約翰霍普金斯醫(yī)學(xué)院Kimmel癌癥中心的研究人員發(fā)現(xiàn),，如果接受卵巢癌治療的婦女之腫瘤細胞含有大量的引發(fā)畸型生長,、降低細胞死亡的結(jié)合蛋白—NAC-1,，腫瘤復(fù)發(fā)的風(fēng)險會增加,。
研究作者Ie-Ming Shih副教授表示,，可以通過檢測手術(shù)摘除的癌癥組織中的檢測NAC-1蛋白,，判斷這些接受手術(shù)的婦女癌癥復(fù)發(fā)的可能性,，提高醫(yī)生和患者警惕,，增加治療效果。文章還強調(diào),，阻斷NAC-1的活性,，是預(yù)防、治療卵巢癌復(fù)發(fā)的一種治療方法,。研究結(jié)果刊登于12月5日的PNAS中,。
根據(jù)統(tǒng)計，接受原發(fā)性腫瘤治療的晚期卵巢癌婦女中,，60％的病例會復(fù)發(fā),。研究人員對比兩個醫(yī)院提供的338個卵巢癌患者的原發(fā)和次發(fā)性腫瘤樣本，發(fā)現(xiàn)次發(fā)性腫瘤樣本中NAC-1的含量,，比同一患者來源的原發(fā)性腫瘤樣本中的含量明顯高出許多,。原發(fā)性癌癥患者如果NAC-1含量高的話，接受手術(shù)一年后更易發(fā)生次發(fā)性癌癥,。
為了研究NAC-1的功能,，研究人員利用遺傳工程修飾細胞，使其能夠產(chǎn)生NAC-1和一種在天然NAC-1末端出現(xiàn)的成分,。結(jié)果顯示,，N130會遮蔽NAC-1蛋白，阻止其互相結(jié)合,，進而預(yù)防腫瘤形成,，而殺死實驗小鼠體內(nèi)的癌細胞。Shih認為,，將來有望發(fā)展出一種N130類似物用于癌癥治療,。
英文原文：
‘CLUMPING’ PROTEIN LINKED TO RETURN OF OVARIAN CANCER
Johns Hopkins scientists have discovered that women treated for ovarian cancer are at increased risk of a rapid and potentially fatal recurrence if their tumor cells have high levels of a binding protein that triggers abnormal growth and slows down cell death, both hallmarks of malignancy.
“Now there’s the possibility that testing for NAC-1 protein in cancer tissue removed during surgery might identify women most at risk for recurrence and guide doctors and patients to greater vigilance and extended therapy,” said Ie-Ming Shih, M.D., Ph.D., associate professor of pathology at Johns Hopkins Kimmel Cancer Center. The research also suggests that drugs capable of blocking NAC-1 activity may be a useful strategy in preventing and treating recurrences as well.
A report on the research, the first to link NAC-1 to cancer, appears in the December 5 issue of the Proceedings of the National Academy of Sciences.
“Because recurrent cancers are often what really kill patients, and most ovarian cancer is diagnosed when it’s already advanced, our findings offer women a better chance of catching or preventing recurrent disease early and increasing survival,” says Shih.
An estimated at least 60 percent of advanced-stage ovarian cancer patients who appear to be disease-free after initial treatment develop recurrent disease, according to the researchers.
When the investigators compared levels of NAC-1 among primary and recurrent tumor samples taken from 338 ovarian cancer patients from two hospitals, they found that levels of NAC-1 were significantly higher in recurrent tumors compared with primary tumors taken from the same patient. Women whose primary cancers had high levels of NAC-1 were more likely to suffer a recurrence within one year.
Studying the functions of NAC-1, the researchers genetically modified cells so they made both NAC-1 and a component of the protein found at the ends of natural NAC-1 that is a binding site. In the modified cells, N130 capped off NAC-1 proteins disrupting their ability to bind with each other. This action can prevent tumor formation and kill cancer cells in experimental mice. Shih says that in the future, drugs that mimic N130 can be used to treat cancer.
This research was supported by the Department of Defense and the National Institutes of Health.
Co-authors of the published research include Kentaro Nakayama, Naomi Nakayama, Jim J.-C. Sheu, Antonio Santillan, Ritu Salani, Natini Jinawath, Robert E. Bristow, Robert J. Kurman, and Tian-Li Wang from Johns Hopkins; Ben Davidson from the Norwegian Radium Hospital, Oslo, Norway; and Patrice J. Morin from the National Institute on Aging, NIH.
