Facilitated transport, tumors

The synthetic pirimidine, 5-fluouracil (5-FU), is used in the treatment of a variety of epithelial tumors including, colorectal, breast cancer, ovarian, head, and neck cancers. 5-FU enters tumor cells by a facilitated nucleobase transporter and is converted into active metabolites (5 -fluoro-2 -deoxyuridine) by a complex metabolic pathway that interferes with both DNA and RNA syntheses. Of particular interest is the conversion of 5-FU to 5 -fluoro-2 -deoxyur-idine (5-FUdR) and subsequent phosphorylation by thymidine kinase to the active metabolite 5 -fluoro-2 -DUMP (5-FdUMP). Unfortunately, the response rate of patients receiving 5-FU-based chemotherapy is relatively poor, varying between 10 and 30%. To further evaluate, 5-FU labeled with F (5- FU) has been used in PET studies to understand the factors behind this strong interindividual variability. As 5- FU is biochemically identical to 5-FU, PET has been used for quantitative pharmacokinetic measurements of 5- FU in human and animal models. 

Okadaic acid (OA), being a polyether, presents ionophoretic properties (facilitation of ion transport across membranes) as does CTX. It has been found that OA causes contraction in smooth muscles even in the absence of Ca (Ozaki and Karaki 1987 Shibata 1985). Ozaki and Karaki (1987) studied the mechanism of action of OA compared to calyculin A (another polyether isolated from a marine sponge). The results of this work suggest that OA has two separate effects activation of calcium channels as well as activating contractile elements to induce smooth muscle contraction. Recently, OA, in addition to other compounds from marine sources, has been found to be a tumor promoter that is, an agent that promotes tumor formation on already initiated cells (Fujiki 1988). It has been found that the OA class of tumor promoters bind to their own receptors which are present in particulate as well as cytosol fractions. The mechanism of action of these compounds has been partially elucidated. 

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