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西妥昔单抗、替拉扎明联合 MnSOD 质粒脂质体基因治疗原位人鳞癌细胞株 Nu/Nu 小鼠的联合模式放疗的疗效。

Effectiveness of combined modality radiotherapy of orthotopic human squamous cell carcinomas in Nu/Nu mice using cetuximab, tirapazamine and MnSOD-plasmid liposome gene therapy.

机构信息

Department of Radiation Oncology, University of Pittsburgh Cancer Institute, 200 Lothrop Street, Pittsburgh, PA 15213, USA.

出版信息

In Vivo. 2010 Jan-Feb;24(1):1-8.

PMID:20133969
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2899489/
Abstract

Hypoxic regions limit the radiocontrollability of head and neck carcinomas. Whether or not combinations of plasmid/liposome mediated overexpression of normal tissue protective manganese superoxide dismutase (MnSOD), cetuximab (C225), and the hypoxic cytotoxin tirapazamine (TPZ) enhanced radiotherapeutic effects was tested in a CAL-33 orthotopic mouse cheek tumor model. The tumor volume continued to increase in the control (untreated) mice, with a ninefold increase by 10 days when the tumors exceeded 2 cm(3). The mice receiving 14 Gy only showed reduced tumor growth to 3.1+/-0.1 fold at day 10. The mice receiving MnSOD-PL, C225, TPZ plus 14 Gy had the best outcome with 0.7+/-0.1 fold increase in tumor volume by 10 days (p=0.015) compared to irradiation only. The addition of MnSOD-PL, TPZ, and C225 to irradiation optimized the therapeutic ratio for the local control of hypoxic region-containing CAL-33 orthotopic tumors.

摘要

缺氧区域限制了头颈部癌的放射可控性。我们在 CAL-33 原位颊肿瘤模型中检测了质粒/脂质体介导的正常组织保护型锰超氧化物歧化酶（MnSOD）、西妥昔单抗（C225）和缺氧细胞毒素替拉扎胺（TPZ）过表达的组合是否增强了放射治疗效果。在未治疗的对照组小鼠中，肿瘤体积持续增加，10 天时肿瘤体积增加了 9 倍，达到 2cm3 以上。仅接受 14 Gy 照射的小鼠在第 10 天肿瘤生长减少至 3.1+/-0.1 倍。接受 MnSOD-PL、C225、TPZ 和 14 Gy 照射的小鼠肿瘤体积增加了 0.7+/-0.1 倍（p=0.015），与单独照射相比，效果最好。MnSOD-PL、TPZ 和 C225 的添加优化了含缺氧区的 CAL-33 原位肿瘤局部控制的治疗比。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd5a/2899489/a2d4a2605ed9/nihms210449f8.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd5a/2899489/a2d4a2605ed9/nihms210449f8.jpg

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