tbuckley/cabot-search huggingface dataset:
177Lu-LNC1004 Radioligand Therapy in Patients with End-Stage Metastatic Cancers: A Single-Center, Single-Arm, Phase II Study
Authors: Hao Fu, Jingxiong Huang, Liang Zhao, Yuhang Chen, Weizhi Xu, Jiayu Cai, Lingyu Yu, Yizhen Pang, Wei Guo, Bishan Su, Long Sun, Hua Wu, Jingjing Zhang, Xiaoyuan Chen, Haojun Chen
Journal: Clinical Cancer Research (2025)

Abstract Purpose: Fibroblast activation protein (FAP) is highly expressed in cancer-associated fibroblasts and certain tumor cells, making it a promising therapeutic target for various malignancies. This study evaluated the efficacy and safety of 177Lu-Evans blue–FAP inhibitor (177Lu-LNC1004) radioligand therapy (RLT) for treating end-stage metastatic tumors. Patients and Methods: This single-arm, single-center, phase II trial included 28 patients with progressive metastatic malignancies (11 types) and high FAP expression (defined as a maximum standardized uptake value ≥10 in &amp;gt;50% of tumors) who had exhausted all approved therapies, screened between June 2022 and April 2024. Patients were scheduled to receive four 177Lu-LNC1004 RLT cycles at 3.33 GBq/cycle every 6 weeks. The primary endpoint was post-RLT radiologic response. The secondary endpoints were progression-free survival (PFS), overall survival (OS), dosimetry, and safety. Results: Eastern Cooperative Oncology Group scores &amp;gt;2 were observed in 68% of patients. Overall, 63 177Lu-LNC1004 RLT cycles were performed, with 19 (68%) patients undergoing ≥2 cycles. Disease control was achieved in 13 (13/28, 46%) patients, with 4 and 9 patients demonstrating partial response and stable disease, respectively, and associated with improved PFS and OS (P &amp;lt; 0.001). The mean absorbed dose in tumors was 4.69 ± 3.83 Gy/GBq (1.18–25.03 Gy/GBq). Treatment-related grade 3/4 hematotoxicity was observed in six (21%) patients, with thrombocytopenia, leukopenia, and neutropenia most prevalent. No grade 3/4 hepatotoxicity or nephrotoxicity was observed. Conclusions: FAP-directed RLT using 177Lu-LNC1004 at 3.33 GBq/cycle was well tolerated with an acceptable toxicity profile. Nearly half of patients achieved disease control, which was associated with prolonged PFS and OS.
Extracellular vesicles in tumor immunity: mechanisms and novel insights
Authors: Liwen Kuang, Lei Wu, Yongsheng Li
Journal: Molecular Cancer (2025)

Extracellular vesicles (EVs), nanoscale vesicles secreted by cells, have attracted considerable attention in recent years due to their role in tumor immunomodulation. These vesicles facilitate intercellular communication by transporting proteins, nucleic acids, and other biologically active substances, and they exhibit a dual role in tumor development and immune evasion mechanisms. Specifically, EVs can assist tumor cells in evading immune surveillance and attack by impairing immune cell function or modulating immunosuppressive pathways, thereby promoting tumor progression and metastasis. Conversely, they can also transport and release immunomodulatory factors that stimulate the activation and regulation of the immune system, enhancing the body's capacity to combat malignant diseases. This dual functionality of EVs presents promising avenues and targets for tumor immunotherapy. By examining the biological characteristics of EVs and their influence on tumor immunity, novel therapeutic strategies can be developed to improve the efficacy and relevance of cancer treatment. This review delineates the complex role of EVs in tumor immunomodulation and explores their potential implications for cancer therapeutic approaches, aiming to establish a theoretical foundation and provide practical insights for the advancement of future EVs-based cancer immunotherapy strategies.
Smartphone administered pulsed radio frequency energy therapy for expedited cutaneous wound healing
Authors: Mengxia Yu, Hongjia Yang, Haoteng Ye, Shuhuang Lin, Yujie Lu, Haoqiang Deng, Lulu Xu, Yongxin Guo, John S. Ho, Terry Tao Ye
Journal: npj Digital Medicine (2025)

Pulsed radio frequency energy (PRFE) therapy is a non-invasive, electromagnetic field-based treatment modality successfully used in clinical applications. However, conventional PRFE devices are often bulky, expensive, and require extended treatment durations, limiting patient adherence and efficacy. Here, we present a lightweight, cost-effective wearable PRFE system consisting of a flexible electronic bandage and a smartphone. The bandage, mainly composed of an NFC Frequency Doubler (NFD) and a Radiofrequency Energy Radiator (RER), is powered and administered by the smartphone to generate 27.12 MHz radio wave pulses, for simplified, smartphone-enabled PRFE therapy. Its ultra-flexible, battery-free design supports personalized wound care at a low-cost (<US$1). Both electromagnetic field simulation and measurement demonstrated that the proposed PRFE bandage achieves the field strength of clinical-grade PRFE equipment. In rat full-thickness wound models, PRFE therapy improved wound closure rates by ~20%, with enhanced re-epithelialization and angiogenesis compared to controls.
Impairment of Innate Immunity and Depletion of Vaccine‐Induced Memory B and T Cells in the Absence of the Spleen
Authors: Veronica Bordoni, Bianca Laura Cinicola, Eva Piano Mortari, Concetta Castilletti, Federica Guarracino, Christian Albano, Silvia Accordini, Anwar Baban, Antonio Di Sabatino, Carlo Maria Rossi, Marco Vincenzo Lenti, Anna Maria Zicari, Riccardo Cirelli, Marco Spada, Gian Luca Forni, Isabella Quinti, Mattia Algeri, Maddalena Casale, Silverio Perrotta, Franco Locatelli, Chiara Agrati, Rita Carsetti
Journal: American Journal of Hematology (2025)

ABSTRACT Splenectomy or congenital asplenia is associated with severe reduction of memory B cells and increased risk of fulminant sepsis by encapsulated bacteria. Current guidelines recommend vaccinations against these pathogens before or after splenectomy, but the longevity of immunity acquired after splenectomy has not been determined. The impact of splenectomy on innate immune cells is unknown. We analyzed frequency, differentiation stage, and function of innate and adaptive immunity in the peripheral blood of adult ( n = 41) and pediatric ( n = 14) patients splenectomized or born asplenic and in spleens of solid organ donors. The absence of the spleen impacts the B‐cell compartment, causing a significant increase of circulating immature transitional and depletion of memory B cells. Using SARS‐CoV‐2 vaccination as a model, we show that 1 year after the last immunization, despite normal levels of neutralizing antibodies, memory B and T cells were significantly reduced. Analysis of post‐pandemic spleens shows that spike‐specific memory B and T cells homed to the spleen. We also show a previously unrecognized role of the spleen in the homeostasis of innate NK and Vδ2 T cells. These populations showed altered phenotype and impaired function in the adults, but not in children, suggesting that other tissues may support innate cell development during early life. The reduced function of innate lymphocytes must be considered as an additional immune impairment and risk factor. These findings emphasize the spleen's irreplaceable role in maintaining immune memory across all ages and suggest that its absence contributes to dysfunctions of innate and adaptive immunity in adults.
Poly(amino acid) nanoformulation of cyclin-dependent kinase 4 and 6 inhibitor for molecularly targeted immunotherapy in triple-negative breast cancer
Authors: Xue Wei, Ming Yang, Haoyang Zou, Songjie Shen, Yuechong Li, Li Chen, Yahui Liu, Di Li, Jianxun Ding
Journal: Journal of Controlled Release (2025)
Pharmacokinetics and protein binding of cholesterol-conjugated heteroduplex oligonucleotide
Authors: Yukitake Yoshioka, Syunsuke Yamamoto, Kosuke Kusamori, Miyu Nakayama, Hisashi Fujita, Akihiko Goto, Shinji Iwasaki, Tetsuya Nagata, Shoko Itakura, Hiroyuki Kusuhara, Takanori Yokota, Hideki Hirabayashi, Makiya Nishikawa
Journal: Journal of Controlled Release (2025)

Heteroduplex oligonucleotide (HDO) is a novel oligonucleotide therapeutic consisting of an antisense oligonucleotide (ASO) and its complementary RNA. A recent report showed that cholesterol-conjugated HDO (Chol-HDO) exhibited antisense activity in various tissues, including the brain; however, little information is available on the pharmacokinetic and plasma protein-binding properties of HDO and Chol-HDO. In the present study, we investigated the tissue distributions of an ASO, HDO, and Chol-HDO in mice and rats after intravenous injection. Tissue distribution was evaluated by measuring the concentration of ASO in tissue samples using liquid chromatography and tandem mass spectroscopy. ASO and HDO disappeared rapidly from the plasma, whereas Chol-HDO showed prolonged retention in the systemic circulation. The amount of ASO in the brain tissue was highest after injection of Chol-HDO, confirming its efficient delivery to the brain. The tissue distribution of oligonucleotides differed less in rats than in mice. Hepatic uptake of ASO and HDO, but not of Chol-HDO, was significantly inhibited by co-administration with the scavenger receptor inhibitor dextran sulfate sodium. The binding to plasma proteins was evaluated. Compared to ASO, HDO showed lower protein binding, but Chol-HDO showed much higher binding, with remarkable differences in binding to high-density and low-density lipoproteins. The binding of Chol-HDO to these proteins was also confirmed in mouse plasma after injection. These results indicate that the binding of Chol-HDO to plasma proteins, especially lipoproteins, is critical for determining tissue distribution and brain delivery after intravenous injection.
Activated platelet membrane vesicles for broad-spectrum bacterial pulmonary infections management
Authors: Anqi Wei, Tianhao Ding, Guanghui Li, Feng Pan, Kaisong Tian, Ziwei Sun, Mengyuan Liu, Yinyu Ma, Zhiwei Guo, Yifei Yu, Changyou Zhan, Zui Zhang, Ye Zhu, Xiaoli Wei
Journal: Journal of Controlled Release (2025)
Ultrasound-triggered topical oxygen delivery enhances synergistic sonodynamic and antibody therapies against hypoxic gastric cancer
Authors: Xinxin Xie, Jinxia Zhang, Lihong Sun, Shuyu Xu, Shiti Sha Ma, Haonan Wang, Xiaoda Li, Qiong Xiang, Ligang Cui, Xiaolong Liang
Journal: Journal of Controlled Release (2025)
Pediatric Drug Reaction with Eosinophilia and Systemic Symptoms: Pharmacovigilance and Prognosis
Authors: Tung S Tran, Trieu M L Tran, Trang M Nguyen, Hilary B Kunkel, Khanh D Nguyen, Vinh T H Nguyen, Megha M Tollefson, David A Wetter, Giang H Nguyen
Journal: Journal of the American Academy of Dermatology (2025)
A-Eval: A benchmark for cross-dataset and cross-modality evaluation of abdominal multi-organ segmentation
Authors: Ziyan Huang, Zhongying Deng, Jin Ye, Haoyu Wang, Yanzhou Su, Tianbin Li, Hui Sun, Junlong Cheng, Jianpin Chen, Junjun He, Yun Gu, Shaoting Zhang, Lixu Gu, Yu Qiao
Journal: Medical Image Analysis (2025)
<i>Salmonella</i> utilizes L-arabinose to silence virulence gene expression for accelerated pathogen growth within the host
Authors: Jingchen Yu, Huang Tang, Yana Chen, Zuoqiang Wang, Wanqiu Huang, Tao Zhou, Bingjie Wen, Chengyue Wang, Shuang Gu, Jinjing Ni, Jing Tao, Danni Wang, Jie Lu, Qing Xie, Yu-Feng Yao
Journal: Gut Microbes (2025)

Carbon source is an important nutrient for bacteria to sustain growth and often acts as a signal that modulates virulence expression. L-arabinose is produced by plants and plays an important role in regulating the global gene expression of bacteria. Previously, we have shown that L-arabinose induces a more severe systemic infection in Salmonella-infected mice with normal microbiota, but does not affect the disease progression in mice with microbiota depleted by antibiotic treatment. The underlying mechanism remains elusive. In this study, we demonstrate that L-arabinose represses the expression of Salmonella type III secretion system 1 (T3SS–1) genes by negatively regulating the activity of the cyclic 3' 5'-AMP (cAMP)-cAMP receptor protein (CRP) complex. The cAMP-CRP complex can activate ribosome-associated inhibitor A, encoded by yfiA, to maintain the stability of HilD, a key transcriptional regulator of T3SS–1. L-arabinose supplementation promotes Salmonella initial bloom in the antibiotic-pretreated mouse gut and ultimately compensates for reduced virulence within the host. These results decipher the molecular mechanism by which cAMP-CRP directs regulatory changes of virulence in response to L-arabinose in Salmonella. It further implies that Salmonella exploits L-arabinose both as a nutrient and a regulatory signal to maintain a balance between growth and virulence within the host.
The proteomic landscape of diffuse midline glioma highlights the therapeutic potential of non-histone protein methyltransferases
Authors: Arun Kumaran Anguraj Vadivel, Sanja Pajovic, Robert Siddaway, Sabrina Zhu, Stefanie-Grace Sbergio, Olivera Matic, Lauren Phillips, Yong Jia Bu, Mark Nitz, Cynthia Hawkins
Journal: Neuro-Oncology (2025)

Abstract Background Diffuse Midline Glioma (DMG) is a highly aggressive pediatric brain tumor with limited treatment options despite extensive genomic characterization. The aim of this study was to investigate the proteomic landscape of DMG to identify potential therapeutic targets. Methods We conducted a comprehensive proteomic analysis using LC-MS3, along with DNA methylation and DNA/RNA sequencing in 55 DMG patients’ samples. PTM profiling (phosphoproteome and methylproteome) was conducted in 30 patient samples. We then investigated the effects of modulating key protein targets on protein methylation, protein synthesis, and DMG cell growth in vitro and in vivo. Results DMGs exhibited high global protein methylation, with significant enrichment of translation machinery proteins and factors involved in apoptosis regulation. Surprisingly, while targets of key kinases were highly phosphorylated, overall protein phosphorylation was lower in DMG compared to normal brain tissues. Non-histone methyltransferases METTL13 and METTL21B, along with protein kinases PAK2, PRKACA, and AKT1, were identified as key players in DMG methylproteome and phosphoproteome, respectively. METTL13 knockdown led to reduced EEF1A1 protein methylation, a shift in oncoprotein synthesis, and inhibited DMG cell growth in vitro and in vivo. Conclusions Our findings highlight the dependency of DMG on methyl-signaling pathways, particularly involving METTL13, which regulates EEF1A1 protein methylation and oncoprotein synthesis. Targeting the non-histone methyltransferases offers a promising therapeutic strategy for DMG. This study underscores the potential of post-translational modifications, specifically methyl-signaling pathways, as novel therapeutic targets for DMG and possibly other currently incurable cancers.
Phase 1 study of lintuzumab-Ac225 combined with CLAG-M salvage therapy in relapsed/refractory acute myeloid leukemia
Authors: Sameem M. Abedin, Guru Subramanian Guru Murthy, Mehdi Hamadani, Laura C. Michaelis, Karen-Sue Carlson, Lyndsey Runaas, Katelyn Gauger, Avinash G. Desai, Mary M. Chen, Kate L. Li, Mojisola Rotibi, Umar Syed, Madhuri Vusirikala, Alexandra Harrington, Ehab L. Atallah
Journal: Leukemia (2025)
Molecular subtypes of intrahepatic cholangiocarcinoma
Authors: Alessandro De Santis, Lei Zhu, Jianxin Tao, Christoph Reißfelder, Sebastian Schölch
Journal: Trends in Molecular Medicine (2025)

Intrahepatic cholangiocarcinoma (iCCA) presents in two clinically distinct subtypes: large duct (LD-iCCA) and small duct (SD-iCCA). These subtypes exhibit significant molecular, genetic, and histopathological differences that impact patient prognosis and treatment responsiveness. This review advocates for a subtype-specific approach to iCCA research and clinical management, including tailored therapeutic strategies that consider distinct genetic profiles and tumor microenvironments. Current therapeutic approaches hold promise, yet efficacy varies by subtype. Additionally, subtype-specific molecular diagnostics, including DNA methylation-based classifiers and transcriptomic sequencing, have shown potential in refining iCCA subclassification, thereby guiding precision medicine efforts. This article outlines existing clinical trials, key research trajectories, and future directions for developing more effective subtype-adapted therapies for iCCA.
“Monitor-and-treat” that integrates bacterio-therapeutics and bio-optics for infected wound management
Authors: Longbao Feng, Qing Peng, Li Miao, Chenghao Cai, Franklin R Tay, Shuqin Zhou, Ying Zhang, Zonghua Liu, Xingang Wang, Yang Jiao, Rui Guo
Journal: Bioactive Materials (2025)
The N terminus-only function of adhesion GPCRs: emerging concepts
Authors: Laura Lehmann, Victoria Elisabeth Groß, Rene Behlendorf, Simone Prömel
Journal: Trends in Pharmacological Sciences (2025)

Adhesion G-protein-coupled receptors (aGPCRs) play key roles in health and disease. They are unique in that they not only activate G-protein pathways but also have distinct functions that rely solely on their N termini, making them complex drug targets. To date there have been only descriptive observations about these enigmatic N terminus-only functions. Emerging evidence from several aGPCRs now indicates that these are a defining characteristic of these receptors that allows them to operate bidirectionally across environments. Recent advances in characterizing aGPCR splice variants and receptor structure have revealed the G protein-independent mechanisms that underlie their N terminus-only functions. This review consolidates current findings, explores how the N termini integrate functions, and identifies common principles across aGPCRs. We consider the therapeutic implications and discuss how specifically targeting N terminus functions provides a novel perspective on the pharmacological potential of aGPCRs.
How to get a better sample from the Scabies tunnel: Sampling under Wood's light.
Authors: Aslan Yürekli, Ayşenur Botsali, Gülşen Akoğlu, Ercan Çalişkan, Mustafa Tunca, İsmail Hakkı Ünal, Gözde Şimşek
Journal: Journal of the American Academy of Dermatology (2025)
Ceramides increase mitochondrial permeabilization to trigger mtDNA-dependent inflammation in astrocytes during brain ischemia
Authors: Feng-Qing Huang, Hong-Fei Wang, Tong Yang, Dai Yang, Peian Liu, Raphael N Alolga, Gaoxiang Ma, Baolin Liu, An Pan, Shi-Jia Liu, Lian-Wen Qi
Journal: Metabolism (2025)
Genetic characterization of Haemophilus ducreyi from non-genital skin lesions in Cameroon
Authors: Philippe Ndzomo, Ala-Eddine Deghmane, Serges Tchatchouang, Rosanne Ngome, Aude Terrade, Mélanie Denizon, Michaël Falguieres, Oumar Doucoure, Tania Crucitti, Onana Boyomo, Michael Marks, Sara Eyangoh, Muhamed-Kheir Taha
Journal: Journal of Infection (2025)

Haemophilus ducreyi, traditionally recognised as the etiological agent of chancroid, a genital ulcer disease, is increasingly being identified as a significant cause of cutaneous ulcers in yaws-endemic regions across the South Pacific, Southeast Asia, and Sub-Saharan Africa. Despite its clinical relevance, this pathogen remains poorly characterized, and comprehensive genetic tools for analysing isolate relationships are still lacking. In this study, we present a follow-up of our previous research and developed a multilocus sequence typing (MLST) approach based on six of the seven loci from the Haemophilus influenzae MLST scheme and applied it to 82 primary clinical samples, previously confirmed to contain H. ducreyi, without culture. We also performed whole-genome sequencing (WGS) and antibiotic susceptibility testing on four cultured isolates obtained from cutaneous ulcers in yaws endemic health districts of Cameroon. Antibiotic susceptibility testing of H. ducreyi cultured isolates revealed sensitivity to all tested antibiotics, including ceftriaxone, azithromycin, and ciprofloxacin. MLST analysis, using data extracted from WGS and directly from clinical samples, identified 38 complete profiles across the six loci (34 from direct samples and four from cultured isolates), identifying 14 distinct sequence types (STs). BURST analysis of the six MLST genes grouped the STs into two distinct clonal complexes. An additional, polymorphism was observed in the ftsI gene, which encodes the penicillin-binding protein 3. This study highlights the need for genetic typing of H. ducreyi strains circulating in the yaws-endemic regions of Cameroon. The developed MLST scheme offered effective strain discrimination and provided valuable insights into their genetic relationships in these areas.
3D-printed Multifunctional Bilayer Scaffold with Sustained Release of Apoptotic Extracellular Vesicles and Antibacterial Coacervates for Enhanced Wound Healing
Authors: Linli Jiang, Jia Dong, Minwen Jiang, Weiwei Tan, Yiwei Zeng, Xuanqi Liu, Pu Wang, Hejin Jiang, Jiajing Zhou, Xiaojing Liu, Hui Li, Lei Liu
Journal: Biomaterials (2025)
Re: Marie-Pier St-Laurent, Bernard Bochner, James Catto, et al. Increasing Life Expectancy in Patients with Genitourinary Malignancies: Impact of Treatment Burden on Disease Management and Quality of Life. Eur Urol. In press. https://doi.org/10.1016/j.eururo.2024.11.026
Authors: Chang-Kun Mao, None Chao-Yang, Jun-Ting Li
Journal: European Urology (2025)
Pilocytic Astrocytoma in a Child with Spinal Muscular Atrophy Treated with Onasemnogene Abeparvovec
Authors: Dorothea Holzwarth, Gabriele Calaminus, Johannes Friese, Thomas Sejersen, Hildegard Büning, Philipp John-Neek, Antonella Lucía Bastone, Michael Rothe, Keith Mansfield, Silvana Libertini, Valérie Dubost, Brent Kuzmiski, Iulian Alecu, Ivan Labik, Janbernd Kirschner
Journal: Molecular Therapy (2025)
Targeting BCL11B in CAR-engineered lymphoid progenitors drives NK-like cell development with prolonged anti-leukemic activity
Authors: Franziska Baatz, Arnab Ghosh, Jessica Herbst, Saskia Polten, Johann Meyer, Manuel Rhiel, Tobias Maetzig, Robert Geffers, Michael Rothe, Antonella Lucia Bastone, Philipp John-Neek, Jörg Frühauf, Britta Eiz-Vesper, Agnes Bonifacius, Christine S Falk, Constantin V Kaisenberg, Toni Cathomen, Axel Schambach, Marcel R M van den Brink, Michael Hust, Martin G Sauer
Journal: Molecular Therapy (2025)
Cascade Targeting Selenium Nanoparticles-Loaded Hydrogel Microspheres for Multifaceted Antioxidant Defense in Osteoarthritis
Authors: Jiacheng Liu, Junyan Liu, Senrui Liu, Pengcheng Xiao, Chengcheng Du, Jingdi Zhan, Zhuolin Chen, Lu Chen, Ke Li, Wei Huang, Yiting Lei
Journal: Biomaterials (2025)