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肺癌患者生长激素-胰岛素样生长因子轴功能的昼夜节律方面。

Circadian aspects of growth hormone-insulin-like growth factor axis function in patients with lung cancer.

机构信息

Department of Internal Medicine and Chronobiology Unit, Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza," S. Giovanni Rotondo (FG), Italy.

出版信息

Clin Lung Cancer. 2012 Jan;13(1):68-74. doi: 10.1016/j.cllc.2011.03.034. Epub 2011 May 19.

Abstract

BACKGROUND AND PURPOSE

Insulin-like growth factor 1 (IGF1) promotes cell cycle progression and inhibition of apoptosis and may have a role in carcinogenesis and cancer promotion. Growth hormone (GH) stimulates IGF1 production in liver and other tissues. The aim of our study was to evaluate differences between healthy subjects and patients with lung cancer in the GH-IGF1 axis function.

PATIENTS AND METHODS

In 11 healthy male patients (mean age ± standard error [SE], 43.6 ± 1.7), and 9 male patients with non-small-cell lung cancer (mean age ± SE, 51.0 ± 2.4), GH, total IGF1, melatonin, and interleukin (IL)-2 serum levels were measured in blood samples collected every 4 hours for 24 hours.

RESULTS

A clear circadian rhythm was present for melatonin and GH serum levels in the group of healthy subjects and for melatonin in the group of patients with cancer. The midline estimating statistic of rhythm (MESOR) of GH was higher in patients with lung cancer (P < .001), the MESOR of IGF1 was higher in healthy subjects (P < .001), the MESOR of melatonin was not different between subjects (P = .383), and the MESOR of IL-2 was higher in patients with cancer (P = .02). The GH/IGF1 ratio was higher in patients with lung cancer (P = .006). Linear regressions across the stages of cancer showed a significant increasing slope for IL-2 (P < .001), GH (P < .001), and the GH/IGF1 ratio (P < .001), a decreasing slope for IGF1 (P < .001), but no significant trend for melatonin (P = .430).

CONCLUSION

There is evidence that in patients with lung cancer there is a severe alteration of GH-IGF1 axis function, with loss of circadian rhythmicity of hormone secretion, which may play a role in the progression of neoplastic disease and must be considered in defining the therapeutic approach.

摘要

背景与目的

胰岛素样生长因子 1(IGF1)促进细胞周期进程并抑制细胞凋亡,可能在致癌作用和癌症促进中发挥作用。生长激素(GH)刺激肝脏和其他组织中 IGF1 的产生。我们研究的目的是评估健康受试者和肺癌患者之间 GH-IGF1 轴功能的差异。

患者与方法

在 11 名健康男性患者(平均年龄 ± 标准误差[SE],43.6 ± 1.7)和 9 名非小细胞肺癌男性患者(平均年龄 ± SE,51.0 ± 2.4)中,每隔 4 小时采集一次血液样本,共 24 小时,测量 GH、总 IGF1、褪黑素和白细胞介素(IL)-2 血清水平。

结果

在健康受试者组中,褪黑素和 GH 血清水平存在明显的昼夜节律,而在癌症患者组中仅存在褪黑素的昼夜节律。肺癌患者的 GH 中值估计节律(MESOR)更高(P<0.001),健康受试者的 IGF1 MESOR 更高(P<0.001),受试者间的 MESOR 褪黑素无差异(P=0.383),癌症患者的 MESOR IL-2 更高(P=0.02)。肺癌患者的 GH/IGF1 比值更高(P=0.006)。癌症各阶段的线性回归显示 IL-2(P<0.001)、GH(P<0.001)和 GH/IGF1 比值(P<0.001)的斜率显著增加,IGF1(P<0.001)的斜率降低,但褪黑素无明显趋势(P=0.430)。

结论

有证据表明,肺癌患者的 GH-IGF1 轴功能严重改变,激素分泌失去昼夜节律性,这可能在肿瘤疾病的进展中发挥作用,在确定治疗方法时必须考虑到这一点。

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