Transport mechanisms cancers

Since many essential nutrients (e.g., monosaccharides, amino acids, and vitamins) are water-soluble, they have low oil/water partition coefficients, which would suggest poor absorption from the GIT. However, to ensure adequate uptake of these materials from food, the intestine has developed specialized absorption mechanisms that depend on membrane participation and require the compound to have a specific chemical structure. Since these processes are discussed in Chapter 4, we will not dwell on them here. This carrier transport mechanism is illustrated in Fig. 9C. Absorption by a specialized carrier mechanism (from the rat intestine) has been shown to exist for several agents used in cancer chemotherapy (5-fluorouracil and 5-bromouracil) [37,38], which may be considered false nutrients in that their chemical structures are very similar to essential nutrients for which the intestine has a specialized transport mechanism. It would be instructive to examine some studies concerned with riboflavin and ascorbic acid absorption in humans, as these illustrate how one may treat urine data to explore the mechanism of absorption. If a compound is... 

Nucleoside analogues are widely used for the treatment of cancers and viral infections. Although there have been considerable advances in the development of new nucleoside analogs, little is known about the transport mechanisms involved in the intestinal absorption of these compounds. Nucleoside transporters have been subdivided into two major classes by Na+-independent equilibrative transporters (ENT family) and Na+-dependent concentrative transporters (CNT family) [77,100-103],... 

Current challenges in clinical and pharmaceutical studies are to explain the mechanism of cytotoxic activity of drugs, their transport into cancer cells, distribution and metabolism in the human body, interaction with proteins and with DNA... 

The brain needs the influx of nucleosides because the brain is deficient in de novo nucleotide synthesis (102). Purine and pyrimidine nucleosides are necessary for the synthesis of DNA and RNA, but nucleosides also influence many other biological processes. In addition, nucleosides play an important role in the treatment of diseases, such as cardiac diseases, brain cancers, and infections [parasitic and viral (103)]. Nucleosides are hydrophilic compounds, and the influx and efflux of these compounds is therefore mediated by a number of distinct transporters (104). Nucleoside transporters are membrane-fixed transporters and are classified by their transport mechanisms (e = equilibrative, c = concentrative), their sensitivity to the transport inhibitor nitrobenzylmercaptopurine riboside (NBMPR s = sensitive, i = insensitive), and their substrates. Presently, there are two equilibrative transporters (ENTs es and ei) and six concentrative nucleoside transporters [CNTs cif (concentrative, NBMPR insensitive, broad specificity Nl), cit (concentrative, NBMPR insensitive, common permeant thymidine N2), cib (concentrative, NBMPR insensitive, broad specificity N3), cib (concentrative, MBMPR insensitive, broad specificity N4), cs (concentrative, NBMPR sensitive N5), and csg (concentrative, NBMPR sensitive, accepts guanosine as permeant N6) (104)]. The equilibrative es and ei nucleoside transporters are widely expressed in mammalian cells and are present at cultured endothelial cells and brain capillaries (105). In these cells, the expression of concentrative transporter cit (N2) was demonstrated also. In other parts of the rat brain, ei and es nucleoside transport systems have... 

Figure 9.1 Pr of drugs in vivo may be affected by several parallel transport mechanisms in both absorptive and secretory directions. A few of the most important transport proteins that may be involved in the intestinal transport of drugs and their metabolites across intestinal epithelial membrane barriers in humans are displayed. P-gp, P-glycoprotein BCRP, breast cancer-...

The following sections of this chapter are focused on the potentialities of SPECT and PET for imaging drug resistance mechanisms mediated by the expression of ABC transporters in cancer. Initially, we will introduce the radiopharmaceuticals available for SPECT imaging, highlighting some of results obtained Irom clinical and pre-clinical studies. Second, an overview over the advances in PET radiopharma-ceuticals that are becoming available for studying MDR will be presented. 

Aside from whether they are directly active per se, or merely as precursors of active metabolic intermediates, carcinogenic polycyclic hydrocarbons can initiate carcinomas (e.g. epithelioma) at the point of application on the skin (the commonest mode of study), or can lead to distant tumours, as in bronchogenic cancer [23]. The mechanism probably includes solubilisation of the carcinogens (by proteins, nucleoproteins, fatty acid esters, etc. or even in aqueous solution [58]), so as to enable them to traverse the dermis (possibly via an external solvent) and thus react in the epidermis, which possesses a lipoid barrier. Alternatively, appendageal transport routes (hair follicles, sweat glands, sebaceous glands) may be used [59]. When carcinogens act at a distance, as with liver, breast, bladder and other internal cancers, an internal transport mechanism or medium is evidently needed. 

---