Previous studies have shown that the V12M and Q141K variants of breast cancer resistance protein (BCRP) can affect expression and function of the transporter. In this study, the effects of the I206L, N590Y, and D620N variants on protein expression, plasma membrane localization, and transport activity of BCRP were investigated. Wild-type BCRP and the three variants were stably expressed in human...

Balanced chromosomal translocations that generate chimeric oncoproteins are considered to be initiating lesions in the pathogenesis of acute myeloid leukemia. The most frequent is the t(15;17)(q22;q21), which fuses th leukemia (APL). An increasing proportion of APL cases are therapy develop following exposure to radiotherapy and/or chemotherapeutic agents that target DNA topoisomerase II (topoI...

BACKGROUND To determine whether patients with high-risk metastatic breast cancer draw benefit from combination chemotherapy as first-line treatment. PATIENTS AND METHODS A total of 260 women with measurable metastatic breast cancer fulfilling high-risk criteria, previously untreated with chemotherapy for their metastatic disease, were randomized to receive either mitoxantrone 12 mg/m(2) or th...

BACKGROUND AND PURPOSE Mitoxantrone is an approved disease modifying agent for treatment of multiple sclerosis (MS). The aim of the study was to assess its efficacy and safety in Indian MS patients. MATERIALS AND METHODS A total of 23 patients with clinically definite MS (Poser criteria) were enrolled in an open label study. Of which, 21 satisfied the McDonald's criteria for MS and two satisf...

PURPOSE The purpose is to determine the dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD) of mitoxantrone and docetaxel administered weekly before prostatectomy in men with localized prostate cancer at high risk for recurrence. EXPERIMENTAL DESIGN Twenty-two patients were treated with four cycles of docetaxel 35 mg/m(2) and increasing doses of mitoxantrone starting at 2 mg/m(2) re...

BACKGROUND The topoisomerase II-targeted drugs, epipodophyllotoxins and anthracyclines, have been shown to induce therapy-related AML (t-AML) characterized by a short latency period after chemotherapy, the absence of prior myelodysplastic syndrome and stereotyped chromosome aberrations. Few reports have been published on patients treated with the anthracenedione mitoxantrone which also targets ...

We sought to characterize the interactions of flavopiridol with members of the ATP-binding cassette (ABC) transporter family. Cells overexpressing multidrug resistance-1 (MDR-1) and multidrug resistance-associated protein (MRP) did not exhibit appreciable flavopiridol resistance, whereas cell lines overexpressing the ABC half-transporter, ABCG2 (MXR/BCRP/ABCP1), were found to be resistant to fl...