6月20日,，Sci Transl Med雜志報(bào)道了一種很有潛力的治療皮膚癌的新手段：DNA酶Dz13。
在世界范圍內(nèi),，三分之一的癌癥是皮膚相關(guān)的,，而且皮膚癌在許多人種中的發(fā)病率都在增加。研究者發(fā)現(xiàn)在小鼠腫瘤模型中,，一種靶向c-Jun mRNA的DNA酶,，Dz13，可抑制兩種常見(jiàn)的皮膚癌：基底細(xì)胞和鱗狀細(xì)胞癌的增長(zhǎng),。
研究發(fā)現(xiàn)，在免疫缺陷和同系免疫健全小鼠模型中,， dz13可抑制腫瘤的生長(zhǎng),，并可減少腫瘤轉(zhuǎn)移小鼠模型中肺轉(zhuǎn)移結(jié)節(jié)的形成。此外，在荷瘤小鼠和斑馬魚(yú)中,，Dz13抑制新生血管形成并使腫瘤細(xì)胞凋亡增加,。 dz13對(duì)腫瘤生長(zhǎng)的抑制，需要一個(gè)完整的催化結(jié)構(gòu)域,，部分原因是由于腫瘤免疫誘導(dǎo),。
經(jīng)一系列符合規(guī)范的獼猴，小型豬,，嚙齒動(dòng)物毒理學(xué)研究,，這種核酶被認(rèn)為是安全和耐受性良好的。經(jīng)過(guò)超過(guò)70項(xiàng)生理有關(guān)體外生物測(cè)定證實(shí),，Dz13對(duì)這些生理指標(biāo)無(wú)影響,，說(shuō)明它具有很小的脫靶效應(yīng)的傾向。如果這些研究結(jié)果,，在臨床試驗(yàn)中得以證實(shí),，Dz13可能提供一種安全，有效治療人類皮膚癌的手段,。(生物谷bioon.com)
doi:10.1016/j.cell.2011.10.017
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DNAzyme Targeting c-jun Suppresses Skin Cancer Growth
Hong Cai1, Fernando S. Santiago1, Leonel Prado-Lourenco1, Bo Wang1,*, Margaret Patrikakis1, Miles P. Davenport1, Ghassan J. Maghzal2, Roland Stocker2, Christopher R. Parish3, Beng H. Chong1, Graham J. Lieschke4,?, Tak-Wah Wong5, Colin N. Chesterman1, Douglas J. Francis6, Fergal J. Moloney7,?, Ross St.C. Barnetson7, Gary M. Halliday7 and Levon M. Khachigian
Worldwide, one in three cancers is skin-related, with increasing incidence in many populations. Here, we demonstrate the capacity of a DNAzyme-targeting c-jun mRNA, Dz13, to inhibit growth of two common skin cancer types—basal cell and squamous cell carcinomas—in a therapeutic setting with established tumors. Dz13 inhibited tumor growth in both immunodeficient and immunocompetent syngeneic mice and reduced lung nodule formation in a model of metastasis. In addition, Dz13 suppressed neovascularization in tumor-bearing mice and zebrafish and increased apoptosis of tumor cells. Dz13 inhibition of tumor growth, which required an intact catalytic domain, was due in part to the induction of tumor immunity. In a series of good laboratory practice–compliant toxicology studies in cynomolgus monkeys, minipigs, and rodents, the DNAzyme was found to be safe and well tolerated. It also did not interfere in more than 70 physiologically relevant in vitro bioassays, suggesting a reduced propensity for off-target effects. If these findings hold true in clinical trials, Dz13 may provide a safe, effective therapy for human skin cancer.
