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Lipid nanoparticles (LNPs) are becoming popular as a means of delivering therapeutics, including those based on nucleic acids and mRNA. The mRNA-based coronavirus disease 2019 vaccines are perfect examples to highlight the role played by drug delivery systems in advancing human health. The fundamentals of LNPs for the delivery of nucleic acid- and mRNA-based therapeutics, are well established. Thus, future research on LNPs will focus on addressing the following: expanding the scope of drug delivery to different constituents of the human body, expanding the number of diseases that can be targeted, and studying the change in the pharmacokinetics of LNPs under physiological and pathological conditions. This review article provides an overview of recent advances aimed at expanding the application of LNPs, focusing on the pharmacokinetics and advantages of LNPs. In addition, analytical techniques, library construction and screening, rational design, active targeting, and applicability to gene editing therapy have also been discussed. 相似文献
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Laurien J. Zeverijn Eleonora J. Looze Subotheni Thavaneswaran J. Maxime van Berge Henegouwen Robert J. Simes Louisa R. Hoes Katrin M. Sjoquist Hanneke van der Wijngaart Lucille Sebastian Birgit S. Geurts Chee K. Lee Gijsbrecht F. de Wit David Espinoza Paul Roepman Frank P. Lin Anne M. L. Jansen Wendy W. J. de Leng Vincent van der Noort Lindsay V. M. Leek Filip Y. F. L. de Vos Carla M. L. van Herpen Hans Gelderblom Henk M. W. Verheul David M. Thomas Emile E. Voest 《International journal of cancer. Journal international du cancer》2023,153(7):1413-1422
The Dutch Drug Rediscovery Protocol (DRUP) and the Australian Cancer Molecular Screening and Therapeutic (MoST) Program are similar nonrandomized, multidrug, pan-cancer trial platforms that aim to identify signals of clinical activity of molecularly matched targeted therapies or immunotherapies outside their approved indications. Here, we report results for advanced or metastatic cancer patients with tumors harboring cyclin D-CDK4/6 pathway alterations treated with CDK4/6 inhibitors palbociclib or ribociclib. We included adult patients that had therapy-refractory solid malignancies with the following alterations: amplifications of CDK4, CDK6, CCND1, CCND2 or CCND3, or complete loss of CDKN2A or SMARCA4. Within MoST, all patients were treated with palbociclib, whereas in DRUP, palbociclib and ribociclib were assigned to different cohorts (defined by tumor type and alteration). The primary endpoint for this combined analysis was clinical benefit, defined as confirmed objective response or stable disease ≥16 weeks. We treated 139 patients with a broad variety of tumor types; 116 with palbociclib and 23 with ribociclib. In 112 evaluable patients, the objective response rate was 0% and clinical benefit rate at 16 weeks was 15%. Median progression-free survival was 4 months (95% CI: 3-5 months), and median overall survival 5 months (95% CI: 4-6 months). In conclusion, only limited clinical activity of palbociclib and ribociclib monotherapy in patients with pretreated cancers harboring cyclin D-CDK4/6 pathway alterations was observed. Our findings indicate that monotherapy use of palbociclib or ribociclib is not recommended and that merging data of two similar precision oncology trials is feasible. 相似文献
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The advent of precision medicine has changed the landscape of oncologic biomarkers, drug discovery, drug development, and, more importantly, outcomes for patients with cancer. Precision oncology entails the genomic profiling of tumors to detect actionable aberrations. The advances in clinical next-generation sequencing from both tumor tissue and liquid biopsy and availability of targeted therapies has rapidly entered mainstream clinical practice. In this review, recent major developments in precision oncology that have affected outcomes for patients with cancer are discussed. Rapid clinical development was seen of targeted agents across various mutational profiles such as KRASG12C (which was considered “undruggable” for almost 4 decades), Exon 20 insertions, and RET mutations. Approaches to precision chemotherapy delivery by the introduction of antibody drug conjugates in the armamentarium against lung cancer has been appreciated. 相似文献
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目的探究腹腔镜精准肝切除术治疗原发性肝癌的临床效果。方法选择2019年1月—2020年6月期间在医院接受腹腔镜肝切除术治疗的80例原发性肝癌患者作为实验分析对象,依据手术治疗方案的不同将患者分为腹腔镜常规肝切除组(对照组)40例和腹腔镜精准肝切除组(观察组)40例,对两组患者手术各项指标、手术前后肝功能指标改善情况及术后并发症发生率进行对比分析。结果观察组患者手术时间明显长于对照组,组间比较进行t检验,差异具有统计学意义(P<0.05);观察组患者术中出血量及术中输血量均少于对照组患者,术后恢复时间明显短于对照组患者,组间比较进行t检验,差异具有统计学意义(P<0.05);术后,两组患者ALT、AST、ALB及TBIL水平均显著降低,组内比较进行t检验,差异具有统计学意义(P<0.05),观察组患者ALT、AST、ALB及TBIL水平降低幅度显著大于对照组患者,组间比较进行t检验,差异具有统计学意义(P<0.05);观察组患者术后并发症发生率为10.00%,对照组患者术后并发症发生率为27.50%,组间比较进行χ2检验,差异具有统计学意义(χ2=4.021;P=0.045)。结论与腹腔镜常规肝切除术比较,腹腔镜精准肝切除术操作精细,手术时间相对较长,患者术中出血量更少,术后恢复时间更短,能够最大限度保护患者的肝脏,减低患者术后并发症发生率,提高手术治疗效果,改善患者预后。 相似文献
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