生物谷：借助于一種從蝎子毒液中提取出來(lái)的“染色劑”,，癌癥手術(shù)將會(huì)更加容易和有效。這種能發(fā)光的染色劑能幫助醫(yī)生分辨出哪是健康的組織,，哪是腫瘤,，即使腫瘤僅僅只有數(shù)百個(gè)細(xì)胞組成。
這種被稱為氯代毒素（Chlorotoxin）的染色劑是由蝎子毒液中的一種蛋白質(zhì)制成的,，它可以選擇性地綁定在癌細(xì)胞上,。美國(guó)西雅圖兒童醫(yī)院的研究人員通過(guò)將氯代毒素和一種名為Cy5.5的熒光指示劑結(jié)合使用，創(chuàng)建了一種使腫瘤突顯于健康細(xì)胞的背景之上的方法,。
該項(xiàng)目的負(fù)責(zé)人詹姆斯.奧爾森希望這種腫瘤染色技術(shù)能夠徹底改善癌癥手術(shù)治療,，因?yàn)檫@種方法可以讓醫(yī)生看見(jiàn)其他方法不能檢測(cè)到的癌細(xì)胞，從而帶給病人更好的治療效果,。
目前,，手術(shù)治療仍然是對(duì)付腫瘤的主要方法。盡管技術(shù)不斷進(jìn)步,，手術(shù)醫(yī)生還是常常依賴顏色,、紋理和血液供應(yīng)等情況來(lái)區(qū)分癌變組織和健康組織。但這樣做有它的局限性，癌變有可能在以后復(fù)發(fā),。比如在腦腫瘤手術(shù)中,，因?yàn)樵谑中g(shù)后，仍遺留有一些癌細(xì)胞,，經(jīng)過(guò)一段時(shí)間,，在原手術(shù)部位的邊緣，80％的惡性腫瘤可能會(huì)歸來(lái),。
核磁共振影像（MRI）掃描技術(shù)可以分辨出腫瘤和健康的組織,，但前提是腫瘤中至少含有100萬(wàn)個(gè)癌細(xì)胞。而使用氯代毒素染色術(shù),，可以分辨出實(shí)驗(yàn)鼠體內(nèi)僅有2000個(gè)癌細(xì)胞的腫瘤,。
利用氯代毒素染色術(shù)來(lái)進(jìn)行腫瘤手術(shù)，將幫助醫(yī)生避免切除正常的組織,，也不會(huì)遺留下任何癌變的組織。
奧爾森表示,，還需要經(jīng)過(guò)幾個(gè)階段的臨床試驗(yàn),，以確認(rèn)這項(xiàng)技術(shù)不會(huì)有毒副作用，才能將之應(yīng)用于癌癥患者,。
這項(xiàng)研究成果發(fā)表在本月出版的《癌癥研究》上,。（科技日?qǐng)?bào)）
原始出處:
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: [email protected] .
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]
