This phase II trial tests how well photoradiation with verteporfin and pembrolizumab plus standard of care chemotherapy works in treating patients with pancreatic cancer that cannot be removed by surgery (unresectable), that has spread to nearby tissue or lymph nodes (locally advanced) or to other places in the body (metastatic). Photoradiation uses light activated drugs, such as verteporfin, that become active when exposed to light. These activated drugs may kill tumor cells. Vertoporfin may also increase tumor response to immunotherapy. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as modified fluorouracil, leucovorin, irinotecan, and oxaliplatin (mFOLFIRINOX), work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Photoradiation with verteporfin and pembrolizumab plus standard of care chemotherapy may kill more tumor cells in patients with unresectable, locally advanced or metastatic pancreatic cancer.

开始日期2024-12-06

申办/合作机构

Mayo Clinic

[+1]

NCT06306638

/ Recruiting临床1/2期IIT

A Phase I/II Study of Interstitial Photodynamic Therapy Following Palliative Radiotherapy for Patients With Inoperable Malignant Central Airway Obstruction

This phase I/II trial studies the side effects of interstitial photodynamic therapy following palliative radiotherapy and how well it works in treating patients with inoperable malignant central airway obstruction. Patients who have advanced stage cancer tumors in the lung can often have the breathing passages to the lung partially or completely blocked. These tumors could be due to lung cancer or other cancers (e.g., renal, breast, kidney, etc.) that spread to the lung. This blockage puts the patient at a higher risk for respiratory failure, post-obstructive pneumonia, and prolonged hospitalizations. Treatment for these patients may include bronchoscopic intervention (such as mechanical removal, stenting, laser cauterization, or ballooning), radiation therapy with and without chemotherapy. While palliative x-ray radiotherapy may help in shrinking the tumor, high dose curative radiotherapy that can ablate (a localized, nonsurgical destruction) the tumor also has high risk to cause significant toxicity, including bleeding, abnormal connections or passageways between organs or vessels and abnormal scar tissue that can also produce airway obstruction. Photodynamic therapy (PDT) is another possible treatment that can provide local control of the tumor. PDT consists of injecting a light sensitive drug (photosensitizer, PS) into the vein, waiting for the PS to accumulate in the tumor, and then activating it with a red laser light. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Giving interstitial photodynamic therapy following palliative radiotherapy may improve tumor response and survival without the serious side effects that are associated with the typical high dose curative x-ray radiotherapy alone in patients with malignant central airway obstruction.

开始日期2024-10-01

申办/合作机构

Roswell Park Comprehensive Cancer Center

[+1]

NCT04075136

/ Withdrawn临床4期IIT

OCTA-Directed PDT Triple Therapy for Treatment-Naïve Patients With Exudative Age-Related Macular Degeneration Versus Standard of Care Anti-VEGF(Anti-vascular Endothelial Growth Factor) Monotherapy

Optical Coherent Tomography Angiography (OCTA)-Directed PDT Triple Therapy for Treatment-Naïve Patients with Exudative Age-related Macular Degeneration (ARMD) versus Standard of Care Anti-VEGF Monotherapy

开始日期2023-03-30

申办/合作机构

Wake Forest School of Medicine

[+1]

100 项与维替泊芬相关的临床结果

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100 项与维替泊芬相关的转化医学

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100 项与维替泊芬相关的专利（医药）

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2,225

项与维替泊芬相关的文献（医药）

2025-01-01·DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY

Muscle satellite cells and fibro‐adipogenic progenitors from muscle contractures of children with cerebral palsy have impaired regenerative capacity

Article

作者: Villalba, Marie ; Leach, J. Kent ; Davids, Jon R. ; Loomis, Taryn ; Smith, Lucas R. ; Kulkarni, Vedant A.

Abstract:

Aim:

To evaluate the mechanosensitivity of muscle satellite cells (MuSCs) and fibro‐adipogenic progenitors (FAPs) in cerebral palsy (CP) and the efficacy of the drug verteporfin in restoring cells' regenerative capacity.

Method:

Muscle biopsies were collected from six children with CP and six typically developing children. MuSCs and FAPs were isolated and plated on collagen‐coated polyacrylamide gels at stiffnesses of 0.2 kPa, 8 kPa, and 25 kPa. Cells were treated with verteporfin to block mechanosensing or with dimethyl sulfoxide as a negative control. MuSC differentiation and FAP activation into myofibroblasts were measured using immunofluorescence staining.

Results:

Surprisingly, MuSC differentiation was not affected by stiffness; however, stiff substrates resulted in large myonuclear clustering. Across all stiffnesses, MuSCs from children with CP had less differentiation than those of their typically developing counterparts. FAP activation into myofibroblasts was significantly higher in children with CP than their typically developing peers, but was not affected by stiffness. Verteporfin did not affect differentiation or activation in either cell population, but slightly decreased myonuclear clustering on stiff substrates.

Interpretation:

Cells from children with CP were less regenerative and more fibrotic compared to those of their typically developing counterparts, with MuSCs being sensitive to increases in stiffness. Therefore, the mechanosensitivity of MuSCs and FAPs may represent a new target to improve differentiation and activation in CP muscle.

2025-01-01·BIOCHEMICAL PHARMACOLOGY

Verteporfin combined with ROCK inhibitor promotes the restoration of corneal endothelial cell dysfunction in rats

Article

作者: Zhang, Xue ; Liu, Hongling ; Wan, Chao ; Yang, Yuli ; Liu, Yong ; Ren, Chunge ; Lu, Jia ; Li, Yijian

Corneal endothelial cells (CECs) dysfunction frequently results in a hazy, edematous cornea due to corneal endothelial decompensation and is a major cause of corneal blindness. Drug interventions provide a less invasive alternative to corneal transplantation surgery. However, endothelial-to-mesenchymal transition (EndMT) limits CECs function. Rho-kinase (ROCK) inhibitors, shown in numerous studies to be an adjunctive therapy for CECs dysfunction, cannot completely reverse pathological EndMT caused by inflammatory environmental damage. Verteporfin (VP) is an inhibitor of Yes-associated protein (YAP) and has significant inhibitory effects on cell fibrosis and mesenchymal transition. Here, we explored VP's utility in mitigating EndMT during ROCK inhibitors treatment of corneal endothelial dysfunction. We surgically constructed a rat model of CECs injury and studied VP and ROCK inhibitors' effects on EndMT, cell proliferation, and corneal edema using RNA-Seq sequencing, immunofluorescence, optical coherence tomography, and qPCR. The results indicated that YAP expression in human fetal CECs was higher than in adults and decreased with age in rats. Moreover, YAP expression in human CECs was negatively correlated with functional genes, such as AQP1 and ATP1A1. VP effectively reversed EndMT and accelerated corneal hydration regression. However, it inhibited CECs proliferation. We also confirmed that the optimal ratio of VP combined with Y-27632 (ROCK inhibitor) was 1:1, promoting CECs proliferation and reversing EndMT by down-regulating transcription factors downstream of TGF-β signaling, thereby increasing CECs functional and intercellular adhesion proteins. These combined effects promote corneal endothelial damage repair, providing a new treatment strategy.

2024-12-31·INTERNATIONAL JOURNAL OF HYPERTHERMIA

Mild heat stress promotes the differentiation of odontoblast-like MDPC-23 cells via yes-associated protein

Article

作者: Guo, Yi ; Li, Zhen ; Wang, Yijie ; Wang, Chenxu ; Niu, Lin ; Liu, Peiqi ; Zou, Rui ; Zou, Yuanwu ; Liao, Yuxin ; Zhang, Hui

PURPOSE:

Dentin hypersensitivity (DH) is a prevalent condition, but long-term effective treatments are scarce. Differentiation of odontoblast-like cells is promising for inducing tertiary dentinogenesis and ensuring sustained therapeutic efficacy against DH. This study examined the effects and mechanism of action of mild heat stress (MHS) on the differentiation of odontoblast-like MDPC-23 cells.

METHODS:

We used a heating device to accurately control the temperature and duration, mimicking the thermal microenvironment of odontoblast-like cells. Using this device, the effects of MHS on cell viability and differentiation were examined. Cell viability was assessed using the MTT assay. The expression and nucleoplasmic ratio of the yes-associated protein (YAP) were examined by western blotting and immunofluorescence. The gene expression levels of heat shock proteins (HSPs) and dentin matrix protein-1 (DMP1) were measured using qPCR. Dentin sialophosphoprotein (DSPP) expression was evaluated using immunofluorescence and immunoblotting. Verteporfin was used to inhibit YAP activity.

RESULTS:

Mild heat stress (MHS) enhanced the odontoblast differentiation of MDPC-23 cells while maintaining cell viability. MHS also increased YAP activity, as well as the levels of HSP25 mRNA, HSP70 mRNA, HSP90α mRNA, DMP1 mRNA, and DSPP protein. However, after YAP inhibition, both cell viability and the levels of HSP90α mRNA, DMP1 mRNA, and DSPP protein were reduced.

CONCLUSION:

YAP plays a crucial role in maintaining cell viability and promoting odontoblast differentiation of MDPC-23 cells under MHS. Consequently, MHS is a potential therapeutic strategy for DH, and boosting YAP activity could be beneficial for maintaining cell viability and promoting odontoblast differentiation.

项与维替泊芬相关的新闻（医药）

2024-02-13

·药渡

溶酶体捕获在药物研发中的意义与体外研究策略

前言溶酶体是细胞内执行消化作用的主要细胞器，也是代谢信号的传递中枢，参与调控了细胞内的多种生理代谢过程。研究表明，多种非化疗药物（如抗疟疾药氯喹、抗抑郁药丙咪嗪、止咳药右美沙芬等）和抗癌药物（如阿霉素、尼达尼布、索拉菲尼等）分子均对溶酶体具有高亲和力。此类药物分子通常具有碱性或弱碱性，容易在溶酶体中发生大量滞留，导致治疗效果不佳，且长期服用也易于引发耐药性和一些不良反应。药物在溶酶体内蓄积会影响其药代动力学特性、有效性和安全性，因此，在药物研发的早期阶段，尽早明确候选药物是否会被溶酶体捕获，能够更好地预测药物在组织和亚细胞内的分布情况，为新药研发过程中的吸收（absorption）、分布（distribution）、代谢（metabolism）及排泄（excretion）性质预测以及早期安全性评估提供参考。本文将从溶酶体的结构与功能出发，综合阐述溶酶体捕获的机理与应用，并提供相应的体外研究策略。溶酶体的结构与功能1溶酶体的结构溶酶体是一种具有单层膜结构的囊泡状、异质化的细胞器（图1），广泛地存在于除成熟红细胞之外的所有动物细胞中。溶酶体膜上存在一种关键蛋白——H+‑ATPase质子泵（V-type ATPase），它能够利用ATP水解释放的能量，驱动H+进入溶酶体腔（pH值大致为4.5~5.0），从而形成溶酶体-细胞质的pH梯度差。V-type ATPase质子泵与膜上其它离子通道蛋白（如Cl-通道蛋白、Na+/K+通道蛋白等）协同作用，以维持腔体内环境的动态平衡。图1. 溶酶体的生理结构[1]2溶酶体的功能溶酶体主要执行消化作用。溶酶体内部含有丰富的酸性水解酶，包括蛋白酶、脂肪酶、磷酸酶等，这些酸性水解酶能够帮助溶酶体消化经自噬或内吞作用运输的多种内源性或外源性大分子物质，也可以消化衰老或损伤的其它细胞器。除了基础的消化功能外，溶酶体还可以通过自噬作用参与细胞的免疫反应。溶酶体膜上的mTOR（雷帕霉素靶蛋白复合体）能够帮助溶酶体感知细胞内营养物质的富集情况，从而调节细胞的能量代谢和信号转导过程[2]。溶酶体捕获的机理及对ADME的影响基于溶酶体内的酸性环境，药物在溶酶体中发生质子化电离，并大量滞留在溶酶体内的过程被称为“溶酶体捕获”。溶酶体捕获的发生需要两个前提条件：（1）药物具有一定的跨膜能力（脂溶性）；（2）药物具有碱性基团，在酸性环境中容易发生质子化。1溶酶体捕获的机理一般而言，油水分配系数ClogP＞2.0，且pKa在6.5~11的化合物极易发生溶酶体捕获。亲脂性的碱性药物在生理pH条件下，主要以非解离型的形式存在，能够自由地穿透生物膜，进入细胞质。当其进入溶酶体后，溶酶体腔的酸性环境会促进药物结构中的碱性基团发生质子化电离。离子型药物的跨膜能力差，从而被滞留在溶酶体中，由此形成了“溶酶体捕获”现象（图2）。图2. 溶酶体捕获的机理2溶酶体捕获与药物ADME药物在人体内的ADME过程会受到诸如给药途径（如口服给药、注射给药、呼吸道吸入给药等）、生理因素（如组织器官血流量、体液pH值、细胞膜转运蛋白表达量等）、药物的固有性质（如脂溶性、酸碱性、血浆蛋白结合率等）和组织成分等多重因素的共同调控。亲溶酶体药物一方面由于其具有良好的脂溶性，药物分子更倾向于分布在脂肪丰富的组织，如脂肪、肝脏、肾脏等；另一方面因其易被溶酶体、高尔基体等酸性细胞器捕获，因此亲溶酶体药物容易在溶酶体丰富的组织器官（如肺、肾脏、肝脏、脾脏、脑和肠道等）中表现出极高的组织分布。药物的表观分布容积越大，相应的药物消除半衰期延长，在体内的存留时间越长。此外，对于口服制剂药物，溶酶体捕获作用可能会降低药物的吸收程度和吸收速率，从而影响药效。例如，右美沙芬在生物药剂学分类系统（Biopharmaceutics Classification System，BCS）中属于BCS I类化合物，在胃肠道中具有高溶解性和高渗透性，但是由于肠细胞的溶酶体捕获作用，使得其口服制剂中药物成分的达峰时间（约2.5小时）明显晚于其他典型的BCS I类药物（如普伐他汀的达峰时间为1~1.5小时）[3]。溶酶体捕获的应用溶酶体通透化介导的肿瘤细胞死亡正常情况下，溶酶体膜高度糖基化，溶酶体内的酸性水解酶被充分隔绝在溶酶体腔中。当溶酶体膜的通透性（Lysosomal membrane permeabilization，LMP）发生改变时，可溶性溶酶体内容物（如组织蛋白酶B、组织蛋白酶D等）释放到细胞质中，会激活细胞内的级联反应和炎症小体，促进细胞凋亡或坏死，这一过程被称为“溶酶体膜通透化介导的细胞死亡”。一般而言，与正常细胞相比，肿瘤细胞中的溶酶体数量增多，体腔变大，且溶酶体内水解酶的水平升高。因此，肿瘤细胞对亲溶酶体药物的毒性作用更敏感。当阳离子两亲性药物（cationic amphiphilic drugs，CADs）在溶酶体中大量蓄积时，会促进酸性鞘磷脂酶从溶酶体膜上分离，溶酶体膜通透化，组织蛋白酶释放增加，从而引起肿瘤细胞死亡（图3）。例如，抗组胺药特非那定（Terfenadine）可诱导前列腺癌细胞死亡；阿司咪唑（Astemizole）可抑制乳腺癌细胞和淋巴癌细胞的增殖[4]。图3. 溶酶体膜通透化介导的细胞死亡基于溶酶体内药物相互作用的联合用药多种抗肿瘤、抗疟疾、抗心律失常以及抗抑郁等中枢神经系统类药物均存在溶酶体捕获现象。当药物的作用靶点位于细胞核/质时，溶酶体捕获会降低靶位点的药物浓度，因此亲溶酶体药物作为单一药物进行治疗时，往往治疗效果有限，可以通过联合用药的方式来改善治疗效果。以索拉菲尼（Sorafenib，SF）和维替泊芬（Verteporfin，VP）的合用为例（图4），索拉菲尼是肝癌治疗的一线用药，但其容易发生溶酶体捕获，无法充分发挥药效。维替泊芬是一种亲溶酶体的自噬抑制剂，采用维替泊芬处理肝癌细胞会导致溶酶体pH值升高，溶酶体膜的通透性发生改变，当二者联合用药时，能够有效地抑制肝癌细胞的生长和增殖[5]。图4. 索拉菲尼联合维替泊芬治疗肝癌的示意图药物性诱导的磷脂沉积研究表明，亲溶酶体药物在细胞内的大量蓄积，容易诱导磷脂沉积症的发生。可能的机制有两种：第一种：药物与溶酶体内的脂质结合，形成难以被脂肪酶降解的药物-脂质复合物；第二种：药物抑制溶酶体脂肪酶的活性，导致磷脂大量蓄积。2021年，Science期刊发表的一篇关于SARS-CoV-2和其它病毒的药物再利用筛选报告指出[6]，近34%的抗病毒“老”药均为CAD药物，此类药物具有亲溶酶体性，而药物的抗病毒活性则与药物性磷脂沉积密切相关，提示溶酶体捕获诱导的药物性磷脂沉积在药物的抗病毒活性中可能发挥一定的作用。尽管如此，更多的研究证据表明药物和磷脂的大量蓄积会损伤溶酶体正常的生理功能，导致巨噬细胞和多种实质细胞出现空泡化，同时引起包括神经系统、心血管系统在内的肝脏、肾脏等多器官功能损伤[7]。因此，提前对药物进行早期磷脂沉积安全性风险评估，能够为先导化合物的筛选和结构优化提供参考，并增加候选药物进入临床试验的可行性。溶酶体捕获的体外研究策略目前，有关溶酶体捕获的体外研究方法主要有两种（表1）：第一种是基于液相色谱‑联质谱（LC-MS/MS）技术的生物分析；第二种是溶酶体特异性荧光探针的细胞蓄积实验。01基于LC-MS/MS技术的直接检测法V-type ATPase抑制剂能够抑制溶酶体酸化，进而降低药物在溶酶体内的蓄积。通过对比加与不加抑制剂处理后，药物在细胞/溶酶体内的浓度差异，可反映出药物在细胞/溶酶体内的蓄积情况。目前，科学家们采用MDCK II细胞、大鼠心肌细胞H9C2和人肝癌细胞Hep G2等多种细胞模型已经成功构建出一套快捷、准确、高通量的溶酶体捕获体外筛选体系[8, 9]。02溶酶体荧光探针蓄积实验（间接检测法）亲溶酶体药物在溶酶体中蓄积，会导致溶酶体腔内的pH值升高，从而降低pH依赖性的溶酶体特异性荧光探针的摄入。加与不加药物处理后，采用高内涵荧光显微镜进行成像，通过对比荧光探针在溶酶体内的荧光强度，能够预测化合物是否存在溶酶体捕获[10]。表1. 溶酶体捕获的体外研究方法溶酶体捕获评估模型的建立由于直接检测法能够更直接、准确地反映药物在溶酶体内的蓄积程度，同时对化合物的测试浓度要求较低，因此，药明康德DMPK团队采用直接检测法，基于MDCK II细胞模型成功建立了评估溶酶体捕获的两种筛选模型：Transwell模型和孔板模型。Transwell模型将MDCK II细胞接种至Transwell板，待细胞形成完整的单层膜结构后开始渗透性实验。化合物在含有或不含抑制剂的条件下，顶端到基底端（A‑B）方向给药。采用LC-MS/MS技术，检测化合物在未知样品中的浓度，通过对比加与不加抑制剂时，化合物在A-B方向的溶液回收率的改变，从而评估其是否被溶酶体捕获。药明康德DMPK挑选了6种性质已知的模型药物（表2）开展验证实验。在测试条件下，加入抑制剂能够显著提高亲溶酶体药物（氯丙嗪、洛哌丁胺、伊马替尼、普萘洛尔和右美沙芬）在A-B方向的溶液回收率（p<0.05），而酸性化合物双氯芬酸的溶液回收率则无明显差异（p>0.05）（图5），这一结果充分证明了该MDCK II细胞Transwell实验模型体系的可行性。表 2. 溶酶体捕获的模型药物信息图5. MDCK II细胞模型药物验证（Transwell模型）（*p<0.05，即有显著性差异）随后，采用MDCK II细胞Transwell实验模型探究化合物A与化合物B是否受溶酶体捕获，如图6所示，加入抑制剂后，化合物A在MDCK II细胞中A-B方向的溶液回收率显著提高，而化合物B的溶液回收率则无明显差异。提示化合物A极可能被MDCK II细胞内的溶酶体捕获，而化合物B不易发生溶酶体捕获。图6. MDCK II细胞测试化合物验证（Transwell模型）（*p<0.05，即有显著性差异）孔板模型将MDCK II细胞接种至96孔板中，培养过夜且达到80-90%融合度后，先将细胞置于含有或不含抑制剂的预孵育液中进行预孵育，随后与测试化合物进行共孵育。孵育结束后，采用LC-MS/MS技术，检测细胞裂解样品中化合物的浓度。最后，通过对比加与不加抑制剂时，化合物在细胞内蓄积量的差异，以评估化合物被溶酶体捕获的程度。为了验证模型的可靠性，采用与Transwell模型相同的模型药物进行验证实验。在测试条件下，加入抑制剂能够明显降低亲溶酶体药物（氯丙嗪、洛哌丁胺、伊马替尼、普萘洛尔和右美沙芬）在胞内的蓄积，而酸性化合物双氯芬酸在胞内的蓄积量则无明显差异（图7），这一结果也充分证明了MDCK II细胞孔板模型实验体系的可行性。图7. MDCK II细胞模型药物验证（孔板模型）随后，采用MDCK II细胞孔板模型同时探究化合物A与化合物B是否受溶酶体捕获，如图8所示，在测试条件下，加入抑制剂后，化合物A在MDCK II细胞内的蓄积量明显降低，而化合物B在胞内的蓄积则无明显差异。表明化合物A极可能被MDCK II细胞内的溶酶体捕获，而化合物B不易发生溶酶体捕获，这与MDCK II细胞Transwell实验模型的结论一致。图8. MDCK II细胞测试化合物验证（孔板模型）两种模型的差异MDCK II细胞Transwell模型与MDCK II细胞孔板模型均可用于体外溶酶体捕获评估的高通量分析。其中，MDCK II细胞Transwell模型可在评估测试化合物被溶酶体捕获程度的同时，对化合物进行渗透性的预测，并可探究溶酶体捕获效应对该测试化合物渗透性的影响。相对于MDCK II细胞Transwell模型而言，MDCK II细胞孔板模型实验周期短、通量高且成本低，更适用于药物研发早期阶段的高通量筛选。结语溶酶体的捕获效应存在于多种已知的上市药物以及在研的候选药物中。药物在溶酶体内蓄积会影响药物的药代动力学特征、有效性和安全性。亲溶酶体药物还可以通过改变溶酶体腔内的pH值、稳态体积以及酶结合位点，从而引起药物相互作用，进一步影响药效或产生毒副作用。因此，尽早明确候选药物是否会被溶酶体捕获，能够为药物的早期研发提供更全面的指导与帮助。参考文献：[1] Trivedi PC, Bartlett JJ, Pulinilkunnil T. Cells. 2020 May 4;9(5):1131.[2] Zhang Z, Yue P, Lu T, Wang Y, Wei Y, Wei X. Role of lysosomes in physiological activities, diseases, and therapy. J Hematol Oncol. 2021 May 14;14(1):79.[3] Bolger MB, Macwan JS, Sarfraz M, Almukainzi M, Löbenberg R. The Irrelevance of In Vitro Dissolution in Setting Product Specifications for Drugs Like Dextromethorphan That are Subject to Lysosomal Trapping. J Pharm Sci. 2019 Jan;108(1):268-278.[4] Serrano-Puebla, A., and Boya, P. (2018). Lysosomal Membrane Permeabilization as a Cell Death Mechanism in Cancer Cells. Biochem. Soc. T 46, 207–215.[5] Gavini J, Dommann N, Jakob MO, Keogh A, Bouchez LC, Karkampouna S, Julio MK, Medova M, Zimmer Y, Schläfli AM, Tschan MP, Candinas D, Stroka D, Banz V. Verteporfin-induced lysosomal compartment dysregulation potentiates the effect of sorafenib in hepatocellular carcinoma. Cell Death Dis. 2019 Oct 3;10(10):749.[6] Tummino TA, Rezelj VV, Fischer B, Fischer A, O'Meara MJ, Monel B, Vallet T, White KM, Zhang Z, Alon A, Schadt H, O'Donnell HR, Lyu J, Rosales R, McGovern BL, Rathnasinghe R, Jangra S, Schotsaert M, Galarneau JR, Krogan NJ, Urban L, Shokat KM, Kruse AC, García-Sastre A, Schwartz O, Moretti F, Vignuzzi M, Pognan F, Shoichet BK. Drug-induced phospholipidosis confounds drug repurposing for SARS-CoV. Science. 2021 Jul 30;373(6554):541-547[7] Breiden B, Sandhoff K. Emerging mechanisms of drug-induced phospholipidosis. Biol Chem. 2019 Dec 18;401(1):31-46.[8] Bednarczyk D, Sanghvi MV. The impact of assay recovery on the apparent permeability, a function of lysosomal trapping. Xenobiotica. 2020 Jul;50(7):753-760.[9] Nadanaciva S, Lu S, Gebhard DF, Jessen BA, Pennie WD, Will Y. A high content screening assay for identifying lysosomotropic compounds. Toxicol In Vitro. 2011 Apr; 25(3):715-23.[10] Schmitt MV, Lienau P, Fricker G, Reichel A. Quantitation of Lysosomal Trapping of Basic Lipophilic Compounds Using In Vitro Assays and In Silico Predictions Based on the Determination of the Full pH Profile of the Endo-/Lysosomal System in Rat Hepatocytes. Drug Metab Dispos. 2019 Jan;47(1):49-57. （下滑查看更多）作者：张喻，刘青，熊涛，陈根富编辑：钱卉娟设计：倪德伟，张莹莹免责声明“药渡”公众号所转载该篇文章来源于其他公众号平台，主要目的在于分享行业相关知识，传递当前最新资讯。图片、文章版权均属于原作者所有，如有侵权，请及时告知，我们会在24小时内删除相关信息。微信公众号的推送规则又双叒叕改啦，如果您不点个“在看”或者没设为"星标"，我们可能就消散在茫茫文海之中~点这里，千万不要错过药渡的最新消息哦！👇👇

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2024-02-03

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Nature新闻：人类肠菌中古怪的微小RNA

02月03日的《热心肠日报》，我们解读了 15 篇文献，关注：RNA，GLP-1RA，植物真菌，微流控，早产儿，脂肪肝，肥胖，纳米医学，噬菌体，菌群多样性，益生菌，菲仕兰，和黄医药，Daehwa，百吉福，Earthful。该篇日报由R·AI辅助创作生成，人工审核校对。 Nature：人类肠道中发现RNA新实体——“方尖碑”（新闻） Nature——[64.8] ① 根据近期发表的一项预印本研究，人类微生物群刚刚收获一个新成员——比病毒还小的微小RNA片段，在人类肠道和口腔细菌内定殖；② 虽然遗传物质片段太小，不足以被视为标准的生命形式，但其是向细胞传递指令的最小已知元素之一，其编码序列是全新的；③ 作者将该新元素称为“方尖碑”，尽管与许多类病毒具有相同的形状，但其基因序列截然不同，表明它们是一个独立但相关的群体；④ 各大洲人类粪便样本中都有大量“方尖碑”，来自身体不同部位微生物中的“方尖碑”具有不同的序列；⑤ 由于“方尖碑”所含基因不同于迄今为止在其他生物中发现的基因，它们包含了一类不同的RNA，这些RNA已经在人类和全球微生物群中定殖，并且未被注意到。【原文信息】 ‘Wildly weird’ RNA bits discovered infesting the microbes in our guts 2024-01-29 , doi: 10.1038/d41586-024-00266-7 国内团队BMJ：15种GLP-1RA在2型糖尿病中的疗效及安全性对比 British Medical Journal——[105.7] ① 北京中医药大学的万瑾毅团队发表的一项荟萃分析结果，总结了15种GLP-1受体激动剂（GLP-1RA）在成人2型糖尿病患者中的疗效和安全性，发现Tirzepatide在血糖控制方面效果最显著，CagriSema在体重管理方面表现最佳；② 纳入76项研究进行荟萃分析，共涉及15种GLP-1RA及39,246名2型糖尿病患者；③ 15种GLP-1RA均可有效降低糖化血红蛋白和空腹血糖，其中Tirzepatide的降糖效果最好；④ CagriSema（司美格鲁肽+卡格雷肽）的减重效果最好；⑤ 司美格鲁肽可有效降低LDL胆固醇和总胆固醇；⑥ 高剂量GLP-1RA可能导致胃肠道不良事件。【原文信息】 Comparative effectiveness of GLP-1 receptor agonists on glycaemic control, body weight, and lipid profile for type 2 diabetes: systematic review and network meta-analysis 2024-01-29 , doi: 10.1136/bmj-2023-076410 Science：受体相关激酶控制植物-真菌共生过程中的脂质供应 Science——[56.9] ① 本研究揭示了植物与丛枝菌根真菌（AM真菌）共生过程中，膜蛋白CKL1和CKL2的关键作用，它们通过调控转录因子影响脂质供应程序，并在内共生体适应中发挥重要作用；② CKL1和CKL2与LysM受体样激酶和DMI2相互作用，并被它们磷酸化，对AM共生至关重要；③ 脂质供应的启动与丛枝菌根真菌分支和RAM1调控元件的启动同时发生，对于内共生体的完全适应至关重要；④ CKL1和CKL2是AM共生所必需的，它们控制着转录因子的表达，而转录因子则调控着部分脂质供应程序；⑤ 这些发现为理解植物与真菌共生关系的分子机制提供了重要线索，有望为农业生产和生物技术领域提供新的思路和方法。【原文信息】 Receptor-associated kinases control the lipid provisioning program in plant-fungal symbiosis 2024-01-25 , doi: 10.1126/science.ade1124 微流控芯片生态进化获得氧化应激适应性益生菌 Small——[13.3] ① 实验室生态进化可克服益生菌工业应用面临氧化应激的缺陷，但目前微流控生态进化技术存在空间定义和细胞传代缺陷；② 本研究利用微流控芯片平台EVoc成功驱动益生菌鼠李糖乳杆菌GG对氧化应激的自适应进化，使其在高H2O2浓度下表现出显著的生长和抵抗能力；③ 经过两次适应性进化，菌株在H2O2浓度为1mM时的生长时间从31小时缩短至21小时，2mM时为28小时，3mM时为42小时；④ 适应性菌株在形态、基因表达模式和基因组序列上与野生型有所不同，蛋白质omega-amidase中存在潜在的有义单核苷酸突变。【原文信息】 Adaptive Laboratory Evolution of Probiotics toward Oxidative Stress Using a Microfluidic-Based Platform 2024-01-21 , doi: 10.1002/smll.202306974 益生菌在术后管理早产儿肠道手术的作用（荟萃分析） Cochrane Database of Systematic Reviews——[8.4] ① 评估在35周孕龄后出生的新生儿进行胃肠手术后给予益生菌的疗效和安全性，用于术后管理；② 与安慰剂相比，补充益生菌对于接受胃肠手术的新生儿在降低获得性败血症的风险（阳性细菌培养，局部或全身性）或达到全肠道喂养的时间上几乎没有影响；③ 两个研究组间都没有报道出院前死亡的情况；④ 相比安慰剂组，益生菌组婴儿肠道双歧杆菌科相对丰度明显更高，但其临床意义仍需探究。【原文信息】 Probiotics for the postoperative management of term neonates after gastrointestinal surgery 2024-01-23 , doi: 10.1002/14651858.CD012265.pub2 国内团队：多形拟杆菌或可治疗脂肪肝 Gut Microbes——[12.2] ① 中国医学科学院彭宗根团队研究了多形拟杆菌（Bt）对非酒精性脂肪肝病（NAFLD）代谢紊乱的作用并阐明其潜在机制；② 给予Bt治疗可显著改善高脂饮食小鼠的代谢综合征，包括减轻体重和脂肪堆积、降低高脂血症和胰岛素抵抗、预防脂肪肝和肝损伤；③ Bt通过调节肠道菌群组成，降低厚壁菌门/拟杆菌门比例，增加肠-肝叶酸水平和肝代谢物，从而缓解代谢功能障碍；④ Bt治疗还可增加小鼠肝脏中多不饱和脂肪酸的比例，改善非酒精性脂肪肝病；⑤ 本研究突出Bt作为潜在NAFLD益生菌的治疗作用，为开发新的治疗策略提供了重要的理论基础。【原文信息】 Bacteroides thetaiotaomicron ameliorates mouse hepatic steatosis through regulating gut microbial composition, gut-liver folate and unsaturated fatty acids metabolism 2024-01-26 , doi: 10.1080/19490976.2024.2304159 肥胖相关的肠菌特征（荟萃分析） Gut Microbes——[12.2] ① 使用来自17个不同国家的3329个样本（肥胖，n=1494；对照，n=1835），揭示肥胖与肠菌间的关联，鉴定出肥胖相关的物种和通路，为其研究和干预提供了重要线索；② 在肥胖者肠道微生物组中观察到多样性显著减少，推测这种减少导致了健康微生物功能的紊乱；③ 鉴定出25种高度预测的物种和37种通路与肥胖的标志相关联，并在独立数据集中得以验证；④ 肥胖者的肠道中SCFAs产生者和促进肠屏障完整性的物种减少，氨基酸、酶辅因子和肽聚糖合成通路显著富集；⑤ 绘制出重要的与肥胖相关功能变化的贡献者，并观察到这些贡献者既是数据集特定的，也是跨数据集共享的。【原文信息】 Meta-analysis reveals obesity associated gut microbial alteration patterns and reproducible contributors of functional shift 2024-01-24 , doi: 10.1080/19490976.2024.2304900 国内团队：纳米粒子声动力疗法治疗幽门螺杆菌感染 Nature Communications——[16.6] ① 中国科学技术大学阳丽华团队开发了一种新的声动力疗法，使用预先加载了Verteporfin的乳磷脂双层包被的聚（乳酸-聚乙二醇）纳米颗粒，Ver-PLGA@Lecithin，利用纳米颗粒和超声波成功治疗了幽门螺杆菌感染，且不影响肠道菌群平衡；② Ver-PLGA@Lecithin纳米颗粒能中和幽门螺杆菌的毒力因子，并通过产生活性氧杀灭细菌；③ 在小鼠模型中，声动力疗法与标准三联抗生素疗法效果相当，且不引起肠道菌群失调，仅引起乳酸菌丰度升高；④ 这一疗法为克服抗生素耐药提供了潜在解决方案，减少了抗生素耐药的风险，且对肠道菌群的干扰最小化。【原文信息】 A nanoparticle-based sonodynamic therapy reduces Helicobacter pylori infection in mouse without disrupting gut microbiota 2024-01-29 , doi: 10.1038/s41467-024-45156-8 Nature子刊：在1300年前人类粪便中发现的古代细菌噬菌体基因组 Nature Communications——[16.6] ① 通过分析先前从古代粪便和人类肠内容物样本中生成的DNA序列数据集，鉴定出一个与现代Mushuvirus mushu完全相同的古代噬菌体基因组（一种感染肠道共生细菌的病毒）；② 基因组的DNA损伤模式与其古老起源一致，尽管经过1300年的进化，古代Mushuvirus基因组与其现代对应物共享97.7%的核苷酸同一性，表明噬菌体和其宿主间存在长期关系；③ 重建并验证了过去5300年中的297个其他噬菌体基因组，包括属于未知家族的噬菌体；④ 这些发现拓展了噬菌体领域，为揭示跨数千年的噬菌体-细菌相互作用提供了重要见解。【原文信息】 Ultraconserved bacteriophage genome sequence identified in 1300-year-old human palaeofaeces 2024-01-23 , doi: 10.1038/s41467-023-44370-0 Cell子刊：纳米比亚居伊桑西人群肠道微生物多样性调查 Cell Reports——[8.8] ① 纳米比亚Ju|'hoansi族群是一个以狩猎和采集为主的族群，很少收到现代工业化社会的影响，本研究对该族群的肠道微生物组进行了调查研究，该族群与其他人群具有不同的肠道微生物核心组成；② 该族群肠道细菌组成与典型的狩猎采集族群类似，富含普雷沃氏菌、布劳蒂亚菌、普拉梭菌亚、琥铂酸弧菌和密螺旋菌等；③ 其肠道真菌主要包括动物病原体和植物腐生菌，如镰刀菌、东方伊萨酵母和扇菇菌等；④ 相比较其他因素，该族群的饮食和文化是其肠道微生物组组成的主要影响因素，。⑤ 这些结果为理解不同生活方式对肠道微生物组的影响提供了新视角，有助于拓展对人类肠道微生物组多样性的认识，为定制个性化的医疗和营养方案提供参考。【原文信息】 Documenting the diversity of the Namibian Ju|'hoansi intestinal microbiome 2024-01-19 , doi: 10.1016/j.celrep.2024.113690 皇家菲仕兰母乳低聚糖原料2'-FL泰国获批 ① 近日，荷兰皇家菲仕兰公司宣布，旗下2’-盐藻基乳糖（2’-FL）原料获得泰国监管部门批准，可用于婴幼儿配方奶粉产品；② 菲仕兰成为泰国唯一一家可同时提供母乳低聚糖和低聚半乳糖的原料供应商；③ 2’-FL已被证实对支持肠道健康和婴儿发育具有重要作用，菲仕兰公司计划将该原料与Vivinal低聚半乳糖等益生元成分复配，为消费者提供更具健康支持功效的婴配产品。【原文信息】 FrieslandCampina Ingredients secures Aequival 2’-FL approval in Thailand 2024-01-30 , Nutraceutical Business Review 和黄医药呋喹替尼中国香港地区获批 ① 1月30日，和黄医药宣布呋喹替尼在中国香港地区获批，用于治疗转移性结直肠癌患者；② 呋喹替尼是一种口服血管内皮生长因子受体（VEGFR）-1、-2及-3抑制剂，在大陆地区、中国澳门以及美国已获批用于结直肠癌治疗；③ 呋喹替尼的独特设计使其激酶选择性更高，具有更低的脱靶毒性、更高的耐受性，以及对靶点更稳定的覆盖；④ 基于中国国家药监局的批准，以及在中国香港当地的临床数据，和黄医药提交了呋喹替尼在中国香港的注册申请。【原文信息】和黄医药「呋喹替尼」在中国香港地区获批 2024-01-31 , 医药观澜 Daehwa二线胃癌药Liporaxel孤儿药资格认定获EMA推荐 ① 1月29日，韩国制药公司Daehwa Pharm宣布，旗下管线药物Liporaxel用于二线治疗胃癌孤儿药资格认定（ODD），获得了欧洲药品管理局积极意见；② Liporaxel是世界上首个口服紫杉醇制剂，Daehwa Pharm公司采用脂质自乳化递送技术开发而来；③ 在中韩两国开展的2个3期临床试验中，Liporaxel表现出非劣效性，不良反应降低；④ Daehwa Pharm国内合作公司海和药物正积极寻求Liporaxel在中国的批准上市。【原文信息】 Daehwa Pharm's Liporaxel receives positive EMA opinion for ODD as 2nd-line gastric cancer drug 2024-01-29 , Korea BIomedical Review 奶酪品牌「百吉福」获得凯辉基金独家战略投资 ① 1月26日，凯辉基金宣布与Savencia建立战略合作伙伴关系，并对Savencia旗下奶酪品牌百吉福进行独家战略投资；② 早在1996年，Savencia便正式进入中国市场，在天津设立了第一家工厂，成为中国首家外商独资的奶酪生产企业；③ Savencia将利用自身在产品创新、市场适应性和技术先进性方面的优势，进一步拓展中国市场；④ 凯辉基金的产业资源和行业洞察也将为百吉福在产品开发、品牌塑造、渠道拓展和供应链管理等方面带来新的发展。【原文信息】凯辉基金对Savencia旗下品牌百吉福进行独家战略投资 2024-01-30 , Foodaily 印度营养品牌「Earthful」获得3.3亿卢比种子轮融资 ① 近日，印度消费者营养品牌Earthful宣布完成3300万卢比（约合人民币285万元）的天使轮融资；② 投资方包括风投机构Green Ivy Venture和几位天使投资人；③ Earthful公司计划用融资进行研发投入、构建多渠道销售体系以及扩大团队规模；④ Earthful公司专注于开发植物基健康营养补充品，包括四种口味的素食蛋白粉、多种维生素、骨骼和皮肤健康保健品。【原文信息】 D2C nutrition brand Earthful raises ₹3.3 cr in pre-seed funding 2024-01-26 , The Hindu Businessline 感谢本期日报的审核者：RZN，aluba，NL，Johnson，九卿臣，圆圈儿，Zhonghua，Richard 点击阅读过去10天的日报： 0202 | 流感肆虐，高分Cell子刊揭示肠菌如何影响呼吸道感染 0201 | 1月，最值得看的40篇肠道健康文献！ 0131 | 今日Cell：于君/沈祖尧团队发现新的促胃癌菌 0130 | 炎症性肠病如何进行营养治疗？胃肠病学顶刊发出最新专家建议 0129 | 国内团队24页综述详解瘤内菌群——肿瘤研究新前沿 0128 | 32分综述详解：饮食如何通过菌群代谢物影响免疫？ 0127 | 今日Cell双发聚焦肠道！揭示肠道免疫和肠肝轴新机制 0126 | 改善心衰，肠菌代谢物提供治疗新思路 0125 | 高糖高油食品如何"绑架"大脑？Cell子刊揭示肠脑机制 0124 | 郝海平等Cell子刊：精神压力如何伤肠道？揭晓肠菌介导的脑-肠轴机制

临床结果

2023-11-01

·GlobeNewswire-Health Care

Research Funded by Bay Area Lyme Foundation Identifies New Investigational Therapy Regimen Capable of Irreversibly Damaging Lyme Bacteria in Laboratory Tests

Inspired by research that targets cancer tumors, these new findings in Lyme could also lead to novel R&D strategies for other diseasesPORTOLA VALLEY, Calif., Nov. 01, 2023 (GLOBE NEWSWIRE) -- Bay Area Lyme Foundation, a leading sponsor of Lyme disease research in the US, today announced the development of a potential new drug, HS-291, that targets and destroys Borrelia burgdorferi, the bacterium that causes Lyme disease. Published in the peer-reviewed journal Cell Chemical Biology, this laboratory study represents a novel paradigm shift for anti-microbial treatment research as it is the first to target and inhibit Borrelia burgdorferi HtpG (high temperature protein G), a specific type of enzyme within the bacteria that causes Lyme disease— a condition affecting nearly 500,000 new patients annually. The research was conducted at Duke University School of Medicine, with collaboration from University of North Carolina, Tulane University, and Stanford University, and HS-291 is currently in preclinical stage testing at UC Davis. “As Lyme disease is currently treated with broad spectrum antibiotics and there are no targeted treatments, we are particularly excited about this discovery, and hopeful that our novel Lyme disease therapeutic HS-291 will specifically destroy the Lyme bacterium without off-target effects or antibiotic resistance,” said Timothy Haystead, PhD, professor of Pharmacology and Cancer Biology, Duke University School of Medicine, Bay Area Lyme Foundation grantee, and co-lead author. “This research has been an incredible opportunity to leverage knowledge from oncology to Lyme disease in order to design an investigational therapeutic that could one day benefit hundreds of thousands of patients with Lyme.” This new discovery has implications beyond Lyme disease as it demonstrates that using the drug HS-291 to deliver cellular toxins to HtpG, a type of non-essential enzyme that assists the folding or unfolding of large and complex proteins, greatly expands what can be considered druggable within any pathogen and opens a whole new area of infectious disease research. When activated, HS-291, an inhibitor of HtpG tethered to the photoactive cellular toxin verteporfin, causes discrete protein modifications, which wreaks havoc on the Lyme disease bacterium’s DNA. This impacts multiple processes including nucleoid collapse and cell wall disruptions. A single dose of HS-291, when activated by light, irreversibly damages Borrelia proteins in close proximity of Bb HtpG in vitro. “Antibiotics used to treat Lyme disease do not always work for all patients, which causes many to suffer for years with extreme symptoms including neurocognitive issues, disabling fatigue and sleep disruption,” said Linda Giampa, executive director of the Bay Area Lyme Foundation. “Bay Area Lyme concentrates on funding innovative research, including projects where knowledge can be deployed from other areas of medicine. We hope that this discovery will inspire others to join us in investing in impactful, translational research to bring relief to patients.” This research was made possible by a 2020 Bay Area Lyme Foundation grant of more than $2 million to Duke University School of Medicine in honor of Neil Spector, MD, a renowned oncologist who passed away from complications of Lyme disease that had been misdiagnosed for years. He encouraged scientists to take cancer staging techniques and immunotherapy learnings from oncology and apply them to Lyme research. Dr. Spector was the Sandra Coates associate professor in the Duke University Department of Medicine and also served on Bay Area Lyme Foundation’s Scientific Advisory Board. Haystead and Spector joined forces as Spector sought to leverage his knowledge of oncology to help better understand Lyme disease, and Haystead’s research is focused on the use of chemical biology approaches to define novel drug targets focused on the treatment of hypertension, obesity, cancer, inflammatory and infectious disease. Bay Area Lyme Foundation also funded University of North Carolina collaborator, Matt Redinbo, PhD’s research on HS-291; his lab’s crystallography work was instrumental in the discovery process. Bay Area Lyme Foundation’s research grant program was made possible by the support from the Fairbairn Family, the Younger Family Fund, and Project Lyme. About Lyme disease The most common vector-borne infectious disease in the US, Lyme disease is a potentially disabling infection caused by bacteria transmitted through the bite of an infected tick to people and pets, and may also be passed from a pregnant mother to her unborn baby. If caught early, most cases of Lyme disease can be effectively treated, but it is commonly misdiagnosed due to lack of awareness and inaccurate diagnostic tests. There are approximately 500,000 new cases of Lyme disease each year, according to statistics released in 2018 by the CDC. As a result of the difficulty in diagnosing and treating Lyme disease, up to two million Americans may be suffering from the impact of its debilitating long-term symptoms and complications, according to Bay Area Lyme Foundation estimates. About Bay Area Lyme Foundation Bay Area Lyme Foundation, a national organization committed to making Lyme disease easy to diagnose and simple to cure, is the leading public not-for-profit sponsor of innovative Lyme disease research in the US. A 501c3 organization based in Silicon Valley, Bay Area Lyme Foundation collaborates with world-class scientists and institutions to accelerate medical breakthroughs for Lyme disease. It is also dedicated to providing reliable, fact-based information so that prevention and the importance of early treatment are common knowledge. A pivotal donation from The LaureL STEM FUND covers overhead costs and allows for 100% of all donor contributions to the Bay Area Lyme Foundation to go directly to research and prevention programs. For more information about Lyme disease or to get involved, visit www.bayarealyme.org or call us at 650-530-2439. Media contact:Tara DiMiliaPhone: 908-369-7168Tara.DiMilia@tmstrat.com

100 项与维替泊芬相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D01162	维替泊芬	S01LA01	DB00460

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
组织胞浆菌病	美国	Valeant Pharmaceuticals Luxembourg SARL	2008-06-30
变性近视	欧盟	CHEPLAPHARM Arzneimittel GmbH	2000-07-27
变性近视	冰岛	CHEPLAPHARM Arzneimittel GmbH	2000-07-27
变性近视	列支敦士登	CHEPLAPHARM Arzneimittel GmbH	2000-07-27
变性近视	挪威	CHEPLAPHARM Arzneimittel GmbH	2000-07-27
湿性年龄相关性黄斑变性	欧盟	CHEPLAPHARM Arzneimittel GmbH	2000-07-27
湿性年龄相关性黄斑变性	冰岛	CHEPLAPHARM Arzneimittel GmbH	2000-07-27
湿性年龄相关性黄斑变性	列支敦士登	CHEPLAPHARM Arzneimittel GmbH	2000-07-27
湿性年龄相关性黄斑变性	挪威	CHEPLAPHARM Arzneimittel GmbH	2000-07-27
年龄相关性黄斑变性	美国	Valeant Pharmaceuticals Luxembourg SARL	2000-04-12
脉络膜新生血管	美国	Valeant Pharmaceuticals Luxembourg SARL	2000-04-12

未上市

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
多发性基底细胞癌	临床3期	-	QLT, Inc.	2002-11-19
多发性基底细胞癌	临床3期	-	Novartis AG	2002-11-19
基底细胞痣综合征	临床3期	-	QLT, Inc.	2002-11-19
基底细胞痣综合征	临床3期	-	Novartis AG	2002-11-19

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临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


EURETINA2024	N/A	脉络膜出血	-	Photodynamic therapy (PDT)	廠鏇顧觸構廠艱鬱窪範(襯窪築選顧範窪壓憲餘) = No irreducible retinal detachment or globe loss were described, while four patients developed chronic neurosensory detachment 網選積願襯齋繭獵淵蓋 (選獵觸製簾廠製選窪鏇 ) 更多	-	2024-09-19
EURETINA2022	N/A	中心性浆液性脉络膜视网膜病变	-	Patients with verteporfin shortage	膚壓鑰顧鹹餘廠構夢範(繭壓醖醖觸顧蓋鬱觸蓋) = There was a significant impact with visual loss in patients with CSCR due to the shortage of verteporfin with the inability to undergo PDT 遞蓋糧壓簾繭糧鏇積繭 (壓鏇膚膚簾襯製襯簾鏇 )	-	2022-09-01
				Patients without verteporfin shortage
ITVT-02 (SNO2021)	临床1/2期	胶质母细胞瘤 EGFR \| PI3K	-	Verteporfin	淵膚憲淵積範鹽獵遞製(鹽顧鬱鏇築範齋觸簾遞) = 憲觸積觸鑰範衊構築廠淵構廠艱積廠餘觸獵積 (觸膚簾憲獵願獵鬱積廠 )	-	2021-11-12
				Verteporfin Photodynamic Therapy	淵膚憲淵積範鹽獵遞製(鹽顧鬱鏇築範齋觸簾遞) = 鏇簾鏇齋醖遞憲範淵窪淵構廠艱積廠餘觸獵積 (觸膚簾憲獵願獵鬱積廠 )
NCT03033225 (Pubmed \| Gastrointest Endosc)	临床2期	胰腺癌	8	EUS-guided verteporfin PDT	遞憲鏇膚築醖獵衊鑰齋(糧鬱糧糧製範鏇窪壓鹹) = 繭製糧願壓顧蓋淵選糧壓壓淵網願鏇網壓衊鏇 (齋觸淵鹽齋製選構積鑰 ) 更多	积极	2021-02-26
AAO2020	N/A	葡萄膜黑色素瘤	26	Primary PDT with Verteporfin	鑰蓋選築衊蓋襯齋膚襯(範製鬱製構鏇鏇網廠鬱) = 窪鏇鹹觸鹹鬱鏇築獵構繭願衊憲觸艱鹽鏇醖醖 (遞觸艱願衊糧構築夢糧 )	不佳	2020-11-13
NCT01846273 (EVEREST II, CTgov)	临床4期	年龄相关性黄斑变性 \| 息肉状脉络膜血管病	321	Ranibizumab (Ranibizumab 0.5 mg + vPDT)	襯觸憲網餘齋構網憲淵(積觸築繭衊衊鏇膚鬱積) = 獵齋鏇餘夢構築網積鏇廠觸窪願襯餘餘顧網蓋 (蓋遞壓憲願遞齋簾遞範, 選壓齋醖鹽選餘鬱網壓 ~ 顧構鹹構網簾壓選選鬱) 更多	-	2019-06-07
				Ranibizumab (Ranibizumab 0.5 mg)	襯觸憲網餘齋構網憲淵(積觸築繭衊衊鏇膚鬱積) = 襯範製憲簾衊鹽餘觸憲廠觸窪願襯餘餘顧網蓋 (蓋遞壓憲願遞齋簾遞範, 遞築淵膚窪膚膚蓋願鑰 ~ 製範廠遞獵衊獵願願鏇) 更多
OR02-4 (ENDO2019)	N/A	肾上腺皮质肿瘤 \| 肾上腺肿瘤辅助 YAP1	-	Verteporfin	襯網醖鑰築餘構顧鏇衊(淵遞鬱積顧壓膚鬱觸壓) = 網餘製壓顧鹹簾鹽糧繭憲獵窪膚糧齋簾廠簾廠 (窪遞構壓繭鏇顧鹹顧廠 ) 更多	积极	2019-04-30
NCT01846273 (Pubmed \| JAMA Ophthalmol) 人工标引	临床4期	息肉状脉络膜血管病	322	verteporfin photodynamic therapy +Ranibizumab	顧願顧憲鹹齋艱範壓鑰(鬱憲蓋膚壓願觸觸淵構) = 糧蓋網餘繭襯鑰艱顧獵製窪築構醖膚鬱壓餘構 (簾齋鹹鹽廠糧鹹簾鹹築 ) 更多	积极	2017-11-01
				Ranibizumab	顧願顧憲鹹齋艱範壓鑰(鬱憲蓋膚壓願觸觸淵構) = 淵繭淵餘齋願窪蓋構鹹製窪築構醖膚鬱壓餘構 (簾齋鹹鹽廠糧鹹簾鹹築 ) 更多
ARVO2017 人工标引	N/A	湿性年龄相关性黄斑变性	16	Adjunctive Indocyanine Green Angiography-Directed Verteporfin Photodynamic Therapy	餘鹽廠選壓構襯願餘壓(憲醖鏇憲醖繭鏇遞膚願) = 範繭齋廠積齋積糧鹽鏇簾壓築願壓鹹醖糧醖醖 (築餘鹹獵膚鑰艱範夢顧 )	积极	2017-06-01
APAO2017	N/A	中心性浆液性脉络膜视网膜病变	-	Focal verteporfin PDT	網衊襯獵顧壓築獵選觸(選鹽鑰糧襯醖醖範夢製) = 齋範餘夢齋獵醖齋選襯築廠製憲鹽鏇簾窪繭築 (簾憲繭鏇壓鑰築積範憲 )	-	2017-03-01
				Conventional verteporfin PDT	網衊襯獵顧壓築獵選觸(選鹽鑰糧襯醖醖範夢製) = 構膚餘鑰蓋憲夢願觸獵築廠製憲鹽鏇簾窪繭築 (簾憲繭鏇壓鑰築積範憲 )