Medline ® Abstracts for References 6,7
of 'Enterotoxicity of chemotherapeutic agents'
Drug insight: gastrointestinal and hepatic adverse effects of molecular-targeted agents in cancer therapy.
Loriot Y, Perlemuter G, Malka D, Penault-Llorca F, Boige V, Deutsch E, Massard C, Armand JP, Soria JC
Nat Clin Pract Oncol. 2008 May;5(5):268-78. Epub 2008 Mar 18.
Recent advances in the understanding of molecular mechanisms of cancer have led to the development of novel compounds that target specific cancer pathways. These drugs encompass monoclonal antibodies and tyrosine and non-tyrosine kinase inhibitors, and have been approved by the FDA and the European Medicines Agency, among others, for cancer treatment. These agents are associated with several toxic effects including potentially unacceptable gastrointestinal adverse effects. Diarrhea and hepatotoxicity, the most common adverse events experienced with these treatments, can frequently lead to treatment discontinuation and consequently decreased cancer control. We review the incidence and clinical patterns of the gastrointestinal and hepatic toxic effects induced by the main molecular-targeted therapies and propose some hypotheses for the causes of each adverse event.
Institute Gustave Roussy, Villejuif, France.
Epidermal growth factor inhibits Ca(2+)-dependent Cl- transport in T84 human colonic epithelial cells.
Uribe JM, Gelbmann CM, Traynor-Kaplan AE, Barrett KE
Am J Physiol. 1996 Sep;271(3 Pt 1):C914-22.
This study examined whether epidermal growth factor (EGF) inhibits Ca(2+)-dependent Cl- secretion by T84 cells. Basolateral EGF inhibited Cl- secretion induced by carbachol or thapsigargin, without blocking the rise in intracellular Ca2+. Studies have shown that carbachol renders T84 cells refractory to subsequent stimulation by thapsigargin, an effect ascribed to D-myo-inositol 3,4,5,6-tetrakisphosphate [D-Ins(3,4,5,6)P4]. EGF also increased DL-Ins(3,4,5,6)P4 to a maximum of 170% above control. However, despite the fact that EGF inhibited Cl- secretion at 1 min, DL-Ins(3,4,5,6)P4 was not elevated at this time point. EGF plus carbachol had a greater inhibitory effect on Cl- secretion than either alone, indicating the likely involvement of an additional inhibitory pathway activated by EGF. Staurosporine did not alter the ability of EGF to inhibit Cl- secretion or increase DL-Ins(3,4,5,6)P4. In contrast, genistein inhibited the rise in DL-Ins(3,4,5,6)P4 and partially reversed EGF's inhibitory effect on Cl- secretion. In conclusion, EGF and carbachol can both inhibit Cl- secretion via D-Ins(3,4,5,6)P4, whereas EGF also generates an additional inhibitory signal.
Department of Medicine, University of California, San Diego, School of Medicine 92103, USA.