東華大學圖書館 |

語系: 繁體中文

說明(常見問題)

回圖書館首頁

手機版館藏查詢

登入

回首頁

切換: 標籤 | MARC模式 | ISBD

Oxidative stress-mediated anticancer...

Loma Linda University.

FindBook

Google Book

Amazon

博客來

Oxidative stress-mediated anticancer activity of novel AhR modulators AF & 5F203.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Oxidative stress-mediated anticancer activity of novel AhR modulators AF & 5F203./
作者:	McLean, Lancelot S.
面頁冊數:	176 p.
附註:	Adviser: Hansel Fletcher.
Contained By:	Dissertation Abstracts International69-04B.
標題:	Biology, Genetics. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3308720
ISBN:	9780549551904

Oxidative stress-mediated anticancer activity of novel AhR modulators AF & 5F203.
McLean, Lancelot S.

Oxidative stress-mediated anticancer activity of novel AhR modulators AF & 5F203. - 176 p.

Adviser: Hansel Fletcher.

Thesis (Ph.D.)--Loma Linda University, 2008.

Estrogen receptor positive (ER+) breast cancer tends to respond to anti-estrogen agents such as Tamoxifen. Approximately 40% of ER+ breast cancer is resistant to these agents and those that initially respond often acquire resistance. Estrogen receptor negative (ER-) breast cancer remains largely unresponsive to these agents. It is therefore vital to discover drugs that are potent in both forms of breast cancer. Aminoflavone, (5-amino-2,3-fluorophenyl)-6,8-difluoro-7-methyl-4H-1-benzopyran-4-one; AF; NSC 686288) and 5F203, (2-[-Amino-3-methy phenyl]-5-flurobenzothiazole) are novel anticancer candidate agents that display potent in vitro and in vivo anti-proliferative activity against select human tumor cells with a unique anticancer activity profile in the National Cancer Institute 60 cell line screen AF and 5F203 activate the aryl hydrocarbon receptor (AhR) signaling pathway resulting in the transcription of genes such as those encoding cytochromes P450 1A1, 1A2 and 1B1. These cytochromes mediate the activity of AF and 5F203 by converting them into reactive intermediates that induce DNA damage in sensitive breast cancer cells. Previous reports indicate 5F203 shows activity in some ER- breast cancer cells including the MDA-MB-468 cell line and we have determined that AF inhibits the growth of MUA-MB-468 cells as well. We have also determined that AF induces S phase arrest with an accumulation of cells in sub G1 indicating the ability of AF to induce apoptosis. A number of chemotherapeutic agents and substances known to activate the AhR pathway and induce CYP1A1, increase intracellular reactive oxygen species (ROS) levels. Our preliminary studies indicated that AF and 5F203 alter intracellular ROS levels in sensitive cells. We hypothesize that AF and 5F203 modulate CYP-dependent ROS levels and mitogen activated protein kinase (MAPK) pathways resulting in the induction of DNA damage and apoptosis in sensitive breast cancer cells. In this project we have demonstrated that (1) ROS play a role in mediating the anticancer activity of AF and 5F203 and determined that AF- and 5F203-induced ROS modulation is CYP-linked, (2) AF and 5F203 induce oxidative DNA damage and subsequently activate caspase-dependent apoptosis and (3) AF and 5F203 modulate the activity of specific (MAPK) pathways to induce apoptosis in ER+ and ER- breast cancer cell lines. This project has defined the role of ROS in mediating the anticancer activity of 5F203 and AF which are currently in Phase I clinical trials in the UK (administered in prodrug form) and US respectively.

ISBN: 9780549551904Subjects--Topical Terms:

1017730
Biology, Genetics.

Oxidative stress-mediated anticancer activity of novel AhR modulators AF & 5F203.
LDR:03465nam 2200277 a 45 001 855194
005 20100708
008 100708s2008 ||||||||||||||||| ||eng d
020 $a 9780549551904
035 $a (UMI)AAI3308720
035 $a AAI3308720
040 $a UMI $c UMI
100 1 $a McLean, Lancelot S. $3 1021735
245 1 0 $a Oxidative stress-mediated anticancer activity of novel AhR modulators AF & 5F203.
300 $a 176 p.
500 $a Adviser: Hansel Fletcher.
500 $a Source: Dissertation Abstracts International, Volume: 69-04, Section: B, page: 2247.
502 $a Thesis (Ph.D.)--Loma Linda University, 2008.
520 $a Estrogen receptor positive (ER+) breast cancer tends to respond to anti-estrogen agents such as Tamoxifen. Approximately 40% of ER+ breast cancer is resistant to these agents and those that initially respond often acquire resistance. Estrogen receptor negative (ER-) breast cancer remains largely unresponsive to these agents. It is therefore vital to discover drugs that are potent in both forms of breast cancer. Aminoflavone, (5-amino-2,3-fluorophenyl)-6,8-difluoro-7-methyl-4H-1-benzopyran-4-one; AF; NSC 686288) and 5F203, (2-[-Amino-3-methy phenyl]-5-flurobenzothiazole) are novel anticancer candidate agents that display potent in vitro and in vivo anti-proliferative activity against select human tumor cells with a unique anticancer activity profile in the National Cancer Institute 60 cell line screen AF and 5F203 activate the aryl hydrocarbon receptor (AhR) signaling pathway resulting in the transcription of genes such as those encoding cytochromes P450 1A1, 1A2 and 1B1. These cytochromes mediate the activity of AF and 5F203 by converting them into reactive intermediates that induce DNA damage in sensitive breast cancer cells. Previous reports indicate 5F203 shows activity in some ER- breast cancer cells including the MDA-MB-468 cell line and we have determined that AF inhibits the growth of MUA-MB-468 cells as well. We have also determined that AF induces S phase arrest with an accumulation of cells in sub G1 indicating the ability of AF to induce apoptosis. A number of chemotherapeutic agents and substances known to activate the AhR pathway and induce CYP1A1, increase intracellular reactive oxygen species (ROS) levels. Our preliminary studies indicated that AF and 5F203 alter intracellular ROS levels in sensitive cells. We hypothesize that AF and 5F203 modulate CYP-dependent ROS levels and mitogen activated protein kinase (MAPK) pathways resulting in the induction of DNA damage and apoptosis in sensitive breast cancer cells. In this project we have demonstrated that (1) ROS play a role in mediating the anticancer activity of AF and 5F203 and determined that AF- and 5F203-induced ROS modulation is CYP-linked, (2) AF and 5F203 induce oxidative DNA damage and subsequently activate caspase-dependent apoptosis and (3) AF and 5F203 modulate the activity of specific (MAPK) pathways to induce apoptosis in ER+ and ER- breast cancer cell lines. This project has defined the role of ROS in mediating the anticancer activity of 5F203 and AF which are currently in Phase I clinical trials in the UK (administered in prodrug form) and US respectively.
590 $a School code: 0106.
650 4 $a Biology, Genetics. $3 1017730
650 4 $a Health Sciences, Oncology. $3 1018566
690 $a 0369
690 $a 0992
710 2 $a Loma Linda University. $3 1020166
773 0 $t Dissertation Abstracts International $g 69-04B.
790 $a 0106
790 1 0 $a Fletcher, Hansel, $e advisor
791 $a Ph.D.
792 $a 2008
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3308720