Anti-tumor effect of radiation response by combined treatment with angiogenesis inhibitor, TNP-470, in oral squamous cell carcinoma

Anti-tumor effect of radiation response by combined treatment with angiogenesis inhibitor, TNP-470, in oral squamous cell carcinoma
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DOI:
10.1016/j.oraloncology.2005.06.010
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发表时间:
2006-01-01
期刊:
影响因子:
4.8
通讯作者:
Hamakawa, H
Hamakawa, H
中科院分区:
医学2区
文献类型:
--
作者:
Shintani, S;Li, CN;Hamakawa, H

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阻断血管生成可以增强常规抗癌治疗,如放射治疗。在这项研究中,我们研究了血管生成抑制剂TNP-470对人口腔鳞状细胞癌细胞系HSC 2和KB的影响,结合放射治疗在裸鼠。我们用背气囊试验评价细胞诱导的新生血管形成,并选择了两种具有不同水平的细胞诱导的新生血管形成的细胞(HSC 2:低,KB:高)。血管生成抑制剂TNP-470以30 mg/kg s.c.第1-5天每天一次,每周第1天给予8戈伊× 1的照射,持续3周。相对于未处理的对照,在KB细胞中实现了肿瘤生长的显著抑制,显示出用TNP-470(P < 0.01)和辐射(P <0.01)以及TNP-470和辐射组合(P < 0.01)的高度诱导的血管生成。TNP-470单独或与辐射联合应用对低诱导血管生成的HSC 2细胞几乎没有影响,提示TNP-470可显著增强辐射对高血管生成细胞的作用。这些发现表明,在决定抗血管生成治疗之前,对每个肿瘤新生血管形成潜力的个体化评估将是重要的。(c)2005爱思唯尔有限公司保留所有权利。
Blocking angiogenesis may enhance conventional anticancer treatments such as radiation therapy. In this study, we examined the effects of the angiogenesis inhibitor TNP-470 on human OSCC cell lines HSC2 and KB, with combining radiation therapy in the nude mouse. We evaluated cell-induced neovascularization with dorsal air sac assay, and selected two cells (HSC2: low, KB: high) with different level of cell-induced angiogenesis. The angiogenesis inhibitor TNP-470 was given 30 mg/kg s.c. daily on day 1-5, and irradiation, 8 Gy x 1, was administered on day 1 each week for 3 weeks. Significant inhibition of tumor growth relative to untreated controls was achieved in KB cells showing high induced angiogenesis with both TNP-470 (P < 0.01) and radiation (P < 0.01) and combining TNP-470 and radiation (P < 0.01). We saw little effect of TNP-470 either alone or in addition to the effect of radiation on the HSC2 cells showing low induced angiogenesis.These results suggested that TNP-470 significantly enhanced the effect of radiation on the cells with high neovascularization. These findings indicated that individual evaluation of each tumor neovascularization potential will be important before deciding the anti-angiogenesis treatment. (c) 2005 Elsevier Ltd. All rights reserved.