Apurinic/apyrimidinic endonuclease activity is associated with response to radiation and chemotherapy in medulloblastoma and primitive neuroectodermal tumors
Apurinic/apyrimidinic endonuclease activity is associated with response to radiation and chemotherapy in medulloblastoma and primitive neuroectodermal tumors
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DOI：
10.1158/1078-0432.ccr-05-1068
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发表时间：
2005-10-15
影响因子：
11.5
通讯作者：
Silber, JR
中科院分区：
文献类型：
--
作者：
Bobola, MS;Finn, LS;Silber, JR
目的：脱嘌呤/脱嘧啶核酸内切酶（Apendo）是一种关键的DNA修复活性，其赋予对人类细胞中辐射和烷化剂诱导的细胞毒性脱碱基位点的抗性。我们测定了脱嘌呤/脱嘧啶核酸内切酶活性髓母细胞瘤和原始神经外胚层肿瘤（PNET）建立相关的肿瘤和患者的特点，并与辅助放疗加多药chemotherapy.Experimental Design：AP endo活性测定在52髓母细胞瘤和10 PNDO患者0.4至21岁。Apel/Ref-1是人类主要的Ap内分泌活性，通过免疫染色在42例髓母细胞瘤中测定。采用考克斯比例风险回归模型分析肿瘤Ap活性与肿瘤进展时间（TTP）的相关性。肿瘤Apel/Ref-1几乎仅在细胞核中检测到。在一个多变量模型中，Ap内分泌活性作为一个连续变量，46例髓母细胞瘤和4例PNM患者辅助治疗后进展的风险比，活性每增加0.01个单位，增加1.073倍（P
Purpose: Apurinic/apyrimidinic endonuclease (Ap endo) is a key DNA repair activity that confers resistance to radiation- and alkylator-induced cytotoxic abasic sites in human cells. We assayed apurinic/apyrimidinic endonuclease activity in medulloblastomas and primitive neuroectodermal tumors (PNET) to establish correlates with tumor and patient characteristics and with response to adjuvant radiation plus multiagent chemotherapy.Experimental Design: Ap endo activity was assayed in 52 medulloblastomas and 10 PNETs from patients 0.4 to 21 years old. Apel/Ref-1, the predominant human Ap endo activity, was measured in 42 medulloblastomas by immunostaining. Cox proportional hazards regression models were used to analyze the association of activity with time to tumor progression (TTP).Results: Tumor Ap endo activity varied 180-fold and was significantly associated with age and gender. Tumor Apel/Ref-1 was detected almost exclusively in nuclei. In a multivariate model, with Ap endo activity entered as a continuous variable, the hazard ratio for progression after adjuvant treatment in 46 medulloblastomas and four PNETs increased by a factor of 1.073 for every 0.01 unit increase in activity (P