Effects of High-Dose Microbeam Irradiation on Tumor Microvascular Function and Angiogenesis
| Autor: | Thies Schroeder, Gregory M. Palmer, Jian Zhang, Mary Keara Boss, Mark W. Dewhirst, M Hadsell, Sha Chang, Katherine Berman, Andrew N. Fontanella |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
medicine.medical_treatment
Biophysics Biology Article Neovascularization Mice In vivo Cell Line Tumor Tumor Microenvironment medicine Bystander effect Animals Radiology Nuclear Medicine and imaging Tumor microenvironment Radiation Neovascularization Pathologic Dose fractionation Dose-Response Relationship Radiation Bystander Effect Neoplasms Experimental Microbeam Radiation therapy Treatment Outcome Microvessels Immunology Cancer research Dose Fractionation Radiation Hypoxia-Inducible Factor 1 Radiotherapy Conformal medicine.symptom Ex vivo |
| DOI: | 10.17615/d031-0f34 |
| Popis: | Microbeam radiation therapy (MRT) is a form of cancer treatment in which a single large dose of radiation is spatially fractionated in-line or grid-like patterns. Preclinical studies have demonstrated that MRT is capable of eliciting high levels of tumor response while sparing normal tissue that is exposed to the same radiation field. Since a large fraction of the MRT-treated tumor is in the dose valley region that is not directly irradiated, tumor response may be driven by radiation bystander effects, which in turn elicit a microvascular response. Differential alterations in hemodynamics between the tumor and normal tissue may explain the therapeutic advantages of MRT. Direct observation of these dynamic responses presents a challenge for conventional ex vivo analysis. Furthermore, knowledge gleaned from in vitro studies of radiation bystander response has not been widely incorporated into in vivo models of tumor radiotherapy, and the biological contribution of the bystander effect within the tumor microenvironment is unknown. In this study, we employed noninvasive, serial observations of the tumor microenvironment to address the question of how tumor vasculature and HIF-1 expression are affected by microbeam radiotherapy. Tumors (approximately 4 mm in diameter) grown in a dorsal window chamber were irradiated in a single fraction using either a single, microplanar beam (300 micron wide swath) or a wide-field setup (whole-window chamber) to a total dose of 50 Gy. The tumors were optically observed daily for seven days postirradiation. Microvascular changes in the tumor and surrounding normal tissue differed greatly between the wide-field and microbeam treatments. We present evidence that these changes may be due to dissimilar spatial and temporal patterns of HIF-1 expression induced through radiation bystander effects. |
| Databáze: | OpenAIRE |
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