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。
英文原题:Gingival-derived mesenchymal stem cell therapy regenerated the radiated salivary glands: functional and histological evidence in murine model.
该研究通过使用GMSCs对受辐射的SG进行重编程,为治疗口干症提供了一种新的潜在治疗策略。
头颈部肿瘤管理中的放疗会导致唾液腺(SG)退化。本研究旨在利用小鼠模型,确定牙龈间充质干细胞(GMSCs)作为基于细胞的疗法,再生受照射的腮腺SG组织并恢复其功能的潜力。
从4只健康豚鼠的牙龈组织中分离培养的细胞,取第3代,通过流式细胞术检测表面标志物及多向分化能力,鉴定为GMSCSs。将21只豚鼠等分为三组:I组/试验组,接受头颈部单次局部照射15 Gy后静脉注射标记的GMSCs;II组/阳性对照组,接受相同照射剂量后注射磷酸盐缓冲液(PBS);III组/阴性对照组,仅注射PBS。在基线、照射后11天、8周、13周和16周测量体重和唾液流率(SFR)。在第16周,采集腮腺以评估腺体重量并进行组织学和免疫组织化学分析。
注射的GMSCs归巢至退化的腺体,随后正常腺体组织学腺泡和管状结构得以恢复,并伴有细胞增殖显著增加和凋亡活性降低。随后,与未治疗的照射组相比,观察到体重和SFR显著增加,以及在第16周时腺体重量增加。
BACKGROUND: Radiotherapy in head and neck cancer management causes degeneration of the salivary glands (SG). This study was designed to determine the potential of gingival mesenchymal stem cells (GMSCs) as a cell-based therapy to regenerate irradiated parotid SG tissues and restore their function using a murine model. METHODS: Cultured isolated cells from gingival tissues of 4 healthy guinea pigs at passage 3 were characterized as GMSCSs using flow cytometry for surface markers and multilineage differentiation capacity. Twenty-one Guinea pigs were equally divided into three groups: Group I/Test, received single local irradiation of 15 Gy to the head and neck field followed by intravenous injection of labeled GMSCs, Group II/Positive control, which received the same irradiation dose followed by injection of phosphate buffer solution (PBS), and Group III/Negative control, received (PBS) injection only. Body weight and salivary flow rate (SFR) were measured at baseline, 11 days, 8-, 13- and 16-weeks post-irradiation. At 16 weeks, parotid glands were harvested for assessment of gland weight and histological and immunohistochemical analysis. RESULTS: The injected GMSCs homed to degenerated glands, with subsequent restoration of the normal gland histological acinar and tubular structure associated with a significant increase in cell proliferation and reduction in apoptotic activity. Subsequently, a significant increase in body weight and SFR, as well as an increase in gland weight at 16 weeks in comparison with the irradiated non-treated group were observed. CONCLUSION: The study provided a new potential therapeutic strategy for the treatment of xerostomia by re-engineering radiated SG using GMSCs.
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