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Differential Localization and Invasion of Tumor Cells in Mouse Models of Human and Murine Leukemias.
Acta Histochemica et Cytochemica ( IF 2.4 ) Pub Date : 2020-06-26 , DOI: 10.1267/ahc.19035
Kiyomi Mashima 1 , Morio Azuma 2 , Ken Fujiwara 3 , Takashi Inagaki 4 , Iekuni Oh 1 , Takashi Ikeda 1 , Kento Umino 1 , Hirofumi Nakano 1 , Kaoru Morita 1 , Kazuya Sato 1 , Daisuke Minakata 1 , Ryoko Yamasaki 1 , Masahiro Ashizawa 1 , Chihiro Yamamoto 1 , Shin-Ichiro Fujiwara 1 , Kaoru Hatano 1 , Ken Ohmine 1 , Kazuo Muroi 1 , Nobuhiko Ohno 3 , Yoshinobu Kanda 1
Affiliation  

Leukemias are refractory hematopoietic malignancies, for which the development of new therapeutic agents requires in vivo studies using tumor-bearing mouse models. Although several organs are commonly examined in such studies to evaluate the disease course, the effectiveness of interventions and the localization of tumor cells in the affected organs are still unclear. In this study, we histologically examined the distribution of leukemia cells in several organs using two leukemic mouse models produced by the administration of two cell lines (THP-1, a human myelomonocytic leukemia, and A20, a mouse B cell leukemia/lymphoma) to severe immunodeficient mice. Survival of the mice depended on the tumor burden. Although A20 and THP-1 tumor cells massively infiltrated the parenchyma of the liver and spleen at 21 days after transplantation, A20 cells were hardly found in connective tissues in Glisson’s capsule in the liver as compared with THP-1 cells. In the bone marrow, there was more severe infiltration of A20 cells than THP-1 cells. THP-1 and A20 cells were widely spread in the lungs, but were rarely observed in the small intestine. These findings suggest that each leukemia model has a unique localization of tumor cells in several affected organs, which could critically affect the disease course and the efficacy of therapeutic agents, including cellular immunotherapies.



中文翻译:

在人类和小鼠白血病小鼠模型中肿瘤细胞的差异定位和侵袭。

白血病是难治性造血系统恶性肿瘤,为此需要在体内开发新的治疗药物使用荷瘤小鼠模型进行研究。尽管在此类研究中通常检查几个器官以评估疾病进程,但尚不清楚干预的效果以及受影响器官中肿瘤细胞的定位。在这项研究中,我们使用两种细胞系(THP-1,一种人骨髓单核细胞白血病和A20,一种小鼠B细胞白血病/淋巴瘤)产生两种白血病小鼠模型,组织学检查了白血病细胞在多个器官中的分布。严重的免疫缺陷小鼠。小鼠的存活取决于肿瘤的负担。尽管在移植后第21天,A20和THP-1肿瘤细胞大量浸润了肝和脾的实质,但是与THP-1细胞相比,在肝的Glisson氏囊的结缔组织中几乎没有发现A20细胞。在骨髓中 A20细胞的浸润比THP-1细胞更严重。THP-1和A20细胞在肺中广泛分布,但在小肠中很少观察到。这些发现表明,每种白血病模型在几个受影响的器官中都有独特的肿瘤细胞定位,这可能会严重影响疾病进程和治疗药物(包括细胞免疫疗法)的功效。

更新日期:2020-08-23
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