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肺癌患者恶性胸腔积液来源的肺癌细胞系建立及小鼠致瘤性研究

Establishment of lung cancer cell lines and tumorigenesis in mice from malignant pleural effusion in patients with lung cancer.

作者信息

Kanaji Nobuhiro, Yokohira Masanao, Inoue Takuya, Watanabe Naoki, Mizoguchi Hitoshi, Komori Yuta, Kawada Kosuke, Kadowaki Norimitsu

机构信息

Division of Hematology, Rheumatology and Respiratory Medicine, Department of Internal Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan.

Onco-Pathology, Department of Pathology and Host-Defense and Department of Medical Education, Faculty of Medicine, Kagawa University, Kagawa, Japan.

出版信息

Transl Lung Cancer Res. 2024 Sep 30;13(9):2340-2351. doi: 10.21037/tlcr-24-143. Epub 2024 Sep 25.

Abstract

BACKGROUND

Lung cancer was often diagnosed by malignant pleural effusion (MPE). Excessive MPE is generally discarded. The establishment of cell lines and the generation of cancer mouse models have the potential to be directly linked to personalized medicine. This study aimed to establish cell lines and generate mouse models using MPE.

METHODS

Cells derived from 5 mL of MPE were cultured in several conditions, including 100% MPE supernatant and Roswell Park Memorial Institute-1640 supplemented with 10% fetal bovine serum (FBS) or 10% MPE supernatant. When steady cell growth was observed, fewer cells were spread and the colonies were selected to establish the cell line. Cells derived from 10 mL of MPE were inoculated subcutaneously into non-obese diabetic-severe combined immunodeficiency (NOD-) and NOD.Cg- /SzJ (NSG) mice to assess tumorigenic potential.

RESULTS

MPEs were obtained from 28 lung cancer patients, 23 of whom had adenocarcinoma. Cell lines were established from 5 patients (18%). Tumorigenesis was observed in 6 of 28 cases (21%). However, in 7 cases, the mice (7 NSG and 1 NOD- mice) became progressively weaker, lost their hair, and died within 12 weeks without tumorigenesis. The appearance and pathological findings were consistent with graft-versus-host disease. Cell line establishment and tumorigenesis in mice were associated with a lower response to first-line therapy and poorer prognosis of patients.

CONCLUSIONS

When MPEs were simply utilized, the cell line establishment rate was 18% and the engraftment rate in mice was 21%. The prognosis of patients who underwent cell line establishment and engraftment in mice was poor.

摘要

背景

肺癌常通过恶性胸腔积液(MPE)进行诊断。过多的MPE通常被丢弃。细胞系的建立和癌症小鼠模型的构建有可能直接与个性化医疗相关联。本研究旨在利用MPE建立细胞系并构建小鼠模型。

方法

将从5毫升MPE中获取的细胞在多种条件下培养,包括100% MPE上清液以及补充有10%胎牛血清(FBS)或10% MPE上清液的罗斯威尔帕克纪念研究所-1640培养基。当观察到细胞稳定生长时,将较少数量的细胞铺板并挑选出集落以建立细胞系。将从10毫升MPE中获取的细胞皮下接种到非肥胖糖尿病-严重联合免疫缺陷(NOD-)和NOD.Cg- /SzJ(NSG)小鼠中,以评估致瘤潜力。

结果

从28例肺癌患者中获取了MPE,其中23例为腺癌。从5例患者(18%)中建立了细胞系。28例中有6例(21%)观察到肿瘤发生。然而,在7例中,小鼠(7只NSG小鼠和1只NOD-小鼠)逐渐衰弱,毛发脱落,并在12周内死亡而未发生肿瘤。外观和病理结果与移植物抗宿主病一致。小鼠中的细胞系建立和肿瘤发生与患者对一线治疗的较低反应和较差预后相关。

结论

当简单利用MPE时,细胞系建立率为18%,小鼠移植率为21%。在小鼠中进行细胞系建立和移植的患者预后较差。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/157d/11484711/84732db5cb43/tlcr-13-09-2340-f1.jpg

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