Keratinocyte growth factor protects mice from chemotherapy and radiation-induced gastrointestinal injury and mortality.

2.50
Hdl Handle:
http://hdl.handle.net/10541/93020
Title:
Keratinocyte growth factor protects mice from chemotherapy and radiation-induced gastrointestinal injury and mortality.
Authors:
Farrell, C L; Bready, J V; Rex, K L; Chen, J N; DiPalma, C R; Whitcomb, K L; Yin, S; Hill, D C; Wiemann, B; Starnes, C O; Havill, A M; Lu, Z N; Aukerman, S L; Pierce, G F; Thomason, A; Potten, Christopher S; Ulich, T R; Lacey, D L
Abstract:
Keratinocyte growth factor (KGF) stimulates the proliferation and differentiation of epithelial cells including those of the gastrointestinal tract. Although chemotherapeutics and radiation exposure kill rapidly proliferating tumor cells, rapidly dividing normal cells of the host's gastrointestinal tract are also frequently damaged, leading to the clinical condition broadly termed "mucositis." In this report, recombinant human KGF used as a pretreatment in several mouse models of chemotherapy and/or radiation-induced gastrointestinal injury significantly improved mouse survival. Using multiple-dose 5-fluorouracil, methotrexate, and radiation in combination and total body radiation alone models, KGF increased survival by 55% or greater. In the models that used chemotherapy with or without radiation, KGF significantly ameliorated weight loss after injury and accelerated weight gain during recovery. The basis of these systemic benefits appears to be due in part to the trophic effects of the growth factor on the intestinal epithelium because KGF pretreatment caused an increase in measures of mucosal thickness (villus height and crypt depth) that persisted during the course of 5-fluorouracil chemotherapy. Treatment with KGF also afforded a 3.5-fold improvement in crypt survival in the small intestine, suggesting that KGF also has a direct effect on the crypt stem cells. These data indicate that KGF may be therapeutically useful to lessen the intestinal side effects of current cancer therapy regimens.
Affiliation:
Amgen Center, Thousand Oaks, California 91320-1789, USA.
Citation:
Keratinocyte growth factor protects mice from chemotherapy and radiation-induced gastrointestinal injury and mortality. 1998, 58 (5):933-9 Cancer Res.
Journal:
Cancer Research
Issue Date:
1-Mar-1998
URI:
http://hdl.handle.net/10541/93020
PubMed ID:
9500453
Type:
Article
Language:
en
ISSN:
0008-5472
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorFarrell, C Len
dc.contributor.authorBready, J Ven
dc.contributor.authorRex, K Len
dc.contributor.authorChen, J Nen
dc.contributor.authorDiPalma, C Ren
dc.contributor.authorWhitcomb, K Len
dc.contributor.authorYin, Sen
dc.contributor.authorHill, D Cen
dc.contributor.authorWiemann, Ben
dc.contributor.authorStarnes, C Oen
dc.contributor.authorHavill, A Men
dc.contributor.authorLu, Z Nen
dc.contributor.authorAukerman, S Len
dc.contributor.authorPierce, G Fen
dc.contributor.authorThomason, Aen
dc.contributor.authorPotten, Christopher Sen
dc.contributor.authorUlich, T Ren
dc.contributor.authorLacey, D Len
dc.date.accessioned2010-02-25T11:14:12Z-
dc.date.available2010-02-25T11:14:12Z-
dc.date.issued1998-03-01-
dc.identifier.citationKeratinocyte growth factor protects mice from chemotherapy and radiation-induced gastrointestinal injury and mortality. 1998, 58 (5):933-9 Cancer Res.en
dc.identifier.issn0008-5472-
dc.identifier.pmid9500453-
dc.identifier.urihttp://hdl.handle.net/10541/93020-
dc.description.abstractKeratinocyte growth factor (KGF) stimulates the proliferation and differentiation of epithelial cells including those of the gastrointestinal tract. Although chemotherapeutics and radiation exposure kill rapidly proliferating tumor cells, rapidly dividing normal cells of the host's gastrointestinal tract are also frequently damaged, leading to the clinical condition broadly termed "mucositis." In this report, recombinant human KGF used as a pretreatment in several mouse models of chemotherapy and/or radiation-induced gastrointestinal injury significantly improved mouse survival. Using multiple-dose 5-fluorouracil, methotrexate, and radiation in combination and total body radiation alone models, KGF increased survival by 55% or greater. In the models that used chemotherapy with or without radiation, KGF significantly ameliorated weight loss after injury and accelerated weight gain during recovery. The basis of these systemic benefits appears to be due in part to the trophic effects of the growth factor on the intestinal epithelium because KGF pretreatment caused an increase in measures of mucosal thickness (villus height and crypt depth) that persisted during the course of 5-fluorouracil chemotherapy. Treatment with KGF also afforded a 3.5-fold improvement in crypt survival in the small intestine, suggesting that KGF also has a direct effect on the crypt stem cells. These data indicate that KGF may be therapeutically useful to lessen the intestinal side effects of current cancer therapy regimens.en
dc.language.isoenen
dc.subjectExperimental Canceren
dc.subject.meshAnimals-
dc.subject.meshAntineoplastic Agents-
dc.subject.meshFemale-
dc.subject.meshFibroblast Growth Factor 10-
dc.subject.meshFibroblast Growth Factor 7-
dc.subject.meshFibroblast Growth Factors-
dc.subject.meshGrowth Substances-
dc.subject.meshHumans-
dc.subject.meshIntestinal Diseases-
dc.subject.meshIntestinal Mucosa-
dc.subject.meshMice-
dc.subject.meshMice, Nude-
dc.subject.meshNeoplasms, Experimental-
dc.subject.meshRadiation Injuries, Experimental-
dc.subject.meshRecombinant Proteins-
dc.subject.meshSurvival Analysis-
dc.titleKeratinocyte growth factor protects mice from chemotherapy and radiation-induced gastrointestinal injury and mortality.en
dc.typeArticleen
dc.contributor.departmentAmgen Center, Thousand Oaks, California 91320-1789, USA.en
dc.identifier.journalCancer Researchen

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