约翰霍普金斯医学院Kimmel癌症中心的研究人员发现，如果接受卵巢癌治疗的妇女之肿瘤细胞含有大量的引发畸型生长、降低细胞死亡的结合蛋白—NAC-1，肿瘤复发的风险会增加。
研究作者Ie-Ming Shih副教授表示，可以通过检测手术摘除的癌症组织中的检测NAC-1蛋白，判断这些接受手术的妇女癌症复发的可能性，提高医生和患者警惕，增加治疗效果。文章还强调，阻断NAC-1的活性，是预防、治疗卵巢癌复发的一种治疗方法。研究结果刊登于12月5日的PNAS中。
根据统计，接受原发性肿瘤治疗的晚期卵巢癌妇女中，60％的病例会复发。研究人员对比两个医院提供的338个卵巢癌患者的原发和次发性肿瘤样本，发现次发性肿瘤样本中NAC-1的含量，比同一患者来源的原发性肿瘤样本中的含量明显高出许多。原发性癌症患者如果NAC-1含量高的话，接受手术一年后更易发生次发性癌症。
为了研究NAC-1的功能，研究人员利用遗传工程修饰细胞，使其能够产生NAC-1和一种在天然NAC-1末端出现的成分。结果显示，N130会遮蔽NAC-1蛋白，阻止其互相结合，进而预防肿瘤形成，而杀死实验小鼠体内的癌细胞。Shih认为，将来有望发展出一种N130类似物用于癌症治疗。
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.
