Megumi Yoshikawa

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Gefitinib ("Iressa", ZD1839) is an orally active, selective epidermal growth factor receptor tyrosine kinase inhibitor, and the single agent is clinically effective in non-small cell lung cancer. Although gefitinib combined with various cytotoxic agents has been reported to enhance cytotoxicity in vitro and in mouse models, the mechanism remains(More)
Breast cancer resistance protein (BCRP/ABCG2) of an ATP-binding cassette half-transporter confers resistance against mitoxantrone and camptothecin derivatives of topotecan and irinotecan. Novobiocin, a coumermycin antibiotic, is known to enhance anticancer drug sensitivity of cancer cells in vitro and in vivo, the mechanism of which remains undetermined.(More)
Irinotecan (CPT-11) is a widely-used potent anticancer drug that inhibits mammalian DNA topoisomerase I, however overexpression of the ATP-binding cassette transporter ABCG2 can confer cancer cells resistance to SN-38, the active form of CPT-11. In the present study, we have examined the contribution of three variant forms of ABCG2 to SN-38 resistance.(More)
SN-38 (7-ethyl-10-hydroxycamptothecin) is an active metabolite derived from the semi-synthetic compound camptothecin (CPT) named Irinotecan (CPT-11). The antitumor activity of SN-38 is 1000-fold more potent than the parent CPT-11. Fourteen new derivatives of camptothecin have recently been developed by Yakult Honsha (Tokyo, Japan). Here we describe a simple(More)
Irinotecan (7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothecin; CPT-11) is a widely used potent antitumor drug that inhibits mammalian DNA topoisomerase I (Topo I); however, overexpression of ABCG2 (BCRP/MXR/ABCP) can confer cancer cell resistance to SN-38, the active form of CPT-11. We have recently demonstrated that plasma membrane(More)
We have cloned a new mouse ATP-binding cassette (ABC) transporter, Abcg4, from a complementary DNA (cDNA) library of mouse brain. The cloned Abcg4 cDNA encodes a protein consisting of 646 amino acids and including one ATP-binding cassette and six transmembrane domains. The Abcg4 protein exhibits high identity (96%) with human ABCG4 in terms of the amino(More)
Accumulating evidence suggests that several ATP-binding cassette (ABC) transporters mediate the elimination of anticancer drugs from cancer cells and thereby confer drug resistance. SN-38-selected PC-6/SN2-5H human lung carcinoma cells were shown to overexpress ABCG2 with the reduced intracellular accumulation of SN-38, the active metabolite of irinotecan.(More)
The highly regioselective hydroselenation of N-vinyl lactams has been revealed to successfully afford the corresponding N,Se-acetals as Markovnikov adducts. In the case of terminal N-vinyl lactams, Markovnikov-selective hydroselenation proceeds efficiently in the absence of any catalyst (or additive), owing to the acidity of the selenols. In contrast, the(More)
Remarkable advances have been made in cancer chemotherapy by developing new anticancer drugs and pharmacogenomics strategies. However, multidrug resistance in human cancers is the major obstacle to long-term, sustained patient response to chemotherapy. Several ATP-binding cassette (ABC) transporters cause multidrug resistance in cancer cells by actively(More)
BACKGROUND Gefitinib competes with topoisomerase I inhibitors at drug efflux pumps in vitro. We evaluated the effects of oral gefitinib on pharmacokinetic parameters of orally coadministered irinotecan. METHODS We measured the serum pharmacokinetic parameters and biliary excretion of irinotecan, SN-38 and its glucuronide after irinotecan (50 or 100 mg/kg)(More)
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