Abstract
Background:
Potential tissue and serum biomarkers were assessed for predicting efficacy of bevacizumab in ovarian cancer (OC).
Patients and methods:
Twenty patients with OC received chemotherapy alone (control group) or in combination with bevacizumab (study group) in this non-randomised study. Pre- and post-treatment serum concentrations of vascular endothelial growth factor (VEGF), 8-hydroxydeoxyguanosine (8-OHdG) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were measured in all patients. In addition, immunohistochemical expressions VEGF receptors (R1, R2), hypoxia-inducible factor 1alpha (HIF-1 alpha), matrix metalloproteinases (-2, -9) and TIMP-2 were analysed in tumours from bevacizumab-treated patients.
Results:
8-OHdG and HIF-1alpha immunostainings were more highly expressed among patients with progression-free survival (PFS) >23 months than in patients with PFS <12 months. Similarly, MMP-9 was more frequently highly expressed in those with long versus short PFS. Serum VEGF concentrations decreased substantially in all bevacizumab-treated patients versus only 20% of the control group.
Conclusion:
Our results indicate differences in MMP-9 and HIF-1alpha expression in relation to duration of PFS and effects on serum VEGF when bevacizumab is used in combination with chemotherapy.
Publication types
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Clinical Trial, Phase II
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Research Support, Non-U.S. Gov't
MeSH terms
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8-Hydroxy-2'-Deoxyguanosine / analogs & derivatives
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Aged
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Antibodies, Monoclonal / administration & dosage
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Antibodies, Monoclonal, Humanized
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
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Bevacizumab
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Biomarkers, Tumor / blood
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Biomarkers, Tumor / metabolism*
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Carboplatin / administration & dosage
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Female
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Guanine / analogs & derivatives
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Guanine / blood
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Guanine / metabolism
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Humans
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Hypoxia-Inducible Factor 1, alpha Subunit / blood
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Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
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Immunohistochemistry
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Matrix Metalloproteinase 2 / blood
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Matrix Metalloproteinase 2 / metabolism
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Matrix Metalloproteinase 9 / blood
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Matrix Metalloproteinase 9 / metabolism
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Middle Aged
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Ovarian Neoplasms / blood
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Ovarian Neoplasms / drug therapy*
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Ovarian Neoplasms / metabolism*
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Ovarian Neoplasms / surgery
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Paclitaxel / administration & dosage
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Receptors, Vascular Endothelial Growth Factor / blood
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Receptors, Vascular Endothelial Growth Factor / metabolism
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Tissue Inhibitor of Metalloproteinase-1 / blood
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Tissue Inhibitor of Metalloproteinase-1 / metabolism
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Vascular Endothelial Growth Factor A / blood
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Vascular Endothelial Growth Factor A / metabolism
Substances
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Antibodies, Monoclonal
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Antibodies, Monoclonal, Humanized
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Biomarkers, Tumor
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HIF1A protein, human
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Hypoxia-Inducible Factor 1, alpha Subunit
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Tissue Inhibitor of Metalloproteinase-1
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VEGFA protein, human
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Vascular Endothelial Growth Factor A
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Bevacizumab
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Guanine
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8-oxo-7,8-dihydrodeoxyguanine
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8-Hydroxy-2'-Deoxyguanosine
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Carboplatin
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Receptors, Vascular Endothelial Growth Factor
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MMP2 protein, human
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Matrix Metalloproteinase 2
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Matrix Metalloproteinase 9
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Paclitaxel