TITLE

IS SURVIVING SIGNIFICANT IN THE P53 APOPTOTIC PATHWAY AFTER SHORT COURSE RADIOTHERAPY?

AUTHOR(S)
Ishiwara, H.; Talbot, I.C.
PUB. DATE
April 2003
SOURCE
Gut;Apr2003 Supplement 1, Vol. 52, pA90
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Aim: We have shown the significance of the p53 apoptotic pathway in short course radiotherapy. Recently, survivin, a novel anti-apoptotic gene, has been identified but its role in vivo is still unclear. We have examined the role of survivin with reference to apoptotic cell death and the expression of apoptosis regulating proteins in short course radiotherapy. Methods: 26 patients underwent operation from June 1982 to October 1984 after short course radiotherapy (15Gy). Patients were aged between 27 and 77 years (median 57), 11 were male. Tumour stages were (Dukes) A (2), B (11), C (13). Sections of paired biopsies and post-irradiated surgical specimens of each tumour were immunohistochemically stained for p53, Bcl-2, BCL-XL, Bax, P21/WAF1, and survivin. The apoptotic index (Al) was the percentage of positive tumour cells using the TUNEL method. Results: After radiotherapy, the average Al increased significantly (2.2 vs 7.5; p < 0.01). Survivin immunostaining was positive in 15/26 (57.7%) of biopsies and in 8/26 (30.8%) of surgical specimens. Bax immunostaining was positive in 3/26 (11.5%) of biopsies and in 15/26 (57.7%) of surgical specimens. There were no correlation of expression between survivin and other proteins in both biopsies and surgical specimens. In surgical specimens, the average Al of survivin-negative subgroup (n = 8) was higher than that of negative one (n = 18) (7.87 vs 6.7; p > 0.05). In biopsies the average Al was almost equal irrespective of survivin expression. However, in surgical specimens, the combination of p53-low/survivin-negative expression formed a group with the highest Al of all other subgroups. Conclusion: Apoptotic cell death and down-regulation of survivin protein were induced by radiation in vivo. These results suggest that survivin has a role, possibly regulatory, in the p53-apoptotic pathway after short course preoperative radiotherapy.
ACCESSION #
9747887

 

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