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1
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Huang TT, Cao YX, Cao L. Novel therapeutic regimens against Helicobacter pylori: an updated systematic review. Front Microbiol 2024; 15:1418129. [PMID: 38912349 PMCID: PMC11190606 DOI: 10.3389/fmicb.2024.1418129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Accepted: 05/27/2024] [Indexed: 06/25/2024] Open
Abstract
Helicobacter pylori (H. pylori) is a strict microaerophilic bacterial species that exists in the stomach, and H. pylori infection is one of the most common chronic bacterial infections affecting humans. Eradicating H. pylori is the preferred method for the long-term prevention of complications such as chronic gastritis, peptic ulcers, gastric mucosa-associated lymphoid tissue lymphoma, and gastric cancer. However, first-line treatment with triple therapy and quadruple therapy has been unable to cope with increasing antibacterial resistance. To provide an updated review of H. pylori infections and antibacterial resistance, as well as related treatment options, we searched PubMed for articles published until March 2024. The key search terms were "H. pylori", "H. pylori infection", "H. pylori diseases", "H. pylori eradication", and "H. pylori antibacterial resistance." Despite the use of antimicrobial agents, the annual decline in the eradication rate of H. pylori continues. Emerging eradication therapies, such as the development of the new strong acid blocker vonoprazan, probiotic adjuvant therapy, and H. pylori vaccine therapy, are exciting. However, the effectiveness of these treatments needs to be further evaluated. It is worth mentioning that the idea of altering the oxygen environment in gastric juice for H. pylori to not be able to survive is a hot topic that should be considered in new eradication plans. Various strategies for eradicating H. pylori, including antibacterials, vaccines, probiotics, and biomaterials, are continuously evolving. A novel approach involving the alteration of the oxygen concentration within the growth environment of H. pylori has emerged as a promising eradication strategy.
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Affiliation(s)
- Ting-Ting Huang
- Department of Pharmacology, School of Basic Medical Science, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi, China
| | - Yong-Xiao Cao
- Department of Pharmacology, School of Basic Medical Science, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi, China
| | - Lei Cao
- Precision Medical Institute, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
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Pourjamal N, Shirkoohi R, Rohani E, Hashemi M. The Expression Analysis of MEST1 and GJA1 Genes in Gastric Cancer in Association with Clinicopathological Characteristics. Int J Hematol Oncol Stem Cell Res 2024; 18:83-91. [PMID: 38680714 PMCID: PMC11055422 DOI: 10.18502/ijhoscr.v18i1.14747] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Accepted: 11/06/2023] [Indexed: 05/01/2024] Open
Abstract
Background: Gastric cancer is an invasive cancer, which is usually diagnosed in advanced stages. However, the markers affecting its progression, and invasion are of great importance in its diagnosis and treatment. The current research aimed to study the correlation of genes that contributed to epithelial-mesenchymal transition (EMT), Mest1, and GjA1, with some clinicopathological specifications in gastric cancer patients to better comprehend the functions of these genes in this tumor. Materials and Methods: RNA was extracted from the tumor, and normal tissues and cDNA were synthesized. Then, by designing specific primers for Gja1 and Mest1 genes, their expressions were studied by RT-PCR. The data was analyzed by GraphPad Prism 8 software. Results: Significant differences among the expressions of mentioned genes associated with clinicopathological variables of gastric cancer patients, including tumor size, grade, stage, metastasis, and lymphatic invasion were seen. Conclusion: The obtained data showed the important role of EMT-related genes, Gja1 and Mest1 in the clinical progression of the tumor. Further studies with larger sample sizes are required to confirm these genes as biomarker candidates for detecting gastric cancer.
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Affiliation(s)
- Nooshin Pourjamal
- Department of Genetics, Islamic Azad University, Tehran Medical Sciences Branch, Tehran, Iran
| | - Reza Shirkoohi
- Cancer Biology Research Center, Cancer Research Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Elham Rohani
- Department of Genetics, Islamic Azad University, Tehran Medical Sciences Branch, Tehran, Iran
| | - Mehrdad Hashemi
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
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Henry A, Mauperin M, Devy J, Dedieu S, Chazee L, Hachet C, Terryn C, Duca L, Martiny L, Devarenne-Charpentier E, Btaouri HE. The endocytic receptor protein LRP-1 modulate P-glycoprotein mediated drug resistance in MCF-7 cells. PLoS One 2023; 18:e0285834. [PMID: 37768946 PMCID: PMC10538702 DOI: 10.1371/journal.pone.0285834] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2022] [Accepted: 05/02/2023] [Indexed: 09/30/2023] Open
Abstract
Multidrug resistance (MDR) is a major obstacle to successful cancer chemotherapy. A typical form of MDR is due to the overexpression of membrane transport proteins., such as Glycoprotein-P (P-gp), resulting in an increased drug efflux preventing drug cytotoxicity. P-gp is mainly localized on the plasma membrane; however, it can also be endocytosed resulting in the trafficking of P-gp in endoplasmic reticulum, Golgi, endosomes, and lysosomes. The lysosomal P-gp has been found to be capable of transporting and sequestering P-gp substrates (e.g., Doxorubicin (Dox)) into lysosomes to protect cells against cytotoxic drugs. Many translational studies have shown that low-density lipoprotein receptor-related protein-1 (LRP-1) is involved in endocytosis and regulation of signalling pathways. LRP-1 mediates the endocytosis of a diverse set of extracellular ligands that play important roles in tumor progression. Here, we investigated the involvement of LRP-1 in P-gp expression and subcellular redistribution from the cell surface to the lysosomal membrane by endocytosis and its potential implication in P-gp-mediated multidrug resistance in MCF-7 cells. Our results showed that MCF-7 resistant cells (MCF-7R) overexpressed the P-gp, LRP-1 and LAMP-1 and were 11.66-fold resistant to Dox. Our study also revealed that in MCF-7R cells, lysosomes were predominantly high density compared to sensitized cells and P-gp was localized in the plasma membrane and lysosomes. LRP-1 blockade reduced lysosomes density and level of LAMP-1 and P-gp. It also affected the subcellular distribution of P-gp. Under these conditions, we restored Dox nuclear uptake and ERK 1/2 activation thus leading to MCF-7R cell sensitization to Dox. Our data suggest that LRP-1 is able to modulate the P-gp expression and subcellular redistribution by endocytosis and to potentiate the P-gp-acquired Dox resistance.
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Affiliation(s)
- Aubery Henry
- UMR-CNRS 7369 Matrice Extracellulaire et Dynamique Cellulaire (MEDyC), UFR SEN, URCA, Reims cedex, France
| | - Marine Mauperin
- UMR-CNRS 7369 Matrice Extracellulaire et Dynamique Cellulaire (MEDyC), UFR SEN, URCA, Reims cedex, France
| | - Jerome Devy
- UMR-CNRS 7369 Matrice Extracellulaire et Dynamique Cellulaire (MEDyC), UFR SEN, URCA, Reims cedex, France
| | - Stephane Dedieu
- UMR-CNRS 7369 Matrice Extracellulaire et Dynamique Cellulaire (MEDyC), UFR SEN, URCA, Reims cedex, France
| | - Lise Chazee
- UMR-CNRS 7369 Matrice Extracellulaire et Dynamique Cellulaire (MEDyC), UFR SEN, URCA, Reims cedex, France
| | - Cathy Hachet
- UMR-CNRS 7369 Matrice Extracellulaire et Dynamique Cellulaire (MEDyC), UFR SEN, URCA, Reims cedex, France
| | - Christine Terryn
- Technical Platform for Cellular and Tissue Imaging (PICT), UFR Pharmacie, URCA, Reims, France
| | - Laurent Duca
- UMR-CNRS 7369 Matrice Extracellulaire et Dynamique Cellulaire (MEDyC), UFR SEN, URCA, Reims cedex, France
| | - Laurent Martiny
- UMR-CNRS 7369 Matrice Extracellulaire et Dynamique Cellulaire (MEDyC), UFR SEN, URCA, Reims cedex, France
| | | | - Hassan El Btaouri
- UMR-CNRS 7369 Matrice Extracellulaire et Dynamique Cellulaire (MEDyC), UFR SEN, URCA, Reims cedex, France
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4
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Holland RL, Bosi KD, Harpring GH, Luo J, Wallig M, Phillips H, Blanke SR. Chronic in vivo exposure to Helicobacter pylori VacA: Assessing the efficacy of automated and long-term intragastric toxin infusion. Sci Rep 2020; 10:9307. [PMID: 32518315 PMCID: PMC7283276 DOI: 10.1038/s41598-020-65787-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2019] [Accepted: 05/04/2020] [Indexed: 12/24/2022] Open
Abstract
Helicobacter pylori (Hp) secrete VacA, a diffusible pore-forming exotoxin that is epidemiologically linked to gastric disease in humans. In vitro studies indicate that VacA modulates gastric epithelial and immune cells, but the in vivo contributions of VacA as an important determinant of Hp colonization and chronic infection remain poorly understood. To identify perturbations in the stomachs of C57BL/6 or BALB/C mice that result specifically from extended VacA exposure, we evaluated the efficacy of administering purified toxin using automated infusion via surgically-implanted, intragastric catheters. At 3 and 30 days of interrupted infusion, VacA was detected in association with gastric glands. In contrast to previously-reported tissue damage resulting from short term exposure to Hp extracts administered by oral gavage, extended infusion of VacA did not damage stomach, esophageal, intestinal, or liver tissue. However, several alterations previously reported during Hp infection were detected in animals infused with VacA, including reduction of the gastric mucus layer, and increased vacuolation of parietal cells. VacA infusion invoked an immune response, as indicated by the detection of circulating VacA antibodies. These foundational studies support the use of VacA infusion for identifying gastric alterations that are unambiguously attributable to long-term exposure to toxin.
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Affiliation(s)
- Robin L Holland
- Department of Pathobiology, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois, 61801, USA
| | - Kristopher D Bosi
- Department of Microbiology, School of Molecular and Cellular Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, 61801, USA
| | - Gregory H Harpring
- Department of Microbiology, School of Molecular and Cellular Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, 61801, USA
| | - Jiayi Luo
- Department of Microbiology, School of Molecular and Cellular Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, 61801, USA
| | - Matthew Wallig
- Department of Pathobiology, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois, 61801, USA
| | - Heidi Phillips
- Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois, 61801, USA
| | - Steven R Blanke
- Department of Pathobiology, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois, 61801, USA. .,Department of Microbiology, School of Molecular and Cellular Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, 61801, USA. .,Carle Illinois College of Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois, 61801, USA.
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5
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Isaeva GS. Pangenomic studies of Helicobacter pylori: a key to understanding pathogenesis and human history. MINERVA BIOTECNOL 2019. [DOI: 10.23736/s1120-4826.19.02564-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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6
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Zhao X, Yu C, Zheng M, Sun J. Prognostic value of the mRNA expression of gap junction α members in patients with gastric cancer. Oncol Lett 2019; 18:1669-1678. [PMID: 31423234 PMCID: PMC6614678 DOI: 10.3892/ol.2019.10516] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2018] [Accepted: 05/02/2019] [Indexed: 12/15/2022] Open
Abstract
Gastric cancer remains one of the primary causes of cancer-associated death worldwide. The gap junction α (GJA) family has been demonstrated to be involved in the cellular proliferation and metastasis of gastric cancer. However, the prognostic value of GJA in gastric cancer is yet to be elucidated. In the present study, the overall survival (OS) of patients with gastric cancer and the mRNA expression of GJA family members, including GJA1, GJA3, GJA4, GJA10 and GJA12, were analyzed using 593 patients with gastric cancer from the Kaplan-Meier plotter database. High GJA1 and GJA10 mRNA expression levels were associated with a poorer patient outcome (P=0.0066 and P=0.015, respectively), whereas high mRNA expression levels of GJA4 and GJA12 were associated with longer survival times (P=0.0056 and P=0.0054, respectively). Furthermore, the values of specific prognostic indicators of different subtypes of gastric cancer, including human epidermal growth factor receptor 2 status, Lauren differentiation and tumor stage, were also analyzed. The findings of the present study suggested a potential role for GJA family members in gastric cancer, which warrants further investigation.
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Affiliation(s)
- Xuan Zhao
- Department of General Surgery, Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China
| | - Chaoran Yu
- Department of General Surgery, Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China
| | - Minhua Zheng
- Department of General Surgery, Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China
| | - Jing Sun
- Department of General Surgery, Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China
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Wu GJ, Pen J, Huang Y, An S, Liu Y, Yang Y, Hao Q, Guo XX, Xu TR. KAP1 inhibits the Raf-MEK-ERK pathway to promote tumorigenesis in A549 lung cancer cells. Mol Carcinog 2018; 57:1396-1407. [PMID: 29917268 DOI: 10.1002/mc.22853] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2017] [Revised: 06/02/2018] [Accepted: 06/12/2018] [Indexed: 12/12/2022]
Abstract
Aberrant activation of the Raf-MEK-ERK pathway has frequently been associated with various cancers, especially lung cancer. However, the key regulators of this pathway are largely unknown. Using functional proteomics screening, we found that KAP1 interacts with c-Raf. Knocking out KAP1 decreased c-Raf phosphorylation at serine 259 and increased its phosphorylation at serine 338, which activated MEK and ERK. We detected higher KAP1 expression in lung cancer tissues than in normal peri-tumoral tissues. KAP1 knockdown arrested A549 lung cancer cells in the G0/G1 phase of the cell cycle and attenuated cell growth, metastasis, the epithelial-mesenchymal transition, angiogenesis, stemness, and colony formation. Furthermore, knocking out KAP1 remarkably increased the susceptibility of A549 cells to the anti-cancer drug 5-Fluorouracil, which correlated with increasing ERK phosphorylation. In vivo xenograft experiments suggested that KAP1 deficiency significantly decreases the tumorigenicity of A549 cells. Taken together, our findings indicate that KAP1 acts as a key module in the c-Raf-interactome complex and regulates lung cancer development through the Raf-MEK-ERK pathway. Therefore, KAP1 may represent a potential diagnosis biomarker and new treatment target for lung cancer.
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Affiliation(s)
- Guo-Jin Wu
- Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan, China
| | - Jun Pen
- The First People's Hospital of Yunnan, Kunming, Yunnan, China
| | - Ying Huang
- Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan, China
| | - Su An
- Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan, China
| | - Ying Liu
- Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan, China
| | - Yang Yang
- Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan, China
| | - Qian Hao
- Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan, China
| | - Xiao-Xi Guo
- Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan, China
| | - Tian-Rui Xu
- Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan, China
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8
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Kabamba ET, Tuan VP, Yamaoka Y. Genetic populations and virulence factors of Helicobacter pylori. INFECTION GENETICS AND EVOLUTION 2018; 60:109-116. [PMID: 29471116 DOI: 10.1016/j.meegid.2018.02.022] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/06/2017] [Revised: 02/15/2018] [Accepted: 02/16/2018] [Indexed: 12/16/2022]
Abstract
Helicobacter pylori is a bacterium that has infected more than half of the human population worldwide. This bacterium is closely associated with serious human diseases, such as gastric cancer, and identifying and understanding factors that predict bacterial virulence is a priority. In addition, this pathogen shows high genetic diversity and co-evolution with human hosts. H. pylori population genetics, therefore, has emerged as a tool to track human demographic history. As the number of genome sequences available is increasing, studies on the evolution and virulence of H. pylori are gaining momentum. This review article summarizes the most recent findings on H. pylori virulence factors and population genetics.
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Affiliation(s)
- Evariste Tshibangu Kabamba
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu-City, Oita 879-5593, Japan; Department of Internal Medicine, University of Mbujimayi Faculty of Medicine, Mbujimayi, The Democratic Republic of Congo
| | - Vo Phuoc Tuan
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu-City, Oita 879-5593, Japan; Department of Endoscopy, Cho Ray Hospital, Ho Chi Minh, Viet Nam
| | - Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu-City, Oita 879-5593, Japan; Department of Medicine-Gastroenterology, Baylor College of Medicine and Michael E. Debakey Veterans Affairs Medical Center, 2002 Holcombe Blvd., Houston, TX 77030, USA.
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9
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Fong Y, Wu CY, Chang KF, Chen BH, Chou WJ, Tseng CH, Chen YC, Wang HMD, Chen YL, Chiu CC. Dual roles of extracellular signal-regulated kinase (ERK) in quinoline compound BPIQ-induced apoptosis and anti-migration of human non-small cell lung cancer cells. Cancer Cell Int 2017; 17:37. [PMID: 28286419 PMCID: PMC5339964 DOI: 10.1186/s12935-017-0403-0] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2016] [Accepted: 02/16/2017] [Indexed: 02/06/2023] Open
Abstract
Background 2,9-Bis[2-(pyrrolidin-1-yl)ethoxy]-6-{4-[2-(pyrrolidin-1-yl)ethoxy] phenyl}-11H-indeno[1,2-c]quinoline-11-one (BPIQ), is a synthetic quinoline analog. A previous study showed the anti-cancer potential of BPIQ through modulating mitochondrial-mediated apoptosis. However, the effect of BPIQ on cell migration, an index of cancer metastasis, has not yet been examined. Furthermore, among signal pathways involved in stresses, the members of the mitogen-activated protein kinase (MAPK) family are crucial for regulating the survival and migration of cells. In this study, the aim was to explore further the role of MAPK members, including JNK, p38 and extracellular signal-regulated kinase (ERK) in BPIQ-induced apoptosis and anti-migration of human non-small cell lung cancer (NSCLC) cells. Methods Western Blot assay was performed for detecting the activation of MAPK members in NSCLC H1299 cells following BPIQ administration. Cellular proliferation was determined using a trypan blue exclusion assay. Cellular apoptosis was detected using flow cytometer-based Annexin V/propidium iodide dual staining. Cellular migration was determined using wound-healing assay and Boyden’s chamber assay. Zymography assay was performed for examining MMP-2 and -9 activities. The assessment of MAPK inhibition was performed for further validating the role of JNK, p38, and ERK in BPIQ-induced growth inhibition, apoptosis, and migration of NSCLC cells. Results Western Blot assay showed that BPIQ treatment upregulates the phosphorylated levels of both MAPK proteins JNK and ERK. However, only ERK inhibitor rescues BPIQ-induced growth inhibition of NSCLC H1299 cells. The results of Annexin V assay further confirmed the pro-apoptotic role of ERK in BPIQ-induced cell death of H1299 cells. The results of wound healing and Boyden chamber assays showed that sub-IC50 (sub-lethal) concentrations of BPIQ cause a significant inhibition of migration in H1299 cells accompanied with downregulating the activity of MMP-2 and -9, the motility index of cancer cells. Inhibition of ERK significantly enhances BPIQ-induced anti-migration of H1299 cells. Conclusions Our results suggest ERK may play dual roles in BPIQ-induced apoptosis and anti-migration, and it would be worthwhile further developing strategies for treating chemoresistant lung cancers through modulating ERK activity. Electronic supplementary material The online version of this article (doi:10.1186/s12935-017-0403-0) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Yao Fong
- Department of Thoracic Surgery, Chi-Mei Medical Center, Tainan, 710 Taiwan
| | - Chang-Yi Wu
- Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung, 804 Taiwan.,Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, 807 Taiwan
| | - Kuo-Feng Chang
- Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, 807 Taiwan
| | - Bing-Hung Chen
- Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, 807 Taiwan.,The Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, 804 Taiwan
| | - Wan-Ju Chou
- Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, 807 Taiwan
| | - Chih-Hua Tseng
- School of Pharmacy, Kaohsiung Medical University, Kaohsiung, 807 Taiwan
| | - Yen-Chun Chen
- Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, 807 Taiwan
| | - Hui-Min David Wang
- Graduate Institute of Biomedical Engineering, National Chung Hsing University, Taichung, 402 Taiwan
| | - Yeh-Long Chen
- Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung, 807 Taiwan
| | - Chien-Chih Chiu
- Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung, 804 Taiwan.,Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, 807 Taiwan.,Translational Research Center, Cancer Center and Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, 807 Taiwan.,Research Center for Environment Medicine, Kaohsiung Medical University, Kaohsiung, 807 Taiwan.,Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807 Taiwan
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10
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Talebi Bezmin Abadi A, Perez-Perez G. Role of dupA in virulence of Helicobacter pylori. World J Gastroenterol 2016; 22:10118-10123. [PMID: 28028359 PMCID: PMC5155170 DOI: 10.3748/wjg.v22.i46.10118] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2016] [Revised: 09/27/2016] [Accepted: 11/16/2016] [Indexed: 02/07/2023] Open
Abstract
Helicobacter pylori (H. pylori) is a gastric human pathogen associated with acute and chronic gastritis, 70% of all gastric ulcers, 85% of all duodenal ulcers, and both forms of stomach cancer, mucosal-associated lymphoid tissue (MALT) lymphoma and adenocarcinoma. Recently, attention has focused on possible relationship between presence of certain virulence factor and H. pylori-associated diseases. Some contradictory data between this bacterium and related disorders has been observed since not all the colonized individuals develop to severe disease. The reported diseases plausibility related to H. pylori specific virulence factors became an interesting story about this organism. Although a number of putative virulence factors have been identified including cytotoxin-associated gene a (cagA) and vacA, there are conflicting data about their actual participation as specific risk factor for H. pylori-related diseases. Duodenal ulcer promoting gene a (dupA) is a virulence factor of H. pylori that is highly associated with duodenal ulcer development and reduced risk of gastric cancer. The prevalence of dupA in H. pylori strains isolated from western countries is relatively higher than in H. pylori strains from Asian countries. Current confusing epidemiological reports will continue unless future sophisticated and molecular studies provide data on functional and complete dupA cluster in H. pylori infected individuals. This paper elucidates available knowledge concerning role of dupA in virulence of H. pylori after a decade of its discovery.
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11
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Abstract
Helicobacter pylori is estimated to infect more than half of the worlds human population and represents a major risk factor for chronic gastritis, peptic ulcer disease, MALT lymphoma, and gastric adenocarcinoma. H. pylori infection and clinical consequences are controlled by highly complex interactions between the host, colonizing bacteria, and environmental parameters. Important bacterial determinants linked with gastric disease development include the cag pathogenicity island encoding a type IV secretion system (T4SS), the translocated effector protein CagA, vacuolating cytotoxin VacA, adhesin BabA, urease, serine protease HtrA, secreted outer membrane vesicles, and many others. The high quantity of these factors and allelic changes in the corresponding genes reveals a sophisticated picture and problems in evaluating the impact of each distinct component. Extensive work has been performed to pinpoint molecular processes related to H. pylori-triggered pathogenesis using Mongolian gerbils, mice, primary tissues, as well as novel in vitro model systems such as gastroids. The manipulation of host signaling cascades by the bacterium appears to be crucial for inducing pathogenic downstream activities and gastric disease progression. Here, we review the most recent advances in this important research area.
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Affiliation(s)
- Steffen Backert
- Division of Microbiology, Department of Biology, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany
| | - Matthias Neddermann
- Division of Microbiology, Department of Biology, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany
| | - Gunter Maubach
- Institute of Experimental Internal Medicine, Otto von Guericke University, Magdeburg, Germany
| | - Michael Naumann
- Institute of Experimental Internal Medicine, Otto von Guericke University, Magdeburg, Germany
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