ABCB1 gene polymorphisms are not associated with treatment outcome in elderly acute myeloid leukemia patients.

Objectives: The classical multidrug resistance (MDR) gene MDR1 (ABCB1) encodes for the drug efflux pump P-glycoprotein (P-gp). P-gp expression is an adverse prognostic factor for treatment outcome in acute myeloid leukemia (AML) and is more frequently observed in older patients. Single-nucleotide polymorphisms of the ABCB1 gene, C1236T, G2677T, and C3435T, have been associated with altered drug metabolism and treatment outcome.

Identification of multidrug resistance-associated protein 1 and glutathione as multidrug resistance mechanisms in human prostate cancer cells: chemosensitization with leukotriene D4 antagonists and buthionine sulfoximine.

Objective: To assess the involvement of the multidrug resistance-associated protein 1 (MRP1) and the glutathione pathway in the multidrug resistant (MDR) phenotype of prostate cancer in vitro.

Materials And Methods: Chemoselection of human prostate cancer cell lines PC3 and DU145 with etoposide resulted in the resistant cell lines PC3-R and DU-R. Resistance against etoposide, doxorubicin and vincristine, and its reversal with leukotriene D4 antagonists MK-571 and zafirlukast, and buthionine sulfoximine (BSO), was assessed using tetrazolium-dye viability assays.

In vivo recovery and safety of human factor VIII product AAFACT in patients with haemophilia A.

AAFACT, a monoclonal purified, solvent/detergent treated human plasma-derived coagulation factor VIII concentrate obtained from plasma of voluntary, non-remunerated blood donors, is manufactured and marketed in the Netherlands by Sanquin Plasma Products since 1995. In a postmarketing surveillance study, 70 previously treated haemophilia A patients were included (73% severe, 14% moderate and 13% mild haemophilia A). Most of these patients were followed during 4 years for the appearance of adverse events, possible transmissions of blood-borne viruses and the occurrence of antibodies against FVIII.

Increased expression of the breast cancer resistance protein (BCRP) in relapsed or refractory acute myeloid leukemia (AML).

Expression of the multidrug resistance proteins P-glycoprotein, encoded by the MDR1 gene, multidrug resistance-associated protein (MRP1) and the lung resistance-related protein or major vault protein (LRP/MVP) is associated with clinical resistance to chemotherapy in acute myeloid leukemia (AML). Recently, the breast cancer-resistant protein (BCRP), the equivalent of mitoxantrone-resistant protein (MXR) or placental ABC transporter (ABCP), was described in AML. We investigated MDR1, MRP1, LRP/MVP and BCRP mRNA expression simultaneously in 20 paired clinical AML samples from diagnosis and relapse or refractory disease, using quantitative Taqman analysis.

Dose-finding study of valspodar (PSC 833) with daunorubicin and cytarabine to reverse multidrug resistance in elderly patients with previously untreated acute myeloid leukemia.

Introduction: This trial was designed to determine the maximum tolerated dose of intravenous daunorubicin (DNR) in combination with valspodar and to test the feasibility of P-glycoprotein modulation using valspodar in elderly patients with previously untreated acute myelogenous leukemia receiving standard induction chemotherapy.

Methods: Patients > or =60 years of age with previously untreated AML received valspodar (10 mg/kg/24 h by continuous intravenous infusion [CIV] on days 1-4 with a 2-mg/kg loading dose on day 1) in conjunction with two cycles of induction chemotherapy consisting of cytarabine (200 mg/m(2) CIV on days 1-7), and DNR (35 mg/m(2) [cohort 1] or 45 mg/m(2) [cohort 2] on days 1-3, intravenous bolus). Patients were assessed for dose-limiting toxicities (DLT), response rate, event-free and overall survival, and pharmacokinetics of valspodar and DNR.