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Korean J Gastroenterol. 2015 Dec;66(6):303-311. Korean.
Published online December 22, 2015.  https://doi.org/10.4166/kjg.2015.66.6.303
Copyright © 2015 The Korean Society of Gastroenterology
Unpleasant Journey from Helicobacter pylori-associated Gastritis to Gastric Cancer: Cancer Prevention by Taking a Detour
Sang Hwan Lee,1 Jong Min Park,2 Young Min Han,2 Weon Jin Ko,1 and Ki Baik Hahm1,2
1Digestive Disease Center, CHA University Bundang Medical Center, Seongnam, Korea.
2CHA Bio Complex, CHA Cancer Prevention Research Center, Seongnam, Korea.

Correspondence to: Ki Baik Hahm. Digestive Disease Center, CHA University Bundang Medical Center, 59 Yatap-ro, Bundang-gu, Seongnam 13496, Korea. Tel: +82-31-780-5005, Fax: +82-31-881-7185, Email: hahmkb@cha.ac.kr

This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Abstract

As a commensal or a pathogen, Helicobacter pylori can change the balance of a complex interaction that exists among gastric epithelial cells, microbes, and their environment. Therefore, unraveling this complex relationship of these mixtures can be expected to help prevent cancer as well as troublesome unmet medical needs of H. pylori infection. Though gastric carcinogenesis is a multi-step process, precancerous lesion can be reversible in the early phase of mucosal damage before reaching the stage of no return. However, biomarkers to predict rejuvenation of precancerous atrophic gastritis have not been identified yet and gastric cancer prevention is still regarded as an impregnable fortress. However, when we take the journey from H. pylori-associated gastritis to gastric cancer, it provides us with the clue for prevention since there are two main preventive strategies: eradication and anti-inflammation. The evidence supporting the former strategy is now ongoing in Japan through a nation-wide effort to eradicate H. pylori in patients with chronic gastritis, but suboptimal apprehension to increasing H. pylori resistance to antibiotics and patient non-compliance still exists. The latter strategy has been continued in the author's research center under siTRP (short-term intervention to revert premalignant lesion) strategy. By focusing on the role of inflammation in the development of H. pylori-associated gastric carcinogenesis, this review is intended to explain the connection between inflammation and gastric cancer. Strategies on H. pylori eradication, removal of inflammation, and reverting preneoplastic lesion will also be introduced. In the end, we expect to be able to prevent gastric cancer by take a detour from the unpleasant journey, i.e. from H. pylori-associated gastritis to gastric cancer.

Keywords: Helicobacter pylori; Inflammation; Nutrition therapy; Gastrointestinal cancer; Rejuvenation

Figures


 Fig. 1
Helicobacter pylori-induced gastric carcinoma. The various factors affect H. pylori-induced carcinogenesis in several ways and driving of the host, environment and bacteria ultimately are acted cell-conversion, proliferation, differentiation, and inflammation, etc. Therefore their players give results like gastritis, ulcer and tumor but H. pylori infection as regards gastric cancer typically induces cancer occurrence via a precancerous lesion. ROS, reactive oxygen species; RNS, reactive nitrogen species; VacA, vacuolating cyotoxin; CagA, cytotoxin-associated antigen A; OMPs, outer membrane proteins; EMT, epithelial mesenchimal transition; EGFR, epidermal growth factor receptor; nuclear factor kappa B, NF-κB; AP-1, activator protein 1; STAT3, signal transducer and activator of transcription 3.
Click for larger image


Fig. 2
The cancer prevention strategy against Helicobacter pylori-infection. The four strategies; eradication, improvement of environment, development of biomarkers (regularly endoscopic trace), and foods as turn back from a precancerous lesion to low-risk canceration (plants derived compound and stem cells etc).
CagA, cytotoxin-associated antigen A; VacA, vacuolating cyotoxin; OMPs, outer membrane proteins; siTRP, short-term intervention to revert premalignant lesion; GWAS, Genome- Wide Association Study; NGS, nextgeneration sequencing.
Click for larger image


Fig. 3
The protective effects of cancer prevention Kimchi (cpKimchi) in Helicobacter pylori-induced gastric cancer. This is methods through daily intake foods. Emphatically, compliance rate of subjects in a clinical trial is very high, and especially, our recently study showed that cpKimchi had protective effects based on like rejuvenation (improvement of chronic atrophic gastritis) against gastric cancer. Therefore realization of this is highly feasible due to high compliance rate of subjects.
siTRP, short-term intervention to revert premalignant lesion; 15-PGDH, 15-hydroxyprostaglandin dehydrogenase.
Click for larger image


Fig. 4
The cancer prevention for Helicobacter pylori-induced gastric cancer using plant-derived compounds (green tea and wormwoodderived compounds). This use of plant derived compounds is available for administering based on safety and easy to intake because it can produce a beverage or preference item and expectation effectiveness is high by intake dose-dependently. Recently, our investigators suggested that it can inhibit transition toward a precancerous lesion and have effects for strong anti-inflammation and anti-oxidant with partial anti-bacterial effects.
siTRP, short-term intervention to revert premalignant lesion; HR-QoL, health-related quality of life.
Click for larger image


Fig. 5
The cancer prevention for H. pylori-induced gastric cancer using mesenchymal stem cells or mesenchymal stem cells-cultured medium. This is ongoing study; stem cells are expected potent multi player based on various functions than other agents. Currently identified mechanism is strong cell-regenerative and protective effects and modulates inflammasome or autophagy activation by H. pylori induced inflammation and damaged mucosa cells are recovered based on cell-regenerative effect in our study. Therefore we studying about stem cells to apply not only injection for cell-therapy but also endoscopic application.
siTRP, short-term intervention to revert premalignant lesion.
Click for larger image

Tables


 Table 1
The Major Virulence Factors of Helicobacter pylori
Click for larger image

Notes

Financial support:This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2014R1A1A2058732, given to Dr. Jong-Min Park, CHA University) and by the Korean College of Helicobacter and Upper Gastrointestinal Research Foundation Grant (2015-04, given to Dr. Weon Jin Ko, CHA University).

Conflict of interest:None.

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