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ABSTRACT: Despite substantial progress in screening, early diagnosis, and the development of noninvasive technology, gastrointestinal (GI) cancer remains a major cause of cancer-associated mortality. Chemoprevention is thought to be a realistic approach for reducing the global burden of GI cancer, and efforts have been made to search for chemopreventive agents that suppress acid reflux, GI inflammation and the eradication of Helicobacter pylori. Thus, proton pump inhibitors, statins, monoclonal antibodies targeting tumor necrosis factor-alpha, and nonsteroidal anti-inflammatory agents have been investigated for their potential to prevent GI cancer. Besides the development of these synthetic agents, a wide variety of the natural products present in a plant-based diet, which are commonly called phytoceuticals, have also sparked hope for the chemoprevention of GI cancer. To perform successful searches of chemopreventive agents for GI cancer, it is of the utmost importance to understand the factors contributing to GI carcinogenesis. Emerging evidence has highlighted the role of chronic inflammation in inducing genomic instability and telomere shortening and affecting polyamine metabolism and DNA repair, which may help in the search for new chemopreventive agents for GI cancer.
Gut and liver 03/2013; 7(2):137-49. · 0.83 Impact Factor
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ABSTRACT: OBJECTIVE: Inflammatory bowel disease (IBD) is a disease showing relapsing and remitting inflammatory courses of the colon and small intestine, mostly Crohn's disease (CD) and ulcerative colitis (UC). Biomarkers discriminating UC and CD, especially in cases with indeterminate type, and reflecting disease activities are still lacking, but advanced technology of label free proteomic quantification can realize discovery of these biomarkers. METHODS: We searched the protein expressions of Korean IBD patients' colonic tissues using label free quantification, the protein profiles of colonic mucosa in 3 normal colonic tissues compared with active and remitted state of 4 UC patients, active and remitted state of 3 CD patients, inflammatory polyps arising in 2 UC patients. A computational framework and tools for discovery-based liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomics was applied to draw biomarkers. RESULTS: Through label free quantification, 339 proteins between normal versus active UC, 217 between normal versus inactive UC, 345 between normal versus active CD, 366 between normal versus inactive CD, and 392 between normal versus inflammatory polyps related to IBD were identified, all were very reproducible. Corra analysis led to discovery of 27 potential biomarkers in UC, 37 biomarkers relevant to CD, and 11 proteins commonly associated with IBD. Three novel genes, PRG2, LCP1, and PSME1, were identified as biomarkers signifying active CD. CONCLUSION: This is the first to apply label free quantification for discovering biomarkers in patients with different type and stage of IBD patients, providing additional insights to reveal molecular pathogenesis of IBD as well as protein biomarkers of IBD predicting the response to treatment.
Journal of Digestive Diseases 01/2013; · 1.59 Impact Factor
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Clinical endoscopy. 11/2012; 45(4):454.
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ABSTRACT: BACKGROUND: Proton pump is an integral membrane protein that is ubiquitous ATP binding cassette (ABC) involved in many transport processes in all living organisms, among which a specialized form of pump, so called p-type proton pump, exists in the parietal cells of stomach. Though proton pump inhibitors (PPIs) are frequently prescribed to prevent nonsteroidal anti-inflammatory drugs (NSAIDs)-induced gastric damage, the acid suppressive actions do not suffice to explain. METHODS: In order to document the effects of pantoprazole, one of PPIs, on the NSAIDs-induced gastric damage, in vitro and in vivo studies were performed. Immunocytochemistry, Western blot analysis, electrophoretic mobility shift assay and RT-PCR were conducted to evaluate the induction of heme oxygenase-1 (HO-1) through Nrf2 activation in normal gastric mucosal RGM-1 cells or in vivo stomach tissues from rats treated with indomethacin and/or pantoprazole. RESULTS: Pantoprazole activated Nrf2 through inactivation of Keap1, after which the expression of HO-1 was significantly increased in a dose-dependent manner in RGM-1 cells. Increased ARE-DNA binding activity was observed maximally at 1 h with 300 muM of pantoprazole. The expression of HO-1 induced by pantoprazole was significantly associated with the increased in vitro tube formation (P < 0.05) and angiogenic factors including VEGF, bFGF, and HIF-1alpha. Indomethacin markedly increased the expressions of TNF-alpha, IL-1ss, IL-8, NOX-1, ICAM-1 and VCAM, whereas pantoprazole significantly decreased the expressions of indomethacin-induced these inflammatory mediators in accord with pantoprazole-induced HO-1 (P < 0.05) as documented with HO-1 inhibitor. In vivo model of indomethacin-induced gastric damage could validate in vitro-drawn results that pantoprazole remarkably protected against indomethacin-induced gastric damage, in which zinc protoporphyrin (5 mg/kg, ip) significantly abolished the protective efficacy of pantoprazole. CONCLUSION: These results demonstrate that Nrf2-mediated HO-1 induction of PPIs afforded a significant protective effect against NSAIDs-induced gastric damage beyond acid suppressive actions.
BMC Gastroenterology 10/2012; 12(1):143. · 2.42 Impact Factor
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ABSTRACT: Proteomics offers considerable opportunities for either enhancing our biological understanding or discovering biomarkers, blood and biopsied specimen-based proteomic approaches, provide reproducible and quantitative tools that can complement clinical assessments and aid clinicians in the diagnosis and treatment of inflammatory bowel disease (IBD). Sometimes a differential diagnosis of Crohn's disease (CD) and ulcerative colitis (UC) and the prediction of treatment response can be deduced by finding meaningful biomarkers, for which the central platform for proteomics is tandem mass spectrometry (MS/MS). A range of workflows are available for protein (or peptide) separation prior to MS/MS as well as bioinformatics analysis to achieve protein identification, for which two-dimensional electrophoresis (2-DE) and subsequent mass spectrometry (MS), liquid chromatography-MS, difference gel electrophoresis following 2-DE, isobaric tags for relative and absolute quantification (iTRAQ), stable isotope labeling by amino acids and label-free quantification are under development. In this article, the current status and perspective of these advanced proteomic technologies are introduced, with examples of recent biomarkers focused on the diagnosis, treatment response, prognosis of IBD, and even colitis-associated carcinogenesis in both animal models and human patients.
Journal of Digestive Diseases 10/2012; 13(10):497-503. · 1.59 Impact Factor
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ABSTRACT: Dietary n-3 polyunsaturated fatty acids (n-3 PUFAs) have well-documented protective effects against obesity-induced insulin resistance and hepatic steatosis. Here, we investigated the effects of endogenous n-3 PUFAs on diet-induced fatty liver disease using fat-1 transgenic mice (fat-1) capable of converting n-6 to n-3 PUFAs. Wild-type (WT) and fat-1 mice were maintained on a high-fat diet (HFD) for 5months. HFD-induced weight gain and fatty liver were more prominent in WT mice than fat-1 mice. Histological analysis indicated that WT mice fed the HFD developed moderate-to-severe macrovesicular steatosis, whereas fat-1 mice developed very mild steatosis. In addition, HFD-induced hepatocyte ballooning and fibrosis were ameliorated in fat-1 mice. Serum alanine transaminase (ALT) and aspartate transaminase (AST) levels were within the respective normal ranges in HFD-fed fat-1 mice, whereas both were significantly elevated in HFD-fed WT mice. The fat-1 mice showed significantly decreased serum lipid levels, including triglycerides, total cholesterol (TC), HDL-C, and LDL-C, compared to WT mice regardless of diet. Specifically, the increases in very low-density lipoprotein cholesterol (VLDL-C) and chylomicrons detected in HFD-fed WT mice were completely blunted in HFD-fed fat-1 mice. Gene expression analysis showed that hepatic Cyp7a1 mRNA and protein expression levels were markedly increased in HFD-fed fat-1 mice. In addition, genes involved in cholesterol uptake (Ldlr) and bile acid excretion (Abcg5 and Abcg8) were increased in the livers of fat-1 mice. These data suggest that n-3 PUFAs ameliorate diet-induced hyperlipidemia and fatty liver through induction of CYP7A1 expression and activation of cholesterol catabolism to bile acid.
Biochemical pharmacology 09/2012; 84(10):1359-65. · 4.25 Impact Factor
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ABSTRACT: Chronic gastric inflammation developing after Helicobacter pylori (H. pylori) infection is responsible for either dyspeptic symptom relevant to gastritis/peptic ulcer or gastric tumorigenesis, in which acid suppressants, especially proton pump inhibitors (PPIs), play role in relieving dyspepsia as well as the eradication regimen. Among several mediators engaged in propagating gastric inflammation after H. pylori infection, cyclooxygenase-2 (COX-2) might be the principal one, and several prescriptions have been made for decreasing the COX-2 levels. Multiple line of evidence are available for anti-inflammatory action of PPIs beyond acid suppression, but revaprazan, a novel acid pump antagonist launched in clinic, has also been suggested to exert significant anti-inflammatory actions as much as PPI. In the current study, we hypothesized that revaprazan could regulate H. pylori-driven COX-2 expression as one of its anti-inflammatory pharmacological actions. The changes of gastric COX-2 expression as well as responsible transcription factors were measured after H. pylori infection in the presence or absence of revaprazan. Infection of AGS cells with H. pylori induced significant up-regulation of COX-2 in time- and concentration-dependent manners, which was mediated by Akt phosphorylation. Revaprazan treatment significantly inhibited IkappaB-alpha degradation as well as Akt inactivation, resulting in attenuation of H. pylori-induced COX-2 expression. Additional rescuing action of revaprazan against H. pylori-induced cytotoxicity was noted. In conclusion, revaprazan imposed significant anti-inflammatory actions on H. pylori infection beyond acid suppression.
Journal of Clinical Biochemistry and Nutrition 09/2012; 51(2):77-83. · 1.98 Impact Factor
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ABSTRACT: Introduction: Increased resistance of Helicobacter pylori to antibiotics has increased the need to develop new first-line treatments for H. pylori. We have prospectively evaluated 10-day sequential versus conventional triple therapy in peptic ulcer patients. Methods: One hundred fifty-nine patients with peptic ulcer diseases were prospectively randomized to receive 10 days of lansoprazole, amoxicillin, and clarithromycin (conventional triple therapy) or 5 days of lansoprazole and amoxicillin followed by 5 days of lansoprazole, clarithromycin, and metronidazole (sequential therapy). Post-treatment H. pylori status was determined by the (13) C-urea breath test. Eradication rates, antibiotic resistance rates by agar dilution method, drug compliance, and side effects were compared. Results: The intention-to-treat eradication rates were 75.9% (95% CI: 66.5-85.3%, 60/79) in the sequential therapy group and 58.7% (95% CI 47.9-69.5%,47/80) in the conventional triple therapy group (P=0.01), while the per-protocol eradication rates were 86.8% (95% CI: 78.7-94.8%, 59/68) and 67.6% (95% CI 56.5-78.7%,46/68) (P=0.01), respectively. Compliance and side effects were similar in the two groups. Culture of H. pylori showed that 18.2% were resistant to clarithromycin, 41.9% to metronidazole. Dual resistance to both antibiotics was 9.6%. Conclusions: Although 10-day sequential therapy yielded a higher H. pylori eradication rate than 10-day conventional triple therapy, the sequential therapy protocol did not result in a sufficiently satisfactory eradication rate. This might be related to the higher antibiotics resistance rate especially to dual resistance. More effective regimens are needed to overcome antibiotic resistance in Korea. © 2012 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.
Journal of Gastroenterology and Hepatology 07/2012; · 2.87 Impact Factor
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ABSTRACT: BACKGROUND/AIMS: Detailed underlying changes have never been explored to explain how old stomach is more susceptible to non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastric damage than young stomach, although presumptively speculated as weakened mucosal defense system as well as attenuated regenerating capacity in old stomach. METHODS: In order to investigate molecular mechanisms relevant to NSAID-induced gastric damage, we administered indomethacin to 6-week-old and 60-week-old rats. RESULTS: In spite of the same oral administration of indomethacin (0.1 mg indomethacin dissolved in 1 ml carboxyl methylcellulose) irrespective of body weights of rat, gastric mucosal damages were significantly increased in the older rats compared to the younger rats (p < 0.05). Before indomethacin administration, inflammatory mediators including cytokines, chemokines, proteases, and adhesion molecules were significantly increased in old stomach and these differences were further increased after indomethacin administration (p < 0.05). Furthermore, the levels of total oxidants and apoptotic executors were significantly increased in old stomach, whereas lipoxin A4 and anti-apoptotic proteins such as survivin and Bcl-2 were significantly decreased. Increased NF-κB-DNA binding activity as well as the activation of JNK and p38 was responsible for the increased expressions of inflammatory mediators as well as oxidants. CONCLUSIONS: A preventive strategy to reduce either redox activation or pro-inflammatory mediators should be considered in older patients taking long-standing NSAID administration.
Digestive Diseases and Sciences 07/2012; · 2.12 Impact Factor
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Myung Ho Jeong,
Jun-Won Chung,
Sang Jin Lee,
Minsu Ha,
Seok Hoo Jeong,
Sunyoung Na,
Byung Soo Na,
Sung Keun Park,
Yoon Jae Kim,
Kwang An Kwon,
Kwang Il Ko,
Yunjeong Jo, Ki Baik Hahm,
Hwoon-Yong Jung
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ABSTRACT: There is increasing need for third-line therapy of Helicobacter pylori due to increasing level of antibiotics resistance. The aim of this study was to compare rifabutin and levofloxacin rescue regimens in patients with first- and second-line Helicobacter pylori eradication failures.
Patients, in whom a first treatment with proton pump inhibitor-clarithromycin-amoxicillin and a second trial with proton pump inhibitor-bismuth-tetracycline-metronidazole had failed, received treatment with either rifabutin or levofloxacin, plus amoxicillin (1 g twice daily) and standard dose proton pump inhibitor. Eradication rates were confirmed with 13C-urea breath test or rapid urease test 4 weeks after the cessation of therapy.
Eradication rates were 71.4% in the rifabutin group, and 57.1% in the levofloxacin group, respectively. Although there was no significant difference in Helicobacter pylori eradication rates between two groups (p=0.656), rifabutin based regimen showed relatively higher eradication rate.
Helicobacter pylori eradication rates of rifabutin- or levofloxacin-based triple therapy could not achieve enough eradication rate. Further studies would be needed on combination of levofloxacin and rifabutin-based regimen or culture based treatment.
The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi 06/2012; 59(6):401-6.
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ABSTRACT: Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal-dominantly inherited disease that occurs in approximately one in 5000 to 8000 people. Clinical diagnosis of HHT is made when a person presents three of the following four criteria: family history, recurrent nosebleeds, mucocutaneous telangiectasis, and arteriovenous malformations (AVM) in the brain, lung, liver and gastrointestinal (GI) tract. Although epistaxis is the most common presenting symptom, AVMs affecting the lungs, brain and GI tract provoke a more serious outcome. Heterozygous mutations in endoglin, activin receptor-like kinase 1 (ACVRL1; ALK1), and SMAD4, the genes involved in the transforming growth factor-β family signaling cascade, cause HHT. We report here the case of a 63 year-old male patient who presented melena and GI bleeding episodes, proven to be caused by bleeding from multiple gastric angiodysplasia. Esophagogastroduodenoscopy revealed multiple angiodysplasia throughout the stomach. Endoscopic argon plasma coagulation was performed to control bleeding from a gastric angiodysplasia. The patient has been admitted several times with episodes of hemoptysis and hematochezia. One year ago, the patient was hospitalized due to right-sided weakness, which was caused by left basal ganglia hemorrhage as the part of HHT presentation. In family history, the patient's mother and elder sister had died, due to intracranial hemorrhage, and his eldest son has been suffered from recurrent epistaxis for 20 years. A genetic study revealed a mutation in exon 3 of ALK1 (c.199C > T; p.Arg67Trp) in the proband and his eldest son presenting epistaxis.
World Journal of Gastroenterology 04/2012; 18(15):1840-4. · 2.47 Impact Factor
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ABSTRACT: Background/Aims: Acute colorectal obstruction with stage IVB colorectal cancer has a poor prognosis and short life expectancy. The effectiveness of self-expanding metal stents (SEMS) has been demonstrated in colorectal cancer patients with obstruction. However, little is known about the palliative efficacy of stent placement in patients with unresectable colorectal cancer. Methodology: The medical records of patients who received SEMS for stage IVB colorectal cancer with acute colorectal obstruction between March 2004 and July 2010 were retrospectively reviewed. A total of 24 patients with unresectable Stage IVB colorectal cancer with acute colorectal obstruction were enrolled in this study. Results: Twenty-four patients received SEMS placement during the study period. The mean age of the patients was 63.0 years (range 35-84 years). Fifteen patients were male and nine were female. The most common obstructive lesion was in the sigmoid colon (70.8%), including the sigmoid-descending and rectosigmoid junctions. Uncovered SEMS were used in 62.5% of patients. On the first attempt, the technical success rate of SEMS was 95.8%. The estimated duration of primary stent patency and overall survival periods after SEMS were 332.0 and 231.8 days, respectively. Conclusions: SEMS insertion may be a useful therapeutic choice for acute colorectal obstruction in patients with unresectable stage IVB colorectal cancer.
Hepato-gastroenterology 04/2012; 59(120). · 0.66 Impact Factor
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ABSTRACT: Cysteamine is a reducing aminothiol used for inducing duodenal ulcer through mechanisms of oxidative stress related to thiol-derived H(2)O(2) reaction. Cochinchina momordica saponins have been suggested to be protective against various gastric diseases based on their cytoprotective and anti-inflammatory mechanisms. This study was aimed to document the preventive effects of Cochinchina momordica seed extract against cysteamine-induced duodenal ulcer as well as the elucidation of its pharmacological mechanisms.
Cochinchina momordica seed extract (50, 100, 200 mg/kg) was administrated intragastrically before cysteamine administration, after which the incidence of the duodenal ulcer, ulcer size, serum gastrin level, and the ratio of reduced glutathione (GSH)/oxidized glutathione disulfide (GSSG) as well as biochemical and molecular measurements of cytoplasmic phospholipase A(2) (cPLA(2)), cyclooxygenase-2 (COX-2), 5-lipoxygenase and the expression of proinflammatory genes including IL-1β, IL-6, COX-2 were measured in rat model. Additional experiments of electron spin resonance measurement and the changes of glutathione were performed.
Cochinchina momordica seed extract effectively prevented cysteamine-induced duodenal ulcer in a dose-dependent manner as reflected with significant decreases in either duodenal ulcerogenesis or perforation accompanied with significantly decreased in serum gastrin in addition to inflammatory mediators including cPLA(2), COX-2, and 5-lipoxygenase. Cochinchina momordica seed extract induced the expression of γ-glutamylcysteine synthetase (γ-GCS)-related glutathione synthesis as well as significantly reduced the expression of cPLA(2). Cochinchina momordica seed extract preserved reduced glutathione through increased expressions of γ-GCS.
Cochinchina momordica seed extracts exerted significantly protective effect against cysteamine-induced duodenal ulcer by either cPLA2 inhibition or glutathione preservation.
Journal of Gastroenterology and Hepatology 04/2012; 27 Suppl 3:13-22. · 2.87 Impact Factor
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ABSTRACT: Oxygen free radicals in excessively high amounts are all very reactive chemically and can impose a detrimental influence on living organisms by provoking "oxidative stress" that can damage major cellular constituents. The latter includes the cell membrane, cytoplasmic proteins, and nuclear DNA. Conversely, nitric oxide (NO), superoxide anion, and related reactive oxygen species (ROS) when present in low amounts play an important role as regulatory mediators in signaling processes, through which, paradoxically, many ROS-mediated responses can protect the cells against oxidative stress by induction of "redox homeostasis." Therefore, diseases associated with free radical overproduction are provoked by "blazed ROS productions" far beyond the host's capacity to quench. Free radicals have been implicated in the pathogenesis of diverse gastrointestinal (GI) diseases including gastroesophageal reflux disease (GERD), gastritis, enteritis, colitis and associated cancers as well as pancreatitis and liver cirrhosis. This article provides an overview of the role of oxidative stress in inflammation-based GI tract diseases, including reflux esophagitis, Helicobacter pylori-associated gastritis, non-steroidal anti-inflammatory drug-induced enteritis, ulcerative colitis, and associated colorectal cancer. The challenging issue that ROS can contribute to diverse gastrointestinal dysfunction, or manifest dual roles in cancer promotion or cancer suppression will also be discussed for the opportunity to enhance understanding of inflammation-based GI diseases.
Journal of Gastroenterology and Hepatology 03/2012; 27(6):1004-10. · 2.87 Impact Factor
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ABSTRACT: An 80-year-old woman with hilar cholangiocarcinoma was hospitalized due to sudden-onset abdominal pain. Computed tomography revealed hepatic necrosis accompanied with emphysematous change in the superior segment of the right liver (S7/S8), implying spontaneous rupture, based on the presence of perihepatic free air. Although urgent percutaneous drainage was performed, neither pus nor fluids were drained. These findings suggest emphysematous hepatitis with a hepatic mass. Despite the application of intensive care, the patient's condition deteriorated rapidly, and she died 3 days after admission to hospital. Liver gas has been reported in some clinical diseases (e.g., liver abscess) to be caused by gas-forming organisms; however, emphysematous hepatitis simulating emphysematous pyelonephritis is very rare. The case reported here was of fatal emphysematous hepatitis in a patient with hilar cholangiocarcinoma.
The Korean journal of hepatology. 03/2012; 18(1):94-7.
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ABSTRACT: Cowden syndrome is a rare autosomal dominant disorder that is characterized by multiple hamartomas in a variety of tissues and this is associated with germline mutations in the phosphatase and tensin homologue (PTEN) gene, which is the tumor suppressor gene located on chromosome 10q23.3. It is characterized by multiple hamartomatous neoplasms of the skin, oral mucosa, gastrointestinal (GI) tract, bones, central nervous system, eyes, and genitourinary tract. Cowden syndrome does not have increased risk of GI malignancy; however, it has an increased risk of breast, thyroid and endometrial cancer development. Here the authors report a rare case of Cowden syndrome incidentally diagnosed from multiple gastric polyposis. A 29-year-old woman presented with multiple gastric polyps. The laboratory results were normal except for mild anemia, with a hemoglobin level of 11.9 g/dL. Esophagogastroduodenoscopy revealed multiple gastric, duodenal polyps and esophageal acanthosis. Colonoscopy revealed possible hamartomatous polyps in the rectum. Under the suspicion of Cowden syndrome, sonography of the thyroid and breasts was carried out, which revealed multiple thyroid masses. Subsequent fine-needle aspiration biopsy revealed the presence of clusters of follicular epithelial cells, and due to the possibility of malignancy, the patient underwent total thyroidectomy. The pathology was reported as invasive follicular carcinoma. A gene study by direct sequencing showed the presence of a PTEN mutation (c.633C > A /p.Cys211*).
World Journal of Gastroenterology 02/2012; 18(8):861-4. · 2.47 Impact Factor
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ABSTRACT: Reactive oxygen species (ROS) attack guanine bases in DNA easily and form 8-hydroxydeoxyguanosine (8-OHdG), which can bind to thymidine rather than cytosine, based on which, the level of 8-OHdG is generally regarded as a biomarker of mutagenesis consequent to oxidative stress. For example, higher levels of 8-OHdG are noted in Helicobacter pylori-associated chronic atrophic gastritis as well as gastric cancer. However, we have found that exogenous 8-OHdG can paradoxically reduce ROS production, attenuate the nuclear factor-κB signaling pathway, and ameliorate the expression of proinflammatory mediators such as interleukin (IL)-1, IL-6, cyclo-oxygenase-2, and inducible nitric oxide synthase in addition to expression of nicotinamide adenine dinucleotide phosphate oxidase (NOX)-1, NOX organizer-1 and NOX activator-1 in various conditions of inflammation-based gastrointestinal (GI) diseases including gastritis, inflammatory bowel disease, pancreatitis, and even colitis-associated carcinogenesis. Our recent finding that exogenous 8-OHdG was very effective in either inflammation-based or oxidative-stress-associated diseases of stress-related mucosal damage has inspired the hope that synthetic 8-OHdG can be a potential candidate for the treatment of inflammation-based GI diseases, as well as the prevention of inflammation-associated GI cancer. In this editorial review, the novel fact that exogenous 8-OHdG can be a functional molecule regulating oxidative-stress-induced gastritis through either antagonizing Rac-guanosine triphosphate binding or blocking the signals responsible for gastric inflammatory cascade is introduced.
World Journal of Gastroenterology 01/2012; 18(4):302-8. · 2.47 Impact Factor
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ABSTRACT: In the Helicobacter pylori (H. Pylori)-negative normal stomach, collecting venules are visible over all the gastric body as numerous minute points evaluated with standard endoscopy. This finding was termed regular arrangement of collecting venules (RAC), and its absence suggests H. pylori gastritis. The aim of this study was to evaluate the correlation between the RAC and rapid urease test.
Two hundred sixty three consecutive adults undergoing upper digestive endoscopy and rapid urease test were included. The lesser curvature of the lower corpus was evaluated for the RAC pattern using a standard endoscope and different hemoglobin index. Two biopsies from the lesser curvature of the antrum and the greater curvature of the body were collected for rapid urease test.
H. pylori were detected in 51.3% (135/263) patients. Of the 57 patients with H. pylori-negative normal stomachs 53 patients (93%) had RAC. As a determinant of the normal stomach without H. pylori infection, the presence of RAC had 41.4% sensitivity, 97.0% specificity, 93.0% positive predictive value and 63.6% negative predictive value.
RAC-positive finding by standard endoscopy showed high positive predictive value and specificity of H. pylori-negative normal stomach. RAC-positive finding by standard endoscopy could be an useful finding to predict H. pylori negativity.
The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi 11/2011; 58(5):252-7.
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ABSTRACT: Colitis-associated cancer (CAC) is one of clear examples of inflammation-carcinogenesis sequence, by which the strict control of colitis with potent anti-inflammatory or antioxidative agent offers the chance of cancer prevention. Supported with the facts that Rac1 binds and activates STAT3, which are significantly upregulated in inflammatory bowel disease (IBD) as well as CAC, but 8-hydroxydeoxyguanosine (8-oxo-7,8-dihydrodeoxyguanosine or 8-OHdG) paradoxically can block Rac1 activation and subsequent NADPH oxidase (NOX) inactivation in various inflammation models, we hypothesized that attenuated Rac1-STAT3 and COX-NF-κB pathway by exogenous 8-OHdG administration may ameliorate inflammatory signaling in dextran sodium sulfate (DSS)-induced colitis and can prevent CAC. Before commencing carcinogenesis model, we checked whether exogenous 8-OHdG can alleviate IBD, for which interleukin (IL)-10 knockout mice were designed to ingest 5% DSS for 1 week, and 8-OHdG is given through intraperitoneal route daily. 8-OHdG treatment groups significantly reduced pathologic grade of DSS-induced colitis as well as various inflammatory mediators such as TNF-α, IL-6, COX-2, and iNOS in a dose-dependent manner. To document the cancer prevention effects of 8-OHdG, mice were injected azoxymethane followed by drinking 2.5% DSS for 1 week, after which 8-OHdG-containing diets were given for 20 weeks. As results, mice that consumed 8-OHdG-containing diet significantly reduced both tumor incidence and multiplicity. Rac1 activity and phosphorylated STAT3 level were significantly attenuated in the 8-OHdG-treated group. Significantly decreased levels of malondialdehyde, monocyte chemotactic protein-1, matrix metalloproteinasess, COX-2, NOX4, and β-catenin nuclear accumulation were responsible for cancer prevention effects of exogenous 8-OHdG. In conclusion, we clearly showed cancer-preventive effect of exogenous 8-OHdG against CAC.
Cancer Prevention Research 07/2011; 4(9):1507-21. · 4.91 Impact Factor
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ABSTRACT: The term "stress-related mucosal disease" (SRMD) represents conditions ranging from superficial mucosal damage to focal deep mucosal damage in the stomach, of which pathogenesis is deduced to be violent mucosal ischemia or excess oxidative stress, but not fully clarified yet. Under the hypothesis that mucosal cell apoptosis subsequent to endoplasmic reticulum (ER) stress might play a crucial role, we evaluated the efficacy and mechanism that novel acid pump antagonist (APA), revaprazan, alleviated water immersion restraint stress (WIRS) induced SRMD in rats.
In order to define whether WIRS-induced SRMD is associated with ER stress, we checked the alteration in the expression of ER stress markers including GRP78, CHOP, XBP-1, BiP as well as apoptosis in WIRS-induced SRMD. The efficacy of revaprazan on either alleviating ER stress or attenuating SRMD was compared with proton pump inhibitor (PPI) and gastroprotectant.
Ten hours of WIRS induced a severe degree of SRMD, in which ER stress markers including CHOP, XBP1, and BiP were significantly overexpressed in the gastric tissues. However, these markers of ER stress were significantly decreased in the group pretreated with revaprazan compared to PPI or gastroprotectant, accompanied with a significant reduction in apoptotic index. In addition to ER stress, revaprazan imposed anti-inflammatory benefit to limit SRMD based on significant levels of inflammatory cell apoptosis.
Endoplasmic reticulum stress accompanied with drastic apoptosis was implicated in the development of SRMD, but revaprazan could rescue the stomach from SRMD through alleviating ER stress in epithelial cells much better than either PPI or gastroprotectant.
Journal of Gastroenterology and Hepatology 07/2011; 27(1):120-9. · 2.87 Impact Factor
