Johns Hopkins大學(xué)的科學(xué)家最近發(fā)明了一種治療直腸結(jié)腸癌的新方法,他們利用小型分子將放射試劑輸送到癌細(xì)胞內(nèi),,而不像目前的方法一樣是利用結(jié)合到細(xì)胞表面來從外部攻擊癌細(xì)胞,,這會造成有害副作用,。
在實驗室中針對正常細(xì)胞和癌細(xì)胞進(jìn)行的實驗中,新的放射試劑輸送系統(tǒng)被證明能特定攻擊腸癌細(xì)胞,,而剩余的物質(zhì)能很容易的被腎臟濾出,,因為輸送系統(tǒng)的分子非常小。
在10月3日的在線版PLoS one上,,Hopkins的腸癌專家John Abraham和Stephen Meltzer博士利用小分子能獲得更好的療效的想法,,設(shè)計了只有10個氨基酸長度的小型蛋白質(zhì),并將其作為他們藥物的基礎(chǔ),。與此相比,,攜帶放療或化療試劑的抗體能超過1000個氨基酸長度。
小組在分子上結(jié)合了放射性磷P32,,以測試他們的多肽能有多好的效果,,結(jié)果Abraham表示:“令人驚訝的是,第一項測試就顯示細(xì)胞能吞入這些分子,,從而將放療劑送入細(xì)胞內(nèi),,并通過破壞DNA和蛋白質(zhì)來殺死癌細(xì)胞。”
科學(xué)家同時警告這種新型放療劑輸送系統(tǒng)還不能用于人類,,但Abraham注意到P32能發(fā)出極高能量,,并穿透5毫米厚的人體組織,這意味著它是治療腸癌的很好試劑,,因為腸癌常常會形成大而厚的組織,,藥物無法很好穿透。除此之外P32結(jié)合的多肽還有一個用處:在腫瘤還很小時發(fā)現(xiàn)腸癌的轉(zhuǎn)移和復(fù)發(fā),。這些多肽能反應(yīng)出漂移的癌細(xì)胞所處位置,。
隨后Abraham、Meltzer以及他們的小組設(shè)計了多種P32-多肽,,并在18份正?;虬┳?nèi)祟惣?xì)胞樣本中進(jìn)行了測試。其中最有效的多肽MA5能和腺癌細(xì)胞結(jié)合,,腺癌構(gòu)成了腸癌的95%,,這比其它細(xì)胞類型強150倍,并能在2小時內(nèi)進(jìn)入到細(xì)胞內(nèi),。(教育部科技發(fā)展中心)
原文鏈接:http://www.physorg.com/news111162280.html
原始出處:
Received: July 11, 2007; Accepted: September 12, 2007; Published: October 3, 2007
Novel Decapeptides that Bind Avidly and Deliver Radioisotope to Colon Cancer Cells
John M. Abraham1*, Fumiaki Sato1, Yulan Cheng1, Bogdan Paun1, Takatsugu Kan1, Alexandru Olaru1, Zhe Jin1, Jian Yang1, Rachana Agarwal1, Stefan David1, James P. Hamilton1, Tetsuo Ito1, Yuriko Mori1, Stephen J. Meltzer1,2
1 Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America, 2 Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
Abstract
Background
The rapidly growing field of targeted tumor therapy often utilizes an antibody, sometimes tagged with a tumor-ablating material such as radioisotope, directed against a specific molecule.
Methodology/Principal Findings
This report describes the discovery of nine novel decapeptides which can be radioactively labeled, bind to, and deliver 32P to colon cancer cells. The decapeptides vary from one another by one to three amino acids and demonstrate vastly different binding abilities. The most avidly binding decapeptide can permanently deliver very high levels of radioisotope to the adenocarcinoma cancer cell lines at an efficiency 35 to 150 times greater than to a variety of other cell types, including cell lines derived from other types of cancer or from normal tissue.
Conclusions/Significance
This experimental approach represents a new example of a strategy, termed peptide binding therapy, for the potential treatment of colorectal and other adenocarcinomas.
全文鏈接:http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0000964