Document Detail


Target therapy using a small molecule inhibitor against angiogenic receptors in pancreatic cancer.
MedLine Citation:
PMID:  17356708     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: PD173074, a small molecule inhibitor of VEGF-RII and FGF-RI, targets neoangiogenesis and mitogenesis. This study aimed to analyze a single-compound-driven inhibition of FGF and VEGF receptors in pancreatic cancer.
EXPERIMENTAL DESIGN: RT-PCR and Western blots were performed to quantify protein expression and phosphorylation. Anchorage dependent and independent growth assays were used to study cell growth. With flow cytometry, cell cycle analysis and apoptosis were studied. In vivo HPAF-II and MIA PaCa-2 cells were xenografted. Animals were treated daily for 10 weeks. Immunohistochemistry was used to quantify microvessel density and apoptosis.
RESULTS: Highest levels of FGF-RI were detectable in MIA PaCa-2 cells, lowest in HPAF-II cells. PD173074 inhibited cell growth most prominently in cells expressing high levels of FGF-RI. Cell cycle progression was inhibited by blocking transition in the G(0)/G(1) phase, and consequently, apoptosis was increased. In vivo significant inhibition of orthotopic tumor growth was achieved by a combination effect of inhibition of mitogenesis, induction of apoptosis, and reduction of angiogenesis in PD173074-treated animals.
CONCLUSIONS: These data highlight VEGF-RII and FGF-RI as therapeutic targets and suggest a potential role for the combined use of tyrosine kinase inhibitors in the management of inoperable pancreatic cancer patients.
Authors:
Peter Büchler; Howard A Reber; Mendel M Roth; Mark Shiroishi; Helmut Friess; Oscar J Hines
Related Documents :
17942438 - Ethanol-induced cytotoxicity in rat pancreatic acinar ar42j cells: role of fatty acid e...
10676888 - Effects of antioxidants on induction of apoptosis in bursal cells of fabricius during i...
7621428 - Berberine complexes with dna in the berberine-induced apoptosis in human leukemic hl-60...
9030578 - Induction of apoptosis and cpp32 expression by thyroid hormone in a myoblastic cell lin...
19383408 - Generating mesc-derived insulin-producing cell lines through an intermediate lineage-re...
1770138 - The genetic control and germ cell kinetics of the female and male germ line in mammals ...
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Neoplasia (New York, N.Y.)     Volume:  9     ISSN:  1476-5586     ISO Abbreviation:  Neoplasia     Publication Date:  2007 Feb 
Date Detail:
Created Date:  2007-03-14     Completed Date:  2007-04-12     Revised Date:  2013-06-06    
Medline Journal Info:
Nlm Unique ID:  100886622     Medline TA:  Neoplasia     Country:  Canada    
Other Details:
Languages:  eng     Pagination:  119-27     Citation Subset:  IM    
Affiliation:
Department of Surgery, UCLA School of Medicine, University of California, Los Angeles, CA 90095-6904, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Angiogenesis Inhibitors / administration & dosage,  pharmacology,  therapeutic use*
Animals
Antineoplastic Agents / administration & dosage,  pharmacology,  therapeutic use*
Apoptosis / drug effects
Carcinoma / blood supply,  drug therapy*,  metabolism
Cell Cycle / drug effects
Cell Division / drug effects
Cell Line, Tumor / drug effects,  transplantation
Humans
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasm Proteins / antagonists & inhibitors*,  biosynthesis,  genetics
Pancreatic Neoplasms / blood supply,  drug therapy*,  metabolism
Protein Kinase Inhibitors / administration & dosage,  pharmacology,  therapeutic use*
Pyrimidines / administration & dosage,  pharmacology,  therapeutic use*
Receptor, Fibroblast Growth Factor, Type 1 / antagonists & inhibitors*,  biosynthesis,  genetics
Reverse Transcriptase Polymerase Chain Reaction
Tumor Stem Cell Assay
Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors*,  biosynthesis,  genetics
Xenograft Model Antitumor Assays
Chemical
Reg. No./Substance:
0/Angiogenesis Inhibitors; 0/Antineoplastic Agents; 0/Neoplasm Proteins; 0/PD 173074; 0/Protein Kinase Inhibitors; 0/Pyrimidines; EC 2.7.10.1/FGFR1 protein, human; EC 2.7.10.1/Receptor, Fibroblast Growth Factor, Type 1; EC 2.7.10.1/Vascular Endothelial Growth Factor Receptor-2
Comments/Corrections

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


Previous Document:  Inhibition of skeletal metastasis by ectopic ERalpha expression in ERalpha-negative human breast can...
Next Document:  Visualizing the acute effects of vascular-targeted therapy in vivo using intravital microscopy and m...