PloS one, 2018-01, Vol.13 (1), p.e0187063-e0187063
2018
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- Autor(en) / Beteiligte
- Titel
- Evaluation of drug mechanism and efficacy of a novel anti-angiogenic agent, TTAC-0001, using multi-modality bioimaging in a mouse breast cancer orthotopic model
- Ist Teil von
- PloS one, 2018-01, Vol.13 (1), p.e0187063-e0187063
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2018
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Targeting of vascular endothelial growth factor receptors (VEGFRs) has potential anti-angiogenic effects because VEGFR-2 is the major signaling regulator of VEGF/VEGFR pathways. We aimed to elucidate the drug mechanism and anti-tumor efficacy of TTAC-0001, a novel, fully human anti-VEGFR-2/KDR monoclonal antibody, in mouse orthotopic breast cancer model using multi-modal bioimaging. We used orthotopic xenograft tumor model in which human breast cancer cells (MDA-MB-231) were injected into the right mammary fat pad of Balb/c nude mice. We investigated its biodistribution using serial fluorescence imaging after injecting fluorescent-labelled-drug and mode of action using Matrigel plug angiogenesis assays. The anti-tumor efficacy of drug was assessed using ultrasonography and bioluminescence imaging. Histopathologic analyses, including hematoxylin and eosin staining and immunohistochemistry with anti-CD31 and anti-Ki-67 antibodies, were performed. Each experiment had four groups: control, bevacizumab 10 mg/kg (BVZ-10 group), TTAC-0001 2 mg/kg (TTAC-2 group), and TTAC-0001 10 mg/kg (TTAC-10 group). The TTAC-10 group showed good tumor targeting that lasted for at least 6 days and had a good anti-angiogenic effect with decreased hemoglobin content and fewer CD31-positive cells in the Matrigel plug. Compared with BVZ-10 and TTAC-2 groups, the TTAC-10 group showed the strongest anti-tumor efficacy, inhibiting tumor growth as detected by ultrasonography and bioluminescence imaging. The TTAC-10 group also showed the lowest viable tumor and micro-vessel areas and the lowest Ki-67 index in histopathologic analyses. We firstly demonstrated that TTAC-0001 effectively inhibited tumor growth and neovascularization in mouse orthotopic breast cancer model. It may provide a future treatment option for breast cancer.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0187063Titel-ID: cdi_plos_journals_2390637513
- Format
- –
- Schlagworte
- Angiogenesis, Angiogenesis Inhibitors - pharmacology, Animals, Antiangiogenic agents, Antiangiogenics, Antibodies, Monoclonal - pharmacology, Antibodies, Monoclonal - therapeutic use, Anticancer properties, Bevacizumab, Biology and Life Sciences, Bioluminescence, Blood vessels, Breast cancer, Breast Neoplasms - blood supply, Breast Neoplasms - diagnostic imaging, Breast Neoplasms - drug therapy, Cancer therapies, Cell Line, Tumor, Chemotherapy, Disease Models, Animal, Drug dosages, Drug Screening Assays, Antitumor, Experiments, Fluorescence, Growth factor receptors, Growth factors, Hemoglobin, Humans, Immunohistochemistry, Inhibition, Kim, Sang, Kinases, Labeling, Life sciences, Lung cancer, Medical imaging, Medical research, Medical schools, Medicine, Medicine and Health Sciences, Mice, Mice, Inbred BALB C, Mice, Nude, Mode of action, Monoclonal antibodies, Multimodal Imaging, Research and Analysis Methods, Targeted cancer therapy, Tumors, Ultrasonic imaging, Vascular endothelial growth factor, Vascular Endothelial Growth Factor Receptor-2 - antagonists & inhibitors, Vascular endothelial growth factor receptors, Vascularization, Xenografts, Xenotransplantation