Skeletal muscle anabolism is a side effect of therapy with the MEK inhibitor: selumetinib in patients with cholangiocarcinoma.
Skeletal muscle anabolism is a side effect of therapy with the MEK inhibitor: selumetinib in patients with cholangiocarcinoma.
复制标题
DOI：
10.1038/bjc.2012.144
复制
发表时间：
2012-05-08
影响因子：
8.8
通讯作者：
Sawyer, M. B.
中科院分区：
文献类型：
--
作者：
Prado, C. M. M.;Bekaii-Saab, T.;Doyle, L. A.;Shrestha, S.;Ghosh, S.;Baracos, V. E.;Sawyer, M. B.
癌症恶病质的特征是骨骼肌萎缩;然而，晚期癌症患者肌肉萎缩的潜力尚未得到证实。一项II期研究中接受司美替尼（AZD 6244; ARRY-142886）治疗的胆管癌患者与单独的标准治疗组相比的肌肉损失/增益的计算机断层扫描图像定量分析。司美替尼是丝裂原活化蛋白/细胞外信号调节激酶和白细胞介素-6分泌的抑制剂，白细胞介素-6是肌肉萎缩的假定介质。总体而言，84.2%的患者在开始司美替尼治疗后肌肉增加;总腰肌横截面积的平均总体增加为13.6 cm 2/100天（全身平均增加2.3 kg）。开始标准治疗的胆管癌患者有明显的分解代谢，总体肌肉损失为-7.3 cm 2/100天（约1.2 kg），相比之下，这些患者中只有16.7%获得肌肉。我们的研究结果表明，司美替尼促进胆管癌患者的肌肉增长。恶病质治疗的具体机制和相关性仍有待研究。
Cancer cachexia is characterised by skeletal muscle wasting; however, potential for muscle anabolism in patients with advanced cancer is unproven. Quantitative analysis of computed tomography images for loss/gain of muscle in cholangiocarcinoma patients receiving selumetinib (AZD6244; ARRY-142886) in a Phase II study, compared with a separate standard therapy group. Selumetinib is an inhibitor of mitogen-activated protein/extracellular signal–regulated kinase and of interleukin-6 secretion, a putative mediator of muscle wasting. Overall, 84.2% of patients gained muscle after initiating selumetinib; mean overall gain of total lumbar muscle cross-sectional area was 13.6 cm2/100 days (∼2.3 kg on a whole-body basis). Cholangiocarcinoma patients who began standard treatment were markedly catabolic, with overall muscle loss of −7.3 cm2/100 days (∼1.2 kg) and by contrast only 16.7% of these patients gained muscle. Our findings suggest that selumetinib promotes muscle gain in patients with cholangiocarcinoma. Specific mechanisms and relevance for cachexia therapy remain to be investigated.
登录
查看更多内容
DOI：
10.1097/mco.0b013e32831cef61
发表时间：
2009-01
影响因子：
3.1
作者：
Durham WJ;Dillon EL;Sheffield-Moore M
通讯作者：
Sheffield-Moore M
影响因子：
3.3
作者：
FRONTERA, WR;MEREDITH, CN;EVANS, WJ
通讯作者：
EVANS, WJ
影响因子：
3.3
作者：
Shen, W;Punyanitya, M;Heshka, S
通讯作者：
Heshka, S
影响因子：
3.3
作者：
Edinger, AL;Thompson, CB
通讯作者：
Thompson, CB
影响因子：
9
作者：
Goydos, JS;Brumfield, AM;Carty, SE
通讯作者：
Carty, SE