Skip to main content
SpringerLink
Log in

Introduction to Radiation Biology When Treating Hyperproliferative Benign Diseases

  • Chapter
  • First Online:
Dupuytren Disease and Related Diseases - The Cutting Edge

  • 783 Accesses

Abstract

For decades, a low-dose irradiation with X-rays has clinically been documented to exert a beneficial effect on hyperproliferative disorders like the Dupuytren disease (DD) and Ledderhose disease (LD). By contrast, experimental studies to unravel underlying cellular and molecular mechanisms are still at their early stages. Recent data, however, indicate the involvement of radiation-sensitive target cells like mitotic fibroblasts/myofibroblasts, induction of free radicals to impair proliferative activity of these cells, interference with growth factors and cytokines and a reduction of activated immune cells interacting with the inflammatory and proliferative processes. We here aim at briefly describing mechanisms contributing to a modulation of fibrogenic and inflammatory components upon exposure to ionizing radiation.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abraham DJ, Eckes B, Rajkumar V, Krieg T (2007) New developments in fibroblast and myofibroblast biology: implications for fibrosis and scleroderma. Curr Rheumatol Rep 9(2):136–143

    Article  CAS  PubMed  Google Scholar 

  • Alioto RJ, Rosier RN, Burton RI, Puzas JE (1994) Comparative effects of growth factors on fibroblasts of Dupuytren’s tissue and normal palmar fascia. J Hand Surg Am 19(3):442–452

    Article  CAS  PubMed  Google Scholar 

  • Alman BA, Naber SP, Terek RM et al (1995) Platelet-derived growth factor in fibrous musculoskeletal disorders: a study of pathologic tissue sections and in vitro primary cell cultures. J Orthop Res 13(1):67–77

    Article  CAS  PubMed  Google Scholar 

  • Andrew JG, Andrew SM, Ash A, Turner B (1991) An investigation into the role of inflammatory cells in Dupuytren’s disease. J Hand Surg Br 16(3):267–271

    Article  CAS  PubMed  Google Scholar 

  • Badalamente MA, Sampson SP, Hurst LC et al (1996) The role of transforming growth factor beta in Dupuytren’s disease. J Hand Surg Am 21(2):210–215

    Article  CAS  PubMed  Google Scholar 

  • Bayreuther K, Francz PI, Rodemann HP (1992) Fibroblasts in normal and pathological terminal differentiation, aging, apoptosis and transformation. Arch Gerontol Geriatr 15(Suppl 1):47–74

    Article  PubMed  Google Scholar 

  • Bayreuther K, Rodemann HP, Francz PI, Maier K (1988a) Differentiation of fibroblast stem cells. J Cell Sci Suppl 10:115–130

    Article  CAS  PubMed  Google Scholar 

  • Bayreuther K, Rodemann HP, Hommel R et al (1988b) Human skin fibroblasts in vitro differentiate along a terminal cell lineage. Proc Natl Acad Sci U S A 85(14):5112–5116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Berndt A, Kosmehl H, Katenkamp D, Tauchmann V (1994) Appearance of the myofibroblastic phenotype in Dupuytren’s disease is associated with a fibronectin, laminin, collagen type IV and tenascin extracellular matrix. Pathobiology 62(2):55–58

    Article  CAS  PubMed  Google Scholar 

  • Bianchi E, Taurone S, Bardella L et al (2015) Involvement of pro-inflammatory cytokines and growth factors in the pathogenesis of Dupuytren’s contracture: a novel target for a possible future therapeutic strategy? Clin Sci (Lond) 129(8):711–720

    Article  CAS  Google Scholar 

  • Bumann J, Santo-Holtje L, Loffler H, Bamberg M, Rodemann HP (1995) Radiation-induced alterations of the proliferation dynamics of human skin fibroblasts after repeated irradiation in the subtherapeutic dose range. Strahlenther Onkol 171(1):35–41

    CAS  PubMed  Google Scholar 

  • Cordova A, Tripoli M, Corradino B et al (2005) Dupuytren’s contracture: an update of biomolecular aspects and therapeutic perspectives. J Hand Surg Br 30(6):557–562

    Article  CAS  PubMed  Google Scholar 

  • Dolmans GH, Werker PM, Hennies HC et al (2011) Wnt signaling and Dupuytren’s disease. N Engl J Med 365(4):307–317

    Article  CAS  PubMed  Google Scholar 

  • Fitzgerald AM, Kirkpatrick JJ, Naylor IL (1999) Dupuytren’s disease. The way forward? J Hand Surg Br 24(4):395–399

    Article  CAS  PubMed  Google Scholar 

  • Gabbiani G, Ryan GB, Majne G (1971) Presence of modified fibroblasts in granulation tissue and their possible role in wound contraction. Experientia 27(5):549–550

    Article  CAS  PubMed  Google Scholar 

  • Grenfell S, Borg M (2014) Radiotherapy in fascial fibromatosis: a case series, literature review and considerations for treatment of early-stage disease. J Med Imaging Radiat Oncol 58(5):641–647

    Article  PubMed  Google Scholar 

  • Herskind C, Rodemann HP (2000) Spontaneous and radiation-induced differentiation of fibroblasts. Exp Gerontol 35(6–7):747–755, doi:S0531-5565(00)00168-6 [pii]

    Article  CAS  PubMed  Google Scholar 

  • Hildebrandt G, Loppnow G, Jahns J et al (2003a) Inhibition of the iNOS pathway in inflammatory macrophages by low-dose X-irradiation in vitro. Is there a time dependence? Strahlenther Onkol 179(3):158–166

    Article  PubMed  Google Scholar 

  • Hildebrandt G, Radlingmayr A, Rosenthal S et al (2003b) Low-dose radiotherapy (LD-RT) and the modulation of iNOS expression in adjuvant-induced arthritis in rats. Int J Radiat Biol 79(12):993–1001

    Article  CAS  PubMed  Google Scholar 

  • Hinz B, Phan SH, Thannickal VJ et al (2007) The myofibroblast: one function, multiple origins. Am J Pathol 170(6):1807–1816

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Iqbal SA, Hayton MJ, Watson JS et al (2014) First identification of resident and circulating fibrocytes in Dupuytren’s disease shown to be inhibited by serum amyloid P and Xiapex. PLoS One 9(6), e99967

    Article  PubMed  PubMed Central  Google Scholar 

  • Kern PM, Keilholz L, Forster C et al (2000) Low-dose radiotherapy selectively reduces adhesion of peripheral blood mononuclear cells to endothelium in vitro. Radiother Oncol 54(3):273–282

    Article  CAS  PubMed  Google Scholar 

  • Kloen P, Jennings CL, Gebhardt MC et al (1995) Transforming growth factor-beta: possible roles in Dupuytren’s contracture. J Hand Surg Am 20(1):101–108

    Article  CAS  PubMed  Google Scholar 

  • Krause C, Kloen P, Ten Dijke P (2011) Elevated transforming growth factor beta and mitogen-activated protein kinase pathways mediate fibrotic traits of Dupuytren’s disease fibroblasts. Fibrogenesis Tissue Repair 4(1):14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lodermann B, Wunderlich R, Frey S et al (2012) Low dose ionising radiation leads to a NF-kappa B dependent decreased secretion of active IL-1 beta by activated macrophages with a discontinuous dose-dependency. Int J Radiat Biol 88(10):727–734

    Article  PubMed  Google Scholar 

  • Meek RM, McLellan S, Crossan JF (1999) Dupuytren’s disease. A model for the mechanism of fibrosis and its modulation by steroids. J Bone Joint Surg Br 81(4):732–738

    Article  CAS  PubMed  Google Scholar 

  • Meek RM, McLellan S, Reilly J, Crossan JF (2002) The effect of steroids on Dupuytren’s disease: role of programmed cell death. J Hand Surg Br 27(3):270–273

    Article  CAS  PubMed  Google Scholar 

  • Murrell GA, Francis MJ, Bromley L (1987) Free radicals and Dupuytren’s contracture. Br Med J (Clin Res Ed) 295(6610):1373–1375

    Article  CAS  Google Scholar 

  • Murrell GA, Francis MJ, Bromley L (1990) Modulation of fibroblast proliferation by oxygen free radicals. Biochem J 265(3):659–665

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nathan C, Cunningham-Bussel A (2013) Beyond oxidative stress: an immunologist’s guide to reactive oxygen species. Nat Rev Immunol 13(5):349–361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rehman S, Goodacre R, Day PJ, Bayat A, Westerhoff HV (2011) Dupuytren’s: a systems biology disease. Arthritis Res Ther 13(5):238

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Richards SA, Muter J, Ritchie P, Lattanzi G, Hutchison CJ (2011) The accumulation of un-repairable DNA damage in laminopathy progeria fibroblasts is caused by ROS generation and is prevented by treatment with N-acetyl cysteine. Hum Mol Genet 20(20):3997–4004

    Article  CAS  PubMed  Google Scholar 

  • Robbins ME, Zhao W (2004) Chronic oxidative stress and radiation-induced late normal tissue injury: a review. Int J Radiat Biol 80(4):251–259

    Article  CAS  PubMed  Google Scholar 

  • Rödel F, Frey B, Capalbo G, Gaipl U, Keilholz L, Voll R, Hildebrandt G, Rodel C (2010) Discontinuous induction of X-linked inhibitor of apoptosis in EA.hy.926 endothelial cells is linked to NF-kappaB activation and mediates the anti-inflammatory properties of low-dose ionising-radiation. Radiother Oncol 97(2):346–351

    Article  PubMed  Google Scholar 

  • Rödel F, Frey B, Manda K, Hildebrandt G, Hehlgans S, Keilholz L, Seegenschmiedt MH, Gaipl US, Rodel C (2012) Immunomodulatory properties and molecular effects in inflammatory diseases of low-dose x-irradiation. Front Oncol 2:120

    Article  PubMed  PubMed Central  Google Scholar 

  • Rödel F, Frey B, Multhoff G, Gaipl U (2015) Contribution of the immune system to bystander and non-targeted effects of ionizing radiation. Cancer Lett 356(1):105–113

    Article  PubMed  Google Scholar 

  • Rödel F, Kley N, Beuscher HU, Hildebrandt G, Keilholz L, Kern P, Voll R, Herrmann M, Sauer R (2002) Anti-inflammatory effect of low-dose X-irradiation and the involvement of a TGF-beta1-induced down-regulation of leukocyte/endothelial cell adhesion. Int J Radiat Biol 78(8):711–719

    Article  Google Scholar 

  • Rodemann HP, Bamberg M (1995) Cellular basis of radiation-induced fibrosis. Radiother Oncol 35(2):83–90

    Article  CAS  PubMed  Google Scholar 

  • Rodemann HP, Peterson HP, Schwenke K, von Wangenheim KH (1991) Terminal differentiation of human fibroblasts is induced by radiation. Scanning Microsc 5(4):1135–1142; discussion 1142–1133

    CAS  PubMed  Google Scholar 

  • Rubin P, Soni A, Williams JP (1999) The molecular and cellular biologic basis for the radiation treatment of benign proliferative diseases. Semin Radiat Oncol 9(2):203–214

    Article  CAS  PubMed  Google Scholar 

  • Rudolph R, Vande Berg J (1991) The myofibroblast in Dupuytren’s contracture. Hand Clin 7(4):683–692; discussion 693–684

    CAS  PubMed  Google Scholar 

  • Schaue D, Marples B, Trott KR (2002) The effects of low-dose X-irradiation on the oxidative burst in stimulated macrophages. Int J Radiat Biol 78(7):567–576

    Article  CAS  PubMed  Google Scholar 

  • Seegenschmiedt MH, Makoski HB, Trott KR, Brady LWE (2008) Radiotherapy for non-malignant disorders. Medical radiology diagnostic imaging and radiation oncology. Springer, Berlin/Heidelberg

    Book  Google Scholar 

  • Seegenschmiedt MH, Micke O, Niewald M, Mucke R, Eich HT, Kriz J, Heyd R (2015) DEGRO guidelines for the radiotherapy of non-malignant disorders : part III: hyperproliferative disorders. Strahlenther Onkol 191(7):541–548

    Article  PubMed  Google Scholar 

  • Shih B, Bayat A (2010) Scientific understanding and clinical management of Dupuytren disease. Nat Rev Rheumatol 6(12):715–726

    Article  CAS  PubMed  Google Scholar 

  • Smitt MC, Donaldson SS (1999) Radiation therapy for benign disease of the orbit. Semin Radiat Oncol 9(2):179–189

    Article  CAS  PubMed  Google Scholar 

  • Speyer CL, Ward PA (2011) Role of endothelial chemokines and their receptors during inflammation. J Invest Surg 24(1):18–27

    Article  PubMed  Google Scholar 

  • Suit H, Spiro I (1999) Radiation treatment of benign mesenchymal disease. Semin Radiat Oncol 9(2):171–178

    Article  CAS  PubMed  Google Scholar 

  • Travis EL (2001) Organizational response of normal tissues to irradiation. Semin Radiat Oncol 11(3):184–196

    Article  CAS  PubMed  Google Scholar 

  • Tsukimoto M, Homma T, Mutou Y, Kojima S (2009) 0.5 Gy gamma radiation suppresses production of TNF-alpha through up-regulation of MKP-1 in mouse macrophage RAW264.7 cells. Radiat Res 171(2):219–224

    Article  CAS  PubMed  Google Scholar 

  • Verjee LS, Verhoekx JS, Chan JK, Krausgruber T, Nicolaidou V, Izadi D, Davidson D, Feldmann M, Midwood KS, Nanchahal J (2013) Unraveling the signaling pathways promoting fibrosis in Dupuytren’s disease reveals TNF as a therapeutic target. Proc Natl Acad Sci U S A 110(10):E928–E937

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wong M, Mudera V (2006) Feedback inhibition of high TGF-beta1 concentrations on myofibroblast induction and contraction by Dupuytren’s fibroblasts. J Hand Surg Br 31(5):473–483

    Article  CAS  PubMed  Google Scholar 

  • Yarnold J, Brotons MC (2010) Pathogenetic mechanisms in radiation fibrosis. Radiother Oncol 97(1):149–161

    Article  CAS  PubMed  Google Scholar 

  • Zhao W, Robbins ME (2009) Inflammation and chronic oxidative stress in radiation-induced late normal tissue injury: therapeutic implications. Curr Med Chem 16(2):130–143

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements and Conflict of Interest Statement

This work has received funding from the European Atomic Energy Community’s Seventh Framework Programme under grant agreement no FP7-249689 (European Network of Excellence, DoReMi) and the German Federal Ministry of Education and Research (GREWIS, 02NUK017F). The authors have no conflict of interest to declare.

Author information

Authors and Affiliations

  1. Department of Radiotherapy and Oncology, Goethe-University Frankfurt am Main, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany

    Franz Rödel

  2. Strahlenzentrum Hamburg Nord, Langenhorner Chaussee 369, 22419, Hamburg, Germany

    M. Heinrich Seegenschmiedt

Authors
  1. Franz Rödel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Heinrich Seegenschmiedt
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Franz Rödel .

Editor information

Editors and Affiliations

  1. University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands

    Paul M. N. Werker

  2. Leicester General Hospital, University Hospitals of Leicester, Leicester, United Kingdom

    Joseph Dias

  3. Dupuytren Foundation, West Palm Beach, Florida, USA

    Charles Eaton

  4. Nürnberg Clinics, Paracelsus Medical University, Nürnberg, Germany

    Bert Reichert

  5. International Dupuytren Society, Übersee, Germany

    Wolfgang Wach

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Rödel, F., Seegenschmiedt, M.H. (2017). Introduction to Radiation Biology When Treating Hyperproliferative Benign Diseases. In: Werker, P., Dias, J., Eaton, C., Reichert, B., Wach, W. (eds) Dupuytren Disease and Related Diseases - The Cutting Edge. Springer, Cham. https://doi.org/10.1007/978-3-319-32199-8_45

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-32199-8_45

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-32197-4

  • Online ISBN: 978-3-319-32199-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation