Fas is a cell surface protein that can mediate apoptosis and belongs to the tumor necrosis factor (TNF) receptor family. Anti-Fas antibody induces apoptotic cell death in sensitive cells. Because many chemotherapeutic drugs are capable of initiating pathways leading to apoptosis, we determined the effect of cyclophosphamide, one of the most widely used anticancer drugs, on Fas mediated apoptosi...

Introduction: Cardiac toxicity is one of the life-threatening complications of cancer therapy. Systemic anticancer treatments may exert their own toxic effects or can aggravate adverse effects of other drugs. We report a case of cyclophosphamide-induced cardiotoxicity in a patient with normal cardiac functions before chemotherapy. Case presentation: A 66-year-old Caucasian woman with a mediasti...

The anticancer drug cyclophosphamide induces granulosa cell apoptosis and is detoxified by glutathione (GSH) conjugation. We previously showed that both cyclophosphamide treatment and GSH depletion induced granulosa cell apoptosis in rats, but the role of GSH in apoptosis in human ovarian cells has not been studied. Using the COV434 human granulosa cell line, we tested the hypotheses that (1) G...

Breast cancer is the most common cancer among women. To date, improvements in hormonal and cytotoxic therapies have not yet led to a sustained remission or cure. In the present study, we investigated the in vitro and in vivo antitumor activities of a novel Calotropis procera protein (CP-P) isolated from root bark. CP-P protein inhibited the proliferation and induced apoptosis of breast cancer c...

The role of microsomal cytochrome b5 (Cyb5) in defining the rate of drug metabolism and disposition has been intensely debated for several decades. Recently we described mouse models involving the hepatic or global deletion of Cyb5, demonstrating its central role in in vivo drug disposition. We have now used the cytochrome b5 complete null (BCN) model to determine the role of Cyb5 in the metabo...

J The present study identifies the specific human cytochrome P-450 (CYP) enzymes involved in hydroxylation leading to activation of the anticancer drug cyclophosphamide and its isomeric analogue, ifosphamide. Substantial interindividual variation (4-9-fold) was observed in the hydroxylation of these oxazaphosphorines by a panel of 12 human liver microsomes, and a significant correlation was obt...

The present study identifies the specific human cytochrome P-450 (CYP) enzymes involved in hydroxylation leading to activation of the anticancer drug cyclophosphamide and its isomeric analogue, ifosphamide. Substantial interindividual variation (4-9-fold) was observed in the hydroxylation of these oxazaphosphorines by a panel of 12 human liver microsomes, and a significant correlation was obtai...

J The present study identifies the specific human cytochrome P-450 (CYP) enzymes involved in hydroxylation leading to activation of the anticancer drug cyclophosphamide and its isomeric analogue, ifosphamide. Substantial interindividual variation (4-9-fold) was observed in the hydroxylation of these oxazaphosphorines by a panel of 12 human liver microsomes, and a significant correlation was obt...

Preclinical studies on pharmacokinetics in animals usually require at least 3-5 animals per time point. The use of several animals in each time point may increase the result variation due to individual dosing errors and interand intraindividual variation among animals. Moreover, a large number of animals has to be euthanized in these experiments. In the present paper, the pharmacokinetics of th...

J The present study identifies the specific human cytochrome P-450 (CYP) enzymes involved in hydroxylation leading to activation of the anticancer drug cyclophosphamide and its isomeric analogue, ifosphamide. Substantial interindividual variation (4-9-fold) was observed in the hydroxylation of these oxazaphosphorines by a panel of 12 human liver microsomes, and a significant correlation was obt...