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Preserved muscle oxidative metabolic phenotype in newly diagnosed non‐small cell lung cancer cachexia

机译:新诊断的非小细胞肺癌恶病质中保留的肌肉氧化代谢表型

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AbstractBackgroundCachexia augments cancer-related mortality and has devastating effects on quality of life. Pre-clinical studies indicate that systemic inflammation-induced loss of muscle oxidative phenotype (OXPHEN) stimulates cancer-induced muscle wasting. The aim of the current proof of concept study is to validate the presence of muscle OXPHEN loss in newly diagnosed patients with lung cancer, especially in those with cachexia.MethodsQuadriceps muscle biopsies of comprehensively phenotyped pre-cachectic (n = 10) and cachectic (n = 16) patients with non-small cell lung cancer prior to treatment were compared with healthy age-matched controls (n = 22). OXPHEN was determined by assessing muscle fibre type distribution (immunohistochemistry), enzyme activity (spectrophotometry), and protein expression levels of mitochondrial complexes (western blot) as well as transcript levels of (regulatory) oxidative genes (quantitative real-time PCR). Additionally, muscle fibre cross-sectional area (immunohistochemistry) and systemic inflammation (multiplex analysis) were assessed.ResultsMuscle fibre cross-sectional area was smaller, and plasma levels of interleukin 6 were significantly higher in cachectic patients compared with non-cachectic patients and healthy controls. No differences in muscle fibre type distribution or oxidative and glycolytic enzyme activities were observed between the groups. Mitochondrial protein expression and gene expression levels of their regulators were also not different.ConclusionMuscle OXPHEN is preserved in newly diagnosed non-small cell lung cancer and therefore not a primary trigger of cachexia in these patients.
机译:摘要背景恶病质会增加与癌症相关的死亡率,并对生活质量造成毁灭性影响。临床前研究表明,全身性炎症引起的肌肉氧化表型丧失(OXPHEN)会刺激癌症引起的肌肉消瘦。当前概念验证研究的目的是验证新诊断的肺癌患者中肌肉OXPHEN缺失的存在,尤其是恶病质的患者。方法对全面表型前恶病质(n = 10)和恶病质(n = 16)将治疗前的非小细胞肺癌患者与年龄匹配的健康对照进行比较(n = 22)。 OXPHEN是通过评估肌肉纤维类型分布(免疫组织化学),酶活性(分光光度法)和线粒体复合物的蛋白质表达水平(western blot)以及(调节性)氧化基因的转录水平(实时定量PCR)来确定的。另外,评估了恶病质患者的肌肉纤维截面积(免疫组织化学)和全身炎症(多重分析)。结果与非非恶病质患者和健康者相比,恶病质患者的肌纤维横截面积更小,白细胞介素6的血浆水平显着更高控制。两组之间没有观察到肌肉纤维类型分布或氧化酶和糖酵解酶活性的差异。线粒体蛋白的表达及其调节子的基因表达水平也没有差异。结论肌肉中的OXPHEN保留在新诊断的非小细胞肺癌中,因此不是这些患者恶病质的主要诱因。

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