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帕唑帕尼联合放疗:体内相互作用模型

Pazopanib combined with radiation: in vivo model of interaction.

作者信息

Meredith Ruby F, Raisch Kevin P, Bonner James A, Buchsbaum Donald J, Grizzle Willliam E, Li Yufeng, Spencer Sharon A

机构信息

1 Department of Radiation Oncology, University of Alabama at Birmingham , Birmingham, Alabama.

出版信息

Cancer Biother Radiopharm. 2014 Aug;29(6):247-50. doi: 10.1089/cbr.2013.1583. Epub 2014 Jun 19.

DOI:10.1089/cbr.2013.1583
PMID:24945464
Abstract

OBJECTIVE

Assess interaction of pazopanib, an oral antivascular endothelial growth factor inhibitor, with radiation in tumor xenograft models.

METHODS

Flank xenografts in female athymic nude mice of human lung cancer cell line, A549, and head and neck cancer cell line, UM-SCC-6, were allowed to grow to ∼5×5 mm. Groups were then treated with pazopanib and/or escalating doses of radiation and tumor measurements over time compared with untreated tumor-bearing controls. Pazopanib (100 mg/kg) began 7 days before radiation and continued for 28 days. Daily radiation was 0.5, 1, 2, or 3 Gy ×5 days.

RESULTS

Tumors in the A549 control group reached >4× the original size by day 36 postradiation. All treatment groups had less robust tumor growth (p<0.05) and the group receiving pazopanib+3 Gy radiation/day had tumor regression to less than baseline. In the UM-SCC-6-tumor-bearing animals, tumors in all treatment groups had less robust growth than untreated controls after day 23 post-treatment.

CONCLUSION

The combination of pazopanib and radiation resulted in a trend of superior tumor growth inhibition compared with either agent alone. All treatment groups had impaired tumor progression compared with untreated controls.

摘要

目的

在肿瘤异种移植模型中评估口服抗血管内皮生长因子抑制剂帕唑帕尼与放疗的相互作用。

方法

将人肺癌细胞系A549和头颈癌细胞系UM-SCC-6接种于雌性无胸腺裸鼠的侧腹,待肿瘤长至约5×5毫米。然后将动物分组,分别给予帕唑帕尼和/或递增剂量的放疗,并与未治疗的荷瘤对照相比,随时间测量肿瘤大小。帕唑帕尼(100毫克/千克)在放疗前7天开始给药,并持续28天。每日放疗剂量为0.5、1、2或3 Gy,共5天。

结果

A549对照组的肿瘤在放疗后36天达到原始大小的4倍以上。所有治疗组的肿瘤生长均较弱(p<0.05),接受帕唑帕尼+3 Gy/天放疗的组肿瘤缩小至基线以下。在荷UM-SCC-6肿瘤的动物中,治疗后23天起,所有治疗组的肿瘤生长均比未治疗的对照组弱。

结论

与单独使用任一药物相比,帕唑帕尼与放疗联合使用有更显著的肿瘤生长抑制趋势。与未治疗的对照组相比,所有治疗组的肿瘤进展均受到抑制。

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