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Silibinin is a polyphenolic flavonoid isolated from milk thistle with anti-neoplastic activity in several in vitro and in vivo models of cancer, including prostate cancer. Silybin-phytosome is a commercially available formulation containing silibinin. This trial was designed to assess the toxicity of high-dose silybin-phytosome and recommend a phase II(More)
12(R)-Hydroxy-5,8,10,14-eicosatetraenoic acid [12(R)-HETE], a cytochrome P450 arachidonate metabolite, is metabolized by corneal tissues via three distinct metabolic pathways: beta-oxidation, omega-hydroxylation, and keto-reduction. The major metabolite released from the intact rabbit corneal epithelium or cultured cells was identified by mass spectrometric(More)
When corneal microsomes were incubated with arachidonic acid in the presence of an NADPH-generating system, two biologically active metabolites of arachidonic acid were formed. The structure of one of the metabolites, compound C, was previously reported to be 12(R)-hydroxy-5,8,10,14-eicosatetraenoic acid and was found to be a potent inhibitor of the(More)
It is known that reactive oxygen species cause lung injury in association with activation of arachidonate metabolism. Because metabolites of the cyclooxygenase pathway do not appear to mediate the injury, we considered that the 5-lipoxygenase pathway might be activated and that inhibition of the pathway could interfere with the development of the injury.(More)
Potentiation of the gamma-aminobutyric acid (GABAA) receptor-gated Cl- channel response has been suggested to be a primary action of some anesthetic agents. We asked whether the GABAA receptor is a target site common for general anesthetics that are chemically and structurally diverse. This hypothesis was tested in Xenopus oocytes expressing mouse cortical(More)
The low-energy collision-induced dissociation (CID) of the carboxylate anions generated by fast atom bombardment ionization of monohydroxy unsaturated fatty acids derived from oleic, linoleic, linolenic and arachidonic acids were studied in a tandem quadrupole mass spectrometer. The collisional activation spectra revealed structurally informative ions as to(More)
We have examined the role of NAD(P)H:quinone oxidoreductase 1 (NQO1) in the bioreductive metabolism of 17-allylamino-demethoxygeldanamycin (17-AAG). High-performance liquid chromatography (HPLC) analysis of the metabolism of 17-AAG by recombinant human NQO1 revealed the formation of a more polar metabolite 17-AAGH2. The formation of 17-AAGH2 was NQO1(More)
ZD6474 [N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]-quinazolin-4-amine; Zactima] is a tyrosine kinase inhibitor with antiangiogenic and antitumor activity currently undergoing human trials for cancer treatment. Pharmacokinetic studies in animal models are an important component in the clinical development of this agent to relate(More)
Docetaxel is a semisynthetic taxane derived from the needles of the European yew (Taxus baccata) and it is an important chemotherapeutic agent in the treatment of recurrent ovarian, breast and non-small-cell lung cancers. Traditional dosing regimens with docetaxel involve doses of 60–100 mg/m2 by infusion every 3 weeks. Now weekly low-dose (30–36 mg/m2)(More)
Negative ion electrospray ionization, fast-atom bombardment, and low energy tandem mass spectrometry were used for the analysis of dihydroxy-eicosatrienoic acids, which contain a vicinol diol and three nonconjugated double bonds, dihydroxy-eicosatetraenoic acids, which contain a conjugated triene structure, and trihydroxy-eicosatetraenoic acids, which(More)