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Article Open Access

Intensity modulated radiotherapy induces pro-inflammatory and pro-survival responses in prostate cancer patients

  • Authors:
    • Houssein El-Saghire
    • Charlot Vandevoorde
    • Piet Ost
    • Pieter Monsieurs
    • Arlette Michaux
    • Gert De Meerleer
    • Sarah Baatout
    • Hubert Thierens
  • View Affiliations / Copyright

    Affiliations: Radiobiology Unit, Molecular and Cellular Biology, Belgian Nuclear Research Centre (SCK·CEN), Mol, Belgium, Department of Basic Medical Sciences, Ghent University, Gent, Belgium, Department of Radiation Oncology, Ghent University Hospital, Gent, Belgium
    Copyright: © El-Saghire et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 1073-1083
    |
    Published online on: January 17, 2014
       https://doi.org/10.3892/ijo.2014.2260
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Abstract

Intensity modulated radiotherapy (IMRT) is one of the modern conformal radiotherapies that is widely used within the context of cancer patient treatment. It uses multiple radiation beams targeted to the tumor, however, large volumes of the body receive low doses of irradiation. Using γ-H2AX and global genome expression analysis, we studied the biological responses induced by low doses of ionizing radiation in prostate cancer patients following IMRT. By means of different bioinformatics analyses, we report that IMRT induced an inflammatory response via the induction of viral, adaptive, and innate immune signaling. In response to growth factors and immune-stimulatory signaling, positive regulation in the progression of cell cycle and DNA replication were induced. This denotes pro-inflammatory and pro-survival responses. Furthermore, double strand DNA breaks were induced in every patient 30 min after the treatment and remaining DNA repair and damage signaling continued after 18-24 h. Nine genes belonging to inflammatory responses (TLR3, SH2D1A and IL18), cell cycle progression (ORC4, SMC2 and CCDC99) and DNA damage and repair (RAD17, SMC6 and MRE11A) were confirmed by quantitative RT-PCR. This study emphasizes that the risk assessment of health effects from the out-of-field low doses during IMRT should be of concern, as these may increase the risk of secondary cancers and/or systemic inflammation.
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View References

1. 

Ahmad SS, Duke S, Jena R, Williams MV and Burnet NG: Advances in radiotherapy. BMJ. 345:e77652012. View Article : Google Scholar : PubMed/NCBI

2. 

Hall EJ and Wuu CS: Radiation-induced second cancers: the impact of 3D-CRT and IMRT. Int J Radiat Oncol Biol Phys. 56:83–88. 2003. View Article : Google Scholar : PubMed/NCBI

3. 

Purdy JA: Dose to normal tissues outside the radiation therapy patient’s treated volume: a review of different radiation therapy techniques. Health Phys. 95:666–676. 2008.

4. 

Hall EJ: Intensity-modulated radiation therapy, protons, and the risk of second cancers. Int J Radiat Oncol Biol Phys. 65:1–7. 2006. View Article : Google Scholar

5. 

Ruben JD, Davis S, Evans C, et al: The effect of intensity-modulated radiotherapy on radiation-induced second malignancies. Int J Radiat Oncol Biol Phys. 70:1530–1536. 2008. View Article : Google Scholar : PubMed/NCBI

6. 

Ost P, Speleers B, De Meerleer G, et al: Volumetric arc therapy and intensity-modulated radiotherapy for primary prostate radiotherapy with simultaneous integrated boost to intraprostatic lesion with 6 and 18 MV: a planning comparison study. Int J Radiat Oncol Biol Phys. 79:920–926. 2011. View Article : Google Scholar

7. 

Murray L, Henry A, Hoskin P, Siebert FA and Venselaar J: BRAPHYQS/PROBATE group of the GEC ESTRO: Second primary cancers after radiation for prostate cancer: a review of data from planning studies. Radiat Oncol. 8:1722013. View Article : Google Scholar : PubMed/NCBI

8. 

Wyrobek AJ, Manohar CF, Krishnan VV, et al: Low dose radiation response curves, networks and pathways in human lymphoblastoid cells exposed from 1 to 10 cGy of acute gamma radiation. Mutat Res. 722:119–130. 2011. View Article : Google Scholar : PubMed/NCBI

9. 

Yunis R, Albrecht H, Kalanetra KM, Wu S and Rocke DM: Genomic characterization of a three-dimensional skin model following exposure to ionizing radiation. J Radiat Res. 53:860–875. 2012. View Article : Google Scholar : PubMed/NCBI

10. 

Ray M, Yunis R, Chen X and Rocke DM: Comparison of low and high dose ionising radiation using topological analysis of gene coexpression networks. BMC Genomics. 13:1902012. View Article : Google Scholar : PubMed/NCBI

11. 

El-Saghire H, Thierens H, Monsieurs P, Michaux A, Vandevoorde C and Baatout S: Gene set enrichment analysis highlights different gene expression profiles in whole blood samples X-irradiated with low and high doses. Int J Radiat Biol. 89:628–638. 2013. View Article : Google Scholar : PubMed/NCBI

12. 

Pernot E, Hall J, Baatout S, et al: Ionizing radiation biomarkers for potential use in epidemiological studies. Mutat Res. 751:258–286. 2012. View Article : Google Scholar : PubMed/NCBI

13. 

Subramanian A, Tamayo P, Mootha VK, et al: Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA. 102:15545–15550. 2005. View Article : Google Scholar : PubMed/NCBI

14. 

Werbrouck J, De Ruyck K, Beels L, et al: Prediction of late normal tissue complications in RT treated gynaecological cancer patients: potential of the gamma-H2AX foci assay and association with chromosomal radiosensitivity. Oncol Rep. 23:571–578. 2010.

15. 

Irizarry RA, Hobbs B, Collin F, et al: Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics. 4:249–264. 2003. View Article : Google Scholar

16. 

Merico D, Isserlin R, Stueker O, Emili A and Bader GD: Enrichment map: a network-based method for gene-set enrichment visualization and interpretation. PLoS One. 5:e139842010. View Article : Google Scholar : PubMed/NCBI

17. 

Pfaffl MW: A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 29:e452001. View Article : Google Scholar : PubMed/NCBI

18. 

Oakley JD, Taher MM, Hershey CM, Aggarwal PC, Estwani IB and Valerie K: Triggering of apoptosis is not sufficient to induce human immunodeficiency virus gene expression. IUBMB Life. 55:415–427. 2003. View Article : Google Scholar : PubMed/NCBI

19. 

Nowarski R, Wilner OI, Cheshin O, et al: APOBEC3G enhances lymphoma cell radioresistance by promoting cytidine deaminase-dependent DNA repair. Blood. 120:366–375. 2012. View Article : Google Scholar : PubMed/NCBI

20. 

Zhu J, Ghosh A, Coyle EM, et al: Differential effects of phenethyl isothiocyanate and D,L-sulforaphane on TLR3 signaling. J Immunol. 190:4400–4407. 2013. View Article : Google Scholar : PubMed/NCBI

21. 

Amarante MK and Watanabe MA: Toll-like receptor 3: involvement with exogenous and endogenous RNA. Int Rev Immunol. 29:557–573. 2010. View Article : Google Scholar : PubMed/NCBI

22. 

Bauernfeind F, Ablasser A, Kim S, Bartok E and Hornung V: An unexpected role for RNA in the recognition of DNA by the innate immune system. RNA Biol. 7:151–157. 2010. View Article : Google Scholar : PubMed/NCBI

23. 

Vercammen E, Staal J and Beyaert R: Sensing of viral infection and activation of innate immunity by toll-like receptor 3. Clin Microbiol Rev. 21:13–25. 2008. View Article : Google Scholar : PubMed/NCBI

24. 

Chuang HC, Wang JM, Hsieh WC, Chang Y and Su IJ: Up-regulation of activating transcription factor-5 suppresses SAP expression to activate T cells in hemophagocytic syndrome associated with Epstein-Barr virus infection and immune disorders. Am J Pathol. 173:1397–1405. 2008. View Article : Google Scholar

25. 

Surjit M, Varshney B and Lal SK: The ORF2 glycoprotein of hepatitis E virus inhibits cellular NF-kappaB activity by blocking ubiquitination mediated proteasomal degradation of IkappaBalpha in human hepatoma cells. BMC Biochem. 13:72012. View Article : Google Scholar

26. 

Hayden MS and Ghosh S: NF-kappaB, the first quarter-century: remarkable progress and outstanding questions. Genes Dev. 26:203–234. 2012. View Article : Google Scholar : PubMed/NCBI

27. 

Liu SZ, Jin SZ, Liu XD and Sun YM: Role of CD28/B7 costimulation and IL-12/IL-10 interaction in the radiation-induced immune changes. BMC Immunol. 2:82001. View Article : Google Scholar : PubMed/NCBI

28. 

Shan YX, Jin SZ, Liu XD, Liu Y and Liu SZ: Ionizing radiation stimulates secretion of pro-inflammatory cytokines: dose-response relationship, mechanisms and implications. Radiat Environ Biophys. 46:21–29. 2007. View Article : Google Scholar : PubMed/NCBI

29. 

Riley JL: PD-1 signaling in primary T cells. Immunol Rev. 229:114–125. 2009. View Article : Google Scholar : PubMed/NCBI

30. 

Kim SJ, Dix DJ, Thompson KE, et al: Effects of storage, RNA extraction, genechip type, and donor sex on gene expression profiling of human whole blood. Clin Chem. 53:1038–1045. 2007. View Article : Google Scholar : PubMed/NCBI

31. 

Liang X, So YH, Cui J, et al: The low-dose ionizing radiation stimulates cell proliferation via activation of the MAPK/ERK pathway in rat cultured mesenchymal stem cells. J Radiat Res. 52:380–386. 2011. View Article : Google Scholar : PubMed/NCBI

32. 

Sofia Vala I, Martins LR, Imaizumi N, et al: Low doses of ionizing radiation promote tumor growth and metastasis by enhancing angiogenesis. PLoS One. 5:e112222010.PubMed/NCBI

33. 

Marcinkowska E, Superat K and Wiedlocha A: FGF-1 as a possible carrier for targeted drug delivery. Oncol Res. 16:27–34. 2006.PubMed/NCBI

34. 

Shi M, Lin TH, Appell KC and Berg LJ: Cell cycle progression following naive T cell activation is independent of Jak3/common gamma-chain cytokine signals. J Immunol. 183:4493–4501. 2009. View Article : Google Scholar : PubMed/NCBI

35. 

Fernet M, Megnin-Chanet F, Hall J and Favaudon V: Control of the G2/M checkpoints after exposure to low doses of ionising radiation: implications for hyper-radiosensitivity. DNA Repair. 9:48–57. 2010. View Article : Google Scholar : PubMed/NCBI

36. 

Wood ME, Vogel V, Ng A, Foxhall L, Goodwin P and Travis LB: Second malignant neoplasms: assessment and strategies for risk reduction. J Clin Oncol. 30:3734–3745. 2012. View Article : Google Scholar : PubMed/NCBI

37. 

Rashi-Elkeles S, Elkon R, Shavit S, et al: Transcriptional modulation induced by ionizing radiation: p53 remains a central player. Mol Oncol. 5:336–348. 2011. View Article : Google Scholar : PubMed/NCBI

38. 

Aviv Y and Kirshenbaum LA: Novel phosphatase PHLPP-1 regulates mitochondrial Akt activity and cardiac cell survival. Circ Res. 107:448–450. 2010. View Article : Google Scholar : PubMed/NCBI

39. 

Alam MJ, Fatima N, Devi GR, Ravins and Singh RK: The enhancement of stability of p53 in MTBP induced p53-MDM2 regulatory network. Biosystems. 110:74–83. 2012. View Article : Google Scholar : PubMed/NCBI

40. 

Newhauser WD and Durante M: Assessing the risk of second malignancies after modern radiotherapy. Nat Rev Cancer. 11:438–448. 2011. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
El-Saghire H, Vandevoorde C, Ost P, Monsieurs P, Michaux A, De Meerleer G, Baatout S and Thierens H: Intensity modulated radiotherapy induces pro-inflammatory and pro-survival responses in prostate cancer patients. Int J Oncol 44: 1073-1083, 2014.
APA
El-Saghire, H., Vandevoorde, C., Ost, P., Monsieurs, P., Michaux, A., De Meerleer, G. ... Thierens, H. (2014). Intensity modulated radiotherapy induces pro-inflammatory and pro-survival responses in prostate cancer patients. International Journal of Oncology, 44, 1073-1083. https://doi.org/10.3892/ijo.2014.2260
MLA
El-Saghire, H., Vandevoorde, C., Ost, P., Monsieurs, P., Michaux, A., De Meerleer, G., Baatout, S., Thierens, H."Intensity modulated radiotherapy induces pro-inflammatory and pro-survival responses in prostate cancer patients". International Journal of Oncology 44.4 (2014): 1073-1083.
Chicago
El-Saghire, H., Vandevoorde, C., Ost, P., Monsieurs, P., Michaux, A., De Meerleer, G., Baatout, S., Thierens, H."Intensity modulated radiotherapy induces pro-inflammatory and pro-survival responses in prostate cancer patients". International Journal of Oncology 44, no. 4 (2014): 1073-1083. https://doi.org/10.3892/ijo.2014.2260
Copy and paste a formatted citation
x
Spandidos Publications style
El-Saghire H, Vandevoorde C, Ost P, Monsieurs P, Michaux A, De Meerleer G, Baatout S and Thierens H: Intensity modulated radiotherapy induces pro-inflammatory and pro-survival responses in prostate cancer patients. Int J Oncol 44: 1073-1083, 2014.
APA
El-Saghire, H., Vandevoorde, C., Ost, P., Monsieurs, P., Michaux, A., De Meerleer, G. ... Thierens, H. (2014). Intensity modulated radiotherapy induces pro-inflammatory and pro-survival responses in prostate cancer patients. International Journal of Oncology, 44, 1073-1083. https://doi.org/10.3892/ijo.2014.2260
MLA
El-Saghire, H., Vandevoorde, C., Ost, P., Monsieurs, P., Michaux, A., De Meerleer, G., Baatout, S., Thierens, H."Intensity modulated radiotherapy induces pro-inflammatory and pro-survival responses in prostate cancer patients". International Journal of Oncology 44.4 (2014): 1073-1083.
Chicago
El-Saghire, H., Vandevoorde, C., Ost, P., Monsieurs, P., Michaux, A., De Meerleer, G., Baatout, S., Thierens, H."Intensity modulated radiotherapy induces pro-inflammatory and pro-survival responses in prostate cancer patients". International Journal of Oncology 44, no. 4 (2014): 1073-1083. https://doi.org/10.3892/ijo.2014.2260
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