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化疗对非小细胞肺癌患者粒细胞和单核细胞中一氧化氮合酶、吲哚胺 2,3-双加氧酶和 CD124 表达的影响。

Influence of chemotherapy on nitric oxide synthase, indole-amine-2,3-dioxygenase and CD124 expression in granulocytes and monocytes of non-small cell lung cancer.

机构信息

Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.

出版信息

Cancer Sci. 2012 Feb;103(2):155-60. doi: 10.1111/j.1349-7006.2011.02158.x. Epub 2011 Dec 23.

Abstract

There is no specific marker to evaluate the immuno-suppressive status of cancer patients. Several markers, such as CD124, latency-associated peptide (LAP), arginase I, indole-amine-2,3-dioxygenase (IDO) and inducible nitric oxide synthase (iNOS), are known to be associated with immune suppression. However, there is little research regarding the change in these parameters after chemotherapy. The present study enrolled 23 chemo-naïve non-small cell lung cancer (NSCLC) patients and 19 healthy donors. From the 23 NSCLC patients, 11 post-chemotherapy samples were collected. Surface and functional markers were analyzed by flow-cytometry. The mean fluorescence intensities (MFI) of iNOS were higher and the MFI of LAP were lower in NSCLC patient than in healthy donors (P < 0.05). In a comparison of pre-chemotherapy and post-chemotherapy groups with NSCLC, the MFI of iNOS on granulocytes and monocytes and IDO on monocytes were significantly lower in the post-chemotherapy group than in the pre-chemotherapy group (P < 0.05). In a serial analysis with 10 patients who had paired samples and who showed clinical benefits from chemotherapy, the MFI of iNOS for both cell types, and of IDO and CD124 for monocytes decreased significantly after chemotherapy, compared with those before chemotherapy (iNOS, 4.79 ± 1.75 vs 2.83 ± 0.77, P = 0.005, for granulocytes and 6.15 ± 2.94 vs 2.76 ± 1.05, P = 0.005 for monocytes; IDO, 6.81 ± 3.43 vs 4.64 ± 1.55, P = 0.012 for monocytes; CD124, 2.31 ± 0.39 vs 1.94 ± 0.43, P = 0.008 for monocytes). The changes in arginase I and LAP expression were not significant. The changes in iNOS, IDO and CD124 expression were significant after chemotherapy in NSCLC. Further evaluation of the possibility of immune status monitoring using these parameters is needed.

摘要

目前尚无评估癌症患者免疫抑制状态的特定标志物。几种标志物,如 CD124、潜伏相关肽 (LAP)、精氨酸酶 I、吲哚胺 2,3-双加氧酶 (IDO) 和诱导型一氧化氮合酶 (iNOS),与免疫抑制有关。然而,关于化疗后这些参数变化的研究甚少。本研究纳入了 23 例未经化疗的非小细胞肺癌 (NSCLC) 患者和 19 名健康供者。从 23 例 NSCLC 患者中,采集了 11 例化疗后的样本。通过流式细胞术分析表面和功能标志物。与健康供者相比,NSCLC 患者的 iNOS 平均荧光强度 (MFI) 较高,LAP 的 MFI 较低 (P < 0.05)。在 NSCLC 患者化疗前和化疗后的比较中,化疗组粒细胞和单核细胞上的 iNOS MFI 以及单核细胞上的 IDO MFI 明显低于化疗前 (P < 0.05)。在对 10 例有配对样本且对化疗有临床获益的患者进行的连续分析中,与化疗前相比,两种细胞类型的 iNOS MFI,以及单核细胞的 IDO 和 CD124 MFI 均显著降低 (iNOS,4.79 ± 1.75 比 2.83 ± 0.77,P = 0.005,粒细胞;6.15 ± 2.94 比 2.76 ± 1.05,P = 0.005,单核细胞;IDO,6.81 ± 3.43 比 4.64 ± 1.55,P = 0.012,单核细胞;CD124,2.31 ± 0.39 比 1.94 ± 0.43,P = 0.008,单核细胞)。精氨酸酶 I 和 LAP 表达的变化不显著。化疗后 NSCLC 中 iNOS、IDO 和 CD124 的表达发生变化。需要进一步评估使用这些参数监测免疫状态的可能性。

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