Impact of Inflammation-Metaplasia-Adenocarcinoma Sequence and Prevention in Surgical Rat Models

Miyashita, Tomoharu; Shah, Furhawn A.; Miwa, Koichi; Sasaki, Shin; Nishijima, Koji; Oyama, Katsunobu; Ninomiya, Itasu; Fushida, Sachio; Fujimura, Takashi; Hattori, Takanori; Harmon, John W.; Ohta, Tetsuo

doi:10.1159/000343896

Cited by 15 publications

(11 citation statements)

References 39 publications

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“…In addition, the conventional treatment for non-erosive reflux disease with gastric acid suppressing medications has been associated with an increased incidence of abnormal microbiota and malignancy [10] . According to a recent study, gastric acid is a strong activator a number of autoprotective mechanisms, including proliferation and differentiation, as well as the production of anti-inflammatory cytokines, growth factors and endogenous antioxidants [4] , [11] , [12] . Conditions such as Barrett’s esophagus, esophageal stricture and esophageal adenocarcinoma, the latter being identified as the most pernicious cancer of the gastrointestinal tract, have sharply risen in incidence over the last decade [9] , [13] .…”

Section: Introductionmentioning

confidence: 99%

“…Development of animal models of non-erosive reflux disease would assist in delineating the early events in its pathogenesis, which would hopefully lead to improved therapies. Indeed, several important advances have been made with respect to understanding the early biochemical and molecular mechanisms of ulceration and healing in other parts of the GI tract [12] , [14] – [16] .…”

Section: Introductionmentioning

confidence: 99%

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Cytoprotective Effects of Hydrogen Sulfide in Novel Rat Models of Non-Erosive Esophagitis

et al. 2014

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Non-erosive esophagitis is a chronic inflammatory condition of the esophagus and is a form of gastroesophageal reflux disease. There are limited treatment options for non-erosive esophagitis, and it often progresses to Barrett’s esophagus and esophageal carcinoma. Hydrogen sulfide has been demonstrated to be a critical mediator of gastric and intestinal mucosal protection and repair. However, roles for H2S in esophageal mucosal defence, inflammation and responses to injury have not been reported. We therefore examined the effects of endogenous and exogenous H2S in rat models of non-erosive esophagitis. Mild- and moderate-severity non-erosive esophagitis was induced in rats through supplementation of drinking water with fructose, plus or minus exposure to water-immersion stress. The effects of inhibitors of H2S synthesis or of an H2S donor on severity of esophagitis was then examined, along with changes in serum levels of a pro- and an anti-inflammatory cytokine (IL-17 and IL-10, respectively). Exposure to water-immersion stress after consumption of the fructose-supplemented water for 28 days resulted in submucosal esophageal edema and neutrophil infiltration and the development of lesions in the muscular lamina and basal cell hyperplasia. Inhibition of H2S synthesis resulted in significant exacerbation of inflammation and injury. Serum levels of IL-17 were significantly elevated, while serum IL-10 levels were reduced. Treatment with an H2S donor significantly reduced the severity of esophageal injury and inflammation and normalized the serum cytokine levels. The rat models used in this study provide novel tools for studying non-erosive esophagitis with a range of severity. H2S contributes significantly to mucosal defence in the esophagus, and H2S donors may have therapeutic value in treating esophageal inflammation and injury.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cytoprotective Effects of Hydrogen Sulfide in Novel Rat Models of Non-Erosive Esophagitis

et al. 2014

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“… 19 Though reflux disease is a key factor for development of Barrett’s esophagus, other factors must underlie its development since it occurs in only a minority of reflux disease patients. 20 However, dominant pathogenic mechanism is that gastroduodenal content reflux from gastroesophageal reflux disease induces the inflammation-mediated progression from hyperplasia to metaplasia, and to adenocarcinoma, 21 by which several pharmacological interventions are anticipated as cancer preventive way, including proton pump inhibitor (PPI including esomeprazole, rabeprazole, and pantoprazole), aspirin, NSAIDs, and some more anti-inflammatory agents. The effect of pharmacological and surgical intervention on the natural history of Barrett’s is a subject of ongoing research, including the Barrett’s Esophagus Surveillance Study and the aspirin and proton pump inhibitor (omeprazole) cancer chemoprevention trial with interesting results.…”

Section: Application Of Sitrp In Gastroenterologymentioning

confidence: 99%

Short-term Intervention to Revert Premalignant Lesions as Strategy to Prevent Gastrointestinal Cancers

Han¹,

Park²,

Lee³

et al. 2013

J Cancer Prev

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“Prevention might be better than treatment in cancer treatment” is brief conclusion drawn from war on cancer through National Cancer Act of 1971 by U.S. President Richard Nixon. However, the clinical practice of chemoprevention is still in its infancy in spite of a wealth of data showing its effectiveness in experimental animals as well as in vitro mechanism research. Recent advances in either high throughput analysis including cancer genomes and tailored medicine or molecular targeted therapeutics, preventive strategies also should be changes as previous preventive strategies including phytoceuticals, life-style modification, and some empirical agents. Furthermore, molecular targeted therapeutics achieved high goal of effectiveness under the concept of therapeutic or preventive “synthetic lethality”, of which extended application can be included within the scope of chemoprevention. Here, we will summarize several recent advances in chemopreventive strategy objected to justify optimism that chemoprevention will be an effective approach for the control of human cancer. siTRP (short-term intervention to revert premalignancy) strategy will be introduced for cancers in gastroenterology.

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“…Lindau et al [17,18,19] reported that the immune system of the tumor bearing host interacts with the tumor throughout its development and hence, this feature serve as a therapeutic target for anti-cancer immunotherapy. A high degree of inflammation was observed in human esophageal cancers [5,8,20,21], animal models of esophageal cancer [22], and esophageal cancer cell lines [23], and this inflammation plays a role in the carcinogenesis of esophageal tumors [5,20,21,24]. Although inflammatory cells have been studied in esophageal squamous cell carcinoma (ESqCC) [10,13,16], esophageal adenocarcinoma [11,25], and other small cell cancers [26], no such information is known in SmCEC.…”

Section: Introductionmentioning

confidence: 99%

Clinical Impact of Tumor-Infiltrating Inflammatory Cells in Primary Small Cell Esophageal Carcinoma

Zhang

Ren

Wang

et al. 2014

IJMS

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Primary small cell esophageal carcinoma is a rare and aggressive type of gastrointestinal cancer with poor prognosis. In the present study, the impact of tumour infiltrating inflammatory cells on clinico-pathological characteristics and the patients’ prognosis were analysed. A total of 36 small cell esophageal carcinomas, 19 adjacent normal tissues and 16 esophageal squamous cell carcinoma samples were collected. Qualified pathologists examined eosinophils, neutrophils, lymphocytes and macrophages on histochemical slides. The infiltration of eosinophils and macrophages in small cell esophageal carcinoma was significantly increased as compared with tumor adjacent normal tissues, and was significantly less in esophageal squamous cell carcinoma. Macrophage count was significantly associated with (p = 0.015) lymph node—stage in small cell esophageal carcinoma. When we grouped patients into two groups by counts of infiltrated inflammatory cells, Kaplan-Meier analysis revealed that high macrophage infiltration group (p = 0.004) and high eosinophil infiltration group (p = 0.027) had significantly enhanced survival. In addition, multivariate analysis unveiled that eosinophil count (p = 0.002) and chemotherapy (Yes vs. No, p = 0.001) were independent prognostic indicators. Taken together, infiltration of macrophages and eosinophils into the solid tumor appear to be important in the progression of small cell esophageal carcinoma and patients’ prognosis.

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Impact of Inflammation-Metaplasia-Adenocarcinoma Sequence and Prevention in Surgical Rat Models

Cited by 15 publications

References 39 publications

Cytoprotective Effects of Hydrogen Sulfide in Novel Rat Models of Non-Erosive Esophagitis

Cytoprotective Effects of Hydrogen Sulfide in Novel Rat Models of Non-Erosive Esophagitis

Short-term Intervention to Revert Premalignant Lesions as Strategy to Prevent Gastrointestinal Cancers

Clinical Impact of Tumor-Infiltrating Inflammatory Cells in Primary Small Cell Esophageal Carcinoma

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