NF- κB, Colorectal Carcinoma and Radiotherapy: Results of a Clinical and Experimental Study
Authors:
R. Vobořil 1,2; J. Weberová-Vobořilová 1; V. Rychterová 3; M. Ambruš 4; L. Horák 2; J. Fanta 2
Authors‘ workplace:
Oddělení buněčné a molekulární biologie, Ústav biochemie, buněčné a molekulární biologie, 3. lékařská fakulta UK, Praha, vedoucí oddělení: doc. RNDr. J. Kovář, DrSc.
1; Chirurgická klinika, 3. lékařská fakulta UK a Fakultní nemocnice Královské Vinohrady, Praha, přednosta: doc. MUDr. J. Fanta, DrSc.
2; Ústav patologie, 3. lékařská fakulta UK a Fakultní nemocnice Královské Vinohrady, Praha, přednosta: prof. MUDr. V. Mandys, CSc.
3; Radioterapeutická a onkologická klinika, 3. lékařská fakulta UK a Fakultní nemocnice Královské Vinohrady, Praha, přednostka: MUDr. M. Kubecová
4
Published in:
Rozhl. Chir., 2007, roč. 86, č. 5, s. 268-272.
Category:
Monothematic special - Original
Overview
Resistance to radiotherapy often seen in rectal cancer patients requires intensive study of mechanisms taking part in this process. It seems that nuclear factor-kappaB (NF- κB), especially its subunit p65, could play an important role in radioresistance. The aims of this study were: 1. to assess expression of p65 in rectal cancer patients and to evaluate its possible predictive role; 2. to determine in in vitro experiments possibilities of p65 modulation and to evaluate, whether this modulation can result in enhacement of efficiency of radiation therapy. We found that the level of NF- κB expression may serve as a predictive marker of overall survival. Further we found that inhibition of NF- κB activity caused by radiation improves impact of radiation therapy.
Key words:
NF-kappaB – rectal cancer – radiotherapy – immunohistochemistry – marker
Sources
1. Taylor, W. E., Donohue, J. H., Gunderson, L. L., Nelson, H., Nagorney, D. M., Devine, R. M., Haddock, M. G., Larson, D. R., Rubin, J., O‘Connell, M. J. The Mayo Clinic experience with multimodality treatment of locally advanced or recurrent colon cancer. Ann. Surg. Oncol., 2002; 9: 177–185.
2. Leith, J., Faulkner, G., Papa, P., Michelson, S. In vitro radiation survival parameters of human colon tumour cells. Int. J. Radiat. Oncol. Biol. Phys., 1991; 20: 203–206.
3. Chapman, J. D., Anderson, P. R. Predicting and overcoming the radioresistance of individual tumors. Int. J. Radiat. Oncol. Biol. Phys., 1999; 44: 477–479.
4. Pahl, H. L. Activators and target genes of Rel/NF-kappaB transcription factors. Oncogene, 1999; 18: 6853–6866.
5. Karin, M., Cao, Y., Greten, F. R., Li, Z. W. NF-κB in cancer: from innocent bystander to major culprit. Nat. Rev. Cancer, 2002; 2: 301–310.
6. Karin, M., Ben-Neriah, Y. Phosphorylation meets ubiquitination: the control of NF-κB activity. Ann. Rev. Immunol., 2000; 18: 621–663.
7. Ghosh, S., May, M. J., Kopp, E. B. NF-κB and Rel proteins: Evolutionarily conserved mediators of immune responses. Ann. Rev. Immunol., 1998; 16: 225–260.
8. Kim, K. M., Zhang, Y., Kim, B. Y., Jeong, S. J., Lee, S. A., Kim, G. D., Dritschilo, A., Jung, M. The p65 subunit of nuclear factor-kappaB is a molecular target for radiation sensitization of human squamous carcinoma cells. Mol. Cancer Ther., 2004; 3: 693–698.
9. Vobořil, R., Weberova-Vobořilová, J. Constitutive NF-κB activity in colorectal cancer cells: impact on radiation-induced NF-κB activity, radiosensitivity, and apoptosis. Neoplasma, 2006; 53: 518–523.
10. Ellis, R. D., Goodland, J. R., Limb, G. A., Powell, J. J., Thompson, R. P. H., Punchard, N. A. Activation of nuclear factor kappa B in Crohn‘s disease. Inflamm. Res., 1998; 47: 440–445.
11. Yu, H. G., Yu, L. L., Yang, Y., Luo, H. S., Yu, J. P., Meier, J. J., Schrader, H., Bastian, A., Schmidt, W. E., Schmitz, F. Increased expression of RelA/Nuclear factor-kB protein correlates with colorectal tumorigenesis. Oncology, 2003; 65: 37–45.
12. Yu, H. G., Zhong, X., Yang, Y. N., Luo, H. S., Yu, J. P., Meier, J. J., Schrader, H., Bastian, A., Schmidt, W. E., Schmitz, F. Increased expression of nuclear factor-kB/RelA is correlated with tumor angiogenesis in human colorectal cancer. Int. J. Colorectal Dis., 2004; 19: 18–22.
13. Evertsson, S., Sun, X. F. Protein expression of NF-κB in human colorectal adenocarcinoma. Int. J. Mol. Med., 2002; 10: 547–550.
14. Blankenstein, T. The role of tumor stroma in the interaction between tumor and immune systém. Curr. Opin. Immunol., 2005; 17: 180-186.
15. Kammertoens, T., Schuler, T., Blankenstein, T. Immunotherapy: target the stroma to hit the tumor. Trends Mol. Med., 2005; 11: 225–231.
16. Gooch, J. L., Lee, A., Yee, D. Interleukin 4 inhibits growth and induces apoptosis in human breast cancer cells. Cancer Res., 1998; 58: 4199–4205.
17. Obiri, N. I., Hillman, G. G., Haas, G. P., Sud, S., Puri, R. K. Expression of high affinity interleukin-4 receptors on human renal cell carcinoma cells and inhibition of tumor cell growth in vitro by interleukin-4. J. Clin. Invest., 1993; 91: 88–93.
18. Oosterling, S. J., van der Bij, G. J., Meijer, G. A., Tuk, C. W., van Garderen, E., van Rooijen, N., Meijer, S., van der Sijp, J. R. M., Beelen, R. H. J., van Egmond, M. Macrophages direct tumour histology and clinical outcome in a colon cancer model. J. Pathol. 2005:207: 147–155.
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