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"A tricin derivative from Deschampsia antarctica Desv. inhibits colorectal carcinoma growth and liver metastasis through the induction of a specific immune response"
Molecular Cancer Therapeutics ( IF 5.7 ) Pub Date : 2018-02-26 , DOI: 10.1158/1535-7163.mct-17-0193
Mariana Malvicini , Ana Gutierrez-Moraga , Marcelo M. Rodriguez , Sofia Gomez-Bustillo , Lorena Salazar , Carlos Sunkel , Leonor Nozal , Antonio Salgado , Manuel Hidalgo , Pedro P. Lopez-Casas , Jose Luis Novella , Juan Jose Vaquero , Julio Alvarez-Builla , Adda Mora , Manuel Gidekel , Guillermo Mazzolini

In colorectal carcinoma patients, distant metastatic disease is present at initial diagnosis in nearly 25% of them. The majority of patients with metastatic colorectal carcinoma have incurable disease; therefore, new therapies are needed. Agents derived from medicinal plants have already demonstrated therapeutic activities in human cancer cells. Antartina is an antitumor agent isolated from Deschampsia antarctica Desv. This study aimed to evaluate the antitumor properties of Antartina in colorectal carcinoma models. We used human and murine colorectal carcinoma cell lines for investigating proliferation, apoptosis, and cell-cycle effects of Antartina therapy in vitro. Avatar and immunocompetent colorectal carcinoma animal models were applied for evaluating the effects of Antartina in vivo. Immune response against colorectal carcinoma model was investigated using CTL assay, analyzing dendritic cell activation and intratumor T-cell subpopulation, and by tumor rechallenge experiments. Antartina inhibits in vitro human colorectal carcinoma cell proliferation; however, in vivo experiments in Avatar colorectal carcinoma model Antartina display a limited antitumor effect. In an immunocompetent colorectal carcinoma mice model, Antartina potently inhibited tumor growth and liver metastases, leading to complete tumor regressions in >30% of mice and increased animal survival. In addition, Antartina induced a potent specific cytotoxic T-cell response against colorectal carcinoma and a long-lasting antitumor immunity. Interestingly, Antartina increased tumor immunogenicity and stimulated dendritic cell activation. No toxic effects were observed at the doses employed. Our findings showed that Antartina has the ability to induce antitumor immunity against colorectal carcinoma and can be used to develop new tools for the treatment of colorectal carcinoma. Mol Cancer Ther; 17(5); 966–76. ©2018 AACR.

中文翻译:

“来自 Deschampsia antarctica Desv. 的tricin 衍生物通过诱导特异性免疫反应抑制结肠直肠癌生长和肝转移”

在结直肠癌患者中,近 25% 的患者在初始诊断时就存在远处转移性疾病。大多数转移性结直肠癌患者患有不治之症;因此,需要新的疗法。来自药用植物的药物已经在人类癌细胞中显示出治疗活性。Antartina 是一种从 Deschampsia antarctica Desv 中分离出的抗肿瘤剂。本研究旨在评估 Antartina 在结直肠癌模型中的抗肿瘤特性。我们使用人和鼠结肠直肠癌细胞系来研究体外 Antartina 治疗的增殖、凋亡和细胞周期效应。应用阿凡达和免疫活性结直肠癌动物模型评估 Antartina 的体内作用。使用 CTL 测定、分析树突细胞活化和肿瘤内 T 细胞亚群以及通过肿瘤再攻击实验研究针对结直肠癌模型的免疫反应。Antartina 抑制体外人结直肠癌细胞增殖;然而,阿凡达结直肠癌模型 Antartina 的体内实验显示出有限的抗肿瘤作用。在具有免疫活性的结直肠癌小鼠模型中,Antartina 有效抑制肿瘤生长和肝转移,导致超过 30% 的小鼠肿瘤完全消退并增加动物存活率。此外,Antartina 诱导了针对结直肠癌的有效特异性细胞毒性 T 细胞反应和持久的抗肿瘤免疫。有趣的是,Antartina 增加了肿瘤免疫原性并刺激了树突细胞活化。在所用剂量下未观察到毒性作用。我们的研究结果表明,Antartina 具有诱导抗大肠癌抗肿瘤免疫的能力,可用于开发治疗大肠癌的新工具。摩尔癌症治疗; 17(5); 966-76。©2018 AACR。
更新日期:2018-02-26
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