帕博利珠单抗联合二甲双胍治疗转移性头颈部癌的 II 期可行性研究
A Phase II Feasibility Study Combining Pembrolizumab and Metformin in Patients with Metastatic Head and Neck Cancer.
二甲双胍联合帕博利珠单抗耐受性良好，仅出现轻度胃肠道不良事件，并展现出有前景的活性，值得在随机试验中进一步研究。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
间充质干细胞来源 HGF 经代偿性增殖减轻唾液腺辐射诱导的衰老
英文原题：Mesenchymal stem cell-derived HGF attenuates radiation-induced senescence in salivary glands via compensatory proliferation.
查看英文原题
Mesenchymal stem cell-derived HGF attenuates radiation-induced senescence in salivary glands via compensatory proliferation.
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研究概要
ADSC 可能通过分泌 HGF 对放射后恢复产生积极作用，并可促进唾液腺干/祖细胞的体外扩增，从而增强共移植 SGSC 的效果。
中文摘要
背景与目的
头颈癌治疗期间对唾液腺进行照射会造成DNA损伤并诱导细胞衰老，损害唾液腺干/祖细胞（SGSC）生态位，从而导致放射性唾液分泌减少。放射等因素诱发的细胞衰老是一种细胞周期停滞状态，并伴有促炎分泌组改变，即衰老相关分泌表型（SASP），可能对周围微环境造成有害影响。我们假设间充质干细胞（MSC）的促再生特性可能减轻照射后的细胞衰老，因此评估了脂肪来源MSC（ADSC）对唾液腺类器官（SGO）放射反应的影响。
方法
对与SGO共培养的ADSC所释放可溶性介质进行蛋白质组学分析，发现ADSC分泌肝细胞生长因子（HGF），提示其可能参与干细胞间相互作用。随后，在离体培养的唾液腺细胞二维单层及三维类器官模型中，测试重组HGF的作用。
结果
HGF处理显著促进唾液腺细胞增殖。重要的是，照射后补充HGF可增强较低辐射剂量（0、3、7 Gy）下的细胞增殖，但在较高剂量（10、14 Gy）下无此作用；此时大多数细胞的衰老相关β-半乳糖苷酶染色呈阳性。此外，HGF不影响受照SGO的SASP，提示其作用可能是促进仍有分裂能力的细胞代偿性增殖，而非逆转照射后的细胞衰老。
结论
ADSC可能通过分泌HGF促进放射损伤后的恢复，并可在体外促进唾液腺干/祖细胞扩增，从而增强共同移植SGSC的效果。
展开英文摘要原文
METHODS
Proteomic analyses to identify soluble mediators released by ADSCs co-cultured with SGOS revealed secretion of hepatocyte growth factor (HGF) in ADSCs, suggesting a possible role in the stem cell crosstalk. Next, the effect of recombinant HGF in the culture media of ex vivo grown salivary gland cells was tested in 2D monolayers and 3D organoid models.
RESULTS
Treatment with HGF robustly increased salivary gland cell proliferation. Importantly, HGF supplementation post-irradiation enhanced proliferation at lower doses of radiation (0, 3, 7 Gy), but not at higher doses (10, 14 Gy) where most cells stained positive for senescence-associated beta-galactosidase. Furthermore, HGF had no effect on the senescence-associated secretory phenotype (SASP) of irradiated SGOs, suggesting there may be compensatory proliferation by cell-division competent cells instead of a reversal of cellular senescence after irradiation.
CONCLUSION
ADSCs may positively influence radiation recovery through HGF secretion and can promote the ex vivo expansion of salivary gland stem/progenitor cells to enhance the effects of co-transplanted SGSC.
论文信息
- 作者
- Soto-Gamez A、van Es M、Hageman E、Serna-Salas SA、Moshage H、Demaria M、Pringle S、Coppes RP
- 第一作者单位
- Dept. of Biomedical Sciences of Cells & Systems, University of Groningen (RUG) and University Medical Center Groningen (UMCG), Groningen, the Netherlands; Dept. of Radiation Oncology, University of Groningen (RUG) and University Medical Center Groningen (UMCG), Groningen, the Netherlands.Netherlands
- 通讯作者单位
- Dept. of Biomedical Sciences of Cells & Systems, University of Groningen (RUG) and University Medical Center Groningen (UMCG), Groningen, the Netherlands; Dept. of Radiation Oncology, University of Groningen (RUG) and University Medical Center Groningen (UMCG), Groningen, the Netherlands. Electronic address: r.p.coppes@umcg.nl.Netherlands
- 期刊
- Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology2024 Jan
- 原文标识
- PubMed 37926332 · DOI 10.1016/j.radonc.2023.109984