Intestinal mucosa remodeling by recombinant human epidermal growth factor1-48 in neonates with severe necrotizing enterocolitis

Sullivan, Peter B.; Lewindon, Peter; Cheng, Carmen Wan Rong; Lenehan, Peter F.; Bo-Sheng, Kuo; Haskins, Jeffrey R.; Goodlad, R A; Wright, Nicholas; Iglesia, Felix A. dela

doi:10.1016/j.jpedsurg.2006.10.039

Cited by 38 publications

(28 citation statements)

References 30 publications

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“…Indeed, a significant finding from our previous study was the lower level of maturity of the colon compared with the small intestine raising the possibility that each segment may not respond equally to a given treatment. To test this hypothesis, we used EGF, which was previously shown in clinical studies to exert positive effects in both the prevention and treatment of neonatal enteropathies (19,48,52,64,69). Consistent with the apparent similar morphological and functional characteristics of the small and large intestine at midgestation (37,41,44,62), the gene expression profiles established by IPA revealed that a large proportion (ϳ80%) of the statistically significant cell, molecular, and physiological functions modulated by EGF were common to the two segments.…”

Section: Discussionmentioning

confidence: 80%

“…Treatment with epidermal growth factor (EGF) is also of great interest as a potential strategy for the prevention of neonatal enteropathies (14,19,48,52). Indeed, exogenous EGF has been proposed as a therapeutic agent to promote the healing of the gastrointestinal tract in pediatric patients (18,48,64,69,77). Enteral administration of EGF has been reported to reduce the incidence of necrotizing enterocolitis in a neonatal rat model (63).…”

mentioning

confidence: 99%

“…The mechanisms underlying the EGF-mediated protective effect in experimental animal models could be related to a reduction of epithelial cell apoptosis (15), a decrease in intestinal permeability (14), angiogenesis (78), and/or a decrease in autophagy (33). The mechanisms by which EGF promotes mucosal healing in the developing human gut are much less characterized (64,69). By using organ culture of the human fetal intestine maintained under welldefined conditions, our group showed that intestinal functions are closely regulated by hormones and growth factors (36,37,41,42).…”

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confidence: 99%

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Anti-inflammatory effects of epidermal growth factor on the immature human intestine

Ménard

Tremblay

Ferretti

et al. 2012

Physiological Genomics

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The inflammatory response of the preterm infants' intestine underlines its inability to respond to hemodynamic stress, microbes, and nutrients. Recent evidence suggests that exogenous epidermal growth factor (EGF) exerts a therapeutic influence on neonatal enteropathies. However, the molecular mechanisms underlying the beneficial effects of EGF remain to be clarified. The purpose of this study was to evaluate the impact of EGF on the gene expression profiles of the developing human small and large intestine at midgestation in serum-free organ cultures using microarrays. The gene expression profiles of cultured human fetal ileal and colonic explants were investigated in the absence or presence of a physiological concentration of 50 ng/ml EGF for 48 h. Data were analyzed with the Ingenuity Pathway Analysis (IPA) software and confirmed by qPCR. We found a total of 6,474 differentially expressed genes in the two segments in response to EGF. IPA functional analysis revealed that in addition to differentially modulating distinct cellular, molecular, and physiological functions in the small and large intestine, EGF regulated the inflammatory response in both intestinal segments in a distinct manner. For instance, several intestinal-derived chemokines such as CCL2, CCL25, CXCL5, and CXCL10 were found to be differentially regulated by EGF in the immature ileum and colon. The findings showing the anti-inflammatory influence of exogenous EGF suggests a mechanistic basis for the beneficial effects of EGF on neonatal enteropathies. These results reinforce growing evidence that by midgestation, the human small intestine and colon rely on specific and distinct regulatory pathways.

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Section: Discussionmentioning

confidence: 80%

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confidence: 99%

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confidence: 99%

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Anti-inflammatory effects of epidermal growth factor on the immature human intestine

Ménard

Tremblay

Ferretti

et al. 2012

Physiological Genomics

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“…The only trial to date is a singlecenter trial that randomized 8 infants who were less than 12 weeks of age with confirmed NEC Bell stage II or more to receive continuous intravenous infusions of EGF versus placebo. The investigators found significantly increased rectal mucosal thickness and crypt surface area in infants receiving EGF [46]. However, the study was discontinued early for administrative reasons; the results were not correlated with clinical outcomes.…”

Section: Epidermal Growthlike Factorsmentioning

confidence: 99%

Necrotizing Enterocolitis

Papillon

Castle

Gayer

et al. 2013

Advances in Pediatrics

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“…Os pacientes que receberam EGF mostraram melhora significativa, tanto clínica quanto histológica, do trato gastrintestinal. Entretanto, esse estudo, que tinha previsão para incluir 20 pacientes, foi interrompido após a inclusão do oitavo RN por questões administrativas (23) .…”

Section: Fator De Crescimento Epidérmicounclassified

Uso de fatores de crescimento epidérmico e estimulador de colônias de granulócitos na prevenção e tratamento da enterocolite necrosante no recém-nascido

Silva

Quinello

Pires

et al. 2008

Rev. paul. pediatr.

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ResUmoObjetivo: Revisar os conhecimentos existentes em relação ao uso de fatores de crescimento epidérmico e estimulador de colônias de granulócitos na prevenção e/ou no tratamento da enterocolite necrosante (ECN) durante o período neonatal. Fontes de dados:Revisão da literatura, nas bases de dados Medline, Lilacs, SciELO e PubMed, utilizando os unitermos "recém-nascidos", "enterocolite" e "fatores de crescimento", no período de 2003 a 2007. Nesta busca, 49 artigos foram encontrados, sendo 17 pertinentes ao tema. Também foram utilizados outros artigos, independente do ano de publicação, relacionados a aspectos definidores da ECN no recém-nascido.Síntese dos dados: A ECN continua sendo responsável por uma elevada morbimortalidade neonatal. Os mecanismos fisiopatológicos vêm sendo elucidados e, a partir deles, são discutidas novas terapias, como o uso de fatores de crescimento, destacando-se o fator de crescimento epidérmico e o fator estimulador de colônias de granulócitos.Conclusões: O uso de fatores de crescimento no tratamento e prevenção da ECN neonatal parece promissor. É necessário maior número de ensaios clínicos para comprovar sua eficácia e segurança. Enquanto isso, a melhor prática médica continua sendo a prevenção da doença.Palavras-chave: recém-nascido; dietoterapia; fatores de crescimento; enterocolite necrosante. Data sources: Literature review of Medline, Lilacs, SciELO and Pubmed databases, using the key-words "newborn", "enterocolitis" and "growth factors", from 2003 to 2007. Fourty-nine papers were retrieved, but only 17 related to the subject. Other studies that described some clinical aspects of enterocolitis were also included, regardless of the year of publication.Data synthesis: Necrotizing and enterocolitis has been an important cause of morbidity and mortality in the neonatal period. As the knowledge about the pathophysiology of this disease improves, new therapies, such as the administration of epidermal growth factor and granulocyte colony-stimulating factor, are being discussed.Conclusions: The use of growth factors for treatment and prevention of NEC seems promising. However, further clinics assays are needed to evaluate the effectiveness and the safety of these growth factors. At this moment, the best clinical practice is the prevention of the disease.Key-words: infant, newborn; diet therapy; growth factors; enterocolitis, necrotizing.

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Intestinal mucosa remodeling by recombinant human epidermal growth factor1-48 in neonates with severe necrotizing enterocolitis

Cited by 38 publications

References 30 publications

Anti-inflammatory effects of epidermal growth factor on the immature human intestine

Anti-inflammatory effects of epidermal growth factor on the immature human intestine

Necrotizing Enterocolitis

Uso de fatores de crescimento epidérmico e estimulador de colônias de granulócitos na prevenção e tratamento da enterocolite necrosante no recém-nascido

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