美國科學家利用異種移植小鼠驗證癌症藥物的個體化療效(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.
通過切取病人腫瘤上的少許組織並移植到小鼠身上，約翰霍普金斯醫學院Kimmel癌症中心的專家可以通過精確的試驗預先獲知哪種化療藥物能夠提供給個體胰腺癌病人以最好治療。

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.
盡管細胞或新鮮組織的異種移植術已經廣泛用於癌症治療研究，但霍普金斯的專家們仍可為初期化療後複發的每一個病人設計出極具個人化的治療方案。霍普金斯醫學院Kimmel癌症中心的的腫瘤學講師Antonio Jimeno說道：“最終我們的方法將可以用於個體化治療的早期從而取代目前治療最初應用於每個病人的標準藥物吉西他濱，這種藥物目前的治療成功率不高於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名手術後的病人進行了預試驗，結果顯示每個異種移植小鼠的遺傳譜經曆3~4代仍保持穩定，因此這種方法可以精確地反映胰腺癌病人腫瘤的的情況。科學家還發現約有80%的胰腺癌病人可以構建出自己的異種移植小鼠。相比結腸癌病人，這是一個相當成功的高比率，後者的比率正常情況下低於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.
他們的工作發表在最近一期的《臨床癌症研究》雜誌上，並在9月份在芝加哥舉辦的美國癌症研究協會的會議上宣讀了結果。霍普金斯的研究小組聲稱僅需要一丁點病人的手術切除後的腫瘤樣本，然後將其移植到一到兩隻小鼠上。這些腫瘤細胞在小鼠身上生長幾個月後，將腫瘤團塊切除，並切碎後移植到更多的小鼠身上，最終構建出20隻包含匹配病人腫瘤樣本的小鼠。

"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說：“依據此法按比例放大，我們可以得到足夠的腫瘤樣本並隨機分組來試驗候選藥物。”據他說這一過程目前需耗時6個月以得到最好藥物的信息。“大多數病人正在進行他們的第一輪化療和放療，起初一旦病人病情複發，異種移植小鼠提供的信息可以指導治療，通常情況下胰腺癌的複發一般在第一輪治療的9~12個月後。”

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.
霍普金斯研究小組在霍普金斯醫院就診的40名非轉移性胰腺癌病人身上進行了異種移植小鼠模型的臨床試驗。試驗中病人的腫瘤樣本由病理學家直接傳遞到霍普金斯實驗室，在這兒將樣本移植到第一隻小鼠身上，而後構建好的20隻小鼠分別試驗大約20種目前用於胰腺癌治療的藥物。

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說：“如果這一模型有效，那我們將把這種方法應用於更廣泛的胰腺癌患者群。對於每一位患者而言，這是相當重要的治療信息。

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.
該項研究的信息或許也可以發現一些新的生物標記來預測藥物反應和關於某種治療手段在體內如何作用的數據，最終他們希望能夠擴大使用異種移植的腫瘤樣本，這些樣本可以通過細針抽吸活檢獲得。。

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.
胰腺癌在美國大概每年有33，000起新發病例，幾乎和死亡人數一樣多。它是最致命癌症的一種，五年生存率低於5%.