Spheroid culture to select theoretical therapeutic drugs in intravascular large B-cell lymphoma.

IF 5.7 2区 医学 Q1 Medicine Cancer Science Pub Date : 2024-10-20 DOI:10.1111/cas.16310
Mika Takai, Kazuyuki Shimada, Katsuya Furukawa, Yusuke Yamaga, Soichi Yoshiyama, Yusuke Kagaya, Takashi Suzuki, Kazuhiko Hayashi, Satoko Shimada, Kennosuke Karube, Hitoshi Kiyoi
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Abstract

Intravascular large B-cell lymphoma (IVLBCL) is a rare type of extranodal large B-cell lymphoma that is characterized by the proliferation of lymphoma cells in the lumina of small vessels. Recent progress uncovering the genetic characteristics associated with MYD88/CD79B mutations has stimulated interest in the use of drugs targeting B-cell receptor signaling, including Bruton's tyrosine kinase. However, difficulties in culturing ex vivo IVLBCL cells has hampered research on the development of novel therapies. In the present study, we demonstrated the establishment of an ex vivo culture system of IVLBCL cells obtained from patient-derived xenograft (PDX) models. The spheroid culture enabled us to culture IVLBCL PDX cells for more than 10 days and to explore the efficacy of drug treatments acting on these cells. We found that carfilzomib and ibrutinib were effective for treating IVLBCL in ex vivo experiments and conducted in vivo analyses to assess the efficacy of these drugs. Although the efficacy of carfilzomib was difficult to confirm due to its toxicity in our models, ibrutinib showed comparable efficacy to a standard combination of chemotherapy drugs. Together, our data provide a new culture method for IVLBCL PDX cells and a rationale for translating ibrutinib to clinical use in IVLBCL patients.

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用球孢子培养法筛选血管内大 B 细胞淋巴瘤的理论治疗药物。
血管内大 B 细胞淋巴瘤(IVLBCL)是一种罕见的结节外大 B 细胞淋巴瘤,其特点是淋巴瘤细胞在小血管管腔内增殖。最近,人们发现了与 MYD88/CD79B 突变相关的遗传特征,这激发了人们对使用靶向 B 细胞受体信号转导(包括布鲁顿酪氨酸激酶)的药物的兴趣。然而,体外培养 IVLBCL 细胞的困难阻碍了新型疗法的开发研究。在本研究中,我们证明了从患者异种移植(PDX)模型中获得的 IVLBCL 细胞体外培养系统的建立。球形培养使我们能够对 IVLBCL PDX 细胞进行超过 10 天的培养,并探索作用于这些细胞的药物疗法的疗效。我们在体外实验中发现卡非佐米和伊布替尼能有效治疗IVLBCL,并进行了体内分析以评估这些药物的疗效。虽然卡非佐米的疗效因其在我们的模型中的毒性而难以确认,但伊布替尼显示出了与标准化疗药物组合相当的疗效。总之,我们的数据为 IVLBCL PDX 细胞提供了一种新的培养方法,并为将伊布替尼应用于 IVLBCL 患者的临床治疗提供了理论依据。
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来源期刊
Cancer Science
Cancer Science ONCOLOGY-
CiteScore
9.90
自引率
3.50%
发文量
406
审稿时长
17 weeks
期刊介绍: Cancer Science (formerly Japanese Journal of Cancer Research) is a monthly publication of the Japanese Cancer Association. First published in 1907, the Journal continues to publish original articles, editorials, and letters to the editor, describing original research in the fields of basic, translational and clinical cancer research. The Journal also accepts reports and case reports. Cancer Science aims to present highly significant and timely findings that have a significant clinical impact on oncologists or that may alter the disease concept of a tumor. The Journal will not publish case reports that describe a rare tumor or condition without new findings to be added to previous reports; combination of different tumors without new suggestive findings for oncological research; remarkable effect of already known treatments without suggestive data to explain the exceptional result. Review articles may also be published.
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