Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Journal of Inflammation
Published in: Journal of Inflammation 1/2015

Open Access 01-12-2015 | Review

Portrait of inflammatory response to ionizing radiation treatment

Authors: Federica Maria Di Maggio, Luigi Minafra, Giusi Irma Forte, Francesco Paolo Cammarata, Domenico Lio, Cristina Messa, Maria Carla Gilardi, Valentina Bravatà

Published in: Journal of Inflammation | Issue 1/2015

Login to get access

Abstract

Ionizing radiation (IR) activates both pro-and anti-proliferative signal pathways producing an imbalance in cell fate decision. IR is able to regulate several genes and factors involved in cell-cycle progression, survival and/or cell death, DNA repair and inflammation modulating an intracellular radiation-dependent response. Radiation therapy can modulate anti-tumour immune responses, modifying tumour and its microenvironment. In this review, we report how IR could stimulate inflammatory factors to affect cell fate via multiple pathways, describing their roles on gene expression regulation, fibrosis and invasive processes. Understanding the complex relationship between IR, inflammation and immune responses in cancer, opens up new avenues for radiation research and therapy in order to optimize and personalize radiation therapy treatment for each patient.
Literature
1.
Bernier J, Hall EJ, Giaccia A. Radiation oncology: a century of achievements. Nat Rev Cancer. 2004;4:737–47.PubMed
2.
Minafra L, Bravatà V. Cell and molecular response to IORT treatment. Transl Cancer Res. 2014;3:32–47.
3.
Wu S, Li Q, Zhou J, Sun J, Li F, Lin Q, et al. Post-mastectomy radiotherapy can improve survival in breast cancer patients aged 35 years or younger with four or more positive nodes but not in one to three positive nodes. Ther Clin Risk Manag. 2014;10:867–74.PubMedCentralPubMed
4.
Rodemann HP, Blaese MA. Responses of normal cells to ionizing radiation. Semin Radiat Oncol. 2007;17:81–8.PubMed
5.
Brigati C, Noonan DM, Albini A, Benelli R. Tumors and inflammatory infiltrates: friends or foes? Clin Exp Metastasis. 2002;19:247–58.PubMed
6.
Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet. 2001;357:539–45.PubMed
7.
Caruso C, Lio D, Cavallone L, Franceschi C. Aging, longevity, inflammation, and cancer. Ann N Y Acad Sci. 2004;1028:1–13.PubMed
8.
9.
10.
Deorukhkar A, Krishnan S. Targeting inflammatory pathways for tumor radiosensitization. Biochem Pharmacol. 2010;80:1904–14.PubMedCentralPubMed
11.
Dent P, Yacoub A, Contessa J, Caron R, Amorino G, Valerie K, et al. Stress and radiation-induced activation of multiple intracellular signaling pathways. Radiat Res. 2003;159:283–300.PubMed
12.
Criswell T, Leskov K, Miyamoto S, Luo G, Boothman DA. Transcription factors activated in mammalian cells after clinically relevant doses of ionizing radiation. Oncogene. 2003;22:5813–27.PubMed
13.
Aggarwal BB, Sethi G, Ahn KS, Sandur SK, Pandey MK, Kunnumakkara AB, et al. Targeting signal-transducer-and-activator-of-transcription-3 for prevention and therapy of cancer: modern target but ancient solution. Ann N Y Acad Sci. 2006;1091:151–69.PubMed
14.
Shimamura H, Terada Y, Okado T, Tanaka H, Inoshita S, Sasaki S. The PI3-kinase-Akt pathway promotes mesangial cell survival and inhibits apoptosis in vitro via NF-kappa B and Bad. J Am Soc Nephrol. 2003;14:1427–34.PubMed
15.
Aravindan S, Natarajan M, Ramraj SK, Pandian V, Khan FH, Herman TS, et al. Abscopal effect of low-LET γ-radiation mediated through Rel protein signal transduction in a mouse model of non targeted radiation response. Cancer Gene Ther. 2014;21:54–9.PubMed
16.
Lin Y, Bai L, Chen W, Xu S. The NF-kappaB activation pathways, emerging molecular targets for cancer prevention and therapy. Expert OpinTher Targets. 2010;14:45–55.
17.
Karin M. Nuclear factor-kappaB in cancer development and progression. Nature. 2006;441:431–6.PubMed
18.
Panta GR, Kaur S, Cavin LG, Cortés ML, Mercurio F, Lothstein L, et al. ATM and the catalytic subunit of DNA-dependent protein kinase activate NF-kappaB through a common MEK/extracellular signal-regulated kinase/p90 (rsk) signaling pathway in response to distinct forms of DNA damage. Mol Cell Biol. 2004;24:1823–35.PubMedCentralPubMed
19.
Rho HS, Kim SH, Lee CE. Mechanism of NF-kappaB activation induced by gamma-irradiation in B lymphoma cells: role of Ras. J Toxicol Environ Health A. 2005;68:2019–31.PubMed
20.
Ahn KS, Aggarwal BB. Transcription factor NF-kappaB: a sensor for smoke and stress signals. Ann N Y Acad Sci. 2005;1056:218–33.PubMed
21.
Janssens S, Tschopp J. Signals from within: the DNA-damage-induced NF-kappaB response. Cell Death Differ. 2006;13:773–84.PubMed
22.
Rasoulpour RJ, Boekelheide K. NF-kappaB activation elicited by ionizing radiation is pro apoptotic in testis. Biol Reprod. 2007;76:279–85.PubMed
23.
McCool KW, Miyamoto S. DNA damage-dependent NF-κB activation: NEMO turns nuclear signaling inside out. Immunol Rev. 2012;246:311–26.PubMedCentralPubMed
24.
Park WY, Hwang CI, Im CN, Kang MJ, Woo JH, Kim JH, et al. Identification of radiation-specific responses from gene expression profile. Oncogene. 2002;21:8521–8.PubMed
25.
Chaudhry MA, Chodosh LA, McKenna WG, Muschel RJ. Gene expression profile of human cells irradiated in G1 and G2 phases of cell cycle. Cancer Lett. 2003;195:221–33.PubMed
26.
Starenki D, Namba H, Saenko V, Ohtsuru A, Yamashita S. Inhibition of nuclear factor-kappaB cascade potentiates the effect of a combination treatment of anaplastic thyroid cancer cells. J Clin Endocrinol Metab. 2004;89:410–8.PubMed
27.
Yamamoto Y, Gaynor RB. Therapeutic potential of inhibition of the NF-kappaB pathway in the treatment of inflammation and cancer. J Clin Invest. 2001;107:135–42.PubMedCentralPubMed
28.
Poczeta M, Bednarek I, Nowak E, Galilejczyk A, Gawlik N. Silencing of the STAT3 gene expression activity and cancer cells metastatic potential at in vitro studies. Wiad Lek. 2013;66:226–32.PubMed
29.
Murray PJ. The JAK-STAT signaling pathway: input and output integration. J Immunol. 2007;178:2623–9.PubMed
30.
Yu H, Pardoll D, Jove R. STATs in cancer inflammation and immunity: a leading role for STAT3. Nat Rev Cancer. 2009;9:798–809.PubMed
31.
Calò V, Migliavacca M, Bazan V, Macaluso M, Buscemi M, Gebbia N, et al. STAT proteins: from normal control of cellular events to tumorigenesis. J Cell Physiol. 2003;197:157–68.PubMed
32.
Shen Y, Devgan G, Darnell Jr JE, Bromberg JF. Constitutively activated Stat3 protects fibroblasts from serum withdrawal and UV-induced apoptosis and antagonizes the proapoptotic effects of activated Stat1. Proc Natl Acad Sci U S A. 2001;98:1543–8.PubMedCentralPubMed
33.
Judd LM, Menheniott TR, Ling H, Jackson CB, Howlett M, Kalantzis A, et al. Inhibition of the JAK2/STAT3 pathway reduces gastric cancer growth In vitro and In vivo. PLoS One. 2014;9:e95993.PubMedCentralPubMed
34.
Yang J, Liao X, Agarwal MK, Barnes L, Auron PE, Stark GR. Unphosphorylated STAT3 accumulates in response to IL-6 and activates transcription by binding to NFkappaB. Genes Dev. 2007;21:1396–408.PubMedCentralPubMed
35.
Lo HW, Cao X, Zhu H, Ali-Osman F. Cyclooxygenase-2 is a novel transcriptional target of the nuclear EGFR-STAT3 and EGFRvIII-STAT3 signaling axes. Mol Cancer Res. 2010;8:232–45.PubMedCentralPubMed
36.
Samavati L, Rastogi R, Du W, Hüttemann M, Fite A, Franchi L. STAT3 tyrosine phosphorylation is critical for interleukin 1 beta and interleukin-6 production in response to lipopolysaccharide and live bacteria. Mol Immunol. 2009;46:1867–77.PubMed
37.
Trevino JG, Gray MJ, Nawrocki ST, Summy JM, Lesslie DP, Evans DB, et al. Src activation of Stat3 is an independent requirement from NF-kappaB activation for constitutive IL-8 expression in human pancreatic adenocarcinoma cells. Angiogenesis. 2006;9:101–10.PubMed
38.
Aggarwal BB, Kunnumakkara AB, Harikumar KB, Gupta SR, Tharakan ST, Koca C, et al. Signal transducer and activator of transcription-3, inflammation, and cancer: how intimate is the relationship? Ann N Y Acad Sci. 2009;1171:59–76.PubMedCentralPubMed
39.
Kim KW, Mutter RW, Cao C, Albert JM, Shinohara ET, Sekhar KR, et al. Inhibition of signal transducer and activator of transcription 3 activity results in down-regulation of Survivin following irradiation. Mol Cancer Ther. 2006;5:2659–65.PubMed
40.
Avalle L, Pensa S, Regis G, Novelli F, Poli V. STAT1 and STAT3 in tumorigenesis: a matter of balance. JAKSTAT. 2012;1:65–72.PubMedCentralPubMed
41.
Khodarev NN, Roach P, Pitroda SP, Golden DW, Bhayani M, Shao MY, et al. STAT1 pathway mediates amplification of metastatic potential and resistance to therapy. PLoS One. 2009;4:e5821.PubMedCentralPubMed
42.
Hui Z, Tretiakova M, Zhang Z, Li Y, Wang X, Zhu JX, et al. Radiosensitization by inhibiting STAT1 in renal cell carcinoma. Int J Radiat Oncol Biol Phys. 2009;73:288–95.PubMed
43.
Sun Y, Cheng MK, Griffiths TR, Mellon JK, Kai B, Kriajevska M, et al. Inhibition of STAT signalling in bladder cancer by diindolylmethane: relevance to cell adhesion, migration and proliferation. Curr Cancer Drug Targets. 2013;13(1):57–68.PubMed
44.
45.
Bravatà V, Cammarata FP, Forte GI, Minafra L. “Omics” of HER2-positive breast cancer. OMICS. 2013;17:119–29.PubMed
46.
Scola L, Vaglica M, Crivello A, Palmeri L, Forte GI, Macaluso MC, et al. Cytokine gene polymorphisms and breast cancer susceptibility. Ann N Y Acad Sci. 2006;1089:104–9.PubMed
47.
Scola L, Di Maggio FM, Vaccarino L, Bova M, Forte GI, Pisano C, et al. Role of TGF-β pathway polymorphisms in sporadic thoracic aortic aneurysm: rs900 TGF-β2 is a marker of differential gender susceptibility. Mediators Inflamm. 2014;2014:165758.PubMedCentralPubMed
48.
Hong JH, Chiang CS, Tsao CY, Lin PY, McBride WH, Wu CJ. Rapid induction of cytokine gene expression in the lung after single and fractionated doses of radiation. Int J Radiat Biol. 1999;75:1421–7.PubMed
49.
Burnette BC, Liang H, Lee Y, Chlewicki L, Khodarev NN, Weichselbaum RR, et al. The efficacy of radiotherapy relies upon induction of type I interferon-dependent innate and adaptive immunity. Cancer Res. 2011;71:2488–96.PubMedCentralPubMed
50.
Hao S, Baltimore D. The stability of mRNA influences the temporal order of the induction of genes encoding inflammatory molecules. Nat Immunol. 2009;10:281–8.PubMedCentralPubMed
51.
Han SK, Song JY, Yun YS, Yi SY. Effect of gamma radiation on cytokine expression and cytokine-receptor mediated STAT activation. Int J Radiat Biol. 2006;82:686–97.PubMed
52.
Shan YX, Jin SZ, Liu XD, Liu Y, Liu SZ. Ionizing radiation stimulates secretion of pro-inflammatory cytokines: dose–response relationship, mechanisms and implications. Radiat Environ Biophys. 2007;46:21–9.PubMed
53.
Dancea HC, Shareef MM, Ahmed MM. Role of Radiation-induced TGF-beta Signaling in Cancer Therapy. Mol Cell Pharmacol. 2009;1:44–56.PubMedCentralPubMed
54.
Hong JH, Chiang CS, Campbell IL, Sun JR, Withers HR, McBride WH. Induction of acute phase gene expression by brain irradiation. Int J Radiat Oncol Biol Phys. 1995;33:619–26.PubMed
55.
56.
Munro AJ. Bystander effects and their implications for clinical radiotherapy. J Radiol Prot. 2009;29:A133–42.PubMed
57.
Chiang CS, Chen FH, Hong JH, Jiang PS, Huang HL, Wang CC, et al. Functional phenotype of macrophages depends on assay procedures. Int Immunol. 2008;20:215–22.PubMed
58.
Venkatesh GH, Manjunath VB, Mumbrekar KD, Negi H, Fernandes DJ, Sharan K, et al. Polymorphisms in radio-responsive genes and its association with acute toxicity among head and neck cancer patients. PLoS One. 2014;9:e89079.PubMedCentralPubMed
59.
Bravatà V, Stefano A, Cammarata FP, Minafra L, Russo G, Nicolosi S, et al. Genotyping analysis and 18FDG uptake in breast cancer patients: a preliminary research. J Exp Clin Cancer Res. 2013;32:23.PubMedCentralPubMed
60.
Kil WJ, Tofilon PJ, Camphausen K. Post-radiation increase in VEGF enhances glioma cell motility in vitro. Radiat Oncol. 2012;7:25.PubMedCentralPubMed
61.
Veeraraghavan J, Natarajan M, Aravindan S, Herman TS, Aravindan N. Radiation-triggered tumor necrosis factor (TNF) alpha-NFkappaB cross-signaling favors survival advantage in human neuroblastoma cells. J Biol Chem. 2011;286:21588–600.PubMedCentralPubMed
62.
O'Brien-Ladner A, Nelson ME, Kimler BF, Wesselius LJ. Release of interleukin-1 by human alveolar macrophages after in vitro irradiation. Radiat Res. 1993;136:37–41.PubMed
63.
Müller K, Meineke V. Radiation-induced alterations in cytokine production by skin cells. Exp Hematol. 2007;35:96–104.PubMed
64.
Chou CH, Chen SU, Cheng JC. Radiation-induced interleukin-6 expression through MAPK/p38/NF-kappaB signaling pathway and the resultant antiapoptotic effect on endothelial cells through Mcl-1 expression with sIL6-Ralpha. Int J Radiat Oncol Biol Phys. 2009;75:1553–61.PubMed
65.
Kondo S, Kono T, Sauder DN, McKenzie RC. IL-8 gene expression and production in human keratinocytes and their modulation by UVB. J Invest Dermatol. 1993;101:690–4.PubMed
66.
Wu CT, Chen MF, Chen WC, Hsieh CC. The role of IL-6 in the radiation response of prostate cancer. Radiat Oncol. 2013;8:159.PubMedCentralPubMed
67.
Koj A. Termination of acute-phase response: role of some cytokines and anti-inflammatory drugs. Gen Pharmacol. 1998;31:9–18.PubMed
68.
Sultani M, Stringer AM, Bowen JM, Gibson RJ. Anti-inflammatory cytokines: important immunoregulatory factors contributing to chemotherapy-induced gastrointestinal mucositis. Chemother Res Pract. 2012;2012:490804.PubMedCentralPubMed
69.
Lee Y, Auh SL, Wang Y, Burnette B, Wang Y, Meng Y, et al. Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment. Blood. 2009;114:589–95.PubMedCentralPubMed
70.
Desai S, Kumar A, Laskar S, Pandey BN. Cytokine profile of conditioned medium from human tumor cell lines after acute and fractionated doses of gamma radiation and its effect on survival of bystander tumor cells. Cytokine. 2013;61:54–62.PubMed
71.
Belletti B, Vaidya JS, D'Andrea S, Entschladen F, Roncadin M, Lovat F, et al. Targeted intraoperative radiotherapy impairs the stimulation of breast cancer cell proliferation and invasion caused by surgical wounding. Clin Cancer Res. 2008;14:1325–32.PubMed
72.
Gajewski TF, Schreiber H, Fu YX. Innate and adaptive immune cells in the tumor microenvironment. Nat Immunol. 2013;14:1014–22.PubMedCentralPubMed
73.
Hao NB, Lü MH, Fan YH, Cao YL, Zhang ZR, Yang SM. Macrophages in tumor microenvironments and the progression of tumors. Clin Dev Immunol. 2012;2012:948098.PubMedCentralPubMed
74.
Tagliabue E, Agresti R, Carcangiu ML, Ghirelli C, Morelli D, Campiglio M, et al. Role of HER2 in wound-induced breast carcinoma proliferation. Lancet. 2003;362:527–33.PubMed
75.
Westbury CB, Yarnold JR. Radiation fibrosis–current clinical and therapeutic perspectives. ClinOncol (R CollRadiol). 2012;24:657–72.
76.
Johnston CJ, Piedboeuf B, Rubin P, Williams JP, Baggs R, Finkelstein JN. Early and persistent alterations in the expression of interleukin-1 alpha, interleukin-1 beta and tumor necrosis factor alpha mRNA levels in fibrosis-resistant and sensitive mice after thoracic irradiation. Radiat Res. 1996;145:762–7.PubMed
77.
Büttner C, Skupin A, Reimann T, Rieber EP, Unteregger G, Geyer P, et al. Local production of interleukin-4 during radiation-induced pneumonitis and pulmonary fibrosis in rats: macrophages as a prominent source of interleukin-4. Am J Respir Cell Mol Biol. 1997;17:315–25.PubMed
78.
Rubin P, Johnston CJ, Williams JP, McDonald S, Finkelstein JN. A perpetual cascade of cytokines post irradiation leads to pulmonary fibrosis. Int J Radiat Oncol Biol Phys. 1995;33:99–109.PubMed
79.
Yarnold J, Brotons MC. Pathogenetic mechanisms in radiation fibrosis. Radiother Oncol. 2010;97:149–61.PubMed
80.
81.
Jobling MF, Mott JD, Finnegan MT, Jurukovski V, Erickson AC, Walian PJ, et al. Isoform-specific activation of latent transforming growth factor beta (LTGF-beta) by reactive oxygen species. Radiat Res. 2006;166:839–48.PubMed
82.
Shi Y, Massagué J. Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell. 2003;113:685–700.PubMed
83.
Roberts AB, Russo A, Felici A, Flanders KC. Smad3: a key player in pathogenetic mechanisms dependent on TGF-beta. Ann N Y Acad Sci. 2003;995:1–10.PubMed
84.
Tomasek JJ, Gabbiani G, Hinz B, Chaponnier C, Brown RA. Myofibroblasts and mechano-regulation of connective tissue remodelling. Nat Rev Mol Cell Biol. 2002;3:349–63.PubMed
85.
Sheppard D. Transforming growth factor beta: a central modulator of pulmonary and airway inflammation and fibrosis. Proc Am Thorac Soc. 2006;3:413–7.PubMedCentralPubMed
86.
Sandler NG, Mentink-Kane MM, Cheever AW, Wynn TA. Global gene expression profiles during acute pathogen-induced pulmonary inflammation reveal divergent roles for Th1 and Th2 responses in tissue repair. J Immunol. 2003;171(7):3655–67.PubMed
87.
Martin M, Lefaix J, Delanian S. TGF-beta1 and radiation fibrosis: a master switch and a specific therapeutic target? Int J Radiat Oncol Biol Phys. 2000;47:277–90.PubMed
88.
Strup-Perrot C, Mathé D, Linard C, Violot D, Milliat F, François A, et al. Global gene expression profiles reveal an increase in mRNA levels of collagens, MMPs, and TIMPs in late radiation enteritis. Am J Physiol Gastrointest Liver Physiol. 2004;287:G875–85.PubMed
89.
Li C, Wilson PB, Levine E, Barber J, Stewart AL, Kumar S. TGF-beta1 levels in pre-treatment plasma identify breast cancer patients at risk of developing post-radiotherapy fibrosis. Int J Cancer. 1999;84:155–9.PubMed
90.
Bouquet F, Pal A, Pilones KA, Demaria S, Hann B, Akhurst RJ, et al. TGFβ1 inhibition increases the radiosensitivity of breast cancer cells in vitro and promotes tumor control by radiation in vivo. Clin Cancer Res. 2011;17:6754–65.PubMedCentralPubMed
91.
Lee CG, Homer RJ, Zhu Z, Lanone S, Wang X, Koteliansky V, et al. Interleukin-13 induces tissue fibrosis by selectively stimulating and activating transforming growth factor beta (1). J Exp Med. 2001;194:809–21.PubMedCentralPubMed
92.
Fichtner-Feigl S, Young CA, Kitani A, Geissler EK, Schlitt HJ, Strober W. IL-13 signaling via IL-13R alpha2 induces major downstream fibrogenic factors mediating fibrosis in chronic TNBS colitis. Gastroenterology. 2008;135:2003–13–2013.e1-7.
93.
Chung EJ, Hudak K, Horton JA, White A, Scroggins BT, Vaswani S, et al. Transforming growth factor alpha is a critical mediator of radiation lung injury. Radiat Res. 2014;182(3):350–62.PubMed
94.
Fichtner-Feigl S, Fuss IJ, Young CA, Watanabe T, Geissler EK, Schlitt HJ, et al. Induction of IL-13 triggers TGF-beta1-dependent tissue fibrosis in chronic 2,4,6-trinitrobenzene sulfonic acid colitis. J Immunol. 2007;178:5859–70.PubMed
95.
Webb DC, Mahalingam S, Cai Y, Matthaei KI, Donaldson DD, Foster PS. Antigen-specific production of interleukin (IL)-13 and IL-5 cooperate to mediate IL-4R alpha-independent airway hyper reactivity. Eur J Immunol. 2003;33:3377–85.PubMed
96.
Lanone S, Zheng T, Zhu Z, Liu W, Lee CG, Ma B, et al. Overlapping and enzyme-specific contributions of matrix metalloproteinases-9 and −12 inIL-13-induced inflammation and remodeling. J Clin Invest. 2002;110:463–74.PubMedCentralPubMed
97.
Liu W, Ding I, Chen K, Olschowka J, Xu J, Hu D, et al. Interleukin 1beta (IL1B) signaling is a critical component of radiation-induced skin fibrosis. Radiat Res. 2006;165:181–91.PubMed
98.
Lee JW, Zoumalan RA, Valenzuela CD, Nguyen PD, Tutela JP, Roman BR, et al. Regulators and mediators of radiation-induced fibrosis: Gene expression profiles and a rationale for Smad3 inhibition. Otolaryngol Head Neck Surg. 2010;143:525–30.PubMed
99.
Oikonomou N, Harokopos V, Zalevsky J, Valavanis C, Kotanidou A, Szymkowski DE, et al. Soluble TNF mediates the transition from pulmonary inflammation to fibrosis. PLoS One. 2006;1:e108.PubMedCentralPubMed
100.
Przybyszewska M, Miłoszewska J, Rzońca S, Trembacz H, Pyśniak K, Kotlarz A, et al. Soluble TNF-α receptor I encoded on plasmid vector and its application in experimental gene therapy of radiation-induced lung fibrosis. Arch Immunol Ther Exp (Warsz). 2011;59:315–26.
101.
Sullivan DE, Ferris M, Pociask D, Brody AR. Tumor necrosis factor-alpha induces transforming growth factor-beta1 expression in lung fibroblasts through the extracellular signal-regulated kinase pathway. Am J Respir Cell Mol Biol. 2005;32:342–9.PubMed
102.
Barcellos-Hoff MH, Park C, Wright EG. Radiation and the microenvironment tumorigenesis and therapy. Nat Rev Cancer. 2005;5:867–75.PubMed
103.
Takahashi H, Jin C, Rajabi H, Pitroda S, Alam M, Ahmad R, et al. MUC1-C activates the TAK1 inflammatory pathway in colon cancer. Oncogene. 2015; [Epub ahead of print].
104.
Rüegg C, Monnier Y, Kuonen F, Imaizumi N. Radiation-induced modifications of the tumor microenvironment promote metastasis. Bull Cancer. 2011;98:47–57.PubMed
105.
Qian LW, Mizumoto K, Urashima T, Nagai E, Maehara N, Sato N, et al. Radiation-induced increase in invasive potential of human pancreatic cancer cells and its blockade by a matrix metalloproteinase inhibitor, CGS27023. Clin Cancer Res. 2002;8:1223–7.PubMed
106.
Speake WJ, Dean RA, Kumar A, Morris TM, Scholefield JH, Watson SA. Radiation induced MMP expression from rectal cancer is short lived but contributes to in vitro invasion. Eur J Surg Oncol. 2005;31:869–74.PubMed
107.
Wang JL, Sun Y, Wu S. Gamma-irradiation induces matrix metalloproteinase II expression in a p53-dependent manner. Mol Carcinog. 2000;27:252–8.PubMed
108.
Zhai GG, Malhotra R, Delaney M, Latham D, Nestler U, Zhang M, et al. Radiation enhances the invasive potential of primary glioblastoma cells via activation of the Rho signaling pathway. J Neurooncol. 2006;76:227–37.PubMed
109.
Pasi F, Facoetti A, Nano R. IL-8 and IL-6 bystander signalling in human glioblastoma cells exposed to gamma radiation. Anticancer Res. 2010;30:2769–72.PubMed
110.
Qazi BS, Tang K, Qazi A. Recent advances in underlying pathologies provide insight into interleukin-8 expression-mediated inflammation and angiogenesis. Int J Inflam. 2011;2011:908468.PubMedCentralPubMed
111.
Hou Y, Ryu CH, Jun JA, Kim SM, Jeong CH, Jeun SS. IL-8 enhances angiogenesis of human bone marrow mesenchymal stem cells by increasing vascular endothelial growth factor. Cell Biol Int. 2014;38:1050–9.PubMed
112.
Karashima T, Sweeney P, Kamat A, Huang S, Kim SJ, Bar-Eli M, et al. Nuclear factor-kappaB mediates angiogenesis and metastasis of human bladder cancer through the regulation of interleukin-8. Clin Cancer Res. 2003;9:2786–97.PubMed
113.
De Larco JE, Wuertz BR, Rosner KA, Erickson SA, Gamache DE, Manivel JC, et al. A potential role for interleukin-8 in the metastatic phenotype of breast carcinoma cells. Am J Pathol. 2001;158:639–46.PubMedCentralPubMed
114.
Singh RK, Gutman M, Reich R, Bar-Eli M. Ultraviolet B irradiation promotes tumorigenic and metastatic properties in primary cutaneous melanoma via induction of interleukin 8. Cancer Res. 1995;55:3669–74.PubMed
115.
Meeren AV, Bertho JM, Vandamme M, Gaugler MH. Ionizing radiation enhances IL-6 and IL-8 production by human endothelial cells. Mediators Inflamm. 1997;6:185–93.PubMedCentralPubMed
116.
Yang Z, Guo L, Liu D, Sun L, Chen H, Deng Q, et al. Acquisition of resistance to trastuzumab in gastric cancer cells is associated with activation of IL-6/STAT3/Jagged-1/Notch positive feedback loop. Oncotarget. 2014; [Epub ahead of print].
117.
118.
Culig Z, Puhr M. Interleukin-6: a multifunctional targetable cytokine in human prostate cancer. Mol Cell Endocrinol. 2012;360:52–8.PubMedCentralPubMed
119.
Guo Y, Xu F, Lu T, Duan Z, Zhang Z. Interleukin-6 signaling pathway intargeted therapy for cancer. Cancer Treat Rev. 2012;38:904–10.PubMed
120.
Salgado R, Junius S, Benoy I, Van Dam P, Vermeulen P, Van Marck E, et al. Circulating interleukin-6 predicts survival in patients with metastatic breast cancer. Int J Cancer. 2003;103:642–6.PubMed
121.
Dethlefsen C, Højfeldt G, Hojman P. The role of intratumoral and systemic IL-6 in breast cancer. Breast Cancer Res Treat. 2013;138:657–64.PubMed
122.
Chang Q, Bournazou E, Sansone P, Berishaj M, Gao SP, Daly L, et al. The IL-6/JAK/Stat3 feed-forwardloop drives tumorigenesis and metastasis. Neoplasia. 2013;15:848–62.PubMedCentralPubMed
123.
Sepah SC, Bower JE. Positive affect and inflammation during radiation treatment for breast and prostate cancer. Brain Behav Immun. 2009;23:1068–72.PubMedCentralPubMed
124.
Paquette B, Therriault H, Wagner JR. Role of interleukin-1β in radiation-enhancement of MDA-MB-231 breast cancer cell invasion. Radiat Res. 2013;180:292–8.PubMed
125.
Katsuno Y, Lamouille S, Derynck R. TGF-β signaling and epithelial-mesenchymal transition in cancer progression. Curr Opin Oncol. 2013;25:76–84.PubMed
126.
Andarawewa KL, Erickson AC, Chou WS, Costes SV, Gascard P, Mott JD, et al. Ionizing radiation predisposes nonmalignant human mammary epithelial cells to undergo transforming growth factor beta induced epithelial to mesenchymal transition. Cancer Res. 2007;67:8662–70.PubMed
127.
Wang M, Hada M, Huff J, Pluth JM, Anderson J, O'Neill P, et al. Heavy ions can enhance TGFβ mediated epithelial to mesenchymal transition. J Radiat Res. 2012;53:51–7.PubMed
128.
Buck E, Eyzaguirre A, Barr S, Thompson S, Sennello R, Young D, et al. Loss of homotypic cell adhesion byepithelial-mesenchymal transition or mutation limits sensitivity to epidermal growth factor receptor inhibition. Mol Cancer Ther. 2007;6:532–41.PubMed
129.
Minafra L, Bravatà V, Forte GI, Cammarata FP, Gilardi MC, Messa C. Gene expression profiling of epithelial-mesenchymal transition in primary breast cancer cell culture. Anticancer Res. 2014;34:2173–83.PubMed
130.
Minafra L, Norata R, Bravatà V, Viola M, Lupo C, Gelfi C, et al. Unmasking epithelial-mesenchymal transition in a breast cancer primary culture: a study report. BMC Res Notes. 2012;5:343.PubMedCentralPubMed
131.
Zhou YC, Liu JY, Li J, Zhang J, Xu YQ, Zhang HW, et al. Ionizing radiation promotes migration and invasion of cancer cells through transforming growth factor-beta-mediated epithelial-mesenchymal transition. Int J Radiat Oncol Biol Phys. 2011;81:1530–7.PubMed
132.
Vacchelli E, Vitale I, Tartour E, Eggermont A, Sautès-Fridman C, Galon J, et al. Trial watch: anticancer radioimmunotherapy. Oncoimmunology. 2013;2:e25595.PubMedCentralPubMed
133.
Vanneman M, Dranoff G. Combining immunotherapy and targeted therapies in cancer treatment. Nat Rev Cancer. 2012;12:237–51.PubMedCentralPubMed
134.
Weiss JM, Subleski JJ, Wigginton JM, Wiltrout RH. Immunotherapy of cancer by IL-12-based cytokine combinations. Expert Opin Biol Ther. 2007;7:1705–21.PubMedCentralPubMed
135.
Formenti SC, Demaria S. Combining radiotherapy and cancer immunotherapy: a paradigm shift. J Natl Cancer Inst. 2013;105:256–65.PubMedCentralPubMed
136.
Begg AC, Stewart FA, Vens C. Strategies to improve radiotherapy with targeted drugs. Nat Rev Cancer. 2011;11:239–53.PubMed
137.
Magné N, Toillon RA, Bottero V, Didelot C, Houtte PV, Gérard JP, et al. NF-kappaB modulation and ionizing radiation: mechanisms and future directions for cancer treatment. Cancer Lett. 2006;231:158–68.PubMed
138.
Pajonk F, Pajonk K, McBride WH. Apoptosis and radiosensitization of Hodgkin cells by proteasome inhibition. Int J Radiat Oncol Biol Phys. 2000;47:1025–32.PubMed
139.
Raju U, Gumin GJ, Tofilon PJ. NF kappa B activity and target gene expression in the rat brain after one and two exposures to ionizing radiation. Radiat Oncol Investig. 1999;7:145–52.PubMed
140.
Yang CR, Wilson-Van Patten C, Planchon SM, Wuerzberger-Davis SM, Davis TW, Cuthill S, et al. Coordinate modulation of Sp1, NF-kappa B, andp53 in confluent human malignant melanoma cells after ionizing radiation. FASEB J. 2000;14:379–90.PubMed
141.
Yamagishi N, Miyakoshi J, Takebe H. Enhanced radiosensitivity by inhibition of nuclear factor kappa B activation in human malignant glioma cells. Int J Radiat Biol. 1997;72:157–62.PubMed
142.
Deorukhkar A, Krishnan S, Sethi G, Aggarwal BB. Back to basics: how natural products can provide the basis for new therapeutics. Expert Opin Investig Drugs. 2007;16:1753–73.PubMed
143.
Singh S, Khar A. Biological effects of curcumin and its role in cancer chemoprevention and therapy. Anticancer Agents Med Chem. 2006;6:259–70.PubMed
144.
Hallahan DE, Virudachalam S, Kuchibhotla J, Kufe DW, Weichselbaum RR. Membrane-derived second messenger regulates x-ray-mediated tumor necrosis factor alpha gene induction. Proc Natl Acad Sci U S A. 1994;91:4897–901.PubMedCentralPubMed
145.
Linard C, Marquette C, Mathieu J, Pennequin A, Clarençon D, Mathé D. Acute induction of inflammatory cytokine expression after gamma-irradiation in the rat: effect of an NF-kappaB inhibitor. Int J Radiat Oncol Biol Phys. 2004;58:427–34.PubMed
146.
Turini ME, DuBois RN. Cyclooxygenase-2: a therapeutic target. Annu Rev Med. 2002;53:35–57.PubMed
147.
Fitz Gerald GA. COX-2 and beyond: approaches to prostaglandin inhibition inhuman disease. Nat Rev Drug Discov. 2003;2:879–90.
148.
Howe LR. Inflammation and breast cancer. Cyclooxygenase/prostaglandin signaling and breast cancer. Breast Cancer Res. 2007;9:210.PubMedCentralPubMed
149.
Aggarwal BB, Gehlot P. Inflammation and cancer: how friendly is the relationship for cancer patients? Curr Opin Pharmacol. 2009;9:351–69.PubMedCentralPubMed
150.
Davis TW, Hunter N, Trifan OC, Milas L, Masferrer JL. COX-2 inhibitors as radiosensitizing agents for cancer therapy. Am J Clin Oncol. 2003;26:S58–61.PubMed
151.
Dittmann KH, Mayer C, Ohneseit PA, Raju U, Andratschke NH, Milas L, et al. Celecoxib induced tumor cell radiosensitization by inhibiting radiation induced nuclear EGFR transport and DNA-repair: a COX-2 independent mechanism. IntJ RadiatOncolBiol Phys. 2008;70:203–12.
152.
Grandis JR, Drenning SD, Zeng Q, Watkins SC, Melhem MF, Endo S, et al. Constitutive activation of Stat3 signaling abrogates apoptosis in squamous cell carcinogenesis in vivo. Proc Natl Acad Sci U S A. 2000;97:4227–32.PubMedCentralPubMed
153.
Konnikova L, Kotecki M, Kruger MM, Cochran BH. Knockdown of STAT3 expression by RNAi induces apoptosis in astrocytoma cells. BMC Cancer. 2003;3:23.PubMedCentralPubMed
154.
Li WC, Ye SL, Sun RX, Liu YK, Tang ZY, Kim Y, et al. Inhibition of growth and metastasis of human hepatocellular carcinoma by antisense oligonucleotide targeting signal transducer and activator of transcription 3. Clin Cancer Res. 2006;12:7140–8.PubMed
155.
Zhang X, Zhang J, Wang L, Wei H, Tian Z. Therapeutic effects of STAT3 decoy oligo deoxynucleotide on human lung cancer in xenograft mice. BMC Cancer. 2007;7:149.PubMedCentralPubMed
156.
Bonner JA, Trummell HQ, Willey CD, Plants BA, Raisch KP. Inhibition of STAT-3 results in radiosensitization of human squamous cell carcinoma. Radiother Oncol. 2009;92:339–44.PubMed
157.
Zhan JF, Chen LH, Yuan YW, Xie GZ, Sun AM, Liu Y, et al. STAT1 promotes radioresistance of CD44 (+)/CD24 (−/low) cells in breast cancer. Exp Biol Med (Maywood). 2011;236:418–22.
158.
Hosseinimehr SJ. The use of angiotensin II receptor antagonists to increase the efficacy of radiotherapy in cancer treatment. Future Oncol. 2014;10(15):2381–90.PubMed
159.
Salem K, Brown CO, Schibler J, Goel A. Combination chemotherapy increases cytotoxicity of multiple myeloma cells by modification of nuclear factor (NF)-κB activity. Exp Hematol. 2013;41:209–18.PubMedCentralPubMed
160.
Levy A, Chargari C, Cheminant M, Simon N, Bourgier C, Deutsch E. Radiation therapy and immunotherapy: implications for a combined cancer treatment. Crit Rev Oncol Hematol. 2013;85:278–87.PubMed
161.
Orecchia R, Leonardo MC. Intraoperative radiation therapy: is it a standard now? Breast. 2011;20:S111–5.PubMed
162.
Wallner P, Arthur D, Bartelink H, Connolly J, Edmundson G, Giuliano A, et al. Workshop Participants. Workshop on partial breast irradiation: state of the art and the science. J Natl Cancer Inst. 2004;96:175–84.PubMed
163.
Smith BD, Arthur DW, Buchholz TA, Haffty BG, Hahn CA, Hardenbergh PH, et al. Accelerated partial breast irradiation consensus statement from the American Society for Radiation Oncology (ASTRO). Int J Radiat Oncol Biol Phys. 2009;74:987–1001.PubMed
164.
Veronesi U, Orecchia R, Luini A, Galimberti V, Zurrida S, Intra M, et al. Intraoperative radiotherapy during breast conserving surgery: a study on 1,822 cases treated with electrons. Breast Cancer Res Treat. 2010;124:141–51.PubMed
165.
Veronesi U, Orecchia R, Maisonneuve P, Viale G, Rotmensz N, Sangalli C, et al. Intraoperative radiotherapy versus external radiotherapy for early breast cancer (ELIOT): a randomised controlled equivalence trial. Lancet Oncol. 2013;14:1269–77.PubMed
166.
Herskind C, Wenz F. Radiobiological aspects of intraoperative tumour-bed irradiation with low-energy X-rays (LEX-IORT). Transl Cancer Res. 2014;3:3–17.
167.
Kobari M, Egawa S, Shibuya K, Sunamura M, Saitoh K, Matsuno S. Effect of intraportal adoptive immunotherapy on liver metastases after resection of pancreatic cancer. Br J Surg. 2000;87(1):43–8.PubMed
Metadata
Title
Portrait of inflammatory response to ionizing radiation treatment
Authors
Federica Maria Di Maggio
Luigi Minafra
Giusi Irma Forte
Francesco Paolo Cammarata
Domenico Lio
Cristina Messa
Maria Carla Gilardi
Valentina Bravatà
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Journal of Inflammation / Issue 1/2015
Electronic ISSN: 1476-9255
DOI
https://doi.org/10.1186/s12950-015-0058-3

Other articles of this Issue 1/2015

Journal of Inflammation 1/2015 Go to the issue

Research

Interleukin-18 expression increases in response to neurovascular damage following soman-induced status epilepticus in rats

Research

Effects of exercise on brain and peripheral inflammatory biomarkers induced by total sleep deprivation in rats

Research

Antioxidant polyphenol-rich extracts from the medicinal plants Antirhea borbonica, Doratoxylon apetalum and Gouania mauritiana protect 3T3-L1 preadipocytes against H2O2, TNFα and LPS inflammatory mediators by regulating the expression of superoxide dismutase and NF-κB genes

Research

Human parainfluenza virus type 3 (HPIV3) induces production of IFNγ and RANTES in human nasal epithelial cells (HNECs)

Research

Nitric oxide secretion in human conjunctival fibroblasts is inhibited by alpha linolenic acid

Research

The protective effects of chronic intermittent hypobaric hypoxia pretreatment against collagen-induced arthritis in rats

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits