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      High-Mobility Group Box 1 expression predicts survival of patients after resection of adenocarcinoma of the ampulla of Vater

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          Abstract

          Background

          Expression of High-Mobility Group Box 1 (HMGB1), a multifunctional protein involved in DNA function as well as cell proliferation, inflammation, and the immune response, has been reported to be prognostic in several types of malignancies. However, the prognostic value of HMGB1 in ampullary cancer has not been studied.

          Methods

          Patients with adenocarcinoma of the ampulla of Vater who underwent R0 resection with pancreaticoduodenectomy between 2001 and 2011 were included in the present multi-institutional study. The degree of HMGB1 expression was examined in each resected specimen by immunohistochemical staining.

          Results

          A total of 101 patients were enrolled of which, 79 patients were eligible. High expression of HMGB1 was observed in 31 (39%) patients. Blood loss, transfusion, tumor stage, nodal status, and HMGB1 expression were identified as predictors with univariate analysis. Multivariate analysis showed that transfusion, lymph-node metastasis, and high HMGB1 expression were independent predictors of poor overall survival. Subgroup analysis showed that high HMGB1 expression was predictive, especially in patients who did not receive adjuvant chemotherapy.

          Conclusions

          High HMGB1 expression is an independent predictor of poor prognosis in patients with adenocarcinoma of the ampulla of Vater not treated with adjuvant chemotherapy.

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          HMG-1 as a late mediator of endotoxin lethality in mice.

          H. Wang, O Bloom, M. Zhang … (1999)
          Endotoxin, a constituent of Gram-negative bacteria, stimulates macrophages to release large quantities of tumor necrosis factor (TNF) and interleukin-1 (IL-1), which can precipitate tissue injury and lethal shock (endotoxemia). Antagonists of TNF and IL-1 have shown limited efficacy in clinical trials, possibly because these cytokines are early mediators in pathogenesis. Here a potential late mediator of lethality is identified and characterized in a mouse model. High mobility group-1 (HMG-1) protein was found to be released by cultured macrophages more than 8 hours after stimulation with endotoxin, TNF, or IL-1. Mice showed increased serum levels of HMG-1 from 8 to 32 hours after endotoxin exposure. Delayed administration of antibodies to HMG-1 attenuated endotoxin lethality in mice, and administration of HMG-1 itself was lethal. Septic patients who succumbed to infection had increased serum HMG-1 levels, suggesting that this protein warrants investigation as a therapeutic target.
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            Blockade of RAGE-amphoterin signalling suppresses tumour growth and metastases.

            A Taguchi, D Blood, G. Del Toro … (2000)
            The receptor for advanced glycation end products (RAGE), a multi-ligand member of the immunoglobulin superfamily of cell surface molecules, interacts with distinct molecules implicated in homeostasis, development and inflammation, and certain diseases such as diabetes and Alzheimer's disease. Engagement of RAGE by a ligand triggers activation of key cell signalling pathways, such as p21ras, MAP kinases, NF-kappaB and cdc42/rac, thereby reprogramming cellular properties. RAGE is a central cell surface receptor for amphoterin, a polypeptide linked to outgrowth of cultured cortical neurons derived from developing brain. Indeed, the co-localization of RAGE and amphoterin at the leading edge of advancing neurites indicated their potential contribution to cellular migration, and in pathologies such as tumour invasion. Here we demonstrate that blockade of RAGE-amphoterin decreased growth and metastases of both implanted tumours and tumours developing spontaneously in susceptible mice. Inhibition of the RAGE-amphoterin interaction suppressed activation of p44/p42, p38 and SAP/JNK MAP kinases; molecular effector mechanisms importantly linked to tumour proliferation, invasion and expression of matrix metalloproteinases.
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              High-mobility group box 1 and cancer.

              Daolin Tang, Rui Kang, Herbert Zeh III … (2010)
              High-mobility group box 1 protein (HMGB1), a chromatin associated nuclear protein and extracellular damage associated molecular pattern molecule (DAMP), is an evolutionarily ancient and critical regulator of cell death and survival. Overexpression of HMGB1 is associated with each of the hallmarks of cancer including unlimited replicative potential, ability to develop blood vessels (angiogenesis), evasion of programmed cell death (apoptosis), self-sufficiency in growth signals, insensitivity to inhibitors of growth, inflammation, tissue invasion and metastasis. Our studies and those of our colleagues suggest that HMGB1 is central to cancer (abnormal wound healing) and many of the findings in normal wound healing as well. Here, we focus on the role of HMGB1 in cancer, the mechanisms by which it contributes to carcinogenesis, and therapeutic strategies based on targeting HMGB1. Copyright 2009 Elsevier B.V. All rights reserved.
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                Author and article information

                Contributors
                Itaru Endo:
                ORCID: http://orcid.org/0000-0001-5520-8114
                81-45-787-2650 , endoit@yokohama-cu.ac.jp
                Journal
                Journal ID (nlm-ta): World J Surg Oncol
                Journal ID (iso-abbrev): World J Surg Oncol
                Title: World Journal of Surgical Oncology
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1477-7819
                Publication date (Electronic): 9 August 2019
                Publication date PMC-release: 9 August 2019
                Publication date Collection: 2019
                Volume: 17
                Electronic Location Identifier: 140
                Affiliations
                [1 ]ISNI 0000 0001 1033 6139, GRID grid.268441.d, Department of Gastroenterological Surgery, Graduate School of Medicine, , Yokohama City University, ; 3-9, Fukuura, Kanazawa-ku, Yokohama, 236-0004 Japan
                [2 ]ISNI 0000 0001 1033 6139, GRID grid.268441.d, Department of Surgery, Gastroenterological Center, , Yokohama City University, ; Yokohama, Japan
                [3 ]ISNI 0000 0004 0377 5418, GRID grid.417366.1, Department of Gastroenterological Surgery, , Yokohama Municipal Citizen’s Hospital, ; Yokohama, Japan
                [4 ]ISNI 0000 0004 0641 0318, GRID grid.417369.e, Department of Surgery, , Yokosuka Kyosai Hospital, ; Yokosuka, Japan
                [5 ]Department of Surgery, Yokosuka City Hospital, Yokosuka, Japan
                [6 ]Department of Surgery, Yokohama City Minato Red Cross Hospital, Yokohama, Japan
                [7 ]ISNI 0000 0004 1772 3686, GRID grid.415120.3, Department of Gastroenterological Surgery, , Fujisawa City Hospital, ; Fujisawa, Japan
                [8 ]Department of Surgery, Saiseikai Yokohama Nanbu Hospital, Yokohama, Japan
                [9 ]Department of Surgery, Yokohama Hodogaya Central Hospital, Yokohama, Japan
                [10 ]GRID grid.416687.a, Department of Surgery, , Saiseikai Wakakusa Hospital, ; Yokohama, Japan
                [11 ]Department of Surgery, Ito Municipal Hospital, Ito, Japan
                [12 ]ISNI 0000 0001 2107 4242, GRID grid.266100.3, Department of Surgery, , University of California, ; San Diego, California USA
                [13 ]ISNI 0000 0004 0461 1271, GRID grid.417448.a, AntiCancer, Inc., ; San Diego, California USA
                Author information
                http://orcid.org/0000-0001-5520-8114
                Article
                Publisher ID: 1675
                DOI: 10.1186/s12957-019-1675-8
                PMC ID: 6689175
                PubMed ID: 31399104
                SO-VID: e65857bc-5889-41bd-a796-6b955781f172
                Copyright © © The Author(s). 2019
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 3 March 2019
                Date accepted : 23 July 2019
                Categories
                Subject: Research
                Custom metadata
                issue-copyright-statement © The Author(s) 2019

                ScienceOpen disciplines: Surgery
                Keywords: hmgb1,adenocarcinoma of the ampulla of vater,overall survival
                Data availability:
                ScienceOpen disciplines: Surgery
                Keywords: hmgb1, adenocarcinoma of the ampulla of vater, overall survival

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