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Transfection of multidrug resistance proteins (MRPs) MRP1 and MRP2 in human ovarian carcinoma 2008 cells conferred a marked level of resistance to short-term (1-4 h) exposure to the polyglutamatable antifolates methotrexate (MTX; 21-74-fold), ZD1694 (4-138-fold), and GW1843 (101-156-fold). Evidence for MRP-mediated antifolate efflux relies upon the(More)
The multidrug-resistance associated protein MRP is a 180- to 195-kDa membrane protein associated with resistance of human tumor cells to cytotoxic drugs. We have investigated how MRP confers drug resistance in SW-1573 human lung carcinoma cells by generating a subline stably transfected with an expression vector containing MRP cDNA. MRP-overexpressing(More)
BACKGROUND Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that regulates gene expression in critical pathways involved in tumor growth and metastases. In this report, we investigated whether the level of HIF-1 alpha is increased during carcinogenesis in breast tissue and is associated with other tumor biomarkers. METHODS Paraffin-embedded(More)
The transport properties and growth-inhibitory potential of 37 classic and novel antifolate compounds have been tested in vitro against human and murine cell lines expressing different levels of the reduced folate carrier (RFC), the membrane-associated folate binding protein (mFBP), or both. The intracellular targets of these drugs were dihydrofolate(More)
Fluorouracil (5FU) is still considered the most active antineoplastic agent in the treatment of advanced colorectal cancer. The drug needs to be converted to the nucleotide level in order to exert its effect. It can be incorporated into RNA leading to interference with the maturation of nuclear RNA. However, its conversion to 5-fluoro-2'deoxy-5'(More)
The antineoplastic drug doxorubicin is capable of generating a variety of free radical species in subcellular systems and this capacity has been considered critical for its antitumor action. However, for most tumor cell lines this mechanism of cytotoxicity does not appear to play a major role. Free radical-independent cytotoxicity mechanisms, taking place(More)
BACKGROUND Colon cancer is curable by surgery, but cure rate depends on the extent of disease. We investigated whether adjuvant active specific immunotherapy (ASI) with an autologous tumour cell-BCG vaccine with surgical resection was more beneficial than resection alone in stage II and III colon cancer. METHODS In a prospective randomised trial, 254(More)
Pharmacokinetic studies were performed in 51 patients who received cisplatin infusions. Two treatment regimens (single-day or daily for 5 days) and three infusion schedules (for 4 to 15 minutes, 2 to 3 hours, or 24 hours) were used. The daily dose of cisplatin varied from 20 to 120 mg/m2. The kinetics of total platinum studied up to day 5 revealed(More)
PURPOSE To determine the time-dependence of fluorouracil (5FU)-induced thymidylate synthase (TS) inhibition in colon cancer patients, the effect of leucovorin (LV), and the relation to response. PATIENTS AND METHODS A 5FU injection (500 mg/m2) was given to 47 patients with advanced colorectal cancer; tumor biopsy specimens were obtained 1 to 72 hours(More)
In this study we report that the multidrug resistance protein (MRP) transports calcein from the cytoplasmic compartment of tumor cells, in contrast to P-glycoprotein which transports calcein acetoxymethyl ester from the plasmamembrane. The transport of calcein by MRP is ATP-dependent and is inhibited by probenecid and vincristine. Intracellular glutathione(More)