Role of Extracellular High-Mobility Group Box-1 as a Therapeutic Target of Gastric Cancer.
Role of Extracellular High-Mobility Group Box-1 as a Therapeutic Target of Gastric Cancer.
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DOI：
10.3390/ijms23063264
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发表时间：
2022-03-17
影响因子：
5.6
通讯作者：
Otsuji E
中科院分区：
文献类型：
--
作者：
Takaki W;Konishi H;Matsubara D;Shoda K;Arita T;Kataoka S;Shibamoto J;Furuke H;Takabatake K;Shimizu H;Komatsu S;Shiozaki A;Kubota T;Okamoto K;Otsuji E
背景：高迁移率组盒-1 （HMGB1）参与多种肿瘤的发生和转移。本研究探讨了细胞外HMGB1在胃癌（GC）进展中的作用，以及靶向HMGB1的重组人可溶性血栓调节素（rTM）的治疗效果。方法：采用增殖法和Transwell法观察细胞外HMGB1和rTM对胃癌细胞的影响。分别用小鼠皮下肿瘤和肝转移模型评价其对局部肿瘤生长和转移的影响。采用ELISA法测定GC患者血浆HMGB1浓度。探讨血浆HMGB1浓度与患者预后及临床病理因素的关系。结果：增加细胞外HMGB1浓度可促进GC的增殖、迁移和侵袭能力，rTM可减轻GC的增殖、迁移和侵袭能力。在皮下肿瘤模型中，添加rhHMGB1可促进局部肿瘤生长，rTM可缓解局部肿瘤生长。在肝转移模型中也发生了类似的变化。血浆HMGB1浓度高的患者无复发生存期（p < 0.01）和总生存期（p = 0.01）明显较差。结论：血浆HMGB1浓度是胃癌患者的预后指标。细胞外HMGB1促进癌症进展，并有潜力成为胃癌细胞治疗rTM的新靶点。
Background: High-mobility group box-1 (HMGB1) is involved in the tumorigenesis and metastasis of various cancers. The present study investigated the roles of extracellular HMGB1 in the progression of gastric cancer (GC) and the therapeutic effects of recombinant human soluble thrombomodulin (rTM) targeting HMGB1. Methods: The effects of extracellular HMGB1 and rTM on GC cells were assessed using proliferation and Transwell assays. Their effects on local tumor growth and metastasis were evaluated using subcutaneous tumor and liver metastasis mouse models, respectively. Plasma HMGB1 concentrations in GC patients were measured using ELISA. The relationships between plasma HMGB1 concentrations and the prognosis and clinicopathological factors of patients were also investigated. Results: GC proliferation, migration, and invasion abilities were promoted by increases in extracellular HMGB1 concentrations and alleviated by rTM. In the subcutaneous tumor model, local tumor growth was promoted by the addition of rhHMGB1 and alleviated by rTM. Similar changes occurred in the liver metastasis model. Recurrence-free survival (p < 0.01) and overall survival (p = 0.01) were significantly worse in patients with high plasma HMGB1 concentrations. Conclusion: Plasma HMGB1 concentrations are a prognostic marker in GC patients. Extracellular HMGB1 promotes cancer progression and has potential as a novel treatment target in GC cells for rTM.
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影响因子：
7.1
作者：
Ikezoe T
通讯作者：
Ikezoe T
DOI：
10.1007/s10120-016-0601-9
发表时间：
2017-03
期刊：
Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association
影响因子：
--
作者：
Sano T;Coit DG;Kim HH;Roviello F;Kassab P;Wittekind C;Yamamoto Y;Ohashi Y
通讯作者：
Ohashi Y
影响因子：
64.8
作者：
Scaffidi, P;Misteli, T;Bianchi, ME
通讯作者：
Bianchi, ME
受辐射的肿瘤细胞释放的 HMGB1 通过旁分泌作用促进活肿瘤细胞增殖
影响因子：
9
作者：
He S;Cheng J;Sun L;Wang Y;Wang C;Liu X;Zhang Z;Zhao M;Luo Y;Tian L;Li C;Huang Q
通讯作者：
Huang Q
影响因子：
3.1
作者：
Cheng, Peng;Ma, Yun;Duan, Lingling
通讯作者：
Duan, Lingling