Ghent University Academic Bibliography

Advanced

Antiangiogenic versus cytotoxic therapeutic approaches in a mouse model of pancreatic cancer: An experimental study with a multitarget tyrosine kinase inhibitor (sunitinib), gemcitabine and radiotherapy

VEERLE CASNEUF UGent, Pieter Demetter, Tom Boterberg UGent, Louke Delrue UGent, Marc Peeters UGent and Nancy Van Damme UGent (2009) ONCOLOGY REPORTS. 22(1). p.105-113
abstract
This work evaluated SU11248 (sunitinib) as a potential therapeutic agent, alone or in combination with the cytotoxic agent gemcitabine or radiotherapy in a murine model of pancreatic cancer. Panc02 cells were injected subcutaneously into HsdOla/MF1 mice (n=222). Treatment was administered during I week: sunitinib (SUN), gemcitabine (GEM), radiotherapy (RT), RT+SUN and GEM+SUN. Mice were sacrificed 14 days after treatment. The effect on microvessel density (MVD) was measured by CD31 staining. Apoptosis (sFAS, cleaved caspase-3) and proangiogenic proteins (VEGF, PIGF, EGF) were measured with ELISA and immunohistochemistry. At day 14, tumors in all groups increased significantly despite treatment. Only after RT/SUN treatment tumor growth slowed down, although the accretion was still significant (P=0.033). Highest levels of apoptosis were seen in GEM/SUN, RT/SUN and RT treated mice (respectively P<0.001, P<0.01 and P<0.05 compared to placebo). MVD was lowest in RT/SUN treated mice [compared to placebo (P<0.05), GEM (P<0.05) and GEM/SUN (P<0.01)]. Highest VEGF levels were seen after RT and RT/SUN treatment [vs. placebo (P<0.001) and vs. other treatments (P<0.01 for all comparisons)]. GEM and SUN in monotherapy lead to an up-regulation of PIGF and EGF, respectively. In conclusion, the combination treatments RT/SUN and GEM/SUN result in a more potent anti-angiogenic and antitumor effect when compared to either treatment alone. Multitargeted angiogenesis inhibitor therapy with sunitinib combined with either radiotherapy or gemcitabine may be a novel approach for human pancreatic cancer.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
keyword
ANGIOGENIC FACTORS, DUCTAL ADENOCARCINOMA, BREAST-CANCER, IONIZING-RADIATION, FACTOR RECEPTOR, PHASE-III TRIAL, RANDOMIZED CONTROLLED-TRIAL, ENDOTHELIAL-GROWTH-FACTOR, RENAL-CELL CARCINOMA, CURATIVE RESECTION
journal title
ONCOLOGY REPORTS
Oncol. Rep.
volume
22
issue
1
pages
9 pages
Web of Science type
Article
Web of Science id
000267259100015
JCR category
ONCOLOGY
JCR impact factor
1.588 (2009)
JCR rank
116/163 (2009)
JCR quartile
3 (2009)
ISSN
1021-335X
DOI
10.3892/or_00000412
language
English
UGent publication?
yes
classification
A1
id
815056
handle
http://hdl.handle.net/1854/LU-815056
date created
2009-12-21 16:30:55
date last changed
2010-01-21 10:43:04
@article{815056,
  abstract     = {This work evaluated SU11248 (sunitinib) as a potential therapeutic agent, alone or in combination with the cytotoxic agent gemcitabine or radiotherapy in a murine model of pancreatic cancer. Panc02 cells were injected subcutaneously into HsdOla/MF1 mice (n=222). Treatment was administered during I week: sunitinib (SUN), gemcitabine (GEM), radiotherapy (RT), RT+SUN and GEM+SUN. Mice were sacrificed 14 days after treatment. The effect on microvessel density (MVD) was measured by CD31 staining. Apoptosis (sFAS, cleaved caspase-3) and proangiogenic proteins (VEGF, PIGF, EGF) were measured with ELISA and immunohistochemistry. At day 14, tumors in all groups increased significantly despite treatment. Only after RT/SUN treatment tumor growth slowed down, although the accretion was still significant (P=0.033). Highest levels of apoptosis were seen in GEM/SUN, RT/SUN and RT treated mice (respectively P{\textlangle}0.001, P{\textlangle}0.01 and P{\textlangle}0.05 compared to placebo). MVD was lowest in RT/SUN treated mice [compared to placebo (P{\textlangle}0.05), GEM (P{\textlangle}0.05) and GEM/SUN (P{\textlangle}0.01)]. Highest VEGF levels were seen after RT and RT/SUN treatment [vs. placebo (P{\textlangle}0.001) and vs. other treatments (P{\textlangle}0.01 for all comparisons)]. GEM and SUN in monotherapy lead to an up-regulation of PIGF and EGF, respectively. In conclusion, the combination treatments RT/SUN and GEM/SUN result in a more potent anti-angiogenic and antitumor effect when compared to either treatment alone. Multitargeted angiogenesis inhibitor therapy with sunitinib combined with either radiotherapy or gemcitabine may be a novel approach for human pancreatic cancer.},
  author       = {CASNEUF, VEERLE and Demetter, Pieter and Boterberg, Tom and Delrue, Louke and Peeters, Marc and Van Damme, Nancy},
  issn         = {1021-335X},
  journal      = {ONCOLOGY REPORTS},
  keyword      = {ANGIOGENIC FACTORS,DUCTAL ADENOCARCINOMA,BREAST-CANCER,IONIZING-RADIATION,FACTOR RECEPTOR,PHASE-III TRIAL,RANDOMIZED CONTROLLED-TRIAL,ENDOTHELIAL-GROWTH-FACTOR,RENAL-CELL CARCINOMA,CURATIVE RESECTION},
  language     = {eng},
  number       = {1},
  pages        = {105--113},
  title        = {Antiangiogenic versus cytotoxic therapeutic approaches in a mouse model of pancreatic cancer: An experimental study with a multitarget tyrosine kinase inhibitor (sunitinib), gemcitabine and radiotherapy},
  url          = {http://dx.doi.org/10.3892/or\_00000412},
  volume       = {22},
  year         = {2009},
}

Chicago
CASNEUF, VEERLE, Pieter Demetter, Tom Boterberg, Louke Delrue, Marc Peeters, and Nancy Van Damme. 2009. “Antiangiogenic Versus Cytotoxic Therapeutic Approaches in a Mouse Model of Pancreatic Cancer: An Experimental Study with a Multitarget Tyrosine Kinase Inhibitor (sunitinib), Gemcitabine and Radiotherapy.” Oncology Reports 22 (1): 105–113.
APA
CASNEUF, VEERLE, Demetter, P., Boterberg, T., Delrue, L., Peeters, M., & Van Damme, N. (2009). Antiangiogenic versus cytotoxic therapeutic approaches in a mouse model of pancreatic cancer: An experimental study with a multitarget tyrosine kinase inhibitor (sunitinib), gemcitabine and radiotherapy. ONCOLOGY REPORTS, 22(1), 105–113.
Vancouver
1.
CASNEUF V, Demetter P, Boterberg T, Delrue L, Peeters M, Van Damme N. Antiangiogenic versus cytotoxic therapeutic approaches in a mouse model of pancreatic cancer: An experimental study with a multitarget tyrosine kinase inhibitor (sunitinib), gemcitabine and radiotherapy. ONCOLOGY REPORTS. 2009;22(1):105–13.
MLA
CASNEUF, VEERLE, Pieter Demetter, Tom Boterberg, et al. “Antiangiogenic Versus Cytotoxic Therapeutic Approaches in a Mouse Model of Pancreatic Cancer: An Experimental Study with a Multitarget Tyrosine Kinase Inhibitor (sunitinib), Gemcitabine and Radiotherapy.” ONCOLOGY REPORTS 22.1 (2009): 105–113. Print.