Functional and prognostic influence of receptor polymorphisms in the vascular endothelial growth factor system in colorectal cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15032-e15032
Author(s):  
T. Hansen ◽  
K. G. Spindler ◽  
D. A. Olsen ◽  
R. F. Andersen ◽  
J. Lindebjerg ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Protein Concentration ◽  
Progression Free Survival ◽  
Vascular Endothelial ◽  
Malignant Tumours ◽  
Free Survival ◽  
Endothelial Growth Factor

e15032 Background: The vascular endothelial growth factor (VEGF) system plays a key role in the angiogenic process ensuring a sufficient blood supply to the growth of malignant tumours. The clinical importance of single nucleotide polymorphisms (SNP's) in the VEGF receptors is still unknown. The aim of this study was to investigate the functional and prognostic influence of the V297I C/T and the -604 T/C SNP's in the VEGFR-2 gene, in tumour and normal tissue from colorectal cancer patients. Methods: Blood samples and tissue were collected from 110 patients, surgically resected for colorectal cancer. Genomic DNA was isolated from whole blood, and SNP's were analysed by PCR. Gene expression analysis was performed by RT-PCR and protein analysis was performed by ELISA. Progression free survival according to genotypes was compared using the Kaplan-Meier method and the logrank test. Results: Median gene expression according to the CC genotype of the -604 T/C SNP, were significantly higher than the median gene expression of the TT genotype (p = 0.045) and the TC genotype (p = 0.033) in CRC tissue. Regarding the V297I C/T SNP, median protein concentration according to the CT genotype was significantly higher than the median protein concentration of the CC genotype, p = 0.005. The CC genotype held prognostic information compared to CT and TT genotypes for both SNP's, p<0.05. Conclusions: The V297I C/T SNP seems to have a functional influence on the VEGFR-2 protein level, and the -604 T/C SNP on the gene expression level in CRC patients. The results furthermore indicate a prognostic influence of both SNP's on progression-free survival. No significant financial relationships to disclose.

scholarly journals Monitoring Dual VEGF Inhibition in Human Pancreatic Tumor Xenografts With Dynamic Contrast-Enhanced Ultrasound

2020 ◽  
Vol 19 ◽  
pp. 153303381988689
Author(s):  
Michele Lamuraglia ◽  
Guillaume Barrois ◽  
Delphine Le Guillou-Buffello ◽  
Mathieu Santin ◽  
Anne Kerbol ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Pancreatic Tumor ◽  
Progression Free Survival ◽  
Vascular Endothelial ◽  
Contrast Enhanced Ultrasound ◽  
Free Survival ◽  
Dynamic Contrast Enhanced ◽  
Contrast Enhanced ◽  
Endothelial Growth Factor

Background: Association of drugs acting against different antiangiogenic mechanisms may increase therapeutic effect and reduce resistance. Noninvasive monitoring of changes in the antiangiogenic response of individual tumors could guide selection and administration of drug combinations. Noninvasive detection of early therapeutic response during dual, vertical targeting of the vascular endothelial growth factor pathway was investigated in an ectopic subcutaneous xenograft model for human pancreatic tumor. Methods: Dynamic contrast-enhanced ultrasound 12 MHz was used to monitor tumor-bearing Naval Medical Research Institute mice beginning 15 days after tumor implantation. Mice received therapy from 15 to 29 days with sorafenib (N = 9), ziv-aflibercept (N = 11), combined antiangiogenic agents (N = 11), and placebo control (N = 14). Sorafenib (BAY 43-9006; Nexavar), a multikinase inhibitor acting on Raf kinase and receptor tyrosine kinases—including vascular endothelial growth factor receptors 2 and 3—was administered daily (60 mg/kg, per os). Ziv-aflibercept (ZALTRAP), a high-affinity ligand trap blocking the activity of vascular endothelial growth factor A, vascular endothelial growth factor B, and placental growth factor was administered twice per week (40 mg/kg, intraperitoneally). Results: Functional evaluation with dynamic contrast-enhanced ultrasound indicated stable tumor vascularization for the control group while revealing significant and sustained reduction after 1 day of therapy in the combined group ( P = .007). There was no survival benefit or penalty due to drug combination. The functional progression-free survival assessed with dynamic contrast-enhanced ultrasound was significantly higher for the 3 treated groups; whereas, the progression-free survival based on tumor size did not discriminate therapeutic effect. Conclusions: Dynamic contrast-enhanced ultrasound, therefore, presents strong potential to monitor microvascular modifications during antiangiogenic therapy, a key role to monitoring antiangiogenic combining therapy to adapt dose range drug.

Vascular endothelial growth factor (VEGF) gene polymorphisms associated with prognosis for patients with colorectal cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4125-4125
Author(s):  
Y. Chae ◽  
J. Kim ◽  
S. Sohn ◽  
Y. Cho ◽  
J. Moon ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Gene Polymorphisms ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Vascular Endothelial ◽  
Vegf Gene ◽  
Tumor Spread ◽  
Endothelial Growth Factor

4125 Background: Vascular endothelial growth factor (VEGF) or its family may be considered to play an important role in lymphangiogenesis and lymphatic tumor spread, thereby affecting prognosis of colorectal cancer. Accordingly, the present study analyzed VEGF gene polymorphisms and their impact on the prognosis for patients with colorectal cancer. Patients and Methods: Four hundred and sixty-five consecutive patients with surgically treated colorectal adenocarcinoma were enrolled in the present study. The genomic DNA was extracted from fresh colorectal tumor tissue and 3 VEGF (-2578C > A, -634G > C, and +936C > T) gene polymorphisms determined using a PCR/DHPLC (Polymerase chain reaction/Denaturing high-performance liquid chromatography) assay. Results: The median age of the patients was 64 years (range, 21–89), and 264 (56.7%) patients had colon cancer and 201 (48.2%) patients rectal cancer. Pathologic stages evaluable (n=464) after surgery were as follows: stage I (n=79, 17.0%), stage II (n=157, 33.8%), stage III (n=157, 33.8%), and stage IV (n=71, 15.3%). Multivariate survival analysis including stage, differentiation, and CEA level showed that survival for patients with the -634CC (overall survival [OS]: hazard ratio [HR]=0.175, P<0.001; progression-free survival [PFS]: HR=0.554, P=0.040) or GC genotype (OS: HR=0.158, P<0.001; PFS: HR=0.630, P=0.044) were better than for patients with the -634GG genotype, whereas the +936TT (OS: HR=65.959, P<0.001; PFS: HR=2.823, P=0.016) or CT genotype (OS: HR=16.116, P<0.001; PFS: HR=3.507, P<0.001) were associated with a worse survival compared to the CC genotype. In haplotype analysis, the -2578A/-634G/+936T haplotype exhibited a significantly worse survival when compared to the wild -2578C/-634G/+936C haplotype (OS: HR=4.670, P<0.001; PFS: HR=3.624, P<0.001). Conclusions: VEGF gene polymorphisms were found to be an independent prognostic marker for patients with colorectal cancer. Accordingly, the analysis of VEGF gene polymorphisms can help identify patient subgroups at high risk of a poor disease outcome. No significant financial relationships to disclose.

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