scholarly journals Utility of Vascular Endothelial Growth Factor Inhibitors in the Treatment of Ovarian Cancer: From Concept to Application

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Afshin Amini ◽  
Samar Masoumi Moghaddam ◽  
David L. Morris ◽  
Mohammad H. Pourgholami
Keyword(s):  
Ovarian Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Treatment Options ◽  
Malignant Ascites ◽  
Vascular Endothelial ◽  
Chemotherapeutic Drugs ◽  
Gynecologic Malignancy ◽  
Preclinical And Clinical Studies ◽  
Endothelial Growth Factor

Despite recent advances in the management of ovarian cancer, it remains the most lethal gynecologic malignancy. Vascular endothelial growth factor (VEGF) has been shown to play a pivotal role in the progression of ovarian cancer leading to the eventual development of malignant ascites. On this basis, agents rendering VEGF ineffective by neutralizing VEGF (bevacizumab), blocking its receptors (aflibercept), or interfering with the postreceptor signaling pathways (sunitinib) provide us with the rational treatment options. These agents are generally used in combination with the standard chemotherapeutic drugs. Here, we discuss the basis of and the logic behind the use of these agents in the treatment of epithelial ovarian cancer, as well as their evaluation in different preclinical and clinical studies.

Coagulopathy, Blood Loss, and Vascular Endothelial Growth Factor in Advanced Epithelial Ovarian Cancer

2006 ◽  
Vol 107 (Supplement) ◽  
pp. 107S
Author(s):  
John P. Geisler ◽  
Georgiann C. Linnemeier ◽  
Michael C. Wiemann ◽  
John Broshears ◽  
Greg A. Miller ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Blood Loss ◽  
Epithelial Ovarian Cancer ◽  
Vascular Endothelial ◽  
Advanced Epithelial Ovarian Cancer ◽  
Endothelial Growth Factor

Vascular endothelial growth factor gene polymorphisms and ovarian cancer survival

2010 ◽  
Vol 119 (3) ◽  
pp. 479-483 ◽  
Author(s):  
Felicity Lose ◽  
Christina M. Nagle ◽  
Tracy O'Mara ◽  
Jyotsna Batra ◽  
Kelly L. Bolton ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Gene Polymorphisms ◽  
Cancer Survival ◽  
Vascular Endothelial ◽  
Factor Gene ◽  
Growth Factor Gene ◽  
Ovarian Cancer Survival ◽  
Endothelial Growth Factor

The Prognostic Value of Plasma YKL-40 in Patients With Chemotherapy-Resistant Ovarian Cancer Treated With Bevacizumab

2016 ◽  
Vol 26 (8) ◽  
pp. 1390-1398 ◽  
Author(s):  
Mogens K. Boisen ◽  
Christine V. Madsen ◽  
Christian Dehlendorff ◽  
Anders Jakobsen ◽  
Julia S. Johansen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Overall Survival ◽  
Growth Factor ◽  
Confidence Interval ◽  
Single Agent ◽  
Vascular Endothelial ◽  
Improved Outcomes ◽  
Median Serum ◽  
Endothelial Growth Factor

ObjectiveYKL-40 is a proangiogenic glycoprotein that is secreted by cancer cells and inflammatory cells. The expression of YKL-40 is induced by vascular endothelial growth factor inhibition. We tested the hypothesis that low baseline plasma YKL-40 is associated with improved outcomes in patients with ovarian cancer treated with bevacizumab.MethodsOne hundred forty patients with chemotherapy-refractory epithelian ovarian cancer were treated with single-agent bevacizumab 10 mg/kg every 3 weeks in a prospective trial. Plasma YKL-40 was determined by enzyme-linked immunosorbent assay before and during treatment. Both raw YKL-40 concentrations and age-corrected percentiles of normal YKL-40 level were used. Associations between plasma YKL-40 level and progression-free survival (PFS) and overall survival were tested using univariate and multivariate Cox proportional hazards models.ResultsBaseline plasma YKL-40 levels were higher in patients with poor performance status, less differentiated tumors, residual disease after primary surgery, higher than the median serum CA-125 level, and higher than the median serum vascular endothelial growth factor level. Age-corrected percentile of normal plasma YKL-40 greater than the lowest quartile (Q1, 85th percentile) was associated with shorter PFS in univariate (hazard ratio, 1.83; 95% confidence interval, 1.15–2.89; P = 0.010) and multivariate analyses and shorter overall survival in univariate analysis (hazard ratio, 1.96; 95% confidence interval, 1.27–3.03; P = 0.003). Increase in plasma YKL-40 during bevacizumab treatment, with correction for baseline plasma YKL-40, was a predictor of shorter PFS. Using normal versus elevated plasma YKL-40 as a cutoff did not provide the same discriminative value.ConclusionsLow plasma YKL-40 at baseline and during treatment is associated with improved outcomes in patients with chemotherapy-refractory advanced ovarian cancer treated with single-agent bevacizumab.

Prognostic significance of vascular endothelial growth factor expression in ovarian cancer patients: a long-term follow-up

2006 ◽  
Vol 16 (Suppl 1) ◽  
pp. 183-189 ◽  
Author(s):  
C. Rudlowski ◽  
A.-K. Pickart ◽  
C. Fuhljahn ◽  
T. Friepoertner ◽  
B. Schlehe ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Cancer Patients ◽  
Peritoneal Fluid ◽  
Vascular Endothelial ◽  
Ovarian Carcinomas ◽  
Borderline Tumors ◽  
Tumor Expression ◽  
Endothelial Growth Factor

The purpose of the study was to determine vascular endothelial growth factor (VEGF) concentrations in ascites from ovarian cancer and to correlate these data with VEGF expression in ovarian tumors, serum VEGF concentrations, and clinicopathologic characteristics. Ascites, serum, and tumor tissue from 65 ovarian carcinomas and eight borderline tumors were collected. VEGF concentration in peritoneal fluids and sera was determined using enzyme immunoassay. VEGF tumor expression was evaluated immunohistochemically. Significantly higher VEGF concentrations were found in ascites from malignant tumors (median, 2575 pg mL−1) compared with borderline tumors (median 181.9 pg mL−1) and benign peritoneal fluid (184.5 pg mL−1). Both VEGF ascites concentration and tumor expression correlated with advanced tumor stages and ascites volume. Elevated VEGF ascites levels were negatively correlated to patient survival. No differences between VEGF serum levels could be observed between ovarian cancer patients and patients with benign cysts. This study showed for the first time the clinical significance of elevated VEGF ascites level in ovarian carcinomas. VEGF is expressed by ovarian tumor cells and locally released in the malignant peritoneal fluid but is not increased in the serum of preoperative ovarian cancer patients. The enhanced VEGF level support novel therapeutic perspectives by VEGF inhibition.

Prognostic significance of tumor angiogenesis in epithelial ovarian cancer: in association with transforming growth factor β and vascular endothelial growth factor

2004 ◽  
Vol 14 (1) ◽  
pp. 82-88
Author(s):  
M. SÖNMEZER ◽  
M. GÜNGÖR ◽  
A. Ensari ◽  
F. Ortaç
Keyword(s):  
Ovarian Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Epithelial Ovarian Cancer ◽  
Transforming Growth Factor ◽  
Prognostic Significance ◽  
Transforming Growth Factor Β ◽  
Vascular Endothelial ◽  
Clinicopathologic Factors ◽  
Endothelial Growth Factor

We aimed to evaluate the prognostic significance of microvessel density (MVD), vascular endothelial growth factor (VEGF), and transforming growth factor β (TGFβ), as well as to find out the relationship between MVD, and VEGF and TGFβ in epithelial ovarian cancer (EOC). Surgical specimens of 47 patients with stage I–IV primary EOC, who underwent extended surgical staging according to FIGO, were investigated. Five-μm thick tissue sections were immunostained with antibody to factor VIII-related antigen, and MVD was assessed at three separate areas of ×200 magnification. Expressions for VEGF and TGFβ were evaluated by immunohistochemical staining using related monoclonal antibodies. Results were correlated with clinicopathologic factors and survival. We did not find any correlation between MVD and clinicopathologic factors, or patient survival. Similarly, there was no association between the degree of VEGF staining and survival or clinicopathologic factors, except preoperative ascites volume, which was higher in patients showing moderate and intense VEGF staining than those with weak VEGF staining (P = 0.052). The expression of TGFβ was inversely correlated with preoperative CA-125 levels (P < 0.05). Furthermore, there was no correlation between MVD and the staining intensity of VEGF or TGFβ. In conclusion, angiogenesis does not appear as a prognostic factor in EOC. We suggest that VEGF is an important mediator of ascites formation, and that TGFβ, which is supposed to have tissue-specific actions in tumorigenesis, may have growth-inhibitory functions in EOC.

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