据美国合众国际社20日报道，美国科学家发现，萤火虫基因能有效测试一种淋巴瘤药物的治疗效果，可用于淋巴癌早期治疗。这项研究成果发表在最近一期的《癌症研究》杂志上。
研究表明，萤火虫能够帮助人们更清晰地观察患有淋巴癌和白血病的成人患者体内的淋巴毒T细胞和白血病分布情况。该项实验的研究人员表示，如何找到这些发生病变的细胞，即如何精确评估这两种疾病的病情一直是医学界的难题。
该研究小组的实验目的在于，利用实验鼠测试一种破骨细胞抑制剂和蛋白酶体抑制剂PS-341的混合物的药物效果。研究人员发现，通过一种控制萤火虫发光的基因，即可得到实验鼠体内病变情况的清晰图片。这种基因能够生产生化酶荧光酶素，通过与氧气的相互作用，像开关一样启动与氧气的相互作用，产生一闪一闪的光亮。
研究人员把荧光酶素注射进已被人工植入改良后的转基因细胞老鼠体内。研究报告称，实验鼠经过扫描后，拍摄出来的影像经过计算机分析可以看到，那些包含荧光素的癌细胞在黑暗中像萤火虫一样的亮光。(科技日报)
原始出处:
Cancer Research 67, 11859-11866, December 15, 2007. doi: 10.1158/0008-5472.CAN-07-1701
A Novel Bioluminescent Mouse Model and Effective Therapy for Adult T-Cell Leukemia/Lymphoma
Sherry T. Shu1,2, Murali V.P. Nadella1,2, Wessel P. Dirksen1,2, Soledad A. Fernandez2,3, Nanda K. Thudi1, Jillian L. Werbeck1, Michael D. Lairmore1,2,4 and Thomas J. Rosol1,2,4
1 Department of Veterinary Biosciences, 2 Center for Retrovirus Research, 3 Center for Biostatistics, and 4 Comprehensive Cancer Center, The Arthur G. James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, Ohio
Requests for reprints: Thomas J. Rosol, Department of Veterinary Biosciences, The Ohio State University, 1925 Coffey Road, Columbus, OH 43214. Phone: 614-292-4265; Fax: 614-292-6473; E-mail: rosol.1@osu.edu .
Adult T-cell /lymphomaleukemia (ATLL) is caused by human T-cell lymphotropic virus type 1 (HTLV-1). Approximately 80% of ATLL patients develop humoral hypercalcemia of malignancy (HHM), a life-threatening complication leading to a poor prognosis. Parathyroid hormone–related protein (PTHrP) and macrophage inflammatory protein-1 (MIP-1) are important factors in the pathogenesis of HHM in ATLL and the expression of PTHrP can be activated by nuclear factor B (NF-B). NF-B is constitutively activated in ATLL cells and is essential for leukemogenesis including transformation of lymphocytes infected by HTLV-1. Our goal was to evaluate the effects of NF-B disruption by a proteasomal inhibitor (PS-341) and osteoclastic inhibition by zoledronic acid (Zol) on the development of ATLL and HHM using a novel bioluminescent mouse model. We found that PS-341 decreased cell viability, increased apoptosis, and down-regulated PTHrP expression in ATLL cells in vitro. To investigate the in vivo efficacy, nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice were xenografted with ATLL cells and treated with vehicle control, PS-341, Zol, or a combination of PS-341 and Zol. Bioluminescent imaging and tumor cell count showed a significant reduction in tumor burden in mice from all treatment groups. All treatments also significantly reduced the plasma calcium concentrations. Zol treatment increased trabecular bone volume and decreased osteoclast parameters. PS-341 reduced PTHrP and MIP-1 expression in tumor cells in vivo. Our results indicate that both PS-341 and Zol are effective treatments for ATLL and HHM, which are refractory to conventional therapy. [Cancer Res 2007;67(24):11859–66]
