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The role of efflux transporters in t...

Su, Yaming.

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The role of efflux transporters in the pharmacokinetics and pharmacodynamics of anti-cancer drugs.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	The role of efflux transporters in the pharmacokinetics and pharmacodynamics of anti-cancer drugs./
作者:	Su, Yaming.
面頁冊數:	188 p.
附註:	Source: Dissertation Abstracts International, Volume: 68-01, Section: B, page: 0235.
Contained By:	Dissertation Abstracts International68-01B.
標題:	Health Sciences, Pharmacology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3249352

The role of efflux transporters in the pharmacokinetics and pharmacodynamics of anti-cancer drugs.
Su, Yaming.

The role of efflux transporters in the pharmacokinetics and pharmacodynamics of anti-cancer drugs. - 188 p.

Source: Dissertation Abstracts International, Volume: 68-01, Section: B, page: 0235.

Thesis (Ph.D.)--Rutgers The State University of New Jersey - New Brunswick, 2006.

Chemotherapy is currently the most effective treatment for metastatic tumors. However, its success in the clinic is significantly impeded by the development of multidrug resistance (MDR), which is often associated with the upregulation of efflux transporters in cancer cells. In addition to extruding chemotherapeutic agents out of cancer cells, efflux transporters at intestine, liver, kidney markedly affect the in vivo absorption and/or disposition of most anticancer drugs.Subjects--Topical Terms:

1017717
Health Sciences, Pharmacology.

The role of efflux transporters in the pharmacokinetics and pharmacodynamics of anti-cancer drugs.
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100 1 $a Su, Yaming. $3 1923129
245 1 4 $a The role of efflux transporters in the pharmacokinetics and pharmacodynamics of anti-cancer drugs.
300 $a 188 p.
500 $a Source: Dissertation Abstracts International, Volume: 68-01, Section: B, page: 0235.
500 $a Adviser: Patrick J. Sinko.
502 $a Thesis (Ph.D.)--Rutgers The State University of New Jersey - New Brunswick, 2006.
520 $a Chemotherapy is currently the most effective treatment for metastatic tumors. However, its success in the clinic is significantly impeded by the development of multidrug resistance (MDR), which is often associated with the upregulation of efflux transporters in cancer cells. In addition to extruding chemotherapeutic agents out of cancer cells, efflux transporters at intestine, liver, kidney markedly affect the in vivo absorption and/or disposition of most anticancer drugs.
520 $a The objectives of current studies were to assess the contribution of efflux transporters to the MDR phenotype in human leukemia cells selected using CPT-11 (CPT-K5 cells), and to investigate the in vivo relevance of intestinal breast cancer resistant protein (BCRP/ABCG2) in the absorption and disposition of topotecan (TPT).
520 $a The results from the present study demonstrate that drug-induced BCRP significantly limits mitoxantrone (MX) accumulation in CPT-K5 cells. The inhibition of BCRP almost completely reversed BCRP-mediated MX efflux, however, drug sensitivity was not restored, suggesting that upregulation of BCRP plays a minimal role in conferring MX resistance to CPT-K5 cells. Further studies revealed that Bcl-2, an antiapoptotic protein, was remarkably overexpressed in CPT-K5 cells, and could be exploited for apoptosis induction by using Bcl-2 antagonists. Taken together, these results lead to a better understanding of the mechanisms of MDR.
520 $a The role of intestinal BCRP in TPT absorption and disposition was mechanistically studied at the in vitro, in situ and in vivo levels. The results showed that novobiocin (NOV) specifically inhibited BCRP but not Pgp. It was also demonstrated that coadministration of NOV significantly increased the oral bioavailability of TPT in rat by enhancing intestinal absorption and decreasing systemic clearance. These findings favor the clinical implementation of TPT/NOV oral dosing regimen. Saquinavir (SQV) was also demonstrated as a potent inhibitor for human BCRP at in vitro level, but BCRP-mediated pharmacokinetic interaction between SQV and TPT was not observed in rat. It remains unclear whether oral SQV could lead to significant drug-drug interaction in human by inhibiting BCRP.
520 $a The studies in appendix demonstrated that organic anion-transporting polypeptides (OATPs) transport SQV in concert with P-glycoprotein (Pgp) and multidrug resistance protein 2 (MRP2).
590 $a School code: 0190.
650 4 $a Health Sciences, Pharmacology. $3 1017717
650 4 $a Health Sciences, Oncology. $3 1018566
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690 $a 0992
710 2 0 $a Rutgers The State University of New Jersey - New Brunswick. $3 1017590
773 0 $t Dissertation Abstracts International $g 68-01B.
790 1 0 $a Sinko, Patrick J., $e advisor
790 $a 0190
791 $a Ph.D.
792 $a 2006
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3249352