Oxidative stress and ERK1/2 phosphorylation as predictors of outcome in hepatocellular carcinoma patients treated with sorafenib plus octreotide LAR.
Oxidative stress and ERK1/2 phosphorylation as predictors of outcome in hepatocellular carcinoma patients treated with sorafenib plus octreotide LAR.
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DOI：
10.1038/cddis.2011.34
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发表时间：
2011-04-28
影响因子：
9
通讯作者：
中科院分区：
文献类型：
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我们报道了索拉非尼和奥曲肽长效释放剂（LAR）联合治疗晚期肝细胞癌（HCC）患者的相关活性。在这项工作中，我们已经研究了，如果氧化应激在血清和外周血单核细胞（PBMC）和pERK激活状态在PBMC可以预测的反应。在20名反应患者中，在索拉非尼给药开始后10天（T10）已经可检测到活性氧水平的降低，索拉非尼+奥曲肽LAR联合治疗（T21）增强了这种作用。这种效应与超氧化物歧化酶（SOD）活性（O2-的生理清除剂）和血清一氧化氮（NO）水平的调节有关。索拉非尼单独诱导增加约40%的NO水平和约2倍的SOD活性的响应患者，这两种效果显着增强的联合治疗。我们发现Erk 1/2活性逐渐减少，细胞荧光分析评价，在15个响应患者达到约50%的最大降幅在T21。另一方面，在17名耐药患者中，Erk 1/2活性在T21时增加了约80%。PBMC中氧化应激状态和pERK活性的测定在预测HCC患者对索拉非尼+奥曲肽治疗的反应中具有很高的价值。
We reported a relevant activity of the combination between sorafenib and octreotide long-acting release (LAR) in advanced hepatocellular carcinoma (HCC) patients. In this work, we have studied if oxidative stress in both serum and peripheral blood mononuclear cells (PBMC) and pERK activation status in PBMC could be predictive of response. In the 20 responsive patients, the decrease of reactive oxygen species levels was already detectable after 10 days (T10) from the beginning of sorafenib administration, and this effect was enhanced by the combined treatment with sorafenib+octreotide LAR (T21). This effect correlated with the modulation of superoxide dismutase (SOD) activity (physiological scavenger of O2−) and of serum nitric oxide (NO) levels. Sorafenib alone induced an increase of about 40% of NO levels and of about two-fold of SOD activity in responsive patients, and both effects were significantly potentiated by the combined treatment. We found a gradual reduction of Erk1/2 activity, as evaluated by cytofluorimetric analysis, in 15 responsive patients reaching about 50% maximal decrease at T21. On the other hand, in 17 resistant patients, Erk1/2 activity was about 80% increased at T21. The determination of both the oxidative stress status and pERK activity in PBMC has high value in the prediction of response to sorafenib+octreotide therapy in HCC patients.
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影响因子：
2.8
作者：
Kim, Woo Hyang;Goo, Sung Young;Park, Soon-Jung
通讯作者：
Park, Soon-Jung
影响因子：
4.2
作者：
Hwang, YH;Choi, JY;Park, YM
通讯作者：
Park, YM
影响因子：
11.2
作者：
Liu, Li;Cao, Yichen;Carter, Christopher
通讯作者：
Carter, Christopher
影响因子：
45.3
作者：
Abou-Alfa, Ghassan K.;Schwartz, Lawrence;Saltz, Leonard B.
通讯作者：
Saltz, Leonard B.
DOI：
10.1111/j.1749-6632.2002.tb04090.x
发表时间：
2002-01-01
期刊：
HORMONE-RELATED TUMORS: NOVEL APPROACHES TO PREVENTION AND TREATMENT
影响因子：
--
作者：
Montalto, G;Cervello, M;Castagnetta, LAM
通讯作者：
Castagnetta, LAM