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Supportive Care in Cancer
Published in: Supportive Care in Cancer 10/2019

01-10-2019 | Special Article

The pathogenesis of mucositis: updated perspectives and emerging targets

Authors: J. Bowen, N. Al-Dasooqi, P. Bossi, H. Wardill, Y. Van Sebille, A. Al-Azri, E. Bateman, M. E. Correa, J. Raber-Durlacher, A. Kandwal, B. Mayo, R. G. Nair, A. Stringer, K. ten Bohmer, D. Thorpe, R. V. Lalla, S. Sonis, K. Cheng, S. Elad, On behalf of The Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO)

Published in: Supportive Care in Cancer | Issue 10/2019

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Abstract

Mucositis research and treatment are a rapidly evolving field providing constant new avenues of research and potential therapies. The MASCC/ISOO Mucositis Study Group regularly assesses available literature relating to pathogenesis, mechanisms, and novel therapeutic approaches and distils this to summary perspectives and recommendations. Reviewers assessed 164 articles published between January 2011 and June 2016 to identify progress made since the last review and highlight new targets for further investigation. Findings were organized into sections including established and emerging mediators of toxicity, potential insights from technological advances in mucositis research, and perspective. Research momentum is accelerating for mucositis pathogenesis, and with this has come utilization of new models and interventions that target specific mechanisms of injury. Technological advances have the potential to revolutionize the field of mucositis research, although focused effort is needed to move rationally targeted interventions to the clinical setting.
Literature
1.
Al-Dasooqi N, Sonis ST, Bowen JM, Bateman E, Blijlevens N, Gibson RJ, Logan RM, Nair RG, Stringer AM, Yazbeck R, Elad S, Lalla RV, Mucositis Study Group of Multinational Association of Supportive Care in Cancer/International Society of Oral O (2013) Emerging evidence on the pathobiology of mucositis. Support Care Cancer 21:2075–2083CrossRefPubMed
2.
Anthony L, Bowen J, Garden A, Hewson I, Sonis S (2006) New thoughts on the pathobiology of regimen-related mucosal injury. Support Care Cancer 14:516–518CrossRefPubMed
3.
Sonis ST, Elting LS, Keefe D, Peterson DE, Schubert M, Hauer-Jensen M, Bekele BN, Raber-Durlacher J, Donnelly JP, Rubenstein EB, Mucositis Study Section of the Multinational Association for Supportive Care in C, and International Society for Oral O (2004) Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients. Cancer 100:1995–2025CrossRefPubMed
4.
Sixou JL, de Medeiros-Batista O, Bonnaure-Mallet M (1996) Modifications of the microflora of the oral cavity arising during immunosuppressive chemotherapy. Eur J Cancer B Oral Oncol 32B:306–310CrossRefPubMed
5.
Donnelly JP, Bellm LA, Epstein JB, Sonis ST, Symonds RP (2003) Antimicrobial therapy to prevent or treat oral mucositis. Lancet Infect Dis 3:405–412CrossRefPubMed
6.
Ye Y, Carlsson G, Agholme MB, Wilson JA, Roos A, Henriques-Normark B, Engstrand L, Modeer T, Putsep K (2013) Oral bacterial community dynamics in paediatric patients with malignancies in relation to chemotherapy-related oral mucositis: a prospective study. Clin Microbiol Infect 19:E559–E567CrossRefPubMedPubMedCentral
7.
De Ryck T, Grootaert C, Jaspaert L, Kerckhof FM, Van Gele M, De Schrijver J, Van den Abbeele P, Swift S, Bracke M, Van de Wiele T, Vanhoecke B (2014) Development of an oral mucosa model to study host-microbiome interactions during wound healing. Appl Microbiol Biotechnol 98:6831–6846CrossRefPubMed
8.
De Ryck T, Van Impe A, Vanhoecke BW, Heyerick A, Vakaet L, De Neve W, Muller D, Schmidt M, Dorr W, Bracke ME (2015) 8-prenylnaringenin and tamoxifen inhibit the shedding of irradiated epithelial cells and increase the latency period of radiation-induced oral mucositis : cell culture and murine model. Strahlenther Onkol 191:429–436CrossRefPubMed
9.
Vanhoecke BW, De Ryck TR, De boel K, Wiles S, Boterberg T, Van de Wiele T, Swift S (2016) Low-dose irradiation affects the functional behavior of oral microbiota in the context of mucositis. Exp Biol Med (Maywood) 241:60–70CrossRef
10.
Vanlancker E, Vanhoecke B, Smet R, Props R, Van de Wiele T (2016) 5-fluorouracil sensitivity varies among oral micro-organisms. J Med Microbiol 65:775–783CrossRefPubMed
11.
Wang A, Ling Z, Yang Z, Kiela PR, Wang T, Wang C, Cao L, Geng F, Shen M, Ran X, Su Y, Cheng T, Wang J (2015) Gut microbial dysbiosis may predict diarrhea and fatigue in patients undergoing pelvic cancer radiotherapy: a pilot study. PLoS One 10:e0126312CrossRefPubMedPubMedCentral
12.
Montassier E, Gastinne T, Vangay P, Al-Ghalith GA, Bruley des Varannes S, Massart S, Moreau P, Potel G, de La Cochetiere MF, Batard E, Knights D (2015) Chemotherapy-driven dysbiosis in the intestinal microbiome. Aliment Pharmacol Ther 42:515–528CrossRefPubMed
13.
Alexander JL, Wilson ID, Teare J, Marchesi JR, Nicholson JK, Kinross JM (2017) Gut microbiota modulation of chemotherapy efficacy and toxicity. Nat Rev Gastroenterol Hepatol 14:356–365CrossRefPubMed
14.
Pontoppidan PE, Shen RL, Cilieborg MS, Jiang P, Kissow H, Petersen BL, Thymann T, Heilmann C, Muller K, Sangild PT (2015) Bovine colostrum modulates Myeloablative chemotherapy-induced gut toxicity in piglets. J Nutr 145:1472–1480CrossRefPubMed
15.
Lin XB, Dieleman LA, Ketabi A, Bibova I, Sawyer MB, Xue H, Field CJ, Baracos VE, Ganzle MG (2012) Irinotecan (CPT-11) chemotherapy alters intestinal microbiota in tumour bearing rats. PLoS One 7:e39764CrossRefPubMedPubMedCentral
16.
Nam YD, Kim HJ, Seo JG, Kang SW, Bae JW (2013) Impact of pelvic radiotherapy on gut microbiota of gynecological cancer patients revealed by massive pyrosequencing. PLoS One 8:e82659CrossRefPubMedPubMedCentral
17.
Stringer AM, Al-Dasooqi N, Bowen JM, Tan TH, Radzuan M, Logan RM, Mayo B, Keefe DM, Gibson RJ (2013) Biomarkers of chemotherapy-induced diarrhoea: a clinical study of intestinal microbiome alterations, inflammation and circulating matrix metalloproteinases. Support Care Cancer 21:1843–1852CrossRefPubMed
18.
Montassier E, Batard E, Massart S, Gastinne T, Carton T, Caillon J, Le Fresne S, Caroff N, Hardouin JB, Moreau P, Potel G, Le Vacon F, de La Cochetiere MF (2014) 16S rRNA gene pyrosequencing reveals shift in patient faecal microbiota during high-dose chemotherapy as conditioning regimen for bone marrow transplantation. Microb Ecol 67:690–699CrossRefPubMed
19.
Cario E (2016) Toll-like receptors in the pathogenesis of chemotherapy-induced gastrointestinal toxicity. Curr Opin Support Palliat Care 10:157–164CrossRefPubMed
20.
Wardill HR, Gibson RJ, Van Sebille YZ, Secombe KR, Coller JK, White IA, Manavis J, Hutchinson MR, Staikopoulos V, Logan RM, Bowen JM (2016) Irinotecan-induced gastrointestinal dysfunction and pain are mediated by common TLR4-dependent mechanisms. Mol Cancer Ther 15:1376–1386CrossRefPubMed
21.
Wong DV, Lima-Junior RC, Carvalho CB, Borges VF, Wanderley CW, Bem AX, Leite CA, Teixeira MA, Batista GL, Silva RL, Cunha TM, Brito GA, Almeida PR, Cunha FQ, Ribeiro RA (2015) The adaptor protein Myd88 is a key signaling molecule in the pathogenesis of irinotecan-induced intestinal mucositis. PLoS One 10:e0139985CrossRefPubMedPubMedCentral
22.
Frank M, Hennenberg EM, Eyking A, Runzi M, Gerken G, Scott P, Parkhill J, Walker AW, Cario E (2015) TLR signaling modulates side effects of anticancer therapy in the small intestine. J Immunol 194:1983–1995CrossRefPubMedPubMedCentral
23.
Kaczmarek A, Brinkman BM, Heyndrickx L, Vandenabeele P, Krysko DV (2012) Severity of doxorubicin-induced small intestinal mucositis is regulated by the TLR-2 and TLR-9 pathways. J Pathol 226:598–608CrossRefPubMed
24.
Piccinini AM, Midwood KS (2010) DAMPening inflammation by modulating TLR signalling. Mediat Inflamm 2010
25.
Pedroso SH, Vieira AT, Bastos RW, Oliveira JS, Cartelle CT, Arantes RM, Soares PM, Generoso SV, Cardoso VN, Teixeira MM, Nicoli JR, Martins FS (2015) Evaluation of mucositis induced by irinotecan after microbial colonization in germ-free mice. Microbiology 161:1950–1960CrossRefPubMed
26.
Burdelya LG, Gleiberman AS, Toshkov I, Aygun-Sunar S, Bapardekar M, Manderscheid-Kern P, Bellnier D, Krivokrysenko VI, Feinstein E, Gudkov AV (2012) Toll-like receptor 5 agonist protects mice from dermatitis and oral mucositis caused by local radiation: implications for head-and-neck cancer radiotherapy. Int J Radiat Oncol Biol Phys 83:228–234CrossRefPubMed
27.
Jones RM, Sloane VM, Wu H, Luo L, Kumar A, Kumar MV, Gewirtz AT, Neish AS (2011) Flagellin administration protects gut mucosal tissue from irradiation-induced apoptosis via MKP-7 activity. Gut 60:648–657CrossRefPubMed
28.
Saha S, Bhanja P, Liu L, Alfieri AA, Yu D, Kandimalla ER, Agrawal S, Guha C (2012) TLR9 agonist protects mice from radiation-induced gastrointestinal syndrome. PLoS One 7:e29357CrossRefPubMedPubMedCentral
29.
Riehl T, Cohn S, Tessner T, Schloemann S, Stenson WF (2000) Lipopolysaccharide is radioprotective in the mouse intestine through a prostaglandin-mediated mechanism. Gastroenterology 118:1106–1116CrossRefPubMed
30.
Bastos RW, Pedroso SH, Vieira AT, Moreira LM, Franca CS, Cartelle CT, Arantes RM, Generoso SV, Cardoso VN, Neves MJ, Nicoli JR, Martins FS (2016) Saccharomyces cerevisiae UFMG A-905 treatment reduces intestinal damage in a murine model of irinotecan-induced mucositis. Benef Microbes 7:549–557CrossRefPubMed
31.
Ciorba MA, Riehl TE, Rao MS, Moon C, Ee X, Nava GM, Walker MR, Marinshaw JM, Stappenbeck TS, Stenson WF (2012) Lactobacillus probiotic protects intestinal epithelium from radiation injury in a TLR-2/cyclo-oxygenase-2-dependent manner. Gut 61:829–838CrossRefPubMed
32.
Justino PF, Melo LF, Nogueira AF, Costa JV, Silva LM, Santos CM, Mendes WO, Costa MR, Franco AX, Lima AA, Ribeiro RA, Souza MH, Soares PM (2014) Treatment with Saccharomyces boulardii reduces the inflammation and dysfunction of the gastrointestinal tract in 5-fluorouracil-induced intestinal mucositis in mice. Br J Nutr 111:1611–1621CrossRefPubMed
33.
Tang Y, Wu Y, Huang Z, Dong W, Deng Y, Wang F, Li M, Yuan J (2016) Administration of probiotic mixture DM#1 ameliorated 5-fluorouracil-induced intestinal mucositis and dysbiosis in rats. Nutrition
34.
Xie JH, Fan ST, Nie SP, Yu Q, Xiong T, Gong D, Xie MY (2016) Lactobacillus plantarum NCU116 attenuates cyclophosphamide-induced intestinal mucosal injury, metabolism and intestinal microbiota disorders in mice. Food Funct 7:1584–1592CrossRefPubMed
35.
Yeung CY, Chan WT, Jiang CB, Cheng ML, Liu CY, Chang SW, Chiang Chiau JS, Lee HC (2015) Amelioration of chemotherapy-induced intestinal mucositis by orally administered probiotics in a mouse model. PLoS One 10:e0138746CrossRefPubMedPubMedCentral
36.
Yuan KT, Yu HL, Feng WD, Chong P, Yang T, Xue CL, Yu M, Shi HP (2015) Bifidobacterium infantis has a beneficial effect on 5-fluorouracil-induced intestinal mucositis in rats. Benefic Microbes 6:113–118CrossRef
37.
Wang H, Brook CL, Whittaker AL, Lawrence A, Yazbeck R, Howarth GS (2013) Effects of Streptococcus thermophilus TH-4 in a rat model of doxorubicin-induced mucositis. Scand J Gastroenterol 48:959–968CrossRefPubMed
38.
Gibson RJ, Keefe DM, Lalla RV, Bateman E, Blijlevens N, Fijlstra M, King EE, Stringer AM, van der Velden WJ, Yazbeck R, Elad S, Bowen JM, Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral O (2013) Systematic review of agents for the management of gastrointestinal mucositis in cancer patients. Support Care Cancer 21:313–326CrossRefPubMed
39.
Lalla RV, Bowen J, Barasch A, Elting L, Epstein J, Keefe DM, McGuire DB, Migliorati C, Nicolatou-Galitis O, Peterson DE, Raber-Durlacher JE, Sonis ST, Elad S, Mucositis guidelines leadership Group of the Multinational Association of supportive Care in C, and International Society of Oral O (2014) MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer 120:1453–1461CrossRefPubMedPubMedCentral
40.
Vanhoecke B, De Ryck T, Stringer A, Van de Wiele T, Keefe D (2015) Microbiota and their role in the pathogenesis of oral mucositis. Oral Dis 21:17–30CrossRefPubMed
41.
Laheij AM, de Soet JJ, von dem Borne PA, Kuijper EJ, Kraneveld EA, van Loveren C, Raber-Durlacher JE (2012) Oral bacteria and yeasts in relationship to oral ulcerations in hematopoietic stem cell transplant recipients. Support Care Cancer 20:3231–3240CrossRefPubMedPubMedCentral
42.
Frings K, Gruber S, Kuess P, Kleiter M, Dorr W (2016) Modulation of radiation-induced oral mucositis by thalidomide : preclinical studies. Strahlenther Onkol 192:561–568CrossRefPubMed
43.
Gruber S, Hamedinger D, Bozsaky E, Schmidt M, Wolfram K, Haagen J, Habelt B, Puttrich M, Dorr W (2015) Local hypoxia in oral mucosa (mouse) during daily fractionated irradiation - effect of pentoxifylline. Radiother Oncol 116:404–408CrossRefPubMed
44.
Gruber S, Schmidt M, Bozsaky E, Wolfram K, Haagen J, Habelt B, Puttrich M, Dorr W (2015) Modulation of radiation-induced oral mucositis by pentoxifylline: preclinical studies. Strahlenther Onkol 191:242–247CrossRefPubMed
45.
Lalla RV, Choquette LE, Curley KF, Dowsett RJ, Feinn RS, Hegde UP, Pilbeam CC, Salner AL, Sonis ST, Peterson DE (2014) Randomized double-blind placebo-controlled trial of celecoxib for oral mucositis in patients receiving radiation therapy for head and neck cancer. Oral Oncol 50:1098–1103CrossRefPubMedPubMedCentral
46.
Jensen SB, Jarvis V, Zadik Y, Barasch A, Ariyawardana A, Hovan A, Yarom N, Lalla RV, Bowen J, Elad S, Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral O (2013) Systematic review of miscellaneous agents for the management of oral mucositis in cancer patients. Support Care Cancer 21:3223–3232CrossRefPubMed
47.
Wu Z, Han X, Qin S, Zheng Q, Wang Z, Xiang D, Zhang J, Lu H, Wu M, Zhu S, Yu Y, Wang Y, Han W (2011) Interleukin 1 receptor antagonist reduces lethality and intestinal toxicity of 5-fluorouracil in a mouse mucositis model. Biomed Pharmacother 65:339–344CrossRefPubMed
48.
Wu ZQ, Han XD, Wang Y, Yuan KL, Jin ZM, Di JZ, Yan J, Pan Y, Zhang P, Huang XY, Wang ZG, Zheng Q (2011) Interleukin-1 receptor antagonist reduced apoptosis and attenuated intestinal mucositis in a 5-fluorouracil chemotherapy model in mice. Cancer Chemother Pharmacol 68:87–96CrossRefPubMed
49.
Xiang D, Guo Y, Zhang J, Gao J, Lu H, Zhu S, Wu M, Yu Y, Han W (2011) Interleukin-1 receptor antagonist attenuates cyclophosphamide-induced mucositis in a murine model. Cancer Chemother Pharmacol 67:1445–1453CrossRefPubMed
50.
Han G, Bian L, Li F, Cotrim A, Wang D, Lu J, Deng Y, Bird G, Sowers A, Mitchell JB, Gutkind JS, Zhao R, Raben D, ten Dijke P, Refaeli Y, Zhang Q, Wang XJ (2013) Preventive and therapeutic effects of Smad7 on radiation-induced oral mucositis. Nat Med 19:421–428CrossRefPubMedPubMedCentral
51.
Al-Asmari AK, Khan AQ, Al-Qasim AM, Al-Yousef Y (2015) Ascorbic acid attenuates antineoplastic drug 5-fluorouracil induced gastrointestinal toxicity in rats by modulating the expression of inflammatory mediators. Toxicol Rep 2:908–916CrossRefPubMedPubMedCentral
52.
Ortiz F, Acuna-Castroviejo D, Doerrier C, Dayoub JC, Lopez LC, Venegas C, Garcia JA, Lopez A, Volt H, Luna-Sanchez M, Escames G (2015) Melatonin blunts the mitochondrial/NLRP3 connection and protects against radiation-induced oral mucositis. J Pineal Res 58:34–49CrossRefPubMed
53.
Arifa RD, Madeira MF, de Paula TP, Lima RL, Tavares LD, Menezes-Garcia Z, Fagundes CT, Rachid MA, Ryffel B, Zamboni DS, Teixeira MM, Souza DG (2014) Inflammasome activation is reactive oxygen species dependent and mediates irinotecan-induced mucositis through IL-1beta and IL-18 in mice. Am J Pathol 184:2023–2034CrossRefPubMed
54.
Arifa RDN, Paula TP, Madeira MFM, Lima RL, Garcia ZM, Yvila TV, Pinho V, Barcelos LS, Pinheiro MVB, Ladeira LO, Krambrock K, Teixeira MM, Souza DG (2016) The reduction of oxidative stress by nanocomposite Fullerol decreases mucositis severity and reverts leukopenia induced by irinotecan. Pharmacol Res 107:102–110CrossRefPubMed
55.
Ashcraft KA, Boss MK, Tovmasyan A, Roy Choudhury K, Fontanella AN, Young KH, Palmer GM, Birer SR, Landon CD, Park W, Das SK, Weitner T, Sheng H, Warner DS, Brizel DM, Spasojevic I, Batinic-Haberle I, Dewhirst MW (2015) Novel manganese-porphyrin superoxide dismutase-mimetic widens the therapeutic margin in a preclinical head and neck Cancer model. Int J Radiat Oncol Biol Phys 93:892–900CrossRefPubMedPubMedCentral
56.
Gao J, Gao J, Qian L, Wang X, Wu M, Zhang Y, Ye H, Zhu S, Yu Y, Han W (2014) Activation of p38-MAPK by CXCL4/CXCR3 axis contributes to p53-dependent intestinal apoptosis initiated by 5-fluorouracil. Cancer Biol Ther 15:982–991CrossRefPubMedPubMedCentral
57.
Lu H, Liu H, Wang J, Shen J, Weng S, Han L, Sun T, Qian L, Wu M, Zhu S, Yu Y, Han W, Zhu J, Moldenhauer A (2015) The chemokine CXCL9 exacerbates chemotherapy-induced acute intestinal damage through inhibition of mucosal restitution. J Cancer Res Clin Oncol 141:983–992CrossRefPubMed
58.
Soares PM, Mota JM, Souza EP, Justino PF, Franco AX, Cunha FQ, Ribeiro RA, Souza MH (2013) Inflammatory intestinal damage induced by 5-fluorouracil requires IL-4. Cytokine 61:46–49CrossRefPubMed
59.
Li K, Qu S, Chen X, Wu Q, Shi M (2017) Promising targets for Cancer immunotherapy: TLRs, RLRs, and STING-mediated innate immune pathways. Int J Mol Sci 18
60.
Linard C, Busson E, Holler V, Strup-Perrot C, Lacave-Lapalun JV, Lhomme B, Prat M, Devauchelle P, Sabourin JC, Simon JM, Bonneau M, Lataillade JJ, Benderitter M (2013) Repeated autologous bone marrow-derived mesenchymal stem cell injections improve radiation-induced proctitis in pigs. Stem Cells Transl Med 2:916–927CrossRefPubMedPubMedCentral
61.
Linard C, Strup-Perrot C, Lacave-Lapalun JV, Benderitter M (2016) Flagellin preconditioning enhances the efficacy of mesenchymal stem cells in an irradiation-induced proctitis model. J Leukoc Biol 100:569–580CrossRefPubMed
62.
Wang R, Yuan W, Zhao Q, Song P, Yue J, Lin SD, Zhao TB (2013) An experimental study of preventing and treating acute radioactive enteritis with human umbilical cord mesenchymal stem cells. Asian Pac J Trop Med 6:968–971CrossRefPubMed
63.
Duan HG, Ji F, Zheng CQ, Wang CH, Li J (2015) Human umbilical cord mesenchymal stem cells alleviate nasal mucosa radiation damage in a guinea pig model. J Cell Biochem 116:331–338CrossRefPubMed
64.
Bessout R, Demarquay C, Moussa L, Rene A, Doix B, Benderitter M, Semont A, Mathieu N (2015) TH17 predominant T-cell responses in radiation-induced bowel disease are modulated by treatment with adipose-derived mesenchymal stromal cells. J Pathol 237:435–446CrossRefPubMed
65.
Schmidt M, Haagen J, Noack R, Siegemund A, Gabriel P, Dorr W (2014) Effects of bone marrow or mesenchymal stem cell transplantation on oral mucositis (mouse) induced by fractionated irradiation. Strahlenther Onkol 190:399–404CrossRefPubMed
66.
Munneke JM, Bjorklund AT, Mjosberg JM, Garming-Legert K, Bernink JH, Blom B, Huisman C, van Oers MH, Spits H, Malmberg KJ, Hazenberg MD (2014) Activated innate lymphoid cells are associated with a reduced susceptibility to graft-versus-host disease. Blood 124:812–821CrossRefPubMed
67.
68.
Sanchez-Lara K, Ugalde-Morales E, Motola-Kuba D, Green D (2013) Gastrointestinal symptoms and weight loss in cancer patients receiving chemotherapy. Br J Nutr 109:894–897CrossRefPubMed
69.
Fijlstra M, Ferdous M, Koning AM, Rings EH, Harmsen HJ, Tissing WJ (2015) Substantial decreases in the number and diversity of microbiota during chemotherapy-induced gastrointestinal mucositis in a rat model. Support Care Cancer 23:1513–1522CrossRefPubMed
70.
Fijlstra M, Rings EH, van Dijk TH, Plosch T, Verkade HJ, Tissing WJ (2013) Continuous enteral administration can overcome the limited capacity to absorb glucose in rats with methotrexate-induced gastrointestinal mucositis. Support Care Cancer 21:863–871CrossRefPubMed
71.
Fijlstra M, Rings EH, Verkade HJ, van Dijk TH, Kamps WA, Tissing WJ (2011) Lactose maldigestion during methotrexate-induced gastrointestinal mucositis in a rat model. Am J Physiol Gastrointest Liver Physiol 300:G283–G291CrossRefPubMed
72.
Gareau MG, Barrett KE (2013) Fluid and electrolyte secretion in the inflamed gut: novel targets for treatment of inflammation-induced diarrhea. Curr Opin Pharmacol 13:895–899CrossRefPubMed
73.
McQuade RM, Stojanovska V, Donald E, Abalo R, Bornstein JC, Nurgali K (2016) Gastrointestinal dysfunction and enteric neurotoxicity following treatment with anticancer chemotherapeutic agent 5-fluorouracil. Neurogastroenterol Motil 28:1861–1875CrossRefPubMed
74.
Robinson AM, Stojanovska V, Rahman AA, McQuade RM, Senior PV, Nurgali K (2016) Effects of Oxaliplatin treatment on the enteric glial cells and neurons in the mouse ileum. J Histochem Cytochem 64:530–545CrossRefPubMedPubMedCentral
75.
Cheadle GA, Costantini TW, Lopez N, Bansal V, Eliceiri BP, Coimbra R (2013) Enteric glia cells attenuate cytomix-induced intestinal epithelial barrier breakdown. PLoS One 8:e69042CrossRefPubMedPubMedCentral
76.
Melichar B, Dvorak J, Hyspler R, Zadak Z (2005) Intestinal permeability in the assessment of intestinal toxicity of cytotoxic agents. Chemotherapy 51:336–338CrossRefPubMed
77.
78.
Wardill HR, Bowen JM, Al-Dasooqi N, Sultani M, Bateman E, Stansborough R, Shirren J, Gibson RJ (2014) Irinotecan disrupts tight junction proteins within the gut : implications for chemotherapy-induced gut toxicity. Cancer Biol Ther 15:236–244CrossRefPubMed
79.
Biju PG, Garg S, Wang W, Choudhry MA, Kovacs EJ, Fink LM, Hauer-Jensen M (2012) Procalcitonin as a predictive biomarker for total body irradiation-induced bacterial load and lethality in mice. Shock 38:170–176CrossRefPubMedPubMedCentral
80.
Russo F, Linsalata M, Clemente C, D'Attoma B, Orlando A, Campanella G, Giotta F, Riezzo G (2013) The effects of fluorouracil, epirubicin, and cyclophosphamide (FEC60) on the intestinal barrier function and gut peptides in breast cancer patients: an observational study. BMC Cancer 13:56CrossRefPubMedPubMedCentral
81.
Beutheu S, Ouelaa W, Guerin C, Belmonte L, Aziz M, Tennoune N, Bole-Feysot C, Galas L, Dechelotte P, Coeffier M (2014) Glutamine supplementation, but not combined glutamine and arginine supplementation, improves gut barrier function during chemotherapy-induced intestinal mucositis in rats. Clin Nutr 33:694–701CrossRefPubMed
82.
Kim HJ, Lee J, Choi JH, Bahinski A, Ingber DE (2016) Co-culture of living microbiome with microengineered human intestinal villi in a gut-on-a-Chip microfluidic device. J Vis Exp
83.
Colley HE, Eves PC, Pinnock A, Thornhill MH, Murdoch C (2013) Tissue-engineered oral mucosa to study radiotherapy-induced oral mucositis. Int J Radiat Biol 89:907–914CrossRefPubMed
84.
Lambros MP, DeSalvo MK, Moreno J, Mulamalla HC, Kondapalli L (2015) Transcriptional profiling of radiation damage and preventive treatments in a 3-dimensional (3D) human cell culture model of oral mucositis. Genom Data 6:40–43CrossRefPubMedPubMedCentral
85.
Lambros MP, DeSalvo MK, Mulamalla HC, Moreno J, Kondapalli L (2016) Genome wide expression after different doses of irradiation of a three-dimensional (3D) model of oral mucosal. Genom Data 7:137–139CrossRefPubMed
86.
Lambros MP, Kondapalli L, Parsa C, Mulamalla HC, Orlando R, Pon D, Huang Y, Chow MS (2015) Molecular signatures in the prevention of radiation damage by the synergistic effect of N-acetyl cysteine and qingre liyan decoction, a traditional chinese medicine, using a 3-dimensional cell culture model of oral mucositis. Evid Based Complement Alternat Med 2015:425760CrossRefPubMedPubMedCentral
87.
Chang PY, Jin X, Jiang YY, Wang LX, Liu YJ, Wang J (2016) Mensenchymal stem cells can delay radiation-induced crypt death: impact on intestinal CD44(+) fragments. Cell Tissue Res 364:331–344CrossRefPubMed
88.
Grabinger T, Delgado E, Brunner T (2016) Analysis of cell death induction in intestinal organoids in vitro. Methods Mol Biol 1419:83–93CrossRefPubMed
89.
Liu F, Huang J, Ning B, Liu Z, Chen S, Zhao W (2016) Drug discovery via human-derived stem cell organoids. Front Pharmacol 7:334PubMedPubMedCentral
90.
Farrell CL, Bready JV, Rex KL, Chen JN, DiPalma CR, Whitcomb KL, Yin S, Hill DC, Wiemann B, Starnes CO, Havill AM, Lu ZN, Aukerman SL, Pierce GF, Thomason A, Potten CS, Ulich TR, Lacey DL (1998) Keratinocyte growth factor protects mice from chemotherapy and radiation-induced gastrointestinal injury and mortality. Cancer Res 58:933–939PubMed
91.
Rosen LS, Abdi E, Davis ID, Gutheil J, Schnell FM, Zalcberg J, Cesano A, Gayko U, Chen MG, Clarke S (2006) Palifermin reduces the incidence of oral mucositis in patients with metastatic colorectal cancer treated with fluorouracil-based chemotherapy. J Clin Oncol 24:5194–5200CrossRefPubMed
92.
Limaye SA, Haddad RI, Cilli F, Sonis ST, Colevas AD, Brennan MT, Hu KS, Murphy BA (2013) Phase 1b, multicenter, single blinded, placebo-controlled, sequential dose escalation study to assess the safety and tolerability of topically applied AG013 in subjects with locally advanced head and neck cancer receiving induction chemotherapy. Cancer 119:4268–4276CrossRefPubMed
93.
Caluwaerts S, Vandenbroucke K, Steidler L, Neirynck S, Vanhoenacker P, Corveleyn S, Watkins B, Sonis S, Coulie B, Rottiers P (2010) AG013, a mouth rinse formulation of Lactococcus lactis secreting human trefoil factor 1, provides a safe and efficacious therapeutic tool for treating oral mucositis. Oral Oncol 46:564–570CrossRefPubMed
94.
Cheah KY, Howarth GS, Bastian SE (2014) Grape seed extract dose-responsively decreases disease severity in a rat model of mucositis; concomitantly enhancing chemotherapeutic effectiveness in colon cancer cells. PLoS One 9:e85184CrossRefPubMedPubMedCentral
95.
Davarmanesh M, Miri R, Haghnegahdar S, Tadbir AA, Tanideh N, Saghiri MA, Garcia-Godoy F, Asatourian A (2013) Protective effect of bilberry extract as a pretreatment on induced oral mucositis in hamsters. Oral Surg Oral Med Oral Pathol Oral Radiol 116:702–708CrossRefPubMed
96.
de Freitas Cuba L, Braga Filho A, Cherubini K, Salum FG, Figueiredo MA (2016) Topical application of Aloe vera and vitamin E on induced ulcers on the tongue of rats subjected to radiation: clinical and histological evaluation. Support Care Cancer 24:2557–2564CrossRefPubMed
97.
Koohi-Hosseinabadi O, Andisheh-Tadbir A, Bahadori P, Sepehrimanesh M, Mardani M, Tanideh N (2015) Comparison of the therapeutic effects of the dietary and topical forms of Zizyphus jujuba extract on oral mucositis induced by 5-fluorouracil: a golden hamster model. J Clin Exp Dent 7:e304–e309CrossRefPubMedPubMedCentral
98.
Sezer A, Usta U, Kocak Z, Yagci MA (2011) The effect of a flavonoid fractions diosmin + hesperidin on radiation-induced acute proctitis in a rat model. J Cancer Res Ther 7:152–156CrossRefPubMed
99.
Shi CJ, Wen XS, Gao HF, Liu ZH, Xu XK, Li LF, Shen T, Xian CJ (2016) Steamed root of Rehmannia glutinosa Libosch (Plantaginaceae) alleviates methotrexate-induced intestinal mucositis in rats. J Ethnopharmacol 183:143–150CrossRefPubMed
100.
Shin YS, Shin HA, Kang SU, Kim JH, Oh YT, Park KH, Kim CH (2013) Effect of epicatechin against radiation-induced oral mucositis: in vitro and in vivo study. PLoS One 8:e69151CrossRefPubMedPubMedCentral
101.
Tang Q, Zuo T, Lu S, Wu J, Wang J, Zheng R, Chen S, Xue C (2014) Dietary squid ink polysaccharides ameliorated the intestinal microflora dysfunction in mice undergoing chemotherapy. Food Funct 5:2529–2535CrossRefPubMed
102.
Tanideh N, Namazi F, Andisheh Tadbir A, Ebrahimi H, Koohi-Hosseinabadi O (2014) Comparative assessment of the therapeutic effects of the topical and systemic forms of Hypericum perforatum extract on induced oral mucositis in golden hamsters. Int J Oral Maxillofac Surg 43:1286–1292CrossRefPubMed
103.
Younes-Sakr L, Senesse P, Laurent C, Rouanet JM, Rugani N, Cristol JP, Gaillet S (2012) Validation of a surgical technique for rat intestinal irradiation: potential side effects prevention by dietary grape phenolics. Dig Dis Sci 57:2562–2570CrossRefPubMed
104.
Zuo T, Li X, Chang Y, Duan G, Yu L, Zheng R, Xue C, Tang Q (2015) Dietary fucoidan of Acaudina molpadioides and its enzymatically degraded fragments could prevent intestinal mucositis induced by chemotherapy in mice. Food Funct 6:415–422CrossRefPubMed
Metadata
Title
The pathogenesis of mucositis: updated perspectives and emerging targets
Authors
J. Bowen
N. Al-Dasooqi
P. Bossi
H. Wardill
Y. Van Sebille
A. Al-Azri
E. Bateman
M. E. Correa
J. Raber-Durlacher
A. Kandwal
B. Mayo
R. G. Nair
A. Stringer
K. ten Bohmer
D. Thorpe
R. V. Lalla
S. Sonis
K. Cheng
S. Elad
On behalf of The Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO)
Publication date
01-10-2019
Publisher
Springer Berlin Heidelberg
Published in
Supportive Care in Cancer / Issue 10/2019
Print ISSN: 0941-4355
Electronic ISSN: 1433-7339
DOI
https://doi.org/10.1007/s00520-019-04893-z

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