dosage , Breath Tests/methods , China/epidemiology , Clarithromycin/administration & dosage , Drug Administration Schedule , Drug Therapy, Combination/methods , Female , Gastritis/diagnosis , Gastritis/drug therapy , Gastritis/microbiology , Helicobacter Infections/diagnosis , Humans , Male , Middle Aged , Peptic Ulcer/diagnosis , Peptic Ulcer/drug therapy , Peptic Ulcer/microbiology , Proton Pump Inhibitors/administration & dosage , Proton Pump Inhibitors/pharmacology , Rabeprazole/administration & dosage , Rabeprazole/pharmacology , Treatment OutcomeABSTRACT
Objective. This prospective and randomized study evaluated the efficacy and safety of the nasopharyngeal airway relative to the nasal oxygen tube in obese patients undergoing painless gastroscopy. Materials and Methods. Obese patients (BMI ≥ 28 kg/m(2); n = 260) were randomly and equally apportioned to the nasopharyngeal airway (Group A) or nasal oxygen tube (Group B) group. Three patients were excluded due to failure of insertion of the nasopharyngeal airway. The duration of endoscopy, anesthetic dose, recovery time, and adverse events were recorded. The satisfaction of the anesthetist, physicians, and patient was scored. Results. The SpO2 reduction was significantly less in Group A than in Group B. Use of a respirator for assisted ventilation occurred significantly less in Group A. The groups were similar regarding mean arterial pressure, heart rate, anesthetic dose, duration of gastroscopy, recovery time, and adverse events. Satisfaction of the physician and anesthetist was greater in Group A; the groups were similar in patient satisfaction. Conclusions. Use of the nasopharyngeal airway for obese patients during painless gastroscopy resulted in less SpO2 reduction relative to the nasal oxygen tube. Altogether, it is a safe and effective device for obese patients undergoing painless gastroscopy.
