Chemotherapy-induced @entity16 is a very important dose-limiting side effect for which there is no definitive prophylaxis or treatment. This is in part due to the lack of understanding of its pathophysiology and impact on intestinal differentiation. The objective of this study was to investigate the gene expression of the small intestinal transcription factors @entity22437 , @entity6733 , @entity7006 in an experimental model of @entity1499 ( @entity1500 )-induced @entity16 , and to correlate these alterations with histological damage, epithelial proliferation and differentiation. @entity22437 , @entity6733 and @entity7006 are critical transcription factors in epithelial differentiation, and in combination they act as promoting factors of the @entity3430 ( @entity3430 ) gene, an enterocyte-specific differentiation marker which is distinctly downregulated after @entity1500 treatment. @entity19 received two doses of @entity1500 i.v. on two consecutive days and were sacrificed 1, 3 and 7 or 9 days after final injection. Segments of the jejunum were taken for morphological, immunohistochemical and quantitative analyses. @entity16 was most severe at day 3 and was associated with decreased expression of the transcriptional factors @entity22437 , @entity6733 and @entity7006 , which correlated well with decreased expression of @entity3430 , and seemed inversely correlated with enhanced proliferation of epithelial crypt cells. During severe damage, the epithelium was preferentially concerned with proliferation rather than differentiation, most likely in order to restore the small intestinal barrier function rather than maintaining its absorptive function. Since @entity22437 , @entity6733 and @entity7006 are critical for intestine-specific gene expression and therefore crucial in epithelial differentiation, these results may explain, at least in part, why intestinal differentiation is compromised during @entity1500 treatment.

The effect of cytostatic drug treatment on intestine-specific transcription factors @entity6733 , @entity7006 and XXXX in @entity19 .

@entity19 :: ('10090', 'Species') :: ['Mice'] @entity16 :: ('MESH:D009422', 'Disease') :: ['Intestinal damage', 'intestinal damage'] @entity22437 :: ('21405(Tax:10090)', 'Gene') :: ['HNF-1alpha'] @entity7006 :: ('14463(Tax:10090)', 'Gene') :: ['GATA-4'] @entity1500 :: ('CHEBI:44185', 'Chemical') :: ['MTX'] @entity3430 :: ('69983(Tax:10090)', 'Gene') :: ['sucrase-isomaltase', 'SI'] @entity6733 :: ('12591(Tax:10090)', 'Gene') :: ['Cdx2'] @entity1499 :: ('MESH:D008727', 'Chemical') :: ['methotrexate']
@entity22437 :: (21405(Tax:10090),Gene) :: ['HNF-1alpha']
