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Cisplatin also target

It was early determined that in the cell, the electrophilic species derived from cisplatin bind to three major targets RNA (which is present at high concentration in cytoplasm, together with nucleoproteins) (50%), DNA (40%) and proteins (10%) [25]. It also binds to cysteine and methionine residues of proteins, to metallothioneins, glutathione, methionine, and glutamate which are good traps for chloro and/or aqua platinum electrophiles [26],... [Pg.227]

The effectiveness of cisplatin depends on its ability to penetrate target tissue. Therefore, we need to estimate its penetration depth from a distributed model such as that represented by Equation 9.1. However, this is difficult to do with ovarian tumors because the permeabilities and reaction rates are not available. Hence, a first estimate is made for penetration of normal peritoneal cavity tissues by ethylenediamine-tetraacetic acid (EDTA), a molecule of molecular weight similar to that of cisplatin. The steady-state concentration profiles of EDTA should resemble those of cisplatin in normal peritoneal tissues because both compounds are cleared primarily by permeation through the fenestrated capillaries in these tissues, and the small molecular weight-related differences in P s and D should cancel out in Equations 9.5 and 9.5T By first focusing on EDTA, experimental data also become available for assessing the ability of the distributed model to account for the observed spatial dependent of concentration. [Pg.111]


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See also in sourсe #XX -- [ Pg.533 ]




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