scholarly journals Elevated expression of vascular endothelial growth factor correlates with increased angiogenesis and decreased progression-free survival among patients with low-grade neuroendocrine tumors

Cancer ◽  
2007 ◽  
Vol 109 (8) ◽  
pp. 1478-1486 ◽  
Author(s):  
Jun Zhang ◽  
Zhiliang Jia ◽  
Qiang Li ◽  
Liwei Wang ◽  
Asif Rashid ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Neuroendocrine Tumors ◽  
Progression Free Survival ◽  
Low Grade ◽  
Vascular Endothelial ◽  
Free Survival ◽  
Elevated Expression ◽  
Endothelial Growth Factor

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.

scholarly journals BEST: A Randomized Phase II Study of Vascular Endothelial Growth Factor, RAF Kinase, and Mammalian Target of Rapamycin Combination Targeted Therapy With Bevacizumab, Sorafenib, and Temsirolimus in Advanced Renal Cell Carcinoma—A Trial of the ECOG–ACRIN Cancer Research Group (E2804)

2015 ◽  
Vol 33 (21) ◽  
pp. 2384-2391 ◽  
Author(s):  
Keith T. Flaherty ◽  
Judith B. Manola ◽  
Michael Pins ◽  
David F. McDermott ◽  
Michael B. Atkins ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Progression Free Survival ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Free Survival ◽  
Endothelial Growth Factor

Purpose On the basis of evidence that resistance to vascular endothelial growth factor (VEGF) receptor inhibition is caused by hypoxia-driven residual VEGF and other proangiogenic factors, combinations of agents from these classes were hypothesized to improve treatment outcomes relative to single-agent VEGF pathway blockade. Patients and Methods A total of 361 patients with metastatic clear cell renal cell carcinoma were randomly assigned equally to arm A (bevacizumab monotherapy 10 mg/kg intravenously [IV] every 2 weeks), B (bevacizumab 10 mg/kg IV every 2 weeks and temsirolimus 25 mg IV every week), C (bevacizumab 5 mg/kg IV every 2 weeks and sorafenib 200 mg orally twice daily on days 1 to 5, 8 to 12, 15 to 19, and 22 to 26), or D (sorafenib 200 mg twice daily and temsirolimus 25 mg IV weekly). Progression-free survival was the primary end point. Results Among 331 eligible treated patients, median PFS was 7.5 months for bevacizumab alone (90% CI, 5.8 to 10.8 months), 7.6 months for bevacizumab plus temsirolimus (90% CI, 6.7 to 9.2 months), 9.2 months for bevacizumab plus sorafenib (90% CI, 7.5 to 11.4 months), and 7.4 months for sorafenib plus temsirolimus (90% CI, 5.6 to 7.9 months). Hazard ratios from stratified Cox proportional hazards models were 1.01, 0.89, and 1.07 (with respective P values of .95, .49, and .68) for the three combinations, respectively, compared with bevacizumab alone. Adverse events did not differ significantly among treatment arms. Conclusion The activity of sorafenib, temsirolimus, and bevacizumab administered in doublet combinations did not significantly improve median progression-free survival in comparison with bevacizumab monotherapy.

Sign in / Sign up

Export Citation Format

Share Document