New investigational gene therapy strategy very successful against human pancreatic cancer in animal model.侦查新的基因治疗策略非常成功,对人类胰腺癌动物模型.

A molecularly engineered gene therapy selectively embeds a cancer-killing gene in pancreatic cancer that shrinks or eradicates tumors, inhibits metastasis, and prolongs survival with virtually no toxicity, researchers from The University of Texas M. D. Anderson Cancer Center report in the July 9, 2007 edition of Cancer Cell .分子工程基因疗法选择性地嵌入肿瘤杀伤基因在胰腺癌中,退缩或杜绝肿瘤抑制转移,延长生存几乎无毒性,这项研究是由德州大学四公尺安德森癌症中心报告,在2007年7月9日版的癌细胞.

“This vehicle, or vector, is so targeted and robust in its cancer-specific expression that it can be used for therapy and perhaps for imaging,” notes senior author Mien-Chie Hung, Ph.D., professor and chair of M. D. Anderson’s Department of Molecular and Cellular Oncology."这车,或载体,如此有针对性的和强有力的肿瘤特异性表达,也可用于治疗,也许象"注资深作者勉治洪,博士,教授,并担任四公尺安达通部分子和细胞肿瘤.

The researchers call the system a versatile expression vector - nicknamed VISA.研究者调用系统灵活的表达载体--绰号签证. It includes a targeting agent, also called a promoter, two components that boost gene expression in the target tissue, and a payload - in this case a gene known to kill cancer cells.它包括了靶向剂,又称为启动,两个组成部分,提高基因在靶组织,和载荷--在本案中的一个已知的基因来杀死癌细胞. It’s all packaged in a fatty ball called a liposome and delivered intravenously.它的所有包装的脂肪球称为脂质并作了静脉注射.

Researchers are working with M. D. Anderson clinicians to move the system, developed and tested in mouse models of pancreatic cancer, to a Phase I clinical trial in people.研究人员目前正与四公尺安德森医生动议系统制定和测试老鼠模型中,胰脏癌,一期临床试验在人.

“This looks like a promising approach to gene therapy for pancreatic cancer and we are working to bring it to a clinical trial,” says James Abbruzzese, M.D., professor and chair of the M. D. Anderson Department of Gastrointestinal Oncology."这看似一个简单的方法是基因治疗胰腺癌,我们正在努力使其临床试验,"祝基阿布鲁泽塞,医学博士,教授,并主持了四公尺安德森部胃肠道肿瘤.

He estimates that it will take between one and two years to complete U.S. Food and Drug Administration requirements for a Phase I trial.他估计将用1至2年时间才能完成,美国食品和药物管理局要求一期试验. Abbruzzese’s clinicians are working with Hung’s group to compile preclinical information for FDA review.阿布鲁泽塞的医护人员正与红组编制前期资料,经FDA审查.

About 37,000 cases of pancreatic cancer are diagnosed annually in the United States.约37000例胰腺癌诊断每年都在美国. Early diagnosis is extremely difficult, so the disease is often discovered at a late stage after it already has spread, or metastasized.早期诊断极为困难,所以疾病是经常发现,在这么晚的阶段后,它已经蔓延或转移. Fewer than 4 percent of pancreatic cancer patients survive five years after diagnosis, one of the lowest cancer survival rates.不到4%的胰腺癌患者生存5年诊断后,其中最低的癌症存活率.

In a test of the therapy against two aggressive lines of human pancreatic cancer cells in two different types of mice, researchers loaded the VISA system with a mutant version of a gene named Bik, which expresses a protein that naturally forces cancer cells to kill themselves.经测试,该疗法对两名进攻线路的人胰腺癌细胞在两种不同类型的小鼠,研究者装货的签证制度与突变版本的基因命名演出,其中表达了蛋白质,在自然力量癌细胞杀死自己. The team created the more lethal mutant and named it BikDD.队创造了更加致命的突变命名bikdd.

Untreated control mice in both experiments all died within 40 days.对照组小鼠在实验全部死亡后40天内. Mice treated with the mutant gene delivered via a less-targeted viral promoter driven expression system employing cytomegalovirus (CMV) all died within 90 days, most much earlier.小鼠突变基因通过一个较低的靶向启动子驱动表达系统采用巨细胞病毒(CMV)全部死亡90天内,大部分早得多. In both trials, the VISA-BikDD mice lived longer, with at least half surviving for 14 months with no detectable sign of cancer recurrence.在这两起案件的审理,签证bikdd小鼠的寿命更长,其中至少有一半存活14个月,并且无迹象探测癌症复发.

The researchers tested both systems in the lab against all 13 human cell lines of pancreatic cancer available worldwide.研究者测试两个系统在实验室对所有13个细胞系胰腺癌于全世界. BikDD killed cells in all lines, with the VISA-delivered gene destroying more cells in all but one case.bikdd细胞杀死所有线路,由于签证输送基因摧毁更多细胞在每一个案件.

One test involved a pancreatic cancer line that spreads swiftly.一测试涉及胰腺癌线蔓延迅速. In that case, live imaging showed that in control mice the cancer spread to the liver, spleen, kidneys, bladder, lungs, bone and intestines.在这种情况下,活的成像结果显示,对照组小鼠的癌症蔓延到肝脏,脾脏,肾脏,膀胱癌肺部,骨骼及内脏. Mice treated with the CMV BikDD showed only a few small tumors in nearby organs.治疗后,小鼠的巨bikdd显示只有少数小肿瘤邻近器官. There were no detectable metastases in mice treated with the VISA-BikDD combination, the authors report.有没有觉察转移小鼠免bikdd组合,作者报告.

“All [conventional] cancer drugs have some toxicity and so cause side effects, which affects the dose that can be administered,” Hung says."所有[常规]抗癌药物有一定的毒性等产生副作用,影响剂量,可以管理",洪说. The team looked for signs of acute systemic toxicity and of pancreatitis, a dangerous inflammation of the pancreas.队寻找迹象,急性全身毒性和胰腺炎,是一种十分危险发炎的胰脏. While the cytomegalovirus-BikDD showed signs of both toxicities, the authors report “VISA-BikDD produces virtually no systemically acute toxicity or acute pancreatitis.” Hung’s team continues research on their gene expression vehicle, VISA.而巨bikdd呈现两种毒性,作者报告"签证bikdd产生几乎无全身急性毒性或急性胰腺炎."红队继续研究它们的基因核表达载体,签证. “VISA is versatile enough that if you change the promoter, you could target other cancers or even other diseases,” Hung says."签证是不够灵活,如果你改变推动者你可以针对其他癌症,甚至是其他疾病的",洪说.

Abbruzzese says any clinical trial will advance under a National Cancer Institute Specialized Programs of Research Excellence (SPORE) grant in pancreatic cancer.阿布鲁泽塞说任何临床试验将提前根据美国国家癌症研究所专门节目的杰出研究(孢子)补助胰腺癌. SPORE awards are designed to translate scientific findings into the clinic.孢子奖的目的是把科学发现进入诊所.

“There are no good options for pancreatic cancer patients now,” says Abbruzzese, “That’s why we are trying new approaches such as this one as part of SPORE.” M. D. Anderson, the source of this news story, has filed for a patent on VISA-BikDD, which has been licensed to Alchemgen Therapeutics Inc. (ATI)."有没有好选择胰腺癌患者,现在,"说阿布鲁泽塞,"这就是为什么我们正在尝试新的办法,如此一作为孢子."简明安德森这条消息的来源故事中,已经申请了专利,签证bikdd,已许可alchemgen疗法公司(ATI)时.