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  • S. Karger AG  (3)
  • Fujishiro, Mitsuhiro  (3)
  • 1
    In: Digestion, S. Karger AG
    Abstract: Introduction: Submucosal invasion is a core hallmark of early gastric cancer (EGC) with poor prognosis. However, the molecular mechanism of the progression from intramucosal gastric cancer (IMGC) to early submucosal-invasive gastric cancer (SMGC) is not fully understood. The objective of this study was to identify genes and pathways involved in the submucosal invasion in EGC using comprehensive gene expression analysis. Methods: Gene expression profiling was performed for eight cases of IMGC and eight cases of early SMGC with submucosal invasion ≥500 μm. To validate the findings of gene expression analysis and to examine the gene expression pattern in tissues, immunohistochemical (IHC) staining was performed for 50 cases of IMGC and SMGC each. Results: Gene expression analysis demonstrated that the expression levels of small intestine-specific genes were significantly decreased in SMGC. Among them, defensin alpha 5 (DEFA5) was the most downregulated gene in SMGC, which was further validated in SMGC tissues by IHC staining. Gene set enrichment analysis showed a strong association between SMGC, the JAK-STAT signaling pathway, and the upregulation of STAT3-activating cytokines. The expression of phosphorylated STAT3 was significant in the nucleus of tumor cells in SMGC tissues but not in areas expressing DEFA5. Conclusion: The results of this study strongly suggest that the downregulation of DEFA5 and the activation of STAT3 play a significant role in the submucosal invasion of EGC.
    Type of Medium: Online Resource
    ISSN: 0012-2823 , 1421-9867
    RVK:
    RVK:
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2023
    detail.hit.zdb_id: 1482218-0
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  • 2
    In: Digestion, S. Karger AG, Vol. 103, No. 6 ( 2022), p. 411-420
    Abstract: 〈 b 〉 〈 i 〉 Introduction: 〈 /i 〉 〈 /b 〉 〈 i 〉 Helicobacter pylori 〈 /i 〉 eradication is expected to significantly change the prevalence of Barrett’s esophagus (BE). However, few reports on this relationship exist. We analyzed the risk factors of BE using the current consensus on length of BE considering 〈 i 〉 H. pylori 〈 /i 〉 infection status. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 We analyzed 10,122 individuals (5,962 men; mean age = 52.9 ± 9.9 years) who had undergone esophagogastroduodenoscopy as part of a medical checkup. Correlations among factors including 〈 i 〉 H. pylori 〈 /i 〉 infectious status, endoscopic findings, and BE ≥1 cm were analyzed. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Prevalence of BE, long-segment BE, and esophageal adenocarcinoma was 22.5%, 0.014%, and 0%, respectively. Logistic regression analysis showed that the risk factors for BE were hiatal hernia (odds ratio [OR]: 2.89 [2.59–3.24] ), female sex (OR: 0.52 [0.46–0.59]), social drinking (OR:0.77 [0.68–0.87] ), 〈 i 〉 H. pylori 〈 /i 〉 eradication therapy (OR: 1.34 [1.19–1.51]), proton pump inhibitor (PPI) use (OR: 1.52 [1.18–1.96] ), bile reflux (OR: 1.18 [1.04–1.33]), age ≥50 years (OR: 1.13 [1.02–1.26] ), and nonsteroidal anti-inflammatory drug (NSAID) use (OR: 1.29 [1.02–1.62]). Although reflux esophagitis (RE) was more common in 〈 i 〉 H. pylori 〈 /i 〉 -negative patients (17.2%) than in those after 〈 i 〉 H. pylori 〈 /i 〉 eradication therapy (11.8%, 〈 i 〉 p 〈 /i 〉 & #x3c; 0.00001), the latter was correlated with BE, disputing RE as a strong risk factor for BE. Therefore, we conducted a subgroup analysis; most of the risk factors except for PPI use ( 〈 i 〉 p 〈 /i 〉 = 0.75), H2-receptor antagonist use ( 〈 i 〉 p 〈 /i 〉 = 0.078), and atrophic gastritis absence ( 〈 i 〉 p 〈 /i 〉 = 0.72) were positively correlated with BE after 〈 i 〉 H. pylori 〈 /i 〉 eradication therapy compared with 〈 i 〉 H. pylori 〈 /i 〉 -negative status. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 〈 i 〉 H. pylori 〈 /i 〉 eradication, bile reflux, PPI use, and NSAID use were risk factors for BE along with hiatal hernia, male sex, and older age.
    Type of Medium: Online Resource
    ISSN: 0012-2823 , 1421-9867
    RVK:
    RVK:
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2022
    detail.hit.zdb_id: 1482218-0
    Location Call Number Limitation Availability
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  • 3
    In: Digestion, S. Karger AG, Vol. 98, No. 4 ( 2018), p. 201-208
    Abstract: Background/Aims: Gastroesophageal reflux disease (GERD)-related disorders of systemic sclerosis (SSc) patients have not been adequately investigated. Methods: Sixty-six SSc patients (5 males and 61 females; 56.6 ± 14.6 years old) who underwent esophagogastroduodenoscopy were analyzed on the basis of 16 background factors. They were additionally compared with 116 matched non-SSc subjects controlling age, sex, and use of proton pump inhibitors (PPIs). Results: The mean disease duration of 66 patients was 5.1 ± 8.1 years, and their breakdown was as follows: 53 (80.3%) with GERD, 38 (57.6%) with GERD-related symptoms, and 20 (30.3%) with reflux esophagitis (RE; LA-A: 10, LA-B: 5, LA-C: 4, LA-D: 1). Use of PPI (p = 0.0455), complication of interstitial lung disease (p = 0.0242), and history of cyclophosphamide therapy (p = 0.0184) denoted significant association with GERD-related symptoms. Older age (p = 0.0211) was significantly associated with RE. None of GERD-related disorders showed any difference between 37 diffuse cutaneous SSc and 29 limited cutaneous SSc patients. The matched analysis indicated that SSc patients had higher prevalence of GERD (p  〈 0.0001), GERD-related symptoms (p = 0.0034), and RE (p = 0.0002). Conclusion: SSc patients tend to have worse GERD symptoms and severer RE. However, most SSc-associated factors did not show significant association with GERD-related disorders, indicating the difficulty in predicting GERD-related disorders among SSc patients.
    Type of Medium: Online Resource
    ISSN: 0012-2823 , 1421-9867
    RVK:
    RVK:
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2018
    detail.hit.zdb_id: 1482218-0
    Location Call Number Limitation Availability
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