Effect of bevacizumab combined with boron neutron capture therapy on local tumor response and lung metastasis.
Effect of bevacizumab combined with boron neutron capture therapy on local tumor response and lung metastasis.
复制标题
DOI：
10.3892/etm.2014.1704
复制
发表时间：
2014-07
影响因子：
2.7
通讯作者：
Ono K
中科院分区：
文献类型：
--
作者：
Masunaga SI;Sakurai Y;Tano K;Tanaka H;Suzuki M;Kondo N;Narabayashi M;Watanabe T;Nakagawa Y;Maruhashi A;Ono K
本研究的目的是评价贝伐单抗在硼中子俘获治疗(BNCT)中对局部肿瘤反应和肺转移潜能的影响，特别是对瘤内静止(Q)细胞的反应。B16-BL6黑色素瘤C57BL/6小鼠连续给予溴脱氧尿嘧啶核苷(BrdU)标记所有增殖(P)肿瘤细胞。在给予10B载体[L-对硼苯丙氨酸-10B(BPA)或硫代十一氢十二硼酸-10B钠(BSH)]后，用热中子束照射肿瘤，并加或不加贝伐单抗。再结合急性缺氧缓释剂(烟酰胺)或亚温加温(MTH，40℃，60min)。照射后，某些肿瘤的细胞立即被分离出来，并与胞质分裂阻滞剂孵育。用BrdU免疫荧光染色，根据微核率评估Q细胞和总(P+Q)细胞群的反应。在其他荷瘤小鼠中，在照射后17天，计数肺转移。贝伐单抗给药3天后，BPA-BNCT治疗后肿瘤细胞总数的敏感性比BSH-BNCT治疗后增加更多。与MTH联合使用，但不与烟酰胺联合使用，进一步提高了总肿瘤细胞群体的敏感性。无论是否存在10B载体，MTH都提高了Q细胞群体的敏感性。与BSH-BNCT相比，贝伐单抗和烟酰胺治疗在减少肺转移数目方面显示出一定的潜力，尤其是在BPA-BNCT中。因此，目前的研究表明，BNCT联合贝伐单抗有可能使总的肿瘤细胞增敏，并导致肺转移数量减少到与烟酰胺类似的水平。
The aim of the present study was to evaluate the effect of bevacizumab on local tumor response and lung metastatic potential during boron neutron capture therapy (BNCT) and in particular, the response of intratumor quiescent (Q) cells. B16-BL6 melanoma tumor-bearing C57BL/6 mice were continuously administered bromodeoxyuridine (BrdU) to label all proliferating (P) tumor cells. The tumors were irradiated with thermal neutron beams following the administration of a 10B-carrier [L-para-boronophenylalanine-10B (BPA) or sodium mercaptoundecahydrododecaborate-10B (BSH)], with or without the administration of bevacizumab. This was further combined with an acute hypoxia-releasing agent (nicotinamide) or mild temperature hyperthermia (MTH, 40°C for 60 min). Immediately following the irradiation, cells from certain tumors were isolated and incubated with a cytokinesis blocker. The responses of the Q cells and the total (P+Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU. In other tumor-bearing mice, 17 days following irradiation, lung metastases were enumerated. Three days following bevacizumab administration, the sensitivity of the total tumor cell population following BPA-BNCT had increased more than that following BSH-BNCT. The combination with MTH, but not with nicotinamide, further enhanced total tumor cell population sensitivity. Regardless of the presence of a 10B-carrier, MTH enhanced the sensitivity of the Q cell population. Regardless of irradiation, the administration of bevacizumab, as well as nicotinamide treatment, demonstrated certain potential in reducing the number of lung metastases especially in BPA-BNCT compared with BSH-BNCT. Thus, the current study revealed that BNCT combined with bevacizumab has the potential to sensitize total tumor cells and cause a reduction in the number of lung metastases to a similar level as nicotinamide.
登录
查看更多内容
影响因子：
2.6
作者：
Ando, K;Koike, S;Urano, M
通讯作者：
Urano, M
DOI：
10.1016/0167-5087(83)90082-0
发表时间：
1983-01-01
期刊：
NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH
影响因子：
--
作者：
KOBAYASHI, T;KANDA, K
通讯作者：
KANDA, K
影响因子：
2.6
作者：
BROWN, JM
通讯作者：
BROWN, JM
DOI：
10.1016/s0360-3016(01)01695-9
发表时间：
2001-11-01
影响因子：
7
作者：
Masunaga, S;Ono, K;Suzuki, M
通讯作者：
Suzuki, M
影响因子：
7.3
作者：
SOLOWAY, AH;HATANAKA, H;DAVIS, MA
通讯作者：
DAVIS, MA