oxyntomodulin and Cell-Transformation--Neoplastic

Developmental events in the large bowel have been studied pre- and post-natally and indicate that by birth, crypt organisation and kinetic activity are organised along adult lines. The period from birth to maturity is marked by an increase in crypt size and a massive increase in their number, with new crypts developing by a process of longitudinal fission from the base of existing ones. We know little of the fate of crypt size and number thereafter. Adaptive responses to resection or bypass of intestine are much less marked in large bowel when compared to small bowel, but in general postoperative responses have not been as extensively examined. Of the factors maintaining mass and cell turnover in large bowel mucosa simple luminal bulk seems to be most important, although a role exists for endocrine and neurovascular influences. Knowledge of growth, kinetic activity and adaptive responses in human large bowel is scanty and represents a large area for further study.

Topics: Animals; Carcinogens; Cell Division; Cell Transformation, Neoplastic; Colectomy; Colon; Colostomy; Diet; Epidermal Growth Factor; Glucagon-Like Peptides; Humans; Intestinal Mucosa; Intestine, Large; Rats

Recent work has established that activation of Hedgehog/patched signalling plays a key role in the development of basal cell carcinomas (BCCs). In Drosophila the effects of hedgehog signalling are mediated by the transcription factor Cubitus interruptus, which is homologous to the mammalian Gli family of transcription factors. In order to investigate the downstream consequences of patched gene inactivation in BCCs, we have investigated the expression of Gli-1 and Gli-3 in normal skin and BCCs by reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization. Gli-3 was found to be expressed in both normal skin and BCCs by both RT-PCR and in situ hybridization using a Gli-3-specific probe. Using a sensitive RT-PCR assay we were unable to detect Gli-1 transcripts in normal skin. Gli-1 was expressed in 13 of 14 BCCs examined, and in situ hybridization confirmed that the transcripts were localized to the epithelial component of the tumours. Our results demonstrate that inactivation of the patched gene BCCs is associated with the accumulation of Gli-1 transcripts. These findings suggest that the Gli-1 transcription factor plays a key role in BCC development.

Topics: Carcinoma, Basal Cell; Cell Transformation, Neoplastic; Gene Expression; Glucagon-Like Peptides; Humans; In Situ Hybridization; Neoplasm Proteins; Peptides; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Skin Neoplasms

The effect of physiologic increases of plasma enteroglucagon, induced by massive bypass or resection of small bowel, on large bowel cell turnover and carcinogenesis was studied in rats in which the distal colon was isolated as a mucous fistula. After injections of azoxymethane, either 85% end-to-side jejunoileal bypass, 85% jejunoileal resection, or sham bypass was performed. Controls underwent colonic transection and resuture, azoxymethane treatment, and then sham bypass. Thirty weeks later the plasma enteroglucagon level had almost trebled after jejunoileal bypass (p less than 0.001) and almost doubled after jejunoileal resection (p less than 0.002) when compared with sham bypass; sham values did not differ from controls. The median number of tumors per rat in the distal (defunctioned) colon fell from 2 to 0 (p less than 0.05). Segmental weight fell by 45% (p less than 0.001) and crypt cell production rate by 75% (p less than 0.001). Neither tumor yield nor adaptation was affected by jejunoileal bypass or jejunoileal resection. Plasma enteroglucagon has no effect on colonic cell turnover or carcinogenesis in the absence of luminal content.

Topics: Animals; Azoxymethane; Cell Transformation, Neoplastic; Colon; Colonic Neoplasms; Gastrointestinal Hormones; Glucagon-Like Peptides; Jejunoileal Bypass; Male; Organ Size; Rats; Rats, Inbred Strains