Chemotherapy- and radiotherapy-induced intestinal damage is regulated by intestinal trefoil factor

Beck, Paul L.; Wong, Jennifer; Li, Y.; Swaminathan, Sunita; Xavier, Ramnik J.; Devaney, Kathryn; Podolsky, Daniel K.

doi:10.1053/j.gastro.2003.12.004

Cited by 116 publications

(81 citation statements)

References 34 publications

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“…14 The different times to normalisation after the various myeloablative regimens suggest that not only is inhibition of intestinal clonogenic stem cell growth important but also that different myeloablative regimens affect the capacity for repairing the mucosa differently, this being mediated by the trefoil factor and other intestinal growth factors produced by goblet cells. 15,16 Wardley et al showed that the myeloablative regimen and not the disease or stem cell source determined the severity of oral mucositis with the highest peak of mucositis occurring after HDM. However, their analysis did not include patients treated with myeloablative regimens containing idarubicin.…”

Section: Discussionmentioning

confidence: 99%

Prospective evaluation of gut mucosal barrier injury following various myeloablative regimens for haematopoietic stem cell transplant

Blijlevens

Donnelly

Pauw

2005

Bone Marrow Transplant

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Summary:We determined gut mucosal barrier injury (MBI) among 129 recipients of an allogeneic or autologous haematopoietic stem cell transplant (HSCT) who had been given different myeloablative regimens by measuring integrity using the lactulose/rhamnose (RHA) ratio and absorption using the ratios of rhamnose/3-O-methylglucose and xylose/3-O-methylglucose. Regimens that did not contain idarubicin induced oral mucositis and disturbed gut integrity and absorption earlier than did those containing the anthracycline. By contrast, regimens containing idarubicin induced more severe and prolonged oral and gut MBI. Gut integrity and absorption of most patients were still abnormal at discharge from hospital. These results confirm that the integrity and absorptive capacity of the gut is affected adversely by myeloablative regimens in general, although only two patterns of mucosal injury emerged depending on whether or not idarubicin was used. Mucosal barrier injury (MBI) of the oral cavity is reported to affect more than 60% of haematopoietic stem cell transplant (HSCT) recipients given myeloablative preparative regimens. 1 Wardley and colleagues showed that the character, onset and progression of oral mucositis were markedly influenced by the nature of the conditioning therapy. For instance, high-dose melphalan aggravated oral mucositis, whereas its onset was delayed after busulphan. 2 Much less is known about the gastrointestinal counterpart of oral mucositis, although gut injury results in significant morbidity and mortality. 3 Sugar permeability tests can objectively determine changes in permeability (integrity and absorption) and have been found to complement the signs and symptoms associated with gut toxicity such as nausea, vomiting, diarrhoea and abdominal cramps. 4 However, it is not known whether gut MBI is also affected differently by the various myeloablative regimens. Moreover, our standard conditioning regimen consists of idarubicin, cyclophosphamide and TBI, 5 and is known to induce prolonged and severe oral mucositis. 6 Therefore, we employed a sugar permeability test to determine differences in gut permeability, integrity and absorption of a cohort of HSCT recipients given different myeloablative regimens. Patients, methods and materials Patients

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Section: Discussionmentioning

confidence: 99%

Prospective evaluation of gut mucosal barrier injury following various myeloablative regimens for haematopoietic stem cell transplant

Blijlevens

Donnelly

Pauw

2005

Bone Marrow Transplant

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“…The previous studies of TFF3 have focused on its maintenance of mucosal integrity and the promotion of repair. Evidence suggests that TFF3 serves as an initiator of mucosal healing to enable the acute restoration of cellular continuity, and TFF3-deficient mice showed an impaired capacity for mucosal recovery after colonic injury even after exposure to antineoplastic agents and total body radiation (Beck et al, 2004;Mashimo et al, 1996). Additionally, a recent clinical report showed that a recombinant human TFF3 (rhTFF3) oral spray formulation was safe and effective for the treatment of chemotherapyassociated oral mucositis in patients with colorectal cancer (Peterson et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

PI3K/Akt Signaling Pathway in the Basolateral Amygdala Mediates the Rapid Antidepressant-like Effects of Trefoil Factor 3

Shi

Zhu

Liu

et al. 2012

Neuropsychopharmacol

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“…We did not see changes in TFF3 expression in Fuc-TVII Ϫ/Ϫ mice (vs. wild-type mice), and there was no difference in Fuc-TVII expression/activity in TFF3 Ϫ/Ϫ mice compared with wild-type animals at baseline. TFF3 expression was not assessed in the IL-2/␤2m Ϫ/Ϫ mice, but one would suspect that it may be increased during the early phases of colitis since TFF3 has been found to be upregulated in forms of intestinal inflammation (3,23). Although there is Fig.…”

Section: Discussionmentioning

confidence: 99%

“…The function of selectin ligands is closely linked to the appropriate posttranslational glycosylation including fucosylation, sialylation, or sulfation. Furthermore, the addition of fucose to the GlcNAc of core 2 decorated O-glycans in ␣1,3 linkage [␣ (1,3) fucosylation] is a key step for synthesis of functional selectin ligands. To date, six ␣(1,3) fucosyltransferases (Fuc-T) have been identified.…”

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confidence: 99%

Exploring the interplay of barrier function and leukocyte recruitment in intestinal inflammation by targeting fucosyltransferase VII and trefoil factor 3

Beck

Ihara

Hirota

et al. 2010

American Journal of Physiology-Gastrointestinal and Liver Physi

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Intestinal mucosal integrity is dependent on epithelial function and a regulated immune response to injury. Fucosyltransferase VII (Fuc-TVII) is an essential enzyme required for the expression of the functional ligand for E- and P-selectin. Trefoil factor 3 (TFF3) is involved in both protecting the intestinal epithelium against injury as well as aiding in wound repair following injury. The aim of the present study was to assess the interplay between barrier function and leukocyte recruitment in intestinal inflammation. More specifically, we aimed to examine how targeted disruption of Fuc-TVII either in wild-type or TFF3−/− mice would alter their susceptibility to colonic injury. TFF3 and Fuc-TVII double-knockout mice (TFF3/Fuc-TVII−/− mice) were generated by mating TFF3−/− and Fuc-TVII−/− mice. Colitis was induced by administration of dextran sodium sulfate (DSS) (2.5% wt/vol) in the drinking water. Changes in baseline body weight, diarrhea, and fecal blood were assessed daily. Upon euthanasia, extents of colonic inflammation were assessed macroscopically, microscopically, and through quantification of myeloperoxidase (MPO) activity. Colonic lymphocyte subpopulations were assessed at 6 days after administration of DSS by flow cytometry and immunohistochemistry. No baseline intestinal inflammation was found in TFF3/Fuc-TVII−/−, TFF3−/−, Fuc-TVII−/−, or wild-type mice. Loss of Fuc-TVII resulted in a reduction in disease severity whereas TFF3−/− mice were markedly more susceptible to DSS-induced colitis. Remarkably, the loss of Fuc-TVII in TFF3−/− mice markedly decreased the severity of DSS-induced colitis as evidenced by reduced weight loss, diarrhea, decreased colonic MPO levels and improved survival. Furthermore, the loss of TFF3 resulted in increased severity of spontaneous colitis in IL-2/β-microglobulin-deficient mice. These studies highlight the importance of the interplay between factors involved in the innate immune response, mucosal barrier function, and genes involved in regulating leukocyte recruitment and other aspects of the immune response.

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Chemotherapy- and radiotherapy-induced intestinal damage is regulated by intestinal trefoil factor

Cited by 116 publications

References 34 publications

Prospective evaluation of gut mucosal barrier injury following various myeloablative regimens for haematopoietic stem cell transplant

Prospective evaluation of gut mucosal barrier injury following various myeloablative regimens for haematopoietic stem cell transplant

PI3K/Akt Signaling Pathway in the Basolateral Amygdala Mediates the Rapid Antidepressant-like Effects of Trefoil Factor 3

Exploring the interplay of barrier function and leukocyte recruitment in intestinal inflammation by targeting fucosyltransferase VII and trefoil factor 3

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