Double-Center Cross-Sectional Study of Contrast-Enhanced Ultrasound With Lumason/Definity as a Screening Tool for Kidney Cancer in Patients With Von-Hippel Lindau

The purpose of this study is to determine if contrast-enhanced ultrasound can detect abnormal features of kidney lesions in patients with Von-Hippel Lindau with the same accuracy as conventional ultrasound and contrast-enhanced magnetic resonance imaging (MRI)

开始日期2019-09-23

申办/合作机构

UNC Lineberger Comprehensive Cancer Center

[+1]

NCT02424955 / CompletedN/AIIT

Feasibility of 3D Perfusion Ultrasound for Liver Cancer SABR Planning and Response Evaluation

The purpose of this study is to prospectively analyze the value of 3D ultrasound perfusion imaging for treatment planning, the prediction of therapy success, and to monitor the treatment response in patients with a primary or metastatic liver tumor undergoing radiation treatment.

开始日期2014-11-18

申办/合作机构

Stanford University

NCT03045497 / Completed临床1期IIT

Contrast-Enhanced Ultrasound for the Evaluation of Transarterial Chemoembolization With Drug Eluting Beads

This pilot clinical trial compares the use of contrast-enhanced ultrasound to contrast-enhanced magnetic response imaging (MRI), the current clinical standard, in predicting treatment response in patients with liver cancer receiving transarterial chemoembolization with drug eluting beads. Comparing results of diagnostic procedures before and after transarterial chemoembolization may help doctors predict a patient's response to treatment and help plan the best treatment. It is not yet known if contrast-enhanced ultrasound works better than contrast-enhanced MRI in predicting treatment response in patients with liver cancer.

开始日期2012-12-12

申办/合作机构

Sidney Kimmel Cancer Center at Thomas Jefferson University

100 项与全氟己烷相关的临床结果

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100 项与全氟己烷相关的转化医学

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100 项与全氟己烷相关的专利（医药）

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182

项与全氟己烷相关的文献（医药）

2024-04-01·Environmental Research

Occurrence, source apportionment, and ecological risk of legacy and emerging per- and poly-fluoroalkyl substances (PFASs) in the Dahei river basin of a typical arid region in China

Article

作者: Duan, Limin ; Wang, Guoqiang ; Li, Jie ; An, Rui ; Li, Xinlei

Per- and poly-fluoroalkyl substances (PFASs) are artificial chemicals with broad commercial and industrial applications. Many studies about PFASs have been conducted in densely industrial and populated regions. However, fewer studies have focused on the PFASs' status in a typical arid region. Here, we investigated 30 legacy and emerging PFASs in surface water from the mainstream and tributaries of the Dahei River. Our results revealed that total PFASs concentrations (∑₃₀PFASs) in water ranged from 3.13 to 289.1 ng/L (mean: 25.40 ng/L). Perfluorooctanoic acid (PFOA) had the highest mean concentration of 2.44 ng/L with a 100% detection frequency (DF), followed by perfluorohexanoic acid (PFHxA) (mean concentration: 1.34 ng/L, DF: 59.26%). Also, perfluorohexane sulfonate (DF: 44.44%), perfluorobutane sulfonate (DF: 88.89%), and perfluorooctane sulfonate (PFOS) (DF: 92.59%) had mean concentrations of 12.94, 2.00, and 1.05 ng/L, respectively. Source apportionment through ratio analysis and principal component analysis-multiple linear regression analysis showed that treated or untreated sewage, aqueous film-forming foam, degradation of precursors, and fluoropolymer production were the primary sources. The PFOS alternatives were more prevalent than those of PFOA. Conductivity, total phosphorus, and chlorophyll a positively correlated with Σ₃₀PFASs and total perfluoroalkane sulfonates concentrations. Furthermore, ecological risk assessment showed that more attention should be paid to perfluorooctadecanoic acid, perfluorohexadecanoic acid, perfluorooctane sulfonate, perfluorohexane sulfonate, and (6:2 and 6:2/8:2) polyfluoroalkyl phosphate mono- and di-esters. The mass load of PFASs to the Yellow River was 1.28 kg/year due to the low annual runoff in the Dahei River in the arid region. This study provides baseline data for PFASs in the Dahei River that can aid in the development of effective management strategies for controlling PFASs pollution in typical arid regions in China.

2024-02-06·Environmental Science & Technology

Assessment of Fetal Exposure and Elimination of Perfluoroalkyl and Polyfluoroalkyl Substances: New Evidence from Paired Serum, Placenta, and Meconium Samples

Article

作者: Wang, Yawei ; He, Anen ; Guan, Ruining ; Li, Juan ; Li, Zhao ; Liu, Chao ; Guo, Binbin ; Qian, Chenge ; Luo, Yadan ; Zhao, Chunyan ; Ma, Donghui ; Jiang, Guibin

Multiple pieces of evidence have shown that prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) is closely related to adverse birth outcomes for infants. However, difficult access to human samples limits our understanding of PFASs transport and metabolism across the human placental barrier, as well as the accurate assessment of fetal PFASs exposure. Herein, we assess fetal exposure to 28 PFASs based on paired serum, placenta, and meconium samples. Overall, 21 PFASs were identified first to be exposed to the fetus prenatally and to be metabolized and excreted by the fetus. In meconium samples, 25 PFASs were detected, with perfluorooctane sulfonate and perfluorohexane sulfonic acid being the dominant congeners, suggesting the metabolism and excretion of PFASs through meconium. Perfluoroalkyl sulfonic acids might be more easily eliminated through the meconium than perfluorinated carboxylic acids. Importantly, based on molecular docking, MRP1, OATP2B1, ASCT1, and P-gp were identified as crucial transporters in the dynamic placental transfer of PFASs between the mother and the fetus. ATSC5p and PubchemFP679 were recognized as critical structural features that affect the metabolism and secretion of PFASs through meconium. With increasing carbon chain length, both the transplacental transfer efficiency and meconium excretion efficiency of PFASs showed a structure-dependent manner. This study reports, for the first time, that meconium, which is a noninvasive and stable biological matrix, can be strong evidence of prenatal PFASs exposure.

2024-02-01·Talanta

Photoelectrochemical sensor for histone deacetylase Sirt1 detection based on Z-scheme heterojunction of CuS–BiVO4 photoactive material and the cyclic etching of MnO2 by NADH

Article

作者: Cao, Lulu ; Yin, Huanshun ; Gao, Lanlan ; Cao, Yaoyuan ; Ai, Shiyun ; Zhang, Miao ; Zhang, Haowei ; Zhou, Yunlei

A novel photoelectrochemical (PEC) biosensor was constructed for histone deacetylase Sirt1 detection based on the Z-Scheme heterojunction of CuS-BiVO₄ and reduced nicotinamide adenine dinucleotide (NADH) induced cyclic etching of MnO₂ triggered by Sirt1 enzyme catalytic histone deacetylation event. Based on the Z-Scheme heterojunction, the photoactivity of the CuS-BiVO₄ was improved greatly due to the highly effective separation of the photogenerated electron-hole pairs. In the presence of MnO₂ nanosheets on the CuS-BiVO₄/ITO electrode surface, the photocurrent decreased due to the inhibition effect of MnO₂. However, this inhibition effect was eliminated by the incubation of MnO₂/CuS-BiVO₄/ITO with NADH, where NADH was produced in the deacetylation process of acetylated peptide catalyzed by Sirt1 with NAD⁺. The formed NADH etched MnO₂, resulting in an increased photocurrent. In this process, NADH was oxidized to produce NAD⁺, which further involved the deacetylation process. Based on this cycle, the photocurrent of the biosensor was improved greatly and the sensitive and selective detection of Sirt1 was achieved. The biosensor presented a wide linear range from 0.005 to 10 nM with the low detection limit of 3.38 pM (S/N = 3). In addition, the applicability of the developed method was evaluated by investigating the effect of sodium butyrate and perfluorohexane sulfonate on Sirt1 activity.

项与全氟己烷相关的新闻（医药）

2024-03-16

·生物制品圈

mRNA靶向研究|PD-L1靶向IL-15 mRNA肿瘤免疫治疗

导读：基于PD-1/PD-L1的免疫检查点阻断（ICB）疗法可阻断肿瘤细胞的免疫逃逸，引发抗肿瘤免疫反应。但由于肿瘤内免疫效应细胞浸润不足，通过PD-1/PD-L1 ICB治疗实现的持久有效的免疫应答的患者数较少，因此，在肿瘤免疫微环境中动员免疫效应细胞是促进上述疗法的有效策略。2024年1月，国内学者在Journal of Controlled Release（影响因子10.8）发表文章：《A combination of PD-L1-targeted IL-15 mRNA nanotherapy and ultrasound-targeted microbubble destruction for tumor immunotherapy 》，研究人员开发了一种“DPPA/IL-15 NPs”纳米平台，利用超声靶向微泡破坏技术（UTMD）将白介素-15（IL-15）mRNA靶向递送至PD-L1。该平台通过诱导免疫原性细胞死亡（ICD）和IL-15表达，介导有效的抗肿瘤免疫治疗。01背景介绍白细胞介素-15（Interleukin-15，IL-15）可增殖、募集和激活细胞毒性T淋巴细胞（CTLs）和自然杀伤细胞（NKs），但半衰期短、毒副作用强。因此，将IL-15 mRNA靶向递送至肿瘤细胞可解决上述问题。脂质纳米颗粒（LNPs）是最有效的非病毒递送载体，免疫原性低、生物安全性高、易于合成，可通过优化脂质的组成和比例将mRNA靶向递送至特定器官，但血管畸形和细胞外基质密度高等肿瘤特征限制LNPs的深度渗透。超声（US）介导的药物递送显示出良好的临床前景，可暂时破坏血管内皮屏障促进细胞内化。超声靶向微泡破坏技术（UTMD）可通过增加细胞内活性氧（ROS）介导多种细胞反应，如自噬、上皮-间充质转化和逆转耐药性。已知ROS诱导的内质网（ER）应激是免疫原性细胞死亡（ICD）的前兆，释放的DAMPs显著促进树突状细胞（DCs）的活化和CTLs的募集，DCs激活是肿瘤免疫周期的初始阶段，UTMD有望成为这一步骤的有效刺激剂。基于以上背景，研究人员提出基于UTMD实现免疫检查点靶向的mRNA纳米疗法，研究将其命名为DPPA/IL-15 NPs。其递送系统的特色在于核心成分为全氟己烷（PFH），赋予其超声响应性和超声造影成像性能，同时脂质层存在抗PD-L1肽DPPA修饰。02DPPA/IL-15 NPs的制备、表征和回声性2.1 DPPA/IL-15 NPs的制备PD-L1靶向性LNP递送系统的制备：将100mg DSPE-PEG-NHS溶于3mL DMF中，加入DPPA肽和三乙胺，使其完全溶解并反应12h。将反应液在纯化水中透析24h，透析液冷冻干燥，得DSPE-PEG-DPPA。MC3和PLGA溶于DMF，DSPE-PEG-DPPA溶于无RNase水中（所有试剂使用前超声处理2min）。在pH3.5下，将固定比例的MC3和mRNA加入柠檬酸盐缓冲液中，混合并孵育20min，MC3-mRNA复合物，200μL PFH和250μg PLGA在冰浴条件下超声处理1min。将1mg DSPE-PEG-DPPA水溶液滴加到混合物中并超声处理3min。用无RNase水离心洗涤3次后，收集DPPA/IL-15 NPs并分散到PBS缓冲液中。通过评估发现在相同mRNA质量下，增加MC3可提高转染和翻译效率，当MC3/mRNA质量比为10达到饱和，后续实验MC3/mRNA=10。为探究DPPA/IL-15 NPs的最佳mRNA封装效率，制备分别含有2%、5%、10%、15%、20%和30% MC3的DPPA/IL-15 NPs，发现随MC3含量增加，包封效率逐渐提高，但伴随的溶血速率也增加，为保证生物安全性，后续实验使用10%的MC3。2.2 IL-15 mRNA纳米颗粒的表征IL-15 NPs和DPPA/IL-15 NPs均带负电荷，平均流体动力学尺寸分别为290.8±9.8 nm和325.9±9.4 nm，PDI分别是0.169±0.015和0.139±0.016，表明均匀性高；透射电镜（TEM）显示，DPPA/IL-15 NPs分散良好，粒径主要分布在300nm处；AFM和SEM图像显示DPPA/IL-15 NPs具有完整的球形结构；纳米复合物中mRNA不易被RNase降解，稳定性好；在含10% FBS的培养基中储存48h的DPPA/IL-15 NPs的血清稳定性好，在血液循环过程中可保持稳定。2.3 回声性给药后24h对Cy5-DPPA-NPs和Cy5-NPs的生物分布进行成像和定量，其主要通过肝肾系统代谢。为评估DPPA/IL-15 NPs作为超声造影剂的回声性，使用灰度和CEUS模式获取体外和体内超声图像，静脉注射DPPA/IL-15 NPs后，荷瘤小鼠的US图像在CEUS模式下表现出回声信号和对比增强（p＜0.01），治疗性超声暴露后，肿瘤灌注面积和造影剂强度均较照射前增加（p＜0.05）。因此，DPPA/IL-15 NPs有望在实时超声成像引导下确定肿瘤位置、监测治疗过程和评估治疗效果，实现诊断和治疗的整合。图1 DPPA/IL-15 NPs合成及特征03mRNA递送至肿瘤细胞进行蛋白质翻译免疫细胞分泌的IFN-γ可上调黑色素瘤细胞中的PD-L1，DPPA-NPs与肿瘤细胞上的PD-L1结合效率实验结果发现：PD-L1在IFN-γ处理的B16F10细胞中高表达(83.6%)，经游离DPPA和DPPA-NPs处理后，PD-L1分别下降至24.6%和26.4%，故DPPA-NPs表面的DPPA与PD-L1具有良好的结合能力。进一步探究Cy5-DPPA-NPs的细胞内化及其在US下的增强作用。相较NPs组，DPPA-NPs+US组中cy5阳性细胞比例比DPPA-NPs组高1.15倍，比NPs+US组高1.21倍，表明DPPA-NPs可通过DPPA介导的主动靶向和UTMD介导的超声加工被肿瘤细胞内化。高翻译效率是mRNA有效治疗的基础，研究人员探究DPPA-NPs联合UTMD的翻译效率，与NPs相比，DPPA-NPs介导的主动靶向增强mRNA翻译。DPPA-NPs组与DPPA-NPs+US组观察结果表明增强的mRNA表达受益于US暴露。DPPA-NPs+US组中GFP阳性细胞的数量最多、百分比最高为9618±191#s，96.2±1.9%，DPPA-NPs组和NPs+US组分别为7671±547#s（76.8±5.5%），7220±688#s（72.2±6.8%），荷瘤小鼠模型体内翻译效率与细胞实验结果一致，综上，DPPA/IL15 NPs与UTMD组合可提高翻译效率。图2 UTMD介导的DPPA-NPs mRNA的体外递送IVIS光谱成像系统结果表明UTMD增加了肿瘤部位的药物富集，对肿瘤组织进行解剖发现DPPA-NPs联合UTMD可深度穿透肿瘤。图3 UTMD介导的DPPA-NPs mRNA的体内递送04UTMD诱导ER应激驱动的ICD增强肿瘤免疫原性对于激活抗肿瘤免疫反应至关重要，肿瘤免疫原性可能由死亡的肿瘤细胞引起，称为ICD。采用膜联蛋白V-FITC/PI染色测定UTMD的细胞毒性，单独用US、NPs和DPPA-NPs（无超声）无法诱导显著的细胞凋亡，NPs＋US和DPPA-NPs+US组诱导的细胞凋亡水平明显高于其他组，且出现细胞膜破裂、细胞内容物渗漏和明显的内质网扩张，表明UTMD的声毒性导致细胞凋亡。利用FCM和荧光显微镜评估细胞内ROS的产生，NPs和DPPA-NPs在US照射后均在细胞内产生超氧化物水平的ROS，表明UTMD可诱导氧化应激，且UTMD组中观察到的GRP78高表达表明UTMD在肿瘤细胞内诱导ER应激。内质网中ROS诱导的氧化应激是ICD的先决条件。产生ICD通常伴随着DAMPs的释放，促进DCs的募集和激活，从而触发针对肿瘤细胞的CTLs。进一步探究发现UTMD可诱导内质网应激以触发ICD并驱动多种DAMPs释放，如CRT暴露、HMGB1释放和HSP70增加，综上，UTMD增加了药物向肿瘤部位的递送及肿瘤微环境（TME）中的抗肿瘤免疫反应。图4 UTMD诱导的内质网应激提高DAMPs释放05UTMD联合DPPA/IL-15NPs在体外进行免疫激活为进一步证明UTMD与DPPA/IL-15 NPs在细胞水平上诱导免疫反应的功能，提取小鼠BMDCs，通过门控CD80/CD86阳性细胞评估UTMD联合DPPA/IL-15 NPs对DCs成熟的影响。DPPA/IL-15 NPs+US组的B16F10细胞与BMDCs共培养后成熟DCs（CD11c+CD80+CD86+）的百分比达29.9±0.4%，高于DPPA-NPs+US组（15.0±1.3%）和DPPA/IL-15 NPs组（19.8±1.6%），表明DPPA/IL-15 NPs联合UTMD有效促进DCs成熟。细胞因子分泌对免疫激活很重要，DPPA/IL-15 NPs与UTMD结合后产生的肿瘤细胞碎片触发BMDCs分泌高水平细胞因子（包括IL-6和TNF-α），增强免疫反应。IL-15（促炎细胞因子）可促进T细胞增殖并维持其存活，DPPA/IL15 NPs+US组中的T细胞增殖率高于DPPA/IL-15 NPs组（p＜0.05），与UTMD高效转染IL-15 mRNA有关。NK细胞在无抗原刺激的情况下通过自发裂解肿瘤细胞来消灭它，DPPA/IL-15 NPs+US组NK细胞细胞毒性最高，其次是DPPA/IL-15 NPs组，表明IL-15 mRNA翻译的IL-15在NK细胞中具刺激作用。综上，DPPA/IL-15 NPs与UTMD的结合足以诱导DCs成熟、T细胞增殖并增强NK细胞毒性，具有增强抗肿瘤免疫力的潜力。图5 UTMD联合DPPA/IL-15 NPs的体外免疫激活06UTMD联合DPPA/IL-15 NPs在小鼠体内的免疫作用为评估UTMD与DPPA/IL-15 NPs在B16F10荷瘤小鼠中的联合作用。在第14d切除肿瘤，与对照组相比，DPPA-NPs +US组和DPPA/IL-15 NPs组表现出中度抑制作用，DPPA/IL-15 NPs+US组几乎完全抑制B16F10肿瘤生长，表明联合疗法抑制肿瘤生长。H&E和TUNEL染色评估B16F10肿瘤内的坏死和凋亡，对照组肿瘤细胞结构完整，DPPA-NPs+US、DPPA/IL-15 NPs、DPPA/IL-15 NPs+US组细胞结构丧失、细胞核萎缩及细胞坏死碎裂，DPPA/IL-15 NPs+US组的坏死区明显大于其他组。PD-L1靶向IL-15 mRNA纳米疗法与UTMD联合使用可有效协同，提高抗肿瘤疗效。生物安全是纳米疗法临床应用的前提，UTMD和DPPA/IL-15 NPs组合未引发显著全身毒性及明显病理损伤和炎症浸润，表明组合疗法对活体动物的高度生物安全性。图6 体内原发性B16F10肿瘤的抑制效果07UTMD联合DPPS/IL-15 NPs诱导体内抗肿瘤免疫应答DCs是激活抗肿瘤免疫反应的桥梁，与体外结果一致，DPPA/IL-15 NPs+US组中成熟DCs（CD11c+CD80+CD86+）水平最高（50.0±1.5%），DPPA-NPs、DPPA-NPs+US、DPPA/IL-15 NPs组和对照组分别为26.7±0.9%、31.3±1.7%、38.3±2.3%和22.2±0.6%，表明可能由于UTMD增强IL-15表达，IL-15与死亡肿瘤细胞释放的DAMPs协同作用，启动抗肿瘤免疫反应。CTLs（CD8+ T细胞）是抗肿瘤免疫疗法中的关键效应细胞。DPPA/IL-15 NPs+US组CD8+ T细胞的浸润率(24.1±2.3%)比DPPA-NPs+US组(11.7±1.0%)高2.05倍，比DPPA/IL-15 NPs组(17.6±2.0%)高1.37倍。表明UTMD和DPPA/IL-15 NPs的协同作用导致CTLs有效浸润到B16F10肿瘤中。与其他组相比，DPPA/IL-15 NPs+US组CD8+CD44+ T细胞百分比显著增加，大量肿瘤浸润CD4+ T细胞、CD8+ T细胞及NK细胞，表明联合治疗可系统增强T细胞免疫。与对照组相比，DPPA/IL-15 NPs+US组中IFN-γ、IL6和TNF-α分别高出6.10、3.83和5.42倍，进一步支持联合疗法诱导有效的抗肿瘤免疫反应。综上，UTMD联合DPPA/IL-15 NPs重塑肿瘤免疫微环境，促进免疫杀伤反应。图7 体内全身抗肿瘤免疫分析08UTMD联合DPPS/IL-15 NPs诱导免疫记忆进一步使用转移性肿瘤模型验证抗复发能力。在实验终端收集肺部，对照组观察到大量转移性结节，DPPA/IL-15 NPs+US组中仅观察到散发性转移灶，结合H&E图像结果表明UTMD联合DPPA/IL-15 NPs显著增强抗转移作用。免疫记忆反应是成功适应性免疫的重要标志，采用流式细胞术检测小鼠脾脏中CD8+CD44highCD62Llow效应记忆T细胞(TEM)和CD8+CD44highCD62Lhigh中枢记忆T细胞(TCM)，DPPA/IL-15 NPs+US组CD8+ TEM(28.2±0.5%)和TCM(17.4±0.6%)的百分比高于DPPA-NPs+US组(分别为20.0±0.2%和11.1±0.5%)和DPPA/IL-15 NPs组(分别为25.5±0.8%和12.9±0.8%)，证实联合治疗可诱导稳健的T细胞记忆。综上，UTMD与DPPA/IL-15 NPs联合有利于建立针对复发肿瘤的免疫记忆，作为新的肿瘤治疗途径。图8 免疫治疗转移性B16F10肿瘤的体内研究09小结本研究建立的PD-L1靶向性递送系统DPPA/IL-15 NPs不仅保护了mRNA，还表现出US响应性和CEUS成像能力。当与UTMD联用时，DPPA/IL-15 NPs实现了PD-L1最佳靶向，促进IL-15 mRNA的递送，并在体外和体内显示出更高的mRNA转染和翻译效率。UTMD可显著增加细胞内ROS，诱导ER应激驱动的ICD，作为启动抗肿瘤免疫的第一步。且UTMD与DPPA/IL-15 NPs组合可增加免疫效应细胞的募集及免疫刺激细胞因子的产生，从而有效抑制肿瘤生长和肿瘤复发。该联合疗法具有通过增强免疫疗法进行临床转化的潜力，并提供实时超声成像指导。参考文献 [1] Wang X, Li F, Zhang J, Guo L, Shang M, Sun X, Xiao S, Shi D, Meng D, Zhao Y, Jiang C, Li J. A combination of PD-L1-targeted IL-15 mRNA nanotherapy and ultrasound-targeted microbubble destruction for tumor immunotherapy. J Control Release. 2024 Jan 24;367:45-60. doi: 10.1016/j.jconrel.2024.01.039.识别微信二维码，添加生物制品圈小编，符合条件者即可加入生物制品微信群！请注明：姓名+研究方向！版权声明本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。END

信使RNA免疫疗法临床研究

2024-01-12

·drugs

Persistent Fluorinated Chemicals Tied to Higher Risk for Inflammatory Bowel Disease

FRIDAY, Jan. 12, 2024 -- Perfluoroalkyl and polyfluoroalkyl substance (PFAS) exposure is associated with later occurrence of inflammatory bowel disease (IBD), according to a research letter published online Dec. 26 in Clinical Gastroenterology and Hepatology . Manasi Agrawal, M.D., from the Icahn School of Medicine at Mount Sinai in New York City, and colleagues examined the association of PFAS mixture concentrations in prediagnostic serum in patients with adult-onset IBD participating in a pilot study within the preclinical Proteomic Evaluation and Discovery in an IBD Cohort of Tri-service Subjects study. The analysis included military personnel with Crohn disease (CD), those with ulcerative colitis (UC), and age-, sex-, and race-matched healthy controls (25 in each group). The researchers found that estimated mean concentrations in the study population were 5.19 µg/L for perfluorooctane sulfonic acid, 2.57 µg/L for perfluorooctanoic acid, and 2.32 µg/L for perfluorohexane sulfonate, which were comparable to PFAS levels in the general U.S. population. Within one year of diagnosis, each one-unit increase in decile mixture of fluorinated compounds in serum samples, including the known PFAS, was associated with higher odds of CD and UC (odds ratios, 2.13 and 1.76, respectively). At all four time points up to 10 years prior to diagnosis, these associations persisted for the PFAS mixture for both CD and UC. "Studies in larger cohorts, including analyses of pathways perturbed due to PFAS and the impact of new PFAS on disease outcomes, will be informative toward understanding IBD pathways and developing health policies to minimize exposure to harmful chemical pollutants," the authors write. Abstract/Full Text (subscription or payment may be required) Disclaimer: Statistical data in medical articles provide general trends and do not pertain to individuals. Individual factors can vary greatly. Always seek personalized medical advice for individual healthcare decisions. Posted January 2024 More news resources FDA Medwatch Drug Alerts Daily MedNews News for Health Professionals New Drug Approvals New Drug Applications Drug Shortages Clinical Trial Results Generic Drug Approvals Subscribe to our newsletter Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

临床结果临床研究

2023-09-07

·PRNewswire

VESSELON TOWN HALL EVENT PROVIDES A GLIMPSE INTO THE FUTURE OF INTRAVENOUS DRUG DEVELOPMENT

Industry experts reveal how Vesselon's drug platform offers a new paradigm for extending patents and improving efficacy. GREENWICH, Conn., Sept. 7, 2023 /PRNewswire/ -- In a digital town hall discussion held with industry analysts, Vesselon CEO and Co-founder Clay Larsen delivered a glimpse into the future of drug development that could revolutionize the pharmaceutical industry. The event, moderated by Endpoints News, showcased how Vesselon's drug platform can extend patents and rapidly create an endless stream of proprietary drugs. The company's bold strategy could yield multiple billion-dollar drug co-formulations by 2030 and redefine the boundaries of drug patents. Sharing the virtual stage with Larsen were EPISTAT CEO Llew Keltner MD, PhD and iECURE Inc. CEO Joe Truitt. The three experts explained how Vesselon's drug platform boosts the effectiveness of treatments by making tissues and tumors more receptive to drugs. This is achieved by combining FDA-approved lipid microspheres and self-assembling liposomes with approved drugs during administration, improving drug distribution at the target. They use existing ultrasound machines readily available at hospitals and cancer centers to trigger various biophysical actions that prime cells to receive the drug. This is done by directing standard diagnostic ultrasound at the diseased tissue during infusion treatment. Vesselon's Four Step Process Vesselon's lipid microspheres have unique characteristics that are fundamentally advantageous for this cutting-edge application of tissue modulation. Larsen outlined the drug platform's 4 step process to the audience as follows. Imagent® is mixed on-site in just five minutes prior to patient administration along with the therapeutic drug it will be used with. The co-formulation consists of a drug encapsulated in 10 billion gas microspheres. It simultaneously creates 50 trillion drug encapsulated self-assembling liposomes in the vial and includes free unencapsulated drug. This co-formulation is called TriForm™ because the co-formulated drug is not changed in any way - it maintains its same molecular mechanism of action. Then Vesselon uses commercially available ultrasound at cleared FDA levels pointed at the tissue of interest for less than 10 minutes. This interaction with the microspheres creates new biophysically initiated modes of action at the cellular level. This is based upon the safe cavitation of the microspheres within the vasculature of the intended target. One of these modes of action has been referred to as sonoporation, where nanoscale pores are opened temporarily in the endothelial wall to allow more drugs to enter the target tissue. "Our technology not only significantly improves a drug's bioavailability by multiple fold, but perhaps more importantly, the co-formulations create a new patentable entity for each drug, again, without needing to alter it in any way," Larsen said. "Our approach is based upon our Imagent® lipid microsphere, which is FDA approved for contrast ultrasound." Creating New Chemical Entities This is the real value proposition for Vesselon's drug platform; it allows pharmaceutical companies to create a new chemical entity that creates new IP, which could extend a drug life cycle for many years under a patent-protected environment—without having to change the active ingredient's manufacturing, packaging, or distribution. Truitt explained, "Unlike improvements to formulation that we often see where you maybe take a one-month injectable and maybe make it three months or six months, where you're not really changing the outcome or the efficacy, in this case, the promise of having a potential better efficacy along with the new chemical entity designation and patent is just really an attractive situation for any franchise." When asked what makes Vesselon an attractive candidate for acquisition, Truitt said that when an acquisition happens, whether it's analysts that are doing the work or bankers or strategic partners, "...there's always a terminal date which is the end of your IP in the financial model. Vesselon's drug platform is extending that terminal date to the new IP, in the new chemical entity. You're talking about a massive value inflection just on that fact alone. But what's also very interesting here is you get a terminal patent expiration, but you could extend that extremely important in any acquisition." As IP diligence is always exhaustive, the fact that Vesselon's drug platform is already well established means an acquiring company is not taking on the CMC risk that they would in a new program. Platform Flexibility Speaking to the flexibility of Vesselon's drug platform, Keltner said: "In terms of where the platform can be used in tissue, if you can image it with ultrasound, you can treat it. That literally is the limit because Vesselon is using diagnostic ultrasound from a normal diagnostic ultrasound machine at FDA approved frequencies. Additionally, Vesselon's microspheres are in fact FDA approved. They've been used in many, many thousands of patients for imaging at very, very high doses and concentrations. There is a very large safety data package on the microspheres themselves." Vesselon's solution modulates the tumor microenvironment with biophysics using a combination of gas microspheres and ultrasound to introduce new cellular-level biophysical modes of action to work in concert with the molecular mechanism of action of a selected active drug. This effect can be limited to the target by aiming the ultrasound transducer and beam only at the tumor area to ensure total tumor coverage as well as treatment to the immediate periphery of tissue. For a comprehensive look at Vesselon's town hall event, including additional insights from industry experts and audience Q&A, visit . Discover how Vesselon is shaping the future of drug development. About Vesselon Inc. Vesselon, Inc. is pioneering the development of patentable drug co-formulations using FDA-approved biophysically activated lipid microspheres and self-assembling liposomes. Their innovations promise to make targeted tissues more receptive to therapeutic drugs, ushering in a new era of unprecedented efficacy in medicine. For business inquiries, please contact Vesselon CFO Neil Edwards at [email protected]. SOURCE Vesselon, Inc.

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02424955 (CTgov)	N/A	肝细胞癌 \| 肝癌	11	3D ultrasound+perflutren lipid microspheres	鹹齋壓淵製選鬱鬱憲鏇(窪遞鑰窪醖積艱淵艱範) = 糧鑰憲醖顧憲醖憲餘鹹範獵廠顧築艱鏇鹽夢築 (衊鏇選窪窪壓糧壓憲願, 獵選鬱簾衊衊憲獵獵繭 ~ 鬱蓋鹽遞積繭鑰醖製艱) 更多	-	2023-07-11
NCT00584402 (CTgov)	N/A	肝癌	8	perflutren lipid microspheres	窪齋獵鑰壓積願齋選網(觸襯鑰鑰壓鏇壓觸構窪) = 壓憲鬱鹽窪鏇夢糧蓋願願範顧築壓糧蓋齋壓獵 (艱憲鏇積艱憲衊夢遞艱, 壓鹽構鑰觸鬱衊鏇窪艱 ~ 餘願願醖窪積衊窪醖鑰) 更多	-	2017-07-11