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Lv XH, Lu Q, Liu JH, Xia BH, Wang ZJ, Wang Z, Yang JL. Proportion and Characteristics of Helicobacter Pylori -Negative Gastric Mucosa-Associated Lymphoid Tissue Lymphoma: A Systematic Review and Meta-Analysis. Clin Transl Gastroenterol 2025; 16:e00781. [PMID: 39450888 PMCID: PMC12020693 DOI: 10.14309/ctg.0000000000000781] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Accepted: 10/14/2024] [Indexed: 10/26/2024] Open
Abstract
INTRODUCTION While Helicobacter pylori ( H . pylori ) infection is common in patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma, there are still individuals who test negative for it. The proportion and characteristics of these patients remain unclear. METHODS We conducted a systematic search of the PubMed, Embase, and Cochrane Library databases for relevant articles. Using a random-effects model, we performed a meta-analysis to assess the pooled proportion of gastric MALT lymphoma patients with negative H. pylori tests. In addition, we compared characteristics between gastric MALT lymphoma patients with and without H. pylori infection to examine clinical features in H. pylori -negative cases. RESULTS A total of 50 studies involving 6,033 patients were included. The overall proportion of gastric MALT lymphoma patients with negative H. pylori tests was 20.5% (95% confidence interval: 17.0%-24.6%). This rate exhibited an increasing trend over the years, particularly in non-Asian countries and in studies published after 2013, as well as in cases with sample sizes exceeding 100 patients, in male individuals, and among those with proximal or multiple lesions, nonsuperficial type morphology, submucosal invasion, and advanced clinical staging. Compared with H. pylori -positive patients, those who tested negative were more likely to be male, have proximal lesions, exhibit submucosal invasion, and present with an advanced clinical stage. DISCUSSION This study provides comprehensive information on the proportion and characteristics of H. pylori -negative gastric MALT lymphoma cases, highlighting the need for future clinical attention to treatment and surveillance in this patient population.
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Affiliation(s)
- Xiu-He Lv
- Department of Gastroenterology and Hepatology, West China Hospital of Sichuan University, Chengdu, Sichuan, China
- Department of Gastroenterology and Hepatology, Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Qing Lu
- Department of Gastroenterology and Hepatology, West China Hospital of Sichuan University, Chengdu, Sichuan, China
- Department of Gastroenterology and Hepatology, Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Jia-Huan Liu
- Department of Gastroenterology and Hepatology, West China Hospital of Sichuan University, Chengdu, Sichuan, China
- Department of Gastroenterology and Hepatology, Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Bi-Han Xia
- Department of Gastroenterology and Hepatology, West China Hospital of Sichuan University, Chengdu, Sichuan, China
- Department of Gastroenterology and Hepatology, Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Zi-Jing Wang
- Department of Gastroenterology and Hepatology, West China Hospital of Sichuan University, Chengdu, Sichuan, China
- Department of Gastroenterology and Hepatology, Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Zhu Wang
- Department of Gastroenterology and Hepatology, West China Hospital of Sichuan University, Chengdu, Sichuan, China
- Department of Gastroenterology and Hepatology, Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Jin-Lin Yang
- Department of Gastroenterology and Hepatology, West China Hospital of Sichuan University, Chengdu, Sichuan, China
- Department of Gastroenterology and Hepatology, Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, West China Hospital of Sichuan University, Chengdu, Sichuan, China
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D’Agostino F, Pinatel E, Meynhardt A, Scarlato V, Vannini A, Roncarati D. RNase Y mediates posttranscriptional control of the virulence-associated CncR1 small-RNA in Helicobacter pylori. iScience 2025; 28:111815. [PMID: 39949958 PMCID: PMC11821409 DOI: 10.1016/j.isci.2025.111815] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Revised: 11/15/2024] [Accepted: 01/10/2025] [Indexed: 02/16/2025] Open
Abstract
Ribonucleases are involved in several biological processes, including the turnover of structural and messenger RNAs and the specific processing of the cellular transcriptome. Here, we characterized the RNase Y from Helicobacter pylori. We found that RNase Y is membrane-associated and its expression is controlled during bacterial growth and by Fur in response to iron. We observed that RNase Y deletion has a limited impact on H. pylori transcriptome and on bacterial growth. Interestingly, we found that RNase Y is involved in the metabolism of CncR1, a virulence-associated sRNA oppositely modulating bacterial motility and adhesion to host cells. Indeed, RNase Y inactivation led to the accumulation of a 3'-extended CncR1 isoform, which appeared unable to interact in vitro with a known target mRNA. The observation that the RNAse Y-mutant strain showed deregulation of several members of the CncR1 regulon suggests this ribonuclease has an important role in H. pylori posttranscriptional regulation.
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Affiliation(s)
- Federico D’Agostino
- Department of Pharmacy and Biotechnology, Alma Mater Studiorum – University of Bologna, Bologna, Italy
| | - Eva Pinatel
- Institute of Biomedical Technologies - National Research Council, Segrate, Italy
| | - Alexandra Meynhardt
- Department of Pharmacy and Biotechnology, Alma Mater Studiorum – University of Bologna, Bologna, Italy
| | - Vincenzo Scarlato
- Department of Pharmacy and Biotechnology, Alma Mater Studiorum – University of Bologna, Bologna, Italy
| | - Andrea Vannini
- Department of Pharmacy and Biotechnology, Alma Mater Studiorum – University of Bologna, Bologna, Italy
| | - Davide Roncarati
- Department of Pharmacy and Biotechnology, Alma Mater Studiorum – University of Bologna, Bologna, Italy
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Properzi S, Stracci F, Rosi M, Lupi C, Villarini A, Gili A. Can a diet rich in Brassicaceae help control Helicobacter pylori infection? A systematic review. Front Med (Lausanne) 2024; 11:1454902. [PMID: 39741515 PMCID: PMC11685009 DOI: 10.3389/fmed.2024.1454902] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Accepted: 11/11/2024] [Indexed: 01/03/2025] Open
Abstract
Introduction Helicobacter pylori (Hp) infection is highly prevalent globally and poses a significant public health challenge due to its link with chronic gastritis, peptic ulcers, and gastric malignancies. Hp's persistence within the gastric environment, particularly in case of infection with virulent strains, triggers chronic inflammatory responses and mucosal damage. Antibiotic therapy is the primary approach for Hp eradication, but antibiotic resistance and adverse effects hinder treatment efficacy. Emerging evidence suggests that Brassicaceae-derived metabolites could serve as adjunctive therapy for Hp infection, offering potential antimicrobial and anti-inflammatory benefits. Methods A systematic literature review was conducted following PRISMA guidelines to assess the impact of Brassicaceae-rich diets on Hp infection control. Searches were performed in MEDLINE PubMed, Web of Science, and the Cochrane Library until 18 October 2023, without language or date restrictions. Eligible studies meeting PICOS criteria were included, encompassing populations infected with Hp or Hp-infected human cell cultures, interventions involving Brassicaceae consumption or its bioactive molecules, and outcomes related to Hp infection control, antibiotic therapy interactions, reduction of antibiotic side effects, and inflammation mitigation. Animal studies, cell line experiments, reviews unrelated to the research objectives, and studies on Hp-related gastric cancer were excluded. Results Available evidence indicates that Brassicaceae consumption exhibits the potential to reduce Hp colonization but achieving complete eradication of the pathogen remains challenging. Conflicting results regarding the efficacy of broccoli in Hp treatment emerge, with certain investigations suggesting limited effectiveness. Other studies point to a potential for heightened eradication rates when combined with standard triple therapy. Furthermore, promising outcomes are observed with broccoli extract supplements, indicating their role in mitigating Hp-induced gastric mucosal damage. In fact, it is noteworthy that sulforaphane and its derivatives manifest notable reductions in pro-inflammatory markers, indicative of their anti-inflammatory properties. Adverse events associated with antibiotic therapy seem unaffected by sulforaphane derivatives or probiotics. However, individual responses to these treatments vary, underscoring the unpredictability of their efficacy in ameliorating antibiotic therapy-related side effects. Conclusion Our systematic review highlights the potential of Brassicaceae-rich diets as adjunctive therapy for Hp infection, offering synergistic interactions with antibiotics and possibly mitigating antibiotic side effects and inflammation. Further research, particularly well-designed randomized trials, is warranted to elucidate the therapeutic efficacy and optimal utilization of Brassicaceae-derived metabolites in managing human Hp-related diseases.
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Affiliation(s)
- Sara Properzi
- Department of Medicine and Surgery, University of Perugia, Perugia, Umbria, Italy
| | - Fabrizio Stracci
- Department of Medicine and Surgery, University of Perugia, Perugia, Umbria, Italy
| | - Margherita Rosi
- Department of Medicine and Surgery, University of Perugia, Perugia, Umbria, Italy
| | - Chiara Lupi
- Department of Medicine and Surgery, University of Perugia, Perugia, Umbria, Italy
| | - Anna Villarini
- Department of Medicine and Surgery, University of Perugia, Perugia, Umbria, Italy
| | - Alessio Gili
- Department of Life Sciences, Health and Health Professions, Link Campus University, Rome, Italy
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Tsai HJ, Yeh KH, Lin CW, Wu MS, Liou JM, Hsu PN, Zeng YS, Wei MF, Shun CT, Wang HP, Chen LT, Cheng AL, Kuo SH. Cooperative participation of CagA and NFATc1 in the pathogenesis of antibiotics-responsive gastric MALT lymphoma. Cancer Cell Int 2024; 24:383. [PMID: 39558403 PMCID: PMC11575159 DOI: 10.1186/s12935-024-03552-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Accepted: 11/01/2024] [Indexed: 11/20/2024] Open
Abstract
BACKGROUND This study aimed to explore whether cytotoxin-associated gene A (CagA) can inhibit cell cycle progression by activating nuclear factor of activated T cells (NFAT) in lymphoma B cells and contribute to Helicobacter pylori eradication (HPE) responsiveness (complete remission [CR] after HPE) in gastric mucosa-associated lymphoid tissue (MALT) lymphoma. MATERIALS AND METHODS We co-cultured three B-lymphoma cell lines (MA-1, OCI-Ly3, and OCI-Ly7) with HP strains (derived from HPE-responsive gastric MALT lymphoma) and evaluated the expression patterns of CagA, phosphorylated (p)-CagA (CagAP-Tyr), and CagA-signaling molecules, cell-cycle inhibitors, p-NFATc1 (Ser172), and NFATc1 using western blotting. Furthermore, we evaluated the association between nuclear NFATc1 expression in the tumor cells of 91 patients who received first-line HPE (59 patients with HPE responsiveness and 32 without HPE responsiveness) and HPE responsiveness and CagA expression in tumor cells. RESULTS In HP strains co-cultured with B cell lymphoma cell lines, CagA was translocated to the nucleus through tyrosine phosphorylation (CagAP-Tyr) and simultaneously dephosphorylated NFATc1, subsequently causing nuclear NFATc1 translocation and stimulating the expression of p-SHP-2/p-ERK/Bcl-xL. Activated NFATc1 causes G1 cell cycle retardation in both MA-1 and OCI-Ly3 cells by triggering p21 and p27 production. Nuclear NFATc1 localization was significantly associated with the presence of CagA in gastric MALT lymphomas (80% [41/51] vs. 33% [13/40]; p < 0.001) and with HPE responsiveness (73% [43/59] vs. 25% [8/32]; p < 0.001). Patients exhibiting both the presence of CagA and nuclear NFATc1 localization responded more rapidly to HPE than those without (median interval to CR, 4.00 vs. 6.00 months, p = 0.003). CONCLUSIONS Our findings indicated that CagA and NFATc1 cooperatively participate in the lymphomagenesis of HPE-responsive gastric MALT lymphoma.
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Affiliation(s)
- Hui-Jen Tsai
- National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Oncology, National Cheng-Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Kun-Huei Yeh
- Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, No. 7, Chung-Shan South Rd, Taipei, Taiwan
- Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan
- Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Chung-Wu Lin
- Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Pathology and Laboratory Medicine, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan
| | - Ming-Shiang Wu
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Jyh-Ming Liou
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University Cancer Center, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Ping-Ning Hsu
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Yi-Shin Zeng
- Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, No. 7, Chung-Shan South Rd, Taipei, Taiwan
- Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Ming-Feng Wei
- Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, No. 7, Chung-Shan South Rd, Taipei, Taiwan
- Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Chia-Tung Shun
- Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Hsiu-Po Wang
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Li-Tzong Chen
- National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Oncology, National Cheng-Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Ann-Lii Cheng
- Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, No. 7, Chung-Shan South Rd, Taipei, Taiwan
- Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan
- Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Medical Oncology, National Taiwan University Cancer Center, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Sung-Hsin Kuo
- Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, No. 7, Chung-Shan South Rd, Taipei, Taiwan.
- Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan.
- Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan.
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Malik K, Kodgire P. Insights into the molecular mechanisms of H. pylori-associated B-cell lymphoma. Crit Rev Microbiol 2024; 50:879-895. [PMID: 38288575 DOI: 10.1080/1040841x.2024.2305439] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2023] [Revised: 12/13/2023] [Accepted: 01/06/2024] [Indexed: 10/09/2024]
Abstract
Cancer research has extensively explored various factors contributing to cancer development, including chemicals, drugs, smoking, and obesity. However, the role of bacterial infections in cancer induction remains underexplored. In particular, the mechanisms underlying H. pylori-induced B-cell lymphoma, a potential consequence of bacterial infection, have received little attention. In recent years, there has been speculation about contagious agents causing persistent inflammation and encouraging B-lymphocyte transition along with lymphomagenesis. MALT lymphoma associated with chronic H. pylori infection, apart from two other central associated lymphomas - Burkitt's Lymphoma and DLBCL, is well studied. Owing to the increasing colonization of H. pylori in the host gut and its possible action in the development of B-cell lymphoma, this review aims to summarize the existing reports on different B-cell lymphomas' probable association with H. pylori infections; also emphasizing the function of the organism in lymphomagenesis; including its interaction with the host, pathogen and host-specific factors, and tumor microenvironment.
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Affiliation(s)
- Kritika Malik
- Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, India
| | - Prashant Kodgire
- Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, India
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Martí-Obiol R, Martí-Fernández R, Fernández-Moreno MC, Barrios-Carvajal ME, López-Mozos F. Characteristics of gastrointestinal stromal tumors associated to other tumors: Características de los tumores del estroma gastrointestinal asociados a otras neoplasias. Cir Esp 2024; 102:135-141. [PMID: 38135151 DOI: 10.1016/j.cireng.2023.11.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Accepted: 11/02/2023] [Indexed: 12/24/2023]
Abstract
INTRODUCTION Our aim is to analyze the differences between sporadic gastrointestinal stromal tumors and those associated with other tumors. METHODS Retrospective cohort study including patients with diagnosis of gastrointestinal stromal tumors operated at our center. Patients were divided into two groups, according to whether or not they had associated other tumors, both synchronously and metachronously. Disease free survival and overall survival were calculated for both groups. RESULTS 96 patients were included, 60 (62.5%) were male, with a median age of 66.8 (35-84). An association with other tumors was found in 33 cases (34.3%); 12 were synchronous (36.3%) and 21 metachronous (63.7%). The presence of mutations in associated tumors was 70% and in non-associated tumors 75%. Associated tumors were classified as low risk tumors based on Fletcher's stratification scale (p = 0.001) as they usually were smaller in size and had less than ≤5 mitosis per 50 HPF compared to non-associated tumors. When analyzing overall survival, there were statistically significant differences (p = 0,035) between both groups. CONCLUSION The relatively high proportion of gastrointestinal stromal tumors cases with associated tumors suggests the need to carry out a study to rule out presence of a second neoplasm and a long-term follow-up should be carried out in order to diagnose a possible second neoplasm. Gastrointestinal stromal tumors associated with other tumors have usually low risk of recurrence with a good long-term prognosis.
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Affiliation(s)
- Roberto Martí-Obiol
- Upper Gastrointestinal Surgery Unit, Hospital Clínico Universitario, Valencia, Spain
| | - Rosa Martí-Fernández
- Upper Gastrointestinal Surgery Unit, Hospital Clínico Universitario, Valencia, Spain.
| | | | | | - Fernando López-Mozos
- Upper Gastrointestinal Surgery Unit, Hospital Clínico Universitario, Valencia, Spain; Department of Surgery, Universidad de Valencia, Valencia, Spain
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Nekooghadam SM, Ghadirzadeh E, Lapevandani MM, Ghorbani P, Yazdi YG, Shafiei S, Rakhshan A, Paraandavaji E, Charkazi E. Waldenström's macroglobulinemia with necrotic extremities: A case with challenging diagnosis. Clin Case Rep 2023; 11:e7809. [PMID: 37663818 PMCID: PMC10474312 DOI: 10.1002/ccr3.7809] [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: 04/10/2023] [Revised: 05/31/2023] [Accepted: 06/29/2023] [Indexed: 09/05/2023] Open
Abstract
Key Clinical Message Waldenström's macroglobulinemia may begin with constitutional symptoms that are common in primary care settings and it is crucial for physicians to be aware of the potential complications of hyperviscosity syndrome and to employ the appropriate diagnostic methods in order to achieve better outcomes. Abstract Waldenström's macroglobulinemia (WM) refers to a type of lymphoplasmacytic lymphoma distinguished by the hyperproliferation of plasma cells, lymphocytes, and plasmacytoid lymphocytes. The disease is primarily diagnosed by increased monoclonal immunoglobulin M (IgM) levels and lymphoplasmacytic cell infiltration into the bone marrow. Individuals exhibit a high risk for hyperviscosity syndrome (HVS) as immunoglobulin levels increase. In addition to constitutional symptoms (fever, night sweats, and unintentional weight loss), clinical findings such as cytopenia, hepatosplenomegaly, and lymphadenopathy, this condition may cause hyperviscosity-related organ failures. Here we discuss a patient with WM who presented with neurological complaints and blurry vision and developed necrosis at distal portions of his body during the 6-month course of the disease.
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Affiliation(s)
- Seyyed Mojtaba Nekooghadam
- Department of Internal Medicine, School of MedicineShahid Beheshti University of Medical SciencesTehranIran
| | - Erfan Ghadirzadeh
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver DiseasesShahid Beheshti University of Medical SciencesTehranIran
- Cardiovascular Research CenterMazandaran University of Medical SciencesSariIran
| | | | - Parastoo Ghorbani
- Cardiovascular Research CenterMazandaran University of Medical SciencesSariIran
| | | | - Sasan Shafiei
- Department of Internal Medicine, School of MedicineShahid Beheshti University of Medical SciencesTehranIran
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver DiseasesShahid Beheshti University of Medical SciencesTehranIran
| | - Azadeh Rakhshan
- Department of Pathology, School of MedicineShahid Beheshti University of Medical SciencesTehranIran
| | - Elham Paraandavaji
- Skull Base Research Center, Loghman Hakim HospitalShahid Beheshti University of Medical SciencesTehranIran
| | - Elham Charkazi
- Medical DoctorSemnan University of Medical SciencesSemnanIran
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Lemos FFB, Silva Luz M, Rocha Pinheiro SL, Teixeira KN, Freire de Melo F. Role of non- Helicobacter pylori gastric Helicobacters in helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma. World J Gastroenterol 2023; 29:4851-4859. [PMID: 37701138 PMCID: PMC10494762 DOI: 10.3748/wjg.v29.i32.4851] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2023] [Revised: 07/18/2023] [Accepted: 08/02/2023] [Indexed: 08/25/2023] Open
Abstract
Marginal zone lymphomas rank as the third most prevalent form of non-Hodgkin B-cell lymphoma, trailing behind diffuse large B-cell lymphoma and follicular lymphoma. Gastric mucosa-associated lymphoid tissue lymphoma (GML) is a low-grade B-cell neoplasia frequently correlated with Helicobacter pylori (H. pylori)-induced chronic gastritis. On the other hand, a specific subset of individuals diagnosed with GML does not exhibit H. pylori infection. In contrast to its H. pylori-positive counterpart, it was previously believed that H. pylori-negative GML was less likely to respond to antimicrobial therapy. Despite this, surprisingly, in-creasing evidence supports that a considerable proportion of patients with H. pylori-negative GML show complete histopathological remission after bacterial eradication therapy. Nonetheless, the precise mechanisms underlying this treatment responsiveness are not yet fully comprehended. In recent years, there has been growing interest in investigating the role of non-H. pylori gastric helicobacters (NHPHs) in the pathogenesis of H. pylori-negative GML. However, additional research is required to establish the causal relationship between NHPHs and GML. In this minireview, we examined the current understanding and proposed prospects on the involvement of NHPHs in H. pylori-negative GML, as well as their potential response to bacterial eradication therapy.
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Affiliation(s)
- Fabian Fellipe Bueno Lemos
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029094, Brazil
| | - Marcel Silva Luz
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029094, Brazil
| | - Samuel Luca Rocha Pinheiro
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029094, Brazil
| | | | - Fabrício Freire de Melo
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029094, Brazil
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Vlasac IM, Christensen BC, Salas LA. Normal gastric tissue Helicobacter pylori infection is associated with epigenetic age acceleration, increased mitotic tick rate, tissue cell composition, and Natural Killer cell methylation alterations. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.06.28.546926. [PMID: 37425894 PMCID: PMC10327075 DOI: 10.1101/2023.06.28.546926] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/11/2023]
Abstract
Background Gastric adenocarcinomas are a leading cause of global mortality, associated with chronic infection with Helicobacter pylori. The mechanisms by which infection with H. pylori contributes to carcinogenesis are not well understood. Recent studies from subjects with and without gastric cancer have identified significant DNA methylation alterations in normal gastric mucosa associated with H. pylori infection and gastric cancer risk. Here we further investigated DNA methylation alterations in normal gastric mucosa in gastric cancer cases (n = 42) and control subjects (n = 42) with H. pylori infection data. We assessed tissue cell type composition, DNA methylation alterations within cell populations, epigenetic aging, and repetitive element methylation. Results In normal gastric mucosa of both gastric cancer cases and control subjects, we observed increased epigenetic age acceleration associated with H. pylori infection. We also observed an increased mitotic tick rate associated with H. pylori infection in both gastric cancer cases and controls. Significant differences in immune cell populations associated with H. pylori infection in normal tissue from cancer cases and controls were identified using DNA methylation cell type deconvolution. We also found natural killer cell-specific methylation alterations in normal mucosa from gastric cancer patients with H. pylori infection. Conclusions Our findings from normal gastric mucosa provide insight into underlying cellular composition and epigenetic aspects of H. pylori associated gastric cancer etiology.
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Affiliation(s)
- Irma M. Vlasac
- Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA
| | - Brock C. Christensen
- Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA
- Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA
| | - Lucas A. Salas
- Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA
- Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA
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10
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Malfertheiner P, Camargo MC, El-Omar E, Liou JM, Peek R, Schulz C, Smith SI, Suerbaum S. Helicobacter pylori infection. Nat Rev Dis Primers 2023; 9:19. [PMID: 37081005 PMCID: PMC11558793 DOI: 10.1038/s41572-023-00431-8] [Citation(s) in RCA: 348] [Impact Index Per Article: 174.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/17/2023] [Indexed: 04/22/2023]
Abstract
Helicobacter pylori infection causes chronic gastritis, which can progress to severe gastroduodenal pathologies, including peptic ulcer, gastric cancer and gastric mucosa-associated lymphoid tissue lymphoma. H. pylori is usually transmitted in childhood and persists for life if untreated. The infection affects around half of the population in the world but prevalence varies according to location and sanitation standards. H. pylori has unique properties to colonize gastric epithelium in an acidic environment. The pathophysiology of H. pylori infection is dependent on complex bacterial virulence mechanisms and their interaction with the host immune system and environmental factors, resulting in distinct gastritis phenotypes that determine possible progression to different gastroduodenal pathologies. The causative role of H. pylori infection in gastric cancer development presents the opportunity for preventive screen-and-treat strategies. Invasive, endoscopy-based and non-invasive methods, including breath, stool and serological tests, are used in the diagnosis of H. pylori infection. Their use depends on the specific individual patient history and local availability. H. pylori treatment consists of a strong acid suppressant in various combinations with antibiotics and/or bismuth. The dramatic increase in resistance to key antibiotics used in H. pylori eradication demands antibiotic susceptibility testing, surveillance of resistance and antibiotic stewardship.
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Affiliation(s)
- Peter Malfertheiner
- Medical Department II, University Hospital, Ludwig-Maximilians-Universität, Munich, Germany.
- Medical Department Klinik of Gastroenterology, Hepatology and Infectiology, Otto-von-Guericke Universität, Magdeburg, Germany.
| | - M Constanza Camargo
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
| | - Emad El-Omar
- Microbiome Research Centre, St George & Sutherland Clinical Campuses, School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Sydney, New South Wales, Australia
| | - Jyh-Ming Liou
- Department of Internal Medicine, National Taiwan University Cancer Center, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Richard Peek
- Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Christian Schulz
- Medical Department II, University Hospital, Ludwig-Maximilians-Universität, Munich, Germany
- DZIF Deutsches Zentrum für Infektionsforschung, Partner Site Munich, Munich, Germany
| | - Stella I Smith
- Department of Molecular Biology and Biotechnology, Nigerian Institute of Medical Research, Yaba, Lagos, Nigeria
| | - Sebastian Suerbaum
- DZIF Deutsches Zentrum für Infektionsforschung, Partner Site Munich, Munich, Germany
- Max von Pettenkofer Institute, Faculty of Medicine, Ludwig-Maximilians-Universität, Munich, Germany
- National Reference Center for Helicobacter pylori, Munich, Germany
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11
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Zhao B, Wu J, Cha X, Mao G, Shi H, Fei S, Miao B. Effect of COP1 in Promoting the Tumorigenesis of Gastric Cancer by Down-Regulation of CDH18 via PI3K/AKT Signal Pathway. Anal Cell Pathol (Amst) 2023; 2023:5617875. [PMID: 37025097 PMCID: PMC10072965 DOI: 10.1155/2023/5617875] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 02/21/2023] [Accepted: 03/10/2023] [Indexed: 03/30/2023] Open
Abstract
In recent years, the involvement of E3 ubiquitin ligase constitutive photomorphogenesis 1 (COP1) in the tumorigenesis of gastric cancer (GC) has been elucidated. However, the exact underlying mechanism remains to be clarified. In the present study, the expression profiles of COP1 in GC were derived from the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) databases, followed by verification via immunohistochemical staining (IHC), Western blotting (WB), and quantitative real-time polymerase chain reaction (qRT-PCR) reaction assays on clinical samples. In vitro, the gain- and loss-of-function experiments of COP1 protein were conducted to explore its role in GC cell lines HGC-27 and SGC-7901. Furthermore, we screened the interaction protein of COP1 by yeast two-hybrid experiment and verified their combination by co-immunoprecipitation (co-IP). We preliminary explored the possible underlying mechanisms of COP1 protein in GC cell lines via WB. COP1 was upregulated in GC tissues compared with the corresponding non-carcinoma tissues. In vitro, the upregulation of COP1 protein promoted the proliferation and migration of GC cells. The yeast two-hybrid experiment and co-IP indicated that Cadherin 18 (CDH18) could constitute a complex with COP1. Moreover, cells with COP1 over-expression showed low levels of CDH18 expression, with the intracellular PI3K/AKT pathway activated and the malignancy of GC cell lines enhanced. Our findings demonstrated that COP1 promoted the GC tumorigenesis by downregulated CDH18 with the involvement of PI3K/AKT signaling pathway in cell lines, suggesting the potential of COP1 as a prognostic biomarker and therapeutic target for GC.
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12
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Prasad SK, Bhat S, Shashank D, C R A, R S, Rachtanapun P, Devegowda D, Santhekadur PK, Sommano SR. Bacteria-Mediated Oncogenesis and the Underlying Molecular Intricacies: What We Know So Far. Front Oncol 2022; 12:836004. [PMID: 35480118 PMCID: PMC9036991 DOI: 10.3389/fonc.2022.836004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Accepted: 02/22/2022] [Indexed: 01/10/2023] Open
Abstract
Cancers are known to have multifactorial etiology. Certain bacteria and viruses are proven carcinogens. Lately, there has been in-depth research investigating carcinogenic capabilities of some bacteria. Reports indicate that chronic inflammation and harmful bacterial metabolites to be strong promoters of neoplasticity. Helicobacter pylori-induced gastric adenocarcinoma is the best illustration of the chronic inflammation paradigm of oncogenesis. Chronic inflammation, which produces excessive reactive oxygen species (ROS) is hypothesized to cause cancerous cell proliferation. Other possible bacteria-dependent mechanisms and virulence factors have also been suspected of playing a vital role in the bacteria-induced-cancer(s). Numerous attempts have been made to explore and establish the possible relationship between the two. With the growing concerns on anti-microbial resistance and over-dependence of mankind on antibiotics to treat bacterial infections, it must be deemed critical to understand and identify carcinogenic bacteria, to establish their role in causing cancer.
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Affiliation(s)
- Shashanka K Prasad
- Department of Biotechnology and Bioinformatics, Faculty of Life Sciences, Jagadguru Sri Shivarathreeshwara (JSS) Academy of Higher Education and Research (JSSAHER), Mysuru, India
| | - Smitha Bhat
- Department of Biotechnology and Bioinformatics, Faculty of Life Sciences, Jagadguru Sri Shivarathreeshwara (JSS) Academy of Higher Education and Research (JSSAHER), Mysuru, India
| | - Dharini Shashank
- Department of General Surgery, Adichunchanagiri Institute of Medical Sciences, Mandya, India
| | - Akshatha C R
- Department of Medical Oncology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Sindhu R
- Department of Microbiology, Faculty of Life Sciences, Jagadguru Sri Shivarathreeshwara (JSS) Academy of Higher Education and Research (JSSAHER), Mysuru, India
| | - Pornchai Rachtanapun
- School of Agro-Industry, Faculty of Agro-Industry, Chiang Mai University, Chiang Mai, Thailand
- Cluster of Agro Bio-Circular-Green Industry (Agro BCG), Chiang Mai University, Chiang Mai, Thailand
| | - Devananda Devegowda
- Centre of Excellence in Molecular Biology and Regenerative Medicine (CEMR), Department of Biochemistry, JSS Medical College, JSS Academy of Higher Education and Research (JSSAHER), Mysuru, India
| | - Prasanna K Santhekadur
- Centre of Excellence in Molecular Biology and Regenerative Medicine (CEMR), Department of Biochemistry, JSS Medical College, JSS Academy of Higher Education and Research (JSSAHER), Mysuru, India
| | - Sarana Rose Sommano
- Cluster of Agro Bio-Circular-Green Industry (Agro BCG), Chiang Mai University, Chiang Mai, Thailand
- Department of Plant and Soil Sciences, Faculty of Agriculture, Chiang Mai University, Chiang Mai, Thailand
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13
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Kuo SH, Yeh KH, Lin CW, Liou JM, Wu MS, Chen LT, Cheng AL. Current Status of the Spectrum and Therapeutics of Helicobacter pylori-Negative Mucosa-Associated Lymphoid Tissue Lymphoma. Cancers (Basel) 2022; 14:1005. [PMID: 35205754 PMCID: PMC8869919 DOI: 10.3390/cancers14041005] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 02/12/2022] [Accepted: 02/14/2022] [Indexed: 12/12/2022] Open
Abstract
Helicobacter pylori (HP)-unrelated mucosa-associated lymphoid tissue (MALT) lymphoma includes the majority of extragastric MALT lymphomas and a small proportion of gastric MALT lymphomas. Although the role of first-line antibiotics in treating HP-negative gastric MALT lymphomas remains controversial, HP eradication therapy (HPE)-like regimens may result in approximately 20-30% complete remission (CR) for patients with localized HP-negative gastric MALT lymphoma. In these patients, H. heilmannii, H. bizzozeronii, and H. suis were detected in sporadic gastric biopsy specimens. Extragastric MALT lymphoma is conventionally treated with radiotherapy for localized disease and systemic chemotherapy for advanced and metastatic diseases. However, a proportion of extragastric MALT lymphomas, such as ocular adnexal lesions and small intestinal lesions, were reported to be controlled by antibiotics for Chlamydophila psittaci and Campylobacter jejuni, respectively. Some extragastric MALT lymphomas may even respond to first-line HPE. These findings suggest that some antibiotic-responsive tumors may exist in the family of HP-negative MALT lymphomas. Two mechanisms underlying the antibiotic responsiveness of HP-negative MALT lymphoma have been proposed. First, an HPE-like regimen may eradicate the antigens of unknown bacteria. Second, clarithromycin (the main component of HPE) may have direct or indirect antineoplastic effects, thus contributing to the CR of these tumors. For antibiotic-unresponsive HP-negative MALT lymphoma, high-dose macrolides and immunomodulatory drugs, such as thalidomide and lenalidomide, have reported sporadic success. Further investigation of new treatment regimens is warranted.
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Affiliation(s)
- Sung-Hsin Kuo
- Department of Oncology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei 100, Taiwan; (S.-H.K.); (K.-H.Y.)
- Cancer Research Center, National Taiwan University College of Medicine, Taipei 100, Taiwan
- Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei 100, Taiwan
| | - Kun-Huei Yeh
- Department of Oncology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei 100, Taiwan; (S.-H.K.); (K.-H.Y.)
- Cancer Research Center, National Taiwan University College of Medicine, Taipei 100, Taiwan
- Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei 100, Taiwan
| | - Chung-Wu Lin
- Department of Pathology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei 100, Taiwan;
| | - Jyh-Ming Liou
- Department of Internal Medicine, National Taiwan University Cancer Center, National Taiwan University College of Medicine, Taipei 106, Taiwan;
| | - Ming-Shiang Wu
- Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei 100, Taiwan;
| | - Li-Tzong Chen
- National Institute of Cancer Research, National Health Research Institutes, Tainan 704, Taiwan;
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Department of Internal Medicine, National Cheng-Kung University Hospital, Tainan 704, Taiwan
| | - Ann-Lii Cheng
- Department of Oncology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei 100, Taiwan; (S.-H.K.); (K.-H.Y.)
- Cancer Research Center, National Taiwan University College of Medicine, Taipei 100, Taiwan
- Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei 100, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei 100, Taiwan;
- Department of Oncology, National Taiwan University Cancer Center, National Taiwan University College of Medicine, Taipei 106, Taiwan
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Chung HU, Son JH. Ocular adnexal mucosa-associated lymphoid tissue lymphoma: a narrative review. JOURNAL OF YEUNGNAM MEDICAL SCIENCE 2022; 39:3-11. [PMID: 34521183 PMCID: PMC8895963 DOI: 10.12701/yujm.2021.01263] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Revised: 08/01/2021] [Accepted: 08/12/2021] [Indexed: 12/02/2022]
Abstract
Lymphoma is the most common primary tumor of the orbit, accounting for 55% of all orbital malignancies. When divided into histopathological subtypes, extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) comprises the largest proportion. Clinical manifestations are unspecific, but in patients with slow-growing painless orbital mass, or red conjunctival lesion suggestive of 'salmon patch', ocular adnexa lymphoma (OAL) should be suspected. Although the pathogenetic mechanism of ocular adnexal MALT lymphoma (OAML) is not yet fully understood, the relationship between OAML and Chlamydia psittaci has been hypothesized recently, similar to that between gastric MALT lymphoma and Helicobacter pylori. This suggests a new treatment option for OAML; bacterial eradication therapy with systemic antibiotics. Several other treatment methods for OAML have been introduced, but no treatment guidelines have been established yet. In this article, we summarize the current knowledge on the clinical features, pathogenesis, diagnostic methods, therapeutic strategies, and prognosis of OAML.
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Affiliation(s)
- Hyun Uk Chung
- Yeungnam Eye Center, Yeungnam University Hospital, Daegu, Korea
| | - Jun Hyuk Son
- Department of Ophthalmology, Yeungnam University College of Medicine, Daegu, Korea
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15
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Eagle ZR, Essien F, Zibert K, Miller C, Van Dellen M, Eden R, Pinson R. Helicobacter pylori-negative extra-nodal marginal zone B-cell lymphoma of Mucosa-Associated Lymphoid Tissue (MALT) type following Roux-en-Y Gastric Bypass (RYGB). Clin Case Rep 2022; 10:e05261. [PMID: 35106160 PMCID: PMC8784857 DOI: 10.1002/ccr3.5261] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Revised: 09/17/2021] [Accepted: 11/19/2021] [Indexed: 11/07/2022] Open
Abstract
Gastric MALT lymphoma is a common type of non-Hodgkin's lymphoma that has the potential for cure in patients found to have concomitant Helicobacter pylori (H. pylori) infection. This case report explores the evaluation, diagnosis, and treatment of H. pylori-negative MALT lymphoma in a patient with a history of a RYGB.
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Affiliation(s)
- Zachary R. Eagle
- Department of Internal MedicineKeesler Medical CenterKeesler Air Force BaseKeesler AFBMississippiUSA
| | - Francis Essien
- Department of Internal MedicineKeesler Medical CenterKeesler Air Force BaseKeesler AFBMississippiUSA
| | - Kimberly Zibert
- Division of GastroenterologyDepartment of Internal MedicineSan Antonio Medical CenterSan AntonioTexasUSA
| | - Charles Miller
- Division of GastroenterologyDepartment of Internal MedicineSan Antonio Medical CenterSan AntonioTexasUSA
| | - Melissa Van Dellen
- Division of PathologyDepartment of Internal MedicineKeesler Medical CenterKeesler Air Force BaseKeesler AFBMississippiUSA
| | - Rina Eden
- Division of PathologyDepartment of Internal MedicineKeesler Medical CenterKeesler Air Force BaseKeesler AFBMississippiUSA
| | - Ross Pinson
- Department of Internal MedicineKeesler Medical CenterKeesler Air Force BaseKeesler AFBMississippiUSA
- Division of GastroenterologyDepartment of Internal MedicineKeesler Medical CenterKeesler Air Force BaseKeesler AFBMississippiUSA
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16
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Kim JS, Park JC, Lee JY, Ahn JY, Kang SH, Yang HJ, Kim SJ, Joo MK, Park JM. Long-Term Clinical Outcomes of Gastric MALT Lymphoma: A Nationwide Multicenter Study in Korea. Front Oncol 2021; 11:681689. [PMID: 34722238 PMCID: PMC8551628 DOI: 10.3389/fonc.2021.681689] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Accepted: 09/28/2021] [Indexed: 12/14/2022] Open
Abstract
Background Treatment recommendations for gastric mucosa-associated lymphoid tissue (MALT) lymphoma are based on case series and expert opinions. Only a few previous studies have focused on the long-term outcomes of gastric MALT lymphoma, especially according to stage. Methods Patients diagnosed with gastric MALT lymphoma from January 2000 to December 2018 at nine university hospitals in Korea were included. Clinical data of medical history, endoscopic features, histological diagnosis, results of Helicobacter pylori (H. pylori) testing, stage, treatment conditions, and outcomes were collected. Results A total of 1,163 patients was enrolled, and 97.6% (n=1,038) of patients were diagnosed as stage IE. 10-year overall survival (OS) for the entire population was 99.1% and was better for patients in stage IE compared with patients in stage III/IV (p=0.002). The 10-year OS for H. pylori-positive patients was better than that of H. pylori-negative patients (p=0.022). Multivariate analyses revealed initial stage III/IV as a prognostic factor associated with over-all survival. Conclusion The majority of gastric MALT lymphoma patients are diagnosed at an early localized stage in Korea. The overall survival rate of gastric MALT lymphoma is excellent and is associated with the initial stage of the disease.
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Affiliation(s)
- Joon Sung Kim
- Division of Gastroenterology, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Jun Chul Park
- Division of Gastroenterology, Yonsei University College of Medicine, Severance Hospital, Seoul, South Korea
| | - Jong Yeul Lee
- Center for Gastric Cancer, National Cancer Center, Goyang, South Korea
| | - Ji Yong Ahn
- Division of Gastroenterology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Sun Hyung Kang
- Division of Gastroenterology, Department of Internal Medicine, Chungnam National University School of Medicine, Dajeon, South Korea
| | - Hyo-Joon Yang
- Division of Gastroenterology, Department of Internal Medicine and Gastrointestinal Cancer Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Su Jin Kim
- Division of Gastroenterology, Department of Internal Medicine, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, South Korea
| | - Moon Kyung Joo
- Division of Gastroenterology, Department of Internal Medicine, Korea University Guro Hospital, Korea University, College of Medicine, Seoul, South Korea
| | - Jae Myung Park
- Division of Gastroenterology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
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17
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Xiao D, Zou Q, Meng L, Xu Y, Zhang H, Meng F, He L, Zhang J. Glycopeptidomics Analysis of a Cell Line Model Revealing Pathogenesis and Potential Marker Molecules for the Early Diagnosis of Gastric MALT Lymphoma. Front Cell Infect Microbiol 2021; 11:715454. [PMID: 34476221 PMCID: PMC8407071 DOI: 10.3389/fcimb.2021.715454] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Accepted: 07/26/2021] [Indexed: 01/17/2023] Open
Abstract
Background & Aims Gastric mucosa-associated lymphoma (GML) is a mature B cell tumor related to Helicobacter pylori (H.pylori) infection. The clinical manifestations of GML are not specific, so GML is often misdiagnosed, leading to excessive treatment. The pathogenesis of H.pylori-induced GML is not well understood and there are no molecular markers for early GML diagnosis. Methods Glycopeptidomics analyses of host cell lines (a BCG823 cell line, C823) and C823 cells infected by H. pylori isolated from patients with GML (GMALT823), gastritis (GAT823), gastric ulcer (GAU823) and gastric cancer (GAC823) were carried out to clarify the host reaction mechanism against GML and to identify potential molecular criteria for the early diagnosis of GML. Results Thirty-three samples were analyzed and approximately 2000 proteins, 200 glycoproteins and 500 glycopeptides were detected in each sample. O-glycans were the dominant glycoforms in GMALT823 cells only. Four specific glycoforms in GMALT823 cells and 2 specific glycoforms in C823 and GMALT823 cells were identified. Eight specific glycopeptides from 7 glycoproteins were found in GMALT823 cells; of these glycopeptides, 6 and 3 specific glycopeptides had high affinity for T cell epitopes and have conformational B cell epitopes, respectively. Conclusion The predominant glycoforms of host cells infected by MALT H. pylori isolates differ from others, and the glycoproteins, glycosylation sites and glycoforms might be closely related to the formation of GML, which provides new insights into the pathogenic mechanisms of H. pylori infection and suggests molecular indicators for the early diagnosis of GML.
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Affiliation(s)
- Di Xiao
- State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Qinghua Zou
- Department of Microbiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Le Meng
- Center for Biomedical Mass Spectrometry, Department of Biochemistry, Boston University, Boston, MA, United States
| | - Yanli Xu
- Hebei University of Engineering, Affiliated Hospital, College of Medicine, Handan, China
| | - Huifang Zhang
- State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Fanliang Meng
- State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Lihua He
- State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Jianzhong Zhang
- State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
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18
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Saifi O, Lester SC, Rule W, Stish BJ, Stafford S, Pafundi DH, Jiang L, Menke D, Moustafa MA, Rosenthal A, Sher T, Ernesto A, Tun HW, Hoppe BS, Peterson JL. Comparable Efficacy of Reduced Dose Radiation Therapy for the Treatment of Early Stage Gastric Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue. Adv Radiat Oncol 2021; 6:100714. [PMID: 34409210 PMCID: PMC8361052 DOI: 10.1016/j.adro.2021.100714] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 04/05/2021] [Accepted: 04/19/2021] [Indexed: 12/15/2022] Open
Abstract
Purpose This study compares reduced (<27 Gy) to standard dose (≥30 Gy) radiation therapy (RT) in the treatment of gastric extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (gMALT lymphoma). Methods and Materials Forty-two patients with stage I or II disease were retrospectively reviewed. Response to RT was assessed with endoscopy after RT. Complete response rate (CR), freedom from treatment failure, and overall survival (OS) were calculated. Results All patients were stage I (n = 40) or II (n = 2). All patients had residual biopsy proven gMALT lymphoma before RT. Twenty-six patients (61.9%) were treated with standard dose RT, 30 to 36 Gy, and 16 (38.1%) with the reduced dose RT, 23.5 to 27 Gy. The median follow-up was 29.5 months (range, 6-85). Thirty-six patients (86%) achieved complete response (CR), and 6 patients (14%) achieved partial response (PR). The complete response rate (CR) at the first endoscopic assessment, median time of 3 months, was 81% (95% confidence interval, 0.61%-0.93%) for standard RT, and 94% (confidence interval, 0.69%-0.99%) for reduced RT. Among CR patients, one patient had locally relapsed disease at 50 months. The 1-year overall survival (OS) was 100% in both groups. The 1-year freedom from treatment failure (FFTF) was 100% in the reduced RT group and 92% in the standard RT group. The 2-year FFTF and OS of the whole cohort were 92% and 96%, respectively. There was no significant difference in the OS, FFTF, and CR between the 2 treatment groups (P = .38, P = .18, and P = .267, respectively). For toxicity, the mean liver dose and the mean V20 heart dose were significantly lower in the reduced RT group (P <.001 and P = .001, respectively). However, incidence and severity of reported toxicities were similar between the 2 groups. Conclusions Reduced dose RT (23.5-27 Gy) achieved excellent complete response rates with minimal toxicity, comparable with standard dose RT (30-36 Gy), for gMALT.
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Affiliation(s)
- Omran Saifi
- Department of Radiation Oncology, Mayo Clinic, Jacksonville, Florida
| | - Scott C Lester
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota
| | - William Rule
- Department of Radiation Oncology, Mayo Clinic, Phoenix, Arizona
| | - Bradley J Stish
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota
| | - Scott Stafford
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota
| | - Deanna H Pafundi
- Department of Radiation Oncology, Mayo Clinic, Jacksonville, Florida
| | - Liuyan Jiang
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Florida
| | - David Menke
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Florida
| | | | | | - Taimur Sher
- Division of Hematology-Oncology, Mayo Clinic, Jacksonville, Florida
| | - Ayala Ernesto
- Division of Hematology-Oncology, Mayo Clinic, Jacksonville, Florida
| | - Han W Tun
- Division of Hematology-Oncology, Mayo Clinic, Jacksonville, Florida
| | - Bradford S Hoppe
- Department of Radiation Oncology, Mayo Clinic, Jacksonville, Florida
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Proteomic and transcriptomic studies of BGC823 cells stimulated with Helicobacter pylori isolates from gastric MALT lymphoma. PLoS One 2020; 15:e0238379. [PMID: 32915799 PMCID: PMC7485896 DOI: 10.1371/journal.pone.0238379] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2020] [Accepted: 08/15/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND The correlation between the infection of H. pylori and the occurrence of gastric MALT lymphoma (GML) has been well documented. However, the mechanism of how GML is caused by this bacterium is not well understood, although some immunologic mechanisms are thought to be involved. MATERIALS AND METHODS In this study, we performed both transcriptomic and proteomic analyses on gastric cancer cells infected by H. pylori isolates from GML patients and the gastric ulcer strain 26695 to investigate the differentially expressed molecular signatures that were induced by GML isolates. RESULTS Transcriptomic analyses revealed that the differentially expressed genes (DEGs) were mainly related to binding, catalytic activity, signal transducer activity, molecular transducer activity, nucleic acid binding transcription factor activity, and molecular function regulator. Fifteen pathways, including the Wnt signaling pathway, the mTOR signaling pathway, the NOD-like receptor signaling pathway and the Hippo signaling pathway, were revealed to be related to GML isolates. Proteomic analyses results showed that there were 116 differentially expressed proteins (DEPs). Most of these DEPs were associated with cancer, and 29 have been used as biomarkers for cancer diagnosis. We also found 63 upstream regulators that can inhibit or activate the expression of the DEPs. Combining the proteomic and transcriptomic analyses revealed 12 common pathways. This study provides novel insights into H. pylori-associated GML. The DEPs we found may be good candidates for GML diagnosis and treatment. CONCLUSIONS This study revealed specific pathways related to GML and potential biomarkers for GML diagnosis.
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Tsai HJ, Tai JJ, Chen LT, Wu MS, Yeh KH, Lin CW, Wang TE, Wang HP, Yu FJ, Liou JM, Hsiao CF, Cheng TY, Yeh HJ, Ko CW, Chen MJ, Lo GH, Hsu PI, Chang CS, Hwang WS, Chuang SS, Lee HW, Shun CT, Chiu CF, Wang WM, Hsieh CY, Liu TW, Lin JT, Kuo SH, Cheng AL, for the Taiwan Cooperative Oncology Group. A multicenter prospective study of first-line antibiotic therapy for early-stage gastric mucosa-associated lymphoid tissue lymphoma and diffuse large B-cell lymphoma with histological evidence of mucosa-associated lymphoid tissue. Haematologica 2020; 105:e349-e354. [PMID: 31727764 PMCID: PMC7327622 DOI: 10.3324/haematol.2019.228775] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Affiliation(s)
- Hui-Jen Tsai
- National Institute of Cancer Research, National Health Research Institutes, Tainan
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung
- Department of Internal Medicine, National Cheng-Kung University Hospital, Tainan
| | - John Jen Tai
- National Institute of Cancer Research, National Health Research Institutes, Tainan
| | - Li-Tzong Chen
- National Institute of Cancer Research, National Health Research Institutes, Tainan
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung
- Department of Internal Medicine, National Cheng-Kung University Hospital, Tainan
| | - Ming-Shiang Wu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei
| | - Kun-Huei Yeh
- Department of Oncology, National Taiwan University Hospital, Taipei
- Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei
- Department of Medical Oncology, National Taiwan University Cancer Center, National Taiwan University College of Medicine, Taipei
| | - Chung-Wu Lin
- Department of Pathology, National Taiwan University Hospital, Taipei
| | - Tsang-En Wang
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei
| | - Hsiu-Po Wang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei
| | - Fang-Jung Yu
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung
| | - Jyh-Ming Liou
- Department of Internal Medicine, National Taiwan University Hospital, Taipei
| | - Chin-Fu Hsiao
- National Institute of Cancer Research, National Health Research Institutes, Tainan
| | - Tsu-Yao Cheng
- Department of Internal Medicine, National Taiwan University Hospital, Taipei
| | - Hong-Jen Yeh
- Department of Internal Medicine, Taichung Veterans General Hospital, Taichung
| | - Chung-Wang Ko
- Department of Internal Medicine, Taichung Veterans General Hospital, Taichung
| | - Ming-Jen Chen
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei
| | - Gin-Ho Lo
- Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung
| | - Ping-I Hsu
- Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung
| | - Cheng-Shyong Chang
- Department of Internal Medicine, Changhua Christian Hospital, Changhua City
| | | | - Shih-Sung Chuang
- Department of Pathology, National Taiwan University Hospital, Taipei
- Department of Pathology, Chi-Mei Medical Center, Tainan
- Department of Pathology, School of Medicine, Taipei Medical University, Taipei
| | - Hsiao-Wei Lee
- Department of Oncology, National Taiwan University Hospital, Taipei
- Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei
| | - Chia-Tung Shun
- Department of Pathology, National Taiwan University Hospital, Taipei
| | - Chang-Fang Chiu
- Department of Internal Medicine, Graduate Institute of Clinical Medicine, China Medical University, Taichung
| | - Wen-Ming Wang
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung
| | - Ching-Yun Hsieh
- Department of Internal Medicine, Graduate Institute of Clinical Medicine, China Medical University, Taichung
| | - Tsang-Wu Liu
- National Institute of Cancer Research, National Health Research Institutes, Tainan
| | - Jaw-Town Lin
- School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan
| | - Sung-Hsin Kuo
- Department of Oncology, National Taiwan University Hospital, Taipei
- Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei
- Department of Medical Oncology, National Taiwan University Cancer Center, National Taiwan University College of Medicine, Taipei
| | - Ann-Lii Cheng
- Department of Internal Medicine, National Taiwan University Hospital, Taipei
- Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei
- Department of Medical Oncology, National Taiwan University Cancer Center, National Taiwan University College of Medicine, Taipei
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21
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Melenotte C, Mezouar S, Mège JL, Gorvel JP, Kroemer G, Raoult D. Bacterial infection and non-Hodgkin's lymphoma. Crit Rev Microbiol 2020; 46:270-287. [PMID: 32412856 DOI: 10.1080/1040841x.2020.1760786] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
One quarter of all cancers are linked to infectious diseases. The link between viral infection and cancer has been widely studied, but few reports have focused on the carcinogenic role of bacterial infection. Nonetheless, Helicobacter pylori, Chlamydia psittaci, Coxiella burnetii, Borrelia burgdorferi and Campylobacter jejuni are bacteria that can be associated with non-Hodgkin's lymphoma (NHL), the most common haematologic malignancy. Here, we review the evidence in favour of a link between these bacterial infections and NHL. Sero-epidemiological observation makes it possible to identify a link between H. pylori, C. burnetii, B. burgdorferi infection and NHL. Helicobacter pylori, Chlamydia psittaci, Coxiella burnetii, Borrelia burgdorferi and Campylobacter jejuni could be identified in NHL tissue samples at the site of chronic inflammation, where B and T lymphocytes are attracted to participate in follicle formation. Lymphoma remissions have been observed under antimicrobial therapies supporting the carcinogenic contribution of bacteria. If the theory of causality is characterized by the lack of universal criteria for establishing a causal link between two diseases, infection and lymphoma, epidemiological, clinical, and histological evidences reported here, should lead clinicians to pay attention to these infectious agents, to detect early lymphoma transformation.
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Affiliation(s)
- Cléa Melenotte
- Aix-Marseille University, IRD, APHM, MEPHI, Marseille, France.,IHU-Méditerranée Infection, Marseille, France
| | - Soraya Mezouar
- Aix-Marseille University, IRD, APHM, MEPHI, Marseille, France.,IHU-Méditerranée Infection, Marseille, France
| | - Jean-Louis Mège
- Aix-Marseille University, IRD, APHM, MEPHI, Marseille, France.,IHU-Méditerranée Infection, Marseille, France
| | | | - Guido Kroemer
- Cell Biology and Metabolomics platforms, Villejuif, France.,INSERM, Paris, France.,Equipe 11 labellisée par la Ligue contre le Cancer, Centre de Recherche des Cordeliers, Paris, France.,Sorbonne Paris Cité, Université Paris Descartes, Paris, France.,Université Pierre et Marie Curie, Paris, France.,Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.,Karolinska Institute, Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden
| | - Didier Raoult
- Aix-Marseille University, IRD, APHM, MEPHI, Marseille, France.,IHU-Méditerranée Infection, Marseille, France
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22
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Zhou H, Yang L, Dang Q, Huang J, Cheng Y, Zhang Y, Shi W. Ibrutinib resistance in a patient with transformed diffuse large B-cell lymphoma from primary pulmonary mucosa-associated lymphoid tissue lymphoma. Cancer Biol Ther 2020; 21:303-308. [PMID: 31931656 DOI: 10.1080/15384047.2019.1700743] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma is rare among lung neoplasia cases, representing only 0.5%-1% of newly diagnosed primary lung lymphoma. MALT lymphoma with relapsed refractory and malignant transformation is highly heterogeneous and consensus therapy remains undetermined. We report a 55 year-old woman with a 3 year history of primary pulmonary MALT lymphoma confined to the lung presenting with massive pleural effusion. After two cycles of R-CHOP and six cycles of R2-CHOP, pleural effusion disappeared but the pulmonary mass remained persistent. Second-line therapies R2-GemOx failed to make any substantial improvement. Core-needle puncture biopsy of the pulmonary mass was obtained and pathological testing revealed transformed diffuse large B-cell lymphoma of germinal center B-cell subtype. Next-generation sequencing confirmed BN2 subtype. The mass showed no reduction after three cycles of R-MINE, following which the BTK inhibitor ibrutinib was administered to this patient. Unfortunately, after two months of ibrutinib treatment, the patient rapidly developed an enlarged mass and hyperprogressive disease, to which she subsequently succumbed.
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Affiliation(s)
- Hong Zhou
- Department of Hematology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China
| | - Li Yang
- Department of Hematology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China
| | - Qingxiu Dang
- Department of Hematology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China
| | - Jianfei Huang
- Clinical Bio-bank, Department of Pathology, Affiliated Hospital of Nantong University, Nantong, China
| | - Yuehua Cheng
- Medical school, Nantong University, Nantong, China
| | - Yaping Zhang
- Department of Hematology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China
| | - Wenyu Shi
- Department of Hematology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.,Department of Oncology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China
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23
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Yin X, Xu A, Fan F, Huang Z, Cheng Q, Zhang L, Sun C, Hu Y. Incidence and Mortality Trends and Risk Prediction Nomogram for Extranodal Diffuse Large B-Cell Lymphoma: An Analysis of the Surveillance, Epidemiology, and End Results Database. Front Oncol 2019; 9:1198. [PMID: 31781500 PMCID: PMC6861389 DOI: 10.3389/fonc.2019.01198] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Accepted: 10/22/2019] [Indexed: 12/13/2022] Open
Abstract
Background: DLBCL is the most commonly occurring type of non-Hodgkin's lymphoma, which may be found at various extranodal sites. But little is known about the particular trends of extranodal DLBCL. Methods: A total of 15,882 extranodal DLBCL patients were included in incidence analysis from the Surveillance, Epidemiology, and End Results (SEER) database (1973-2015). The joinpoint regression software was used to calculate the annual percent change (APC) in rates. Nomograms were established by R software to predict overall survival (OS). Results: The extranodal DLBCL incidence continued to rise at a rate of 1.6% (95% CI, 0.4-2.8, p < 0.001) per year over the study period, until it declined around 2003. The incidence-based mortality trend of extranodal DLBCL had a similar pattern, with a decrease happening around 1993. Five-year survival rates improved dramatically from the 1970s to 2010s (44.15 vs. 63.7%), and the most obvious increase occurred in DLBCL patients with primary site in the head/neck. The C-index showed a value for OS of 0.708, which validated the nomograms performed well and were able to forecast the prognosis of patients with extranodal DLBCL. The calibration curves showed satisfactory consistency between true values and predicted values for 1-, 5-, and 10-year overall survival, respectively. Conclusions: The incidence and incidence-based mortality of extranodal DLBCL had been increasing for decades, followed by a promising downward trend in recent years. These findings may help scientists identify disease-related risk factors and better manage the disease. The prediction signature cloud identifies high-risk patients who should receive effective therapies to prevent the fatal nature of this disease, and low-risk patients to reduce over-treatment.
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Affiliation(s)
- Xuejiao Yin
- Institute of Hematology, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Aoshuang Xu
- Institute of Hematology, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Fengjuan Fan
- Institute of Hematology, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Zhenli Huang
- Institute of Hematology, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Qianwen Cheng
- Institute of Hematology, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Lu Zhang
- Institute of Hematology, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Chunyan Sun
- Institute of Hematology, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, China.,Collaborative Innovation Center of Hematology, Huazhong University of Science and Technology, Wuhan, China
| | - Yu Hu
- Institute of Hematology, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, China.,Collaborative Innovation Center of Hematology, Huazhong University of Science and Technology, Wuhan, China
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24
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Shirwaikar Thomas A, Schwartz M, Quigley E. Gastrointestinal lymphoma: the new mimic. BMJ Open Gastroenterol 2019; 6:e000320. [PMID: 31645987 PMCID: PMC6782046 DOI: 10.1136/bmjgast-2019-000320] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Revised: 08/21/2019] [Accepted: 08/27/2019] [Indexed: 12/11/2022] Open
Abstract
Background Gastrointestinal (GI) lymphomas comprise a group of distinct clinicopathological entities of B- or T- cell type, with primary gastrointestinal Hodgkin lymphoma being extremely uncommon. The GI tract is the predominant site of extranodal non-Hodgkin lymphoma accounting for 30–40% of all extranodal lymphomas. In the Western world, the stomach is the most commonly involved site followed by the small bowel. Several chronic inflammatory and immune-mediated disorders which predispose to accelerated cell turnover may lead to the malignant transformation of gut lymphocytes and ultimately manifest as GI lymphoma. The challenge for the clinical gastroenterologist is that these tumors may have varied presentations, ranging from nonspecific symptoms such as dyspepsia or bloating to abdominal pain, nausea, vomiting, GI bleeding, diarrhea, weight loss or bowel obstruction. Objective We illustrate the range of presentations of GI lymphoma with examples based on consecutive cases evaluated at our institution over a 6-month period. These cases demonstrate how appropriately directed endoscopic evaluation with biopsies has the potential to provide a definitive diagnosis and allow the patient to proceed to definitive therapy. Conclusions The GI tract is the most commonly involved site for extranodal lymphoma with the stomach being most frequently involved organ. Chronic Helicobacter pylori infection, celiac disease, inflammatory bowel disease and autoimmune disorders may predispose to GI lymphoma. This heterogenous group of diseases has varied presentations that may mimic several other GI clinico-pathologic entities. GI lymphomas may be diagnosed with appropriately directed endoscopic evaluation coupled with generous tissue sampling and expert pathologic assessment. Management may range from antibiotic therapy, in the case of Helicobacter pylori-associated gastric MALT lymphoma, to chemotherapy with or without radiation and, in rare instances, surgery. There are presently no guidelines to direct endoscopic surveillance of GI lymphomas following treatment.
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Affiliation(s)
- Anusha Shirwaikar Thomas
- Department of Gastroenterology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Mary Schwartz
- Hepatology and Nutrition, Houston Methodist Hospital, Houston, Texas, USA
| | - Eamonn Quigley
- Hepatology and Nutrition, Houston Methodist Hospital, Houston, Texas, USA
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25
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Kuo SH, Wu MS, Yeh KH, Lin CW, Hsu PN, Chen LT, Cheng AL. Novel Insights of Lymphomagenesis of Helicobacter pylori-Dependent Gastric Mucosa-Associated Lymphoid Tissue Lymphoma. Cancers (Basel) 2019; 11:547. [PMID: 30999581 PMCID: PMC6520890 DOI: 10.3390/cancers11040547] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2019] [Revised: 04/09/2019] [Accepted: 04/12/2019] [Indexed: 02/06/2023] Open
Abstract
Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is the most common subtype of gastric lymphoma. Most gastric MALT lymphomas are characterized by their association with the Helicobacter pylori (HP) infection and are cured by first-line HP eradication therapy (HPE). Several studies have been conducted to investigate why most gastric MALT lymphomas remain localized, are dependent on HP infection, and show HP-specific intratumoral T-cells (e.g., CD40-mediated signaling, T-helper-2 (Th2)-type cytokines, chemokines, costimulatory molecules, and FOXP3+ regulatory T-cells) and their communication with B-cells. Furthermore, the reason why the antigen stimuli of these intratumoral T-cells with tonic B-cell receptor signaling promote lymphomagenesis of gastric MALT lymphoma has also been investigated. In addition to the aforementioned mechanisms, it has been demonstrated that the translocated HP cytotoxin-associated gene A (CagA) can promote B-cell proliferation through the activation of Src homology-2 domain-containing phosphatase (SHP-2) phosphorylation-dependent signaling, extracellular-signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (MAPK), B-cell lymphoma (Bcl)-2, and Bcl-xL. Furthermore, the expression of CagA and these CagA-signaling molecules is closely associated with the HP-dependence of gastric MALT lymphomas (completely respond to first-line HPE). In this article, we summarize evidence of the classical theory of HP-reactive T-cells and the new paradigm of direct interaction between HP and B-cells that contributes to the HP-dependent lymphomagenesis of gastric MALT lymphomas. Although the role of first-line HPE in the treatment of HP-negative gastric MALT lymphoma remains uncertain, several case series suggest that a proportion of HP-negative gastric MALT lymphomas remains antibiotic-responsive and is cured by HPE. Considering the complicated interaction between microbiomes and the genome/epigenome, further studies on the precise mechanisms of HP- and other bacteria-directed lymphomagenesis in antibiotic-responsive gastric MALT lymphomas are warranted.
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Affiliation(s)
- Sung-Hsin Kuo
- Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100, Taiwan.
- Cancer Research Center, National Taiwan University College of Medicine, Taipei 100, Taiwan.
- Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei 100, Taiwan.
- National Taiwan University Cancer Center, National Taiwan University College of Medicine, Taipei 106, Taiwan.
| | - Ming-Shiang Wu
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100, Taiwan.
| | - Kun-Huei Yeh
- Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100, Taiwan.
- Cancer Research Center, National Taiwan University College of Medicine, Taipei 100, Taiwan.
- Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei 100, Taiwan.
- National Taiwan University Cancer Center, National Taiwan University College of Medicine, Taipei 106, Taiwan.
| | - Chung-Wu Lin
- Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100, Taiwan.
| | - Ping-Ning Hsu
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100, Taiwan.
| | - Li-Tzong Chen
- National Institute of Cancer Research, National Health Research Institutes, Tainan 704, Taiwan.
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
- Department of Internal Medicine, National Cheng-Kung University Hospital, Tainan 704, Taiwan.
| | - Ann-Lii Cheng
- Cancer Research Center, National Taiwan University College of Medicine, Taipei 100, Taiwan.
- Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei 100, Taiwan.
- National Taiwan University Cancer Center, National Taiwan University College of Medicine, Taipei 106, Taiwan.
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100, Taiwan.
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26
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Xie H, Lv J, Ji Y, Du X, Yang X. Primary hepatic mucosa-associated lymphoid tissue lymphoma: A case report and literature review. Medicine (Baltimore) 2019; 98:e15034. [PMID: 30921228 PMCID: PMC6456129 DOI: 10.1097/md.0000000000015034] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
RATIONALE Primary hepatic mucosa-associated lymphoid tissue (MALT) lymphoma is a rare disease, and there is no consensus yet on the treatment modalities. Here, we report a new case of MALT lymphoma and review the current literature on this disease. PATIENT CONCERNS A 73-year-old man was admitted to our department following the incidental finding of a solitary 1.8-cm diameter mass in the liver. DIAGNOSIS Microscopic findings identified the mass as a tumor with infiltration of diffuse atypical B lymphocytes. Immunohistochemical analysis showed positivity for CD20 and CD79a, and negativity for CD3 and CD5. These collective data led to the diagnosis of primary hepatic MALT lymphoma. INTERVENTIONS The tumor was removed by surgical resection. The patient refused additional treatment after the surgery. OUTCOMES At the time of writing this report, the patient has been disease free for 6 months postsurgery. LESSONS Review of the previously published case reports on this rare tumor type indicates that in addition to chronic liver inflammation due to infection or other reasons, genetic aberrations can also contribute to the development of hepatic MALT lymphoma. Additionally, IgH rearrangement is a good genetic hallmark of this tumor. Owing to no specific clinical or radiologic features to define the disease profile for diagnosis, surgery may be a good choice for both diagnosis and therapy if the patient's condition permits.
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27
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Salar A. Gastric MALT lymphoma and Helicobacter pylori. Med Clin (Barc) 2018; 152:65-71. [PMID: 30424932 DOI: 10.1016/j.medcli.2018.09.006] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2018] [Revised: 09/10/2018] [Accepted: 09/12/2018] [Indexed: 02/07/2023]
Abstract
Marginal zone lymphomas of the MALT type are a type of B-cell neoplasms that involve extranodal tissues and have an indolent clinical behaviour. The stomach is the most common site and most patients are infected by Helicobacter pylori. An increase in the resistance of this bacterium to several antibiotics has been observed in the last years and this fact has determined the review of treatment guidelines. In areas with resistance to clarithromycin greater than 15%, classical triple therapy should be abandoned and quadruple regimens with or without bismuth are currently recommended. Thus, these new guidelines for eradication treatment should be applied to patients with gastric MALT lymphoma associated with H. pylori infection.
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Affiliation(s)
- Antonio Salar
- Servicio de Hematología, Hospital del Mar, Barcelona, España; Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, España.
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28
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Hyeon J, Lee B, Shin SH, Yoo HY, Kim SJ, Kim WS, Park WY, Ko YH. Targeted deep sequencing of gastric marginal zone lymphoma identified alterations of TRAF3 and TNFAIP3 that were mutually exclusive for MALT1 rearrangement. Mod Pathol 2018; 31:1418-1428. [PMID: 29765142 DOI: 10.1038/s41379-018-0064-0] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2017] [Revised: 03/06/2018] [Accepted: 03/07/2018] [Indexed: 11/10/2022]
Abstract
Gastric extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue is a distinct entity in that Helicobacter pylori infection plays the most important causative role in the development of the disease. To investigate the genomic alteration in gastric marginal zone lymphoma that was resistant to the H. pylori eradication therapy, we analyzed 19 cases of the gastric marginal zone lymphoma using fluorescence in situ hybridization for MALT1, BCL10 rearrangement, and targeted sequencing using an Illumina platform. Major genetic alterations affected genes involved in nuclear factor (NF)-κB pathway activation and included MALT1 rearrangement (39%), and somatic mutations of TRAF3 (21%), TNFAIP3 (16%), and NOTCH1 (16%). In the MALT1 rearrangement-negative group, disruptive somatic mutations of TRAF3 were the most common alterations (4/12, 33%), followed by somatic mutations of TNFAIP3 (3/12, 25%), and NOTCH1 (3/12, 25%). The present study confirms that genes involved in activation of NF-κB-signaling pathways are a major driver in oncogenesis of H. pylori eradication-resistant gastric marginal zone lymphoma and revealed that TRAF3 mutation is a major contributor in MALT1 rearrangement-negative gastric marginal zone lymphoma.
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Affiliation(s)
- Jiyeon Hyeon
- Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Boram Lee
- Samsung Genome Institute, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Korea.,Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Korea
| | - So-Hyun Shin
- Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hae Yong Yoo
- Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Korea
| | - Seok Jin Kim
- Division of hematology-oncology, Department of Internal medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Won Seog Kim
- Division of hematology-oncology, Department of Internal medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Woong-Yang Park
- Samsung Genome Institute, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Korea.
| | - Young-Hyeh Ko
- Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
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29
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Kuo SH, Yeh KH, Wu MS, Lin CW, Wei MF, Liou JM, Wang HP, Chen LT, Cheng AL. First-line antibiotic therapy in Helicobacter pylori-negative low-grade gastric mucosa-associated lymphoid tissue lymphoma. Sci Rep 2017; 7:14333. [PMID: 29084984 PMCID: PMC5662601 DOI: 10.1038/s41598-017-14102-8] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2017] [Accepted: 10/02/2017] [Indexed: 12/13/2022] Open
Abstract
First-line antibiotic treatment for eradicating Helicobacter pylori (HP) infection is effective in HP-positive low-grade gastric mucosa-associated lymphoid tissue lymphoma (MALToma), but its role in HP-negative cases is uncertain. In this exploratory retrospective study, we assessed the outcome and potential predictive biomarkers for 25 patients with HP-negative localized gastric MALToma who received first-line HP eradication (HPE) therapy. An HP-negative status was defined as negative results on histology, rapid urease test, 13C urea breath test, and serology. We observed an antibiotic response (complete remission [CR], number = 8; partial remission, number = 1) in 9 (36.0%) out of 25 patients. A t(11;18)(q21;q21) translocation was detected in 7 (43.8%) of 16 antibiotic-unresponsive cases, but in none of the 9 antibiotic-responsive cases (P = 0.027). Nuclear BCL10 expression was significantly higher in antibiotic-unresponsive tumors than in antibiotic-responsive tumors (14/16 [87.5%] vs. 1/9 [11.1%]; P = 0.001). Nuclear NF-κB expression was also significantly higher in antibiotic-unresponsive tumors than in antibiotic-responsive tumors (12/16 [75.0%] vs. 1/9 [11.1%]; P = 0.004). A substantial portion of patients with HP-negative gastric MALToma responded to first-line HPE. In addition to t(11;18)(q21;q21), BCL10 and NF-κB are useful immunohistochemical biomarkers to predict antibiotic-unresponsive status in this group of tumors.
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Affiliation(s)
- Sung-Hsin Kuo
- Department of Oncology, National Taiwan University, Taipei, Taiwan
- Cancer Research Center, College of Medicine, National Taiwan University, Taipei, Taiwan
- Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan
- National Taiwan University Cancer Center, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Kun-Huei Yeh
- Department of Oncology, National Taiwan University, Taipei, Taiwan
- Cancer Research Center, College of Medicine, National Taiwan University, Taipei, Taiwan
- Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan
- National Taiwan University Cancer Center, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Ming-Shiang Wu
- Department of Internal Medicine, National Taiwan University, Taipei, Taiwan
| | - Chung-Wu Lin
- Department of Pathology, National Taiwan University, Taipei, Taiwan
| | - Ming-Feng Wei
- Department of Oncology, National Taiwan University, Taipei, Taiwan
- Cancer Research Center, College of Medicine, National Taiwan University, Taipei, Taiwan
- Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan
- National Taiwan University Cancer Center, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Jyh-Ming Liou
- Department of Internal Medicine, National Taiwan University, Taipei, Taiwan
| | - Hsiu-Po Wang
- Department of Internal Medicine, National Taiwan University, Taipei, Taiwan
| | - Li-Tzong Chen
- National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, National Cheng-Kung University Hospital, Tainan, Taiwan
| | - Ann-Lii Cheng
- Department of Oncology, National Taiwan University, Taipei, Taiwan.
- Department of Internal Medicine, National Taiwan University, Taipei, Taiwan.
- Cancer Research Center, College of Medicine, National Taiwan University, Taipei, Taiwan.
- Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan.
- National Taiwan University Cancer Center, College of Medicine, National Taiwan University, Taipei, Taiwan.
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30
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Hepatitis C virus - Associated marginal zone lymphoma. Best Pract Res Clin Haematol 2017; 30:41-49. [PMID: 28288715 DOI: 10.1016/j.beha.2017.02.001] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2017] [Accepted: 02/06/2017] [Indexed: 12/18/2022]
Abstract
The link between hepatitis C virus (HCV) infection and the development of B-cell non-Hodgkin lymphoma is now well established and based on a number of epidemiological studies. It is further supported by the observation of lymphoma regression after HCV eradication by antiviral treatment. The far most frequent entities are marginal zone lymphoma (MZL) and diffuse large B-cell lymphoma (DLBCL). MZL usually emerge on a background of mixed cryoglobulinemia, a low-grade lymphoproliferation, and often transform into DLBCL, thereby following a multistep oncogenesis process. The role of HCV in lymphomagenesis is not yet fully understood but several mechanisms have been proposed including (i) chronic external stimulation through the B-cell receptor and other surface receptors, and (ii) direct transformation by intracellular viral proteins, the former being probably predominant in MZL. Regression of HCV-associated MZL can be achieved with antiviral therapy and the novel generation of direct-acting antiviral agents appears highly effective and safe for the treatment of these lymphoma.
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Kuo SH, Chen LT, Lin CW, Yeh KH, Shun CT, Tzeng YS, Liou JM, Wu MS, Hsu PN, Cheng AL. Expressions of the CagA protein and CagA-signaling molecules predict Helicobacter pylori dependence of early-stage gastric DLBCL. Blood 2017; 129:188-198. [PMID: 27864293 DOI: 10.1182/blood-2016-04-713719] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2016] [Accepted: 11/09/2016] [Indexed: 02/08/2023] Open
Abstract
We previously reported that early-stage gastric diffuse large B-cell lymphomas (DLBCLs), including DLBCLs with mucosa-associated lymphoid tissue (DLBCL[MALT]) and without ("pure" DLBCL) the features of MALT lymphomas, can achieve long-term complete remission after frontline Helicobacter pylori (HP) eradication (HPE). We recently reported that expression of cytotoxin-associated gene A (CagA) and CagA-signaling molecules (phospho-Src homology-2 domain-containing phosphatase [p-SHP2] and phospho-extracellular signal-regulated kinase [p-ERK]) is associated with HP dependence of gastric MALT lymphoma. However, the significance of CagA and CagA-signaling molecules in gastric DLBCL remains unexplored. The association between expression of CagA, p-SHP-2, and p-ERK in malignant B cells and tumor response to HPE was evaluated in 63 patients with stage IE/IIE1 HP-positive gastric DLBCL who received HPE as frontline treatment. We detected CagA expression in 20 of 42 DLBCL (MALT) cases (47.6%) and in 13 of 21 "pure" DLBCL cases (61.9%). CagA expression was higher in HP-dependent tumors than in HP-independent tumors (74.3% [26 of 35] vs 25.0% [7 of 28]). Patients with CagA expression responded to HPE quicker than those without expression (median time to complete remission, 4.0 months vs 5.0 months). The expression of CagA was closely associated with p-SHP-2 and p-ERK expression. Combined CagA, p-SHP-2, and p-ERK expression showed an increased positive predictive value (81.8% vs 75.9%) and an increased specificity (84.0% vs 75.0%) for HP dependence compared with CagA expression alone. Our results indicated that CagA and its signaling molecules can be detected in the malignant B cells of gastric DLBCL, and the expression of these molecules is clinically and biologically associated with HP dependence.
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Affiliation(s)
- Sung-Hsin Kuo
- Department of Oncology and
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- National Taiwan University Cancer Center and
- Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Li-Tzong Chen
- National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, National Cheng-Kung University Hospital, Tainan, Taiwan; and
| | - Chung-Wu Lin
- Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan
| | - Kun-Huei Yeh
- Department of Oncology and
- National Taiwan University Cancer Center and
- Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Chia-Tung Shun
- Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan
| | - Yi-Shin Tzeng
- Department of Oncology and
- Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Jyh-Ming Liou
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Ming-Shiang Wu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Ping-Ning Hsu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Ann-Lii Cheng
- Department of Oncology and
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- National Taiwan University Cancer Center and
- Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan
- National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan
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CagA Phosphorylation in Helicobacter pylori-Infected B Cells Is Mediated by the Nonreceptor Tyrosine Kinases of the Src and Abl Families. Infect Immun 2016; 84:2671-80. [PMID: 27382024 PMCID: PMC4995908 DOI: 10.1128/iai.00349-16] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2016] [Accepted: 06/25/2016] [Indexed: 02/08/2023] Open
Abstract
CagA is one of the most important virulence factors of the human pathogen Helicobacter pylori. CagA expression can be associated with the induction of severe gastric disorders such as gastritis, ulceration, gastric cancer, or mucosa-associated lymphoid tissue (MALT) lymphoma. After translocation through a type IV secretion system into epithelial cells, CagA is tyrosine phosphorylated by kinases of the Src and Abl families, leading to drastic cell elongation and motility. While the functional role of CagA in epithelial cells is well investigated, knowledge about CagA phosphorylation and its associated signal transduction pathways in B cells is only marginal. Here, we established the B cell line MEC1 derived from a B cell chronic lymphocytic leukemia (B-CLL) patient as a new infection model to study the signal transduction in B cells controlled by H. pylori. We observed that CagA was rapidly injected, strongly tyrosine phosphorylated, and cleaved into a 100-kDa N-terminal and a 40-kDa C-terminal fragment. To identify upstream signal transduction pathways of CagA phosphorylation in MEC1 cells, pharmacological inhibitors were employed to specifically target Src and Abl kinases. We observed that CagA phosphorylation was strongly inhibited upon treatment with an Src inhibitor and slightly diminished when the Abl kinase inhibitor imatinib mesylate (Gleevec) was applied. The addition of dasatinib to block c-Abl and Src kinases led to a complete loss of CagA phosphorylation. In conclusion, these results demonstrate an important role for Src and Abl tyrosine kinases in CagA phosphorylation in B cells, which represent druggable targets in H. pylori-mediated gastric MALT lymphoma.
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Gong EJ, Ahn JY, Jung HY, Jung K, Cho CJ, Na HK, Jung KW, Kim DH, Lee JH, Choi KD, Song HJ, Lee GH, Kim JH, Yoon DH. Bone marrow involvement is not associated with the clinical outcomes of gastric mucosa-associated lymphoid tissue lymphoma. Scand J Gastroenterol 2016; 51:942-8. [PMID: 27149022 DOI: 10.3109/00365521.2016.1151929] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Objective Bone marrow (BM) examination is recommended as part of the initial staging work-up in patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma. However, the clinical significance of BM involvement in gastric MALT lymphoma patients has not been evaluated. Materials and methods From November 1995 to September 2014, 496 subjects who were diagnosed with gastric MALT lymphoma and underwent BM examination were eligible to be included in this study. BM involvement was found in 33 patients (6.7%) by retrospective review, and after exclusions, the clinical outcomes of 28 patients with BM involvement and 412 patients without BM involvement were evaluated. Results When comparing the characteristics of patients, age (median 60 vs. 53 years, p = 0.007) and Helicobacter pylori infection rate (71.0% vs. 85.5%, p = 0.040) were different between patients with and without BM involvement, while the location, macroscopic findings, and depth of invasion were similar. The overall complete remission (CR) rate was 85.2% during a median follow-up period of 42 months (interquartile range, 23-66 months) and did not differ between the two groups (78.6 and 85.7%, p = 0.280). Eradication therapy was performed as the first-line treatment in 18 of the 28 patients (64.3%) with BM involvement, and CR was achieved in 13 patients (72.2%). Logistic regression analysis showed that age and location in the upper part of the stomach were factors related to remission failure. Conclusion Gastric MALT lymphoma has a favorable outcome, and eradication therapy can be justified in selected cases even with BM involvement, when these patients are closely monitored.
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Affiliation(s)
- Eun Jeong Gong
- a Department of Gastroenterology , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
| | - Ji Yong Ahn
- a Department of Gastroenterology , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
| | - Hwoon-Yong Jung
- a Department of Gastroenterology , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
| | - Kyoungwon Jung
- a Department of Gastroenterology , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
| | - Charles J Cho
- a Department of Gastroenterology , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
| | - Hee Kyong Na
- a Department of Gastroenterology , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
| | - Kee Wook Jung
- a Department of Gastroenterology , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
| | - Do Hoon Kim
- a Department of Gastroenterology , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
| | - Jeong Hoon Lee
- a Department of Gastroenterology , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
| | - Kee Don Choi
- a Department of Gastroenterology , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
| | - Ho June Song
- a Department of Gastroenterology , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
| | - Gin Hyug Lee
- a Department of Gastroenterology , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
| | - Jin-Ho Kim
- a Department of Gastroenterology , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
| | - Dok Hyun Yoon
- b Department of Oncology , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
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Joo JH, Lee SW, Huh J, Suh C, Yoon DH, Ahn SD, Choi EK, Kim JH. Recurrence patterns of mucose-associated lymphoid tissue lymphoma after definitive radiation treatment: A single center experience. ACTA ACUST UNITED AC 2016; 21:542-8. [PMID: 27168138 DOI: 10.1080/10245332.2016.1164933] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
OBJECTIVES To evaluate the treatment outcomes in non-gastric and non-nodal mucose-associated lymphoid tissue (MALT) lymphoma patients treated by definitive radiation therapy (RT). METHODS A total of 134 patients were analyzed. The RT dose was 30.6 or 36 Gy. RESULTS The median follow-up duration for all patients was 51.1 months (range, 3.0-132.4 months). Among the 88 orbital MALT lymphoma patients, 12 had disease recurrence. There were 23 head and neck tumor patients. Two patients experienced relapse, all at out-of-field locations. Gastrointestinal MALT lymphoma was diagnosed in 13 patients, and three showed local (n = 1), distant (n = 1), or local/distant (n = 1) relapse. CONCLUSION RT alone is highly effective in achieving local control and long-term survival in localized MALT lymphoma. In orbital MALT, excellent local control is achieved, and relapse is predominantly observed in the contralateral eye. Other head and neck lymphomas are also well controlled.
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Affiliation(s)
- Ji Hyeon Joo
- a Department of Radiation Oncology, Asan Medical Center , University of Ulsan College of Medicine , Seoul , Korea
| | - Sang-Wook Lee
- a Department of Radiation Oncology, Asan Medical Center , University of Ulsan College of Medicine , Seoul , Korea
| | - Jooryung Huh
- b Department of Pathology, Asan Medical Center , University of Ulsan College of Medicine , Seoul , Korea
| | - Cheolwon Suh
- c Department of Oncology, Asan Medical Center , University of Ulsan College of Medicine , Seoul , Korea
| | - Dok Hyun Yoon
- c Department of Oncology, Asan Medical Center , University of Ulsan College of Medicine , Seoul , Korea
| | - Seung Do Ahn
- a Department of Radiation Oncology, Asan Medical Center , University of Ulsan College of Medicine , Seoul , Korea
| | - Eun Kyung Choi
- a Department of Radiation Oncology, Asan Medical Center , University of Ulsan College of Medicine , Seoul , Korea
| | - Jong Hoon Kim
- a Department of Radiation Oncology, Asan Medical Center , University of Ulsan College of Medicine , Seoul , Korea
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Review article: Mucosa-associated lymphoid tissue (MALT)-type lymphoma of ocular adnexa. Biology and treatment. Crit Rev Oncol Hematol 2016; 100:37-45. [DOI: 10.1016/j.critrevonc.2016.01.009] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2015] [Revised: 12/08/2015] [Accepted: 01/14/2016] [Indexed: 12/27/2022] Open
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Abstract
Ocular adnexal lymphoma (OAL) is a relatively common lesion in the practice of ophthalmic oncology. Although OALs are usually primary tumors, secondary involvement of the ocular adnexae by systemic lymphoma is also possible. The clinical and radiological features of OAL are non-specific. Thorough morphological evaluation, aided by immunostaining, cytogenetic studies and molecular testing, are necessary for accurate diagnosis.
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Affiliation(s)
- Kaustubh Mulay
- National Reporting Centre for Ophthalmic Pathology (NRCOP), Centre For Sight, Hyderabad, India.
| | - Santosh G Honavar
- Oculoplastics, Facial Aesthetics and Ocular Oncology, Centre For Sight, Hyderabad, India
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Vogtmann E, Goedert JJ. Epidemiologic studies of the human microbiome and cancer. Br J Cancer 2016; 114:237-42. [PMID: 26730578 PMCID: PMC4742587 DOI: 10.1038/bjc.2015.465] [Citation(s) in RCA: 145] [Impact Index Per Article: 16.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2015] [Revised: 10/30/2015] [Accepted: 11/10/2015] [Indexed: 12/17/2022] Open
Abstract
The human microbiome, which includes the collective genome of all bacteria, archaea, fungi, protists, and viruses found in and on the human body, is altered in many diseases and may substantially affect cancer risk. Previously detected associations of individual bacteria (e.g., Helicobacter pylori), periodontal disease, and inflammation with specific cancers have motivated studies considering the association between the human microbiome and cancer risk. This short review summarises microbiome research, focusing on published epidemiological associations with gastric, oesophageal, hepatobiliary, pancreatic, lung, colorectal, and other cancers. Large, prospective studies of the microbiome that employ multidisciplinary laboratory and analysis methods, as well as rigorous validation of case status, are likely to yield translational opportunities to reduce cancer morbidity and mortality by improving prevention, screening, and treatment.
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Affiliation(s)
- Emily Vogtmann
- Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 9609 Medical Center Drive, Bethesda, MD 20892, USA
| | - James J Goedert
- Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 9609 Medical Center Drive, Bethesda, MD 20892, USA
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Hermouet S, Bigot-Corbel E, Gardie B. Pathogenesis of Myeloproliferative Neoplasms: Role and Mechanisms of Chronic Inflammation. Mediators Inflamm 2015; 2015:145293. [PMID: 26538820 PMCID: PMC4619950 DOI: 10.1155/2015/145293] [Citation(s) in RCA: 63] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2015] [Accepted: 08/19/2015] [Indexed: 12/18/2022] Open
Abstract
Myeloproliferative neoplasms (MPNs) are a heterogeneous group of clonal diseases characterized by the excessive and chronic production of mature cells from one or several of the myeloid lineages. Recent advances in the biology of MPNs have greatly facilitated their molecular diagnosis since most patients present with mutation(s) in the JAK2, MPL, or CALR genes. Yet the roles played by these mutations in the pathogenesis and main complications of the different subtypes of MPNs are not fully elucidated. Importantly, chronic inflammation has long been associated with MPN disease and some of the symptoms and complications can be linked to inflammation. Moreover, the JAK inhibitor clinical trials showed that the reduction of symptoms linked to inflammation was beneficial to patients even in the absence of significant decrease in the JAK2-V617F mutant load. These observations suggested that part of the inflammation observed in patients with JAK2-mutated MPNs may not be the consequence of JAK2 mutation. The aim of this paper is to review the different aspects of inflammation in MPNs, the molecular mechanisms involved, the role of specific genetic defects, and the evidence that increased production of certain cytokines depends or not on MPN-associated mutations, and to discuss possible nongenetic causes of inflammation.
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Affiliation(s)
- Sylvie Hermouet
- Inserm UMR 892, CNRS UMR 6299, Centre de Recherche en Cancérologie Nantes-Angers, Institut de Recherche en Santé, Université de Nantes, 44007 Nantes, France
- Laboratoire d'Hématologie, Centre Hospitalier Universitaire de Nantes, 44093 Nantes Cedex, France
| | - Edith Bigot-Corbel
- Inserm UMR 892, CNRS UMR 6299, Centre de Recherche en Cancérologie Nantes-Angers, Institut de Recherche en Santé, Université de Nantes, 44007 Nantes, France
- Laboratoire de Biochimie, Centre Hospitalier Universitaire de Nantes, 44093 Nantes Cedex, France
| | - Betty Gardie
- Inserm UMR 892, CNRS UMR 6299, Centre de Recherche en Cancérologie Nantes-Angers, Institut de Recherche en Santé, Université de Nantes, 44007 Nantes, France
- Ecole Pratique des Hautes Etudes, Laboratoire de Génétique Oncologique, 44007 Nantes, France
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Zucca E, Bertoni F, Vannata B, Cavalli F. Emerging role of infectious etiologies in the pathogenesis of marginal zone B-cell lymphomas. Clin Cancer Res 2015; 20:5207-16. [PMID: 25320370 DOI: 10.1158/1078-0432.ccr-14-0496] [Citation(s) in RCA: 69] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Extranodal marginal zone B-cell lymphomas of the mucosa-associated lymphoid tissue (MALT) arise from lymphoid populations that are induced by chronic inflammation in extranodal sites. The most frequently affected organ is the stomach, where MALT lymphoma is incontrovertibly associated with a chronic gastritis induced by a microbial pathogen, Helicobacter pylori. Gastric MALT lymphoma therefore represents a paradigm for evaluating inflammation-associated lymphomagenesis, which may lead to a deeper understanding of a possible etiologic association between other microorganisms and nongastric marginal zone lymphomas. Besides infectious etiology, chronic inflammation caused by autoimmune diseases, such as Sjögren syndrome or Hashimoto thyroiditis, can also carry a significant risk factor for the development of marginal zone lymphoma. In addition to the continuous antigenic drive, additional oncogenic events play a relevant role in lymphoma growth and progression to the point at which the lymphoproliferative process may eventually become independent of antigenic stimulation. Recent studies on MALT lymphomas have in fact demonstrated genetic alterations affecting the NF-κB) pathway, a major signaling pathway involved in many cancers. This review aims to present marginal zone lymphoma as an example of the close pathogenetic link between chronic inflammation and tumor development, with particular attention to the role of infectious agents and the integration of these observations into everyday clinical practice. See all articles in this CCR Focus section, "Paradigm Shifts in Lymphoma."
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Affiliation(s)
- Emanuele Zucca
- Lymphoma Unit, Division of Research, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
| | - Francesco Bertoni
- Lymphoma Unit, Division of Research, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland. Lymphoma and Genomics Research Program, IOR Institute of Oncology Research, Bellinzona, Switzerland
| | - Barbara Vannata
- Lymphoma Unit, Division of Research, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
| | - Franco Cavalli
- Lymphoma Unit, Division of Research, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
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Paydas S. Helicobacter pylori eradication in gastric diffuse large B cell lymphoma. World J Gastroenterol 2015; 21:3773-3776. [PMID: 25852262 PMCID: PMC4385524 DOI: 10.3748/wjg.v21.i13.3773] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2014] [Revised: 11/18/2014] [Accepted: 12/16/2014] [Indexed: 02/06/2023] Open
Abstract
Diffuse large B cell lymphoma (DLBCL) of the stomach is a heterogenous disease. There are tumors without histological evidence of mucosa-associated lymphoid tissue (MALT) lymphoma, which are classified as pure or de novo DLBCL and those with evidence of MALT, which are classified as DLBCL (MALT). The association between Helicobacter pylori (H. pylori) and gastric MALT lymphoma and remission with H. pylori eradication was shown in the 1990s. In recent years, scientists from Taiwan and others have shown that high-grade gastric lymphomas may be dependent on H. pylori and eradication of this microorganism is effective in these cases. This entity is biologically distinct from H. pylori (-) cases and has a better clinical outcome. There are sufficient data about the complete remission in some of these cases with brief treatment with antibiotics. With this strategy, it is possible to save some of these cases from the harmful effects of standard chemotherapy. It is time to treat these cases with H. pylori eradication. However, strict histopathological follow-up is crucial and histopathological response must be evaluated according to the scoring system proposed by Groupe d’Etude des Lymphomes de l’Adulte. If there is no sufficient response, chemotherapy must be given immediately. These results suggest that H. pylori dependency and high-grade transformation in gastric MALT lymphomas are distinct events.
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Abstract
Primary gastrointestinal (GI) lymphomas are uncommon diseases that can involve the whole GI tract. The etiologies of the disease remain unclear, and potential risk factors include celiac disease, Helicobacter pylori infection, use of immunosuppressive agents, human immunodeficiency virus (HIV) or Epstein-Barr virus (EBV) infection and inflammatory bowel disease, etc. Diffuse large B-cell lymphoma (DLBCL) and mucosa-associated lymphoid tissue (MALT) lymphoma are the most common subtypes of GI lymphomas. B-cell lymphomas of the GI tract are more common in Western countries, while in Asia-Pacific region T-cell lymphomas are more frequently reported. In this review, lymphomas in the esophagus, stomach and intestine are described, including their epidemiology, histology, clinical manifestations, endoscopic findings, radiological features and treatment.
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Affiliation(s)
- Jiang Chen Peng
- State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai Inflammatory Bowel Disease Research Center, Shanghai, China
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Dhull AK, Kaushal V, Singh S, Pal M, Lathwal A. A journey into insidious world of MALT lymphoma of the ileum: from the beginning to the end. J Gastrointest Oncol 2014; 5:E125-7. [PMID: 25436136 DOI: 10.3978/j.issn.2078-6891.2014.063] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2014] [Accepted: 08/05/2014] [Indexed: 01/22/2023] Open
Abstract
INTRODUCTION Lymphoma of the mucosa-associated lymphoid tissue (MALT) has been used to describe a marginal zone B-cell lymphoma derived from gastrointestinal lymphoid tissue. mucosa-associated lymphoid tissue lymphoma (MALToma) of the ileum are extremely rare and only few reports with endoscopic features have been reported. CASE STUDY We present a 55-year-old male patient with history of abdominal pain and loss of appetite since 2½ years. Abdomino-pelvic ultrasonography was normal, but computed tomography (CT) scan of the abdomen showed, dilated segment of ileum containing both contrast and debris. He underwent segmental resection of ileum associated with stricture site, histopathology of which revealed MALToma of ileum. Patient was subsequently treated with low dose chemotherapy and strictly followed up. DISCUSSION Primary treatment possibility should be considered as the treatment of H. pylori infection while surgical resection for superficial lesions followed by low dose chemotherapy is recommended. The present case report explore MALToma of the GI tract, its diagnostic criterions, role of radiological and pathological tools, various investigative techniques and role of surgery and chemotherapy in such cases.
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Affiliation(s)
- Anil Kumar Dhull
- 1 Radiation Oncology, 2 Pathology, Post Graduate Institute of Medical Sciences, Rohtak, India ; 3 Radiation Oncology, Rajiv Gandhi Cancer Institute & Research Centre, Delhi, India ; 4 Hospital Administration, All India Institute of Medical Sciences, New Delhi, India
| | - Vivek Kaushal
- 1 Radiation Oncology, 2 Pathology, Post Graduate Institute of Medical Sciences, Rohtak, India ; 3 Radiation Oncology, Rajiv Gandhi Cancer Institute & Research Centre, Delhi, India ; 4 Hospital Administration, All India Institute of Medical Sciences, New Delhi, India
| | - Sunita Singh
- 1 Radiation Oncology, 2 Pathology, Post Graduate Institute of Medical Sciences, Rohtak, India ; 3 Radiation Oncology, Rajiv Gandhi Cancer Institute & Research Centre, Delhi, India ; 4 Hospital Administration, All India Institute of Medical Sciences, New Delhi, India
| | - Manoj Pal
- 1 Radiation Oncology, 2 Pathology, Post Graduate Institute of Medical Sciences, Rohtak, India ; 3 Radiation Oncology, Rajiv Gandhi Cancer Institute & Research Centre, Delhi, India ; 4 Hospital Administration, All India Institute of Medical Sciences, New Delhi, India
| | - Amit Lathwal
- 1 Radiation Oncology, 2 Pathology, Post Graduate Institute of Medical Sciences, Rohtak, India ; 3 Radiation Oncology, Rajiv Gandhi Cancer Institute & Research Centre, Delhi, India ; 4 Hospital Administration, All India Institute of Medical Sciences, New Delhi, India
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Ruggiero P. Use of probiotics in the fight against Helicobacter pylori. World J Gastrointest Pathophysiol 2014; 5:384-91. [PMID: 25400981 PMCID: PMC4231502 DOI: 10.4291/wjgp.v5.i4.384] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2014] [Revised: 03/19/2014] [Accepted: 07/15/2014] [Indexed: 02/07/2023] Open
Abstract
After the discovery of Helicobacter pylori (H. pylori), and the evidence of its relationship with gastric diseases, antibiotic-based therapies were developed, which efficacy was however limited by antibiotic resistance and lack of patient compliance. A vaccine would overcome these drawbacks, but currently there is not any H. pylori vaccine licensed. In the frame of the studies aimed at finding alternative therapies or at increasing the efficacy of the current ones and/or reducing their side effects, the investigation on the use of probiotics plays an interesting role. In vitro and preclinical studies have shown the feasibility of this approach. Several clinical trials indicated that administration of probiotics can reduce the side effects of H. pylori eradication treatment, increasing tolerability, and often increases the overall efficacy. The results of these trials vary, likely reflecting the variety of probiotics assessed and that of the eradication treatment, as well as the differences in the geographic area that imply different H. pylori strains distribution, host susceptibility, and therapy efficacy. In conclusion, the use of probiotics appears promising as an adjuvant for the current H. pylori eradication treatment, though it still requires optimization.
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Park JB, Koo JS. Helicobacter pylori infection in gastric mucosa-associated lymphoid tissue lymphoma. World J Gastroenterol 2014; 20:2751-2759. [PMID: 24659867 PMCID: PMC3961970 DOI: 10.3748/wjg.v20.i11.2751] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2013] [Revised: 10/15/2013] [Accepted: 11/03/2013] [Indexed: 02/06/2023] Open
Abstract
Gastrointestinal lymphoma is the most common type of extranodal lymphoma, and most commonly affects the stomach. Marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) and diffuse large B-cell lymphoma are the most common histologic types of gastric lymphoma. Despite its increasing incidence, diagnosis of gastric lymphoma is difficult at an earlier stage due to its nonspecific symptoms and endoscopic findings, and, thus, a high index of suspicion, and multiple, deep, repeated biopsies at abnormally and normally appearing sites in the stomach are needed. In addition, testing for Helicobacter pylori (H. pylori) infection and endoscopic ultrasonography to determine the depth of tumor invasion and involvement of regional lymph nodes is essential for predicting response to H. pylori eradication and for assessment of disease progression. In addition, H. pylori infection and MALT lymphoma development are associated, and complete regression of low-grade MALT lymphomas after H. pylori eradication has been demonstrated. Radiotherapy and/or chemotherapy can be used in cases that show poor response to H. pylori eradication, negativity for H. pylori infection, or high-grade lymphoma.
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Govi S, Resti AG, Modorati G, Dolcetti R, Colucci A, Ferreri AJM. Marginal zone B-cell lymphoma of the conjunctiva. EXPERT REVIEW OF OPHTHALMOLOGY 2014. [DOI: 10.1586/eop.10.11] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Moslehi R, Schymura MJ, Nayak S, Coles FB. Ocular adnexal non-Hodgkin's lymphoma: a review of epidemiology and risk factors. EXPERT REVIEW OF OPHTHALMOLOGY 2014; 6:181-193. [PMID: 23976898 DOI: 10.1586/eop.11.15] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Ocular adnexal non-Hodgkin's lymphoma (NHL), the most common form of ophthalmic NHL, has a unique incidence pattern showing a steady and rapid increase in the past few decades, nearly equal rates among both genders, and predominance among Asians/Pacific Islanders. No major cause for ocular adnexal NHL has been identified, although infectious agents, immune disorders and genetic/epigenetic factors have all been implicated in its etiology. Identifying putative risk factors and biologic mechanisms leading to carcinogenesis in ocular adnexal NHL may enable implementation of effective preventive and/or therapeutic approaches for this malignancy. This article summarizes current knowledge on epidemiology of ocular adnexal NHL and the role of various potential risk factors in its etiology.
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Affiliation(s)
- Roxana Moslehi
- Department of Epidemiology and Biostatistics, School of Public Health, State University of New York at Albany, NY, USA ; Cancer Research Center, State University of New York at Albany, NY, USA
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Kuo SH, Chen LT, Lin CW, Wu MS, Hsu PN, Tsai HJ, Chu CY, Tzeng YS, Wang HP, Yeh KH, Cheng AL. Detection of the Helicobacter pylori CagA protein in gastric mucosa-associated lymphoid tissue lymphoma cells: clinical and biological significance. Blood Cancer J 2013; 3:e125. [PMID: 23852160 PMCID: PMC3730200 DOI: 10.1038/bcj.2013.22] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2013] [Revised: 05/29/2013] [Accepted: 06/04/2013] [Indexed: 12/14/2022] Open
Abstract
We previously reported that CagA can be translocated into B cells in Helicobacter pylori (HP) coculture media, and the translocation appears biologically significant as activation of the relevant cellular pathways was noticed. In this study, we further explore if CagA can be detected in malignant B cells of HP-positive gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Expression of CagA was evaluated by immunohistochemistry. CagA expression was further confirmed by western blot analysis. The association between CagA expression in malignant B cells and tumor response to HP eradication therapy (HPE) was evaluated in 64 stage IE gastric MALT lymphoma patients. We detected CagA expression in 31 (48.4%) of 64 patients: 26 (68.4%) of the 38 HP-dependent cases and 5 (19.2%) of the 26 HP-independent cases (P<0.001). Patients with CagA expression responded to HPE quicker than those without (median time to complete remission, 3.0 vs 6.5 months, P=0.025). Our results indicated that CagA can be translocated into malignant B cells of MALT lymphoma, and the translocation is clinically and biologically significant.
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Affiliation(s)
- S-H Kuo
- Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
- Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan
- Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan
| | - L-T Chen
- National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan
- Department of Internal Medicine, Kaoshiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
| | - C-W Lin
- Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - M-S Wu
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - P-N Hsu
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - H-J Tsai
- National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan
- Department of Internal Medicine, Kaoshiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - C-Y Chu
- National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan
| | - Y-S Tzeng
- Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
- Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan
| | - H-P Wang
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - K-H Yeh
- Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
- Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan
- Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan
| | - A-L Cheng
- Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
- Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan
- Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan
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Zhang X, Zhang J, Zhang R, Guo Y, Wu C, Mao X, Guo G, Zhang Y, Li D, Zou Q. Structural, enzymatic and biochemical studies on Helicobacter pylori arginase. Int J Biochem Cell Biol 2013; 45:995-1002. [PMID: 23454280 DOI: 10.1016/j.biocel.2013.02.008] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2012] [Revised: 01/25/2013] [Accepted: 02/11/2013] [Indexed: 11/25/2022]
Abstract
Arginase is an enzyme involved in the last step of the urea cycle, where it catalyses the hydrolysis of l-arginine to generate l-ornithine and urea. Compared to the well-characterised arginases from animals, yeast and other bacteria, Helicobacter pylori arginase, or RocF, is unique in at least three aspects. Firstly, it has been identified as an important factor in evasion of the host's immune system and thus contributes to persistent infection by the bacterium. Secondly, the optimal catalytic conditions of RocF are different from those of other arginases. Finally, sequence alignment indicates that RocF possesses considerable differences at its N- and C-terminal from other arginases and harbours an insertion of 13 residues in the middle of the sequence. To better understand these unique biochemical and enzymatic properties, we therefore have embarked on determining the structure of RocF. In this study, the crystal structure of RocF was solved with the molecular replacement method. Based on the structure and systematic mutagenesis studies, we confirmed that the inserted residues form a helix that was not observed in other arginases and was able to raise the arginase activity by 30% probably by change the conformation of the substrate binding pocket. Six residues were involved in Mn(2+) binding, all of which were essential for arginase activity. The C-terminal motif is not sufficient in establishing the oligomeric state of RocF, and no disulphide bonds were observed in RocF.
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Affiliation(s)
- Xiaoli Zhang
- Department of Clinical Microbiology and Immunology, College of Medical Laboratory, Third Military Medical University, Chongqing 400038, China
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Kozanoglu I, Yandim MK, Cincin ZB, Ozdogu H, Cakmakoglu B, Baran Y. New indication for therapeutic potential of an old well-known drug (propranolol) for multiple myeloma. J Cancer Res Clin Oncol 2013; 139:327-35. [PMID: 23080133 DOI: 10.1007/s00432-012-1331-y] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2012] [Accepted: 10/02/2012] [Indexed: 10/27/2022]
Abstract
PURPOSE Propranolol, a non-selective β-adrenergic receptor blocker, has been used for the treatment of the patients with hypertension for more than 50 years. There are several in vitro and in vivo evidences that β-adrenergic receptor antagonists inhibit proliferation and angiogenesis and also increase apoptosis in breast, skin, and colon cancers. The aim of this study was to investigate the cytotoxic and apoptotic effects of propranolol and the genes involved in propranolol-induced apoptosis in multiple myeloma cells. METHODS Time-dependent antiproliferation and apoptotic effects of propranolol were subsequently determined by MTT cell proliferation assay, changes in caspase-3 activity, loss of mitochondrial membrane potential (MMP), and also the localization of phosphatidylserine in the plasma membrane. Changes in expression levels of NF-ΚB pathway were examined by qRT-PCR array. RESULTS IC50 values of propranolol on U266 cells were calculated as 141, 100, and 75 μM after 24-, 48-, and 72-h propranolol exposure, respectively. There were significant increases in caspase-3 activity, loss of MMP, and increases in apoptotic cell population in response to propranolol in U266 cells in a time- and dose-dependent manner. There were increases in expression levels of BCL10, TRAF family members, interleukins, TLR1-4, TNFRSF10B, NF-κB, and the inhibitors of NF-κB genes, and significant decreases in expression levels of Bcl-2 in response to propranolol treatment were observed. CONCLUSION These results revealed that propranolol has antiproliferative and apoptotic effects on multiple myeloma cells. Being supported with in vivo analyses, propranolol can be a good and economical way to treat multiple myeloma patients.
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Affiliation(s)
- Ilknur Kozanoglu
- Adana Adult Bone Marrow Center, Cell Processing Unit, Baskent University, Ankara, Turkey
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