Apurinic/apyrimidinic endonuclease is inversely associated with response to radiotherapy in pediatric ependymoma.
Apurinic/apyrimidinic endonuclease is inversely associated with response to radiotherapy in pediatric ependymoma.
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DOI：
10.1002/ijc.25900
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发表时间：
2011-11-15
影响因子：
6.4
通讯作者：
Silber, John R.
中科院分区：
文献类型：
--
作者：
Bobola, Michael S.;Jankowski, Pawel P.;Gross, Mary E.;Schwartz, Jeffery;Finn, Laura S.;Blank, A.;Ellenbogen, Richard G.;Silber, John R.
脱嘌呤/脱嘧啶核酸内切酶(AP Endo)是一种重要的DNA修复活性，在人体细胞中具有辐射抗性。在这里，我们研究了儿科室管膜瘤中AP Endo活性与放射治疗反应之间的关系，这种肿瘤的治疗选择有限，存活率仅为50%左右。我们用免疫组织化学方法检测了36例室管膜瘤中AP Endo的活性和44例肿瘤中APE1/Ref-1的表达。用COX比例风险回归模型分析活性或表达与无进展生存期或总生存期的关系。活动变化13倍，与肿瘤或患者特征无关。在AP Endo活性作为连续变量进入的单变量模型中，在24个II级室管膜瘤中，活动每增加0.01个单位，进展的危险比增加2.18倍(P≤0.003)。在同一人群中，死亡风险增加了1.89倍(P≤0.02)。APE1/Ref-1免疫阳性细胞的比例在个体肿瘤中差异很大，与无进展或总体生存无关。抑制儿科室管膜瘤细胞中的AP Endo活性显著增加了辐射敏感性，这表明活性与辐射反应的关联至少部分反映了辐射诱导的DNA损伤的修复。我们的数据表明，AP Endo活性可以预测放疗后的结果，并提示APE1/Ref-1促进了儿科室管膜瘤的放射抵抗。我们的发现支持使用AP Endo活性的抑制剂来克服耐药性。
Apurinic/apyrimidinic endonuclease (Ap endo) is a key DNA repair activity that confers radiation resistance in human cells. Here we examined the association between Ap endo activity and response to radiotherapy in pediatric ependymomas, tumors for which treatment options are limited and survival rates are only about 50%. We assayed Ap endo activity in 36 ependymomas and expression of Ape1/Ref-1, the predominant Ap endo activity in humans, in 44 tumors by immunostaining. Cox proportional hazards regression models were used to analyze the association of activity or expression with progression-free survival or with overall survival. Activity varied 13-fold and was not associated with tumor or patient characteristics. In univariate models with Ap endo activity entered as a continuous variable, the hazard ratio for progression increased by a factor of 2.18 for every 0.01 unit increase in activity (P ≤ 0.003) in 24 grade II ependymomas. Risk for death increased by a factor of 1.89 (P ≤ 0.02) in the same population. The fraction of Ape1/Ref-1 immunopositive cells varied widely within individual tumors and was not associated with either progression-free or with overall survival. Suppressing Ap endo activity in pediatric ependymoma cells significantly increased radiation sensitivity, suggesting that the association of activity with radiation response reflected, at least in part, repair of radiation-induced DNA lesions. Our data indicate that Ap endo activity is predictive of outcome following radiotherapy, and suggest that Ape1/Ref-1 promotes radiation resistance in pediatric ependymomas. Our findings support the use of inhibitors of Ap endo activity to overcome resistance.
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影响因子：
15.9
作者：
Ridley, Lee;Rahman, Ruman;Grundy, Richard G.
通讯作者：
Grundy, Richard G.
影响因子：
11.5
作者：
Bobola, MS;Finn, LS;Silber, JR
通讯作者：
Silber, JR
影响因子：
4.6
作者：
BOBOLA, MS;BLANK, A;SILBER, JR
通讯作者：
SILBER, JR
影响因子：
7.3
作者：
Zawahir, Zahrah;Dayam, Raveendra;Neamati, Nouri
通讯作者：
Neamati, Nouri
影响因子：
1.4
作者：
Mack, Stephen C.;Taylor, Michael D.
通讯作者：
Taylor, Michael D.