Roato I, Gorassini E, Buffoni L, Lyberis P, Ruffini E, Bonello L, Baldi I, Ciuffreda L, Mussa A, Ferracini R
CeRMS (Center for Experimental Research and Medical Studies) University and A.S.O. San Giovanni Battista, Turin, Italy.
Lung Cancer. 2008 Jul;61(1):109-16. doi: 10.1016/j.lungcan.2007.10.016. Epub 2007 Dec 3.
Lung cancer is a widespread disease and its incidence is growing. Since therapies have increased the life expectancy of lung cancer patients, the development of bone osteolytic metastases is becoming a common cause of morbidity. Osteolysis is caused by an increased osteoclast activity and may be reduced by inhibiting their formation and activity. We studied 60 male patients affected by NSCLC, divided in early and advanced stage disease. Patients' blood and urinary samples were collected at tumor diagnosis and at follow-up. PBMCs were cultured to investigate the spontaneous osteoclastogenesis. IL-7 was dosed in serum and its quantitative gene expression was evaluated on tumor and healthy tissues by RQ-PCR. Both at diagnosis and follow-up, osteolytic bone patients showed high spontaneous osteoclastogenesis level compared to non-bone metastatic and healthy controls. The presence of spontaneous osteoclastogenesis correlated with urinary crosslinks increase. Serum IL-7 levels were higher in bone metastatic patients than in patients without bone lesions and healthy controls. The serum IL-7 increase correlated with the osteoclastogenesis and, at least in part, depended on an increased IL-7 production by tumor cells. At follow-up, patients with increased osteoclastogenesis and serum IL-7 levels, were subjected to standard clinical analysis, which showed early secondary bone lesions. The in vitro assay for spontaneous osteoclastogenesis and serum IL-7 dosage could be useful for diagnostic purposes and it might be able to monitor cancer patients with a high risk to develop osteolytic metastases at follow-up, especially after a curative treatment.
肺癌是一种广泛传播的疾病，其发病率正在上升。由于治疗方法提高了肺癌患者的预期寿命，骨溶骨性转移的发生正成为发病的常见原因。骨溶解是由破骨细胞活性增加引起的，通过抑制其形成和活性可以减轻骨溶解。我们研究了60例受非小细胞肺癌影响的男性患者，分为疾病早期和晚期。在肿瘤诊断时和随访时采集患者的血液和尿液样本。培养外周血单核细胞以研究自发破骨细胞生成。测定血清中的白细胞介素-7，并通过实时定量聚合酶链反应评估其在肿瘤组织和健康组织中的定量基因表达。在诊断和随访时，与非骨转移患者和健康对照相比，骨溶解性骨转移患者的自发破骨细胞生成水平较高。自发破骨细胞生成的存在与尿交联增加相关。骨转移患者的血清白细胞介素-7水平高于无骨病变患者和健康对照。血清白细胞介素-7的增加与破骨细胞生成相关，并且至少部分取决于肿瘤细胞白细胞介素-7产生的增加。在随访时，对破骨细胞生成增加和血清白细胞介素-7水平升高的患者进行标准临床分析，结果显示早期继发性骨病变。自发破骨细胞生成的体外测定和血清白细胞介素-7定量测定可用于诊断目的，并且可能能够监测随访中发生骨溶骨性转移风险高的癌症患者，尤其是在进行根治性治疗后。
