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Roedel, Franz; Frey, Benjamin; Leitmann, Werner M.S.; Capalbo, Gianni; Weiss, Christian; Roedel, Claus, E-mail: franz.roedel@kgu.de2008
AbstractAbstract
[en] Purpose: Survivin shows a radiation resistance factor in colorectal cancer. In the present study, we determined whether survivin messenger RNA levels in patients with rectal cancer predict tumor response after neoadjuvant radiochemotherapy and whether inhibition of survivin by the use of antisense oligonucleotides (ASOs) enhances radiation responses. Methods and Materials: SW480 colorectal carcinoma cells were transfected with survivin ASO (LY2181308) and irradiated with doses ranging from 0-8 Gy. Survivin expression, cell-cycle distribution, γH2AX fluorescence, and induction of apoptosis were monitored by means of immunoblotting, flow cytometry, and caspase 3/7 activity. Clonogenic survival was determined by using a colony-forming assay. An SW480 xenograft model was used to investigate the effect of survivin attenuation and irradiation on tumor growth. Furthermore, survivin messenger RNA levels were studied in patient biopsy specimens by using Affymetrix microarray analysis. Results: In the translational study of 20 patients with rectal cancer, increased survivin levels were associated with significantly greater risk of local tumor recurrence (p = 0.009). Treatment of SW480 cells with survivin ASOs and irradiation resulted in an increased percentage of apoptotic cells, caspase 3/7 activity, fraction of cells in the G2/M phase, and H2AX phosphorylation. Clonogenic survival decreased compared with control-treated cells. Furthermore, treatment of SW480 xenografts with survivin ASOs and irradiation resulted in a significant delay in tumor growth. Conclusion: Survivin appears to be a molecular biomarker in patients with rectal cancer. Furthermore, in vitro and in vivo data suggest a potential role of survivin as a molecular target to improve treatment response to radiotherapy in patients with rectal cancer
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Source
2007 interorganizational symposium on quality assurance of radiation therapy: Challenges of advanced technology; Dallas, TX (United States); 20-22 Feb 2007; S0360-3016(08)00286-1; Available from http://dx.doi.org/10.1016/j.ijrobp.2008.02.011; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Record Type
Journal Article
Literature Type
Conference
Journal
International Journal of Radiation Oncology, Biology and Physics; ISSN 0360-3016;
; CODEN IOBPD3; v. 71(1); p. 247-255

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