Nagah Bobtina, Maysa Alhawamdeh, Khaled Habas, Mohamed Isreb, Bayan Aburas, Andrew T Harris, Mojgan Najafzadeh, Diana Anderson
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引用次数: 0
摘要
Pembrolizumab 对多种人类癌症具有显著的抗癌效果。本研究调查了 Pembrolizumab 脂质体和纳米(裸体)形式在头颈部鳞状细胞癌(HNSCC)患者淋巴细胞中的作用,并与健康人进行了比较。此外,还研究了过氧化氢(H2O2)诱导的 DNA 氧化损伤水平。根据初步剂量优化试验,在彗星试验和微核试验中使用浓度为 10 µg/ml 的 pembrolizumab 脂质体处理淋巴细胞。为了确定pembrolizumab对H2O2的保护作用所涉及的细胞通路,对参与细胞凋亡的几种蛋白质(P53、P21和Bcl-2)进行了评估。Pembrolizumab 能显著减少 HNSCC 患者淋巴细胞中的 DNA 损伤和微核数量(p 2O2 ),并且在健康组和 HNSCC 组的彗星试验和微核试验中均有效(p
Genoprotective role of pembrolizumab liposome in isolated lymphocytes from head and neck squamous cell carcinoma patients compared to those from healthy individuals in vitro.
Pembrolizumab has shown significant anticancer effects against various human cancers. The present study investigated the effects of pembrolizumab liposome and nano (naked) forms in treated lymphocytes from head and neck squamous cell carcinoma (HNSCC) patients compared to healthy individuals. The level of oxidative DNA damage induced by hydrogen peroxide (H2O2) was also investigated. A concentration of 10 µg/ml of pembrolizumab liposome was used to treat the lymphocytes in the Comet and micronucleus assays based on the preliminary dosage optimization tests. To determine the cellular pathways involved in the protective role of pembrolizumab against H2O2, several proteins involved in apoptosis (P53, P21 and Bcl-2) were assessed. Pembrolizumab significantly reduced DNA damage and decreased the number of micronuclei in lymphocytes from HNSCC patients (p < 0.01) compared with healthy individuals. The 10 µg/ml of pembrolizumab liposome significantly reduced the oxidative stress induced by H2O2 and was effective in healthy and HNSCC groups using the Comet and micronucleus assays (p < 0.001). To our knowledge, this is the first report of pembrolizumab in liposome and naked forms exhibiting a protective effect on DNA damage in the treatment of HNSCC patients.
期刊介绍:
Nanotoxicology invites contributions addressing research relating to the potential for human and environmental exposure, hazard and risk associated with the use and development of nano-structured materials. In this context, the term nano-structured materials has a broad definition, including ‘materials with at least one dimension in the nanometer size range’. These nanomaterials range from nanoparticles and nanomedicines, to nano-surfaces of larger materials and composite materials. The range of nanomaterials in use and under development is extremely diverse, so this journal includes a range of materials generated for purposeful delivery into the body (food, medicines, diagnostics and prosthetics), to consumer products (e.g. paints, cosmetics, electronics and clothing), and particles designed for environmental applications (e.g. remediation). It is the nano-size range if these materials which unifies them and defines the scope of Nanotoxicology .
While the term ‘toxicology’ indicates risk, the journal Nanotoxicology also aims to encompass studies that enhance safety during the production, use and disposal of nanomaterials. Well-controlled studies demonstrating a lack of exposure, hazard or risk associated with nanomaterials, or studies aiming to improve biocompatibility are welcomed and encouraged, as such studies will lead to an advancement of nanotechnology. Furthermore, many nanoparticles are developed with the intention to improve human health (e.g. antimicrobial agents), and again, such articles are encouraged. In order to promote quality, Nanotoxicology will prioritise publications that have demonstrated characterisation of the nanomaterials investigated.