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
英文原题:Ganoderma spore lipid ameliorates docetaxel, cisplatin, and 5-fluorouracil chemotherapy-induced damage to bone marrow mesenchymal stem cells and hematopoiesis.
Ganoderma spore lipid ameliorates docetaxel, cisplatin, and 5-fluorouracil chemotherapy-induced damage to bone marrow mesenchymal stem cells and hematopoiesis.
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GSL 有效保护 BMSC 免受 TPF 所致的损伤,并恢复了造血功能。
多西他赛、顺铂和5-氟尿嘧啶(TPF)三药化疗用于治疗头颈部鳞状细胞癌,但会损伤骨髓间充质干细胞(BMSC)。我们此前已证明灵芝孢子脂质(GSL)可保护BMSC免受环磷酰胺毒性。本研究探讨GSL对TPF诱导的BMSC损伤和造血损伤的保护作用。
将BMSC和C57BL/6小鼠分为对照组、TPF组、共同治疗组(GSL与TPF同时给药2天)和预处理组(先给予GSL 7天,再给予TPF 2天)。体外评估BMSC形态、表型、增殖、衰老、凋亡、活性氧(ROS)及分化。体内测定小鼠静脉血中的外周血小板(PLT)和白细胞(WBC),并分离骨髓细胞进行造血集落形成实验。
体外与TPF组相比,GSL显著减轻TPF对BMSC造成的损伤,恢复其形态、表型、增殖和分化能力(p<0.05)。Annexin V/PI和衰老相关β-半乳糖苷酶染色显示,GSL抑制TPF处理BMSC凋亡并延缓细胞衰老(p<0.05)。GSL下调caspase-3表达并减少ROS形成(p<0.05)。体内GSL恢复外周PLT和WBC数量,并保护骨髓细胞集落形成能力(p<0.05)。
GSL可有效保护BMSC免受TPF造成的损伤并恢复造血功能。
A triplet chemotherapy regimen of docetaxel, cisplatin, and 5-fluorouracil (TPF) is used to treat head and neck squamous cell carcinoma; however, it is toxic to bone marrow mesenchymal stem cells (BMSCs). We previously demonstrated that Ganoderma spore lipid (GSL) protect BMSCs against cyclophosphamide toxicity. In this study, we investigated the protective effects of GSL against TPF-induced BMSCs and hematopoietic damage.
BMSCs and C57BL/6 mice were divided into control, TPF, co-treatment (simultaneously treated with GSL and TPF for 2 days), and pre-treatment (treated with GSL for 7 days before 2 days of TPF treatment) groups. In vitro, morphology, phenotype, proliferation, senescence, apoptosis, reactive oxygen species (ROS), and differentiation of BMSCs were evaluated. In vivo, peripheral platelets (PLTs) and white blood cells (WBCs) from mouse venous blood were quantified. Bone marrow cells were isolated for hematopoietic colony-forming examination.
In vitro, GSL significantly alleviated TPF-induced damage to BMSCs compared with the TPF group, recovering their morphology, phenotype, proliferation, and differentiation capacity (p < 0.05). Annexin V/PI and senescence-associated -galactosidase staining showed that GSL inhibited apoptosis and delayed senescence in TPF-treated BMSCs (p < 0.05). GSL downregulated the expression of caspase-3 and reduced ROS formation (p < 0.05). In vivo, GSL restored the number of peripheral PLTs and WBCs and protected the colony-forming capacity of bone marrow cells (p < 0.05).
GSL efficiently protected BMSCs from damage caused by TPF and recovered hematopoiesis.
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