美国科学家利用异种移植小鼠验证癌症药物的个体化疗效(ZT)

By slicing up bits of patient tumors and grafting them into mice, Johns Hopkins Kimmel Cancer Center specialists have figured out how to accurately "test drive" chemotherapy drugs to learn in advance which drug treatments offer each individual pancreatic cancer patient the best therapeutic journey.
通过切取病人肿瘤上的少许组织并移植到小鼠身上，约翰霍普金斯医学院Kimmel癌症中心的专家可以通过精确的试验预先获知哪种化疗药物能够提供给个体胰腺癌病人以最好治疗。

Although "xenografting" with either cells or fresh tissue is already used widely to test cancer therapies, the Hopkins design is personalized to each patient who has relapsed after an initial course of chemotherapy. "Eventually our approach offers a promising way to individualize therapy earlier in treatment instead of first giving everyone the standard drug gemcitabine, which has a success rate of less than 10 percent," says Antonio Jimeno, M.D., instructor in oncology at the Johns Hopkins Kimmel Cancer Center.
尽管细胞或新鲜组织的异种移植术已经广泛用于癌症治疗研究，但霍普金斯的专家们仍可为初期化疗后复发的每一个病人设计出极具个人化的治疗方案。霍普金斯医学院Kimmel癌症中心的的肿瘤学讲师Antonio Jimeno说道：“最终我们的方法将可以用于个体化治疗的早期从而取代目前治疗最初应用于每个病人的标准药物吉西他滨，这种药物目前的治疗成功率不高于10%。”

Results of preliminary tests of the Hopkins method in 14 patient samples taken after surgery shows that each xenografts' genetic profile remained stable through three and four generations of mice so that "test drives" would accurately represent a patient's tumor. The scientists also found they could build xenografts in 80 percent of their pancreatic patients, a success rate higher than efforts with colon cancer patients, for which rates are typically less at about 50 percent.
霍普金斯方法利用14名手术后的病人进行了预试验，结果显示每个异种移植小鼠的遗传谱经历3~4代仍保持稳定，因此这种方法可以精确地反映胰腺癌病人肿瘤的的情况。科学家还发现约有80%的胰腺癌病人可以构建出自己的异种移植小鼠。相比结肠癌病人，这是一个相当成功的高比率，后者的比率正常情况下低于50%。

Reporting on their work in a recent issue of Clinical Cancer Research and at the September meeting of the American Association for Cancer Research in Chicago, the Hopkins team said it took tiny bits of a patient's tumor removed after surgery, and implanted them into one or two mice. After letting the resulting tumor grow for several months, they removed the mass and cut it into pieces to implant into additional mice, eventually creating 20 animals containing matching samples of a single patient's tumor.
他们的工作发表在最近一期的《临床癌症研究》杂志上，并在9月份在芝加哥举办的美国癌症研究协会的会议上宣读了结果。霍普金斯的研究小组声称仅需要一丁点病人的手术切除后的肿瘤样本，然后将其移植到一到两只小鼠上。这些肿瘤细胞在小鼠身上生长几个月后，将肿瘤团块切除，并切碎后移植到更多的小鼠身上，最终构建出20只包含匹配病人肿瘤样本的小鼠。

"By scaling up this way, we got enough tumor samples to randomize mice into groups for testing candidate drugs," says Manuel Hidalgo, M.D., Ph.D., associate professor at Hopkins' Kimmel Cancer Center, who says the process currently requires about six months to get information on which drugs work best. "In the meantime, most patients are receiving their first rounds of chemotherapy and radiation. Initially, xenograft information can guide therapy once patients relapse, which is generally in nine to twelve months with pancreatic cancer."
霍普金斯Kimmel癌症中心的副教授Manuel Hidalgo说：“依据此法按比例放大，我们可以得到足够的肿瘤样本并随机分组来试验候选药物。”据他说这一过程目前需耗时6个月以得到最好药物的信息。“大多数病人正在进行他们的第一轮化疗和放疗，起初一旦病人病情复发，异种移植小鼠提供的信息可以指导治疗，通常情况下胰腺癌的复发一般在第一轮治疗的9~12个月后。”

The Hopkins group is conducting a clinical trial of the xenograft model in 40 patients undergoing surgery at Johns Hopkins for non-metastatic pancreas cancer. In the trial, a portion of each patient's tumor is shuttled directly from the pathologist to the Hopkins' laboratory where the first mice are implanted and the 20 mice "built" to test the 20 or so drugs currently available against pancreatic cancer.
霍普金斯研究小组在霍普金斯医院就诊的40名非转移性胰腺癌病人身上进行了异种移植小鼠模型的临床试验。试验中病人的肿瘤样本由病理学家直接传递到霍普金斯实验室，在这儿将样本移植到第一只小鼠身上，而后构建好的20只小鼠分别试验大约20种目前用于胰腺癌治疗的药物。

Says Jimeno, "If this model works, then we'll need to develop ways to apply it to a broader population of pancreatic cancer patients since there are significant laboratory resources necessary for each patient."
Jimeno说：“如果这一模型有效，那我们将把这种方法应用于更广泛的胰腺癌患者群。对于每一位患者而言，这是相当重要的治疗信息。

Information from the study also may reveal new biomarkers that predict drug response and data on how certain therapies act within the body. Ultimately, they hope to broaden use of xenografting to tumor samples that can be accessed via biopsy through fine needle aspiration.
该项研究的信息或许也可以发现一些新的生物标记来预测药物反应和关于某种治疗手段在体内如何作用的数据，最终他们希望能够扩大使用异种移植的肿瘤样本，这些样本可以通过细针抽吸活检获得。。

Pancreatic cancer accounts for more than 33,000 new cases in the United States and almost as many deaths. It is one of the deadliest cancers, with less than five percent of patients living beyond five years.
胰腺癌在美国大概每年有33，000起新发病例，几乎和死亡人数一样多。它是最致命癌症的一种，五年生存率低于5%.