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In vitro and in vivo pharmacologic e...

Hurh, Eunju.

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In vitro and in vivo pharmacologic evaluation of novel lysophospholipid analogs as anticancer agents.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	In vitro and in vivo pharmacologic evaluation of novel lysophospholipid analogs as anticancer agents./
作者:	Hurh, Eunju.
面頁冊數:	260 p.
附註:	Source: Dissertation Abstracts International, Volume: 66-11, Section: B, page: 5923.
Contained By:	Dissertation Abstracts International66-11B.
標題:	Health Sciences, Pharmacy. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3197797
ISBN:	0542421038

In vitro and in vivo pharmacologic evaluation of novel lysophospholipid analogs as anticancer agents.
Hurh, Eunju.

In vitro and in vivo pharmacologic evaluation of novel lysophospholipid analogs as anticancer agents. - 260 p.

Source: Dissertation Abstracts International, Volume: 66-11, Section: B, page: 5923.

Thesis (Ph.D.)--The Ohio State University, 2005.

Advanced prostate cancer is treated with androgen ablation therapy, but virtually all patients receiving this treatment relapse and develop androgen-independent tumors for which only experimental treatments exist. One of the possible mechanisms that could lead to the development of androgen-independent prostate cancer involves overactivation of signal transduction pathways. Lysophospholipids are phospholipid growth factors that promote tumor cell proliferation, survival, and invasion by binding to a family of G protein-coupled receptors collectively referred to as lysophospholipid receptors. Due to their involvement in cancer progression and overexpression of their receptors in cancer, novel agents that inhibit molecules in the lysophospholipid signal transduction pathways hold promise as potential chemotherapeutic agents for advanced prostate cancer. The goals of the current research were to characterize structure-activity relationships for a series of lysophospholipid analogs and define their mechanism of action, while integrating in vivo studies to explore the physicochemical and pharmacokinetic properties that govern their in vivo anticancer activity.

ISBN: 0542421038Subjects--Topical Terms:

1017737
Health Sciences, Pharmacy.

In vitro and in vivo pharmacologic evaluation of novel lysophospholipid analogs as anticancer agents.
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245 1 0 $a In vitro and in vivo pharmacologic evaluation of novel lysophospholipid analogs as anticancer agents.
300 $a 260 p.
500 $a Source: Dissertation Abstracts International, Volume: 66-11, Section: B, page: 5923.
500 $a Adviser: James T. Dalton.
502 $a Thesis (Ph.D.)--The Ohio State University, 2005.
520 $a Advanced prostate cancer is treated with androgen ablation therapy, but virtually all patients receiving this treatment relapse and develop androgen-independent tumors for which only experimental treatments exist. One of the possible mechanisms that could lead to the development of androgen-independent prostate cancer involves overactivation of signal transduction pathways. Lysophospholipids are phospholipid growth factors that promote tumor cell proliferation, survival, and invasion by binding to a family of G protein-coupled receptors collectively referred to as lysophospholipid receptors. Due to their involvement in cancer progression and overexpression of their receptors in cancer, novel agents that inhibit molecules in the lysophospholipid signal transduction pathways hold promise as potential chemotherapeutic agents for advanced prostate cancer. The goals of the current research were to characterize structure-activity relationships for a series of lysophospholipid analogs and define their mechanism of action, while integrating in vivo studies to explore the physicochemical and pharmacokinetic properties that govern their in vivo anticancer activity.
520 $a Prostate cancer presents a unique disease model to study the role of lysophospholipid growth factor signaling pathways. PC-3, LNCaP, DU 145, PPC-1, and TSU-Pr1 human prostate cancer cell lines represent a wide range of clinically relevant prostate tumor types demonstrating various stages of the disease, different sites of metastasis, and differences in androgen dependence for cell growth. Moreover, these cell lines demonstrate differential expression and activity profiles of the LPL receptors and downstream mediators including PTEN lipid phosphatase and AKT and MAPK.
520 $a Three classes of lysophospholipid analogs were synthesized and tested in the aforementioned prostate cancer cell lines and a negative control cell line that lacks lysophospholipid receptors (RH7777 rat hepatoma cells). Active serine amide derivatives (Generation 1) showed potency similar to that of 5-fluorouracil but they also affected growth of the negative control cell line. Thiazolidinone analogs (Generation 2), where the phosphate group of lysophospholipids is replaced with a thiazolidinone moiety were equipotent to serine amides with improved selectivity. Thiazolidine analogs (Generation 3) were the most potent and selective of all three groups of lysophospholipid analogs examined. Further, thiazolidine analogs almost completely inhibited AKT phosphorylation, consequently inducing apoptosis. However, these analogs failed to interact directly with lysophosphatidic acid receptors as proven by absence of inhibitory action on lysophosphatidic acid-driven calcium mobilization. (Abstract shortened by UMI.)
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773 0 $t Dissertation Abstracts International $g 66-11B.
790 1 0 $a Dalton, James T., $e advisor
790 $a 0168
791 $a Ph.D.
792 $a 2005
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