A Multicentre, Randomised, Double-blind, Placebo-controlled Proof of Concept Study to Compare the Efficacy and Safety of r-hLIF (Emfilermin) for Improving Embryo Implantation Following in Vitro Fertilization (IVF) and Embryo Transfer (ET) in Women With Recurrent Implantation Failure

The primary objective of the study was to provide further clinical and statistical evidence of the efficacy of r-hLIF, in comparison with placebo, administered during the luteal phase after IVF and ET for improving embryo implantation in infertile women with a history of at least 2 implantation failures following transfer of fresh embryos. The secondary objective of the study was to assess the safety profile of r-hLIF in the proposed indication.

开始日期2003-04-01

申办/合作机构

Merck KGaA

NCT00504530 / Completed临床1/2期

A Randomised, Double-blind, Placebo Controlled, Proof of Concept Study to Assess the Efficacy, Safety and Acceptability of r-hLIF for Improving Embryo Implantation Following in Vitro Fertilisation (IVF) and Embryo Transfer (ET) in Women With Recurrent Implantation Failure.

This study was designed to obtain pilot clinical evidence of the efficacy, safety and acceptability of r-hLIF administered during the luteal phase after IVF/intra-cytoplasmic sperm injection (ICSI) and ET for improving embryo implantation in infertile women with a history of at least three implantation failures following ART. Based on LIF expression patterns and experimental data from animal research a role of LIF in embryo implantation is anticipated.

开始日期2001-09-01

申办/合作机构

Merck KGaA

100 项与 Emfilermin 相关的临床结果

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100 项与 Emfilermin 相关的转化医学

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100 项与 Emfilermin 相关的专利（医药）

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377

项与 Emfilermin 相关的文献（医药）

2024-08-01·Current medicinal chemistry

Leukemia Inhibitory Factor Protects against Degeneration of Cone Photoreceptors Caused by RPE65 Deficiency

Article

作者: Zhou, Yongwei ; Zhen, Fangyuan ; Zou, Tongdan ; Zhang, Houbin ; Wang, Ting ; Wu, Jiahui ; Dong, Shuqian

Background:::

Retinal pigment epithelium (RPE) 65 is a key enzyme in the visual cycle involved in the regeneration of 11-cis-retinal. Mutations in the human RPE65 gene cause Leber’s congenital amaurosis (LCA), a severe form of an inherited retinal disorder. Animal models carrying Rpe65 mutations develop early-onset retinal degeneration. In particular, the cones degenerate faster than the rods. To date, gene therapy has been used successfully to treat RPE65-associated retinal disorders. However, gene therapy does not completely prevent progressive retinal degeneration in patients, possibly due to the vulnerability of cones in these patients. In the present study, we tested whether leukemia inhibitory factor (LIF), a trophic factor, protects cones in rd12 mice harboring a nonsense mutation in Rpe65.

Methods:::

LIF was administered to rd12 mice by intravitreal microinjection. Apoptosis of retinal cells was analyzed by TUNEL assay. The degeneration of cone cells was evaluated by immunostaining of retinal sections and retinal flat-mounts. Signaling proteins regulated by LIF in the retinal and cultured cells were determined by immunoblotting.

Results:::

Intravitreal administration of LIF activated the STAT3 signaling pathway, thereby inhibiting photoreceptor apoptosis and preserving cones in rd12 mice. Niclosamide (NCL), an inhibitor of STAT3 signaling, effectively blocked STAT3 signaling and autophagy in cultured 661W cells treated with LIF. Co-administration of LIF with NCL to rd12 mice abolished the protective effect of LIF, suggesting that STAT3 signaling and autophagy mediate the protection.

Conclusion:::

LIF is a potent factor that protects cones in rd12 mice. This finding implies that LIF can be used in combination with gene therapy to achieve better therapeutic outcomes for patients with RPE65-associated LCA.

2024-07-01·Small (Weinheim an der Bergstrasse, Germany)

Construction of Inorganic/Polymer Tandem Layer on Li Metal with Long‐Term Stability by LiNO₃ Concentration Gradient Electrolyte

Article

作者: Guo, Zhijie ; Zhao, Yong ; Zhang, Qi ; Zhou, Yamei ; Liu, Zewen ; Shi, Yue ; Chen, Silei ; Chen, Zhonghui ; He, Jinling ; Liu, Xiao ; Zhu, Xuebing ; Feng, Yunchong ; Song, Xiaosheng

Abstract:

Metal electrode with long cycle life is decisive for the actual use of metal rechargeable batteries, while the dendrite growth and side reaction limit their cyclic stability. Herein, the construction of polymer and inorganic‐rich SEI tandem layer structure on Li metal can be used for extraordinarily extending its cycle life is reported, which is generated by an in situ PVDF/LiF/LiNO3 (PLL) gel layer on the surface of Li metal with a chemically compatible ether solvent. The cycle life of Li//Li cells with the tandem layer structure is over 6000 h, six times longer than those with LiNO3 homogeneous electrolyte. It highlights the importance of LiNO3 concentration gradient electrolyte formed by the in situ PLL gel layer, in which highly concentrated LiNO3 is confined on the surface of Li metal to generate the uniform and inorganic‐rich LiF/Li2O/Li3N layer on the bottom of PVDF/LiF with good mechanical strength, resulting in the dendrite free anode in cell cycling. The assembled Li//LiFePO4 and Li//NMC811 batteries show the capacity retention rate of 80.9% after 800 cycles and 82.3% after 500 cycles, respectively, much higher than those of references.

2024-06-01·Journal of spine surgery (Hong Kong)

Lateral interbody fusion for adjacent segment disease: a narrative review

Review

作者: Wellington, Ian J ; Antonacci, Christopher L ; Esmende, Sean M ; Patel, Seema M ; Jackson, Casey ; Zeng, Francine

Background and Objective:

Adjacent segment disease (ASD) is a late complication of lumbar fusion characterized by persistent symptoms correlating to radiographic changes in the levels immediately above or below the prior fusion. Lateral interbody fusion (LIF) through a direct lateral approach is a minimally invasive and effective surgical treatment for ASD. Biomechanically, LIF for ASD provides significantly decreased motion in multiple planes. While hardware failure and injury to the lumbar plexus are potential complications, these risks may be outweighed by decreased blood loss, shorter operating room (OR) times, and possibly superior patient reported visual analog scale (VAS) scores compared to traditional posterior spinal fusion (PSF) alone. The purpose of this review is to summarize the history, uses, outcomes, and future directions of LIF for ASD.

Methods:

A review of national databases (PubMed and SCOPUS) was performed using literature from 1900 to 2022. Keywords included terms "LATERAL" and "LUMBAR" and "INTERBODY" and "FUSION" and "ADJACENT" and "SEGMENT" and "DISEASE". Studies that aimed to describe the biomechanical, clinical course and complications, radiological outcomes, biomechanical aspects, need for revision surgery, and/or patient reported outcomes of the XLIF/LIF technique were included.

Key Content and Findings:

This review includes a brief overview of the natural history of ASD and current approaches to address it. It then summarizes the main indications and utilization of LIF to address ASD, summarizing reported outcomes in regard to biomechanical, clinical, and radiographic outcomes.

Conclusions:

LIF has emerged as a minimally invasive and effective surgical treatment for ASD. This mini-review suggests that LIF provides a solid foundational biomechanical construct that has been paired with good patient-reported, clinical, and radiographic outcomes. While further research is required, current literature suggests that LIF for ASD results in fewer complications, decreased morbidity, and decreased need for subsequent surgery compared to other commonly utilized techniques.

项与 Emfilermin 相关的新闻（医药）

2024-03-22

·奇点网

找到了癌症控制大脑的惯用伎俩

*仅供医学专业人士阅读参考近年来越来越多的证据表明，神经系统不仅在人体发育、维持生理平衡及再生中发挥重要作用，同样在癌症发病机制中发挥着核心作用，对癌症发生、生长、传播和治疗耐药性造成直接和间接影响。反过来，癌症也会重塑和劫持神经系统的结构和功能。这些发现开辟了一个全新的医学研究领域，即癌症神经科学。去年，斯坦福大学著名神经肿瘤学家Michelle Monje领衔的研究团队发表重要研究成果[1]，表明胶质瘤细胞能够加强自身与神经突触的连接，利用神经可塑性过程来促进自身的分裂增殖，让我们对癌症神经科学有了更深刻的理解。近日，北京大学生命科学学院杨竞团队的最新研究成果发表在《细胞研究》期刊上[2]，表明多种癌症类型以共有的机制劫持大脑，为癌症神经科学提供了新颖的见解。他们发现，多种癌症类型的细胞都能够释放白细胞介素抑制因子（LIF）和半乳糖结合凝集素-3（Gal3），通过激活特定的大脑区域来促进肿瘤生长。阻断这些信号能够抑制肿瘤进展，并通过减少髓源性抑制细胞（MDSCs）的生成和增加CD8阳性T细胞的招募、活性来增强抗肿瘤免疫反应。论文截图尽管癌症神经科学的研究领域取得了众多进展，但肿瘤与神经系统之间串扰的病理机制仍未完全阐明，比如肿瘤细胞如何释放特定的信号分子来诱导大脑反应。在这项研究中，杨竞团队使用了肺腺癌小鼠模型、前列腺癌小鼠模型、结直肠癌小鼠模型、乳腺癌小鼠模型进行探索。他们对小鼠脑部进行了全面评估，从脑最前端的嗅球一直延伸到最后端的脑干。结果发现，虽然荷瘤小鼠的癌症类型不同，但都共享一种大脑反应模式：下丘脑室旁核（PVN）、视交叉上核（SCN）等脑区激活，孤束核（NTS）、弓状核（ARC）等与内脏或代谢信号相关的脑区未被激活。不同癌症类型的小鼠具有相同的大脑反应研究团队还给野生型小鼠植入了由医用级硅制成的假肿瘤。尽管这些假肿瘤与真实肿瘤的体积和重量相似，但未能激活大脑关键区域的神经活动，意味着肿瘤的物理存在并不是触发大脑特殊反应的主要因素。 RNA-seq和蛋白质组学分析结果显示，不同癌症类型的肿瘤细胞都会释放白血病抑制因子（LIF）和半乳糖凝集素3（Gal3）来与大脑交流，LIF和Gal3以协同方式上述触发大脑反应。给野生型小鼠同时注射LIF和Gal3后，小鼠的大脑反应模式与荷瘤小鼠相同。此外，前列腺癌、膀胱癌、输尿管癌、非小细胞肺癌、结直肠癌、肾癌等癌症患者的LIF和Gal3血浆水平显著提升，支持其在肿瘤激活大脑特定区域中的关键作用。多种癌症类型患者的LIF、Gal3血浆水平提高基因敲除的结果证明，肿瘤细胞正是利用LIF和Gal3来劫持大脑为自己的发展铺路。下丘脑室旁核是负责启动传出交感神经信号的关键中枢大脑区域。肿瘤细胞释放的LIF和Gal3激活下丘脑室旁核后，通过交感神经信号促进髓源性抑制细胞（MDSCs）的生成，从而减少CD8阳性T细胞的活性。机制通过基因敲除，或者使用LIF小分子抑制剂（EC330）或Gal3小分子抑制剂（GB1107）来阻断LIF、Gal3介导的信号通路，可以减少癌症诱导的特定大脑区域活动；另一方面，能够延缓荷瘤小鼠的肿瘤生长，并增强抗肿瘤免疫，增加CD8阳性T细胞在肿瘤中的招募，降低MDSCs的数量。敲除后肿瘤生长被抑制不仅如此，使用交感神经切除术移除荷瘤小鼠脾脏的交感神经输入，也可以减少MDSCs的数量。相反，体外实验结果表明，交感神经递质去甲肾上腺素（NE）能够增强MDSCs的免疫抑制基因表达，β-肾上腺素受体拮抗药（普萘洛尔）处理可以完全逆转这种效果。 MDSCs血浆水平下降总之，杨竞团队找到了不同类型肿瘤细胞劫持神经信号的惯用伎俩，表明多种癌症类型可以共享特定的信号通路来与神经系统进行通信。LIF和Gal3诱导大脑反应的具体机制，有待更加深入的探索。参考文献：[1]Taylor KR, Barron T, Hui A, et al. Glioma synapses recruit mechanisms of adaptive plasticity. Nature. 2023;10.1038/s41586-023-06678-1. doi:10.1038/s41586-023-06678-1[2]https://www.nature.com/articles/s41422-024-00946-z本文作者丨张艾迪

细胞疗法

100 项与 Emfilermin 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB06562

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
植入并发症	临床2期	-	Merck KGaA	2003-04-01
女性不孕症	临床2期	-	Merck KGaA	2001-09-01
不孕	临床2期	-	Zenyth Advisors LLC	-
不孕	临床2期	-	Merck Serono SA	-
不孕	临床2期	-	The Walter & Eliza Hall Institute of Medical Research	-
神经肌肉疾病	临床2期	美国	-	-
神经肌肉疾病	临床2期	澳大利亚	-	-
神经肌肉疾病	临床2期	-	Merck Serono SA	-
神经肌肉疾病	临床2期	-	Zenyth Advisors LLC	-
神经肌肉疾病	临床2期	-	The Walter & Eliza Hall Institute of Medical Research	-