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Unlocking Delivery Strategies for mRNA Therapeutics. 解开 mRNA 治疗的传递策略。
IF 2.8 4区 医学 Q3 ONCOLOGY Pub Date : 2024-01-01 DOI: 10.2174/1574892818666230607093231
Zhiyuan Luo, Yangchao Chen

mRNA emerged as an attractive therapy modality with the development of mRNA structure engineering techniques and delivery platforms. mRNA therapeutics, applied for vaccine therapy, protein replacement therapy, and chimeric antigen receptor (CAR) T cell-based therapy, has shown huge potential in treating a wide range of diseases, such as cancer and rare genetic diseases, with successful and exciting preclinical and clinical progress. In mRNA therapeutics, a potent delivery system is key to the success of its application for disease treatment. Herein, different types of mRNA delivery strategies, including nanoparticles produced from lipid or polymer materials, virus-based platforms, and exosome-based platforms, are mainly focused.

随着 mRNA 结构工程技术和递送平台的发展,mRNA 成为一种极具吸引力的治疗方式。mRNA 疗法应用于疫苗疗法、蛋白质替代疗法和基于嵌合抗原受体(CAR)T 细胞的疗法,在治疗癌症和罕见遗传病等多种疾病方面展现出巨大潜力,并取得了令人振奋的临床前和临床进展。在 mRNA 疗法中,有效的递送系统是其成功应用于疾病治疗的关键。这里主要介绍不同类型的 mRNA 递送策略,包括由脂质或聚合物材料制成的纳米颗粒、基于病毒的平台和基于外泌体的平台。
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引用次数: 0
Competitive Effect of Overexpressed C-terminal of Snail-1 (CSnail) in Control of the Growth and Metastasis of Melanoma Cells. 过表达的蜗牛-1(CSnail)C-末端在控制黑色素瘤细胞生长和转移中的竞争效应
IF 2.8 4区 医学 Q3 ONCOLOGY Pub Date : 2024-01-01 DOI: 10.2174/1574892818666230330105016
Sadegh Paydari Rostami, Negar Moghare Dehkordi, Yazdan Asgari, Mohammad Reza Bolouri, Nasrin Shayanfar, Reza Falak, Gholam Ali Kardar

Background: Epithelial-to-mesenchymal transition (EMT) plays a role in the invasion and metastasis of cancer cells. During this phenomenon, Snail can promote tumor progression by upregulating mesenchymal factors and downregulating the expression of pro-apoptotic proteins.

Objective: Therefore, interventions on the expression rate of Snails may show beneficial therapeutic applications.

Methods: In this study, the C-terminal region of Snail1, capable of binding to E-box genomic sequences, was subcloned into the pAAV-IRES-EGFP backbone to make complete AAV-CSnail viral particles. B16F10 as a metastatic melanoma cell line, with a null expression of wild type TP53 was transduced by AAV-CSnail. Moreover, the transduced cells were analyzed for in vitro expression of apoptosis, migration, and EMT-related genes, and in vivo inhibition of metastasis.

Results: In more than 80% of the AAV-CSnail transduced cells, the CSnail gene expression competitively reduced the wild-type Snail functionality and consequently lowered the mRNA expression level of EMT-related genes. Furthermore, the transcription level of cell cycle inhibitory factor p21 and pro-apoptotic factors were promoted. The scratch test showed a decrease in the migration ability of AAV-CSnail transduced group compared to control. Finally, metastasis of cancer cells to lung tissue in the AAV-CSnail-treated B16F10 melanoma mouse model was significantly reduced, pointing out to prevention of EMT by the competitive inhibitory effect of CSnail on Snail1 and increased apoptosis of B16F10 cells.

Conclusion: The capability of this successful competition in reducing the growth, invasion, and metastasis of melanoma cells indicates that gene therapy is a promising strategy for the control of the growth and metastasis of cancer cells.

背景:上皮细胞向间质转化(EMT)在癌细胞的侵袭和转移中起着一定的作用。在这一过程中,蜗牛可通过上调间质因子和下调促凋亡蛋白的表达来促进肿瘤进展:因此,干预蜗牛的表达率可能会带来有益的治疗效果:本研究将能与 E-box 基因组序列结合的蜗牛 1 的 C 端区域亚克隆到 pAAV-IRES-EGFP 骨架中,制成完整的 AAV-CSnail 病毒颗粒。AAV-CSnail 转染了野生型 TP53 空表达的转移性黑色素瘤细胞系 B16F10。此外,还对转导的细胞进行了体外凋亡、迁移和 EMT 相关基因表达以及体内转移抑制分析:结果:在超过 80% 的 AAV-CSnail 转导细胞中,CSnail 基因的表达竞争性地降低了野生型 Snail 的功能,从而降低了 EMT 相关基因的 mRNA 表达水平。此外,细胞周期抑制因子 p21 和促凋亡因子的转录水平也得到了提高。划痕试验显示,与对照组相比,AAV-CSnail 转导组的迁移能力下降。最后,AAV-CSnail处理的B16F10黑色素瘤小鼠模型中癌细胞向肺组织的转移明显减少,这表明CSnail对Snail1的竞争性抑制作用防止了EMT,并增加了B16F10细胞的凋亡:结论:这种成功的竞争能够减少黑色素瘤细胞的生长、侵袭和转移,这表明基因治疗是一种很有前景的控制癌细胞生长和转移的策略。
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引用次数: 0
Chebulinic Acid: An Incipient Anticancer Agent. 诃子林酸:一种新型抗癌剂
IF 2.8 4区 医学 Q3 ONCOLOGY Pub Date : 2024-01-01 DOI: 10.2174/1574892819666230821110429
Aashima, Mehak Rathi, Shilpi, Akash, Kamaljeet Kaur, Priyanka Kriplani, Kumar Guarve

Background: Terminalia chebula (T. chebula) comprising chebulinic acid as its principle active constituent is used to cure various diseases. T. chebula and chebulinic acid are used as antimicrobial, antioxidant, antidiabetic, anti-inflammatory, hepatoprotective, antimutagenic, radioprotective, cardioprotective, antiproliferative, antiarthritic, anticaries, and so on.

Objective: The objective of this current study is to give an overview of the recent literature and patents of T. chebula and chebulinic acid including methods of its isolation/extraction and their application in the prevention of various cancers and other diseases.

Methods: Present research and patents highlighting the anti-cancer potential of T. chebula and chebulinic acid have been studied and discussed keeping in view the scientific novelty and impact.

Results: Both T. chebula and chebulinic acid are currently being explored for their anticancer potential in vitro and in vivo. They are either incorporated alone or in combination with other plants or drugs to show their activity and many clinical trials are also going on various potentials of the plant and chebulinic acid. Novel extraction techniques are also explored and patented. Efforts are being made to improve the bioavailability by developing Novel herbal drug delivery systems of the plant extract or chebulinic acid itself.

Conclusion: Anti-cancer potential of T. chebula and chebulinic acid may be well established by promising clinical trials and may open new interventions in various tumors. Clinical trials in conjunction with standard therapies are required to explore and validate the actual potential of T. chebula and chebulinic acid respectively.

背景:以诃子林酸为主要活性成分的诃子树(Terminalia chebula)被用于治疗各种疾病。诃子叶和诃子林酸可用于抗菌、抗氧化、抗糖尿病、抗炎、保肝、抗突变、放射保护、心脏保护、抗增生、抗关节炎、抗龋齿等:本研究的目的是概述有关嚼草和嚼草酸的最新文献和专利,包括其分离/提取方法及其在预防各种癌症和其他疾病中的应用:方法:研究和讨论了目前有关星云树和诃子林酸抗癌潜力的研究和专利,同时考虑到其科学新颖性和影响:结果:目前正在对咀嚼糖和诃子布洛酸进行体外和体内抗癌潜力研究。它们或单独使用,或与其他植物或药物结合使用,以显示其活性,许多临床试验也在对植物和诃子林酸的各种潜力进行研究。此外,还探索了新的提取技术并申请了专利。目前正在努力通过开发植物提取物或诃子林鞣酸本身的新型草药给药系统来提高生物利用率:结论:诃子叶和诃子林鞣酸的抗癌潜力可能会在前景看好的临床试验中得到充分证实,并可能为各种肿瘤的干预开辟新途径。需要结合标准疗法进行临床试验,以探索和验证诃子叶和诃子林酸的实际潜力。
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引用次数: 0
A Descriptive Review of Cannabis sativa Patents for Cancer Treatment. 对用于癌症治疗的大麻专利的描述性回顾。
IF 2.8 4区 医学 Q3 ONCOLOGY Pub Date : 2024-01-01 DOI: 10.2174/1574892818666230213095717
Isabela Fernandes Pereira, Ana Maria Santos Oliveira, Anamaria Mendonça Santos, Denis de Melo Soares, Mairim Russo Serafini, Izabel Almeida Alves

Background: Cannabis use for tumor treatment has been explored in several areas, and its potential for tumor remission is currently being studied after the discovery of the endogenous cannabinoid.

Objective: The study aimed to conduct a critical patent review to identify and explore the latest advances and therapeutic strategies using Cannabis to treat cancer.

Methods: The research was carried out in the free and online database Espacenet, using the descriptors "cancer" and "Cannabis or cannabidiol" in the title or abstract. A total of 95 patents were identified for preliminary evaluation in the database. Six duplicate patents were excluded, 12 referring to traditional Chinese medicine and 36 with a title in disagreement with the scope of this review. In addition the final selection involved 21 patents that were in line with the objective of the study.

Results: As observed in the reading of patents, the interest of pharmaceutical industries and researchers and the development of new products to fight cancer have increased in recent years. The main cannabinoids present in the patents are tetrahydrocannabinol, cannabidiol, and hemp. Moreover, the patents were classified and the main applicant countries were the United States followed by Japan, with a higher filing rate in 2019 and, mainly by the industry.

Conclusion: In conclusion we can say that, the importance of parliamentary approval in the cultivation and investments that, in addition to bringing innovation to the industrial sector, enriches research in the area, contributing to the creation of new medicines.

背景:在发现内源性大麻素之后,目前正在研究大麻用于治疗肿瘤的潜力:本研究旨在开展一项重要的专利综述,以确定和探索利用大麻治疗癌症的最新进展和治疗策略:研究在免费在线数据库 Espacenet 中进行,在标题或摘要中使用了 "癌症 "和 "大麻或大麻二酚 "描述符。数据库中共确定了 95 项专利进行初步评估。排除了 6 项重复专利、12 项涉及传统中药的专利和 36 项标题与本综述范围不符的专利。此外,最终选择了 21 项符合研究目标的专利:从专利阅读中可以看出,近年来制药业和研究人员对开发抗癌新产品的兴趣与日俱增。专利中主要的大麻素有四氢大麻酚、大麻二酚和大麻。此外,对专利进行了分类,主要申请国是美国,其次是日本,2019 年申请率较高,主要是工业界:总之,我们可以说,议会批准在种植和投资方面的重要性,除了为工业部门带来创新,还丰富了该领域的研究,有助于创造新的药物。
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引用次数: 0
Acknowledgement To Reviewers 审稿人致谢
4区 医学 Q3 ONCOLOGY Pub Date : 2023-11-01 DOI: 10.2174/157489281804230217112618
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引用次数: 0
Patent Selections 专利的选择
4区 医学 Q3 ONCOLOGY Pub Date : 2023-11-01 DOI: 10.2174/157489281804230217112506
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引用次数: 0
Patent Selections 专利的选择
4区 医学 Q3 ONCOLOGY Pub Date : 2023-08-01 DOI: 10.2174/157489281803230127123426
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引用次数: 0
The Causal Effects of Cholelithiasis on Acute Pancreatitis and Pancreatic Cancer: A Large Sample Size Mendelian Randomization Analysis. 胆石症对急性胰腺炎和胰腺癌的因果影响:大样本孟德尔随机化分析。
IF 2.8 4区 医学 Q3 ONCOLOGY Pub Date : 2023-06-26 DOI: 10.2174/1574892818666230609121409
Moshi Rao, Xiaoshun Ai, Zijian Huang

Background: The aim of two-sample Mendelian randomization (MR) with a large sample size was to explore the causal cholelithiasis impact on acute pancreatitis and pancreatic cancer.

Methods: We performed the two-sample MR analysis with two models. Publicly available summary- level information for cholelithiasis was acquired from the Genome-Wide Summary Association Studies (GWAS) of FinnGen Biobank. The inverse variance weighted (IVW) method was the main method to obtain the MR estimates. Other methods were also used as supplementary methods, including MR-Egger, maximum likelihood, MR-Robust Adjusted Profile Score (MR-RAPS), weighted median, penalised weighted median method, and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) method.

Results: After the selection of genetic instrumental variables (IVs), 11 single nucleotide polymorphisms (SNPs) (Model 1) and 22 SNPs (Model 2) were used to explore the effect of cholelithiasis on acute pancreatitis, and 10 SNPs (Model 1) and 24 SNPs (Model 2) on pancreatic cancer. The findings obtained by the fixed-effect IVW method with both Model 1 and Model 2 showed that genetically predicted cholelithiasis was significantly related to the elevated acute pancreatitis risk (Model 1: OR: 1.001, 95% CI: 1.000-1.002, p <0.001; Model 2: OR: 1.001, 95% CI: 1.000-1.002, p <0.001). Moreover, cholelithiasis would also raise the pancreatic cancer risk (Model 1: OR: 1.676, 95% CI: 1.228-2.288, p = 0.001; Model 2: OR: 1.432, 95% CI: 1.116-1.839, p = 0.005).

Conclusion: Genetically predicted cholelithiasis was significantly related to the elevated risk of acute pancreatitis and pancreatic cancer. More attention should be paid to patients with cholelithiasis for the primary prevention of pancreatic-related diseases.

背景:大样本量双样本孟德尔随机化(MR)的目的是探讨胆石症对急性胰腺炎和胰腺癌的因果影响。方法:采用两种模型进行两样本MR分析。从FinnGen生物银行的全基因组汇总关联研究(GWAS)中获得了胆石症的公开摘要级信息。方差反加权(IVW)法是获得MR估计的主要方法。其他方法也被用作补充方法,包括MR-Egger法、最大似然法、mr -稳健调整后的特征评分法(MR-RAPS)、加权中位数法、惩罚加权中位数法和孟德尔随机化多效性残差和异常值法(MR-PRESSO)。结果:选择遗传工具变量(IVs)后,利用11个单核苷酸多态性(SNPs)(模型1)和22个SNPs(模型2)探讨胆石症对急性胰腺炎的影响,10个SNPs(模型1)和24个SNPs(模型2)探讨胆石症对胰腺癌的影响。模型1和模型2的固定效应IVW方法结果显示,遗传预测的胆石症与急性胰腺炎风险升高显著相关(模型1:OR: 1.001, 95% CI: 1.000-1.002, p)。结论:遗传预测的胆石症与急性胰腺炎和胰腺癌风险升高显著相关。胆石症患者应引起重视,作为胰腺相关疾病的一级预防。
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引用次数: 0
Meet the Editorial Board Member 与编辑委员会成员见面
IF 2.8 4区 医学 Q3 ONCOLOGY Pub Date : 2023-05-01 DOI: 10.2174/157489281802221028105228
V. Apostolopoulos
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引用次数: 0
Patent Selections 专利的选择
4区 医学 Q3 ONCOLOGY Pub Date : 2023-05-01 DOI: 10.2174/157489281802221028143545
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引用次数: 0
期刊
Recent patents on anti-cancer drug discovery
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