Immodin及其免疫系统在紫杉醇治疗4T1小鼠乳腺癌中的支持作用。,Biomedicine & Pharmacotherapy

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Immodin及其免疫系统在紫杉醇治疗4T1小鼠乳腺癌中的支持作用。
Biomedicine & Pharmacotherapy ( IF 6.9 ) Pub Date : 2017-02-27 , DOI: 10.1016/j.biopha.2017.02.034
Vlasta Demečková ₁ , Peter Solár ₂ , Gabriela Hrčková ₃ , Dagmar Mudroňová ₄ , Bianka Bojková ₁ , Monika Kassayová ₁ , Soňa Gancarčiková ₄

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显然，标准化疗药物可能对肿瘤和宿主免疫系统都有影响。紫杉醇（PTX）是一种来自紫杉烷家族的非常有效的抗癌药物，由于其对包括乳腺癌在内的多种肿瘤的功效，在临床肿瘤学上已取得了突出的成绩。然而，显着的毒性，例如骨髓抑制，限制了基于紫杉醇的治疗方案的有效性。Immodin（IM）是由人白细胞制成的匀浆的低分子透析液部分。它包含迄今为止已描述的物质的混合物，例如分别由二肽酪氨酸-甘氨酸和三肽酪氨酸-甘氨酸-甘氨酸形成的Imreg 1和Imreg 2。这项研究的目的是使用强免疫原性4T1小鼠乳腺癌模型探索IM的免疫药理活性，并评估其对PTX癌症反应性和疗效的影响。该结果突出了IM在减轻乳腺癌治疗期间PTX诱导的毒性，特别是对非特异性免疫的毒性方面的潜在有益作用。共同治疗表现出抗肿瘤作用，包括减少肿瘤生长，延长荷瘤小鼠的存活时间，增加外周血中单核细胞和淋巴细胞的数量。在脾脏中，IM + PTX治疗增加了全淋巴细胞的比例，原因是具有CD11c +和Fc受体（CD16 / 32）低表达的特征性骨髓单核细胞，以及T淋巴细胞，NK细胞和树突状细胞。还记录了PTX治疗组的基质中与肿瘤相关的粒细胞的积累以及共同治疗后肿瘤中的密集的4T1-坏死/凋亡。

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Immodin and its immune system supportive role in paclitaxel therapy of 4T1 mouse breast cancer.

It is evident that standard chemotherapy agents may have an impact on both tumor and host immune system. Paclitaxel (PTX), a very potent anticancer drug from a taxane family, has achieved prominence in clinical oncology for its efficacy against a wide range of tumors including breast cancer. However, significant toxicity, such as myelosuppression, limit the effectiveness of Paclitaxel-based treatment regimens. Immodin (IM) is low molecular dialysate fraction of homogenate made from human leukocytes. It contains a mixture of substances from which so far have been described e.g. Imreg 1 and Imreg 2 formed by the dipeptide tyrosine-glycine and the tripeptide tyrosine-glycine-glycine, respectively. The aim of this study was to explore immunopharmacological activities of IM, using the strongly immunogenic 4T1 mouse breast cancer model, and evaluate its effect on the reactivity and the efficiency of PTX cancer therapy. The results highlight a potentially beneficial role for IM in alleviating PTX-induced toxicity, especially on the nonspecific immunity, during breast cancer therapy. Co-treatment exhibited an antitumor effect including reduced tumor growth, prolonged survival of tumor bearing mice, increased number of monocytes and lymphocytes in peripheral blood. In spleens, IM+PTX therapy elevated proportion of whole lymphocytes in the account of myelo-monocytic cells characteristic with low expression of CD11c+ and bearing Fc receptor (CD16/32) as well as T-lymphocytes, NK cells and dendritic cells. Accumulation of tumor-associated granulocytes in stroma of PTX-treated group and intensive 4T1-necrosis/apoptosis in tumors after co-treatment were also recorded. These findings suggest the possibility of using IM alongside PTX treatment for maintaining the immune system functions and increasing patient survival.

更新日期：2019-11-01

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