In Vivo Imaging Reveals Significant Tumor Vascular Dysfunction and Increased Tumor Hypoxia-Inducible Factor-1α Expression Induced by High Single-Dose Irradiation in a Pancreatic Tumor Model
| Autor: | Jiachuan Bu, Hilda Mujcic, Bradly G. Wouters, Ralph S. DaCosta, Azusa Maeda, Yonghong Chen |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cancer Research Pathology medicine.medical_specialty Time Factors Vascular permeability Hindlimb Capillary Permeability 03 medical and health sciences Platelet Adhesiveness 0302 clinical medicine Vascularity Mice Inbred NOD Pancreatic tumor Cell Adhesion Leukocytes Tumor Microenvironment Animals Medicine Radiology Nuclear Medicine and imaging Platelet Ultrasonography Radiation Tumor hypoxia business.industry Radiotherapy Dosage Hypoxia-Inducible Factor 1 alpha Subunit medicine.disease Cell Hypoxia Tumor Burden Pancreatic Neoplasms Dorsal Skinfold Window Chamber Model 030104 developmental biology Microscopy Fluorescence Oncology 030220 oncology & carcinogenesis Heterografts Female Endothelium Vascular Neoplasm Recurrence Local medicine.symptom business Preclinical imaging |
| Zdroj: | International Journal of Radiation Oncology*Biology*Physics. 97:184-194 |
| ISSN: | 0360-3016 |
| DOI: | 10.1016/j.ijrobp.2016.09.005 |
| Popis: | Purpose To investigate the effect of high-dose irradiation on pancreatic tumor vasculature and microenvironment using in vivo imaging techniques. Methods and Materials A BxPC3 pancreatic tumor xenograft was established in a dorsal skinfold window chamber model and a subcutaneous hind leg model. Tumors were irradiated with a single dose of 4, 12, or 24 Gy. The dorsal skinfold window chamber model was used to assess tumor response, vascular function and permeability, platelet and leukocyte adhesion to the vascular endothelium, and tumor hypoxia for up to 14 days after 24-Gy irradiation. The hind leg model was used to monitor tumor size, hypoxia, and vascularity for up to 65 days after 24-Gy irradiation. Tumors were assessed histologically to validate in vivo observations. Results In vivo fluorescence imaging revealed temporary vascular dysfunction in tumors irradiated with a single dose of 4 to 24 Gy, but most significantly with a single dose of 24 Gy. Vascular functional recovery was observed by 14 days after irradiation in a dose-dependent manner. Furthermore, irradiation with 24 Gy caused platelet and leukocyte adhesion to the vascular endothelium within hours to days after irradiation. Vascular permeability was significantly higher in irradiated tumors compared with nonirradiated controls 14 days after irradiation. This observation corresponded with increased expression of hypoxia-inducible factor-1α in irradiated tumors. In the hind leg model, irradiation with a single dose of 24 Gy led to tumor growth delay, followed by tumor regrowth. Conclusions Irradiation of the BxPC3 tumors with a single dose of 24 Gy caused transient vascular dysfunction and increased expression of hypoxia-inducible factor-1α. Such biological changes may impact tumor response to high single-dose and hypofractionated irradiation, and further investigations are needed to better understand the clinical outcomes of stereotactic body radiation therapy. |
| Databáze: | OpenAIRE |
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