两个基因比一个更好:联合疗法选择性地杀死胰腺癌细胞

P&S研究人员在试管和动物研究中报告了有希望的结果

纽约，NY -AUG。2001年27日 - 一种两拳，基于基因的治疗可能有一天会为其疾病提供胰腺癌的另一种治疗选择，这是一个特别激进的癌症和诊断后不久的真正死刑。哥伦比亚大学医师和外科医生（P＆S）研究人员报告说，一种阻止肿瘤生长的基因 - 称为MDA-7 - 与试管中杀死K-RAS癌细胞杀死胰腺癌细胞的DNA片段实验。组合方法还防止了动物的肿瘤生长。调查结果在8月28日刊上报告了国家科学院的诉讼。“我认为观察结果非常挑衅，随着较小的调整，可能导致有效的治疗毁灭性和侵略性的疾病，”P＆S和铅研究员临床病理学教授Paul B. Fisher博士说。根据美国癌症协会，2001年，美国的29,200人将被诊断为2001年的胰腺癌，约28,900人死于该疾病。在发现癌症后，大约2％的胰腺癌患者至少一年，甚至很少生存五年。目前的手术，化疗和放射治疗不是很有效。 Dr. Fisher decided to test the combination approach because his prior research had shown the mda-7 protein could stop the growth of a variety of cancer cells, but not pancreatic cancer cells. “The mda-7 protein is a good candidate as a possible therapy because it does not have a deleterious effect on normal cells,” Fisher says. In fact, clinical studies elsewhere are testing the safety of mda-7 in other types of cancers. K-ras is a type of protein inside a cell involved in controlling cell division and cell signaling. Scientists believe a change in the K-ras gene, which occurs in 85 percent to 95 percent of pancreatic cancers, may lead to tumors, or the uncontrolled growth of cells. Mutated ras proteins, which includes altered K-ras, are targets in several ongoing cancer clinical trials. In the study, Dr. Fisher and researchers in his laboratory genetically engineered an adenovirus, a common virus that causes respiratory problems, to contain the mda-7 gene. The virus delivers the mda-7 gene to pancreatic cells but cannot reproduce, thereby persisting in cells only for a few generations. Adenovirus has been used previously as a carrier in gene therapy experiments. Using what is called antisense methodology, Dr. Fisher also worked with a small piece of DNA, 18 base pairs long, that acts to prevent the formation of the K-ras protein. Such DNA, when introduced inside a cell, blocks the initiation of K-ras gene expression and prevents the protein from being made. Scientists have also investigated giving patients pieces of antisense DNA for treatment in a variety of diseases. In the PNAS study, the researchers found the mda-7 gene and the antisense K-ras DNA combination killed pancreatic cancer cells in test tube experiments after three days of treatment. Pancreatic cancer cells continued to grow if they were treated with either the mda-7 alone or the antisense K-ras DNA. The scientists also showed the combination prevented tumor growth in animals. The investigators now believe they understand why mda-7 introduced on its own cannot kill pancreatic cancer cells. Although the gene is expressed and a chemical intermediary, messenger RNA, is manufactured, the actual functioning protein is not made in these cells. But when the scientists also blocked K-ras, the cells were able to make mda-7 protein. Dr. Fisher’s laboratory now is working to improve the way the mda-7 gene and K-ras antisense DNA get into pancreatic cancer cells. While the two pieces of DNA were introduced separately in the current research, getting both into one delivery system, called a bipartite virus, might be even more efficient, Dr. Fisher says.

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·PNAS新闻办公室的记者可获得该文件的副本，电话:202-334-2138或pnasnews@nas.edu.．

·P＆S助理科学家Zao-Zhong Su博士伊琳娜V.Lebeva博士和Rahul V.Gopallrishnan博士参加了Cy Stein博士，临床医学副教授（在药理学中）。

· Collaborators on this project included Dr. John C. Reed, scientific director, Burnham Institute, La Jolla, Calif., Dr. Neil I. Goldstein, vice president, DGI Biotechnologies, Edison, N.J., and Dr. Paul Dent, associate professor, Medical College of Virginia, Richmond.

·Michael and Stella Chernow捐赠基金和Samuel Waxman癌症研究基金会支持了这项研究。Fisher博士也是P&S的神经肿瘤学研究主任和Michael and Stella Chernow泌尿系统癌症研究科学家。

·6英寸长的胰腺是一个位于腹部的腺体，它分泌胰液，包括帮助消化食物的激素和胰岛素。

胰腺癌的存活率很低，因为它很难早期发现。当一个人出现黄疸或腹痛等症状时，癌细胞可能已经扩散到其他器官。

·美国国家癌症研究所(National Cancer Institute)表示，尽管传统疗法可以缓解症状，但由于现有疗法效果不佳，任何阶段的胰腺癌患者都可以考虑进行临床试验。

患胰腺癌的风险随着年龄的增长而增加。吸烟和糖尿病是胰腺癌的其他危险因素。