Unnithan Jaya, Macklis Roger M
Department of Radiation Oncology, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Cancer Invest. 2004;22(4):522-5. doi: 10.1081/cnv-200026397.
TRAIL/Apo-2 L, a member of the Tumor Necrosis Factor cytokine family, induces apoptosis specifically in malignant cells. A combination of TRAIL and radiation is highly synergistic in in vitro experiments. In addition to this additive effect, we observed that TRAIL is induced by irradiation of certain cell lines. The induction begins approximately 2 hours after irradiation. This might even enhance the antineoplastic effect of ionizing radiation and partially explain the abscopal effect observed in hematopoietic malignancies. TRAIL levels were evaluated in 17 patients treated with radiation for Hodgkin's and non-Hodgkin's lymphoma. We did not observe a specific TRAIL expression pattern that could be correlated with histology, disease status, volume of disease, radiation dose, and other antineoplastic therapies, but a definite pattern observed in a single patient remained constant over time. TRAIL and interferons display a common pattern of gene expression at certain nodal points of interaction between the two physiologic pathways. Our hypothesis is that the radiation-induced changes in TRAIL expression observed in patients undergoing therapeutic radiation may be emblematic of the various physiologic pathways induced or inhibited by ionizing radiation and may even be partially responsible for the "bystander effect" observed in unirradiated cells in close proximity to irradiated cells.
肿瘤坏死因子相关凋亡诱导配体（TRAIL）/Apo-2配体是肿瘤坏死因子细胞因子家族的一员，可特异性诱导恶性细胞凋亡。在体外实验中，TRAIL与放疗联合具有高度协同作用。除了这种相加效应外，我们还观察到某些细胞系经照射后可诱导TRAIL表达。诱导作用在照射后约2小时开始。这甚至可能增强电离辐射的抗肿瘤作用，并部分解释在造血系统恶性肿瘤中观察到的远隔效应。对17例接受放疗的霍奇金淋巴瘤和非霍奇金淋巴瘤患者的TRAIL水平进行了评估。我们未观察到与组织学、疾病状态、疾病体积、放疗剂量及其他抗肿瘤治疗相关的特定TRAIL表达模式，但在一名患者中观察到的明确模式随时间保持不变。TRAIL与干扰素在这两种生理途径相互作用的某些节点上表现出共同的基因表达模式。我们的假设是，在接受治疗性放疗的患者中观察到的放疗诱导的TRAIL表达变化可能是电离辐射诱导或抑制的各种生理途径的标志，甚至可能部分导致在紧邻受照射细胞的未受照射细胞中观察到的“旁观者效应”。
