Antitumor effects of bevacizumab in a microenvironment-dependent human adult T-cell leukemia/lymphoma mouse model
Antitumor effects of bevacizumab in a microenvironment-dependent human adult T-cell leukemia/lymphoma mouse model
复制标题
贝伐珠单抗在微环境依赖性成人 T 细胞白血病/淋巴瘤小鼠模型中的抗肿瘤作用
DOI：
10.1111/ejh.12231
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发表时间：
2014
影响因子：
3.1
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;Narita T;Suzuki S;Yamada T;Takino H;Ri M;Kusumoto S;Komatsu H;Hishizawa M;Imada K;Takaori-Kondo A;Niimi A;Ueda R;Inagaki H;Iida S
本研究的目的是评估贝伐单抗联合或不联合全身化疗对成人T细胞白血病/淋巴瘤（ATL）的治疗潜力，并阐明血管生成对ATL发病机制的意义。方法NOD/Shi-scid，IL-2 R γnull（NOG）小鼠被用作来自ATL患者的肿瘤细胞的受体，这些肿瘤细胞以微环境依赖的方式移植和增殖。ATL细胞可以连续移植在NOG小鼠，但不能保持在vitrocultures.ResultsInjection的贝伐单抗单独显着增加坏死和减少血管形成的肿瘤组织。贝伐珠单抗治疗小鼠血清中人可溶性白细胞介素2受体水平（反映ATL肿瘤负荷）显著低于未治疗小鼠。虽然贝伐单抗单药治疗显示出这些明确的抗血管生成作用，但它并没有延长生存期。相比之下，注射贝伐单抗与环磷酰胺，阿霉素，长春新碱，泼尼松龙（CHOP）导致一个显着延长的ATL小鼠的生存期相对于CHOP单独conclusionsThis是第一份报告，以评估贝伐单抗的疗效ATL在肿瘤微环境依赖模型。贝伐单抗联合化疗可能是一种有价值的治疗策略，该亚组的ATL可能在很大程度上依赖于血管内皮生长因子的血管生成。
ObjectiveThe objective of this study was to evaluate the therapeutic potential of bevacizumab with or without systemic chemotherapy for adult T‐cell leukemia/lymphoma (ATL) and clarify the significance of angiogenesis for ATL pathogenesis.MethodsNOD/Shi‐scid, IL‐2Rγnull(NOG) mice were used as recipients of tumor cells from a patient with ATL, which engraft and proliferate in a microenvironment‐dependent manner. The ATL cells could be serially transplanted in NOG mice, but could not be maintained inin vitrocultures.ResultsInjection of bevacizumab alone significantly increased necrosis and decreased vascularization in the tumor tissue. Levels of human soluble interleukin two receptor in the serum (reflecting the ATL tumor burden) of bevacizumab‐treated mice were significantly lower than in untreated mice. Although bevacizumab monotherapy showed these clear anti‐angiogenesis effects, it did not prolong survival. In contrast, injection of bevacizumab together with cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP) led to a significant prolongation of survival of the ATL mice relative to CHOP alone.ConclusionsThis is the first report to evaluate the efficacy of bevacizumab for ATL in a tumor microenvironment‐dependent model. Bevacizumab therapy combined with chemotherapy could be a valuable treatment strategy for that subgroup of ATL probably depending to a large extent on angiogenesis via vascular endothelial growth factor.