This study demonstrates that for patients with locally advanced carcinoma of the cervix, the combination of 5-FU and CF with RT offers patients better PFS and overall survival than HU, and with manageable toxicity.

As compared with intravenous cisplatin, intraperitoneal cisplatin significantly improves survival and has significantly fewer toxic effects in patients with stage III ovarian cancer and residual tumor masses of 2 cm or less.

Hydration with saline or saline + furosemide appears to be associated with less cisplatin nephrotoxicity than saline + mannitol.

No abstract

Estradiol is converted to catechol estrogens via 2-and 4-hydroxylation by cytochrome P450 enzymes. 4-Hydroxyestradiol elicits biological activities distinct from estradiol, most notably an oxidant stress response induced by free radicals generated by metabolic redox cycling reactions. In this study, we have examined 2-and 4-hydroxylation of estradiol by microsomes ofhuman uterine myometrium and of associated myomata. In all eight cases studied, estradiol 4-hydroxylation by myoma has been substantially elevated relative to surrounding myometrial tissue (minimum, 2-fold; mean, 5-fold). Estradiol 2-hydroxylation in myomata occurs at much lower rates than 4-hydroxylation (ratio of 4-hydroxyestradiol/2-hydroxyestradiol, 7.9 + 1.4) and does not significantly differ from rates in surrounding myometrial tissue. Rates of myometrial 2-hydroxylation of estradiol were also not significantly different from values in patients without myomata. We have used various inhibitors to establish that 4-hydroxylation is catalyzed by a completely different cytochrome P450 than 2-hydroxylation. In myoma, at-naphthoflavone and a set of ethynyl polycyclic hydrocarbon inhibitors (5 ,uM) each inhibited 4-hydroxylation more efficiently (up to 90%o) than 2-hydroxylation (up to 40%o), indicating >10-fold differences in Kj (<0.5 ,uM vs. >5 ,uM). These activities were clearly distinguished from the selective 2-hydroxylation of estradiol in placenta by aromatase reported previously (low K., inhibition by Fadrozole hydrochloride or ICI D1033).4-Hydroxylation was also selectively inhibited relative to 2-hydroxylation by antibodies raised against cytochrome P450 IBN (rat) (53 vs. 17%). These data indicate that specific 4-hydroxylation of estradiol in human uterine tissues is catalyzed by a form(s) ofcytochrome P450 related to P450 IBi, which contribute(s) little to 2-hydroxylation. This enzyme(s) is therefore a marker for uterine myomata and may play a role in the etiology of the tumor. (E2) is the primary metabolic oxidation of this hormone in most mammalian species (1, 2). In human liver, this metabolic oxidation is catalyzed mainly by cytochrome P450 IIIA and, to a lesser extent, IA family enzymes (2, 3). Cytochrome P450 IA enzymes have also been identified as estrogen 2-hydroxylases in extrahepatic tissues and in MCF-7 human breast cancer cells (2, 4, 5). In addition, aromatase has been reported to catalyze the 2-hydroxylation of E2 in placenta (6). Aromatic hydroxylations of estrogens by these enzymes mainly result in 2-hydroxylated catechol estrogens (CE) accompanied by small amounts of 4-hydroxylated estrogens (<20% of total CE metabolites) (1, 2). Therefore, 4-hydroxyestradiol (4-OH-E2) has been considered as an unimportant by-product of 2-hydroxyestradiol (2-OH-E2) formation because rates of its formation by microsomal preparations are low relative to total CE formation (1, 2) and also because urinary concentrations of 4-hydroxylated estrogens are much lower than those of 2-hydroxylated metabolites (7,8). In contrast, in microsomes o...