Potent antitumor effects of bevacizumab in a microenvironment-dependent human lymphoma mouse model.
Potent antitumor effects of bevacizumab in a microenvironment-dependent human lymphoma mouse model.
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DOI：
10.1038/bcj.2012.12
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发表时间：
2012-04
影响因子：
12.8
通讯作者：
Iida, S.
中科院分区：
文献类型：
--
作者：
Mori, F.;Ishida, T.;Ito, A.;Sato, F.;Masaki, A.;Takino, H.;Ri, M.;Kusumoto, S.;Komatsu, H.;Ueda, R.;Inagaki, H.;Iida, S.
我们建立了微环境依赖性人类淋巴瘤的小鼠模型，并评估了贝伐单抗（一种作用于微环境的抗肿瘤药物）的治疗潜力。使用NOD/Shi-scid，IL-2 R γnull（NOG）小鼠作为来自弥漫性大B细胞淋巴瘤（DLBCL）患者的原发性肿瘤细胞的受体，其以微环境依赖性方式移植和增殖。淋巴瘤细胞可连续移植于NOG小鼠，但不能在体外培养中维持。与CHOP单药相比，贝伐单抗联合CHOP（环磷酰胺、阿霉素、长春新碱、泼尼松龙）注射显著增加肿瘤坏死和减少血管形成。贝伐珠单抗+CHOP治疗小鼠血清中人可溶性白细胞介素2受体（sIL 2 R）水平（反映DLBCL肿瘤负荷）显著低于CHOP接受者。接受贝伐单抗单药治疗的小鼠在肿瘤坏死和血管形成方面也显示出显著的益处，以及血清sIL 2 R浓度降低。本DLBCL模型比使用已建立的肿瘤细胞系的当前小鼠模型更适当地反映人DLBCL体内环境。这是第一份报告，以评估贝伐单抗在这种肿瘤微环境依赖性模型的疗效。贝伐单抗可能是DLBCL患者的潜在治疗策略。
We established a mouse model of microenvironment-dependent human lymphoma, and assessed the therapeutic potential of bevacizumab, an antitumor agent acting on the microenvironment. NOD/Shi-scid, IL-2Rγnull (NOG) mice were used as recipients of primary tumor cells from a patient with diffuse large B-cell lymphoma (DLBCL), which engraft and proliferate in a microenvironment-dependent manner. The lymphoma cells could be serially transplanted in NOG mice, but could not be maintained in in vitro cultures. Injection of bevacizumab together with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) significantly increased necrosis and decreased vascularization in the tumor, compared with CHOP alone. Levels of human soluble interleukin-2 receptor (sIL2R) in the serum of bevacizumab+CHOP-treated mice (reflecting the DLBCL tumor burden) were significantly lower than in CHOP recipients. Mice receiving bevacizumab monotherapy also showed significant benefit in terms of tumor necrosis and vascularization, as well as decreased serum sIL2R concentrations. The present DLBCL model reflects the human DLBCL in vivo environment more appropriately than current mouse models using established tumor cell lines. This is the first report to evaluate the efficacy of bevacizumab in such a tumor microenvironment-dependent model. Bevacizumab may be a potential treatment strategy for DLBCL patients.
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