In vivo imaging enables high resolution preclinical trials on patients' leukemia cells growing in mice.
In vivo imaging enables high resolution preclinical trials on patients' leukemia cells growing in mice.
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DOI：
10.1371/journal.pone.0052798
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Jeremias I
中科院分区：
文献类型：
--
作者：
Terziyska N;Castro Alves C;Groiss V;Schneider K;Farkasova K;Ogris M;Wagner E;Ehrhardt H;Brentjens RJ;zur Stadt U;Horstmann M;Quintanilla-Martinez L;Jeremias I
异种移植小鼠模型为人类肿瘤的临床前研究提供了有用的工具。在模拟人类疾病的复杂性方面，原代肿瘤细胞远远优于已建立的细胞系。作为合格的示范模型，患者的急性淋巴细胞白血病细胞可靠地移植到小鼠体内，诱导出与男性相似的原位播散性白血病。不幸的是，由于缺乏合适的读数参数，对小鼠急性淋巴细胞白血病的疾病监测受到阻碍。患者的急性淋巴细胞白血病细胞被慢病毒转导以表达膜结合形式的Gaussia荧光素酶。在单个患者的白血病中建立了体内成像，并得到了广泛的验证。体内生物发光成像使对单个小鼠的可靠和持续跟踪成为可能。光发射与死后白血病负担的量化严格相关，并显示出对数、时间和细胞数量依赖的生长模式。在有限稀释度移植试验中，成像方便地量化了白血病启动细胞的频率。当在10,000多个骨髓细胞中检测到单个白血病细胞时，成像能够监测最小的残留病、肿瘤重新生长和复发的时间。影像以低方差准确地量化治疗效果，区分治疗失败和部分和完全反应。第一次，我们详细描述了体内成像如何随着监测分辨率的提高而改变患者来源的肿瘤的临床前研究。未来，活体成像将能够对广泛的高要求临床挑战进行精确的临床前研究，例如治疗失败、白血病启动细胞的耐药性、最小残留疾病和复发。
Xenograft mouse models represent helpful tools for preclinical studies on human tumors. For modeling the complexity of the human disease, primary tumor cells are by far superior to established cell lines. As qualified exemplary model, patients’ acute lymphoblastic leukemia cells reliably engraft in mice inducing orthotopic disseminated leukemia closely resembling the disease in men. Unfortunately, disease monitoring of acute lymphoblastic leukemia in mice is hampered by lack of a suitable readout parameter. Patients’ acute lymphoblastic leukemia cells were lentivirally transduced to express the membrane-bound form of Gaussia luciferase. In vivo imaging was established in individual patients’ leukemias and extensively validated. Bioluminescence in vivo imaging enabled reliable and continuous follow-up of individual mice. Light emission strictly correlated to post mortem quantification of leukemic burden and revealed a logarithmic, time and cell number dependent growth pattern. Imaging conveniently quantified frequencies of leukemia initiating cells in limiting dilution transplantation assays. Upon detecting a single leukemia cell within more than 10,000 bone marrow cells, imaging enabled monitoring minimal residual disease, time to tumor re-growth and relapse. Imaging quantified therapy effects precisely and with low variances, discriminating treatment failure from partial and complete responses. For the first time, we characterized in detail how in vivo imaging reforms preclinical studies on patient-derived tumors upon increasing monitoring resolution. In the future, in vivo imaging will enable performing precise preclinical studies on a broad range of highly demanding clinical challenges, such as treatment failure, resistance in leukemia initiating cells, minimal residual disease and relapse.
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DOI：
10.1158/1078-0432.ccr-09-0931
发表时间：
2009-10-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Francia G;Man S;Lee CJ;Lee CR;Xu P;Mossoba ME;Emmenegger U;Medin JA;Kerbel RS
通讯作者：
Kerbel RS
影响因子：
46.9
作者：
Ntziachristos, V;Ripoll, J;Weissleder, R
通讯作者：
Weissleder, R
影响因子：
5.4
作者：
Dull, T;Zufferey, R;Naldini, L
通讯作者：
Naldini, L
影响因子：
9
作者：
通讯作者：
--
影响因子：
3.9
作者：
Petitjean, Audrey;Mathe, Ewy;Olivier, Magali
通讯作者：
Olivier, Magali