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Combination of bevacizumab and irradiation on uveal melanoma: an in vitro and in vivo preclinical study

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Summary

Background Radiotherapy (RT) is the standard treatment for uveal melanoma. However it can cause damage to the retina and optic nerve. This study examined the in vitro and in vivo effects of the anti-VEGF monoclonal antibody bevacizumab associated with radiotherapy (RT) on tumor growth and tumor proliferation and vasculature on OCM-1 human uveal melanoma cell line. Methods The anti-proliferative effects of bevacizumab, RT and their combination were tested both in vitro (OCM-1 cells co-cultured with HUVEC cells in Transwell plates) and in vivo (OCM-1 tumor xenografts in nude mice). In addition, treatment effects in vitro on VEGF secretion, as well as treatment effects in vivo on tumor proliferation (Ki67 labelling), tumor vasculature (VEGFR2 labelling) and VEGF tumoral concentration were analyzed. Results Bevacizumab given alone had a significant impact on tumor growth in vivo (and moderate effects in vitro). The bevacizumab-RT combination had additive effects in vitro (tumor cell proliferation) and in vivo (tumor growth), which translated into a significant decrease in Ki67 expression, VEGFR2 labelling and VEGF tumoral content. Conclusions The bevacizumab-RT combination could be a promising clinical option to explore for the management of human uveal melanoma, since it may allow RT dose reduction without loss of antitumor efficacy.

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Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Pathology unit, Centre Antoine Lacassagne, 33 Av de Valombrose, 06189, Nice cedex 2, France

    Anne Sudaka & Nicolas Toussan

  2. Ophthalmology Department, Nice General Hospital, 5 Rue Pierre Devoluy, BP319, 06006, Nice Cedex 1, France

    Antoine Susini

  3. Laboratory of Cancer Genetics and Translational Oncology, Santa Croce General Hospital, Via Carle 25, 12100, Cuneo, Italy

    Cristiana Lo Nigro, Federica Tonissi, Laura Lattanzio & Marco Merlano

  4. Oncopharmacology unit, Centre Antoine Lacassagne, 33 Av de Valombrose, 06189, Nice Cedex 2, France

    Jean-Louis Fischel, Patricia Formento, Marie-Christine Etienne-Grimaldi & Gérard Milano

  5. Radiation Therapy Department, Santa Croce General Hospital, Via Carle 25, 12100, Cuneo, Italy

    Elvio Russi

Authors
  1. Anne Sudaka
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  2. Antoine Susini
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  3. Cristiana Lo Nigro
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  4. Jean-Louis Fischel
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  7. Federica Tonissi
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  9. Elvio Russi
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  10. Marie-Christine Etienne-Grimaldi
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  11. Marco Merlano
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  12. Gérard Milano
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Correspondence to Gérard Milano.

Additional information

Results presented in part during the 2009 annual meeting of the American Association for Cancer Research (AACR)

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Sudaka, A., Susini, A., Lo Nigro, C. et al. Combination of bevacizumab and irradiation on uveal melanoma: an in vitro and in vivo preclinical study. Invest New Drugs 31, 59–65 (2013). https://doi.org/10.1007/s10637-012-9834-6

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  • DOI: https://doi.org/10.1007/s10637-012-9834-6

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