Abstract
Microvascular damage is an important component of late radiation-induced morbidity. In our pre-clinical models, we demonstrated that repair of vessel injury is dependent on proper endoglin-mediated transforming growth factor-beta (TGF-β) signalling and that it can be affected by infiltrating macrophages. We now wanted to extend these findings in irradiated patients, using skin as a model system, and assess whether bisphosphonates could modulate the response. Paired skin biopsies from irradiated and non-irradiated sites were obtained from 48 breast cancer patients. In 8 patients, biopsies were repeated after 4months of bisphosphonate treatment. Immunohistochemistry was used to assess vascular alterations and leucocyte infiltration. Western Blot and qPCR were used to assess expression of growth factors and their receptors. Decreased blood vessel numbers at early time points were followed by increased endoglin expression and restoration of vessel number. Loss of small lymphatic vessels was associated with increased TGF-β levels, whereas dilation of lymphatic vessels correlated with increased macrophage infiltration. Bisphosphonate treatment reduced leucocyte infiltration, but also prevented restoration of blood vessel numbers afte...Continue Reading
References
Jan 1, 1992·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·S L TuckerH D Thames
Dec 1, 1990·International Journal of Radiation Oncology, Biology, Physics·I Turesson
Mar 17, 2000·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·S WachterR Pötter
Feb 16, 2002·Acta Oncologica·F A StewartL G Dewit
Sep 3, 2004·The Journal of Clinical Investigation·Enrico GiraudoDouglas Hanahan
Jun 27, 2007·The American Journal of Pathology·Susanne JackowskiPeter Helmbold
Oct 11, 2007·Cancer Science·Yusuke N KimuraMayumi Ono
Mar 4, 2008·Blood·Masako OkaKohei Miyazono
May 20, 2009·Annals of Surgical Oncology·Iris M C van der PloegEmiel J T Rutgers
Jul 7, 2009·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·Marion ScharpfeneckerFiona A Stewart
Nov 12, 2009·Blood·Kyle NiessenMinhong Yan
Jul 27, 2010·American Journal of Physiology. Heart and Circulatory Physiology·José M López-Novoa, Carmelo Bernabeu
Jun 28, 2011·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·Marion ScharpfeneckerFiona A Stewart
Nov 25, 2011·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·Ingar SeemannFiona A Stewart
Dec 28, 2011·Thorax·G GhobadiP van Luijk
Oct 18, 2012·Blood·Elisa RossiCarmelo Bernabeu
Jul 16, 2013·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·Marion ScharpfeneckerFiona A Stewart
May 7, 2014·International Journal of Radiation Biology·Karin de CortieMarion Scharpfenecker
Oct 15, 2014·Human Molecular Genetics·Christine MalletEmmanuelle Tillet
Mar 11, 2015·International Journal of Radiation Oncology, Biology, Physics·Ravi A ChandraAlphonse G Taghian
Citations
Sep 20, 2015·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·H Peter Rodemann, Stephan Bodis
Apr 12, 2016·Frontiers in Pharmacology·Natacha LeroiPhilippe Martinive
Dec 8, 2017·Radiation Research·Jianyuan SongShuyu Zhang
Aug 15, 2018·Frontiers in Immunology·Inigo Martinez-ZubiaurreTurid Hellevik
Mar 23, 2019·Scientific Reports·Felicitas RappClaudia Fournier
Jan 20, 2019·International Journal of Molecular Sciences·Raffaella MarconiLidia Strigari
Dec 14, 2018·Medicine·Kohei MoritaNoriyoshi Fukushima
Oct 2, 2020·Molecular Medicine Reports·Fei XuJingcheng Dong
Mar 4, 2021·Macromolecular Bioscience·Feng-Mei CuiGuo-Jing Wang
Mar 7, 2021·International Journal of Molecular Sciences·Wineke BakkerMarie José T H Goumans
Jun 16, 2021·International Journal of Radiation Biology·Marjan BoermaJacqueline P Williams