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HET0016 静脉制剂降低人胶质母细胞瘤生长并提示在大鼠异种移植模型中具有生存获益。

Intravenous Formulation of HET0016 Decreased Human Glioblastoma Growth and Implicated Survival Benefit in Rat Xenograft Models.

机构信息

Tumor Angiogenesis Laboratory, Georgia Cancer Center, Augusta University, Augusta, GA, USA.

Cellular and Molecular Imaging Laboratory, Henry Ford Health System, Detroit, MI, USA.

出版信息

Sci Rep. 2017 Jan 31;7:41809. doi: 10.1038/srep41809.

DOI:10.1038/srep41809
PMID:28139732
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5282583/
Abstract

Glioblastoma (GBM) is a hypervascular primary brain tumor with poor prognosis. HET0016 is a selective CYP450 inhibitor, which has been shown to inhibit angiogenesis and tumor growth. Therefore, to explore novel treatments, we have generated an improved intravenous (IV) formulation of HET0016 with HPßCD and tested in animal models of human and syngeneic GBM. Administration of a single IV dose resulted in 7-fold higher levels of HET0016 in plasma and 3.6-fold higher levels in tumor at 60 min than that in IP route. IV treatment with HPßCD-HET0016 decreased tumor growth, and altered vascular kinetics in early and late treatment groups (p < 0.05). Similar growth inhibition was observed in syngeneic GL261 GBM (p < 0.05). Survival studies using patient derived xenografts of GBM811, showed prolonged survival to 26 weeks in animals treated with focal radiation, in combination with HET0016 and TMZ (p < 0.05). We observed reduced expression of markers of cell proliferation (Ki-67), decreased neovascularization (laminin and αSMA), in addition to inflammation and angiogenesis markers in the treatment group (p < 0.05). Our results indicate that HPßCD-HET0016 is effective in inhibiting tumor growth through decreasing proliferation, and neovascularization. Furthermore, HPßCD-HET0016 significantly prolonged survival in PDX GBM811 model.

摘要

胶质母细胞瘤（GBM）是一种血管丰富的原发性脑肿瘤，预后不良。HET0016 是一种选择性 CYP450 抑制剂，已被证明可抑制血管生成和肿瘤生长。因此，为了探索新的治疗方法，我们生成了一种用 HPßCD 改良的 HET0016 静脉（IV）制剂，并在人类和同源 GBM 的动物模型中进行了测试。单次 IV 给药后，HET0016 在血浆中的水平提高了 7 倍，在肿瘤中的水平提高了 3.6 倍，而 IP 给药途径的水平则提高了 7 倍。60 分钟时，HPßCD-HET0016 的 IV 治疗降低了肿瘤生长，并改变了早期和晚期治疗组的血管动力学（p<0.05）。在同源 GL261 GBM 中也观察到了类似的生长抑制（p<0.05）。使用源自 GBM811 的患者异种移植物的生存研究表明，与 HET0016 和 TMZ 联合使用，接受局部放射治疗的动物的存活时间延长至 26 周（p<0.05）。我们观察到治疗组的细胞增殖标志物（Ki-67）、新生血管标志物（层粘连蛋白和αSMA）表达减少，以及炎症和血管生成标志物减少（p<0.05）。我们的结果表明，HPßCD-HET0016 通过降低增殖和新生血管化来有效抑制肿瘤生长。此外，HPßCD-HET0016 显著延长了 PDX GBM811 模型的生存时间。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/859d/5282583/8192064fe2cc/srep41809-f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/859d/5282583/f8365aba8636/srep41809-f1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/859d/5282583/a2e4f3061ab6/srep41809-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/859d/5282583/4f4618372137/srep41809-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/859d/5282583/82bd72d62d75/srep41809-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/859d/5282583/766036de33c4/srep41809-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/859d/5282583/c21a18750477/srep41809-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/859d/5282583/8192064fe2cc/srep41809-f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/859d/5282583/f8365aba8636/srep41809-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/859d/5282583/2bbc5d2c2482/srep41809-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/859d/5282583/8d3b4daae57c/srep41809-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/859d/5282583/a2e4f3061ab6/srep41809-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/859d/5282583/4f4618372137/srep41809-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/859d/5282583/82bd72d62d75/srep41809-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/859d/5282583/766036de33c4/srep41809-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/859d/5282583/c21a18750477/srep41809-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/859d/5282583/8192064fe2cc/srep41809-f9.jpg

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3
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