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首页> 外文期刊>Journal of Translational Medicine >Basal cytokines profile in metastatic renal cell carcinoma patients treated with subcutaneous IL-2-based therapy compared with that of healthy donors
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Basal cytokines profile in metastatic renal cell carcinoma patients treated with subcutaneous IL-2-based therapy compared with that of healthy donors

机译：与健康供体相比，经皮下IL-2治疗的转移性肾细胞癌患者的基础细胞因子谱

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Background and purpose Metastatic renal cell carcinoma (MRCC) has a poor prognosis with a median overall survival of about one year. Since only a minority of patients experienced therapeutic benefit to current treatments, several studies have attempted to identify factors that may have an impact on response and survival. Cytokines play a crucial role in the host's immune response by regulating the development and function of a lot of biological compartments. Nevertheless, available data on basal cytokine levels in MRCC are very few and no clear profile of serum cytokines has been identified yet in these patients population. Thus, determining the levels of cytokines in MRCC could not only help in understanding the biological mechanisms of the tumor growth, but also in evaluating if different cytokine profiles are correlated with particular clinical behaviors. Materials and methods In 144 healthy donors and 55 MRCC treated with subcutaneous IL-2-based regimens, we analysed a panel of basal cytokines particularly involved in the neoplastic progression (IL-1beta, IL-6, IL-8, IL-10, IL-12, alpha-TNF) and C-reactive protein (CRP) in order to compare their levels in the two groups, and to verify their impact on patient response and survival. We first compared cytokines levels in patients population and healthy donors. Than, in definite patients group, univariate and multivariate analyses were performed to evaluate the correlation existing between each factor considered and clinical outcomes. For these analyses, baseline values were included as dichotomous variables using the median values (above and below) of control group. Results In general, higher levels of cytokines were found in patients with respect to those of healthy donors, both in term of percentage of undetectable levels or median values. The impact on response was insignificant, except for higher levels of CRP that were strongly correlated with a worse response (p Conclusion Higher cytokines levels characterize patients population with respect to healthy donors. Moreover, higher basal level of some immunosuppressive cytokines (CRP, IL-6, IL-8) result correlated with a poorer survival, whereas higher levels of IL-12, a cytokine with a potent antineoplastic activity, was associated with a better survival. A wider sample of patients is needed to better clarify if our findings are intrinsically related to patients population or if they are simply an epiphenomenon of disease progression.
机译：背景与目的转移性肾细胞癌（MRCC）的预后较差，中位总生存期约为一年。由于只有少数患者对当前治疗有治疗益处，因此数项研究试图确定可能对反应和生存产生影响的因素。细胞因子通过调节许多生物区室的发育和功能，在宿主的免疫反应中起着至关重要的作用。然而，关于这些患者中MRCC中基础细胞因子水平的可用数据很少，并且尚未鉴定出血清细胞因子的明确特征。因此，确定MRCC中的细胞因子水平不仅可以帮助理解肿瘤生长的生物学机制，而且可以帮助评估不同的细胞因子谱与特定的临床行为是否相关。材料和方法在144位健康供体和55位MRCC接受基于皮下IL-2的方案治疗后，我们分析了一组特别参与肿瘤进展的基础细胞因子（IL-1beta，IL-6，IL-8，IL-10， IL-12，α-TNF）和C反应蛋白（CRP），以便比较它们在两组中的水平，并验证它们对患者反应和生存的影响。我们首先比较了患者人群和健康供体中的细胞因子水平。然后，在确定的患者组中，进行了单因素和多因素分析以评估所考虑的每个因素与临床结果之间的相关性。对于这些分析，使用对照组的中值（上下）将基线值作为二分变量包括在内。结果总的来说，无论是检测不到的百分比还是中位值，患者体内的细胞因子水平都高于健康供体。对反应的影响微乎其微，除了较高的CRP水平与较差的反应密切相关（p结论较高的细胞因子水平是患者相对于健康供体的特征。此外，一些免疫抑制细胞因子（CRP，IL- （参见图6，IL-8）结果与较差的生存率相关，而较高水平的IL-12（具有较强抗肿瘤活性的细胞因子）则与较好的生存率相关，需要更广泛的患者样本以更好地阐明我们的发现是否本质上与患者群体有关，或者仅仅是疾病进展的表象。

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