一項對酞谷酰亞胺（反應停）衍生物進行的研究結(jié)果提示,，酞谷酰亞胺導致的聲名狼藉的出生缺陷很可能源于它中止了新血管的生長,。多年以來，酞谷酰亞胺被選擇性地用作抗癌藥物,，這主要是由于它具有抑制新血管生長的能力,，這讓它可以有效地對抗腫瘤。但是酞谷酰亞胺在體內(nèi)有許多分解產(chǎn)物,，尚不清楚哪種產(chǎn)物起了作用——科學家也無法準確解釋酞谷酰亞胺如何導致了出生缺陷,。
Christina Therapontos及其同事證明了一種合成的酞谷酰亞胺類似體CPS49基本中止了正在發(fā)育的胚胎的新血管生長,。這組作者在雞和斑馬魚的胚胎、培養(yǎng)的小鼠心臟以及一個人類細胞系中進行了實驗,?？瓷先ブ挥行卵苁艿搅擞绊懀貏e是肢芽的新血管,，而且它們早在被認為可能造成了出生缺陷的幾個細胞事件出現(xiàn)之前就停止生長了,。這些結(jié)果解釋了酞谷酰亞胺引發(fā)的出生缺陷如何發(fā)生在如此短的時間窗口內(nèi)。這組作者說,，這項工作可能幫助科學家尋求理解酞谷酰亞胺在抗癌治療中的作用,。（生物谷Bioon.com）
生物谷推薦原始出處：
PNAS May 11, 2009, doi: 10.1073/pnas.0901505106
Thalidomide induces limb defects by preventing angiogenic outgrowth during early limb formation
Christina Therapontosa,b, Lynda Erskineb, Erin R. Gardnerc, William D. Figgd and Neil Vargessona,b,1
Thalidomide is a potent teratogen that induces a range of birth defects, most commonly of the developing limbs. The mechanisms underpinning the teratogenic effects of thalidomide are unclear. Here we demonstrate that loss of immature blood vessels is the primary cause of thalidomide-induced teratogenesis and provide an explanation for its action at the cell biological level. Antiangiogenic but not antiinflammatory metabolites/analogues of thalidomide induce chick limb defects. Both in vitro and in vivo, outgrowth and remodeling of more mature blood vessels is blocked temporarily, whereas newly formed, rapidly developing, angiogenic vessels are lost. Such vessel loss occurs upstream of changes in limb morphogenesis and gene expression and, depending on the timing of drug application, results in either embryonic death or developmental defects. These results explain both the timing and relative tissue specificity of thalidomide embryopathy and have significant implications for its use as a therapeutic agent.
