|Title:||Anti-angiogenic treatment (Bevacizumab) improves the responsiveness of photodynamic therapy in colorectal cancer||Authors:||Peng C.-L.
|Keywords:||Angiogenesis; Bevacizumab; Cancer; Photodynamic therapy||Issue Date:||2018||Publisher:||Elsevier B.V.||Journal Volume:||23||Start page/Pages:||111-118||Source:||Photodiagnosis and Photodynamic Therapy||Abstract:||
Photodynamic therapy (PDT) is a treatment utilizing the combined action of photosensitizers and light for the treatment of various cancers. The mechanisms for tumor destruction after PDT include direct tumor cell kill by singlet oxygen species (OS), indirect cell kill via vascular damage, and an elicited immune response. However, it has been reported that many cellular activators, including vascular endothelial growth factor (VEGF), are produced by tumor cells after PDT. In this study, we demonstrate that meta-tetra(hydroxyphenyl) chlorin (mTHPC)-based photodynamic therapy combined with bevacizumab (Avastin?), an anti-VEGF neutralizing monoclonal antibody that blocks the binding of VEGF to its receptor, can enhance the effectiveness of each treatment modality. We evaluated the efficacy of bevacizumab-based anti-angiogenesis in combination with PDT as well as the resulting VEGF levels and microvessel density (MVD) in a mouse model of human colon cancer. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) were performed to assess VEGF concentrations and microvessel density in the various treatment groups, and confocal imaging and high performance liquid chromatography (HPLC) analyses were used to measure the distribution and concentration of mTHPC in tumors. Our results demonstrate that combination of PDT followed by bevacizumab significantly elicits a greater tumor response whereas bevacizumab treatment prior to PDT led to a reduced tumor response. Immunostaining and ELISA analyses revealed a lower expression of VEGF in tumors treated with combination therapy of PDT followed by bevacizumab. However, bevacizumab treatment decreased the accumulation of mTHPC in tumors 24 h after administration, which complemented the results of decreased anti-tumor efficacy of bevacizumab followed by PDT. ? 2018 Elsevier B.V.
|ISSN:||1572-1000||DOI:||10.1016/j.pdpdt.2018.06.008||SDG/Keyword:||3 tetra(hydroxyphenyl)chlorin; angiogenesis inhibitor; antineoplastic agent; bevacizumab; silver; temoporfin; unclassified drug; angiogenesis inhibitor; bevacizumab; mesoporphyrin; photosensitizing agent; vasculotropin A; vasculotropin receptor; animal experiment; animal model; antiangiogenic activity; antiangiogenic therapy; Article; cancer radiotherapy; capillary density; colorectal cancer; controlled study; drug effect; drug efficacy; enzyme linked immunosorbent assay; female; high performance liquid chromatography; human; human cell; immunohistochemistry; mouse; nonhuman; photodynamic therapy; priority journal; radiation dose; treatment response; animal; antagonists and inhibitors; Bagg albino mouse; colorectal tumor; combination drug therapy; disease model; dose response; Kaplan Meier method; metabolism; neovascularization (pathology); photochemotherapy; procedures; tumor volume; Angiogenesis Inhibitors; Animals; Bevacizumab; Colorectal Neoplasms; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Therapy, Combination; Enzyme-Linked Immunosorbent Assay; Female; Kaplan-Meier Estimate; Mesoporphyrins; Mice; Mice, Inbred BALB C; Neovascularization, Pathologic; Photochemotherapy; Photosensitizing Agents; Receptors, Vascular Endothelial Growth Factor; Tumor Burden; Vascular Endothelial Growth Factor A
|Appears in Collections:||醫學工程學研究所|
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