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两种源自骨巨细胞瘤的新型患者来源细胞系的建立与鉴定:NCC-GCTB11-C1和NCC-GCTB12-C1。

Establishment and characterization of two novel patient-derived cell lines from giant cell tumor of bone: NCC-GCTB11-C1 and NCC-GCTB12-C1.

作者信息

Adachi Yuki, Ono Takuya, Noguchi Rei, Osaki Julia, Iwata Shuhei, Akiyama Taro, Yanagihara Kazuyoshi, Nishino Shogo, Ogura Koichi, Yoshida Akihiko, Yokoo Hideki, Kawai Akira, Kondo Tadashi

机构信息

Division of Rare Cancer Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan.

Division of Hepato-Biliary-Pancreatic Surgery and Transplant Surgery, Department of Surgery, Asahikawa Medical University, 2-1-1 Midorigaoka Higashi, Asahikawa, Hokkaido, Japan.

出版信息

Hum Cell. 2025 Jul 12;38(5):128. doi: 10.1007/s13577-025-01254-3.

Abstract

Giant cell tumor of bone (GCTB) is locally aggressive and rarely metastasizing mesenchymal tumor, molecularly characterized by the presence of H3-3A mutation. The management of GCTB is problematic because of local recurrence after curative surgical treatment, and complex biological and molecular backgrounds of etiology and disease progression. Development of multidisciplinary therapy has been required in GCTB, and targeting treatments against nuclear factor kappa-B ligand and epidermal growth factor receptor to neoplastic stromal cells were applied to the clinical practice. To promote the translational research of GCTB, we developed two cell lines from primary tumor tissues. The established cell lines exhibited H3-3A gene mutations: NCC-GCTB11-C1 (p.Gly35Leu), and NCC-GCTB12-C1 (p.Gly35Trp). The p.Gly35Leu (G35L) is a rare variant, and NCC-GCTB11-C1 is the first GCTB cell line holding it. The two cell lines showed constant proliferation, spheroid formation, and invasion, making them suitable for in vitro studies. We demonstrated that the two cell lines were useful for drug screening using 221 anti-cancer agents. NCC-GCTB11-C1 and NCC-GCTB12-C1 will be critical resources for the development of novel targeted treatments by their application for drug screening.

摘要

骨巨细胞瘤(GCTB)是一种具有局部侵袭性且很少发生转移的间充质肿瘤,其分子特征为存在H3-3A突变。由于根治性手术治疗后局部复发,以及病因和疾病进展的复杂生物学和分子背景,GCTB的治疗存在问题。GCTB需要多学科治疗的发展,针对肿瘤基质细胞的核因子κB配体和表皮生长因子受体的靶向治疗已应用于临床实践。为了促进GCTB的转化研究,我们从原发性肿瘤组织中建立了两个细胞系。所建立的细胞系表现出H3-3A基因突变:NCC-GCTB11-C1(p.Gly35Leu)和NCC-GCTB12-C1(p.Gly35Trp)。p.Gly35Leu(G35L)是一种罕见的变异体,NCC-GCTB11-C1是首个携带该变异体的GCTB细胞系。这两个细胞系表现出持续增殖、球体形成和侵袭能力,使其适用于体外研究。我们证明这两个细胞系可用于使用221种抗癌药物进行药物筛选。NCC-GCTB11-C1和NCC-GCTB12-C1通过应用于药物筛选,将成为开发新型靶向治疗的关键资源。

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