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1
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Singh RD, Dholariya S, Shekher A, Avadhesh, Parchwani D, Gupta SC. Role of IL-1 gene polymorphisms in common solid cancers. MULTIFACETED ROLE OF IL-1 IN CANCER AND INFLAMMATION 2023:1-69. [DOI: 10.1016/b978-0-12-824273-5.00002-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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2
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Janiczek-Polewska M, Szylberg Ł, Malicki J, Marszałek A. Role of Interleukins and New Perspectives in Mechanisms of Resistance to Chemotherapy in Gastric Cancer. Biomedicines 2022; 10:1600. [PMID: 35884907 PMCID: PMC9312950 DOI: 10.3390/biomedicines10071600] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Revised: 06/26/2022] [Accepted: 06/30/2022] [Indexed: 11/17/2022] Open
Abstract
Gastric cancer (GC) is the fourth most common cancer in the world in terms of incidence and second in terms of mortality. Chemotherapy is the main treatment for GC. The greatest challenge and major cause of GC treatment failure is resistance to chemotherapy. As such, research is ongoing into molecular evaluation, investigating mechanisms, and screening therapeutic targets. Several mechanisms related to both the tumor cells and the tumor microenvironment (TME) are involved in resistance to chemotherapy. TME promotes the secretion of various inflammatory cytokines. Recent studies have revealed that inflammatory cytokines affect not only tumor growth, but also chemoresistance. Cytokines in TME can be detected in blood circulation and TME cells. Inflammatory cytokines could serve as potential biomarkers in the assessment of chemoresistance and influence the management of therapeutics in GC. This review presents recent data concerning research on inflammatory cytokines involved in the mechanisms of chemoresistance and provides new clues in GC treatment.
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Affiliation(s)
- Marlena Janiczek-Polewska
- Department of Electroradiology, Poznan University of Medical Sciences, 61-701 Poznan, Poland;
- Department of Clinical Oncology, Greater Poland Cancer Center, 61-866 Poznan, Poland
| | - Łukasz Szylberg
- Department of Perinatology, Gynaecology and Gynaecologic Oncology, Collegium Medicum, Nicolaus Copernicus University, 85-067 Bydgoszcz, Poland;
- Department of Tumor Pathology and Pathomorphology, Oncology Centrer of Franciszek Łukaszczyk Memorial Hospital, 85-796 Bydgoszcz, Poland
| | - Julian Malicki
- Department of Electroradiology, Poznan University of Medical Sciences, 61-701 Poznan, Poland;
| | - Andrzej Marszałek
- Department of Oncologic Pathology, Prophylaxis Poznan University, Medical Sciences and Greater Poland Cancer Center, 61-866 Poznan, Poland;
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3
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Mărginean CO, Meliț LE, Săsăran MO. Traditional and Modern Diagnostic Approaches in Diagnosing Pediatric Helicobacter pylori Infection. CHILDREN 2022; 9:children9070994. [PMID: 35883980 PMCID: PMC9316053 DOI: 10.3390/children9070994] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/05/2022] [Revised: 06/24/2022] [Accepted: 06/29/2022] [Indexed: 01/10/2023]
Abstract
Helicobacter pylori (H. pylori) is the most common bacterial infection worldwide, is usually acquired during childhood and is related to gastric carcinogenesis during adulthood. Therefore, its early proper diagnosis and subsequent successful eradication represent the cornerstones of gastric cancer prevention. The aim of this narrative review was to assess traditional and modern diagnostic methods in terms of H. pylori diagnosis. Several invasive and non-invasive methods were described, each with its pros and cons. The invasive diagnostic methods comprise endoscopy with biopsy, rapid urease tests, histopathological exams, cultures and biopsy-based molecular tests. Among these, probably the most available, accurate and cost-effective test remains histology, albeit molecular tests definitely remain the most accurate despite their high costs. The non-invasive tests consist of urea breath tests, serology, stool antigens and non-invasive molecular tests. Urea breath tests and stool antigens are the most useful in clinical practice both for the diagnosis of H. pylori infection and for monitoring the eradication of this infection after therapy. The challenges related to accurate diagnosis lead to a choice that must be based on H. pylori virulence, environmental factors and host peculiarities.
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Affiliation(s)
- Cristina Oana Mărginean
- Department of Pediatrics I, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, Gheorghe Marinescu Street No. 38, 540136 Targu Mures, Romania;
| | - Lorena Elena Meliț
- Department of Pediatrics I, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, Gheorghe Marinescu Street No. 38, 540136 Targu Mures, Romania;
- Correspondence:
| | - Maria Oana Săsăran
- Department of Pediatrics III, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, Gheorghe Marinescu Street No. 38, 540136 Targu Mures, Romania;
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Cardos AI, Maghiar A, Zaha DC, Pop O, Fritea L, Miere (Groza) F, Cavalu S. Evolution of Diagnostic Methods for Helicobacter pylori Infections: From Traditional Tests to High Technology, Advanced Sensitivity and Discrimination Tools. Diagnostics (Basel) 2022; 12:508. [PMID: 35204598 PMCID: PMC8871415 DOI: 10.3390/diagnostics12020508] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Revised: 02/06/2022] [Accepted: 02/14/2022] [Indexed: 01/10/2023] Open
Abstract
Rapid diagnosis and treatment application in the early stages of H. pylori infection plays an important part in inhibiting the transmission of this infection as this bacterium is involved in various gastric pathologies such as gastritis, gastro-duodenal ulcer, and even gastric neoplasia. This review is devoted to a quick overview of conventional and advanced detection techniques successfully applied to the detection of H. pylori in the context of a compelling need to upgrade the standards of the diagnostic methods which are currently being used. Selecting the best diagnostic method implies evaluating different features, the use of one or another test depending on accessibility, laboratories equipment, and the clinical conditions of patients. This paper aims to expose the diagnosis methods for H. pylori that are currently available, highlighting their assets and limitations. The perspectives and the advantages of nanotechnology along with the concept of nano(bio)sensors and the development of lab-on-chip devices as advanced tools for H. pylori detection, differentiation, and discrimination is also presented, by emphasizing multiple advantages: simple, fast, cost-effective, portable, miniaturized, small volume of samples required, highly sensitive, and selective. It is generally accepted that the development of intelligent sensors will completely revolutionize the acquisition procedure and medical decision in the framework of smart healthcare monitoring systems.
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Affiliation(s)
| | - Adriana Maghiar
- Faculty of Medicine and Pharmacy, University of Oradea, P-ta 1 December 10, 410087 Oradea, Romania; (A.I.C.); (D.C.Z.); (O.P.); (L.F.); (F.M.)
| | | | | | | | | | - Simona Cavalu
- Faculty of Medicine and Pharmacy, University of Oradea, P-ta 1 December 10, 410087 Oradea, Romania; (A.I.C.); (D.C.Z.); (O.P.); (L.F.); (F.M.)
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5
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Zhu W, Zhai X, Jia Z, Wang Y, Mo Y. Bioinformatics analysis of sequential gene expression profiling after skin and skeletal muscle wound in mice. Leg Med (Tokyo) 2021; 54:101982. [PMID: 34687982 DOI: 10.1016/j.legalmed.2021.101982] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2021] [Revised: 09/26/2021] [Accepted: 10/14/2021] [Indexed: 10/20/2022]
Abstract
It is of great value to use bioinformatics methods to screen the core differentially expressed genes (DEGs) at different times after mouse skin and skeletal muscle wound, and to explore the relationship between them and the wound age. To this end, we downloaded the gene expression profiles of GSE140517 and GSE23006 from the NCBI-GEO gene database, used GEO2R online tools and Venn diagrams to screen out DEGs at different times and common-DEGs. The Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) channel analysis were carried out through the DAVID website respectively. Use STRING tool to build a Protein-protein Interaction (PPI) network, and use Cytoscape software to screen out core DEGs. The results showed that 13, 53, 43 and 13 core DEGs were screened out in the 6 h, 12 h, 24 h and common-DEGs group after wound. There were 7 core DEGs (Cxcl2, Cxcl3, Il1b, Ptgs2, Cxcl1, Timp1, Ccl3) in both the different time point and the common DEGs group. Meanwhile, there are 1 core DEGs (Ccl4) specifically expressed in the 6 h, 29 specifically expressed core DEGs (Isg20, Rtp4, Fcgr1, Ifi44, Trim30a, etc.) in the 12 h, and 18 specifically expressed core DEGs (Ccr7, Myd88, Igsf6, Ccr2, Gpsm3, etc.) in the 24 h, there are 6 core DEGs (Ccl4, Ccl7, Saa3, Cxcl5, Ccl2, Lcn2) specifically expressed in the common-DEGs group. The results of GO and KEGG analysis showed that the deterioration and exudation of the inflammatory response were the main cause at 6 h after wound. In addition to inflammation at 12 h and 24 h, the systemic immune response against viral and bacterial infections also gradually increased. In summary, the core DEGs selected in this study have combined characteristics, consistent with the healing function at the corresponding time point, and they are also has specificity and correlation with wound age. Therefore, by detecting the changes in the expression of co-expressed core DEGs at different times after wound, as well as detecting specific expressed DEGs at a specific time point or a specific period of time, it is very promising to provide help for the wound age estimation. However, limited by the GSE140517 gene expression profile in the database, only the difference in gene expression at different times within 24 h after wound was explored, and the research on the late wound age still needs to be further in-depth.
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Affiliation(s)
- Weihao Zhu
- School of Forensic Medicine, Henan University of Science and Technology, Luoyang 471003, China
| | - Xiandun Zhai
- School of Forensic Medicine, Henan University of Science and Technology, Luoyang 471003, China
| | - Zelei Jia
- School of Forensic Medicine, Henan University of Science and Technology, Luoyang 471003, China
| | - Yingyi Wang
- School of Forensic Medicine, Henan University of Science and Technology, Luoyang 471003, China; First Affiliated Hospital of Zhengzhou University, Zhengzhou 450046, China
| | - Yaonan Mo
- School of Forensic Medicine, Henan University of Science and Technology, Luoyang 471003, China.
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6
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Carrero YN, Callejas DE, Mosquera JA. In situ immunopathological events in human cervical intraepithelial neoplasia and cervical cancer: Review. Transl Oncol 2021; 14:101058. [PMID: 33677234 PMCID: PMC7937982 DOI: 10.1016/j.tranon.2021.101058] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2021] [Accepted: 02/22/2021] [Indexed: 12/15/2022] Open
Abstract
Neoplasia of the cervix represents one of the most common cancers in women. Clinical and molecular research has identified immunological impairment in squamous intraepithelial cervical lesions and cervical cancer patients. The in-situ expression of several cytokines by uterine epithelial cells and by infiltrating leukocytes occurs during the cervical intraepithelial neoplasia and cervical cancer. Some of these cytokines can prevent and others can induce the progression of the neoplasm. The infiltrating leukocytes also produce cytokines and growth factors relate to angiogenesis, chemotaxis, and apoptosis capable of modulating the dysplasia progression. In this review we analyzed several interleukins with an inductive effect or blocking effect on the neoplastic progression. We also analyze the genetic polymorphism of some cytokines and their relationship with the risk of developing cervical neoplasia. In addition, we describe the leukocyte cells that infiltrate the cervical uterine tissue during the neoplasia and their effects on neoplasia progression.
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Affiliation(s)
- Yenddy N Carrero
- Facultad de Ciencias de la Salud. Carrera de Medicina, Universidad Técnica de Ambato, Ambato, Ecuador.
| | - Diana E Callejas
- Departamento de Ciencias Biológicas, Facultad de Ciencias de la Salud, Universidad Técnica de Manabí, Portoviejo, Ecuador.
| | - Jesús A Mosquera
- Instituto de Investigaciones Clínicas Dr. Américo Negrette. Facultad de Medicina, Universidad del Zulia. Maracaibo, Venezuela.
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7
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Idris AB, Idris EB, Ataelmanan AE, Mohamed AEA, Osman Arbab BM, Ibrahim EAM, Hassan MA. First insights into the molecular basis association between promoter polymorphisms of the IL1B gene and Helicobacter pylori infection in the Sudanese population: computational approach. BMC Microbiol 2021; 21:16. [PMID: 33413117 PMCID: PMC7792167 DOI: 10.1186/s12866-020-02072-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Accepted: 12/15/2020] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) infects nearly half of the world's population with a variation in incidence among different geographic regions. Genetic variants in the promoter regions of the IL1B gene can affect cytokine expression and creates a condition of hypoacidity which favors the survival and colonization of H. pylori. Therefore, the aim of this study was to characterize the polymorphic sites in the 5'- region [-687_ + 297] of IL1B in H. pylori infection using in silico tools. RESULTS A total of five nucleotide variations were detected in the 5'-regulatory region [-687_ + 297] of IL1B which led to the addition or alteration of transcription factor binding sites (TFBSs) or composite regulatory elements (CEs). Genotyping of IL1B - 31 C > T revealed a significant association between -31 T and susceptibility to H. pylori infection in the studied population (P = 0.0363). Comparative analysis showed conservation rates of IL1B upstream [-368_ + 10] region above 70% in chimpanzee, rhesus monkey, a domesticated dog, cow and rat. CONCLUSIONS In H. pylori-infected patients, three detected SNPs (- 338, - 155 and - 31) located in the IL1B promoter were predicted to alter TFBSs and CE, which might affect the gene expression. These in silico predictions provide insight for further experimental in vitro and in vivo studies of the regulation of IL1B expression and its relationship to H. pylori infection. However, the recognition of regulatory motifs by computer algorithms is fundamental for understanding gene expression patterns.
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Affiliation(s)
- Abeer Babiker Idris
- Department of Medical Microbiology, Faculty of Medical Laboratory Sciences, University of Khartoum, Khartoum, Sudan.
| | - Einas Babiker Idris
- Medical Laboratory Specialist, Department of Medical Microbiology, Rashid Medical Complex, Riyadh, Saudi Arabia
| | - Amany Eltayib Ataelmanan
- Department of Medical Microbiology, Faculty of Medical Laboratory Sciences, University of Al-Gazirah, Wad Madani, Sudan
| | | | | | - El-Amin Mohamed Ibrahim
- Department of Medical Microbiology, Faculty of Medical Laboratory Sciences, University of Khartoum, Khartoum, Sudan
| | - Mohamed A Hassan
- Department of Bioinformatics, Africa city of technology, Khartoum, Sudan.,Department of Bioinformatics, DETAGEN Genetic Diagnostics Center, Kayseri, Turkey.,Department of Translation Bioinformatics, Detavax Biotech, Kayseri, Turkey
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8
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A decade in unravelling the etiology of gastric carcinogenesis in Kashmir, India – A high risk region. GENE REPORTS 2020. [DOI: 10.1016/j.genrep.2020.100832] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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9
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Panarese A, Galatola G, Armentano R, Pimentel-Nunes P, Ierardi E, Caruso ML, Pesce F, Lenti MV, Palmitessa V, Coletta S, Shahini E. Helicobacter pylori-induced inflammation masks the underlying presence of low-grade dysplasia on gastric lesions. World J Gastroenterol 2020; 26:3834-3850. [PMID: 32774061 PMCID: PMC7383846 DOI: 10.3748/wjg.v26.i26.3834] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Revised: 06/20/2020] [Accepted: 06/29/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) infection has been associated with a long-term risk of precancerous gastric conditions (PGC) even after H. pylori eradication.
AIM To investigate the efficacy of High-Resolution White-Light Endoscopy with Narrow-Band Imaging in detecting PGC, before/after H. pylori eradication.
METHODS We studied 85 consecutive patients with H. pylori-related gastritis with/without PGC before and 6 mo after proven H. pylori eradication. Kimura-Takemoto modified and endoscopic grading of gastric intestinal metaplasia classifications, were applied to assess the endoscopic extension of atrophy and intestinal metaplasia. The histological result was considered to be the gold standard. The Sydney System, the Operative-Link on Gastritis-Assessment, and the Operative-Link on Gastric-Intestinal Metaplasia were used for defining histological gastritis, atrophy and intestinal metaplasia, whereas dysplasia was graded according to World Health Organization classification. Serum anti-parietal cell antibody and anti-intrinsic factor were measured when autoimmune atrophic gastritis was suspected.
RESULTS After H. pylori eradication histological signs of mononuclear/polymorphonuclear cell infiltration and Mucosal Associated Lymphoid Tissue-hyperplasia, disappeared or decreased in 100% and 96.5% of patients respectively, whereas the Operative-Link on Gastritis-Assessment and Operative-Link on Gastric-Intestinal Metaplasia stages did not change. Low-Grade Dysplasia prevalence was similar on random biopsies before and after H. pylori eradication (17.6% vs 10.6%, P = 0.19), but increased in patients with visible lesions (0% vs 22.4%, P < 0.0001). At a multivariate analysis, the probability for detecting dysplasia after resolution of H. pylori-related active inflammation was higher in patients with regression or reduction of Mucosal Associated Lymphoid Tissue hyperplasia, greater alcohol consumption, and anti-parietal cell antibody and/or anti-intrinsic factor positivity [odds ratio (OR) = 3.88, 95% confidence interval (CI): 1.31-11.49, P = 0.01; OR = 3.10, 95%CI: 1.05-9.12, P = 0.04 and OR = 5.47, 95%CI: 1.33-22.39, P < 0.04, respectively].
CONCLUSION High-Resolution White-Light Endoscopy with Narrow-Band Imaging allows an accurate diagnosis of Low-Grade Dysplasia on visible lesions after regression of H. pylori-induced chronic gastritis. Patients with an overlap between autoimmune/H. pylori-induced gastritis may require more extensive gastric mapping.
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Affiliation(s)
- Alba Panarese
- Department of Gastroenterology and Digestive Endoscopy, National Institute of Gastroenterology "S De Bellis", Research Hospital, Castellana Grotte 70013, Italy
| | | | - Raffaele Armentano
- Sergio Coletta Department of Clinical Pathology, National Institute of Gastroenterology "S De Bellis", Research Hospital, Castellana Grotte 70013, Italy
| | - Pedro Pimentel-Nunes
- Center for Research in Health Technologies and Information Systems, Faculty of Medicine, Porto 4200072, Portugal
- Surgery and Physiology Department, Faculty of Medicine of the University of Porto, Porto 4200072, Portugal
| | - Enzo Ierardi
- Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Maria Lucia Caruso
- Sergio Coletta Department of Clinical Pathology, National Institute of Gastroenterology "S De Bellis", Research Hospital, Castellana Grotte 70013, Italy
| | - Francesco Pesce
- Nephrology Section, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Marco Vincenzo Lenti
- First Department of Internal Medicine, San Matteo Hospital Foundation, University of Pavia, Pavia 27100, Italy
| | - Valeria Palmitessa
- Laboratory of Microbiology and Virology, National Institute of Gastroenterology "S De Bellis", Research Hospital, Castellana Grotte 70013, Italy
| | | | - Endrit Shahini
- Department of Gastroenterology and Digestive Endoscopy, National Institute of Gastroenterology "S De Bellis", Research Hospital, Castellana Grotte 70013, Italy
- Giovanni Galatola Gastroenterology Unit, Institute for Cancer Research and Treatment, Turin 10121, Italy
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10
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de Almeida NM, Fernandes A, Romãozinho JM, Freire P, Donato MM, Cardoso O, Luxo C, Cipriano MA, Marinho C, Calhau C, Figueiredo P. Correlation of
NOD2
genotypes with
Helicobacter pylori
infection in a
South‐European
country. ADVANCES IN DIGESTIVE MEDICINE 2020. [DOI: 10.1002/aid2.13210] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Nuno Miguel de Almeida
- Gastroenterology Department Centro Hospitalar e Universitário de Coimbra Coimbra Portugal
- Faculty of Medicine University of Coimbra Coimbra Portugal
| | | | - José Manuel Romãozinho
- Gastroenterology Department Centro Hospitalar e Universitário de Coimbra Coimbra Portugal
- Faculty of Medicine University of Coimbra Coimbra Portugal
| | - Paulo Freire
- Faculty of Medicine University of Coimbra Coimbra Portugal
| | - Maria M. Donato
- CIMAGO, Faculty of Medicine University of Coimbra Coimbra Portugal
| | - Olga Cardoso
- Laboratory of Microbiology, Faculty of Pharmacy University of Coimbra Coimbra Portugal
- CIEPQPF, Faculty of Sciences and Technology University of Coimbra Coimbra Portugal
| | - Cristina Luxo
- Laboratory of Microbiology, Faculty of Pharmacy University of Coimbra Coimbra Portugal
- CIEPQPF, Faculty of Sciences and Technology University of Coimbra Coimbra Portugal
| | | | - Carol Marinho
- Pathology Department Centro Hospitalar e Universitário de Coimbra Coimbra Portugal
| | - Carlos Calhau
- Gastroenterology Department Centro Hospitalar e Universitário de Coimbra Coimbra Portugal
| | - Pedro Figueiredo
- Gastroenterology Department Centro Hospitalar e Universitário de Coimbra Coimbra Portugal
- Faculty of Medicine University of Coimbra Coimbra Portugal
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Catani MV, Savini I, Tullio V, Gasperi V. The "Janus Face" of Platelets in Cancer. Int J Mol Sci 2020; 21:ijms21030788. [PMID: 31991775 PMCID: PMC7037171 DOI: 10.3390/ijms21030788] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Revised: 01/21/2020] [Accepted: 01/22/2020] [Indexed: 12/20/2022] Open
Abstract
Besides their vital role in hemostasis and thrombosis, platelets are also recognized to be involved in cancer, where they play an unexpected central role: They actively influence cancer cell behavior, but, on the other hand, platelet physiology and phenotype are impacted by tumor cells. The existence of this platelet-cancer loop is supported by a large number of experimental and human studies reporting an association between alterations in platelet number and functions and cancer, often in a way dependent on patient, cancer type and treatment. Herein, we shall report on an update on platelet-cancer relationships, with a particular emphasis on how platelets might exert either a protective or a deleterious action in all steps of cancer progression. To this end, we will describe the impact of (i) platelet count, (ii) bioactive molecules secreted upon platelet activation, and (iii) microvesicle-derived miRNAs on cancer behavior. Potential explanations of conflicting results are also reported: Both intrinsic (heterogeneity in platelet-derived bioactive molecules with either inhibitory or stimulatory properties; features of cancer cell types, such as aggressiveness and/or tumour stage) and extrinsic (heterogeneous characteristics of cancer patients, study design and sample preparation) factors, together with other confounding elements, contribute to “the Janus face” of platelets in cancer. Given the difficulty to establish the univocal role of platelets in a tumor, a better understanding of their exact contribution is warranted, in order to identify an efficient therapeutic strategy for cancer management, as well as for better prevention, screening and risk assessment protocols.
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Affiliation(s)
- Maria Valeria Catani
- Correspondence: (M.V.C.); (V.G.); Tel.: +39-06-72596465 (M.V.C.); +39-06-72596465 (V.G.)
| | | | | | - Valeria Gasperi
- Correspondence: (M.V.C.); (V.G.); Tel.: +39-06-72596465 (M.V.C.); +39-06-72596465 (V.G.)
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12
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Hirbod-Mobarakeh A, Shabani M, Keshavarz-Fathi M, Delavari F, Amirzargar AA, Nikbin B, Kutikhin A, Rezaei N. Immunogenetics of Cancer. CANCER IMMUNOLOGY 2020:417-478. [DOI: 10.1007/978-3-030-30845-2_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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13
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Voynovan IN, Embutnieks YV, Mareeva DV, Kolbasnikov SV, Bordin DS. Helicobacter pylori as a risk factor for gastric cancer: the evidence and primary prevention strategy. ALMANAC OF CLINICAL MEDICINE 2019; 47:535-547. [DOI: 10.18786/2072-0505-2019-47-052] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/20/2023]
Abstract
Russia is a country with a high prevalence of Helicobacter pylori (HP) infection, a high incidence of gastric cancer, and its late diagnosis. HР infection has been recognized as the leading manageable risk factor for gastric cancer. Accurate diagnostic tests must be used to identify and control the effectiveness of HP eradication, and effective schemes must be implemented for HP eradication. The aim of this article was to analyze the latest consensus documents, systematic reviews and meta-analyzes that reflected the role of HP as a risk factor for the development of gastric cancer, as well as measures for the risk reduction. We describe in detail the diagnostic methods for HP infection, provide data on their use in the Russian Federation, and analyze the efficacy of eradication regimens. In all HPinfected individuals, HP leads to chronic inflammation in the gastric mucosa and launches a precancerous cascade (Correa's cascade). The risk of gastric cancer increases with severe atrophy, intestinal metaplasia and dysplasia. Primary prevention of gastric cancer is most effective if the eradication is performed before atrophic gastritis develops. The available consensus documents underline the importance of HP infection identification by accurate diagnostics at this stage of chronic gastritis. In Russia, the primary HP diagnosis is based on histology (37.7%), rapid urease test (29.2%), and serology (29.7%). HP stool antigen test (31.3%), 13C-urea breath test (23.4%) and the histological method (23.3%) are most often used to control eradication. Currently, the first line of eradication therapy is recommended as triple therapy with clarithromycin prescribed for 14 days. It is recommended to use double dose of proton pump inhibitors and bismuth to increase the effectiveness of this scheme. A 14-days triple regimen enhanced by bismuth has been recommended as the first-line therapy in the Russian Federation.
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Affiliation(s)
- I. N. Voynovan
- Loginov Moscow Clinical Scientific Center, Moscow Healthcare Department
| | - Yu. V. Embutnieks
- Loginov Moscow Clinical Scientific Center, Moscow Healthcare Department
| | - D. V. Mareeva
- Loginov Moscow Clinical Scientific Center, Moscow Healthcare Department
| | | | - D. S. Bordin
- Loginov Moscow Clinical Scientific Center, Moscow Healthcare Department;
Tver State Medical University;
A.I. Yevdokimov Moscow State University of
Medicine and Dentistry
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14
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Negovan A, Iancu M, Fülöp E, Bănescu C. Helicobacter pylori and cytokine gene variants as predictors of premalignant gastric lesions. World J Gastroenterol 2019; 25:4105-4124. [PMID: 31435167 PMCID: PMC6700706 DOI: 10.3748/wjg.v25.i30.4105] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2019] [Revised: 07/12/2019] [Accepted: 07/19/2019] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer remains the third leading cause of mortality from cancer worldwide and carries a poor prognosis, due largely to late diagnosis. The importance of the interaction between Helicobacter pylori (H. pylori) infection, the main risk factor, and host-related genetic factors has been studied intensively in recent years. The genetic predisposition for non-hereditary gastric cancer is difficult to assess, as neither the real prevalence of premalignant gastric lesions in various populations nor the environmental risk factors for cancer progression are clearly defined. For non-cardiac intestinal-type cancer, identifying the factors that modulate the progression from inflammation toward cancer is crucial in order to develop preventive strategies. The role of cytokines and their gene variants has been questioned in regard to non-self-limiting H. pylori gastritis and its evolution to gastric atrophy and intestinal metaplasia; the literature now includes various and non-conclusive results on this topic. The influence of the majority of cytokine single nucleotide polymorphisms has been investigated for gastric cancer but not for preneoplastic gastric lesions. Among the investigated gene variants onlyIL10T-819C, IL-8-251, IL-18RAP917997, IL-22 rs1179251, IL1-B-511, IL1-B-3954, IL4R-398 and IL1RN were identified as predictors for premalignant gastric lesions risk. One of the most important limiting factors is the inhomogeneity of the studies (e.g., the lack of data on concomitant H. pylori infection, methods used to assess preneoplastic lesions, and source population). Testing the modifying effect of H. pylori infection upon the relationship between cytokine gene variants and premalignant gastric lesions, or even testing the interaction between H. pylori and cytokine gene variants in multivariable models adjusted for potential covariates, could increase generalizability of results.
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Affiliation(s)
- Anca Negovan
- Department of Clinical Science-Internal Medicine, University of Medicine, Pharmacy, Sciences and Technology of Târgu Mureș, Mureș 540139, Romania
| | - Mihaela Iancu
- Department of Medical Informatics and Biostatistics, “Iuliu Hațieganu” University of Medicine and Pharmacy, Cluj-Napoca, Cluj 400349, Romania
| | - Emőke Fülöp
- Department of Morphological Sciences, Histology, University of Medicine, Pharmacy, Sciences and Technology of Târgu Mureș, Mureș 540139, Romania
| | - Claudia Bănescu
- Genetics Laboratory, Center for Advanced Medical and Pharmaceutical Research, University of Medicine, Pharmacy, Sciences and Technology of Târgu Mureș, Mureș 540139, Romania
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15
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Wang J, Wen T, Li Z, Che X, Gong L, Yang X, Zhang J, Tang H, He L, Qu X, Liu Y. MicroRNA-1224 Inhibits Tumor Metastasis in Intestinal-Type Gastric Cancer by Directly Targeting FAK. Front Oncol 2019; 9:222. [PMID: 31019895 PMCID: PMC6458237 DOI: 10.3389/fonc.2019.00222] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2019] [Accepted: 03/13/2019] [Indexed: 12/20/2022] Open
Abstract
Intestinal-type gastric cancer (GC) of the Lauren classification system has specific epidemiological characteristics and carcinogenesis patterns. MicroRNAs (miRNAs) have prognostic significance, and some can be used as prognostic biomarkers in GC. In this study, we identified miR-1224 as a potential survival-related miRNA in intestinal-type GC patients by The Cancer Genome Atlas (TCGA) analysis. Using quantitative real-time PCR (qRT-PCR), we showed that the relative expression of miR-1224 was significantly decreased in intestinal-type GC tissues compared to matched adjacent normal mucosa tissues (p < 0.01). We found that high miR-1224 expression was associated with no lymph-node metastasis (p < 0.05) and good prognosis (p = 0.028) in 90 intestinal-type GC tissues. Transfection of intestinal-type GC cells with miR-1224 mimics showed that miR-1224 suppressed cell migration in vitro (wound healing assay and Transwell migration assay), whereas the transfection of cells with miR-1224 inhibitor promoted cell migration in vitro. miR-1224 also suppressed intestinal-type GC cell metastasis in a xenograft mouse model. Furthermore, bioinformatics, luciferase reporter, Western blotting, and immunohistochemistry (IHC) studies demonstrated that miR-1224 directly bound to the focal adhesion kinase (FAK) gene, and downregulated its expression, which decreased STAT3 and NF-κB signaling and subsequent the epithelial-to-mesenchymal transition (EMT). Repression of FAK is required for the miR-1224-mediated inhibition of cell migration in intestinal-type GC. The present study demonstrated that miR-1224 is downregulated in intestinal-type GC. miR-1224 inhibits the metastasis of intestinal-type GC by suppressing FAK-mediated activation of the STAT3 and NF-κB pathways, and subsequent EMT. miR-1224 could represent an important prognostic factor in intestinal-type GC.
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Affiliation(s)
- Jin Wang
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.,Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
| | - Ti Wen
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.,Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
| | - Zhi Li
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.,Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
| | - Xiaofang Che
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.,Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
| | - Libao Gong
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.,Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
| | - Xianghong Yang
- Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Jingdong Zhang
- Department of Medical Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China
| | - Huali Tang
- Department of Medical Oncology, The Central Hospital of Zhuanghe, Zhuanghe, China
| | - Lingzi He
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.,Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
| | - Xiujuan Qu
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.,Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
| | - Yunpeng Liu
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.,Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
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16
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Yusupova LF, Nurgalieva AK, Gilyazova IR, Prokofyeva DS, Munasypov FR, Khusnutdinov SM, Rakhimov RR, Abdeev RR, Sakaeva DD, Khusnutdinova EK. The Role of Allelic Variants of Several Genes of Cytokines in the Development of Gastric Cancer. RUSS J GENET+ 2019. [DOI: 10.1134/s1022795419030165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
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17
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Hishida A, Okugawa Y, Morimoto Y, Shirai Y, Okamoto K, Momokita S, Ogawa A, Tanaka K, Nishikawa R, Toiyama Y, Inoue Y, Sakurai H, Urata H, Tanaka M, McMillan DC, Miki C. Genetic influence of cytokine polymorphisms on the clinical outcome of Japanese gastrointestinal cancer patients in palliative care. Oncol Lett 2019; 17:623-629. [PMID: 30655809 DOI: 10.3892/ol.2018.9614] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2017] [Accepted: 10/23/2018] [Indexed: 11/05/2022] Open
Abstract
Gastrointestinal cancer is one of the most common causes of mortality globally. The present study examined the influence of cytokine genetic polymorphisms [interleukin (IL)-1B C-31T, IL-1RN VNTR, IL-6 C-634G, IL-8 T-251A, IL-10 T-819C and IL-10 A-1082G] on clinical outcomes in patients with gastrointestinal cancer in palliative care. A total of 59 patients with gastrointestinal cancer who were admitted to Iga City General Hospital were analyzed. Genotyping was conducted using a polymerase chain reaction with confronting two-pair primers. Patients with at least one IL-1RN 2 allele demonstrated a significantly better survival (P=0.0275) while those with IL-6-634 G/G demonstrated a worse survival (P=0.0024). Multivariate analyses using the Cox proportional hazard model revealed that those with at least one IL-1RN 2 allele, IL-6-634 G/G or IL-10-1082 A/G had a significantly elevated adjusted hazard ratio of 9.20 (P=0.014), 41.01 (P=0.001) or 6.49 (P=0.046), respectively, compared with those with each homozygous wild-type polymorphism. In addition, the evaluation of weight loss by genotype revealed the potential influence of IL-10 T-819C genotype (P=0.072). IL-1RN, IL-6 and IL-10 polymorphisms were associated with the survival of patients with gastrointestinal cancer, suggesting the clinical feasibility of genetic testing in patients with gastrointestinal cancer in palliative care.
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Affiliation(s)
- Asahi Hishida
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan
| | - Yoshinaga Okugawa
- Department of Surgery, Iga City General Hospital, Iga, Mie 518-0823, Japan.,Department of Medical Oncology, Iga City General Hospital, Iga, Mie 518-0823, Japan.,Department of Biochemical Laboratory, Iga City General Hospital, Iga, Mie 518-0823, Japan
| | - Yuhki Morimoto
- Department of Surgery, Iga City General Hospital, Iga, Mie 518-0823, Japan
| | - Yumiko Shirai
- Department of Nutrition, Iga City General Hospital, Iga, Mie 518-0823, Japan
| | - Kyoko Okamoto
- Department of Nursing, Iga City General Hospital, Iga, Mie 518-0823, Japan
| | - Sachiko Momokita
- Department of Biochemical Laboratory, Iga City General Hospital, Iga, Mie 518-0823, Japan
| | - Aki Ogawa
- Department of Nursing, Iga City General Hospital, Iga, Mie 518-0823, Japan
| | - Koji Tanaka
- Department of Surgery, Iga City General Hospital, Iga, Mie 518-0823, Japan.,Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan
| | - Ryutaro Nishikawa
- Department of Surgery, Iga City General Hospital, Iga, Mie 518-0823, Japan
| | - Yuji Toiyama
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan
| | - Yasuhiro Inoue
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan
| | - Hiroyuki Sakurai
- Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan
| | - Hisashi Urata
- Department of Surgery, Iga City General Hospital, Iga, Mie 518-0823, Japan
| | - Motoyoshi Tanaka
- Department of Medical Oncology, Iga City General Hospital, Iga, Mie 518-0823, Japan
| | - Donald C McMillan
- Department of Surgical Science, University of Glasgow School of Medicine, Dentistry and Nursing, Glasgow G4 0SF, UK
| | - Chikao Miki
- Department of Surgery, Iga City General Hospital, Iga, Mie 518-0823, Japan.,Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan
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18
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Ghanavat M, Ebrahimi M, Rafieemehr H, Maniati M, Behzad MM, Shahrabi S. Thrombocytopenia in solid tumors: Prognostic significance. Oncol Rev 2019; 13:413. [PMID: 31205603 PMCID: PMC6542370 DOI: 10.4081/oncol.2019.413] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2019] [Accepted: 03/18/2019] [Indexed: 01/01/2023] Open
Abstract
Solid tumors are a heterogeneous group of malignancies that result from out-of-control proliferation of cells. Thrombocytopenia is a common complication among patients with solid tumors that predispose them to bleeding disorders. The aim of this review article is to investigate the underlying mechanisms of the risk and incidence of thrombocytopenia in solid tumors. It can be argued that thrombocytopenia is a poor prognostic factor in solid tumors that can result from several factors such as polymorphism and mutation in some transcription factors and cytokines involved in megakaryocytic maturation or from the adverse effects of treatment. Therefore, an understanding of the exact mechanism of thrombocytopenia pathogenesis in each stage of solid tumors can help in developing therapeutic strategies to decrease bleeding complications in these malignancies.
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Affiliation(s)
- Majid Ghanavat
- Child Growth and Development Research Center, Isfahan University of Medical Sciences, Isfahan
| | - Mina Ebrahimi
- Thalassemia and Hemoglobinopathy Research Center, Research Institute of Health, Ahvaz Jundishapur University of Medical Sciences, Ahvaz
| | - Hassan Rafieemehr
- Department of Medical Laboratory Sciences, School of Paramedicine, Hamadan University of Medical Sciences, Hamadan
| | - Mahmood Maniati
- Thalassemia and Hemoglobinopathy Research Center, Research Institute of Health, Ahvaz Jundishapur University of Medical Sciences, Ahvaz
| | - Masumeh Maleki Behzad
- Thalassemia and Hemoglobinopathy Research Center, Research Institute of Health, Ahvaz Jundishapur University of Medical Sciences, Ahvaz
| | - Saeid Shahrabi
- Department of Biochemistry and Hematology, Faculty of Medicine, Semnan University Of Medical Sciences, Semnan, Iran
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19
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Helicobacter pylori, Peptic Ulcer Disease and Gastric Cancer. GASTROINTESTINAL DISEASES AND THEIR ASSOCIATED INFECTIONS 2019. [DOI: 10.1016/b978-0-323-54843-4.00002-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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20
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Park JW, Choi JS, Han KJ, Lee SH, Kim EJ, Cho JH. Association of a genetic polymorphism of IL1RN with risk of acute pancreatitis in a Korean ethnic group. Korean J Intern Med 2018; 33:1103-1110. [PMID: 29117667 PMCID: PMC6234396 DOI: 10.3904/kjim.2017.133] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2017] [Accepted: 05/29/2017] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND/AIMS Several epidemiological studies have validated the association of interleukin gene polymorphisms with acute pancreatitis (AP) in different populations. However, there have been few studies in Asian ethnic groups. We aimed to investigate the relationships between inflammatory cytokine polymorphisms and AP as pilot research in a Korean ethnic group. METHODS Patients who had been diagnosed with AP were prospectively enrolled. DNA was extracted from whole blood, and DNA sequencing was subsequently performed. Single-nucleotide polymorphisms (SNPs) of the interleukin 1β (IL1B), interleukin 1 receptor antagonist (IL1RN), and tumor necrosis factor α (TNFA) genes of patients with AP were compared to those of normal controls. RESULTS Between January 2011 and January 2013, a total of 65 subjects were enrolled (40 patients with AP vs. 25 healthy controls). One intronic SNP (IL1RN -1129T>C, rs4251961) was significantly associated with the risk of AP (odds ratio, 0.304; 95% confidence interval, 0.095 to 0.967; p = 0.043). However, in our study, AP was not found to be associated with polymorphisms in the promoter regions of inflammatory cytokine genes, including IL1B (-118C>T, c47+242C>T, +3954C/T, and -598T>C) and TNFA (-1211T>C, -1043C>A, -1037C>T, -488G>A, and -418G>A). CONCLUSION IL1RN -1129T>C (rs4251961) genotypes might be associated with a significant increase of AP risk in a Korean ethnic group.
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Affiliation(s)
- Jin Woo Park
- Division of Gastroenterology, Department of Internal Medicine, International St. Mary’s Hospital, Catholic Kwandong University College of Medicine, Incheon, Korea
| | - Ja Sung Choi
- Division of Gastroenterology, Department of Internal Medicine, International St. Mary’s Hospital, Catholic Kwandong University College of Medicine, Incheon, Korea
| | - Ki Joon Han
- Division of Gastroenterology, Department of Internal Medicine, International St. Mary’s Hospital, Catholic Kwandong University College of Medicine, Incheon, Korea
| | - Sang Heun Lee
- Division of Gastroenterology, Department of Internal Medicine, International St. Mary’s Hospital, Catholic Kwandong University College of Medicine, Incheon, Korea
| | - Eui Joo Kim
- Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
| | - Jae Hee Cho
- Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
- Correspondence to Jae Hee Cho, M.D. Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, 21 Namdong-daero 774beon-gil, Namdong-gu, Incheon 21565, Korea Tel: +82-32-460-3778 Fax: +82-32-460-3408 E-mail:
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21
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de Brito BB, da Silva FAF, de Melo FF. Role of polymorphisms in genes that encode cytokines and Helicobacter pylori virulence factors in gastric carcinogenesis. World J Clin Oncol 2018; 9:83-89. [PMID: 30254963 PMCID: PMC6153128 DOI: 10.5306/wjco.v9.i5.83] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2018] [Revised: 06/23/2018] [Accepted: 06/28/2018] [Indexed: 02/06/2023] Open
Abstract
The Helicobacter pylori (H. pylori) infection is a determinant factor in gastric cancer (GC) development. However, the infection outcomes are variable and depend on both host and bacterial characteristics. Some host cytokines such as interleukin (IL)-1β, IL-1Ra, IL-8, IL-10 and tumor necrosis factor-α play important roles in the host immune system response to the pathogen, in the development of gastric mucosal lesions and in cell malignant transformation. Therefore, these host factors are crucial in neoplastic processes. Certain polymorphisms in genes that encode these cytokines have been associated with an increased risk of GC. On the other hand, various virulence factors found in distinct H. pylori bacterial strains, including cytotoxin-associated antigen A, vacuolating cytotoxin, duodenal ulcer promoting gene A protein, outer inflammatory protein and blood group antigen binding adhesin, have been associated with the pathogenesis of different gastric diseases. The virulent factors mentioned above allow the successful infection by the bacterium and play crucial roles in gastric mucosa lesions, including malignant transformation. Moreover, the role of host polymorphisms and bacterial virulence factors in gastric carcinogenesis seems to vary among different countries and populations. The identification of host and bacterium factors that are associated with an increased risk of GC development may be useful in determining the prognosis of infection in patients, what could help in clinical decision-making and in providing of an optimized clinical approach.
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Affiliation(s)
- Breno Bittencourt de Brito
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Brazil
| | | | - Fabrício Freire de Melo
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Brazil
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22
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Pucułek M, Machlowska J, Wierzbicki R, Baj J, Maciejewski R, Sitarz R. Helicobacter pylori associated factors in the development of gastric cancer with special reference to the early-onset subtype. Oncotarget 2018; 9:31146-31162. [PMID: 30123433 PMCID: PMC6089554 DOI: 10.18632/oncotarget.25757] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2018] [Accepted: 06/22/2018] [Indexed: 02/07/2023] Open
Abstract
Nowadays, gastric cancer is one of the most common neoplasms and the fourth cause of cancer-related death on the world. Regarding the age at the diagnosis it is divided into early-onset gastric carcinoma (45 years or younger) and conventional gastric cancer (older than 45). Gastric carcinomas are rarely observed in young population and rely mostly on genetic factors, therefore provide the unique model to study genetic and environmental alternations. The latest research on early-onset gastric cancer are trying to explain molecular and genetic basis, because young patients are less exposed to environmental factors predisposing to cancer. In the general population, Helicobacter pylori, has been particularly associated with intestinal subtype of gastric cancers. The significant association of Helicobacter pylori infection in young patients with gastric cancers suggests that the bacterium has an etiologic role in both diffuse and intestinal subtypes of early-onset gastric cancers. In this paper we would like to ascertain the possible role of Helicobacter pylori infection in the development of gastric carcinoma in young patients. The review summarizes recent literature on early-onset gastric cancers with special reference to Helicobacter pylori infection.
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Affiliation(s)
| | | | - Ryszard Wierzbicki
- 2 Department of Surgery with Trauma, Orthopaedic and Urological Subunit, Independent Public Health Care Center of the Ministry of Interior and Administration in Lublin, Poland
- 3 Department of Surgical Oncology, Medical University of Lublin, Poland
| | - Jacek Baj
- 1 Department of Human Anatomy, Medical University of Lublin, Poland
| | | | - Robert Sitarz
- 1 Department of Human Anatomy, Medical University of Lublin, Poland
- 2 Department of Surgery with Trauma, Orthopaedic and Urological Subunit, Independent Public Health Care Center of the Ministry of Interior and Administration in Lublin, Poland
- 4 Department of Surgery, St. John's Cancer Center, Lublin, Poland
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23
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Xuan Y, Wang YN. Hypoxia/IL-1α axis promotes gastric cancer progression and drug resistance. J Dig Dis 2017; 18:511-520. [PMID: 28608600 DOI: 10.1111/1751-2980.12496] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2017] [Revised: 05/13/2017] [Accepted: 06/08/2017] [Indexed: 12/11/2022]
Abstract
OBJECTIVE The microenvironment of tumors constitutes a unique niche that promotes cancer metastasis and resistance. Two remarkable characteristics of this microenvironment are hypoxia and inflammation. Interleukin-1α (IL-1α), an important inflammatory factor, is frequently upregulated in a variety of cancers. This study aimed to investigate the expression of IL-1α in gastric cancer (GC) and explore the relationship between IL-1α and hypoxia. METHODS Reverse-transcription polymerase chain reaction was performed to characterize IL-1α expression in different GC cell lines under normoxia or hypoxia. IL-1α expression was characterized in relation to tumor stage and lymph node metastasis of GC and the survival of patients. The effect of IL-1α knockdown under normoxia or hypoxia on cell proliferation, migration and sensitivity to cisplatin was also evaluated. Additionally, hypoxia-inducible factor-1α (HIF-1α) expression in KATO-III cells was either upregulated by ectopic HIF-1α expression or downregulated through shHIF-1α transfection, the effects of which on IL-1α expression was subsequently evaluated. RESULTS There was a positive correlation between IL-1α, which was upregulated during hypoxia, and tumor stage, lymph node metastasis and resistance to cisplatin in GC. IL-1α was regulated by HIF1α, and a change in HIF1α expression altered the tumor-promoting effect of IL-1α. CONCLUSION The IL-1α/hypoxia axis may be a valuable target for diagnosis and treatment of GC.
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Affiliation(s)
- Yi Xuan
- Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Ya Nong Wang
- Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
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24
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Banday MZ, Mir AH, Sameer AS, Chowdri NA, Haq E. Interleukin-1β (IL-1β) -31C/T and -511T/C promoter single nucleotide polymorphism in colorectal cancer in ethnic Kashmiri population - a case control study. Meta Gene 2017. [DOI: 10.1016/j.mgene.2017.02.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
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25
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MIFTAHUSSURUR MUHAMMAD, YAMAOKA YOSHIO, GRAHAM DAVIDY. Helicobacter pylori as an oncogenic pathogen, revisited. Expert Rev Mol Med 2017; 19:e4. [PMID: 28322182 PMCID: PMC6905048 DOI: 10.1017/erm.2017.4] [Citation(s) in RCA: 53] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Gastric cancer is an inflammation-associated malignancy aetiologically related to infection with the bacterium, Helicobacter pylori, which is considered a necessary but insufficient cause. Unless treated, H. pylori causes life-long acute and chronic gastric inflammation resulting in progressive gastric mucosal damage that may result in gastric cancer. The rate of progression from superficial gastritis, to an atrophic metaplastic mucosa, and ultimately to cancer relates to the virulence of the infecting H. pylori as well as host and environmental factors. H. pylori virulence is a reflection of its propensity to cause severe gastric inflammation. Both mucosal inflammation and H. pylori can cause host genomic instability, including dysregulation of DNA mismatch repair, stimulation of expression of activation-induced cytidine deaminase, abnormal DNA methylation and dysregulation of micro RNAs, which may result in an accumulation of mutations and loss of normal regulation of cell growth. The difference in cancer risk between the most and least virulent H. pylori strain is only approximately 2-fold. Overall, none of the putative virulence factors identified to date have proved to be disease-specific. The presence, severity, extent and duration of inflammation appear to be the most important factors and current evidence suggests that any host, environmental or bacterial factor that reliably enhances the inflammatory response to the H. pylori infection increases the risk of gastric cancer.
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Affiliation(s)
- MUHAMMAD MIFTAHUSSURUR
- Department of Medicine, Gastroenterology and Hepatology Section, Baylor College of Medicine, Houston, Texas 77030, USA
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu 879-5593, Japan
- Gastroentero-Hepatology Division, Department of Internal Medicine, Faculty of Medicine – Dr Soetomo Teaching Hospital – Institute of Tropical Disease, Universitas Airlangga, Surabaya 60115, Indonesia
| | - YOSHIO YAMAOKA
- Department of Medicine, Gastroenterology and Hepatology Section, Baylor College of Medicine, Houston, Texas 77030, USA
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu 879-5593, Japan
| | - DAVID Y. GRAHAM
- Department of Medicine, Gastroenterology and Hepatology Section, Baylor College of Medicine, Houston, Texas 77030, USA
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26
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Yu SB, Gao Q, Lin WW, Kang MQ. Proteomic analysis indicates the importance of TPM3 in esophageal squamous cell carcinoma invasion and metastasis. Mol Med Rep 2017; 15:1236-1242. [PMID: 28138712 PMCID: PMC5367371 DOI: 10.3892/mmr.2017.6145] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2015] [Accepted: 11/17/2016] [Indexed: 01/06/2023] Open
Abstract
Numerous esophageal squamous cell carcinoma (ESCC) patients exhibit tumor recurrence following radical resection. Invasion and metastasis are key factors in poor prognosis following esophagectomy. In the present study, two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry were used to define patterns of protein expression in ESCC tissues at different pathological stages. The expression levels of identified proteins were determined by immunohistochemistry and western blotting. A total of fifteen protein spots with >2-fold differences were observed when comparing results of 2-DE for stage III and stage I ESCC tissue sample. A total of 12 proteins were identified by mass spectrometry analysis and database searches. The results of immunohistochemistry and western blotting demonstrated expression levels of tropomyosin 3 (TPM3) were higher in stage III ESCC tissue compared with stage I (P<0.05). The findings of the present study identified twelve proteins, which are closely associated with ESCC invasion and metastasis, apoptosis and cell signal transduction. Furthermore, the overexpression of TPM3 may be important in ESCC invasion and metastasis.
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Affiliation(s)
- Shao-Bin Yu
- Second Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
| | - Qin Gao
- Department of General Surgery, Fuzhou General Hospital of Nanjing Military Area Command, Fuzhou, Fujian 350025, P.R. China
| | - Wen-Wei Lin
- Second Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
| | - Ming-Qiang Kang
- Second Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
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Wang H, Hua M, Wang S, Yu J, Chen C, Zhao X, Zhang C, Zhong C, Wang R, He N, Hou M, Ma D. Genetic polymorphisms of IL-18 rs1946518 and IL-1β rs16944 are associated with prognosis and survival of acute myeloid leukemia. Inflamm Res 2016; 66:249-258. [PMID: 27928589 DOI: 10.1007/s00011-016-1012-4] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2016] [Revised: 11/16/2016] [Accepted: 11/22/2016] [Indexed: 11/29/2022] Open
Abstract
BACKGROUND Though the pathogenesis of AML is still unknown, accumulating evidence revealed that immune response plays a vital part in it. NLRP3 inflammasome as a component of immune system has been found related to several cancers. The single nucleotide polymorphisms (SNPs) of NLRP3 inflammasome genes may be related to pathogenesis and prognosis of AML. METHODS AND RESULTS We determined polymorphisms of NLRP3 (rs35829419), CARD8 (rs2043211), IL-1β (rs16944), IL-18 (rs1946518) and NF-κB -94 ins/del ATTG in de novo AML patients to find out whether they play roles in the susceptibility and severity of AML. In our study, 383 AML cases and 300 randomly selected healthy individuals were examined for the polymorphisms and expression of NLRP3 genes. IL-1β (rs16944) polymorphism in different risk AML subgroups was found statistically different, with more GA genotype in favorable-risk cytogenetics group. We also demonstrated that the bone marrow blasts of patients carrying IL-18 (rs1946518) GG or GT genotype were higher than patients of TT genotype. IL-18 plasma level of patients with IL-18 (rs1946518) GT or TT genotype was higher than GG genotype. Moreover, the GT genotype of IL-18 (rs1946518) led to statistically poorer AML-specific survival. CONCLUSION IL-1β (rs16944) and IL-18 (rs1946518) may be served as potential predictors for AML.
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Affiliation(s)
- Hong Wang
- Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Rd, Jinan, 250012, People's Republic of China.,Department of Hematology, Zibo Central Hospital, Zibo, Shandong, People's Republic of China
| | - Mingqiang Hua
- Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Rd, Jinan, 250012, People's Republic of China
| | - Shukang Wang
- Department of Epidemiology and Biostatistics, School of Public Health, Shandong University, Jinan, People's Republic of China
| | - Jie Yu
- Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Rd, Jinan, 250012, People's Republic of China
| | - Chen Chen
- Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Rd, Jinan, 250012, People's Republic of China
| | - Xueyun Zhao
- Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Rd, Jinan, 250012, People's Republic of China
| | - Chen Zhang
- Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Rd, Jinan, 250012, People's Republic of China
| | - Chaoqin Zhong
- Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Rd, Jinan, 250012, People's Republic of China
| | - Ruiqing Wang
- Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Rd, Jinan, 250012, People's Republic of China
| | - Na He
- Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Rd, Jinan, 250012, People's Republic of China
| | - Ming Hou
- Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Rd, Jinan, 250012, People's Republic of China
| | - Daoxin Ma
- Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Rd, Jinan, 250012, People's Republic of China.
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Hugen S, Thomas RE, German AJ, Burgener IA, Mandigers PJJ. Gastric carcinoma in canines and humans, a review. Vet Comp Oncol 2016; 15:692-705. [PMID: 27549077 DOI: 10.1111/vco.12249] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2015] [Revised: 05/06/2016] [Accepted: 05/20/2016] [Indexed: 02/06/2023]
Abstract
Gastric carcinoma (GC) is the most common neoplasm in the stomach of dogs. Although incidence in the general population is reported to be low, breed-specific GC has a high incidence. Median age at presentation ranges from 8 to approximately 10 years. The disease is mostly located in the lesser curvature and antropyloric region of the stomach. Unfortunately, diagnosis is usually made when the disease is at an advanced stage and, therefore, prognosis is poor. Due to similarities in clinical presentation, diagnosis, histology and prognosis, canine GC may serve as a valuable model for human GC. Extensive pedigrees of canine gastric carcinoma cases could reveal insights for human gastric carcinoma. Putative species differences include the role of Helicobacter in pathogenesis, the wide array of genetic data and screening available for humans, and treatment protocols that are available for human GC.
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Affiliation(s)
- S Hugen
- Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
| | - R E Thomas
- Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
| | - A J German
- School of Veterinary Science, University of Liverpool, Neston, UK
| | - I A Burgener
- Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
| | - P J J Mandigers
- Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
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Torrealba N, Rodríguez-Berriguete G, Fraile B, Olmedilla G, Martínez-Onsurbe P, Guil-Cid M, Paniagua R, Royuela M. Expression of several cytokines in prostate cancer: Correlation with clinical variables of patients. Relationship with biochemical progression of the malignance. Cytokine 2016; 89:105-115. [PMID: 27527810 DOI: 10.1016/j.cyto.2016.08.008] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2015] [Revised: 07/12/2016] [Accepted: 08/08/2016] [Indexed: 11/27/2022]
Abstract
BACKGROUND This work is focused on finding new markers that complement or diagnoses currently used towards improving knowledge histological and statistical aspects that allow us to predict the local stage carcinomas and to identify and understand all the factors related to the progression of this disease. MATERIALS AND METHODS Prostates were obtained from: normal prostates from 20 men, diagnosis of BPH (Benign Prostatic Hyperplasia) from 35 men and prostate cancer from 86 men. We studied the behavior of cytokines that have been implicated in inflammatory processes: TNF-alfa, IL-6, IL-1, EGF and TGF-B. Expression of these cytokines and its receptors was analyzed by immunohistochemistry. Spearman's test, Kaplan-Meier curves, univariate and multivariate Cox proportional hazard regression analyses were performed. RESULTS Spearman's analysis showed that there was at least one correlation between TGFB-B, IL-6, gp-130, IL-1B, IL-1R, IL-1RII and clinic pathological feature (preoperative serum PSA, clinical t stage, pathological t stage, positive surgical margins, biochemical progression, survival). Immunostaining score was correlated with some of the clinicopathological feature. In Cox multivariate analysis between the prognostic variables (pathological T stage, Gleason score and lymph node) and immunohistochemical parameters (TGF-B, IL-1a, intensity TGFBRI and intensity TGFBRII) only the expression of IL-1a was retained as independent predictors of biochemical progression after radical prostatectomy. CONCLUSIONS Our results suggest a role for prostatic expression of TGF-B, IL-1a, TGFBRI and TGFBRII as prognostic markers for prostate cancer. The rational combination of novel agents directed toward the inactivation of TGF-B, IL-1a, TGFBRI and TGFBRII could disrupt complementary tumor cell proliferation pathways.
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Affiliation(s)
- Norelia Torrealba
- Department of Biomedicine and Biotechnology, University of Alcalá, Spain.
| | | | - Benito Fraile
- Department of Biomedicine and Biotechnology, University of Alcalá, Spain.
| | - Gabriel Olmedilla
- Department of Pathology, Príncipe de Asturias Hospital, Alcalá de Henares, Madrid, Spain.
| | - Pilar Martínez-Onsurbe
- Department of Pathology, Príncipe de Asturias Hospital, Alcalá de Henares, Madrid, Spain.
| | - Manuel Guil-Cid
- Department of Urology, Príncipe de Asturias Hospital, Alcalá de Henares, Madrid, Spain.
| | - Ricardo Paniagua
- Department of Biomedicine and Biotechnology, University of Alcalá, Spain.
| | - Mar Royuela
- Department of Biomedicine and Biotechnology, University of Alcalá, Spain.
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Drici AEM, Moulessehoul S, Tifrit A, Diaf M, Turki DK, Bachir M, Tou A. Effect of IL-1β and IL-1RN polymorphisms in carcinogenesis of the gastric mucosa in patients infected with Helicobacter pylori in Algeria. Libyan J Med 2016; 11:31576. [PMID: 27340011 PMCID: PMC4919366 DOI: 10.3402/ljm.v11.31576] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2016] [Accepted: 05/27/2016] [Indexed: 12/12/2022] Open
Abstract
Background Infection with Helicobacter pylori is considered a potential risk of developing gastric cancer in association with contributing host genetic factor. IL-1β and IL-1RN polymorphisms appear to maintain and promote Helicobacter pylori infection and to stimulate neoplastic growth of the gastric mucosa. Objective and methods In order to elucidate the effect of these polymorphisms in combination with gastric cancer in a population from northwestern Algeria, a case-control study was carried out on 79 patients infected with H. pylori with chronic atrophic gastritis and/or gastric carcinoma, and 32 subjects were recruited as case-control. IL-1β-31 bi-allelic and IL-1β-511 bi-allelic polymorphisms and IL-1RN penta-allelic were genotyped. Results IL-1β-31C was associated with an increased risk of developing gastric carcinoma (OR=4.614 [1.43−14.81], p=0.01). However, IL-1RN2 heterozygous allele type was significantly associated with chronic atrophic gastritis (OR=4.2 [1.23−3.61], p=0.022). IL-1β-511T was associated with an increased risk of development of chronic atrophic gastritis (OR=4.286 [1.54−11.89], p=0.005). Conclusion IL-1β and IL-1RN polymorphisms associated with H. pylori infection contribute to the development of chronic atrophic gastritis and gastric carcinomas in an Algerian population. The alleles IL-1β-31C and IL-1RN were associated with an increased risk of developing gastric carcinoma, and IL-1β-511T with an increased risk of developing chronic atrophic gastritis with no significant association of developing gastric carcinoma.
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Affiliation(s)
- Amine El-Mokhtar Drici
- Department of Biology, Faculty of Natural and Life Sciences, Djillali LIABES University, Sidi-Bel-Abbes, Algeria;
| | - Soraya Moulessehoul
- Department of Biology, Faculty of Natural and Life Sciences, Djillali LIABES University, Sidi-Bel-Abbes, Algeria
| | - Abdelkarim Tifrit
- Department of Biology, Faculty of Natural and Life Sciences, Djillali LIABES University, Sidi-Bel-Abbes, Algeria
| | - Mustapha Diaf
- Department of Biology, Faculty of Natural and Life Sciences, Djillali LIABES University, Sidi-Bel-Abbes, Algeria
| | - Douidi Kara Turki
- Department of Gastroenterology, University Hospital of Sidi-Bel-Abbes, Sidi-Bel-Abbes, Algeria
| | - Meryem Bachir
- Department of Biology, Faculty of Sciences, Hassiba Ben Bouali University, Chlef, Algeria
| | - Abdenacer Tou
- Anatomopathology Department, University Hospital of Sidi-Bel-Abbes, Sidi-Bel-Abbes, Algeria
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Chen B, Luo MX, Zhou X, Lv Y, Su GQ. Correlation Between Interleukin-1β-511 C/T Polymorphism and Gastric Cancer in Chinese Populations: A Meta-Analysis. Med Sci Monit 2016; 22:1742-50. [PMID: 27215350 PMCID: PMC4915325 DOI: 10.12659/msm.895771] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Background Several studies have indicated that interleukin (IL)-1β-511 C/T polymorphism may contribute to individual susceptibility to gastric cancer, but the results vary among regions and races. No relevant meta-analysis has been conducted in a Chinese population. Therefore, we performed the current meta-analysis to investigate the possible correlation between IL-1β-511 C/T polymorphism and gastric cancer susceptibility in Chinese subjects. Material/Methods PubMed, EmBase, Cochrane Library, Chinese Biology Medicine (CBM), Chinese National Knowledge Infrastructure (CNKI), and Wanfang databases were searched for case-control studies published before 21 January 2015 and investigating a correlation between IL-1β-511 C/T polymorphism and gastric cancer susceptibility. Two investigators independently screened the studies, extracted data, and evaluated the quality of included studies with the Newcastle-Ottawa scale. Meta-analysis was conducted with STATA 12.0. Results A total of 27 articles from 28 case-control studies were collected. Meta-analysis showed that IL-1β-511C/T polymorphism was related to increased susceptibility to gastric cancer in Chinese subjects [T vs. C: OR=1.21, 95%CI (1.07–1.37), P<0.01; TT vs. CC: OR=1.41, 95%CI (1.11–1.80), P<0.01; CT vs. CC: OR=1.26, 95% CI (1.05–1.50), P<0.01; TT+CT vs. CC: OR=1.31, 95%CI (1.08–1.58), P<0.01; and TT vs. CT+CC: OR=1.24, 95%CI (1.05–1.47), P<0.01]. Subgroup analysis showed a significant correlation between IL-1β-511C/T polymorphism and susceptibility to gastric cancer in residents of southern China and in patients with intestinal-type gastric cancer, but not in residents of northern China or in patients with diffuse gastric cancer. Moreover, H. pylori-infected subjects carrying T (CT+TT) exhibited a relatively higher risk of GC [OR=2.4, 95% CI (1.2–5.1), P=0.02]. Conclusions IL-1β-511C/T polymorphism is significantly associated with increased susceptibility to gastric cancer in residents of southern China and in intestinal-type gastric cancer. We also found a synergistic interaction between IL-1β-511C/T polymorphism and H. pylori infection in the development of GC.
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Affiliation(s)
- Bo Chen
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China (mainland)
| | - Ming-Xu Luo
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China (mainland)
| | - Xin Zhou
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China (mainland)
| | - Yo Lv
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China (mainland)
| | - Guo-Qiang Su
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China (mainland)
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Skierucha M, Milne ANA, Offerhaus GJA, Polkowski WP, Maciejewski R, Sitarz R. Molecular alterations in gastric cancer with special reference to the early-onset subtype. World J Gastroenterol 2016; 22:2460-74. [PMID: 26937134 PMCID: PMC4768192 DOI: 10.3748/wjg.v22.i8.2460] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2015] [Revised: 11/06/2015] [Accepted: 12/30/2015] [Indexed: 02/06/2023] Open
Abstract
Currently, gastric cancer (GC) is one of the most frequently diagnosed neoplasms, with a global burden of 723000 deaths in 2012. It is the third leading cause of cancer-related death worldwide. There are numerous possible factors that stimulate the pro-carcinogenic activity of important genes. These factors include genetic susceptibility expressed in a single-nucleotide polymorphism, various acquired mutations (chromosomal instability, microsatellite instability, somatic gene mutations, epigenetic alterations) and environmental circumstances (e.g., Helicobcter pylori infection, EBV infection, diet, and smoking). Most of the aforementioned pathways overlap, and authors agree that a clear-cut pathway for GC may not exist. Thus, the categorization of carcinogenic events is complicated. Lately, it has been claimed that research on early-onset gastric carcinoma (EOGC) and hereditary GC may contribute towards unravelling some part of the mystery of the GC molecular pattern because young patients are less exposed to environmental carcinogens and because carcinogenesis in this setting may be more dependent on genetic factors. The comparison of various aspects that differ and coexist in EOGCs and conventional GCs might enable scientists to: distinguish which features in the pathway of gastric carcinogenesis are modifiable, discover specific GC markers and identify a specific target. This review provides a summary of the data published thus far concerning the molecular characteristics of GC and highlights the outstanding features of EOGC.
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Wang YM, Li ZX, Tang FB, Zhang Y, Zhou T, Zhang L, Ma JL, You WC, Pan KF. Association of genetic polymorphisms of interleukins with gastric cancer and precancerous gastric lesions in a high-risk Chinese population. Tumour Biol 2016; 37:2233-42. [PMID: 26358252 DOI: 10.1007/s13277-015-4022-x] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2015] [Accepted: 08/31/2015] [Indexed: 12/20/2022] Open
Abstract
Helicobacter pylori (H. pylori) infection and cytokine-mediated inflammatory responses play important roles in gastric cancer (GC) pathogenesis. To investigate an association between genetic polymorphisms in interleukin (IL)-1β, IL-4R, IL-8, IL-10, IL-16, IL-18RAP, IL-22, and IL-32 and risks of GC and its precursors, a population-based study was conducted in Linqu County. Genotypes were determined by Sequenom MassARRAY platform in 132 GC cases and 1198 subjects with gastric lesions. The H. pylori status was determined by (13)C-urea breath test ((13)C-UBT) or enzyme-linked immunosorbent assay (ELISA). Among 11 candidate single nucleotide polymorphisms (SNPs), subjects carrying IL-18RAP rs917997 AA genotype were associated with risk of GC [adjusted odds ratio (OR) = 1.83, 95 % confidence interval (CI) 1.14-2.92] or chronic atrophic gastritis (CAG; OR = 1.55, 95 % CI 1.07-2.24). The risk of GC was also increased in subjects carrying IL-32 rs2015620 A allele (AA + AT; OR = 1.92, 95 % CI 1.09-3.39). Moreover, elevated risks of CAG (OR = 2.64, 95 % CI 1.89-3.69), intestinal metaplasia (IM; OR = 5.58, 95 % CI 3.86-8.05), and dysplasia (DYS; OR = 1.64, 95 % CI 1.18-2.26) were observed in subjects with IL-22 rs1179251 CC genotype. Stratified analysis indicated that risks of GC and its precursors were elevated in subjects with IL-32 rs2015620 A allele (AA + AT) or IL-22 rs1179251 CC genotype and H. pylori infection, and significant interactions between these two SNPs and H. pylori infection were found. These findings suggested that IL-18RAP rs917997, IL-32 rs2015620, IL-22 rs1179251, and interactions between these polymorphisms and H. pylori infection were associated with risks of gastric lesions. Genetic polymorphisms of interleukins may play crucial roles in H. pylori-induced gastric carcinogenesis.
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Affiliation(s)
- Yu-Mei Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, 52 Fu-cheng Road, Hai-dian District, Beijing, 100142, People's Republic of China
| | - Zhe-Xuan Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, 52 Fu-cheng Road, Hai-dian District, Beijing, 100142, People's Republic of China
| | - Fu-Bing Tang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, 52 Fu-cheng Road, Hai-dian District, Beijing, 100142, People's Republic of China
| | - Yang Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, 52 Fu-cheng Road, Hai-dian District, Beijing, 100142, People's Republic of China
| | - Tong Zhou
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, 52 Fu-cheng Road, Hai-dian District, Beijing, 100142, People's Republic of China
| | - Lian Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, 52 Fu-cheng Road, Hai-dian District, Beijing, 100142, People's Republic of China
| | - Jun-Ling Ma
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, 52 Fu-cheng Road, Hai-dian District, Beijing, 100142, People's Republic of China
| | - Wei-Cheng You
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, 52 Fu-cheng Road, Hai-dian District, Beijing, 100142, People's Republic of China.
| | - Kai-Feng Pan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, 52 Fu-cheng Road, Hai-dian District, Beijing, 100142, People's Republic of China.
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Ying HY, Yu BW, Yang Z, Yang SS, Bo LH, Shan XY, Wang HJ, Zhu YJ, Wu XS. Interleukin-1B 31 C>T polymorphism combined with Helicobacter pylori-modified gastric cancer susceptibility: evidence from 37 studies. J Cell Mol Med 2016; 20:526-36. [PMID: 26805397 PMCID: PMC4759475 DOI: 10.1111/jcmm.12737] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2015] [Accepted: 10/16/2015] [Indexed: 12/25/2022] Open
Abstract
Gastric cancer is one of the most common malignancies worldwide. Interleukin‐1‐beta (IL‐1β) is a pro‐inflammatory cytokine and potent inhibitor of gastric acid secretion. Some studies provided evidence of the association between IL‐1B 31 polymorphism and gastric cancer risk while other studies did not. Therefore, we conducted a comprehensive meta‐analysis to reassess the association. A systematic literature search of the PubMed and EMBASE databases identified 37 studies with 6108 cases and 8980 controls for this meta‐analysis. The crude odd ratios (ORs) and the 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. Meta‐regression was used to determine the major source of heterogeneity across the studies. The pooled analysis did not suggest the significant association of IL‐1B 31 C>T polymorphism with gastric cancer risk. Stratified analysis was performed by ethnicity, source of control, genotype method, and indicated a significantly increased gastric cancer risk associated with IL‐1B 31T variant in the population‐based subgroup (heterozygous model: OR = 1.22, 95% CI = 1.03–1.45). Moreover, stratified analysis by Helicobacter pylori infection status indicated that IL‐1B 31 polymorphism increased gastric cancer risk in infection‐positive subgroup (homozygous model: OR = 1.35, 95% CI = 1.02–1.78; heterozygous model: OR = 1.31, 95% CI = 1.04–1.66; recessive model: OR = 1.29, 95% CI = 1.04–1.61). The study suggested that IL‐1B 31 polymorphism might confer susceptibility to gastric cancer in the presence of H. pylori infection, indicating a gene–environment interaction in gastric carcinogenesis.
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Affiliation(s)
- Hua-Yong Ying
- Department of Laboratory Medicine, Jinhua Central Hospital, Jinhua, Zhejiang, China
| | - Bei-Wei Yu
- Department of Laboratory Medicine, Jinhua People's Hospital, Jinhua, Zhejiang, China
| | - Zong Yang
- The Fifth Medical Team, Xinjiang Uygur Autonomous Region Corps of Chinese People's Armed Police Forces, Xinjiang, China
| | - Shan-Shan Yang
- Department of Laboratory Medicine, Jinhua Woman & Children Health Hospital, Jinhua, Zhejiang, China
| | - Li-Hong Bo
- Department of Laboratory Medicine, Jinhua Central Hospital, Jinhua, Zhejiang, China
| | - Xiao-Yun Shan
- Department of Laboratory Medicine, Jinhua Central Hospital, Jinhua, Zhejiang, China
| | - Hui-Jiao Wang
- Department of Laboratory Medicine, Jinhua People's Hospital, Jinhua, Zhejiang, China
| | - Yi-Jun Zhu
- Department of Laboratory Medicine, Jinhua Central Hospital, Jinhua, Zhejiang, China
| | - Xue-Song Wu
- School of Humanities and Social Science, Harbin Medical University, Harbin, Heilongjiang, China
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Figura N, Marano L, Moretti E, Ponzetto A. Helicobacter pylori infection and gastric carcinoma: Not all the strains and patients are alike. World J Gastrointest Oncol 2016; 8:40-54. [PMID: 26798436 PMCID: PMC4714145 DOI: 10.4251/wjgo.v8.i1.40] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2015] [Revised: 10/06/2015] [Accepted: 11/03/2015] [Indexed: 02/05/2023] Open
Abstract
Gastric carcinoma (GC) develops in only 1%-3% of Helicobacter pylori (H. pylori) infected people. The role in GC formation of the bacterial genotypes, gene polymorphisms and host's factors may therefore be important. The risk of GC is enhanced when individuals are infected by strains expressing the oncoprotein CagA, in particular if CagA has a high number of repeats containing the EPIYA sequence in its C'-terminal variable region or particular amino acid sequences flank the EPIYA motifs. H. pylori infection triggers an inflammatory response characterised by an increased secretion of some chemokines by immunocytes and colonised gastric epithelial cells; these molecules are especially constituted by proteins composing the interleukin-1beta (IL-1β) group and tumour necrosis factor-alpha (TNF-α). Polymorphisms in the promoter regions of genes encoding these molecules, could account for high concentrations of IL-1β and TNF-α in the gastric mucosa, which may cause hypochlorhydria and eventually GC. Inconsistent results have been attained with other haplotypes of inflammatory and anti-inflammatory cytokines. Genomic mechanisms of GC development are mainly based on chromosomal or microsatellite instability (MSI) and deregulation of signalling transduction pathways. H. pylori infection may induce DNA instability and breaks of double-strand DNA in gastric mucocytes. Different H. pylori strains seem to differently increase the risk of cancer development run by the host. Certain H. pylori genotypes (such as the cagA positive) induce high degrees of chronic inflammation and determine an increase of mutagenesis rate, oxidative-stress, mismatch repair mechanisms, down-regulation of base excision and genetic instability, as well as generation of reactive oxygen species that modulate apoptosis; these phenomena may end to trigger or concur to GC development.
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Hong JB, Zuo W, Wang AJ, Lu NH. Helicobacter pylori Infection Synergistic with IL-1β Gene Polymorphisms Potentially Contributes to the Carcinogenesis of Gastric Cancer. Int J Med Sci 2016; 13:298-303. [PMID: 27076787 PMCID: PMC4829543 DOI: 10.7150/ijms.14239] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2015] [Accepted: 03/31/2016] [Indexed: 12/14/2022] Open
Abstract
Helicobacter pylori (H. pylori) infection is the most common chronic bacterial infection in the world and the etiological agent for most gastric cancer (GC). Interleukin-1β (IL-1β) is a potent proinflammatory cytokine, and its deregulation is closely associated with the tumorigenesis of several cancers. Recent studies have revealed that the IL-1β-31 and -511T alleles are closely associated with gastric carcinogenesis due to their roles in the induction of gastric precancerous lesions and hypochlorhydria. Furthermore, H. pylori infection has a synergistic effect on the development of GC with IL-1β gene polymorphisms, and the highest prevalence of severe gastric abnormalities are found in patients with both host and bacterial high-risk genotypes (cagA(+)/vacAs1(+)/IL-1β-511T). Therefore, these recent advances demonstrate that H. pylori synergistic with IL-1β gene polymorphisms contribute to the gastric carcinogenesis by their involvement in precancerous gastric lesions and low gastric acid secretion.
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Affiliation(s)
- Jun-Bo Hong
- 1. Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China
| | - Wei Zuo
- 2. Department of Respiratory Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China
| | - An-Jiang Wang
- 1. Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China
| | - Nong-Hua Lu
- 1. Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China
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Ahn HJ, Lee DS. Helicobacter pylori in gastric carcinogenesis. World J Gastrointest Oncol 2015; 7:455-65. [PMID: 26690981 PMCID: PMC4678392 DOI: 10.4251/wjgo.v7.i12.455] [Citation(s) in RCA: 73] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2015] [Revised: 10/10/2015] [Accepted: 11/03/2015] [Indexed: 02/05/2023] Open
Abstract
Gastric cancer still is a major concern as the third most common cancer worldwide, despite declining rates of incidence in many Western countries. Helicobacter pylori (H. pylori) is the major cause of gastric carcinogenesis, and its infection insults gastric mucosa leading to the occurrence of atrophic gastritis which progress to intestinal metaplasia, dysplasia, early gastric cancer, and advanced gastric cancer consequently. This review focuses on multiple factors including microbial virulence factors, host genetic factors, and environmental factors, which can heighten the chance of occurrence of gastric adenocarcinoma due to H. pylori infection. Bacterial virulence factors are key components in controlling the immune response associated with the induction of carcinogenesis, and cagA and vacA are the most well-known pathogenic factors. Host genetic polymorphisms contribute to regulating the inflammatory response to H. pylori and will become increasingly important with advancing techniques. Environmental factors such as high salt and smoking may also play a role in gastric carcinogenesis. It is important to understand the virulence factors, host genetic factors, and environmental factors interacting in the multistep process of gastric carcinogenesis. To conclude, prevention via H. pylori eradication and controlling environmental factors such as diet, smoking, and alcohol is an important strategy to avoid H. pylori-associated gastric carcinogenesis.
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Stubljar D, Skvarc M. Helicobacter pylori vs immune system or antibiotics. World J Immunol 2015; 5:142-151. [DOI: 10.5411/wji.v5.i3.142] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Revised: 06/18/2015] [Accepted: 07/27/2015] [Indexed: 02/05/2023] Open
Abstract
Helicobacter pylori (H. pylori) infection has often no clinical signs and is one of the most common bacterial infections. All infected subjects have histology of active chronic gastritis. In some cases patients develop peptic ulcer and minority of them develop gastric cancer. Gastric cancer is multifactorial disease, thus various progressions of H. pylori infection and disease are dependent on the host genetic factors, the characteristics of the individual’s immune response, environmental factors, and different bacterial virulence factors of the individual bacterial strains. Eradication of the bacteria plays a crucial role in the treatment of these cases however antibiotic therapy does not always help. Bacteria often develop resistance to antibiotics so we recommend that not only screening for H. pylori also the strain determination should have some diagnostic value, especially in the patients who already developed gastritis. Furthermore, for such patients assessment of disease progression (atrophic or metaplastic gastritis) could be followed by polymorphism determination. Until now we cannot predict the disease based only on single polymorphism. Bacteria successfully neutralize the responses of the immune systems using different enzymes or even components of the host immune response. However, the influence of immune system and its components could represent new ways of treatments and could help to eradicate the infection.
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Lin SJ, Gagnon-Bartsch JA, Tan IB, Earle S, Ruff L, Pettinger K, Ylstra B, van Grieken N, Rha SY, Chung HC, Lee JS, Cheong JH, Noh SH, Aoyama T, Miyagi Y, Tsuburaya A, Yoshikawa T, Ajani JA, Boussioutas A, Yeoh KG, Yong WP, So J, Lee J, Kang WK, Kim S, Kameda Y, Arai T, zur Hausen A, Speed TP, Grabsch HI, Tan P. Signatures of tumour immunity distinguish Asian and non-Asian gastric adenocarcinomas. Gut 2015; 64:1721-31. [PMID: 25385008 PMCID: PMC4680172 DOI: 10.1136/gutjnl-2014-308252] [Citation(s) in RCA: 179] [Impact Index Per Article: 17.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2014] [Accepted: 09/09/2014] [Indexed: 12/12/2022]
Abstract
OBJECTIVE Differences in gastric cancer (GC) clinical outcomes between patients in Asian and non-Asian countries has been historically attributed to variability in clinical management. However, recent international Phase III trials suggest that even with standardised treatments, GC outcomes differ by geography. Here, we investigated gene expression differences between Asian and non-Asian GCs, and if these molecular differences might influence clinical outcome. DESIGN We compared gene expression profiles of 1016 GCs from six Asian and three non-Asian GC cohorts, using a two-stage meta-analysis design and a novel biostatistical method (RUV-4) to adjust for technical variation between cohorts. We further validated our findings by computerised immunohistochemical analysis on two independent tissue microarray (TMA) cohorts from Asian and non-Asian localities (n=665). RESULTS Gene signatures differentially expressed between Asians and non-Asian GCs were related to immune function and inflammation. Non-Asian GCs were significantly enriched in signatures related to T-cell biology, including CTLA-4 signalling. Similarly, in the TMA cohorts, non-Asian GCs showed significantly higher expression of T-cell markers (CD3, CD45R0, CD8) and lower expression of the immunosuppressive T-regulatory cell marker FOXP3 compared to Asian GCs (p<0.05). Inflammatory cell markers CD66b and CD68 also exhibited significant cohort differences (p<0.05). Exploratory analyses revealed a significant relationship between tumour immunity factors, geographic locality-specific prognosis, and postchemotherapy outcomes. CONCLUSIONS Analyses of >1600 GCs suggest that Asian and non-Asian GCs exhibit distinct tumour immunity signatures related to T-cell function. These differences may influence geographical differences in clinical outcome, and the design of future trials particularly in immuno-oncology.
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Affiliation(s)
- Suling J Lin
- Department of Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, Singapore, Singapore
| | | | - Iain Beehuat Tan
- Department of Medical Oncology, National Cancer Centre, Singapore, Singapore
| | - Sophie Earle
- Section of Pathology and Tumour Biology, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK
| | - Louise Ruff
- Section of Pathology and Tumour Biology, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK
| | - Katherine Pettinger
- Section of Pathology and Tumour Biology, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK
| | - Bauke Ylstra
- Department of Pathology, Free University Medical Center Amsterdam, Amsterdam, The Netherlands
| | - Nicole van Grieken
- Department of Pathology, Free University Medical Center Amsterdam, Amsterdam, The Netherlands
| | - Sun Young Rha
- Department of Internal Medicine, Yonsei Cancer Center, Seoul, South Korea
| | - Hyun Cheol Chung
- Department of Internal Medicine, Yonsei Cancer Center, Seoul, South Korea
| | - Ju-Seog Lee
- Division of Cancer Medicine, Department of Systems Biology, MD Anderson Cancer Center, Houston, Texas, USA
| | - Jae Ho Cheong
- Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea
| | - Sung Hoon Noh
- Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea
| | - Toru Aoyama
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center Hospital, Yokohama, Japan
| | - Yohei Miyagi
- Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan
| | - Akira Tsuburaya
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Takaki Yoshikawa
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center Hospital, Yokohama, Japan
| | - Jaffer A Ajani
- Departments of Gastrointestinal Medical Oncology, MD Anderson Cancer Center, Houston, USA
| | - Alex Boussioutas
- Cancer Genomics and Biochemistry Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia,Department of Medicine Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia
| | - Khay Guan Yeoh
- Department of Medicine, National University Health System, Singapore, Singapore,Department of Gastroenterology and Hepatology, National University Health System, Singapore, Singapore
| | - Wei Peng Yong
- National University Cancer Institute, Singapore, Singapore
| | - Jimmy So
- Department of Surgery, National University Health System, Singapore, Singapore
| | - Jeeyun Lee
- Department of Medicine, Division of Haematology-Oncology, Samsung Medical Centre, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Won Ki Kang
- Department of Medicine, Division of Haematology-Oncology, Samsung Medical Centre, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Sung Kim
- Department of Surgery, Gastric Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Yoichi Kameda
- Department of Pathology, Kanagawa Cancer Center Hospital, Yokohama, Japan
| | - Tomio Arai
- Department of Pathology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan
| | - Axel zur Hausen
- Department of Pathology, Maastricht University Medical Center, Maastricht, The Netherlands,GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, Netherlands
| | - Terence P Speed
- Department of Statistics, University of California at Berkeley, Berkeley, California, USA,Bioinformatics Division, Walter and Eliza Hall Institute, Victoria, Australia,Department of Mathematics and Statistics, University of Melbourne, Australia
| | - Heike I Grabsch
- Section of Pathology and Tumour Biology, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK,Department of Pathology, Maastricht University Medical Center, Maastricht, The Netherlands,GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, Netherlands
| | - Patrick Tan
- Department of Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, Singapore, Singapore,Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore, Singapore,Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore,Cellular and Molecular Research, National Cancer Centre, Singapore, Singapore
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Evaluation of selected interleukins in patients with different gastric neoplasms: a preliminary report. Sci Rep 2015; 5:14382. [PMID: 26486258 PMCID: PMC4613562 DOI: 10.1038/srep14382] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2015] [Accepted: 08/21/2015] [Indexed: 12/25/2022] Open
Abstract
Abnormal interactions between cytokines may be an overlooked mechanism linking the development of different types of gastric neoplasms. In this study a comprehensive analysis of the systemic levels of interleukins (IL-1,IL-6, IL-8,IL-10 and IL-12) was performed in 75 patients with different gastric neoplasms (cancer, gastrointestinal stromal tumors, neuroendocrine neoplasms, lymphomas) and 40 healthy volunteers. Patients with gastric cancer (GC) have significantly higher IL-6 levels, and lower IL-8 and IL-10 concentrations, in comparison to controls and patients with other gastric neoplasms. Analogous results were observed in terms of IL-6/IL-8 and IL-6/IL-10 ratios, whose values were also higher in GC patients. In GC patients no associations were detected between the systemic levels/values of interleukins (ratios) and TNM staging. IL-6, IL-10, IL-6/IL-8 and IL-6/IL-10 ratios appeared to hold diagnostic potential in confirming/excluding the presence of GC. Their sensitivity/specificity in GC detection/exclusion was approximately 54–72%. In conclusion, disturbed systemic biochemical balance in multiple interleukins exists at the earliest stages of and appears to be specific to GC. The interleukin ratios proposed here seem to be more promising indicators of GC in humans than direct systemic levels of interleukins, and probably possess the potential to be applied as a supporting factor for techniques routinely used.
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The influence of cytokine gene polymorphisms on the risk of developing gastric cancer in patients with Helicobacter pylori infection. Radiol Oncol 2015; 49:256-64. [PMID: 26401131 PMCID: PMC4577222 DOI: 10.2478/raon-2014-0041] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2014] [Accepted: 08/27/2014] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Helicobacter pylori infection is the main cause of gastric cancer. The disease progression is influenced by the host inflammatory responses, and cytokine single nucleotide polymorphisms (SNPs) may have a role in the course of the disease. The aim of our study was to investigate proinflammatory cytokine polymorphisms, previously associated with the development of gastric cancer, in a Slovenian population. PATIENTS AND METHODS In total 318 patients and controls were selected for the study and divided into three groups: (i) patients with gastric cancer (n = 58), (ii) patients with chronic gastritis (n = 60) and (iii) healthy control group (n = 200). H. pylori infection in patient groups was determined by serology, histology and culture. Four proinflammatory gene polymorphisms were determined (IL-1β, IL-1ra, TNF-α, TLR-4) in all subjects. RESULTS We found a statistically significant difference between males and females for the groups (p = 0.025). Odds ratio (OR) for gastric cancer risk for females was 0.557 (95% confidence interval [CI]: 0.233-1.329) and for chronic gastritis 2.073 (95% CI: 1.005-4.277). IL-1B-511*T/T homozygous allele for cancer group had OR = 2.349 (95% CI: 0.583-9.462), heterozygous IL-1B-511*T had OR = 1.470 (95% CI: 0.583-3.709) and heterozygotes in TNF-A-308 genotype for chronic gastritis had OR = 1.402 (95% CI: 0.626-3.139). Other alleles had OR less than 1. CONCLUSIONS We could not prove association between gastric cancer and chronic gastritis due to H. pylori in any cytokine SNPs studied in Slovenian population. Other SNPs might be responsible besides infection with H. pylori for the progression from atrophy to neoplastic transformation.
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Sun X, Xu Y, Zhang F, Jing T, Han J, Zhang J. Association between the IL1B -31C > T polymorphism and Helicobacter pylori infection in Asian and Latin American population: A meta-analysis. Microb Pathog 2015; 86:45-52. [PMID: 26188264 DOI: 10.1016/j.micpath.2015.07.010] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2015] [Revised: 07/11/2015] [Accepted: 07/13/2015] [Indexed: 12/18/2022]
Abstract
BACKGROUND Host genetic factors that control the production of cytokines, including interleukin-1β (IL-1β), possibly affect susceptibility to many Helicobacter pylori-related diseases. There is a complex interplay between H. pylori infection, the subsequent production of certain cytokines, and H. pylori-related diseases. We conducted a meta-analysis to clarify the association between the IL1B -31C > T polymorphism and H. pylori infection, and possible subsequent pathogenic mechanisms. METHODS Published literature contained within PubMed, Embase, and the Cochrane Library was used in our meta-analysis. Data were analyzed with the STATA 13.1 software package using pooled odds ratios (ORs) with 95% confidence intervals (95% CI). Egger's regression test, Begg's rank correlation test, and Begg's funnel plot were used to test publication bias. RESULTS A total of 12 case-control studies comprising 5827 subjects (3335 cases and 2492 controls) were available for our meta-analysis. The IL1B -31C > T polymorphism was associated with an increased risk of H. pylori infection in Asian and Latin American population (TT + CT vs. CC, OR = 1.29, 95% CI = 1.14-1.46; TT vs. CT + CC, OR = 1.23, 95% CI = 1.09-1.39; TT vs. CC, OR = 1.43, 95% CI = 1.22-1.67; T allele vs. C allele, OR = 1.19, 95% CI = 1.10-1.29). A significant association was also found for all genetic models in various subgroups (cancer and no-cancer, hospital- and population-based). CONCLUSION Our meta-analysis demonstrated that IL1B -31C > T polymorphism might increase H. pylori infection risk in Asian and Latin American population. Further studies with different ethnicities and larger sample size are required to validate this result.
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Affiliation(s)
- Xudong Sun
- Department of Pathogenic Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China
| | - Yuanyuan Xu
- Department of Pathogenic Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China
| | - Fuhua Zhang
- Department of Gastroenterology, Second Hospital of Gansu Province, Lanzhou 730000, China
| | - Tao Jing
- Department of Pathogenic Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China
| | - Jian Han
- Department of Pathogenic Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China.
| | - Jinhua Zhang
- Department of Gastroenterology, Second Hospital of Gansu Province, Lanzhou 730000, China.
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Giraldo NA, Becht E, Vano Y, Sautès-Fridman C, Fridman WH. The immune response in cancer: from immunology to pathology to immunotherapy. Virchows Arch 2015; 467:127-35. [DOI: 10.1007/s00428-015-1787-7] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2015] [Revised: 04/26/2015] [Accepted: 05/06/2015] [Indexed: 02/07/2023]
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Hasan AN, Ahmad MW, Madar IH, Grace BL, Hasan TN. An in silico analytical study of lung cancer and smokers datasets from gene expression omnibus (GEO) for prediction of differentially expressed genes. Bioinformation 2015; 11:229-35. [PMID: 26124566 PMCID: PMC4464538 DOI: 10.6026/97320630011229] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2015] [Revised: 03/31/2015] [Accepted: 04/15/2015] [Indexed: 01/02/2023] Open
Abstract
Smoking is the leading cause of lung cancer development and several genes have been identified as potential biomarker for lungs cancer. Contributing to the present scientific knowledge of biomarkers for lung cancer two different data sets, i.e. GDS3257 and GDS3054 were downloaded from NCBI׳s GEO database and normalized by RMA and GRMA packages (Bioconductor). Diffrentially expressed genes were extracted by using and were R (3.1.2); DAVID online tool was used for gene annotation and GENE MANIA tool was used for construction of gene regulatory network. Nine smoking independent gene were found whereas average expressions of those genes were almost similar in both the datasets. Five genes among them were found to be associated with cancer subtypes. Thirty smoking specific genes were identified; among those genes eight were associated with cancer sub types. GPR110, IL1RN and HSP90AA1 were found directly associated with lung cancer. SEMA6A differentially expresses in only non-smoking lung cancer samples. FLG is differentially expressed smoking specific gene and is related to onset of various cancer subtypes. Functional annotation and network analysis revealed that FLG participates in various epidermal tissue developmental processes and is co-expressed with other genes. Lung tissues are epidermal tissues and thus it suggests that alteration in FLG may cause lung cancer. We conclude that smoking alters expression of several genes and associated biological pathways during development of lung cancers.
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Affiliation(s)
- Atif Noorul Hasan
- Dept. of Bioinformatics, Jamia Millia Islamia, New Delhi, India
- Division of Bioinformatics, Noor-Amna Foundation for Research and Education, Bettiah, Bihar, India
| | - Mohammad Wakil Ahmad
- Dept. of Software Engg, College of Computer Science, King Saud University, Riyadh, Saudi Arabia
| | - Inamul Hasan Madar
- Dept. of Biotechnology and Bioinformatics, Bishop Heber College, Tiruchirappalli, TN, India
| | - B Leena Grace
- Dept of Biotechnology, Vinayaka Missions University, Salem, TN, India
| | - Tarique Noorul Hasan
- Division of Bioinformatics, Noor-Amna Foundation for Research and Education, Bettiah, Bihar, India
- R & D Center, Bharathiar University, Coimbatore-641046, TN,India
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Abstract
BACKGROUND Infection is a common phenomenon following stroke, and adversely affects outcome. Previous studies suggest that interleukin-1 receptor antagonist (IL-1ra) and single nucleotide polymorphisms (SNPs) in the IL1RN gene might influence the risk of post-stroke infection and outcome. In this study, we addressed the effects of the rs4251961 SNP in IL1RN on infection risk and outcome. METHODS Subjects with acute ischemic stroke were enrolled within 72 h of symptom onset and followed up to 1 year. Plasma IL-1ra was measured at multiple time points and outcome assessed at 1, 3, 6, and 12 months. Active surveillance for infection occurred while subjects were hospitalized. Subjects were genotyped for the IL1RN rs4251961 polymorphism. RESULTS In the population of 113 subjects for this study, those with the minor C allele of rs4251961 polymorphism in IL1RN were more likely to be Caucasian, hypertensive, and to be afflicted with coronary heart disease. Higher plasma IL-1ra was associated with an increased risk of infection (other than pneumonia), and the minor C allele of rs4251961 was independently associated with a decreased risk of infection (other than pneumonia). Initial plasma IL-1ra was not predictive of long-term outcome, but patients with the minor C allele of rs4251961 were more likely to experience good (modified Rankin Score <2) long-term outcome. CONCLUSIONS These data indicate that IL-1ra and IL1RN may influence the risk of infection after stroke, but this influence seems limited to infections other than pneumonia. Further studies are needed to better understand the complexities of immune regulation on infection and outcome after stroke.
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Role of IL-38 and its related cytokines in inflammation. Mediators Inflamm 2015; 2015:807976. [PMID: 25873772 PMCID: PMC4383490 DOI: 10.1155/2015/807976] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2014] [Accepted: 10/13/2014] [Indexed: 12/13/2022] Open
Abstract
Interleukin- (IL-) 38 is a recently discovered cytokine and is the tenth member of the IL-1 cytokine family. IL-38 shares structural features with IL-1 receptor antagonist (IL-1Ra) and IL-36Ra. IL-36R is the specific receptor of IL-38, a partial receptor antagonist of IL-36. IL-38 inhibits the production of T-cell cytokines IL-17 and IL-22. IL-38 also inhibits the production of IL-8 induced by IL-36γ, thus inhibiting inflammatory responses. IL-38-related cytokines, including IL-1Ra and IL-36Ra, are involved in the regulation of inflammation and immune responses. The study of IL-38 and IL-38-related cytokines might provide new insights for developing anti-inflammatory treatments in the near future.
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Yu CY, Chen HY. Genetic Variations and Gastric Cancer. Gastrointest Tumors 2015. [DOI: 10.1159/000431265] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
<b><i>Background:</i></b> Gastric cancer (GC) has an apparent hereditary component. However, in a large fraction of gastric cases, no known genetic syndrome or family history can be identified, suggesting the presence of ‘missing heritability' in GC etiology. Genome-wide association studies (GWAS) and traditional candidate gene studies have both led to the identification of multiple replicable common genetic variants associated with GC risk. <b><i>Summary:</i></b> We summarize the genetic variants associated with GC risk identified up to date. Achievements derived from translational cancer research including the following aspects: (a) contribution to the our understanding of gastric tumorigenesis, (b) guidance to individualized treatment and (c) prediction of patient prognosis. We also prospect future research direction such as post-GWAS analyses and rare variants studies. <b><i>Key Message:</i></b> Many genetic variants were found through GWAS or candidate gene studies, and interpreting their underlying mechanisms will help us translate risk profiles generated from these variations into use in the clinical setting for targeted screening and treatment. <b><i>Practical Implications:</i></b> Investigation of the potential use of genetic variations as prognostic and predictive markers is a developing field. Many people could benefit from a better understanding of genetic polymorphisms to potentially identify a priori individuals who might have the best chance of survival and therefore derive most clinical benefit from treatment. Outcomes of particular scientific interest for molecular epidemiologic studies should include overall survival, recurrence- and progression-free survival, response to treatment, and early and late toxicities stemming from chemotherapy and radiation.
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The course of gastric cancer following surgery is associated with genetic variations of the interleukin-1 receptor antagonist and interleukin-1β. Gastric Cancer 2015; 18:77-83. [PMID: 24557417 DOI: 10.1007/s10120-014-0349-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2013] [Accepted: 02/01/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND Inflammation, especially the cytokine response of the IL-1 family, has been shown to influence susceptibility to gastric cancer. In addition, several other pro-inflammatory cytokines have been demonstrated to influence metastasis and resistance to chemotherapy. Therefore, genetic variations within these genes may not only affect susceptibility but also influence the outcome of gastric cancer patients. A limited number of studies showed indeed an association of IL-1β and IL-1RN variations with survival of gastric cancer patients. However, results are inconsistent, possibly because of different patient cohorts and different therapies. METHODS In this retrospective cohort study we genotyped 154 patients with gastric cancer for IL-1β and IL-1RN variations. Patients had undergone pathologically proven R0 resection and had received no additional adjuvant treatment. RESULTS We show here a protective association with disease-free survival for both heterozygous genotypes, IL-1β SNP C-511T (rs16944) and IL-1RN VNTR. The combination of both heterozygous genotypes is the strongest predictor independent of UICC stage. CONCLUSION Genetic variations in the IL-1β and IL-1RN genes influence disease progression in gastric cancer. Screening for these genetic variations might help to stratify therapies for gastric cancer patients in the future.
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Hirbod-Mobarakeh A, Amirzargar AA, Nikbin B, Nicknam MH, Kutikhin A, Rezaei N. Immunogenetics of Cancer. CANCER IMMUNOLOGY 2015:295-341. [DOI: 10.1007/978-3-662-44006-3_17] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Abstract
Gastric cancer remains highly prevalent and accounts for a notable proportion of global cancer mortality. This cancer is also associated with poor survival rates. Understanding the genetic basis of gastric cancer will offer insights into its pathogenesis, help identify new biomarkers and novel treatment targets, aid prognostication and could be central to developing individualized treatment strategies in the future. An inherited component contributes to <3% of gastric cancers; the majority of genetic changes associated with gastric cancer are acquired. Over the past few decades, advances in technology and high-throughput analysis have improved understanding of the molecular aspects of the pathogenesis of gastric cancer. These aspects are multifaceted and heterogeneous and represent a wide spectrum of several key genetic influences, such as chromosomal instability, microsatellite instability, changes in microRNA profile, somatic gene mutations or functional single nucleotide polymorphisms. These genetic aspects of the pathogenesis of gastric cancer will be addressed in this Review.
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Affiliation(s)
- Mairi H McLean
- National Cancer Institute, Laboratory of Molecular Immunoregulation, Cancer &Inflammation Program, 1050 Boyles Street, Frederick, MD 21702-1201, USA
| | - Emad M El-Omar
- Division of Applied Medicine, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB51 5ER, UK
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