生物谷:借助于一种从蝎子毒液中提取出来的“染色剂”,癌症手术将会更加容易和有效。这种能发光的染色剂能帮助医生分辨出哪是健康的组织,哪是肿瘤,即使肿瘤仅仅只有数百个细胞组成。
这种被称为氯代毒素(Chlorotoxin)的染色剂是由蝎子毒液中的一种蛋白质制成的,它可以选择性地绑定在癌细胞上。美国西雅图儿童医院的研究人员通过将氯代毒素和一种名为Cy5.5的荧光指示剂结合使用,创建了一种使肿瘤突显于健康细胞的背景之上的方法。
该项目的负责人詹姆斯.奥尔森希望这种肿瘤染色技术能够彻底改善癌症手术治疗,因为这种方法可以让医生看见其他方法不能检测到的癌细胞,从而带给病人更好的治疗效果。
目前,手术治疗仍然是对付肿瘤的主要方法。尽管技术不断进步,手术医生还是常常依赖颜色、纹理和血液供应等情况来区分癌变组织和健康组织。但这样做有它的局限性,癌变有可能在以后复发。比如在脑肿瘤手术中,因为在手术后,仍遗留有一些癌细胞,经过一段时间,在原手术部位的边缘,80%的恶性肿瘤可能会归来。
核磁共振影像(MRI)扫描技术可以分辨出肿瘤和健康的组织,但前提是肿瘤中至少含有100万个癌细胞。而使用氯代毒素染色术,可以分辨出实验鼠体内仅有2000个癌细胞的肿瘤。
利用氯代毒素染色术来进行肿瘤手术,将帮助医生避免切除正常的组织,也不会遗留下任何癌变的组织。
奥尔森表示,还需要经过几个阶段的临床试验,以确认这项技术不会有毒副作用,才能将之应用于癌症患者。
这项研究成果发表在本月出版的《癌症研究》上。(科技日报)
原始出处:
Cancer Research 67, 6882-6888, July 15, 2007. doi: 10.1158/0008-5472.CAN-06-3948
Experimental Therapeutics, Molecular Targets, and Chemical Biology
Tumor Paint: A Chlorotoxin:Cy5.5 Bioconjugate for Intraoperative Visualization of Cancer Foci
Mandana Veiseh1, Patrik Gabikian2, S-Bahram Bahrami1, Omid Veiseh3, Miqin Zhang2,3, Robert C. Hackman1,4, Ali C. Ravanpay1,8, Mark R. Stroud1, Yumiko Kusuma1, Stacey J. Hansen1, Deborah Kwok1, Nina M. Munoz1, Raymond W. Sze5, William M. Grady6,10,11, Norman M. Greenberg1, Richard G. Ellenbogen2,9 and James M. Olson1,4,7,8,9
1 Clinical Research Division, Fred Hutchinson Cancer Research Center; Departments of 2 Neurosurgery, 3 Material Science, 4 Pathology, 5 Radiology, 6 Medicine, and 7 Pediatrics, and 8 Program in Neurobiology and Behavior, University of Washington; 9 Children's Hospital and Regional Medical Center; and 10 Puget Sound Health Care System, Seattle, Washington; and 11 Cancer Biology Department, Vanderbilt University Medical School, Nashville, Tennessee
Requests for reprints: James M. Olson, Fred Hutchinson Cancer Research Center, Mailstop D4-100, 1100 Fairview Avenue N., Seattle, WA 98109. Phone: 206-667-7955; Fax: 206-667-2917; E-mail: jolson@fhcrc.org .
Toward the goal of developing an optical imaging contrast agent that will enable surgeons to intraoperatively distinguish cancer foci from adjacent normal tissue, we developed a chlorotoxin:Cy5.5 (CTX:Cy5.5) bioconjugate that emits near-IR fluorescent signal. The probe delineates malignant glioma, medulloblastoma, prostate cancer, intestinal cancer, and sarcoma from adjacent non-neoplastic tissue in mouse models. Metastatic cancer foci as small as a few hundred cells were detected in lymph channels. Specific binding to cancer cells is facilitated by matrix metalloproteinase-2 (MMP-2) as evidenced by reduction of CTX:Cy5.5 binding in vitro and in vivo by a pharmacologic blocker of MMP-2 and induction of CTX:Cy5.5 binding in MCF-7 cells following transfection with a plasmid encoding MMP-2. Mouse studies revealed that CTX:Cy5.5 has favorable biodistribution and toxicity profiles. These studies show that CTX:Cy5.5 has the potential to fundamentally improve intraoperative detection and resection of malignancies. [Cancer Res 2007;67(14):6882–8]