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Soluble VEGFR-2 as a surrogate bioma...

University of Toronto (Canada).

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Soluble VEGFR-2 as a surrogate biomarker for tumor angiogenesis and anti-angiogenic therapy.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Soluble VEGFR-2 as a surrogate biomarker for tumor angiogenesis and anti-angiogenic therapy./
Author:	Ebos, John Michael Louis.
Description:	231 p.
Notes:	Source: Dissertation Abstracts International, Volume: 69-06, Section: B, page: 3524.
Contained By:	Dissertation Abstracts International69-06B.
Subject:	Biology, Cell. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoeng/servlet/advanced?query=NR39860
ISBN:	9780494398609

Soluble VEGFR-2 as a surrogate biomarker for tumor angiogenesis and anti-angiogenic therapy.
Ebos, John Michael Louis.

Soluble VEGFR-2 as a surrogate biomarker for tumor angiogenesis and anti-angiogenic therapy. - 231 p.

Source: Dissertation Abstracts International, Volume: 69-06, Section: B, page: 3524.

Thesis (Ph.D.)--University of Toronto (Canada), 2008.

Unrestricted tumor growth requires blood vessel development, a process called tumor angiogenesis, and therapeutic inhibition of this process is now a validated anti-cancer treatment strategy. This thesis introduces a novel soluble form of the vascular endothelial growth factor receptor 2 (sVEGFR-2) and outlines studies designed to assess the potential exploitation of this protein as a surrogate biomarker of tumor angiogenesis and anti-angiogenic drug activity/efficacy---particularly for those drugs that target the vascular endothelial growth factor (VEGF) system.

ISBN: 9780494398609Subjects--Topical Terms:

1017686
Biology, Cell.

Soluble VEGFR-2 as a surrogate biomarker for tumor angiogenesis and anti-angiogenic therapy.
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020 $a 9780494398609
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100 1 $a Ebos, John Michael Louis. $3 1025258
245 1 0 $a Soluble VEGFR-2 as a surrogate biomarker for tumor angiogenesis and anti-angiogenic therapy.
300 $a 231 p.
500 $a Source: Dissertation Abstracts International, Volume: 69-06, Section: B, page: 3524.
502 $a Thesis (Ph.D.)--University of Toronto (Canada), 2008.
520 $a Unrestricted tumor growth requires blood vessel development, a process called tumor angiogenesis, and therapeutic inhibition of this process is now a validated anti-cancer treatment strategy. This thesis introduces a novel soluble form of the vascular endothelial growth factor receptor 2 (sVEGFR-2) and outlines studies designed to assess the potential exploitation of this protein as a surrogate biomarker of tumor angiogenesis and anti-angiogenic drug activity/efficacy---particularly for those drugs that target the vascular endothelial growth factor (VEGF) system.
520 $a sVEGFR-2 is a &sim;160 kDa soluble protein that can be detected in both mouse and human plasma, as described in Chapter 2. The sVEGFR-2 was found in conditioned media of mouse and human endothelial cells, thus suggesting that it may be secreted or proteolytically cleaved from the cell, and potential biological activity was inferred from experiments in which mouse sVEGFR-2 could bind to VEGF-coated plates, implying possible endogenous functionality in VEGF signaling.
520 $a Pre-clinical studies were subsequently undertaken evaluating the relationship between sVEGFR-2 and tumor burden as well as an assessment of underlying factors governing in vivo protein level modulation, as described in Chapter 3. Various mouse cancer models uncovered an inverse relationship between the levels of sVEGFR-2 and tumor burden and further experiments demonstrated that plasma sVEGFR-2 decreases are mediated largely by tumor-derived VEGF down-regulation of VEGFR-2 receptor expression.
520 $a The role of sVEGFR-2, as well as other circulating proteins, as surrogate biomarkers for anti-angiogenic inhibitors was evaluated, and my results demonstrated that clinically observed molecular changes can be recapitulated in drug-treated tumor-free mice in a dose-dependent manner which plateau after 4 days of consecutive treatment, reverse following discontinuation of therapy, and correlate with anti-tumor activity.
520 $a Taken together, this work introduces a new and potentially important component of angiogenesis and pre-clinically examines sVEGFR-2 for its potential utility to be clinically exploited as a surrogate biomarker of both VEGF-dependent tumor growth as well as a tumor-independent measure of anti-angiogenic drug activity---possibly aiding in defining optimal biologic dose range for such drugs and in interpreting emerging clinical findings related to this protein.
590 $a School code: 0779.
650 4 $a Biology, Cell. $3 1017686
650 4 $a Biology, Molecular. $3 1017719
650 4 $a Health Sciences, Oncology. $3 1018566
690 $a 0307
690 $a 0379
690 $a 0992
710 2 $a University of Toronto (Canada). $3 1017674
773 0 $t Dissertation Abstracts International $g 69-06B.
790 $a 0779
791 $a Ph.D.
792 $a 2008
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoeng/servlet/advanced?query=NR39860