文章：

贝伐单抗在微环境依赖性人淋巴瘤小鼠模型中的有效抗肿瘤作用

Potent antitumor effects of bevacizumab in a microenvironment-dependent human lymphoma mouse model

原文发布日期：2012-04-20

DOI: 10.1038/bcj.2012.12

类型: Original Article

开放获取: 是

英文摘要：

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-2Rγ^null (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.

摘要翻译： 

我们建立了微环境依赖性人淋巴瘤的小鼠模型，并评估了作用于微环境的抗肿瘤药物贝伐珠单抗的治疗潜力。使用NOD/Shi-scid IL-2Rγ^null（NOG）小鼠作为弥漫大B细胞淋巴瘤（DLBCL）患者原代肿瘤细胞的受体，这些细胞以微环境依赖性方式定植和增殖。该淋巴瘤细胞可在NOG小鼠中连续移植，但无法在体外培养中维持。与单独使用CHOP（环磷酰胺、多柔比星、长春新碱、泼尼松龙）相比，联合注射贝伐珠单抗可显著增加肿瘤坏死并减少血管形成。贝伐珠单抗+CHOP治疗组小鼠血清中的人可溶性白细胞介素-2受体（sIL2R）水平（反映DLBCL肿瘤负荷）显著低于CHOP治疗组。接受贝伐珠单抗单药治疗的小鼠在肿瘤坏死、血管形成以及血清sIL2R浓度降低方面也显示出显著获益。本DLBCL模型比目前使用已建立肿瘤细胞系的小鼠模型更能准确反映人DLBCL体内环境。这是首个在此类肿瘤微环境依赖性模型中评估贝伐珠单抗疗效的报告。贝伐珠单抗可能成为DLBCL患者的潜在治疗策略。

原文链接：

Potent antitumor effects of bevacizumab in a microenvironment-dependent human lymphoma mouse model