BACKGROUND Anlotinib is a novel, orally administered, multitarget receptor tyrosine kinase inhibitor. It functions by inhibiting tumor angiogenesis and proliferative signaling pathways. In this study, we aimed to investigate the efficacy and safety of anlotinib plus epirubicin in a sarcoma patient-derived xenografts (PDX) model. METHODS We firstly established a PDX model using fresh tumor tissues that were surgically removed from a patient diagnosed with malignant fibrous histiocytoma. Thirty-six PDX models were divided into six groups and treated with anlotinib alone (low-dose, 1.5 or high-dose, 3.0 mg/kg/day, oral gavage), or with anlotinib plus epirubicin (3.0 mg/kg/once weekly, i.p.) when the tumors grew to 150-200 mm3 . After 5 weeks of treatment, the mice were sacrificed, and the tumors were measured by weight and processed for IHC and H&E staining. IHC staining was performed to detect CD31, EGFR, MVD, and Ki-67 on paraffin sections. H&E stainings were performed to examine the microcosmic changes that occurred in the tumor tissues and myocardium, respectively. RESULTS After 5 weeks, treatment with anlotinib or epirubicin alone significantly inhibited tumor growth in the sarcoma PDX model compared with the vehicle control. Tumor volume in the high-dose anlotinib group was significantly smaller than the low-dose anlotinib group (P < .001). Combined high-dose anlotinib and epirubicin treatment resulted in the most pronounced tumor inhibition. In the groups treated with the anlotinib-containing regimen, the expression levels of CD31, EGFR, MVD, and Ki-67 were significantly low. The weight in each group had no statistical differences; the same applied to the hepatic function, cardiac function, and toxicity. CONCLUSIONS High-dose anlotinib combined with epirubicin was an effective and safe therapy for STS.

中文翻译：

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安罗替尼（一种多激酶血管生成抑制剂）联合表柔比星在软组织肉瘤临床前模型中的疗效和安全性。

背景安罗替尼是一种新型口服多靶点受体酪氨酸激酶抑制剂。它通过抑制肿瘤血管生成和增殖信号通路发挥作用。在这项研究中，我们旨在研究安罗替尼加表柔比星在肉瘤患者来源的异种移植（PDX）模型中的疗效和安全性。方法 我们首先使用从诊断为恶性纤维组织细胞瘤的患者手术切除的新鲜肿瘤组织建立 PDX 模型。36 个 PDX 模型分为六组，单独使用安罗替尼（低剂量、1.5 或高剂量、3.0 mg/kg/天，口服灌胃）或安罗替尼加表阿霉素（3.0 mg/kg/每周一次）治疗, ip) 当肿瘤生长到 150-200 mm3 时。治疗5周后，处死小鼠，测量肿瘤重量并进行IHC和H&E染色。进行 IHC 染色以检测石蜡切片上的 CD31、EGFR、MVD 和 Ki-67。进行H&E染色以分别检查肿瘤组织和心肌中发生的微观变化。结果 5 周后，与载体对照相比，单独使用安罗替尼或表柔比星治疗可显着抑制肉瘤 PDX 模型中的肿瘤生长。高剂量安罗替尼组的肿瘤体积显着小于低剂量安罗替尼组 (P < .001)。高剂量安罗替尼和表柔比星联合治疗产生了最显着的肿瘤抑制作用。在接受含安罗替尼方案治疗的组中，CD31、EGFR、MVD和Ki-67的表达水平显着较低。各组体重无统计学差异；这同样适用于肝功能、心脏功能和毒性。结论大剂量安罗替尼联合表阿霉素是治疗STS的有效且安全的方法。