據(jù)美國合眾國際社20日報道,，美國科學家發(fā)現(xiàn)，螢火蟲基因能有效測試一種淋巴瘤藥物的治療效果,，可用于淋巴癌早期治療,。這項研究成果發(fā)表在最近一期的《癌癥研究》雜志上,。
研究表明,，螢火蟲能夠幫助人們更清晰地觀察患有淋巴癌和白血病的成人患者體內的淋巴毒T細胞和白血病分布情況。該項實驗的研究人員表示,，如何找到這些發(fā)生病變的細胞，即如何精確評估這兩種疾病的病情一直是醫(yī)學界的難題,。
該研究小組的實驗目的在于,，利用實驗鼠測試一種破骨細胞抑制劑和蛋白酶體抑制劑PS-341的混合物的藥物效果。研究人員發(fā)現(xiàn),，通過一種控制螢火蟲發(fā)光的基因,，即可得到實驗鼠體內病變情況的清晰圖片,。這種基因能夠生產(chǎn)生化酶熒光酶素,，通過與氧氣的相互作用,，像開關一樣啟動與氧氣的相互作用，產(chǎn)生一閃一閃的光亮,。
研究人員把熒光酶素注射進已被人工植入改良后的轉基因細胞老鼠體內,。研究報告稱，實驗鼠經(jīng)過掃描后,，拍攝出來的影像經(jīng)過計算機分析可以看到,，那些包含熒光素的癌細胞在黑暗中像螢火蟲一樣的亮光,。(科技日報)
原始出處:
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: [email protected] .
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]
