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Won

Synergistic Cytotoxicity and Pharmacogenetics of Gemcitabine and Pemetrexed Combination in Pancreatic Cancer Cell Lines

In the last decade, the availability of several new active drugs has improved the efficacy of combination regimens and substantially increased the response rate of refractory tumors, including pancreatic cancer. Antimetabolites are widely used in combination regimens because of their activity and generally manageable toxicities; however, several preclinical studies have shown schedule-dependent drug interaction . For example, gemcitabine (2',2'-difluoro-2'-deoxycytidine) is synergistic in vitro with cisplatin in non-small cell lung cancer cell lines and this interaction is most pronounced when gemcitabine precedes this drug . Similar results were obtained using PANC-1 and BxPc3 pancreatic cancer cells for which the most synergistic schedule is gemcitabine followed by cisplatin , whereas additive to slightly synergistic or antagonistic effects are observed with gemcitabine followed by topotecan, paclitaxel, and docetaxel in various non-small cell lung cancer cell lines.......

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ABCG2 Pharmacogenetics
Ethnic Differences in Allele Frequency and Assessment of Influence on Irinotecan Disposition

The ATP-binding cassette (ABC) transporters represent the largest family of transmembrane proteins that bind ATP and use the energy to drive the transport of various molecules across cell membranes (1) . On the basis of the arrangement of molecular structural components, i.e., the nucleotide binding domain and the topology of transmembrane domains, human proteins are classified into seven distinct families (ABCA to ABCG; ref. 1 ). The ABCG subfamily consists of several half transporters that are generally thought to form homo- or heterodimers to create the active transporter (2 , 3) . Very recently, it was reported that human ABCG2 probably exists as a homotetramer with a possibility of a higher form of oligomerization (3) . The human ABCG2 gene is located on chromosome 4q22 and encodes a 655 amino acid polypeptide (4 , 5) . In vitro studies have indicated that, apart from topotecan (6 , 7) , the irinotecan metabolites 7-ethyl-10-hydroxycamptothecin (SN-38) and its glucuronide conjugate SN-38G (8 , 9) are very good substrates for ABCG2. Furthermore, overexpression of ABCG2 reportedly .

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