Is polyamine synthesis involved in the proliferative response of the intestinal epithelium to urogastrone-epidermal growth factor?

1989 ◽  
Vol 76 (6) ◽  
pp. 595-598 ◽  
Author(s):  
R. A. Goodlad ◽  
H. Gregory ◽  
N. A. Wright
Keyword(s):  
Cell Proliferation ◽  
Small Intestine ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Proliferative Response ◽  
Intestinal Cell ◽  
Intestinal Epithelial ◽  
Polyamine Synthesis ◽  
Proliferative Effect ◽  
Epidermal Growth

1. Intestinal epithelial cell proliferation was measured in rats maintained on total parenteral nutriton (TPN), in TPN rats given 300 μg of recombinant human epidermal growth factor (urogastrone-epidermal growth factor, URO-EGF) day−1 kg−1, and in further groups given URO-EGF and difluoromethylornithine (DFMO), an inhibitor of the enzyme ornithine decarboxylase (ODC). 2. URO-EGF significantly increased intestinal cell proliferation throughout the gastrointestinal tract. The proliferative response of the colon was particularly pronounced. 3. DFMO reduced the proliferative effect of urogastrone in the stomach and small intestine. DFMO also reduced URO-EGF-stimulated intestinal cell proliferation in the colon, but to a lesser extent. 4. It is concluded that ODC is essential for effecting the proliferative response of the stomach and small intestine to URO-EGF, but this role may be less important in the colon.

Effect of epidermal growth factor administration on intestinal cell proliferation, crypt fission and polyp formation in multiple intestinal neoplasia (Min) mice

2003 ◽  
Vol 105 (3) ◽  
pp. 323-330 ◽  
Author(s):  
O. BASHIR ◽  
A. J. FITZGERALD ◽  
J. BERLANGA-ACOSTA ◽  
R. J. PLAYFORD ◽  
R. A. GOODLAD
Keyword(s):  
Cell Proliferation ◽  
Small Intestine ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Intestinal Cell ◽  
Polyp Size ◽  
Polyp Formation ◽  
Intestinal Neoplasia ◽  
Crypt Fission ◽  
Epidermal Growth

Recombinant epidermal growth factor (EGF) may be useful to treat severe ulcerative gastrointestinal injury. There is concern, however, that systemic use of this potent mitogen might increase tumour development and/or progression in susceptible subjects. We therefore examined the effect of chronic administration of systemic EGF to multiple intestinal neoplasia (Min) mice, who have a genetic defect in the adenomatous polyposis coli (APC) gene, leading to increased polyp development. Min mice (n=26) and wild-type littermates (n=26) received saline or EGF (223 μg of EGF/kg per day) for 4 weeks using subcutaneous osmotic mini-pumps. Cell proliferation and crypt fission were analysed using microdissection techniques and the number and size of polyps in the small and large intestines were determined. EGF increased wet weight and crypt cell proliferation rate by approx. 20% (all P<0.01 compared with the relevant control) in the small intestine and colon of both control and Min mice. In both groups, EGF reduced the colonic fission index by approx. 40% (P<0.01), but did not affect crypt fission in the small intestine. In Min mice, administration of EGF did not increase numbers of polyps or degree of dysplasia, but resulted in a 40% increase in the polyp size in the proximal intestine (P<0.02), but not in the remainder of the small intestine or colon. No polyps were found in control mice given EGF. EGF did not initiate polyp formation in control or Min mice. However, as polyp size is an important determinant for subsequent risk of malignant change in human colon cancer, further studies appear justified.

INTRAVENOUS EPIDERMAL GROWTH FACTOR/UROGASTRONE INCREASES SMALL-INTESTINAL CELL PROLIFERATION IN CONGENITAL MICROVILLOUS ATROPHY

The Lancet ◽  
1985 ◽  
Vol 326 (8466) ◽  
pp. 1239-1240 ◽  
Author(s):  
J.A. Walker-Smith ◽  
A.D. Phillips ◽  
N. Walford ◽  
H. Gregory ◽  
J.D. Fitzgerald ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Intestinal Cell ◽  
Epidermal Growth ◽  
Small Intestinal

Mushroom lectin, epidermal growth factor and intestinal epithelial cell proliferation

2000 ◽  
Vol 118 (4) ◽  
pp. A558
Author(s):  
Robert A. Goodlad ◽  
Carvalho J. Ralph ◽  
Mandir Nikki ◽  
FitzGerald J. Anthony
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Epithelial Cell ◽  
Epidermal Growth Factor ◽  
Intestinal Epithelial Cell ◽  
Intestinal Epithelial ◽  
Epithelial Cell Proliferation ◽  
Epidermal Growth ◽  
Mushroom Lectin

Does resection enhance the response of the intestine to urogastrone-epidermal growth factor in the rat?

1988 ◽  
Vol 75 (2) ◽  
pp. 121-126 ◽  
Author(s):  
R. A. Goodlad ◽  
A. P. Savage ◽  
W. Lenton ◽  
M. A. Ghatei ◽  
H. Gregory ◽  
...  
Keyword(s):  
Small Intestine ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Intestinal Resection ◽  
Small Bowel Resection ◽  
Control Group ◽  
Positive Interaction ◽  
Proliferative Effect ◽  
Small Rise ◽  
Epidermal Growth

1. The objective of this study was to see whether another proliferative stimulus could modify the marked proliferative effect of human epidermal growth factor (urogastrone-epidermal growth factor, URO-EGF) on the gastrointestinal epithelium. 2. The response of the gastrointestinal tract to URO-EGF was investigated in rats maintained on total parenteral nutrition (TPN) with or without 75% small bowel resection. 3. Continuous infusion of 60 μg of recombinant β-urogastrone/day per rat increased proliferation in the stomach by over four times (P < 0.01), doubled proliferation in the small intestine (P < 0.001) and increased it by four and a half times in the colon (P < 0.001) in the control group. No significant effect of urogastrone was observed in the stomach of the resected groups, but proliferation was also increased in the small intestine by one and a half times (P < 0.001) and by nearly four times in the colon (P < 0.001). 4. Two-way analysis of variance showed that resection had a significant effect (P < 0.01) on proliferation below the anastamosis and in the ileum. However, the response of the ileum was only half that observed in orally fed rats, which confirms the importance of ‘luminal nutrition’ in the response to resection. 5. Intestinal resection in the TPN rat was associated with a small rise in plasma enteroglucagon levels, suggesting that this hormone may be implicated in the adaptive response of the small intestine to resection. However, the proliferative effects of URO-EGF were not associated with increased plasma enteroglucagon and thus the two agents probably exert their proliferative effects via separate mechanisms. 6. There was no evidence for a significant positive interaction between the effects of URO-EGF and resection. Thus loss of intestinal mass had no influence on the susceptibility of the intestine to the effects of URO-EGF. Although URO-EGF significantly increased intestinal epithelial cell proliferation, it could not entirely compensate for the lack of luminal contents.

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