Toll like receptors (TLR) play important roles in the signaling of many pathogen‐related molecules and endogenous proteins associated with immune activation. The –196 to –174del polymorphism affects ...the TLR2 gene and alters its promoter activity. We investigated the influence of the TLR2–196 to –174del polymorphism on the occurrence of non‐cardiac gastric cancer (NCGC) in a Japanese population. The study was carried out with 289 patients with NCGC, 309 non‐cancer patients with abdominal discomfort and 146 healthy controls. The –196 to –174del TLR2 polymorphism was investigated using the allele‐specific polymerase chain reaction method in all of the subjects. The –196 to –174del/del genotype of TLR2 showed a significantly higher frequency in NCGC patients than in healthy controls (adjusted odds ratio OR = 6.06; 95% confidence interval CI = 1.86–19.72). Similarly, the frequency of the –196 to –174del/del genotype was significantly higher among NCGC patients than in non‐cancer patients (adjusted OR = 2.02; 95% CI = 1.22–3.34). The same genotype was associated with an increased risk of both intestinal (OR = 2.00, 95% CI = 1.12–3.60) and diffuse‐type (OR = 2.05; 95% CI = 1.11–3.79) histopathology. There were no significant associations between TLR2 genotypes and tumor stage and anatomical location. Our data suggest that the –196 to –174del/del genotype of TLR2 may increase the risk of gastric cancer in the Japanese population. (Cancer Sci 2007; 98: 1790–1794)
Background Magnifying narrow-band imaging (NBI) endoscopy clearly visualizes superficial gastric mucosal patterns and capillary patterns. Objective To investigate gastric mucosal patterns by using ...magnifying NBI endoscopy and identify any relationship between those patterns and Helicobacter pylori –induced gastritis. Design Gastric mucosal patterns seen with magnifying NBI in uninvolved gastric corpus were divided into the following categories: normal—small, round pits with regular subepithelial capillary networks; type 1—slightly enlarged, round pits with unclear or irregular subepithelial capillary networks; type 2—obviously enlarged, oval or prolonged pits with increased density of irregular vessels; and type 3—well-demarcated oval or tubulovillous pits with clearly visible coiled or wavy vessels. Setting Department of Gastroenterology, Fujita Health University. Patients This study involved 106 participants undergoing upper endoscopy. Results H pylori infection–positive ratios of normal and types 1, 2, and 3 patterns were 7.5%, 92.9%, 94.5%, and 66.7%, respectively. Sensitivity and specificity for types 1 + 2 + 3 for detection of H pylori positivity and type 3 for detection of intestinal metaplasia were 95.2%, 82.2%, 73.3%, and 95.6%, respectively. Development of mucosal patterns from normal to types 1, 2, and 3 was correlated with all histological parameters ( P < .0001), lower pepsinogen I/II ratios ( P < .0001), and degree of endoscopic atrophy ( P < .0001). Sensitivity and specificity of type 3 for the prediction of severe histological atrophy was also better than those of serum pepsinogen level and standard endoscopy. Limitations Only 1 endoscopist performed endoscopic procedures, and interobserver agreement could not be assessed. Conclusions Magnifying NBI endoscopy is useful for predicting H pylori infection and the histological severity of gastritis and is valuable for predicting gastric atrophy in the entire stomach.
We herein report the case of a 79-year-old patient with unresectable stage III non-small cell lung cancer who developed immune-related hepatitis caused by durvalumab administration. Durvalumab was ...administered at 10 mg/kg every two weeks after the treatment with carboplatin (AUC2), paclitaxel (35 mg/m2), and 60 Gy radiation. At the day 208 in which the 14th durvalumab administration was scheduled, the patient was urgently hospitalized due to CTCAE Grade 4 hepatic dysfunction detected during the an outpatient blood sampling test. He was diagnosed with immune-related hepatitis and started on methylprednisolone 60 mg/day. After 51 days, his liver dysfunction improved and he was discharged.
Background: Common single‐nucleotide polymorphisms (SNPs) in microRNAs (miRNA) have been shown to be associated with susceptibility to several human cancers. We evaluated the associations of three ...SNPs (rs11614913, rs2910164, and rs3746444) in pre‐miRNAs (miR‐196a2, miR‐146a, and miR‐499) with the risk of gastric cancer (GC) and peptic ulcer diseases, and with the severity of Helicobacter pylori‐induced gastritis in Japanese population.
Methods: The rs11614913 (C>T), rs2910164 (G>C), and rs3746444 (A>G) SNPs were genotyped in 552 GC, and 697 non‐cancer subjects, including 141 gastric and 73 duodenal ulcer, and 483 non‐ulcer subjects. The degree of histologic gastritis was classified according to the updated Sydney System, and the serum pepsinogen levels were measured in selected 579 and 204 cases.
Results: The rs2910164 CC genotype held a significantly higher risk of GC when compared to non‐cancer subjects (adjusted odds ratio (OR) = 1.30, 95% confidence interval (CI) = 1.02–1.66, p =.03). Similarly, the rs2910164 C carrier was associated with higher risk of GC when compared to both non‐cancer and non‐ulcer subjects (OR = 1.39, 95%CI = 1.00–1.93, p =.05, adjusted OR = 1.57, 95%CI = 1.09–2.27, p =.016, respectively). The rs2910164 CC genotype was associated with non‐cardia and upper third, diffuse type and advanced stage GC. The rs11614913 TT genotype was associated with higher degree of mononuclear cell infiltration (score 0–1 vs 2∼, adjusted OR = 1.62, 95%CI = 1.05–2.49, p =.03).
Conclusions: The rs2910164 (G>C) SNP in the miR‐146a is associated with susceptibility to GC. In addition, the rs11614913 (C>T) SNP in the miR‐196a2 is associated with the degree of H. pylori‐induced mononuclear cell infiltration.
Objective In general, surface ulceration in gastric gastrointestinal stromal tumor (GIST) is considered a malignant feature; however, the mechanism underlying its formation has not been evaluated in ...detail. In this study, we analyzed the factors involved in ulceration using resected specimens of gastric GIST. Methods A total of 48 samples were retrospectively analyzed. We examined the association of surface ulceration of gastric GIST with the MIB-1 labeling index, mitotic number, tumor size, endoscopic ultrasound (EUS) findings and growth pattern on computed tomography (CT). Results The proportion of men was significantly higher in the ulceration group than in the non-ulceration group (p=0.04146), whereas age was not significantly different between the groups. Tumor was significantly larger in the ulceration group than in the non-ulceration group (p=0.0048). There was no correlation between tumor size and ulcer number. The MIB-1 index was not related to ulceration, nor were EUS findings. The number of mitotic cells tended to be higher in the ulceration group than in the non-ulceration group (p=0.05988). Intraluminal growth pattern was strongly associated with ulceration (p=0.00019). After a multivariate analysis, the growth pattern was the only factor associated with ulceration of gastric GIST. Conclusion Although formation of surface ulceration in gastric GIST was partially associated with the degree of malignancy, the growth pattern was the most important factor associated with ulceration in gastric GIST.
Background and Aims
Fusobacterium
species are part of the gut microbiome in humans, but some species have been recognized as opportunistic pathogens implicated in inflammatory diseases including ...inflammatory bowel diseases. Here, we performed prevalence screening of
Fusobacterium
in ulcerative colitis (UC) in Japanese patients.
Methods
We examined
Fusobacterium nucleatum
(
F. nucleatum
) and whole
Fusobacterium
species
(
Pan
-
fusobacterium
) by quantitative real-time PCR in 163 inflamed mucosae from 152 UC patients. Data were correlated with clinical subtypes of UC.
Results
In an initial prevalence screen,
F. nucleatum
and
Pan
-
fusobacterium
were detected in 6.3 % (4/64) and 53.1 % (34/64). For all 163 mucosae, the prevalence of
Pan
-
fusobacterium
was 54.6 % (89/163).
Pan
-
fusobacterium
status was concordant in inflamed and normal adjacent samples, and the matched cases during 1-year follow-up colonoscopy. The higher amount of
Pan
-
fusobacterium
was observed in chronic continuous type compared to one attack and relapse/remitting type (
p
= 0.039). The higher amount of
Pan
-
fusobacterium
was also associated with rather mild clinical course of disease, such as non-steroid dependency (
p
= 0.015), non-refractory phenotype (
p
= 0.013), and non-severe phenotype (
p
= 0.04). Based on the distribution of
Pan
-
fusobacterium
measurable cases, we identified 10 cases as having a high amount of
Pan
-
fusobacterium
(FB-high). The clinicopathological features of FB-high UC cases were also highlighted by chronic continuous type and mild phenotypes of disease.
Conclusion
Whole
Fusobacterium
species, but not
F. nucleatum
, are common in UC patients and have a role in persistence of colonic inflammation in UC. However,
Fusobacterium
infection is associated with rather mild clinical phenotypes of UC.
We investigated the association between ulcerative colitis (UC) and polymorphisms of IL-17A (rs2275913, G-197A) and IL-17F (rs763780, 7488T/C) genes. We employed the multiplex PCR-SSCP method to ...detect gene polymorphisms. Both the numbers of -197A (IL-17A) and 7488T (IL-17F) alleles were significantly correlated to the development of UC. The frequencies of -197A/A and 7488T/T genotypes in the UC group were significantly higher than those in the non-UC group. An adjusted analysis revealed that -197A and 7488T alleles were independent risk factors for the developing UC. In addition, both polymorphisms were significantly associated with the pancolitis phenotype. Furthermore, -197A allele was significantly correlated to the chronic relapsing phenotype and -197A/A homozygote was more frequent in steroid-dependent cases, whereas 7488T allele was correlated with the chronic continuous phenotype. Our results provided the first evidence that -197A (IL-17A) and 7488T (IL-17F) alleles may influence the susceptibility to and pathophysiological features of UC independently.
Background Magnifying narrow-band imaging (NBI) endoscopy visualizes superficial gastric mucosal and capillary patterns. We aimed to investigate changes in gastric mucosal patterns seen by magnifying ...NBI endoscopy after Helicobacter pylori eradication. Methods Gastric mucosal patterns in non-pathological gastric corpus were observed by magnifying NBI endoscopy before and 12 weeks after H. pylori eradication in thirty patients. By using paired photographs of each case, changes in NBI mucosal patterns during H. pylori eradication were judged in a consensus manner by three blinded endoscopists. Results At 12 weeks after H. pylori eradication, 20 of 24 subjects who had been successfully treated showed remarkable changes in gastric mucosal patterns (sensitivity 83.3%, specificity 100%). In the specimens from these subjects, the patterns of enlarged or elongated pits were improved to small oval or pinhole-like round pits, and the density of fine irregular vessels was decreased. Histological assessment showed alleviation of chronic inflammation in all subjects (p < 0.0001), while such a change was not observed for four subjects showing severe gastric atrophy and intestinal metaplasia. When the subjects were divided according to the presence of severe gastric atrophy, the diagnostic efficacy of magnifying NBI for predicting the results of H. pylori eradication was excellent in subjects without severe gastric atrophy and intestinal metaplasia (sensitivity and specificity, 100%). However, no change in the NBI mucosal pattern was observed in subjects with severe gastric atrophy and intestinal metaplasia, regardless of the H. pylori eradication result. Conclusions At least in subjects without severe gastric atrophy or intestinal metaplasia, successful H. pylori eradication treatment shows improvements in gastric mucosal patterns with the use of magnifying NBI endoscopy early after successful treatment.
Epithelial-to-mesenchymal transition (EMT) is a phenomenon that allows the conversion of adherent epithelial cells to a mesenchymal cell phenotype, which enhances migratory capacity and invasiveness. ...Recent studies have suggested that EMT contributes to the pathogenesis of ulcerative colitis (UC). We investigated the promoter DNA methylation status of EMT-related genes in the colonic mucosa in UC.
Colonic biopsies were obtained from the rectal inflammatory mucosa of 86 UC patients and the non-inflammatory proximal colonic mucosa of 10 paired patients. Bisulfite pyrosequencing was used to quantify the methylation of 5 candidate CpG island promoters (NEUROG1, CDX1, miR-1247, CDH1, and CDH13) and LINE1.
Using an unsupervised hierarchical clustering analysis, inflamed rectal mucosa was well separated from mucosa that appeared normal. The CDH1 and CDH13 promoters were significantly associated with patient age (p = 0.04, 0.03, respectively). A similar trend was found between those genes and the duration of disease (CDH1: p = 0.07, CDH13: p = 0.0002, mean of both: p<0.00001). Several positive associations were found between hypermethylation and severe clinical phenotypes (CDX1 and miR-1247 and a refractory phenotype: p = 0.04 and 0.006, respectively. miR-1247 and CDH1 hyper methylation and a more severe Mayo endoscopic subscore: miR-1247: p = 0.0008, CDH1: p = 0.03, mean of both: p = 0.003). When the severe clinical phenotype was defined as having any of five phenotypes (hospitalized more than twice, highest Mayo endoscopic subscore, steroid dependence, refractory, or a history of surgery) miR-1247 hypermethylation was associated with the same phenotype (p = 0.008).
Our data suggest that variability in the methylation status of EMT-related genes is associated with more severe clinical phenotypes in UC.
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