Basics of Radiation Biology When Treating Hyperproliferative Benign Diseases

Franz Rödel, Claudia Fournier, Julia Wiedemann, Felicitas Merz, Udo S Gaipl, Benjamin Frey, Ludwig Keilholz, M Heinrich Seegenschmiedt, Claus Rödel, Stephanie Hehlgans, Franz Rödel, Claudia Fournier, Julia Wiedemann, Felicitas Merz, Udo S Gaipl, Benjamin Frey, Ludwig Keilholz, M Heinrich Seegenschmiedt, Claus Rödel, Stephanie Hehlgans

Abstract

For decades, low- and moderate-dose radiation therapy (RT) has been shown to exert a beneficial therapeutic effect in a multitude of non-malignant conditions including painful degenerative muscoloskeletal and hyperproliferative disorders. Dupuytren and Ledderhose diseases are benign fibroproliferative diseases of the hand/foot with fibrotic nodules and fascial cords, which determine debilitating contractures and deformities of fingers/toes, while keloids are exuberant scar formations following burn damage, surgery, and trauma. Although RT has become an established and effective option in the management of these diseases, experimental studies to illustrate cellular composites and factors involved remain to be elucidated. More recent findings, however, indicate the involvement of radiation-sensitive targets like mitotic fibroblasts/myofibroblasts as well as inflammatory cells. Radiation-related molecular mechanisms affecting these target cells include the production of free radicals to hamper proliferative activity and interference with growth factors and cytokines. Moreover, an impairment of activated immune cells involved in both myofibroblast proliferative and inflammatory processes may further contribute to the clinical effects. We here aim at briefly describing mechanisms contributing to a modulation of proliferative and inflammatory processes and to summarize current concepts of treating hyperproliferative diseases by low and moderate doses of ionizing radiation.

Keywords: anti-inflammatory effect; antiproliferative effect; cytokines; fibroblasts/myofibroblast; hyperproliferative diseases; low-dose radiation therapy.

Figures

Figure 1
Figure 1
Model of modulation of cellular components and factors by low-dose radiotherapy for the treatment of hyperproliferative/fibrotic benign diseases. Progenitor mitotic fibroblasts are activated by transforming growth factor-β1 (TGF-β1) and additional factors to differentiate into myofibroblasts/fibrocytes, resulting in increased extracellular matrix (ECM) synthesis and deposition. In contrast, irradiation might interfere with these processes by increasing free radicals, inactivating radiosensitive mitotic fibroblasts/myofibroblasts, and promoting terminal differentiation into senescent fibrocytes. Further, low-dose irradiation modulates inflammatory components in modulating cytokine expression, macrophage, and endothelial cell activity. Abbreviations and details are given in the text.

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