Porphyromonas gingivalis Lipopolysaccharide Damages Mucosal Barrier to Promote Gastritis-Associated Carcinogenesis.

BACKGROUND: Recent epidemiological studies suggested correlation between gastric cancer (GC) and periodontal disease. AIMS: We aim to clarify involvement of lipopolysaccharide of Porphyromonas gingivalis (Pg.), one of the red complex periodontal pathogens, in the GC development. METHODS: To evaluate barrier function of background mucosa against the stimulations, we applied biopsy samples from 76 patients with GC using a Ussing chamber system (UCs). K19-Wnt1/C2mE transgenic (Gan) mice and human GC cell-lines ± THP1-derived macrophage was applied to investigate the role of Pg. lipopolysaccharide in inflammation-associated carcinogenesis. RESULTS: In the UCs, Pg. lipopolysaccharide reduced the impedance of metaplastic and inflamed mucosa with increases in mRNA expression of toll-like receptor (TLR) 2, tumor necrosis factor (TNF) α, and apoptotic markers. In vitro, Pg. lipopolysaccharide promoted reactive oxidative stress (ROS)-related apoptosis as well as activated TLR2-ß-catenin-signaling on MKN7, and it increased the TNFα production on macrophages, respectively. TNFα alone activated TLR2-ß-catenin-signaling in MKN7, while it further increased ROS and TNFα in macrophages. Under coculture with macrophages isolated after stimulation with Pg. lipopolysaccharide, ß-catenin-signaling in MKN7 was activated with an increase in supernatant TNFα concentration, both of which were decreased by adding a TNFα neutralization antibody into the supernatant. In Gan mice with 15-week oral administration of Pg. lipopolysaccharide, tumor enlargement with ß-catenin-signaling activation were observed with an increase in TNFα with macrophage infiltration. CONCLUSIONS: Local exposure of Pg. lipopolysaccharide may increase ROS on premalignant gastric mucosa to induce apoptosis-associated barrier dysfunction and to secrete TNFα from activated macrophages, and both stimulation of Pg. lipopolysaccharide and TNFα might activate TLR2-ß-catenin-signaling in GC.

A rare case of gastric squamous-cell carcinoma metastasized from the cervix.

Gastric squamous-cell carcinoma (SqCC) metastasized form the cervix is rarely detected in endoscopic examination, although cervical carcinoma is the second most common in gynecologic malignancy. A 59-year-old female visited a clinic for anorexia, and an esophago-gastro-duodenoscopy (EGD) revealed multiple submucosal tumors (SMTs) of the stomach. After she was referred, an image-enhanced endoscopy enhanced multiple SMTs with white spots, whose findings were irregular micro-vascular patterns in the mucosa with irregular/absent micro-surface pattern. We took endoscopic biopsies, whose histological diagnoses were SqCC in the layer of the lamina propria under normal epithelium. Positron emission tomography-CT, CT and magnetic resonance imaging revealed an irregularly enhanced mass of the cervix, the irregularly thickening wall of the stomach and peritoneal nodules. Palliative care alone was administered based on poor condition associated with the Stage IV cervical carcinoma. In this case, endoscopic detection of gastric SqCC might provide a tip to make final diagnosis of primary site of cervical SqCC. The numbers of endoscopic examination become increasing, so further deep awareness of such patterns of metastasis in cervical cancer are required.