Ionizing radiation, ion transports, and radioresistance of cancer cells

Frontiers in Physiology

Volumn 4 AUG, Issue , 2013, Pages

  Huber, Stephan M ^a   Butz, Lena ^a   Stegen, Benjamin ^a   Klumpp, Dominik ^a   Braun, Norbert ^a   Ruth, Peter ^a   Eckert, Franziska ^a  

^a UNIVERSITY OF TÜBINGEN   (Germany)

Author keywords

Cell cycle; DNA repair; Ion channels; Radiation therapy

Indexed keywords

ADENOSINE TRIPHOSPHATE; ANTINEOPLASTIC AGENT; CALCIUM; CELL DNA; DOUBLE STRANDED DNA; GLUCOSE; ION CHANNEL; REACTIVE OXYGEN METABOLITE;

ADVANCED CANCER; ALPHA RADIATION; BETA RADIATION; CANCER ADJUVANT THERAPY; CANCER CELL; CANCER CHEMOTHERAPY; CANCER RADIOTHERAPY; CANCER RESISTANCE; CANCER STEM CELL; CANCER SURGERY; CELL CYCLE REGULATION; CELL DEATH; CELL HYPOXIA; CELL MEMBRANE TRANSPORT; CELL NUCLEUS; CELL STRESS; CELL SURVIVAL; CHROMATIN; DNA REPAIR; HEAD AND NECK CANCER; HEAD AND NECK SURGERY; HUMAN; ION TRANSPORT; IONIZING RADIATION; ISCHEMIC PRECONDITIONING; MALIGNANT NEOPLASTIC DISEASE; MOTOR PERFORMANCE; NONHUMAN; OXIDATIVE PHOSPHORYLATION UNCOUPLING; PREOPERATIVE RADIOTHERAPY; PROSTATE CANCER; PROSTATE SURGERY; PROTEIN MODIFICATION; RADIATION DOSE DISTRIBUTION; RADIATION DOSE FRACTIONATION; RADIOSENSITIVITY; RECTUM CANCER; RECTUM SURGERY; REOXYGENATION; REVIEW; SARCOMA; SEWAGE TREATMENT; SMALL CELL CARCINOMA;

EID: 84884583548     PISSN: None     EISSN: 1664042X     Source Type: Journal    
DOI: 10.3389/fphys.2013.00212     Document Type: Review

References (171)

1. Anderson, E. J., Yamazaki, H., and Neufer, P. D. (2007). Induction of endogenous uncoupling protein 3 suppresses mitochondrial oxidant emission during fatty acid-supported respiration. J. Biol. Chem. 282, 31257-31266. doi: 10.1074/jbc.M706129200
2. Arcangeli, A. (2011). Ion channels and transporters in cancer. 3. Ion channels in the tumor cell-microenvironment cross talk. Am. J. Physiol. Cell Physiol. 301, C762-C771.
3. Asuthkar, S., Nalla, A. K., Gondi, C. S., Dinh, D. H., Gujrati, M., Mohanam, S., et al. (2011). Gadd45a sensitizes medulloblastoma cells to irradiation and suppresses MMP-9-mediated EMT. Neuro Oncol. 13, 1059-1073. doi: 10.1093/neuonc/nor109
4. Auperin, A., Arriagada, R., Pignon, J. P., Le Pechoux, C., Gregor, A., Stephens, R. J., et al. (1999). Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. prophylactic cranial irradiation overview collaborative group. N. Engl. J. Med. 341, 476-484. doi: 10.1056/NEJM199908123410703
5. Ayyasamy, V., Owens, K. M., Desouki, M. M., Liang, P., Bakin, A., Thangaraj, K., et al. (2011). Cellular model of Warburg effect identifies tumor promoting function of UCP2 in breast cancer and its suppression by genipin. PLoS ONE 6:e24792. doi: 10.1371/journal.pone.0024792
6. Badiga, A. V., Chetty, C., Kesanakurti, D., Are, D., Gujrati, M., Klopfenstein, J. D., et al. (2011). MMP-2 siRNA inhibits radiation-enhanced invasiveness in glioma cells. PLoS ONE 6:e20614. doi: 10.1371/journal.pone.0020614
7. Baffy, G. (2010). Uncoupling protein-2 and cancer. Mitochondrion 10, 243-252. doi: 10.1016/j.mito.2009.12.143
8. Baffy, G., Derdak, Z., and Robson, S. C. (2011). Mitochondrial recoupling: a novel therapeutic strategy for cancer. Br. J. Cancer 105, 469-474.
9. Barendsen, G. W. (1982). Dose fractionation, dose rate and iso-effect relationships for normal tissue responses. Int. J. Radiat. Oncol. Biol. Phys. 8, 1981-1997. doi: 10.1016/0360-301690459-X
10. Bernier, J., Hall, E. J., and Giaccia, A. (2004). Radiation oncology: a century of achievements. Nat. Rev. Cancer 4, 737-747. doi: 10.1038/nrc1451
11. Canazza, A., Calatozzolo, C., Fumagalli, L., Bergantin, A., Ghielmetti, F., Fariselli, L., et al. (2011). Increased migration of a human glioma cell line after in vitro CyberKnife irradiation. Cancer Biol. Ther. 12, 629-633. doi: 10.4161/cbt.12.7.16862
12. Caraceni, P., Ryu, H. S., Van Thiel, D. H., and Borle, A. B. (1995). Source of oxygen free radicals produced by rat hepatocytes during postanoxic reoxygenation. Biochim. Biophys. Acta 1268, 249-254. doi: 10.1016/0167-488900077-6
13. Casneuf, V. F., Fonteyne, P., Van Damme, N., Demetter, P., Pauwels, P., De Hemptinne, B., et al. (2008). Expression of SGLT1, Bcl-2 and p53 in primary pancreatic cancer related to survival. Cancer Invest. 26, 852-859. doi: 10.1080/07357900801956363
14. Catacuzzeno, L., Aiello, F., Fioretti, B., Sforna, L., Castigli, E., Ruggieri, P., et al. (2010). Serum-activated K and Cl currents underlay U87-MG glioblastoma cell migration. J. Cell Physiol. 226, 1926-1933. doi: 10.1002/jcp.22523
15. Chakraborty, M., Abrams, S. I., Coleman, C. N., Camphausen, K., Schlom, J., and Hodge, J. W. (2004). External beam radiation of tumors alters phenotype of tumor cells to render them susceptible to vaccine-mediated T-cell killing. Cancer Res. 64, 4328-4337. doi: 10.1158/0008-5472.CAN-04-0073
16. Crompton, M. (1999). The mitochondrial permeability transition pore and its role in cell death. Biochem. J. 341, 233-249.
17. Cuddapah, V. A., and Sontheimer, H. (2010). Molecular interaction and functional regulation of ClC-3 by Ca2+/calmodulin-dependent protein kinase II (CaMKII) in human malignant glioma. J. Biol. Chem. 285, 11188-11196. doi: 10.1074/jbc.M109.097675
18. Cullis, P. M., Jones, G. D. D., Lea, J., Symons, M. C. R., and Sweeney, M. (1987). The effects of ionizing radiation on deoxyribonucleic acid. Part 5. The role of thiols in chemical repair. J. Chem. Soc., Perkin Trans. 2, 1907-1914. doi: 10.1039/p29870001907
19. Dale, R. G. (1985). The application of the linear-quadratic dose-effect equation to fractionated and protracted radiotherapy. Br. J. Radiol. 58, 515-528. doi: 10.1259/0007-1285-58-690-515
20. Dalla Pozza, E., Fiorini, C., Dando, I., Menegazzi, M., Sgarbossa, A., Costanzo, C., et al. (2012). Role of mitochondrial uncoupling protein 2 in cancer cell resistance to gemcitabine. Biochim. Biophys. Acta 1823, 1856-1863. doi: 10.1016/j.bbamcr.2012.06.007
21. Dando, I., Fiorini, C., Pozza, E. D., Padroni, C., Costanzo, C., Palmieri, M., et al. (2013). UCP2 inhibition triggers ROS-dependent nuclear translocation of GAPDH and autophagic cell death in pancreatic adenocarcinoma cells. Biochim. Biophys. Acta 1833, 672-679. doi: 10.1016/j.bbamcr.2012.10.028
22. Darby, S., Mcgale, P., Correa, C., Taylor, C., Arriagada, R., Clarke, M., et al. (2011). Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10, 801 women in 17 randomised trials. Lancet 378, 1707-1716. doi: 10.1016/S0140-673661629-2
23. Demaria, S., and Formenti, S. C. (2012). Radiation as an immunological adjuvant: current evidence on dose and fractionation. Front. Oncol. 2:153. doi: 10.3389/fonc.2012.00153
24. Deng, S., Yang, Y., Han, Y., Li, X., Wang, X., Li, X., et al. (2012). UCP2 inhibits ROS-mediated apoptosis in A549 under hypoxic conditions. PLoS ONE 7:e30714. doi: 10.1371/journal.pone.0030714
25. Derdak, Z., Mark, N. M., Beldi, G., Robson, S. C., Wands, J. R., and Baffy, G. (2008). The mitochondrial uncoupling protein-2 promotes chemoresistance in cancer cells. Cancer Res. 68, 2813-2819. doi: 10.1158/0008-5472.CAN-08-0053
26. Dittmann, K., Mayer, C., Kehlbach, R., Rothmund, M. C., and Peter Rodemann, H. (2009). Radiation-induced lipid peroxidation activates src kinase and triggers nuclear EGFR transport. Radiother. Oncol. 92, 379-382. doi: 10.1016/j.radonc.2009.06.003
27. Dittmann, K., Mayer, C., Rodemann, H. P., and Huber, S. M. (2013). EGFR cooperates with glucose transporter SGLT1 to enable chromatin remodeling in response to ionizing radiation. Radiother. Oncol. 107, 247-251. doi: 10.1016/j.radonc.2013.03.016
28. Dorn, G. W. 2nd. (2013). Molecular mechanisms that differentiate apoptosis from programmed necrosis. Toxicol. Pathol. 41, 227-234. doi: 10.1177/0192623312466961
29. Echtay, K. S., Roussel, D., St-Pierre, J., Jekabsons, M. B., Cadenas, S., Stuart, J. A., et al. (2002). Superoxide activates mitochondrial uncoupling proteins. Nature 415, 96-99. doi: 10.1038/415096a
30. Eckert, F., Alloussi, S., Paulsen, F., Bamberg, M., Zips, D., Spillner, P., et al. (2013). Prospective evaluation of a hydrogel spacer for rectal separation in dose-escalated intensity-modulated radiotherapy for clinically localized prostate cancer. BMC Cancer 13:27. doi: 10.1186/1471-2407-13-27
31. Eckert, F., Fehm, T., Bamberg, M., and Muller, A. C. (2010a). Small cell carcinoma of vulva: curative multimodal treatment in face of resistance to initial standard chemotherapy. Strahlenther. Onkol. 186, 521-524.
32. Eckert, F., Matuschek, C., Mueller, A. C., Weinmann, M., Hartmann, J. T., Belka, C., et al. (2010b). Definitive radiotherapy and single-agent radiosensitizing ifosfamide in patients with localized, irresectable soft tissue sarcoma: a retrospective analysis. Radiat. Oncol. 5, 55.
33. Eckert, F., Gani, C., Bamberg, M., and Muller, A. C. (2012). Cerebral metastases in extrapulmonary cell carcinoma: implications for the use of prophylactic cranial irradiation. Strahlenther. Onkol. 188, 478-483. doi: 10.1007/s00066-012-0084-5
34. Ernest, N. J., Weaver, A. K., Van Duyn, L. B., and Sontheimer, H. W. (2005). Relative contribution of chloride channels and transporters to regulatory volume decrease in human glioma cells. Am. J. Physiol. Cell Physiol. 288, C1451-1460. doi: 10.1152/ajpcell.00503.2004
35. Fink, B. D., Hong, Y. S., Mathahs, M. M., Scholz, T. D., Dillon, J. S., and Sivitz, W. I. (2002). UCP2-dependent proton leak in isolated mammalian mitochondria. J. Biol. Chem. 277, 3918-3925. doi: 10.1074/jbc.M107955200
36. Finkelstein, S. E., Iclozan, C., Bui, M. M., Cotter, M. J., Ramakrishnan, R., Ahmed, J., et al. (2012). Combination of external beam radiotherapy (EBRT) with intratumoral injection of dendritic cells as neo-adjuvant treatment of high-risk soft tissue sarcoma patients. Int. J. Radiat. Oncol. Biol. Phys. 82, 924-932. doi: 10.1016/j.ijrobp.2010.12.068
37. Formenti, S. C., and Demaria, S. (2013). Combining radiotherapy and cancer immunotherapy: a paradigm shift. J. Natl. Cancer Inst. 105, 256-265. doi: 10.1093/jnci/djs629
38. Fuessel, S., Meye, A., Schmitz, M., Zastrow, S., Linne, C., Richter, K., et al. (2006). Vaccination of hormone-refractory prostate cancer patients with peptide cocktail-loaded dendritic cells: results of a phase I clinical trial. Prostate 66, 811-821. doi: 10.1002/pros.20404
39. Fyles, A., Milosevic, M., Hedley, D., Pintilie, M., Levin, W., Manchul, L., et al. (2002). Tumor hypoxia has independent predictor impact only in patients with node-negative cervix cancer. J. Clin. Oncol. 20, 680-687. doi: 10.1200/JCO.20.3.680
40. Fyles, A., Milosevic, M., Pintilie, M., Syed, A., Levin, W., Manchul, L., et al. (2006). Long-term performance of interstial fluid pressure and hypoxia as prognostic factors in cervix cancer. Radiother. Oncol. 80, 132-137. doi: 10.1016/j.radonc.2006.07.014
41. Ganapathy, V., Thangaraju, M., and Prasad, P. D. (2009). Nutrient transporters in cancer: relevance to Warburg hypothesis and beyond. Pharmacol. Ther. 121, 29-40. doi: 10.1016/j.pharmthera.2008.09.005
42. Garcia-Martinez, C., Sibille, B., Solanes, G., Darimont, C., Mace, K., Villarroya, F., et al. (2001). Overexpression of UCP3 in cultured human muscle lowers mitochondrial membrane potential, raises ATP/ADP ratio, and favors fatty acid vs. glucose oxidation. FASEB J. 15, 2033-2035.
43. German-Cancer-Aid. (2013a). Homepage. Available online at: http://www.krebshilfe.de/krebszahlen.html
44. German-Cancer-Aid. (2013b). Information Booklet. Available online at: http://www.krebshilfe.de/fileadmin/Inhalte/Downloads/PDFs/Blaue_Ratgeber/053_strahlen.pdf.
45. Glenny, A. M., Furness, S., Worthington, H. V., Conway, D. I., Oliver, R., Clarkson, J. E., et al. (2010). Interventions for the treatment of oral cavity and oropharyngeal cancer: radiotherapy. Cochrane Database Syst. Rev. CD006387. doi: 10.1002/14651858.CD006387.pub2
46. Gomez-Ospina, N., Tsuruta, F., Barreto-Chang, O., Hu, L., and Dolmetsch, R. (2006). The C terminus of the L-type voltage-gated calcium channel Ca(V)1.2 encodes a transcription factor. Cell 127, 591-606. doi: 10.1016/j.cell.2006.10.017
47. Gonidi, M., Athanassiadou, A. M., Patsouris, E., Tsipis, A., Dimopoulos, S., Kyriakidou, V., et al. (2011). Mitochondrial UCP4 and bcl-2 expression in imprints of breast carcinomas: relationship with DNA ploidy and classical prognostic factors. Pathol. Res. Pract. 207, 377-382. doi: 10.1016/j.prp.2011.03.007
48. Grills, I. S., Hope, A. J., Guckenberger, M., Kestin, L. L., Werner-Wasik, M., Yan, D., et al. (2012). A collaborative analysis of stereotactic lung radiotherapy outcomes for early-stage non-small-cell lung cancer using daily online cone-beam computed tomography image-guided radiotherapy. J. Thorac. Oncol. 7, 1382-1393. doi: 10.1097/JTO.0b013e318260e00d
49. Gross, G. J., and Peart, J. N. (2003). KATP channels and myocardial preconditioning: an update. Am. J. Physiol. Heart Circ. Physiol. 285, H921-H930.
50. Grosso, J. F., and Jure-Kunkel, M. N. (2013). CTLA-4 blockade in tumor models: an overview of preclinical and translational research. Cancer Immun. 13, 5.
51. Haas, B. R., Cuddapah, V. A., Watkins, S., Rohn, K. J., Dy, T. E., and Sontheimer, H. (2011). With-No-Lysine Kinase 3 (WNK3) stimulates glioma invasion by regulating cell volume. Am. J. Physiol. Cell Physiol. 301, C1150-C1160. doi: 10.1152/ajpcell.00203.2011
52. Haas, B. R., and Sontheimer, H. (2010). Inhibition of the sodium-potassium-chloride cotransporter isoform-1 reduces glioma invasion. Cancer Res. 70, 5597-5606. doi: 10.1158/0008-5472.CAN-09-4666
53. Hanahan, D., and Weinberg, R. A. (2011). Hallmarks of cancer: the next generation. Cell 144, 646-674. doi: 10.1016/j.cell.2011.02.013
54. Harada, H. (2011). How can we overcome tumor hypoxia in radiation therapy. J. Radiat. Res. 52, 545-556.
55. Harper, M. E., Antoniou, A., Villalobos-Menuey, E., Russo, A., Trauger, R., Vendemelio, M., et al. (2002). Characterization of a novel metabolic strategy used by drug-resistant tumor cells. FASEB J. 16, 1550-1557. doi: 10.1096/fj.02-0541com
56. Hartung, F., Stuhmer, W., and Pardo, L. A. (2011). Tumor cell-selective apoptosis induction through targeting of K(V)10.1 via bifunctional TRAIL antibody. Mol. Cancer 10, 109.
57. Hatzikirou, H., Basanta, D., Simon, M., Schaller, K., and Deutsch, A. (2012). 'Go or Grow': the key to the emergence of invasion in tumour progression. Math. Med. Biol. 29, 49-65. doi: 10.1093/imammb/dqq011
58. Heise, N., Palme, D., Misovic, M., Koka, S., Rudner, J., Lang, F., et al. (2010). Non-selective cation channel-mediated Ca2+-entry and activation of Ca2+/calmodulin-dependent kinase II contribute to G2/M cell cycle arrest and survival of irradiated leukemia cells. Cell Physiol. Biochem. 26, 597-608. doi: 10.1159/000322327
59. Helmke, B. M., Reisser, C., Idzko, M., Dyckhoff, G., and Herold-Mende, C. (2004). Expression of SGLT-1 in preneoplastic and neoplastic lesions of the head and neck. Oral Oncol. 40, 28-35. doi: 10.1016/S1368-837500129-5
60. Hockaday, D. C., Shen, S., Fiveash, J., Raubitschek, A., Colcher, D., Liu, A., et al. (2005). Imaging glioma extent with 131I-TM-601. J. Nucl. Med. 46, 580-586.
61. Horimoto, M., Resnick, M. B., Konkin, T. A., Routhier, J., Wands, J. R., and Baffy, G. (2004). Expression of uncoupling protein-2 in human colon cancer. Clin. Cancer Res. 10, 6203-6207. doi: 10.1158/1078-0432.CCR-04-0419
62. Horiot, J. C., Le Fur, R., N'guyen, T., Chenal, C., Schraub, S., Alfonsi, S., et al. (1992). Hyperfractionation versus conventional fractionation in oropharyngeal carcinoma: final analysis of a randomized trial of the EORTC cooperative group of radiotherapy. Radiother. Oncol. 25, 231-241. doi: 10.1016/0167-814090242-M
63. Huber, S. M. (2013). Oncochannels. Cell Calcium. 53, 241-255. doi: 10.1016/j.ceca.2013.01.001
64. Huber, S. M., Misovic, M., Mayer, C., Rodemann, H. P., and Dittmann, K. (2012). EGFR-mediated stimulation of sodium/glucose cotransport promotes survival of irradiated human A549 lung adenocarcinoma cells. Radiother. Oncol. 103, 373-379. doi: 10.1016/j.radonc.2012.03.008
65. Ishikawa, N., Oguri, T., Isobe, T., Fujitaka, K., and Kohno, N. (2001). SGLT gene expression in primary lung cancers and their metastatic lesions. Jpn. J. Cancer Res. 92, 874-879. doi: 10.1111/j.1349-7006.2001.tb01175.x
66. Johnson, J., Nowicki, M. O., Lee, C. H., Chiocca, E. A., Viapiano, M. S., Lawler, S. E., et al. (2009). Quantitative analysis of complex glioma cell migration on electrospun polycaprolactone using time-lapse microscopy. Tissue Eng. Part C Methods 15, 531-540. doi: 10.1089/ten.tec.2008.0486
67. Jones, B., Dale, R. G., and Gaya, A. M. (2006). Linear quadratic modeling of increased late normal-tissue effects in special clinical situations. Int. J. Radiat. Oncol. Biol. Phys. 64, 948-953. doi: 10.1016/j.ijrobp.2005.10.016
68. Jung, J. W., Hwang, S. Y., Hwang, J. S., Oh, E. S., Park, S., and Han, I. O. (2007). Ionising radiation induces changes associated with epithelial-mesenchymal transdifferentiation and increased cell motility of A549 lung epithelial cells. Eur. J. Cancer 43, 1214-1224. doi: 10.1016/j.ejca.2007.01.034
69. Kadenbach, B. (2003). Intrinsic and extrinsic uncoupling of oxidative phosphorylation. Biochim. Biophys. Acta 1604, 77-94. doi: 10.1016/S0005-272800027-6
70. Kargiotis, O., Chetty, C., Gogineni, V., Gondi, C. S., Pulukuri, S. M., Kyritsis, A. P., et al. (2008). uPA/uPAR downregulation inhibits radiation-induced migration, invasion and angiogenesis in IOMM-Lee meningioma cells and decreases tumor growth in vivo. Int. J. Oncol. 33, 937-947.
71. Kil, W. J., Tofilon, P. J., and Camphausen, K. (2012). Post-radiation increase in VEGF enhances glioma cell motility in vitro. Radiat. Oncol. 7, 25. doi: 10.1186/1748-717X-7-25
72. Kim, J. S., Chang, J. W., Yun, H. S., Yang, K. M., Hong, E. H., Kim, D. H., et al. (2010). Chloride intracellular channel 1 identified using proteomic analysis plays an important role in the radiosensitivity of HEp-2 cells via reactive oxygen species production. Proteomics 10, 2589-2604. doi: 10.1002/pmic.200900523
73. Klotz, L., Venier, N., Colquhoun, A. J., Sasaki, H., Loblaw, D. A., Fleshner, N., et al. (2011). Capsaicin, a novel radiosensitizer, acts via a TRPV6 mediated phenomenon. J. Clin. Oncol. 29(Suppl. 7; Abstr. 23).
74. Koebel, C. M., Vermi, W., Swann, J. B., Zerafa, N., Rodig, S. J., Old, L. J., et al. (2007). Adaptive immunity maintains occult cancer in an equilibrium state. Nature 450, 903-907. doi: 10.1038/nature06309
75. Korshunov, S. S., Skulachev, V. P., and Starkov, A. A. (1997). High protonic potential actuates a mechanism of production of reactive oxygen species in mitochondria. FEBS Lett. 416, 15-18. doi: 10.1016/S0014-579301159-9
76. Kotecha, R., Yamada, Y., Pei, X., Kollmeier, M. A., Cox, B., Cohen, G. N., et al. (2013). Clinical outcomes of high-dose-rate brachytherapy and external beam radiotherapy in the management of clinically localized prostate cancer. Brachytherapy 12, 44-49. doi: 10.1016/j.brachy.2012.05.003
77. Kuai, X. Y., Ji, Z. Y., and Zhang, H. J. (2010). Mitochondrial uncoupling protein 2 expression in colon cancer and its clinical significance. World J. Gastroenterol. 16, 5773-5778. doi: 10.3748/wjg.v16.i45.5773
78. Kuo, S. S., Saad, A. H., Koong, A. C., Hahn, G. M., and Giaccia, A. J. (1993). Potassium-channel activation in response to low doses of gamma-irradiation involves reactive oxygen intermediates in nonexcitatory cells. Proc. Natl. Acad. Sci. U.S.A. 90, 908-912. doi: 10.1073/pnas.90.3.908
79. Langenbacher, M., Abdel-Jalil, R. J., Voelter, W., Weinmann, M., and Huber, S. M. (2013). In vitro hypoxic cytotoxicity and hypoxic radiosensitization. Efficacy of the novel 2-nitroimidazole N, N, N-tris[2-(2-nitro-1H-imidazol-1-yl)ethyl]amine. Strahlenther. Onkol. 189, 246-254. doi: 10.1007/s00066-012-0273-2
80. Le Pechoux, C., Laplanche, A., Faivre-Finn, C., Ciuleanu, T., Wanders, R., Lerouge, D., et al. (2011). Clinical neurological outcome and quality of life among patients with limited small-cell cancer treated with two different doses of prophylactic cranial irradiation in the intergroup phase III trial (PCI99-01, EORTC 22003-08004, RTOG (0212). and IFCT 99-01). Ann. Oncol. 22, 1154-1163. doi: 10.1093/annonc/mdq576
81. Leiprecht, N., Munoz, C., Alesutan, I., Siraskar, G., Sopjani, M., Foller, M., et al. (2011). Regulation of Na(+)-coupled glucose carrier SGLT1 by human papillomavirus 18 E6 protein. Biochem. Biophys. Res. Commun. 404, 695-700. doi: 10.1016/j.bbrc.2010.12.044
82. Li, C., and Jackson, R. M. (2002). Reactive species mechanisms of cellular hypoxia-reoxygenation injury. Am. J. Physiol. Cell Physiol. 282, C227-241. doi: 10.1152/ajpcell.00112.2001
83. Liu, X., Chang, Y., Reinhart, P. H., Sontheimer, H., and Chang, Y. (2002). Cloning and characterization of glioma BK, a novel BK channel isoform highly expressed in human glioma cells. J. Neurosci. 22, 1840-1849.
84. Lobikin, M., Chernet, B., Lobo, D., and Levin, M. (2012). Resting potential, oncogene-induced tumorigenesis, and metastasis: the bioelectric basis of cancer in vivo. Phys. Biol. 9, 065002. doi: 10.1088/1478-3975/9/6/065002
85. Lu, Z., and Sack, M. N. (2008). ATF-1 is a hypoxia-responsive transcriptional activator of skeletal muscle mitochondrial-uncoupling protein 3. J. Biol. Chem. 283, 23410-23418. doi: 10.1074/jbc.M801236200
86. Lui, V. C., Lung, S. S., Pu, J. K., Hung, K. N., and Leung, G. K. (2010). Invasion of human glioma cells is regulated by multiple chloride channels including ClC-3. Anticancer Res. 30, 4515-4524.
87. Lutz, S. (2007). Palliative whole-brain radiotherapy fractionation: convenience versus cognition. Cancer 110, 2363-2365.
88. Lyons, S. A., O'neal, J., and Sontheimer, H. (2002). Chlorotoxin, a scorpion-derived peptide, specifically binds to gliomas and tumors of neuroectodermal origin. Glia 39, 162-173. doi: 10.1002/glia.10083
89. Maftei, C. A., Bayer, C., Shi, K., Astner, S. T., and Vaupel, P. (2011). Changes in the fraction of total hypoxia and hypoxia subtypes in human squamous cell carcinomas upon fractionated irradiation: evaluation using pattern recognition in microcirculatory supply units. Radiother. Oncol. 101, 209-216. doi: 10.1016/j.radonc.2011.05.023
90. Mailloux, R. J., Adjeitey, C. N., and Harper, M. E. (2010). Genipin-induced inhibition of uncoupling protein-2 sensitizes drug-resistant cancer cells to cytotoxic agents. PLoS ONE 5:e13289. doi: 10.1371/journal.pone.0013289
91. Mamelak, A. N., and Jacoby, D. B. (2007). Targeted delivery of antitumoral therapy to glioma and other malignancies with synthetic chlorotoxin (TM-601). Expert Opin. Drug Deliv. 4, 175-186. doi: 10.1517/17425247.4.2.175
92. Marks, L. B., and Dewhirst, M. (1991). Accelerated repopulation: friend or foe. Exploiting changes in tumor growth characteristics to improve the "efficiency" of radiotherapy. Int. J. Radiat. Oncol. Biol. Phys. 21, 1377-1383. doi: 10.1016/0360-301690301-J
93. Masumoto, K., Tsukimoto, M., and Kojima, S. (2013). Role of TRPM2 and TRPV1 cation channels in cellular responses to radiation-induced DNA damage. Biochim. Biophys. Acta 1830, 3382-3390. doi: 10.1016/j.bbagen.2013.02.020
94. Mccoy, E. S., Haas, B. R., and Sontheimer, H. (2010). Water permeability through aquaporin-4 is regulated by protein kinase C and becomes rate-limiting for glioma invasion. Neuroscience 168, 971-981. doi: 10.1016/j.neuroscience.2009.09.020
95. Mccoy, E., and Sontheimer, H. (2007). Expression and function of water channels (aquaporins) in migrating malignant astrocytes. Glia 55, 1034-1043. doi: 10.1002/glia.20524
96. Mcferrin, M. B., and Sontheimer, H. (2006). A role for ion channels in glioma cell invasion. Neuron Glia Biol. 2, 39-49. doi: 10.1017/S1740925X06000044
97. Mcleod, C. J., Aziz, A., Hoyt, R. F. Jr., Mccoy, J. P. Jr., and Sack, M. N. (2005). Uncoupling proteins 2 and 3 function in concert to augment tolerance to cardiac ischemia. J. Biol. Chem. 280, 33470-33476. doi: 10.1074/jbc.M505258200
98. Montana, V., and Sontheimer, H. (2011). Bradykinin promotes the chemotactic invasion of primary brain tumors. J. Neurosci. 31, 4858-4867. doi: 10.1523/JNEUROSCI.3825-10.2011
99. Muller, A. C., Eckert, F., Heinrich, V., Bamberg, M., Brucker, S., and Hehr, T. (2011). Re-surgery and chest wall re-irradiation for recurrent breast cancer: a second curative approach. BMC Cancer 11:197. doi: 10.1186/1471-2407-11-197
100. Muller, A. C., Gani, C., Weinmann, M., Mayer, F., Sipos, B., Bamberg, M., et al. (2012). Limited disease of extra-pulmonary small cell carcinoma. Impact of local treatment and nodal status, role of cranial irradiation. Strahlenther. Onkol. 188, 269-273. doi: 10.1007/s00066-011-0045-4
101. Murata, M., Akao, M., O'rourke, B., and Marban, E. (2001). Mitochondrial ATP-sensitive potassium channels attenuate matrix Ca(2+) overload during simulated ischemia and reperfusion: possible mechanism of cardioprotection. Circ. Res. 89, 891-898. doi: 10.1161/hh2201.100205
102. Nalla, A. K., Asuthkar, S., Bhoopathi, P., Gujrati, M., Dinh, D. H., and Rao, J. S. (2010). Suppression of uPAR retards radiation-induced invasion and migration mediated by integrin beta1/FAK signaling in medulloblastoma. PLoS ONE 5:e13006. doi: 10.1371/journal.pone.0013006
103. Narita, T., Aoyama, H., Hirata, K., Onodera, S., Shiga, T., Kobayashi, H., et al. (2012). Reoxygenation of glioblastoma multiforme treated with fractionated radiotherapy concomitant with temozolomide: changes defined by 18F-fluoromisonidazole positron emission tomography: two case reports. Jpn. J. Clin. Oncol. 42, 120-123. doi: 10.1093/jjco/hyr181
104. Nelson, J. A., and Falk, R. E. (1993). The efficacy of phloridzin and phloretin on tumor cell growth. Anticancer Res. 13, 2287-2292.
105. Nguyen, L. N., and Ang, K. K. (2002). Radiotherapy for cancer of the head and neck: altered fractionation regimens. Lancet Oncol. 3, 693-701. doi: 10.1016/S1470-204500906-3
106. Niyazi, M., Siefert, A., Schwarz, S. B., Ganswindt, U., Kreth, F. W., Tonn, J. C., et al. (2011). Therapeutic options for recurrent malignant glioma. Radiother. Oncol. 98, 1-14. doi: 10.1016/j.radonc.2010.11.006
107. Ohshima, Y., Tsukimoto, M., Harada, H., and Kojima, S. (2012). Involvement of connexin43 hemichannel in ATP release after gamma-irradiation. J. Radiat. Res. 53, 551-557. doi: 10.1093/jrr/rrs014
108. Oleinika, K., Nibbs, R. J., Graham, G. J., and Fraser, A. R. (2013). Suppression, subversion and escape: the role of regulatory T cells in cancer progression. Clin. Exp. Immunol. 171, 36-45. doi: 10.1111/j.1365-2249.2012.04657.x
109. Olsen, M. L., Schade, S., Lyons, S. A., Amaral, M. D., and Sontheimer, H. (2003). Expression of voltage-gated chloride channels in human glioma cells. J. Neurosci. 23, 5572-5582.
110. Ozcan, C., Palmeri, M., Horvath, T. L., Russell, K. S., and Russell, R. R. (2013). Role of uncoupling protein 3 in ischemia-reperfusion injury, arrhythmias and preconditioning. Am. J. Physiol. Heart Circ. Physiol. 304, H1192-H1200. doi: 10.1152/ajpheart.00592.2012
111. Pajonk, F., Vlashi, E., and Mcbride, W. H. (2010). Radiation resistance of cancer stem cells: the 4 R's of radiobiology revisited. Stem Cells 28, 639-648. doi: 10.1002/stem.318
112. Palme, D., Misovic, M., Schmid, E., Klumpp, D., Salih, H. R., Rudner, J., et al. (2013). Kv3.4 potassium channel-mediated electrosignaling controls cell cycle and survival of irradiated leukemia cells. Pflugers Archiv 465, 1209-1221. doi: 10.1007/s00424-013-1249-5
113. Pawlik, T. M., and Keyomarsi, K. (2004). Role of cell cycle in mediating sensitivity to radiotherapy. Int. J. Radiat. Oncol. Biol. Phys. 59, 928-942. doi: 10.1016/j.ijrobp.2004.03.005
114. Pfefferle, A., Mailloux, R. J., Adjeitey, C. N., and Harper, M. E. (2012). Glutathionylation of UCP2 sensitizes drug resistant leukemia cells to chemotherapeutics. Biochim. Biophys. Acta 1833, 80-89. doi: 10.1016/j.bbamcr.2012.10.006
115. Pickhard, A. C., Margraf, J., Knopf, A., Stark, T., Piontek, G., Beck, C., et al. (2011). Inhibition of radiation induced migration of human head and neck squamous cell carcinoma cells by blocking of EGF receptor pathways. BMC Cancer 11:388. doi: 10.1186/1471-2407-11-388
116. Pizzo, P., Drago, I., Filadi, R., and Pozzan, T. (2012). Mitochondrial Ca(2)(+) homeostasis: mechanism, role, and tissue specificities. Pflugers Arch. 464, 3-17. doi: 10.1007/s00424-012-1122-y
117. Pons, D. G., Sastre-Serra, J., Nadal-Serrano, M., Oliver, A., Garcia-Bonafe, M., Bover, I., et al. (2012). Initial activation status of the antioxidant response determines sensitivity to carboplatin/paclitaxel treatment of ovarian cancer. Anticancer Res. 32, 4723-4728.
118. Prasad, A., Stone, G. W., Holmes, D. R., and Gersh, B. (2009). Reperfusion injury, microvascular dysfunction, and cardioprotection: the "dark side" of reperfusion. Circulation 120, 2105-2112. doi: 10.1161/CIRCULATIONAHA.108.814640
119. Rades, D., Kieckebusch, S., Lohynska, R., Veninga, T., Stalpers, L. J., Dunst, J., et al. (2007a). Reduction of overall treatment time in patients irradiated for more than three brain metastases. Int. J. Radiat. Oncol. Biol. Phys. 69, 1509-1513.
120. Rades, D., Lohynska, R., Veninga, T., Stalpers, L. J., and Schild, S. E. (2007b). Evaluation of 2 whole-brain radiotherapy schedules and prognostic factors for brain metastases in breast cancer patients. Cancer 110, 2587-2592.
121. Ransom, C. B., Liu, X., and Sontheimer, H. (2002). BK channels in human glioma cells have enhanced calcium sensitivity. Glia 38, 281-291. doi: 10.1002/glia.10064
122. Ransom, C. B., and Sontheimer, H. (2001). BK channels in human glioma cells. J. Neurophysiol. 85, 790-803.
123. Rasola, A., and Bernardi, P. (2011). Mitochondrial permeability transition in Ca(2+)-dependent apoptosis and necrosis. Cell Calcium 50, 222-233. doi: 10.1016/j.ceca.2011.04.007
124. Rieken, S., Habermehl, D., Mohr, A., Wuerth, L., Lindel, K., Weber, K., et al. (2011). Targeting alphanubeta3 and alphanubeta5 inhibits photon-induced hypermigration of malignant glioma cells. Radiat. Oncol. 6, 132. doi: 10.1186/1748-717X-6-132
125. Robbins, D., and Zhao, Y. (2011). New aspects of mitochondrial uncoupling proteins (UCPs) and their roles in tumorigenesis. Int. J. Mol. Sci. 12, 5285-5293. doi: 10.3390/ijms12085285
126. Rodrigues, G., Zindler, J., Warner, A., and Lagerwaard, F. (2013). Recursive partitioning analysis for the prediction of stereotactic radiosurgery brain metastases lesion control. Oncologist 18, 330-335. doi: 10.1634/theoncologist.2012-0316
127. Ruggieri, P., Mangino, G., Fioretti, B., Catacuzzeno, L., Puca, R., Ponti, D., et al. (2012). The inhibition of KCa3.1 channels activity reduces cell motility in glioblastoma derived cancer stem cells. PLoS ONE 7:e47825. doi: 10.1371/journal.pone.0047825
128. Sack, M. N. (2006). Mitochondrial depolarization and the role of uncoupling proteins in ischemia tolerance. Cardiovasc. Res. 72, 210-219. doi: 10.1016/j.cardiores.2006.07.010
129. Samudio, I., Fiegl, M., Mcqueen, T., Clise-Dwyer, K., and Andreeff, M. (2008). The warburg effect in leukemia-stroma cocultures is mediated by mitochondrial uncoupling associated with uncoupling protein 2 activation. Cancer Res. 68, 5198-5205. doi: 10.1158/0008-5472.CAN-08-0555
130. Santandreu, F. M., Valle, A., Fernandez De Mattos, S., Roca, P., and Oliver, J. (2009). Hydrogen peroxide regulates the mitochondrial content of uncoupling protein 5 in colon cancer cells. Cell Physiol. Biochem. 24, 379-390. doi: 10.1159/000257430
131. Sastre-Serra, J., Nadal-Serrano, M., Pons, D. G., Valle, A., Garau, I., Garcia-Bonafe, M., et al. (2013). The oxidative stress in breast tumors of postmenopausal women is ERalpha/ERbeta ratio dependent. Free Radic. Biol. Med. 61C, 11-17. doi: 10.1016/j.freeradbiomed.2013.03.005
132. Sauer, R., Liersch, T., Merkel, S., Fietkau, R., Hohenberger, W., Hess, C., et al. (2012). Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J. Clin. Oncol. 30, 1926-1933. doi: 10.1200/JCO.2011.40.1836
133. Schwab, A., Fabian, A., Hanley, P. J., and Stock, C. (2012). Role of ion channels and transporters in cell migration. Physiol. Rev. 92, 1865-1913. doi: 10.1152/physrev.00018.2011.
134. Schwab, A., Nechyporuk-Zloy, V., Fabian, A., and Stock, C. (2007). Cells move when ions and water flow. Pflugers Arch. 453, 421-432. doi: 10.1007/s00424-006-0138-6
135. Sciaccaluga, M., Fioretti, B., Catacuzzeno, L., Pagani, F., Bertollini, C., Rosito, M., et al. (2010). CXCL12-induced glioblastoma cell migration requires intermediate conductance Ca2+-activated K+ channel activity. Am. J. Physiol. Cell Physiol. 299, C175-C184. doi: 10.1152/ajpcell.00344.2009
136. Shields, J. D., Kourtis, I. C., Tomei, A. A., Roberts, J. M., and Swartz, M. A. (2010). Induction of lymphoidlike stroma and immune escape by tumors that express the chemokine CCL21. Science 328, 749-752. doi: 10.1126/science.1185837
137. Singh, H., Stefani, E., and Toro, L. (2012). Intracellular BK(Ca) (iBK(Ca)) channels. J. Physiol. 590, 5937-5947. doi: 10.1113/jphysiol.2011.215533
138. Skulachev, V. P. (1998). Uncoupling: new approaches to an old problem of bioenergetics. Biochim. Biophys. Acta 1363, 100-124. doi: 10.1016/S0005-272800091-1
139. Sofia Vala, I., Martins, L. R., Imaizumi, N., Nunes, R. J., Rino, J., Kuonen, F., et al. (2010). Low doses of ionizing radiation promote tumor growth and metastasis by enhancing angiogenesis. PLoS ONE 5:e11222. doi: 10.1371/journal.pone.0011222
140. Sontheimer, H. (2008). An unexpected role for ion channels in brain tumor metastasis. Exp. Biol. Med. (Maywood) 233, 779-791. doi: 10.3181/0711-MR-308
141. Sreekumar, A., Nyati, M. K., Varambally, S., Barrette, T. R., Ghosh, D., Lawrence, T. S., et al. (2001). Profiling of cancer cells using protein microarrays: discovery of novel radiation-regulated proteins. Cancer Res. 61, 7585-7593.
142. Steinle, M., Palme, D., Misovic, M., Rudner, J., Dittmann, K., Lukowski, R., et al. (2011). Ionizing radiation induces migration of glioblastoma cells by activating BK K(+) channels. Radiother. Oncol. 101, 122-126. doi: 10.1016/j.radonc.2011.05.069
143. Stock, C., and Schwab, A. (2009). Protons make tumor cells move like clockwork. Pflugers Arch. 458, 981-992. doi: 10.1007/s00424-009-0677-8
144. Stupp, R., Van Den Bent, M. J., and Hegi, M. E. (2005). Optimal role of temozolomide in the treatment of malignant gliomas. Curr. Neurol. Neurosci. Rep. 5, 198-206. doi: 10.1007/s11910-005-0047-7
145. Su, W. P., Lo, Y. C., Yan, J. J., Liao, I. C., Tsai, P. J., Wang, H. C., et al. (2012). Mitochondrial uncoupling protein 2 regulates the effects of paclitaxel on Stat3 activation and cellular survival in lung cancer cells. Carcinogenesis 33, 2065-2075. doi: 10.1093/carcin/bgs253
146. Szabo, I., Leanza, L., Gulbins, E., and Zoratti, M. (2012). Physiology of potassium channels in the inner membrane of mitochondria. Pflugers Arch. 463, 231-246. doi: 10.1007/s00424-011-1058-7
147. Talbot, D. A., and Brand, M. D. (2005). Uncoupling protein 3 protects aconitase against inactivation in isolated skeletal muscle mitochondria. Biochim. Biophys. Acta 1709, 150-156.
148. Tanchot, C., Terme, M., Pere, H., Tran, T., Benhamouda, N., Strioga, M., et al. (2013). Tumor-infiltrating regulatory T cells: phenotype, role, mechanism of expansion in situ and clinical significance. Cancer Microenviron. 6, 147-157. doi: 10.1007/s12307-012-0122-y
149. Teng, M. W., Swann, J. B., Koebel, C. M., Schreiber, R. D., and Smyth, M. J. (2008). Immune-mediated dormancy: an equilibrium with cancer. J. Leukoc. Biol. 84, 988-993. doi: 10.1189/jlb.1107774
150. Tolon, R. M., Sanchez-Franco, F., Lopez Fernandez, J., Lorenzo, M. J., Vazquez, G. F., and Cacicedo, L. (1996). Regulation of somatostatin gene expression by veratridine-induced depolarization in cultured fetal cerebrocortical cells. Brain Res. Mol. Brain Res. 35, 103-110. doi: 10.1016/0169-328X(95)00188-X
151. Vanan, I., Dong, Z., Tosti, E., Warshaw, G., Symons, M., and Ruggieri, R. (2012). Role of a DNA damage checkpoint pathway in ionizing radiation-induced glioblastoma cell migration and invasion. Cell Mol. Neurobiol. doi: 10.1007/s10571-012-9846-y
152. Veiseh, M., Gabikian, P., Bahrami, S. B., Veiseh, O., Zhang, M., Hackman, R. C., et al. (2007). Tumor paint: a chlorotoxin:Cy5.5 bioconjugate for intraoperative visualization of cancer foci. Cancer Res. 67, 6882-6888. doi: 10.1158/0008-5472.CAN-06-3948
153. Verheij, M. (2008). Clinical biomarkers and imaging for radiotherapy-induced cell death. Cancer Metastasis Rev. 27, 471-480. doi: 10.1007/s10555-008-9131-1
154. Vianello, F., Papeta, N., Chen, T., Kraft, P., White, N., Hart, W. K., et al. (2006). Murine B16 melanomas expressing high levels of the chemokine stromal-derived factor-1/CXCL12 induce tumor-specific T cell chemorepulsion and escape from immune control. J. Immunol. 176, 2902-2914.
155. Vidal-Puig, A. J., Grujic, D., Zhang, C. Y., Hagen, T., Boss, O., Ido, Y., et al. (2000). Energy metabolism in uncoupling protein 3 gene knockout mice. J. Biol. Chem. 275, 16258-16266. doi: 10.1074/jbc.M910179199
156. Voehringer, D. W., Hirschberg, D. L., Xiao, J., Lu, Q., Roederer, M., Lock, C. B., et al. (2000). Gene microarray identification of redox and mitochondrial elements that control resistance or sensitivity to apoptosis. Proc. Natl. Acad. Sci. U.S.A. 97, 2680-2685. doi: 10.1073/pnas.97.6.2680
157. Watanabe, H., Bohensky, J., Freeman, T., Srinivas, V., and Shapiro, I. M. (2008). Hypoxic induction of UCP3 in the growth plate: UCP3 suppresses chondrocyte autophagy. J. Cell Physiol. 216, 419-425. doi: 10.1002/jcp.21408
158. Watkins, S., and Sontheimer, H. (2011). Hydrodynamic cellular volume changes enable glioma cell invasion. J. Neurosci. 31, 17250-17259. doi: 10.1523/JNEUROSCI.3938-11.2011
159. Weaver, A. K., Bomben, V. C., and Sontheimer, H. (2006). Expression and function of calcium-activated potassium channels in human glioma cells. Glia 54, 223-233. doi: 10.1002/glia.20364
160. Weber, D. C., Casanova, N., Zilli, T., Buchegger, F., Rouzaud, M., Nouet, P., et al. (2009). Recurrence pattern after [(18)F]fluoroethyltyrosine-positron emission tomography-guided radiotherapy for high-grade glioma: a prospective study. Radiother. Oncol. 93, 586-592. doi: 10.1016/j.radonc.2009.08.043
161. Weihua, Z., Tsan, R., Huang, W. C., Wu, Q., Chiu, C. H., Fidler, I. J., et al. (2008). Survival of cancer cells is maintained by EGFR independent of its kinase activity. Cancer Cell 13, 385-393. doi: 10.1016/j.ccr.2008.03.015
162. Wick, W., Wick, A., Schulz, J. B., Dichgans, J., Rodemann, H. P., and Weller, M. (2002). Prevention of irradiation-induced glioma cell invasion by temozolomide involves caspase 3 activity and cleavage of focal adhesion kinase. Cancer Res. 62, 1915-1919.
163. Wild-Bode, C., Weller, M., Rimner, A., Dichgans, J., and Wick, W. (2001). Sublethal irradiation promotes migration and invasiveness of glioma cells: implications for radiotherapy of human glioblastoma. Cancer Res. 61, 2744-2750.
164. Withers, H. R. (Ed). (1975). "The four R's of radiotherapy," in Advances in Radiation Biology, Vol. 5, ed J. T. A. H. Lett (New York, NY: Academic Press).
165. Wright, E. M., Loo, D. D., and Hirayama, B. A. (2011). Biology of human sodium glucose transporters. Physiol. Rev. 91, 733-794. doi: 10.1152/physrev.00055.2009
166. Wulff, H., and Castle, N. A. (2010). Therapeutic potential of KCa3.1 blockers: recent advances and promising trends. Expert Rev. Clin. Pharmacol. 3, 385-396. doi: 10.1586/ecp.10.11
167. Yellon, D. M., and Hausenloy, D. J. (2007). Myocardial reperfusion injury. N. Engl. J. Med. 357, 1121-1135. doi: 10.1056/NEJMra071667
168. Yu, L. C., Huang, C. Y., Kuo, W. T., Sayer, H., Turner, J. R., and Buret, A. G. (2008). SGLT-1-mediated glucose uptake protects human intestinal epithelial cells against Giardia duodenalis-induced apoptosis. Int. J. Parasitol. 38, 923-934. doi: 10.1016/j.ijpara.2007.12.004
169. Zhao, J., Du, C. Z., Sun, Y. S., and Gu, J. (2012). Patterns and prognosis of locally recurrent rectal cancer following multidisciplinary treatment. World J. Gastroenterol. 18, 7015-7020. doi: 10.3748/wjg.v18.i47.7015
170. Zhau, H. E., He, H., Wang, C. Y., Zayzafoon, M., Morrissey, C., Vessella, R. L., et al. (2011). Human prostate cancer harbors the stem cell properties of bone marrow mesenchymal stem cells. Clin. Cancer Res. 17, 2159-2169. doi: 10.1158/1078-0432.CCR-10-2523
171. Zhou, Y. C., Liu, J. Y., Li, J., Zhang, J., Xu, Y. Q., Zhang, H. W., et al. (2011). Ionizing radiation promotes migration and invasion of cancer cells through transforming growth factor-beta-mediated epithelial-mesenchymal transition. Int. J. Radiat. Oncol. Biol. Phys. 81, 1530-1537. doi: 10.1016/j.ijrobp.2011.06.1956