Rozel Stefan, Galbán Craig J, Nicolay Klaas, Lee Kuei C, Sud Sudha, Neeley Chris, Snyder Linda A, Chenevert Thomas L, Rehemtulla Alnawaz, Ross Brian D, Pienta Kenneth J
Department of Biomedical Engineering, Biomedical NMR, Eindhoven, University of Technology, Eindhoven, The Netherlands.
J Cell Biochem. 2009 May 1;107(1):58-64. doi: 10.1002/jcb.22056.
Metastatic prostate cancer continues to be the second leading cause of cancer death in American men with an estimated 28,660 deaths in 2008. Recently, monocyte chemoattractant protein-1 (MCP-1, CCL2) has been identified as an important factor in the regulation of prostate metastasis. CCL2, shown to attract macrophages to the tumor site, has a direct promotional effect on tumor cell proliferation, migration, and survival. Previous studies have shown that anti-CCL2 antibodies given in combination with docetaxel were able to induce tumor regression in a pre-clinical prostate cancer model. A limitation for evaluating new treatments for metastatic prostate cancer to bone is the inability of imaging to objectively assess response to treatment. Diffusion-weighted MRI (DW-MRI) assesses response to anticancer therapies by quantifying the random (i.e., Brownian) motion of water molecules within the tumor mass, thus identifying cells undergoing apoptosis. We sought to measure the treatment response of prostate cancer in an osseous site to docetaxel, an anti-CCL2 agent, and combination treatments using DW-MRI. Measurements of tumor apparent diffusion coefficient (ADC) values were accomplished over time during a 14-day treatment period and compared to response as measured by bioluminescence imaging and survival studies. The diffusion data provided early predictive evidence of the most effective therapy, with survival data results correlating with the DW-MRI findings. DW-MRI is under active investigation in the pre-clinical and clinical settings to provide a sensitive and quantifiable means for early assessment of cancer treatment outcome.
转移性前列腺癌仍是美国男性癌症死亡的第二大主要原因，2008年估计有28,660人死亡。最近，单核细胞趋化蛋白-1（MCP-1，CCL2）已被确定为前列腺转移调控中的一个重要因素。CCL2可吸引巨噬细胞至肿瘤部位，对肿瘤细胞的增殖、迁移和存活具有直接促进作用。先前的研究表明，抗CCL2抗体与多西他赛联合使用能够在临床前前列腺癌模型中诱导肿瘤消退。评估转移性前列腺癌骨转移新疗法的一个限制是成像无法客观评估治疗反应。扩散加权磁共振成像（DW-MRI）通过量化肿瘤块内水分子的随机（即布朗）运动来评估对抗癌疗法的反应，从而识别正在经历凋亡的细胞。我们试图使用DW-MRI测量骨部位前列腺癌对多西他赛、抗CCL2药物及联合治疗的反应。在14天的治疗期间内，随时间测量肿瘤表观扩散系数（ADC）值，并与通过生物发光成像和生存研究所测量的反应进行比较。扩散数据提供了最有效疗法的早期预测证据，生存数据结果与DW-MRI结果相关。DW-MRI正在临床前和临床环境中积极研究，以提供一种敏感且可量化的手段用于早期评估癌症治疗结果。
