PloS one, 2017-11, Vol.12 (11), p.e0187824-e0187824
2017
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- Autor(en) / Beteiligte
- Titel
- Functional evaluation of therapeutic response of HCC827 lung cancer to bevacizumab and erlotinib targeted therapy using dynamic contrast-enhanced and diffusion-weighted MRI
- Ist Teil von
- PloS one, 2017-11, Vol.12 (11), p.e0187824-e0187824
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2017
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- This study aimed to investigate the therapeutic responses of lung cancer mice models with adenocarcinoma HCC827 (gefitinib sensitive) and HCC827R (gefitinib resistant) to the epidermal growth factor receptor-tyrosine kinase inhibitor erlotinib alone and in combination with the anti-angiogenesis agent bevacizumab using dynamic contrast enhanced (DCE) and diffusion-weighted MRI. In the HCC827 model, temporal changes in DCE-MRI derived parameters (Ktrans, kep, and iAUC90) and apparent diffusion coefficient (ADC) were significantly correlated with tumor size. Ktrans and iAUC90 significantly decreased at week 2 in the groups receiving erlotinib alone and in combination with bevacizumab, whereas kep decreased at week 1 and 2 in both treatment groups. In addition, there was a significant difference in iAUC90 between the treatment groups at week 1. Compared to the control group of HCC827, there was a significant reduction in microvessel density and increased tumor apoptosis in the two treatment group. ADC value increased in the erlotinib alone group at week 1 and week 2, and in the erlotinib combined with bevacizumab group at week 2. Enlarged areas of central tumor necrosis were associated with a higher ADC value. However, progressive enlargement of the tumors but no significant differences in DCE parameters or ADC were noted in the HCC827R model. These results showed that both erlotinib alone and in combination with bevacizumab could effectively inhibit tumor growth in the gefitinib-sensitive lung cancer mice model, and that this was associated with decreased vascular perfusion, increased ADC percentage, decreased microvessel density, and increased tumor apoptosis with a two-week treatment cycle.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0187824Titel-ID: cdi_plos_journals_1962253666
- Format
- –
- Schlagworte
- Adenocarcinoma, Angiogenesis, Angiogenesis Inhibitors - administration & dosage, Angiogenesis Inhibitors - pharmacology, Animal models, Animals, Antineoplastic Combined Chemotherapy Protocols - administration & dosage, Antineoplastic Combined Chemotherapy Protocols - pharmacology, Apoptosis, Bevacizumab, Bevacizumab - administration & dosage, Bevacizumab - pharmacology, Biology and Life Sciences, Cancer, Cell Line, Tumor, Cell Proliferation - drug effects, Cell Survival - drug effects, Contrast Media, Development and progression, Diffusion, Diffusion coefficient, Dosage and administration, Drug Resistance, Neoplasm - drug effects, Enlargement, Enzyme inhibitors, Epidermal growth factor, Erlotinib, Erlotinib Hydrochloride - administration & dosage, Erlotinib Hydrochloride - pharmacology, Gefitinib, Health aspects, Humans, Immunotherapy, Inhibitor drugs, Kinases, Lung cancer, Lung diseases, Lung Neoplasms - diagnostic imaging, Lung Neoplasms - drug therapy, Lung Neoplasms - genetics, Lung Neoplasms - pathology, Magnetic resonance imaging, Magnetic Resonance Imaging - methods, Mathematical models, Medical imaging, Medicine and Health Sciences, Mice, Molecular Targeted Therapy, Monoclonal antibodies, Mutation, NMR, Nuclear magnetic resonance, Perfusion, Protein Kinase Inhibitors - administration & dosage, Protein Kinase Inhibitors - pharmacology, Protein-tyrosine kinase, Receptor, Epidermal Growth Factor - genetics, Research and Analysis Methods, Sequence Deletion, Targeted cancer therapy, Treatment Outcome, Tumor Burden, Tumors, Tyrosine, Vascular endothelial growth factor, Xenograft Model Antitumor Assays