Department of Nursing, Far Eastern Memorial Hospital, New Taipei City, Taiwan; Department of Nursing, Oriental Institute of Technology, New Taipei City, Taiwan; School of Nursing, National Yang-Ming University, Taipei, Taiwan.
Division of Hematology/Oncology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University-Shuang Ho Hospital; Division of Hematology/Oncology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Eur J Pharmacol. 2019 Mar 5;846:38-48. doi: 10.1016/j.ejphar.2019.01.011. Epub 2019 Jan 15.
Tartrate-resistant acid phosphatase 5a (TRACP5a) is mainly secreted by activated macrophages in chronic inflammation. Serum TRACP5a is associated with symptom distress in lung cancer patients during chemotherapy. Therefore, this study aimed to investigate whether chemotherapy drugs modulate TRACP5a as an inducible marker for symptom distress in lung cancer patients during chemotherapy. In clinical analysis, lung cancer participants completely received the six-cycle chemotherapy process (n = 42). Clinical determinations for TRACP5a, C-reactive protein (CRP), interleukin-6 (IL-6), white blood cells, monocytes, and hemoglobin were analyzed at six time points: BL, C1d8, C2d1, C4d1, C4d8, and Ed28. Meanwhile, five questionnaires for fatigue, sleep disturbance, pain, depression, and confusion were finished before drug treatment. For monocyte-to-macrophage differentiation, THP-1 cells were treated with phorbol 12-myristate 13-acetate (PMA). TRACP5a secretion in THP-1 cells was determined at the following days up to 6 days after 1-day incubation of chemotherapy drugs by dot blotting. Clinical analysis revealed that TRACP5a significantly increased at C1d8 and C4d8, but dropped at C2d1 and Ed28. CRP and IL-6 displayed a broad-range variation, resulting in no significant difference among the assessment time points. In contrast, monocytes decreased at C1d8 and C4d8, but rose again at C2d1 and Ed28. In symptom distress, the changes only in fatigue and sleep disturbance were positively associated with the trend in TRACP5a. In PMA-treated THP-1 cells, TRACP5a significantly increased after stimulation with gemcitabine and paclitaxel. Taken together, induction of TRACP5a by chemotherapy drugs might be generated from monocyte-differentiated macrophages, further causing clinical symptom distress in lung cancer patients.
抗酒石酸酸性磷酸酶 5a（TRACP5a）主要由慢性炎症中激活的巨噬细胞分泌。血清 TRACP5a 与肺癌患者化疗期间的症状困扰有关。因此，本研究旨在探讨化疗药物是否调节 TRACP5a 作为肺癌患者化疗期间症状困扰的诱导标志物。在临床分析中，肺癌患者完全接受了六个周期的化疗过程（n=42）。在六个时间点（BL、C1d8、C2d1、C4d1、C4d8 和 Ed28）分析了 TRACP5a、C-反应蛋白（CRP）、白细胞介素 6（IL-6）、白细胞、单核细胞和血红蛋白的临床测定。同时，在药物治疗前完成了五个疲劳、睡眠障碍、疼痛、抑郁和困惑问卷。对于单核细胞向巨噬细胞分化，用佛波醇 12-肉豆蔻酸 13-醋酸盐（PMA）处理 THP-1 细胞。通过斑点印迹法测定化疗药物孵育 1 天后第 6 天的 TRACP5a 分泌。临床分析表明，TRACP5a 在 C1d8 和 C4d8 时明显增加，但在 C2d1 和 Ed28 时下降。CRP 和 IL-6 表现出广泛的变化，在评估时间点之间没有差异。相比之下，单核细胞在 C1d8 和 C4d8 时减少，但在 C2d1 和 Ed28 时再次增加。在症状困扰方面，疲劳和睡眠障碍的变化仅与 TRACP5a 的趋势呈正相关。在 PMA 处理的 THP-1 细胞中，吉西他滨和紫杉醇刺激后 TRACP5a 明显增加。综上所述，化疗药物诱导的 TRACP5a 可能来自单核细胞分化的巨噬细胞，进一步导致肺癌患者的临床症状困扰。
