Document Detail


Vascular disrupting effect of CKD-516: preclinical study using DCE-MRI.
MedLine Citation:
PMID:  23299389     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Vascular disrupting agents (VDAs) are new class of anti-cancer drugs targeting pre-existing tumor vasculature which lead to tumor ischemia and necrosis. An innovative tubulin polymerization inhibitor, CKD-516, was recently developed as a VDA. We attempted to evaluate its tubulin destabilizing effect using immunofluorescence staining on human endothelial cells (HUVECs) and to ascertain its antivascular effect in a rabbit VX2 tumor model using dynamic contrast-enhanced (DCE) MRI by measuring the changes in kinetic parameters such as K-trans and IAUGC. Immunofluorescence staining using anti-tubulin and anti-actin antibodies on HUVECs showed that CKD-516 selectively disrupted tubulin component of the endothelial cytoskeleton. Serial DCE-MRI showed a significant decrease in K-trans and IAUGC parameters from baseline at 4 h (39.9 % in K-trans; -45.0 % in IAUGC) and at 24 h (-32.2 % in K-trans; -36.5 % in IAUGC), and a significant recovery at 48 h (22.9 % in K-trans; 34.8 % in IAUGC) following administration of CKD-516 at a 0.7-mg/kg dose. When the tumors were stratified according to the initial K-trans value of 0.1, tumors with a high K-trans > 0.1 which was indicative of having well-developed pre-existing vessels, showed greater reduction in K-trans and IAUGC values. On histologic examination, the degree of necrosis of treated tumors was significantly greater than that of untreated tumors. In summary, CKD-516 is an effective VDA which results in rapid vascular shutdown by targeting the tubulin component of tumor vessels and thus leads to necrosis.
Authors:
Kyung Won Kim; Jeong Min Lee; Yong Sik Jeon; In Joon Lee; Yoonseok Choi; Jisuk Park; Berthold Kiefer; Chin Kim; Joon Koo Han; Byung Ihn Choi
Related Documents :
11867199 - Reduction of in vivo tumor growth by mmi-166, a selective matrix metalloproteinase inhi...
23673539 - U1 adaptor oligonucleotides targeting bcl2 and grm1 suppress growth of human melanoma x...
9472089 - Polymorphonuclear elastase in human colorectal carcinoma.
20127359 - Expression of metalloproteases and their inhibitors by tumor and stromal cells in ducta...
24269209 - Gx1 targeting delivery of rmhtnfα evaluated using multimodality imaging.
18061419 - Src kinase regulates metalloproteinase-9 secretion induced by type iv collagen in mcf-7...
7171129 - Interaction of the b locus and the gvhr-selected lines in the graft-versus-host reactio...
10378379 - Migratory potential of transplantable neural tumor cell lines.
19096769 - Transmission electron microscopy of vx2 liver tumors after high-intensity focused ultra...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-9
Journal Detail:
Title:  Investigational new drugs     Volume:  -     ISSN:  1573-0646     ISO Abbreviation:  Invest New Drugs     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8309330     Medline TA:  Invest New Drugs     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Dana-Farber Cancer Institute, Boston, MA, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Sustained inhibition of deacetylases is required for the antitumor activity of the histone deactylas...
Next Document:  Tetra-O-methyl nordihydroguaiaretic acid, an inhibitor of Sp1-mediated survivin transcription, induc...