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Richard Makins

Publications and source records attributed to Richard Makins.

5 recordsLinked to original sources
PubMed2005

Interleukin-5 potentiates the growth response of Caco-2 cells to IGF-II: a role in colonic carcinogenesis complicating ulcerative colitis?

UNLABELLED: Longstanding ulcerative and Crohn's colitis increases the risk of colorectal cancer (CRC) compared to the general population. Elevated IGF-II mRNA and protein have been found in tumour tissue in sporadic CRC. The association of IGF-II in colitis-related-CRC is unknown. OBJECTIVES: To determine whether pro-inflammatory cytokines associated with colitis, namely IL-5, TNF-alpha and IL-1beta, alter the proliferative effect of IGF-II on the colorectal cancer cell line, Caco-2. DESIGN: Caco-2 cells were cultured with IGF-II and IL-5, TNF-alpha or IL-1beta. At 24 h intervals cell proliferation was assessed. The mechanism of action of any synergistic affect was investigated by RT-PCR to determine change in mRNA expression of IGF-II, IGF-1R or IGF-2R. RESULTS: After 72 h, IGF-II increased absorption (corresponding to cell density) compared to controls by 25% (p < 0.02). Co-incubation with IGF-II and IL-5 increased absorption by 42% (p < 0.001) compared to controls and 18% (p < 0.03) compared to IGF-II alone. Enhanced growth response was also seen with TNF-alpha and IL-1beta, but less so than IL-5. The IL-5 receptor was not expressed by Caco-2 cells and mRNA expression of the IGF-1R or IGF-2R was unchanged by incubation with cytokines. CONCLUSIONS: IGF-II promotes Caco-2 growth, an effect enhanced with IL-5, TNF-alpha and IL-1beta. The greatest response was with IL-5. This was IL-5 receptor-independent. Possible mechanisms include IL-5 interaction on an un-identified receptor or interference with IGF-binding proteins, as occurs with IL-1beta and IL-6. The enhanced growth response of Caco-2 cells to pro-inflammatory cytokines and IGF-II may have implications for the pathogenesis of CRC formation in colitis.

Caco-2 Cells↗
PubMed2003

Gastrointestinal side effects of drugs.

Drugs can have adverse effects on any part of the gastrointestinal (GI) tract from mouth to colon. It is essential that a detailed and accurate drug history is taken in patients presenting with GI complaints. Many drug-induced effects will regress or heal on cessation of treatment. NSAIDs are usually associated with gastric and duodenal ulcers but are also recognised to cause lichen planus in the mouth, oesophageal inflammation and strictures, and small bowel and colonic ulcers and strictures. A newer class of anti-inflammatory drugs, the cyclooxygenase-2 (COX-2)-selective inhibitors, have been developed and have a more favourable GI safety profile than standard NSAIDs. Acute diarrhoea, relapse of inflammatory bowel disease (IBD), microscopic colitis and acute pancreatitis are also induced by ingestion of standard NSAIDs. The calcium antagonists, phenytoin and cyclosporin, induce gum hyperplasia, particularly in patients with poor oral hygiene. Alendronate, a bisphosphonate, has been associated with development of oesophageal ulcers, and specific recommendations are now given to reduce this complication. Of the many different forms of colitis associated with drug ingestion, the most frequent is pseudomembranous colitis. This is a complication of antibiotics and is caused by the toxin produced by Clostridium difficile. Many drugs have been associated with the development of acute pancreatitis, although a definite cause and effect relationship has been shown for only a few drugs. These include didanosine, furosomide, corticosteroids, azathioprine and sodium valproate.

Drug-Related Side Effects and Adverse Reactions↗