|
1
|
Lopes C, Almeida TC, Pimentel-Nunes P, Dinis-Ribeiro M, Pereira C. Linking dysbiosis to precancerous stomach through inflammation: Deeper than and beyond imaging. Front Immunol 2023; 14:1134785. [PMID: 37063848 PMCID: PMC10102473 DOI: 10.3389/fimmu.2023.1134785] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Accepted: 03/17/2023] [Indexed: 04/03/2023] Open
Abstract
Upper gastrointestinal endoscopy is considered the gold standard for gastric lesions detection and surveillance, but it is still associated with a non-negligible rate of missing conditions. In the Era of Personalized Medicine, biomarkers could be the key to overcome missed lesions or to better predict recurrence, pushing the frontier of endoscopy to functional endoscopy. In the last decade, microbiota in gastric cancer has been extensively explored, with gastric carcinogenesis being associated with progressive dysbiosis. Helicobacter pylori infection has been considered the main causative agent of gastritis due to its interference in disrupting the acidic environment of the stomach through inflammatory mediators. Thus, does inflammation bridge the gap between gastric dysbiosis and the gastric carcinogenesis cascade and could the microbiota-inflammation axis-derived biomarkers be the answer to the unmet challenge of functional upper endoscopy? To address this question, in this review, the available evidence on the role of gastric dysbiosis and chronic inflammation in precancerous conditions of the stomach is summarized, particularly targeting the nuclear factor-κB (NF-κB), toll-like receptors (TLRs) and cyclooxygenase-2 (COX-2) pathways. Additionally, the potential of liquid biopsies as a non-invasive source and the clinical utility of studied biomarkers is also explored. Overall, and although most studies offer a mechanistic perspective linking a strong proinflammatory Th1 cell response associated with, but not limited to, chronic infection with Helicobacter pylori, promising data recently published highlights not only the diagnostic value of microbial biomarkers but also the potential of gastric juice as a liquid biopsy pushing forward the concept of functional endoscopy and personalized care in gastric cancer early diagnosis and surveillance.
Collapse
Affiliation(s)
- Catarina Lopes
- Precancerous Lesions and Early Cancer Management Group, Research Center of IPO Porto (CI‐IPOP)/Rise@CI‐IPOP (Health Research Group), Portuguese Institute of Oncology of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), Porto, Portugal
- CINTESIS – Center for Health Technology and Services Research, University of Porto, Porto, Portugal
- ICBAS-UP – Institute of Biomedical Sciences Abel Salazar, University of Porto, Porto, Portugal
| | - Tatiana C. Almeida
- Precancerous Lesions and Early Cancer Management Group, Research Center of IPO Porto (CI‐IPOP)/Rise@CI‐IPOP (Health Research Group), Portuguese Institute of Oncology of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), Porto, Portugal
| | - Pedro Pimentel-Nunes
- Department of Surgery and Physiology, Faculty of Medicine, University of Porto (FMUP), Porto, Portugal
- Department of Gastroenterology, Unilabs, Porto, Portugal
| | - Mário Dinis-Ribeiro
- Precancerous Lesions and Early Cancer Management Group, Research Center of IPO Porto (CI‐IPOP)/Rise@CI‐IPOP (Health Research Group), Portuguese Institute of Oncology of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), Porto, Portugal
- Department of Gastroenterology, Portuguese Institute of Oncology of Porto, Porto, Portugal
| | - Carina Pereira
- Precancerous Lesions and Early Cancer Management Group, Research Center of IPO Porto (CI‐IPOP)/Rise@CI‐IPOP (Health Research Group), Portuguese Institute of Oncology of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), Porto, Portugal
- CINTESIS – Center for Health Technology and Services Research, University of Porto, Porto, Portugal
- *Correspondence: Carina Pereira,
| |
Collapse
|
|
2
|
Esmaeilzadeh A, Goshayeshi L, Bergquist R, Jarahi L, Khooei A, Fazeli A, Mosannen Mozaffari H, Bahari A, Oghazian MB, Hoseini B. Characteristics of gastric precancerous conditions and Helicobacter pylori infection among dyspeptic patients in north-eastern Iran: is endoscopic biopsy and histopathological assessment necessary? BMC Cancer 2021; 21:1143. [PMID: 34702194 PMCID: PMC8546943 DOI: 10.1186/s12885-021-08626-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Accepted: 07/26/2021] [Indexed: 01/06/2023] Open
Abstract
Background Early detection and appropriate treatment of precancerous, mucosal changes could significantly decrease the prevalence of life-threatening gastric cancer. Biopsy of the normal-appearing mucosa to detect Helicobacter pylori and these conditions is not routinely obtained. This study assesses the prevalence and characteristics of H. pylori infection and precancerous conditions in a group of patients suffering from chronic dyspepsia who were subjected to gastric endoscopy and biopsy mapping. Methods This cross-sectional study included dyspeptic patients, not previously treated for H. pylori, undergoing esophagogastroduodenoscopy (EGD) with their gastric endoscopic biopsies obtained for examination for evidence of H. pylori infection and precancerous conditions. Demographic and clinical data on the gender, smoking, opium addiction, alcohol consumption, medication with aspirin, corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs) and family history of cancer were collected by interviewing the patients and evaluating their health records. The cohort examined consisted of 585 patients with a mean (SD) age of 48.0 (14.46) years, 397 (67.9%) of whom were women. Results H. pylori infection was identified in 469 patients (80.2%) with the highest prevalence (84.2%) in those aged 40–60 years. Opium addiction correlated with a higher a H. pylori infection rate, while alcohol consumption was associated with a lower rate by Odds Ratio 1.98 (95% CI 1.11–3.52) and 0.49 (95% CI 0.26–0.92), respectively. The prevalence of intestinal metaplasia, gastric atrophy and gastric dysplasia was 15.2, 12.6 and 7.9%, respectively. Increased age, positive H. pylori infection, endoscopic abnormal findings and opium addiction showed a statistically significant association with all precancerous conditions, while NSAID consumption was negatively associated with precancerous conditions. For 121 patients (20.7% of all), the EGD examination revealed normal gastric mucosa, however, for more than half (68/121, 56.2%) of these patients, the histological evaluation showed H. pylori infection, and also signs of atrophic mucosa, intestinal metaplasia and dysplasia in 1.7, 4.1 and 1.7%, respectively. Conclusion EGD with gastric biopsy mapping should be performed even in the presence of normal-appearing mucosa, especially in dyspeptic patients older than 40 years with opium addiction in north-eastern Iran. Owing to the high prevalence of precancerous conditions and H. pylori infection among patients with dyspepsia in parts of Iran, large-scale national screening in this country should be beneficial.
Collapse
Affiliation(s)
- Abbas Esmaeilzadeh
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Ladan Goshayeshi
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.,Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Robert Bergquist
- Ingerod, SE-454 94, Brastad, Sweden.,Formerly UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR), World Health Organization, Geneva, Switzerland
| | - Lida Jarahi
- Community Medicine Department, Faculty of Medicine, Mashhad University of Medical sciences, Mashhad, Iran
| | - Alireza Khooei
- Department of Pathology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Alireza Fazeli
- Cardiology Resident, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hooman Mosannen Mozaffari
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Ali Bahari
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammad Bagher Oghazian
- Department of Internal Medicine, Faculty of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran.
| | - Benyamin Hoseini
- Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. .,Department of Health Information Technology, Neyshabur University of Medical Sciences, Neyshabur, Iran.
| |
Collapse
|
|
3
|
Jauhari N, Raina H, Soni G, Chadha N, Bharadvaja N. Mechanistic insights into the anticancer mode of action of an herbal drug. BIOINSPIRED BIOMIMETIC AND NANOBIOMATERIALS 2018. [DOI: 10.1680/jbibn.17.00003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Medicinal plants are a vast repository of natural compounds with therapeutic effects against various ailments. Bioactive compounds of these plants have shown to possess anticancer activities. Cancer is one of the fatal diseases causing premature deaths across the world. Two important metabolites, serpentine, a major secondary metabolite of Rauwolfia serpentina, and amarogentin, isolated from Swertia chirata, are found to possess anticancer properties. A comparable in silico analysis of the two anticancer agents serpentine and amarogentin has been done to evaluate their ability to inhibit two potential molecular targets for cancer, nuclear factor-κB (NF-κB) and cyclo-oxygenase-2 (COX-2). The least binding energies of amarogentin with NF-κB and COX-2 are −7·173 and −7·649, respectively, which are better than that of serpentine. The molecular simulation of amarogentin and serpentine suggests that amarogentin has better binding affinities with both cancer targets. Amarogentin is thermodynamically more stable with COX-2 than with NF-κB. Amarogentin is a potent anticancer agent as evidenced by the inhibition of COX-2. This finding would be beneficial to people with cancer.
Collapse
Affiliation(s)
| | | | - Garima Soni
- Delhi Technological University, Delhi, India
| | - Nidhi Chadha
- Institute of Nuclear Medicine and Allied Sciences, Delhi, India
| | | |
Collapse
|
|
4
|
Zhang Y, Pan KF, Zhang L, Ma JL, Zhou T, Li JY, Shen L, You WC. Helicobacter pylori, cyclooxygenase-2 and evolution of gastric lesions: results from an intervention trial in China. Carcinogenesis 2015; 36:1572-9. [PMID: 26449252 DOI: 10.1093/carcin/bgv147] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2015] [Accepted: 10/01/2015] [Indexed: 12/15/2022] Open
Abstract
To investigate the role of cyclooxygenase (COX)-2/prostaglandin E2 (PGE2) in the process of Helicobacter pylori-induced gastric carcinogenesis, a prospective study based on an intervention trial was conducted in Linqu County, China. A total of 1401 subjects with histopathologic diagnosis were investigated at baseline, among those, 919 completed subsequent interventions (anti-H.pylori and/or celecoxib treatment). Expressions of COX-2 and Ki-67 were assessed by immunohistochemistry, and PGE2 levels were measured by enzyme immunoassay before and after interventions, respectively. We found a grade-response relationship between COX-2 expression level and risk of advanced gastric lesions at baseline. Stratified analysis indicated an additive interaction between COX-2 expression and H.pylori infection on the elevated risk of advanced gastric lesions. The odds ratios (ORs) for both factors combined were 9.31 [95% confidence interval (CI): 4.13-20.95] for chronic atrophic gastritis, 16.26 (95% CI: 7.29-36.24) for intestinal metaplasia and 21.13 (95% CI: 7.87-56.75) for dysplasia, respectively. After interventions, COX-2 expression and Ki-67 labeling index (LI) were decreased in anti-H.pylori group (OR: 1.65, 95% CI: 1.36-1.99 for COX-2; OR: 1.78, 95% CI: 1.49-2.12 for Ki-67) or anti-H.pylori followed by celecoxib group (OR: 1.41, 95% CI: 1.17-1.70 for COX-2; OR: 1.63, 95% CI: 1.37-1.94 for Ki-67). PGE2 levels were decreased in all treatment groups. Furthermore, the regression of gastric lesions was associated with the decrease of COX-2 expression or Ki-67 LI after interventions. Our findings indicate that H.pylori-induced COX-2/PGE2 pathways play an important role on the progression of precancerous gastric lesions in a Chinese population.
Collapse
Affiliation(s)
| | | | | | | | | | - Ji-You Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Pathology and
| | - Lin Shen
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | | |
Collapse
|
|
5
|
Shukla S, Bafna K, Sundar D, Thorat SS. The bitter barricading of prostaglandin biosynthesis pathway: understanding the molecular mechanism of selective cyclooxygenase-2 inhibition by amarogentin, a secoiridoid glycoside from Swertia chirayita. PLoS One 2014; 9:e90637. [PMID: 24603686 PMCID: PMC3946170 DOI: 10.1371/journal.pone.0090637] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2013] [Accepted: 02/04/2014] [Indexed: 12/24/2022] Open
Abstract
Swertia chirayita, a medicinal herb inhabiting the challenging terrains and high altitudes of the Himalayas, is a rich source of essential phytochemical isolates. Amarogentin, a bitter secoiridoid glycoside from S. chirayita, shows varied activity in several patho-physiological conditions, predominantly in leishmaniasis and carcinogenesis. Experimental analysis has revealed that amarogentin downregulates the cyclooxygenase-2 (COX-2) activity and helps to curtail skin carcinogenesis in mouse models; however, there exists no account on selective inhibition of the inducible cyclooxygenase (COX) isoform by amarogentin. Hence the computer-aided drug discovery methods were used to unravel the COX-2 inhibitory mechanism of amarogentin and to check its selectivity for the inducible isoform over the constitutive one. The generated theoretical models of both isoforms were subjected to molecular docking analysis with amarogentin and twenty-one other Food and Drug Authority (FDA) approved lead molecules. The post-docking binding energy profile of amarogentin was comparable to the binding energy profiles of the FDA approved selective COX-2 inhibitors. Subsequent molecular dynamics simulation analysis delineated the difference in the stability of both complexes, with amarogentin-COX-2 complex being more stable after 40ns simulation. The total binding free energy calculated by MMGBSA for the amarogentin-COX-2 complex was −52.35 KCal/mol against a binding free energy of −8.57 KCal/mol for amarogentin-COX-1 complex, suggesting a possible selective inhibition of the COX-2 protein by the natural inhibitor. Amarogentin achieves this potential selectivity by small, yet significant, structural differences inherent to the binding cavities of the two isoforms. Hypothetically, it might block the entry of the natural substrates in the hydrophobic binding channel of the COX-2, inhibiting the cyclooxygenation step. To sum up briefly, this work highlights the mechanism of the possible selective COX-2 inhibition by amarogentin and endorses the possibility of obtaining efficient, futuristic and targeted therapeutic agents for relieving inflammation and malignancy from this phytochemical source.
Collapse
Affiliation(s)
- Shantanu Shukla
- Bioresource Database and Bioinformatics Division, Regional Center of Institute of Bioresources and Sustainable Development, Tadong, Gangtok, Sikkim, India
| | - Khushboo Bafna
- Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology Delhi, Hauz Khas, New Delhi, India
| | - Durai Sundar
- Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology Delhi, Hauz Khas, New Delhi, India
- * E-mail: (SST); (DS)
| | - Sunil S. Thorat
- Bioresource Database and Bioinformatics Division, Regional Center of Institute of Bioresources and Sustainable Development, Tadong, Gangtok, Sikkim, India
- Distributed Information Sub-Centre, Institute of Bioresources and Sustainable Development, Imphal, Manipur, India
- * E-mail: (SST); (DS)
| |
Collapse
|
|
6
|
Young Oh T, Ok Ahn B, Jung Jang E, Sang Park J, Jong Park S, Wook Baik H, Hahm KB. Accelerated Ulcer Healing and Resistance to Ulcer Recurrence with Gastroprotectants in Rat Model of Acetic Acid-induced Gastric Ulcer. J Clin Biochem Nutr 2011; 42:204-14. [PMID: 18545642 PMCID: PMC2386523 DOI: 10.3164/jcbn.2008030] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2006] [Accepted: 10/26/2006] [Indexed: 12/11/2022] Open
Abstract
Quality of ulcer healing (QOUH) is defined as ideal ulcer healing featuring with the fine granular ulcer scar, high functional restoration and the resistance to recurrence. This study was designed to compare the rates of QOUH achievement in rat gastric ulcer model between acid suppressant treated group and gastroprotectant treated group accompanied with elucidations of molecular mechanisms. Serosal injection of acetic acids for generating gastric ulcer and intraperitoneal (ip) injection of recombinant interleukin 1-beta (IL-1β) for recurring healed ulcer was done in SD rats. The 72 rats were divided into three groups according to treatment as follows; Group I, no further treatment, Group II, 8 weeks treatment of omeprazole, and Group III, 8 weeks of gastroprotectant treatment. IL-1β was administered for ulcer recurrence after 28 weeks of acetic acid injection. At four weeks after gastric ulcerogenesis, 58.3% (7/12) of active gastric ulcer were converted to healing stage in Group III, but 16.7% (2/12) in Group II and none in Group I, for which significant levels of epidermal growth factor, mucin, and pS2/trefoil peptide1 were contributive to these accelerated healings of Group III. ip injections of rIL-1β (200 µg/kg) at 28 weeks after acetic acid injection led to 100% of ulcer recurrence in Group I and 75.0% in Group II, but only 16.7% of Group III rats showed ulcer recurrence. Significantly attenuated levels of inflammatory cytokines including IL-2, transforming growth factor-alpha (TNF-α), cyclooxygenase-2 (COX-2), nitrotyrosine were responsible for the resistance to ulcer recurrence in Group III. Conclusively, gastroprotectant might be prerequisite in order to achieve ideal QOUH through significant inductions of remodeling.
Collapse
Affiliation(s)
- Tae Young Oh
- Dong A Pharmaceutical Research Institute, Yongin 130-708, Korea
| | | | | | | | | | | | | |
Collapse
|
|
7
|
Kim HJ, Hong SJ, Ko BM, Cho WY, Cho JY, Lee JS, Lee MS. Helicobacter pyloriEradication Suppresses Metachronous Gastric Cancer and Cyclooxygenase-2 Expression after Endoscopic Resection of Early Gastric Cancer. THE KOREAN JOURNAL OF HELICOBACTER AND UPPER GASTROINTESTINAL RESEARCH 2011. [DOI: 10.7704/kjhugr.2011.11.2.117] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Hwa Jong Kim
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon, Korea
| | - Su Jin Hong
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon, Korea
| | - Bong Min Ko
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon, Korea
| | - Won Young Cho
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon, Korea
| | - Joo Young Cho
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon, Korea
| | - Joon Seong Lee
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon, Korea
| | - Moon Sung Lee
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon, Korea
| |
Collapse
|
|
8
|
Yanaoka K, Oka M, Yoshimura N, Deguchi H, Mukoubayashi C, Enomoto S, Maekita T, Inoue I, Ueda K, Utsunomiya H, Iguchi M, Tamai H, Fujishiro M, Nakamura Y, Tsukamoto T, Inada K, Takeshita T, Ichinose M. Preventive effects of etodolac, a selective cyclooxygenase-2 inhibitor, on cancer development in extensive metaplastic gastritis, a Helicobacter pylori-negative precancerous lesion. Int J Cancer 2010; 126:1467-73. [PMID: 19711347 DOI: 10.1002/ijc.24862] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The present study investigated the preventive effects of etodolac, a selective cyclo-oxygenase (COX)-2 inhibitor, on metachronous cancer development after endoscopic resection of early gastric cancer. Among 267 early gastric cancer patients who underwent endoscopic resection, 47 patients with extensive metaplastic gastritis were selected based on endoscopic findings and our previously described criteria of serum pepsinogen (PG) test-positive and Helicobacter pylori antibody-negative conditions. Nonrandomized etodolac treatment (300 mg/day) was administered to 26 patients (Group A), while the remaining 21 patients were untreated (Group B). No significant differences in age, sex distribution, lifestyle factors or extent of metaplastic gastritis at baseline were identified between groups. Patients were followed for metachronous cancer development with endoscopy every 6-12 months for up to 5 years. Mean (standard deviation) follow-up period was 4.2 (0.9) years. In Group B, 5 cancers developed (incidence rate = 6,266/100,000 person-years), significantly more than the 1 cancer in Group A (incidence rate = 898/100,000 person-years; p < 0.05). Long-term etodolac treatment did not influence the extent of metaplastic gastritis as revealed by endoscopic findings or by serum PG levels, but effectively reduced metachronous cancer development in patients with extensive metaplastic gastritis. These results strongly suggest that chemoprevention of cancer in the metaplastic stomach is possible by controlling COX-2 expression.
Collapse
Affiliation(s)
- Kimihiko Yanaoka
- Department of Gastroenterology, School of Medicine, Wakayama Medical University, Wakayama City, Wakayama 641-0012, Japan
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
9
|
Noyan T, Guducuoglu H, Ilhan M. A study of oxidative stress parameters in anti-helicobacter pylorus immunoglobulin g positive and negative gastric cancer patients. Yonsei Med J 2009; 50:677-82. [PMID: 19881972 PMCID: PMC2768243 DOI: 10.3349/ymj.2009.50.5.677] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2007] [Revised: 11/20/2007] [Accepted: 11/20/2007] [Indexed: 12/19/2022] Open
Abstract
PURPOSE Helicobacter pylorus (HP) is a Gram-negative spiral-shaped microaerophilic bacterium, which colonizes in the gastric mucosa of humans. The gastric human pathogen HP causes chronic gastritis and ulcers, and has a strong relationship with gastric cancer. The aim of this study was to determine advanced oxidation protein products (AOPP) levels, activities of myeloperoxidase (MPO) and catalase (CAT) in two groups. MATERIALS AND METHODS For this aim, one group included 30 patients with gastric cancer (Group 1) and the other included 30 subjects with non-gastric cancer and Anti-HP immunoglobulin (Ig) G antibody positive (group 2). Anti-HP IgG antibody test values were found as positive in fifty percent of group 1 and all of the group 2 patients. RESULTS Significantly increased AOOP levels were found in group 1 (p < 0.05) compared to group 2. There were no significant differences between the groups in regard to activities of MPO and CAT. In addition, AOPP level, MPO and CAT activities were similar among the Anti-HP IgG positive and negative subgroups of group 1 patients. CONCLUSION The result of this study indicated that gastric cancer patients were characterized by increased protein oxidation, whereas there was no significant difference in oxidative stress parameters and antioxidant enzyme activity between the Anti-HP IgG positive and negative gastric cancer patients.
Collapse
Affiliation(s)
- Tevfik Noyan
- Department of Biochemistry, Yuzuncu Yil University, Medical Faculty, Van, Turkey.
| | | | | |
Collapse
|
|
10
|
Kabir S. Effect of Helicobacter pylori eradication on incidence of gastric cancer in human and animal models: underlying biochemical and molecular events. Helicobacter 2009; 14:159-71. [PMID: 19702845 DOI: 10.1111/j.1523-5378.2009.00677.x] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Gastric cancer remains one of the most common cancers worldwide. A strong association exists between Helicobacter pylori infection and the risk of developing noncardia gastric cancer. H. pylori eradication by antibiotic treatment is regarded as a primary chemoprevention strategy to reduce gastric cancer incidence. AIM To analyze the efficacy of H. pylori eradication in preventing gastric cancer in human and animal models, and to discuss whether biochemical, genetic, and epigenetic changes associated with H. pylori infection are reversible after curing the infection. RESULTS Several intervention trials have indicated that in some patients, H. pylori eradication leads to regression and prevents the progression of precancerous lesions. The eradication therapy reduces gastric cancer incidence in patients without any precancerous lesions at the baseline and is most effective before the development of atrophic gastritis. A few recent intervention studies in Japan have demonstrated significant prophylactic effects of eradication therapy on the development of gastric cancer, suggesting the use of eradication therapy in high-risk populations as a gastric cancer reduction strategy. However, gastric cancer may still develop despite successful eradication therapy. Studies in animal models have confirmed the use of eradication therapy at an early point of infection to prevent gastric cancer development. CONCLUSION H. pylori eradication may not completely abolish the risk of gastric cancer. However, eradication therapy may be used in high-risk populations to reduce gastric cancer incidence. It can reverse many biochemical, genetic, and epigenetic changes that H. pylori infection induces in the stomach.
Collapse
Affiliation(s)
- Shahjahan Kabir
- Academic Research and Information Management, Uppsala, Sweden.
| |
Collapse
|
|
11
|
Take S, Mizuno M, Ishiki K, Nagahara Y, Yoshida T, Yokota K, Oguma K. Baseline gastric mucosal atrophy is a risk factor associated with the development of gastric cancer after Helicobacter pylori eradication therapy in patients with peptic ulcer diseases. J Gastroenterol 2007; 42 Suppl 17:21-7. [PMID: 17238021 DOI: 10.1007/s00535-006-1924-9] [Citation(s) in RCA: 93] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND We previously reported that eradication of Helicobacter pylori could reduce the risk of developing gastric cancer in patients with peptic ulcer diseases. In the present study, we further followed up our patient groups to identify factors associated with the development of gastric cancer. METHODS Prospective posteradication evaluations were conducted in 1342 consecutive patients (1191 men and 151 women; mean age, 50 years) with peptic ulcer disease who had received H. pylori eradication therapy. The patients had undergone endoscopic examination before eradication therapy to evaluate peptic ulcers, background gastric mucosa, and H. pylori infection. After confirmation of eradication, follow-up endoscopy was performed yearly. RESULTS A total of 1131 patients were followed for up to 9.5 years (mean, 3.9 years). Gastric cancer developed in 9 of 953 patients cured of infection and in 4 of 178 who had persistent infection (P=0.04). The risk of developing gastric cancer after receiving H. pylori eradication therapy was increased according to the grade of baseline gastric mucosal atrophy (P=0.01). In patients with peptic ulcer diseases, persistent infection of H. pylori (hazard ratio, 3.9; P=0.03), the grade of baseline gastric mucosal atrophy (3.3, P=0.01) and age (2.0, P=0.04) were identified as significant risk factors for developing gastric cancer. CONCLUSIONS The grade of gastric atrophy was closely related to the development of gastric cancer after receiving H. pylori eradication therapy. Thus, eradication of H. pylori before the significant expansion of atrophy is most beneficial to prevent gastric cancer.
Collapse
Affiliation(s)
- Susumu Take
- Fukuwatari Municipal Hospital, Okayama, Japan
| | | | | | | | | | | | | |
Collapse
|
|
12
|
Akcam M, Elmas O, Yilmaz A, Cağlar S, Artan R, Gelen T, Alicigüzel Y. Myeloperoxidase, xanthine oxidase and superoxide dismutase in the gastric mucosa of Helicobacter pylori positive and negative pediatric patients. Mol Cell Biochem 2006; 290:125-30. [PMID: 16758302 DOI: 10.1007/s11010-006-9176-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2005] [Accepted: 03/02/2006] [Indexed: 12/13/2022]
Abstract
The aim of this study was determination and comparison of the levels of myeloperoxidase (MPO), xanthine oxidase (XO), and superoxide dismutase (SOD) in gastric mucosa of children who were infected and noninfected with Helicobacter pylori (HP). The MPO, and XO enzyme activities were detected via kinetic measurement, and the MPO, XO and SOD enzyme protein levels were detected via Western blot, in antral mucosa specimens of 43 patients who underwent upper gastrointestinal endoscopy with various indications. The diagnosis of HP infection was made with a positive rapid urease test and histopathologic detection. MPO activity and enzyme protein levels were measured in 14 [8 HP (+) and 6 HP (-)], and in 9 [5 HP (+) and 4 HP (-)] while XO activity and enzyme protein levels were measured in 16 [10 HP (+) and 6 HP (-)] and in 9 [5 HP (+) and 4 HP (-)] patients, respectively. SOD protein level was detected in 13 [7 HP (+) and 6 HP (-)] patients. Of 43 patients 25 were HP (+) and 18 were HP (-). MPO activities were 75.6 +/- 40.5 and 98.8 +/- 44.1 U/g. protein (p = 0.302) while XO activities were 0.5 +/- 0.3 and 0.4 +/- 0.2 U/g. protein in HP (+) and HP (-) patients, respectively (p = 0.625). Measured enzyme protein levels of MPO, XO and SOD were found statistically indifferent in HP (+) and HP (-) patients (p = 0.327, p = 0.086, and p = 0.775, respectively). The results of this study revealed that, MPO, XO and SOD conditions in gastric mucosa alone were not affected from HP presence. That's why MPO, XO, and SOD may not have important roles in the pathogenesis of HP related gastric disease in children.
Collapse
Affiliation(s)
- Mustafa Akcam
- Medical School, Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Akdeniz University, Antalya, Turkey.
| | | | | | | | | | | | | |
Collapse
|
|
13
|
Tsuji S, Tsujii M, Murata H, Nishida T, Komori M, Yasumaru M, Ishii S, Sasayama Y, Kawano S, Hayashi N. Helicobacter pylori eradication to prevent gastric cancer: underlying molecular and cellular mechanisms. World J Gastroenterol 2006; 12:1671-1680. [PMID: 16586533 PMCID: PMC4124339 DOI: 10.3748/wjg.v12.i11.1671] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2005] [Revised: 09/25/2005] [Accepted: 11/10/2005] [Indexed: 02/06/2023] Open
Abstract
Numerous cellular and molecular events have been described in development of gastric cancer. In this article, we overviewed roles of Helicobacter pylori (H pylori) infection on some of the important events in gastric carcinogenesis and discussed whether these cellular and molecular events are reversible after cure of the infection. There are several bacterial components affecting gastric epithelial kinetics and promotion of gastric carcinogenesis. The bacterium also increases risks of genetic instability and mutations due to NO and other reactive oxygen species. Epigenetic silencing of tumor suppressor genes such as RUNX3 may alter the frequency of phenotype change of gastric glands to those with intestinal metaplasia. Host factors such as increased expression of growth factors, cytokines and COX-2 have been also reported in non-cancerous tissue in H pylori-positive subjects. It is noteworthy that most of the above phenomena are reversed after the cure of the infection. However, some of them including overexpression of COX-2 continue to exist and may increase risks for carcinogenesis in metaplastic or dysplastic mucosa even after successful H pylori eradication. Thus, H pylori eradication may not completely abolish the risk for gastric carcinogenesis. Efficiency of the cure of the infection in suppressing gastric cancer depends on the timing and the target population, and warrant further investigation.
Collapse
Affiliation(s)
- Shingo Tsuji
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine (K1), 2-2 Yamadaoka, Suita, 565-0871 Japan.
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
14
|
Malfertheiner P, Sipponen P, Naumann M, Moayyedi P, Mégraud F, Xiao SD, Sugano K, Nyrén O. Helicobacter pylori eradication has the potential to prevent gastric cancer: a state-of-the-art critique. Am J Gastroenterol 2005; 100:2100-15. [PMID: 16128957 DOI: 10.1111/j.1572-0241.2005.41688.x] [Citation(s) in RCA: 146] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Helicobacter pylori infection continues to play a key role in gastric diseases. Colonization of the gastric mucosa with the bacterium invariably results in the development of chronic gastritis and subsets of patients have a progression of the chronic gastritis to either ulcer or cancer. Epidemiological evidence indicates that the proportion of all gastric cancers attributable to H. pylori infection, and hence potentially preventable upon elimination of this risk factor, is somewhere in the range of 60% to 90%. This portends significant benefit in terms of morbidity and mortality, not least in populations with high prevalence of H. pylori infection coupled with high incidence of gastric cancer. The effect of prophylactic H. pylori eradication on gastric cancer incidence in humans remains unknown, however. Results from randomized trials are eagerly awaited, but availability of strong conclusive results may take many years. A growing number of studies show considerable variation in risk for gastric cancer development, depending on H. pylori strain type and the genetic predisposition of the host. There is also a remote possibility that elimination of the infection may have adverse health implications (e.g., antibiotic resistance), and therefore "simple" risk stratification and targeted chemoprevention is required. Based on "in depth" evidence presented at this workshop, the majority of the scientific task force favored a search-and-treat strategy in first-degree relatives of gastric cancer patients and an overwhelming majority felt that a more general screen-and-treat strategy should be focused in the first instance on a population with a high incidence of H. pylori-associated diseases.
Collapse
Affiliation(s)
- Peter Malfertheiner
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Germany
| | | | | | | | | | | | | | | |
Collapse
|
|
15
|
Gudis K, Tatsuguchi A, Wada K, Futagami S, Nagata K, Hiratsuka T, Shinji Y, Miyake K, Tsukui T, Fukuda Y, Sakamoto C. Microsomal prostaglandin E synthase (mPGES)-1, mPGES-2 and cytosolic PGES expression in human gastritis and gastric ulcer tissue. J Transl Med 2005; 85:225-36. [PMID: 15531909 DOI: 10.1038/labinvest.3700200] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
Abstract
Recently, three different prostaglandin E2 synthases have been identified: microsomal prostaglandin E synthase (mPGES)-1, cytosolic PGES (cPGES), and mPGES-2; however, their role and connection to cyclooxygenase (COX)-2 in the gastric ulcer repair process remain unknown. Therefore, we examined mPGES-1, cPGES, and mPGES-2 expression and localization in the stomach in vitro and in vivo. Tissues were obtained from Helicobacter pylori (H. pylori)-infected patients and consisted of surgical resections of gastric ulcers, or biopsies of gastric ulcers or gastritis. mPGES-1 mRNA and protein expression levels were examined by real-time polymerase chain reaction (PCR) and Western blot analysis, respectively. mPGES-1, cPGES, and mPGES-2 localization were analyzed immunohistochemically. Induction of PGES expression in response to interleukin (IL)-1beta was examined in vitro in the cultured human gastric fibroblast line Hs262.St. Real-time PCR analysis of mPGES-1 mRNA expression in biopsy samples showed significantly higher expression levels in open than in closed gastric ulcer tissue. Western blot analysis showed mPGES-1 protein expression limited to open ulcer tissue, while mPGES-2 and cPGES immunoreactivities were seen in both open and closed ulcer tissue. Immunohistochemical analysis showed strong mPGES-1 expression in fibroblasts and macrophages of the ulcer bed, paralleling COX-2 expression. cPGES and mPGES-2 expression levels were seen in both fibroblasts of the ulcer bed and in epithelial cells. Furthermore, stronger cPGES and mPGES-2 immunoreactivities were seen in scattered mast cell-like cells and neuroendocrine-like cells, respectively. Induction of mPGES-1 expression in response to IL-1beta was seen in cultured gastric fibroblasts in vitro, and double immunostaining showed mPGES-1 coexpression with COX-2 in fibroblasts of the ulcer bed in vivo. In conclusion, mPGES-1, cPGES, and mPGES-2 are all expressed in gastric ulcer tissue, but only mPGES-1 parallels COX-2 expression in mesenchymal and inflammatory cells of the ulcer bed, suggesting a key role for this enzyme in the ulcer repair process.
Collapse
Affiliation(s)
- Katya Gudis
- Third Department of Internal Medicine, Nippon Medical School, Sendagi, Bunkyo-ku, Tokyo, Japan
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
16
|
De Luca A, Iaquinto G. Helicobacter pylori and gastric diseases: a dangerous association. Cancer Lett 2004; 213:1-10. [PMID: 15312678 DOI: 10.1016/j.canlet.2004.06.006] [Citation(s) in RCA: 56] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2004] [Accepted: 06/01/2004] [Indexed: 12/13/2022]
Abstract
The bacterium Helicobacter pylori is linked to the appearance of several gastric diseases and in particular is associated with a progression to gastric cancer. Thistrun -1 bacterium colonizes the gastric mucosa directly interacting with epithelial cells. It is well known that H. pylori is associated with alterations in the gastric epithelial cell cycle, and apoptosis, higher levels of mononuclear and neutrophilic infiltrates, more severe atrophy and intestinal metaplasia. In last years, two mechanisms that interact with each other or not have been proposed: the hyperproliferation of gastric cells and oxidative damage of stomach mucosa. In particular, cell cycle alterations induce mitogenic signals and proto-oncogene expression that may trigger the development of cancer. Contemporary, H. pylori is able to induce polymorphonuclear and mononuclear cells that produce oxygen free radicals that could cause DNA damage to the adjacent cells leading to cancer development. Due to dangerous infection of this bacterium, the scientific community must point out its attention on the development of detection and prevention strategies.
Collapse
Affiliation(s)
- Antonio De Luca
- Department of Medicine and Public Health, Section of Clinical Anatomy, Second University of Naples, Naples, Italy
| | | |
Collapse
|
|
17
|
Wambura C, Aoyama N, Shirasaka D, Kuroda K, Maekawa S, Ebara S, Watanabe Y, Tamura T, Kasuga M. Influence of gastritis on cyclooxygenase-2 expression before and after eradication of Helicobacter pylori infection. Eur J Gastroenterol Hepatol 2004; 16:969-79. [PMID: 15371919 DOI: 10.1097/00042737-200410000-00004] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES Helicobacter pylori infection causes chronic gastritis and induces cyclooxygenase (COX)-2 expression. The relationship between gastritis and COX-2 expression is not well understood, especially long after the organism has been eradicated. We designed a study to elucidate this relationship. METHODS Four endoscopic gastric biopsies from each of 118 H. pylori-infected subjects were assessed for COX-2 expression immunohistochemically, gastritis, by an updated Sydney System. In the 107 successfully eradicated subjects, the assessment was repeated once yearly, for 3 years. RESULTS After successful eradication, COX-2 expression was reduced significantly regardless of site. Atrophy improved significantly and intestinal metaplasia improved but not in the antrum greater curvature. After 1 year COX-2 expression was not significantly different in the epithelia with and without intestinal metaplasia. Correlation between COX-2 expression and neutrophil score in the antrum (r = 0.214, P = 0.042) and inflammation in the corpus (r = 0.234, P = 0.025) disappeared after eradication. COX-2 expression correlated well with atrophy and metaplasia before and after eradication. No significant reduction in COX-2 or improvement in gastritis was found in subjects with eradication failure. CONCLUSION H. pylori infection is associated with the enhancement of COX-2 expression in the gastric mucosa. Eradication therapy reduces COX-2 expression and hence may reduce the risk of cancer development.
Collapse
Affiliation(s)
- Casmir Wambura
- Division of Diabetes, Digestive and Kidney Diseases, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Japan
| | | | | | | | | | | | | | | | | |
Collapse
|
|
18
|
Sun WH, Yu Q, Shen H, Ou XL, Cao DZ, Yu T, Qian C, Zhu F, Sun YL, Fu XL, Su H. Roles of Helicobacter pylori infection and cyclooxygenase-2 expression in gastric carcinogenesis. World J Gastroenterol 2004; 10:2809-13. [PMID: 15334675 PMCID: PMC4572107 DOI: 10.3748/wjg.v10.i19.2809] [Citation(s) in RCA: 40] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
AIM: Cyclooxygenase (COX)-2 is over expressed in gastrointestinal neoplasm. Helicobacter pylori (H pylori) infection is causally linked to gastric cancer. However, the expression of COX-2 in various stages of H pylori-associated gastric carcinogenesis pathway has not been elucidated. Therefore, the aim of this study was to clarify the role of H pylori induced COX-2 expression during carcinogenesis in the stomach.
METHODS: Gastric biopsies from 138 subjects [30 cases of chronic superficial gastritis (CSG), 28 cases of gastric glandular atrophy (GA), 45 cases of gastric mucosal intestinal metaplasia (IM), 12 cases of moderate gastric epithelial dysplasia and 23 cases of gastric cancer] were enrolled. H pylori infection was assessed by a rapid urease test and histological examination (modified Giemsa staining). The expression of COX-1 and COX-2 in human gastric mucosa was detected by immunohistochemical staining.
RESULTS: H pylori infection rate was 64.3% in GA and 69.5% in gastric cancer, which was significantly higher than that (36.7%) in CSG (P < 0.05). The positive expression rates of COX-2 were 10.0%, 35.7%, 37.8%, 41.7% and 69.5% in CSG, GA, IM, dysplasia and gastric cancer, respectively. From CSG to GA, IM, dysplasia and finally to gastric cancer, expression of COX-2 showed an ascending tendency, whereas COX-1 expression did not change significantly in the gastric mucosa. The level of COX-2 expression in IM and dysplasia was significantly higher in H pylori-positive than in H pylori-negative subjects (P < 0.01).
CONCLUSION: COX-2 expression induced by H pylori infection is a relatively early event during carcinogenesis in the stomach.
Collapse
Affiliation(s)
- Wei-Hao Sun
- Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China.
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
19
|
Iacopini F, Consolazio A, Bosco D, Marcheggiano A, Bella A, Pica R, Paoluzi OA, Crispino P, Rivera M, Mottolese M, Nardi F, Paoluzi P. Oxidative damage of the gastric mucosa in Helicobacter pylori positive chronic atrophic and nonatrophic gastritis, before and after eradication. Helicobacter 2003; 8:503-12. [PMID: 14535997 DOI: 10.1046/j.1523-5378.2003.00172.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Helicobacter pylori is the main cause of gastritis and a primary carcinogen. The aim of this study was to assess oxidative damage in mucosal compartments of gastric mucosa in H. pylori positive and negative atrophic and nonatrophic gastritis. MATERIALS AND METHODS Five groups of 10 patients each were identified according to H. pylori positive or negative chronic atrophic (Hp-CAG and CAG, respectively) and nonatrophic gastritis (Hp-CG and CG, respectively), and H. pylori negative normal mucosa (controls). Oxidative damage was evaluated by nitrotyrosine immunohistochemistry in the whole mucosa and in each compartment at baseline and at 2 and 12 months after eradication. Types of intestinal metaplasia were classified by histochemistry. RESULTS Total nitrotyrosine levels appeared significantly higher in H. pylori positive than in negative patients, and in Hp-CAG than in Hp-CG (p <.001); no differences were found between H. pylori negative gastritis and normal mucosa. Nitrotyrosine were found in foveolae and intestinal metaplasia only in Hp-CAG. At 12 months after H. pylori eradication, total nitrotyrosine levels showed a trend toward a decrease in Hp-CG and decreased significantly in Hp-CAG (p =.002), disappearing from the foveolae (p =.002), but remaining unchanged in intestinal metaplasia. Type I and II of intestinal metaplasia were present with the same prevalence in Hp-CAG and CAG, and did not change after H. pylori eradication. CONCLUSIONS Oxidative damage of the gastric mucosa increases from Hp-CG to Hp-CAG, involving the foveolae and intestinal metaplasia. H. pylori eradication induces a complete healing of foveolae but not of intestinal metaplasia, reducing the overall oxidative damage in the mucosa.
Collapse
Affiliation(s)
- Federico Iacopini
- Gastroenterology Unit, Department of Clinical Sciences, University La Sapienza of Rome, Italy
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
20
|
Tsuji S, Kawai N, Tsujii M, Kawano S, Hori M. Review article: inflammation-related promotion of gastrointestinal carcinogenesis--a perigenetic pathway. Aliment Pharmacol Ther 2003; 18 Suppl 1:82-9. [PMID: 12925144 DOI: 10.1046/j.1365-2036.18.s1.22.x] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Chronic inflammation has been reported to accelerate neoplasmas in gastrointestinal tract. Certain bacteria including Helicobacter pylori directly interact with host cells, induce proinflammatory cytokines and stimulate production of free radicals. Free radicals cause mutations in target cells so that neoplastic clones are established. Accumulation of such genetic alterations may cause malignant transformation of some established clones. In addition, inflammatory alterations may promote growth, expansion and invasion of gastrointestinal epithelial cells. The latter changes caused by inflammation may occur even without further genetic mutations or epigenetic alterations, and therefore may be categorized as 'perigenetic alterations' of neoplastic cells. For an example, tumour necrosis factor alpha (TNF-alpha) plays pivotal roles not only in the reduction but also in the growth, invasion and metastases of certain neoplasmas. Our studies show that TNF-alpha increases intracellular radical production, degradates E-cadherin / beta-catenin complex and promotes dispersion and migration in epithelial cells transformed with an activated src oncogene (v-src). These data indicate that an inflammatory cytokine induces the malignant potential of src-activated neoplastic cells. Interestingly, TNF-alpha also induced these phenotypic changes in nonmutated cells whose c-Src was activated by TGF-alpha, suggesting that the invasive properties of the cell were not necessarily related to gene mutation. Furthermore, certain radical scavengers suppressed the invasive phenotype of the cells. These results indicate that perigenetic alterations are an important target of pharmacological intervention of carcinogenesis.
Collapse
Affiliation(s)
- S Tsuji
- Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Japan.
| | | | | | | | | |
Collapse
|
|
21
|
Wang N, Yao XX, Zhang L, Bai WY, Feng LY. Histologic changes after H.pylori eradication with Killing Hp decoction for chronic gastritis. Shijie Huaren Xiaohua Zazhi 2003; 11:558-561. [DOI: 10.11569/wcjd.v11.i5.558] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM To study the histologic changes after H.pylori eradication with Killing Hp decoction for chronic gastritis.
METHODS Total 81 cases of chronic gastritis with H.pylori infection were prospectively studied. After a 7-day triple therapy (bismuth potassium citrate, clarithromycin and tinidazole), the patients were divided randomly into 3 groups. Group A (n = 23): Killing Hp decoction, 1 Bid; GroupB (n = 15): marzulene-s-granules, 1 Tid; Group C (n = 15): aluminium hydroxide compound, 3-5 Bid; An endoscopy was performed at the frist and third months. Histological changes of gastric mucosa were compared before and after the treatment according to Sydney classification. COX-2(cyclooxygenase-2) protein was detected by immunohistochemical method, and the computer image processing system was used. For the patients of no eradication after one course therapy, anti-H.pylori treatment continued.
RESULTS H.pylori eradication got a very good curative effect in 81.9% of the patients. A favourable histologic change of acute inflammatory infiltration was found (average values from 0.79±0.78 to 0.042±0.14) (P<0.001).The mean percentage of COX-2 positive cells significantly decreased after H.pylori eradication [(43.5±12.3)%, (32.3±8.3)%, P<0.001]. No chronic inflammation was observed after one month therapy (1.90±0.68, 1.67±0.76, P>0.05. Compared to the controls, after Killing Hp decoction treatment for three months, the score corresponding to chronic gastritis declined progressively (average values from 2.9±0.6 to 1.30±0.60, P<0.001), and the mean percentage of COX-2 positive cells staining got further decreased and reached a statistically significant difference, compared with the results obtained at the first month. [(31.6±5.9)%, (27.09±5.16)%, P<0.05]. Gastric atrophic lesions were improved after "killing Hp decoction" for three-month treatment.
CONCLUSION H. pylori related gastritis should be treated further with Killing Hp decoction after H.pylori eradication.
Collapse
Affiliation(s)
- Na Wang
- The 2nd Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
| | - Xi-Xian Yao
- The 2nd Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
| | - Lin Zhang
- The 2nd Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
| | - Wen-Yuan Bai
- The 2nd Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
| | - Li-Ying Feng
- The 2nd Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
| |
Collapse
|
|
22
|
Gisbert JP, Pajares JM. [Helicobacter pylori, cyclooxygenase-2 and gastric cancer]. Med Clin (Barc) 2003; 120:189-93. [PMID: 12605827 DOI: 10.1016/s0025-7753(03)73644-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Affiliation(s)
- Javier P Gisbert
- Servicio de Aparato Digestivo. Hospital Universitario de la Princesa. Madrid. España.
| | | |
Collapse
|
|
23
|
Hojo M, Miwa H, Ohkusa T, Ohkura R, Kurosawa A, Sato N. Alteration of histological gastritis after cure of Helicobacter pylori infection. Aliment Pharmacol Ther 2002; 16:1923-32. [PMID: 12390101 DOI: 10.1046/j.1365-2036.2002.01346.x] [Citation(s) in RCA: 56] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND It is still disputed whether gastric atrophy or intestinal metaplasia improves after the cure of Helicobacter pylori infection. AIM To clarify the histological changes after the cure of H. pylori infection through a literature survey. METHODS Fifty-one selected reports from 1066 relevant articles were reviewed. The extracted data were pooled according to histological parameters of gastritis based on the (updated) Sydney system. RESULTS Activity improved more rapidly than inflammation. Eleven of 25 reports described significant improvement of atrophy. Atrophy was not improved in one of four studies with a large sample size (> 100 samples) and in two of five studies with a long follow-up period (> 12 months), suggesting that disagreement between the studies was not totally due to sample size or follow-up period. Methodological flaws, such as patient selection, and statistical analysis based on the assumption that atrophy improves continuously and generally in all patients might be responsible for the inconsistent results. Four of 28 studies described significant improvement of intestinal metaplasia [corrected]. CONCLUSIONS Activity and inflammation were improved after the cure of H. pylori infection. Atrophy did not improve generally among all patients, but improved in certain patients. Improvement of intestinal metaplasia was difficult to analyse due to methodological problems including statistical power.
Collapse
Affiliation(s)
- M Hojo
- Department of Gastroenterology, Juntendo University, School of Medicine, Tokyo, Japan
| | | | | | | | | | | |
Collapse
|
|
24
|
Walker MM. Cyclooxygenase-2 expression in early gastric cancer, intestinal metaplasia and Helicobacter pylori infection. Eur J Gastroenterol Hepatol 2002; 14:347-9. [PMID: 11943943 DOI: 10.1097/00042737-200204000-00001] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Cyclooxygenase (COX) is the crucial enzyme for synthesis of prostaglandins and occurs in two isoforms COX-1 and COX-2. Whilst COX-1 is constantly expressed in the gastrointestinal tract in large quantities and probably maintains mucosal integrity through constant generation of prostaglandins, COX-2 is induced principally during inflammation. In early gastric cancer and in intestinal metaplasia the expression of COX-2 in patients infected by Helicobacter pylori is increased in intestinal type compared to diffuse type gastric cancer and in intestinal metaplasia. In tumours of mixed type, COX-2 is also increased in the intestinal component compared to the diffuse component. Whilst there has been success of COX-2 inhibition for chemoprevention in colon cancer, a similar role in gastric cancer needs to be carefully assessed in the light of reported adverse effects and whether the precancerous condition, intestinal metaplasia, can truly regress.
Collapse
Affiliation(s)
- Marjorie M Walker
- Department of Histopathology, Faculty of Medicine, Imperial College School of Science, Technology and Medicine, St Mary's Campus, Norfolk Place, London W2 1PG, UK.
| |
Collapse
|