Protection against mucosal injury by growth factors and cytokines.
This article provides an overview of published studies in which growth factors and cytokines were used to modify the sensitivity of intestinal stem cells to a dose of radiation. In these experiments, growth factors were used to manipulate the sensitivity of stem cells in the gastrointestinal tract to reduce the severity of gastrointestinal mucositis in cancer therapy patients. Transforming growth factor beta3, interleukin 11, and keratinocyte growth factor were used. All three agents, given according to appropriate protocols, can result in a threefold to fourfold increase in the number of intestinal stem cells that survive a dose of radiation therapy. This result was assessed by using the crypt microcolony assay of stem cell functional capacity. The changes in stem cell survival that were observed resulted in increased animal survival. This increased survival was taken as a surrogate for improvement in patient well-being. The severity of diarrhea, a marker of functional impairment, was concomitantly reduced.
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Cancer Research Campaign Epithelial Biology Group, Paterson Institute for Cancer Research, Christie Hospital, Manchester, UK.
Potten
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D000818:Animals; D002470:Cell Survival; D016207:Cytokines / Q000494:pharmacology*; D003967:Diarrhea / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D017370:Interleukin-11 / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009092:Mucous Membrane / Q000187:drug effects* / Q000293:injuries* / Q000528:radiation effects*; D011878:Radiotherapy / Q000009:adverse effects* / Q000379:methods; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053782:Transforming Growth Factor beta3
D016207:Cytokines; C496453:FGF7 protein, human; C496454:Fgf7 protein, mouse; D006133:Growth Substances; D017370:Interleukin-11; C509045:Tgfb3 protein, mouse; D016212:Transforming Growth Factor beta; D053782:Transforming Growth Factor beta3; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors