Rödel Franz, Fournier Claudia, Wiedemann Julia, Merz Felicitas, Gaipl Udo S, Frey Benjamin, Keilholz Ludwig, Seegenschmiedt M Heinrich, Rödel Claus, Hehlgans Stephanie
Department of Radiotherapy and Oncology, University Hospital of Frankfurt, Goethe-Universität, Frankfurt am Main, Germany.
Department of Biophysics, GSI Helmholtz Centre for Heavy Ion Research, Darmstadt, Germany.
Front Immunol. 2017 May 3;8:519. doi: 10.3389/fimmu.2017.00519. eCollection 2017.
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.
几十年来,低剂量和中剂量放射治疗(RT)已被证明在多种非恶性疾病中具有有益的治疗效果,包括疼痛性退行性肌肉骨骼疾病和过度增殖性疾病。掌腱膜挛缩症和足底纤维瘤病是手足部的良性纤维增生性疾病,伴有纤维化结节和筋膜索带,可导致手指/脚趾的致残性挛缩和畸形,而瘢痕疙瘩是烧伤、手术和创伤后形成的过度增生性瘢痕。尽管放射治疗已成为这些疾病治疗中既定且有效的选择,但阐明其中涉及的细胞复合物和因素的实验研究仍有待开展。然而,最近的研究结果表明,有丝分裂成纤维细胞/肌成纤维细胞以及炎性细胞等放射敏感靶点参与其中。影响这些靶细胞的辐射相关分子机制包括产生自由基以阻碍增殖活性以及干扰生长因子和细胞因子。此外,参与肌成纤维细胞增殖和炎症过程的活化免疫细胞功能受损可能会进一步影响临床疗效。我们在此旨在简要描述对增殖和炎症过程进行调节的机制,并总结低剂量和中剂量电离辐射治疗过度增殖性疾病的当前概念。