東華大學圖書館 |

Language: English

Help

回圖書館首頁

手機版館藏查詢

Back

Switch To: Labeled | MARC Mode | ISBD

Development and evaluation of bevaci...

Kuesters, Geoffrey M.

Linked to FindBook

Google Book

Amazon

博客來

Development and evaluation of bevacizumab-modified pegylated cationic liposomes using cellular and in vivo models of human pancreatic cancer.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Development and evaluation of bevacizumab-modified pegylated cationic liposomes using cellular and in vivo models of human pancreatic cancer./
Author:	Kuesters, Geoffrey M.
Description:	119 p.
Notes:	Source: Dissertation Abstracts International, Volume: 71-05, Section: B, page: 3332.
Contained By:	Dissertation Abstracts International71-05B.
Subject:	Nanotechnology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3398900
ISBN:	9781109732153

Development and evaluation of bevacizumab-modified pegylated cationic liposomes using cellular and in vivo models of human pancreatic cancer.
Kuesters, Geoffrey M.

Development and evaluation of bevacizumab-modified pegylated cationic liposomes using cellular and in vivo models of human pancreatic cancer. - 119 p.

Source: Dissertation Abstracts International, Volume: 71-05, Section: B, page: 3332.

Thesis (Ph.D.)--Northeastern University, 2010.

Targeting the tumor vascular supply in a homogenous manner is a difficult task to achieve with the use of pegylated cationic liposomes (PCLs) alone. Our formulation consisting of bevacizumab conjugated to the distal end of PEG on PCLs was thus developed in an effort to eliminate some of this heterogeneity as well as to increase tumor targeting overall. This study focuses on pancreatic cancer, which has the poorest five-year survival rate of all cancers because of its late diagnosis. The addition of bevacizumab will target tumor areas because it binds to VEGF which is secreted by tumors in high levels. In vitro, we showed that pancreatic cancer cells (Capan-1, HPAF-II and PANC-1) all secrete VEGF into media at different levels, with Capan-1 producing the most and HPAF-II producing the least. A murine endothelial cell line, MS1-VEGF, produces and secretes the most VEGF. A human microvascular endothelial cell line (HMEC-1) was grown in two different conditions, with and without VEGF in the media. Modifying PCLs with bevacizumab enhanced the binding and uptake of PCLs by some pancreatic and endothelial cells in vitro, particularly the cells that had or secreted the most significant amount of VEGF in the media. This translated into enhanced tumor targeting in a biodistribution study using a Capan-1 subcutaneous pancreatic tumor model. This also showed enhanced blood retention compared to the unmodified PCLs while it diminished uptake by the spleen and increased uptake by the kidney. To test the therapeutic benefit of this enhanced uptake and targeting, an anti-angiogenic agent, 2-methoxyestradiol was incorporated into the formulation with 20% incorporation efficiency. Both the unmodified and modified drug-loaded PCLs were the least efficacious against Capan-1, moderately effective against HPAF-II, PANC-1, MS1-VEGF and HMEC-1 grown without VEGF in the media and most efficacious against HMEC-1 grown with VEGF which had the most VEGF present in the media. Multiple in vivo experiments were performed using two different pancreatic cancer models, one with HPAF-II and the other with Capan-1. The HPAF-II study showed that bevacizumab-modified PCLs significantly enhanced the therapeutic effect over unmodified PCLs, which were ineffective when compared to the untreated control. However, bevacizumab alone was just as efficacious as the bevacizumab-modified PCLs. In the Capan-1 study, both the modified and unmodified PCLs were efficacious but the bevacizumab-modified PCLs were the most efficacious. The addition of bevacizumab not only increased the tumor targeting but also the therapeutic efficacy of 2-methoxyestradiol. Attaching bevacizumab to the distal end of PEG on 2-methoxyestradiol-loaded PCLs was effective at limiting tumor growth. The potential for this formulation is not limited to therapy but also for imaging tumors as well as monitoring the therapeutic response.

ISBN: 9781109732153Subjects--Topical Terms:

526235
Nanotechnology.

Development and evaluation of bevacizumab-modified pegylated cationic liposomes using cellular and in vivo models of human pancreatic cancer.
LDR:04079nam 2200325 4500 001 1403523
005 20111118095948.5
008 130515s2010 ||||||||||||||||| ||eng d
020 $a 9781109732153
035 $a (UMI)AAI3398900
035 $a AAI3398900
040 $a UMI $c UMI
100 1 $a Kuesters, Geoffrey M. $3 1682791
245 1 0 $a Development and evaluation of bevacizumab-modified pegylated cationic liposomes using cellular and in vivo models of human pancreatic cancer.
300 $a 119 p.
500 $a Source: Dissertation Abstracts International, Volume: 71-05, Section: B, page: 3332.
500 $a Adviser: Robert B. Campbell.
502 $a Thesis (Ph.D.)--Northeastern University, 2010.
520 $a Targeting the tumor vascular supply in a homogenous manner is a difficult task to achieve with the use of pegylated cationic liposomes (PCLs) alone. Our formulation consisting of bevacizumab conjugated to the distal end of PEG on PCLs was thus developed in an effort to eliminate some of this heterogeneity as well as to increase tumor targeting overall. This study focuses on pancreatic cancer, which has the poorest five-year survival rate of all cancers because of its late diagnosis. The addition of bevacizumab will target tumor areas because it binds to VEGF which is secreted by tumors in high levels. In vitro, we showed that pancreatic cancer cells (Capan-1, HPAF-II and PANC-1) all secrete VEGF into media at different levels, with Capan-1 producing the most and HPAF-II producing the least. A murine endothelial cell line, MS1-VEGF, produces and secretes the most VEGF. A human microvascular endothelial cell line (HMEC-1) was grown in two different conditions, with and without VEGF in the media. Modifying PCLs with bevacizumab enhanced the binding and uptake of PCLs by some pancreatic and endothelial cells in vitro, particularly the cells that had or secreted the most significant amount of VEGF in the media. This translated into enhanced tumor targeting in a biodistribution study using a Capan-1 subcutaneous pancreatic tumor model. This also showed enhanced blood retention compared to the unmodified PCLs while it diminished uptake by the spleen and increased uptake by the kidney. To test the therapeutic benefit of this enhanced uptake and targeting, an anti-angiogenic agent, 2-methoxyestradiol was incorporated into the formulation with 20% incorporation efficiency. Both the unmodified and modified drug-loaded PCLs were the least efficacious against Capan-1, moderately effective against HPAF-II, PANC-1, MS1-VEGF and HMEC-1 grown without VEGF in the media and most efficacious against HMEC-1 grown with VEGF which had the most VEGF present in the media. Multiple in vivo experiments were performed using two different pancreatic cancer models, one with HPAF-II and the other with Capan-1. The HPAF-II study showed that bevacizumab-modified PCLs significantly enhanced the therapeutic effect over unmodified PCLs, which were ineffective when compared to the untreated control. However, bevacizumab alone was just as efficacious as the bevacizumab-modified PCLs. In the Capan-1 study, both the modified and unmodified PCLs were efficacious but the bevacizumab-modified PCLs were the most efficacious. The addition of bevacizumab not only increased the tumor targeting but also the therapeutic efficacy of 2-methoxyestradiol. Attaching bevacizumab to the distal end of PEG on 2-methoxyestradiol-loaded PCLs was effective at limiting tumor growth. The potential for this formulation is not limited to therapy but also for imaging tumors as well as monitoring the therapeutic response.
590 $a School code: 0160.
650 4 $a Nanotechnology. $3 526235
650 4 $a Health Sciences, Oncology. $3 1018566
690 $a 0652
690 $a 0992
710 2 $a Northeastern University. $b Pharmaceutics and Drug Delivery Systems. $3 1682792
773 0 $t Dissertation Abstracts International $g 71-05B.
790 1 0 $a Campbell, Robert B., $e advisor
790 1 0 $a Schatz, Robert A. $e committee member
790 1 0 $a Gatley, Samuel John $e committee member
790 1 0 $a Torchilin, Vladimir P. $e committee member
790 1 0 $a Moore, Anna $e committee member
790 $a 0160
791 $a Ph.D.
792 $a 2010
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3398900