tbuckley/cabot-search huggingface dataset:
Three-year analysis of adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia treated with brexucabtagene autoleucel in ZUMA-3
Authors: Bijal D. Shah, Ryan D. Cassaday, Jae H. Park, Roch Houot, Aaron C. Logan, Nicolas Boissel, Thibaut Leguay, Michael R. Bishop, Max S. Topp, Kristen M. O’Dwyer, Dimitrios Tzachanis, Martha L. Arellano, Yi Lin, Maria R. Baer, Gary J. Schiller, Marion Subklewe, Mehrdad Abedi, Monique C. Minnema, William G. Wierda, Daniel J. DeAngelo, Patrick Stiff, Deepa Jeyakumar, Daqin Mao, Sabina Adhikary, Lang Zhou, Tsveta Hadjivassileva, Rita Damico Khalid, Armin Ghobadi, Olalekan O. Oluwole
Journal: Leukemia (2025)

Brexucabtagene autoleucel (brexu-cel) is an autologous anti-CD19 CAR T-cell therapy approved in the US to treat adults aged ≥18 years (≥26 years in the EU) with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). Brexu-cel showed an overall complete remission (CR)/CR with incomplete hematologic recovery (CRi) rate of 73% (CR rate 60%) and median overall survival (OS) of 25.4 months in 78 patients with R/R B-ALL after 2 years in ZUMA-3. Here, we report updated outcomes after >3 years median follow-up. As of July 23, 2022, median follow-up in all patients (N = 78) was 41.6 months. Median OS (95% CI) was 25.6 months (1.2-47.0; N = 78) and was 38.9 months (25.4–not estimable) for responders (n = 58), with 9 patients in ongoing remission without subsequent therapies. Five deaths (none deemed brexu-cel–related) occurred since prior data cut. Benefits from brexu-cel were maintained regardless of age, prior therapies, and subsequent allogeneic stem cell transplantation (alloSCT). Subsequent alloSCT was not associated with survival benefit among responders versus responders without subsequent alloSCT. No secondary T-cell malignancies were reported in ZUMA-3 with long-term follow-up.
[18F]SiTATE Uptake in a Pancreatic Metastasis From a Renal Cell Carcinoma on a Long Axial Field of View PET/CT
Authors: Moritz Mattke, Leander Schwaibold, Patrick Krumm, Stephan Singer, Nils F. Trautwein
Journal: Clinical Nuclear Medicine (2025)

Here we present a 61-year-old woman with a history of renal cell carcinoma after nephrectomy and complete response to immunotherapy. Follow-up MRI revealed a contrast-enhanced lesion in the pancreatic tail, suspicious for a pancreatic neuroendocrine tumor. Subsequently, a SSTR-PET/CT with [ 18 F]SiTATE was conducted on a Biograph Vision Quadra. The pancreatic lesion showed intensive tracer uptake. Thus, a pancreatic tail resection was performed. Histopathologic results revealed no synaptophysin expression, but positivity for PAX8 and carboanhydrase 9. The final diagnosis was a solitary metastasis of the known renal cell carcinoma with SSTR2 expression in the intratumoral vascular network, explaining the [ 18 F]SiTATE uptake.
FDG PET/CT Images Demonstrating Subclinical Pancreatitis in a Patient on a GLP-1 Receptor Agonist
Authors: Robert Lenkov, Tyler Berman, Inderjit Mehmi, Pareen Mehta
Journal: Clinical Nuclear Medicine (2025)

An 83-year-old man with basal cell carcinoma was referred for an 18 F-FDG PET/CT scan for staging. The FDG PET/CT scan revealed diffuse increased radiotracer uptake within the pancreas without CT abnormality, which raised concern for pancreatitis. Although this man was clinically asymptomatic, a lipase level obtained after the PET/CT scan was elevated, confirming the diagnosis. This man was noted to be on tirzepatide, which is a GLP-1 receptor agonist medication used for type 2 diabetes and weight loss. No other causes of pancreatitis were identified in this man, and therefore, the cause was attributed to this medication.
Extracellular vesicles in cancer´s communication: messages we can read and how to answer
Authors: Alena Semeradtova, Michaela Liegertova, Regina Herma, Magdalena Capkova, Chiara Brignole, Genny Del Zotto
Journal: Molecular Cancer (2025)

Abstract Extracellular vesicles (EVs) are emerging as critical mediators of intercellular communication in the tumor microenvironment (TME), profoundly influencing cancer progression. These nano-sized vesicles, released by both tumor and stromal cells, carry a diverse cargo of proteins, nucleic acids, and lipids, reflecting the dynamic cellular landscape and mediating intricate interactions between cells. This review provides a comprehensive overview of the biogenesis, composition, and functional roles of EVs in cancer, highlighting their significance in both basic research and clinical applications. We discuss how cancer cells manipulate EV biogenesis pathways to produce vesicles enriched with pro-tumorigenic molecules, explore the specific contributions of EVs to key hallmarks of cancer, such as angiogenesis, metastasis, and immune evasion, emphasizing their role in shaping TME and driving therapeutic resistance. Concurrently, we submit recent knowledge on how the cargo of EVs can serve as a valuable source of biomarkers for minimally invasive liquid biopsies, and its therapeutic potential, particularly as targeted drug delivery vehicles and immunomodulatory agents, showcasing their promise for enhancing the efficacy and safety of cancer treatments. By deciphering the intricate messages carried by EVs, we can gain a deeper understanding of cancer biology and develop more effective strategies for early detection, targeted therapy, and immunotherapy, paving the way for a new era of personalized and precise cancer medicine with the potential to significantly improve patient outcomes.
Comparison of 68Ga-FAPI-04 PET/CT and 18F-FDG PET/CT in Evaluating Lesion Stages in Constrictive Pericarditis
Authors: Yaqun Jiang, Zhenxiong Chen, Yong He
Journal: Clinical Nuclear Medicine (2025)

Constrictive pericarditis, an uncommon cause of diastolic heart failure, is reversible if identified and treated promptly and appropriately. The treatment approach may vary significantly depending on the disease stage of constrictive pericarditis. Here, we report a case of 18 F-FDG and 68 Ga-FAPI-04 PET/CT imaging in a 70-year-old woman with chronic constrictive pericarditis. The thickened pericardium showed mild uptake of 18 F-FDG but intense uptake of 68 Ga-FAPI-04, indicating that the lesion was at the fibrotic phase. This case suggests a promising role of combination of 18 F-FDG and 68 Ga-FAPI PET/CT in accurately and timely assessing the lesion stage in constrictive pericarditis.
Wearable data reveals distinct characteristics of individuals with persistent symptoms after a SARS-CoV-2 infection
Authors: Katharina Ledebur, Marc Wiedermann, Christian Puta, Stefan Thurner, Peter Klimek, Dirk Brockmann
Journal: npj Digital Medicine (2025)

Abstract Understanding the factors associated with persistent symptoms after SARS-CoV-2 infection is critical to improving long-term health outcomes. Using a wearable-derived behavioral and physiological dataset ( n = 20,815), we identified individuals characterized by self-reported persistent fatigue and shortness of breath after SARS-CoV-2 infection. Compared with symptom-free COVID-19 positive (n = 150) and negative controls ( n = 150), these individuals ( n = 50) had higher resting heart rates (mean difference 2.37/1.49 bpm) and lower daily step counts (mean 3030/2909 steps fewer), even at least three weeks prior to SARS-CoV-2 infection. In addition, persistent fatigue and shortness of breath were associated with a significant reduction in mean quality of life (WHO-5, EQ-5D), even before infection. Here we show that persistent symptoms after SARS-CoV-2 infection may be associated with pre-existing lower fitness levels or health conditions. These findings additionally highlight the potential of wearable devices to track health dynamics and provide valuable insights into long-term outcomes of infectious diseases.
Renal Safety Assessment of Lipid-Lowering Drugs: Between Old Certainties and New Questions
Authors: Daniele Tramontano, Simone Bini, Carlo Maiorca, Alessia Di Costanzo, Martina Carosi, Jacopo Castellese, Ina Arizaj, Daniela Commodari, Stella Covino, Giorgia Sansone, Ilenia Minicocci, Marcello Arca, Laura D’Erasmo
Journal: Drugs (2025)

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD). Quantitative and qualitative changes in plasma lipoprotein profiles are frequently associated with CKD and represent a significant risk factor for CVD in patients with CKD. Guidelines from the European Society of Cardiology and the European Atherosclerosis Society classify CKD as a condition with high or very high cardiovascular risk and set specific low-density lipoprotein cholesterol targets. Conventional lipid-lowering therapies (LLTs), such as statins, ezetimibe, and fibrates, can control CKD-associated dyslipidemia and, to some extent, prevent major atherosclerotic events in patients with CKD, but their use in clinical practice presents challenges because of the potential renal safety concerns. In recent years, novel therapies with the ability to lower both low-density lipoprotein cholesterol and triglycerides have been introduced to the market (e.g., proprotein convertase subtilisin/kexin type 9 inhibitors, bempedoic acid, lomitapide, volanesorsen) to improve our ability to control lipid abnormalities. However, their impact on kidney functionality has not been fully elucidated. The aim of this review was to examine the renal safety profiles of various LLTs, with special reference to novel medications, and to highlight important considerations and guidance for the use of these medications in overt CKD or in patients with some degree of renal function impairment. We underscore the lack of a comprehensive understanding of kidney safety, particularly for novel LLT therapies, and strongly emphasize the importance of future dedicated research to fully assess the safety and efficacy of these agents in patients with kidney abnormalities.
Autophagy in tumor immune escape and immunotherapy
Authors: Huan Wang, Peng Sun, Xijing Yuan, Zhiyong Xu, Xinyuan Jiang, Mingshu Xiao, Xin Yao, Yueli Shi
Journal: Molecular Cancer (2025)

The immunotherapy targeting tumor immune escape mechanisms has become a critical strategy in anticancer treatment; however, the challenge of immune resistance remains significant. Autophagy, a cellular response to various stressors, involves the degradation of damaged proteins and organelles via lysosomal pathways, maintaining cellular homeostasis. This process not only supports tumor cell survival but also profoundly impacts the efficacy of cancer immunotherapies. The modulation of autophagy in tumor cells or immune cells exerts dual effects on tumor immune escape and immunotherapy. However, the mechanistic details of how autophagy influences the immune system and therapy remain inadequately understood. Given this complexity, a deeper understanding of the role of autophagy in the tumor-immune landscape could reveal novel therapeutic avenues. By manipulating autophagy appropriately, it may be possible to overcome immune resistance and enhance the effectiveness of immunotherapeutic strategies. This article summarizes the role of autophagy in tumor immunity, its relationship with immunotherapy, and the potential therapeutic benefits of targeting autophagy to strengthen antitumor immune responses and optimize the outcomes of immunotherapy.
<i>In vitro</i> competition with <i>Bifidobacterium</i> strains impairs potentially pathogenic growth of <i>Clostridium perfringens</i> on 2′-fucosyllactose
Authors: Aruto Nakajima, Aleksandr A. Arzamasov, Mikiyasu Sakanaka, Ryuta Murakami, Tomoya Kozakai, Keisuke Yoshida, Toshihiko Katoh, Miriam N. Ojima, Junko Hirose, Saeko Nagao, Jin-Zhong Xiao, Toshitaka Odamaki, Dmitry A. Rodionov, Takane Katayama
Journal: Gut Microbes (2025)

Fortifying infant formula with human milk oligosaccharides, such as 2'-fucosyllactose (2'-FL), is a global trend. Previous studies have shown the inability of pathogenic gut microbes to utilize 2'-FL. However, the present study demonstrates that the type strain (JCM 1290T) of Clostridium perfringens, a pathobiont species often more prevalent and abundant in the feces of C-section-delivered infants, exhibits potentially pathogenic growth on 2'-FL. The expression of genes for α-toxin, an activator of NLRP3 inflammasome, and ethanolamine ammonia-lyase, a factor responsible for the progression of gas gangrene, was significantly upregulated during 2'-FL assimilation compared to growth on lactose. However, colony-forming unit of C. perfringens JCM 1290T markedly decreased when co-cultivated with selected strains of Bifidobacterium, a taxon frequently detected in the breastfed infant gut. Moreover, during co-cultivation, the expression of virulence-related genes, including the gene for perfringolysin O – another activator of NLRP3 inflammasome – were significantly downregulated, while the lactate oxidation genes were upregulated. This can occur through two different mechanisms: direct competition for 2'-FL between the two organisms, or cross-feeding of lactose, released from 2'-FL by C. perfringens JCM 1290T, to Bifidobacterium. Attenuation of α-toxin production by the selected Bifidobacterium strains was observed to varying extents in 2'-FL-utilizing C. perfringens strains clinically isolated from healthy infants. Our results warrant detailed in vivo studies using animal models with dysbiotic microbiota dominated by various types of C. perfringens strains to further validate the safety of 2'-FL for clinical interventions, particularly on vulnerable preterm infants.
Cyclin E1 overexpression triggers interferon signaling and is associated with antitumor immunity in breast cancer
Authors: Shibo Yu, Chantal Stappenbelt, Mengting Chen, Mirte Dekker, Arkajyoti Bhattacharya, Tineke van der Sluis, Mieke C Zwager, Carolien P Schröder, Rudolf S N Fehrmann, Marcel A T M van Vugt, Bert van der Vegt
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Cyclin E1 overexpression drives oncogenesis in several cancers through deregulation of DNA replication and induction of genomic instability, which may potentially trigger immune signaling via cytoplasmic DNA. However, the effects of cyclin E1 overexpression on tumor immunity and its effects on the response to immune checkpoint inhibitors remain largely unclear. Methods Tissue microarrays and clinical outcomes of 398 patients with breast cancer were analyzed to explore the correlation between cyclin E1 expression, patient survival, and immune cell infiltration using immunohistochemistry. Genomic data from publicly available data sets and three clinical trials evaluating immunotherapy were assessed to measure the impact of cyclin E1 expression on the immune cells in the tumor microenvironment and response to immunotherapy in patients with breast cancer. In addition, breast cancer cell lines with inducible cyclin E1 overexpression were employed to analyze the effects of cyclin E1 on inflammatory signaling. Results Increased cyclin E1 expression in breast cancer was positively correlated with immune cell infiltration, including T cells, B cells, and natural killer cells, and activation of interferon-related pathways. Importantly, higher cyclin E1 expression or CCNE1 amplification was associated with better response to immunotherapy in three clinical trials. Mechanistically, cyclin E1 overexpression resulted in micronuclei formation and activation of innate immune signaling, resulting in increased immune cell migration. Conclusions Our data show that cyclin E1 overexpression associate with antitumor immunity through activation of innate inflammatory signaling and warrants investigation into amplification or overexpression of cyclin E1 in identifying patients with breast cancer eligible for immunotherapy.
Subsequent Survival and Loss of Lifetime for Patients With Progression‐Free 24 Months After Treatment in Nasopharyngeal Carcinoma: A Comprehensive Nationwide Population‐Based Analysis
Authors: Yang Liu, Yaqian Han, Mei Feng, Ye Zhang, Kai Wang, Yuan Qu, Xuesong Chen, Jianghu Zhang, Jingwei Luo, Runye Wu, Ye‐Xiong Li, Xiaodong Huang, Qiuyan Chen, Jingbo Wang, Junlin Yi
Journal: MedComm (2025)

ABSTRACT Currently, there is little evidence supporting the use of early endpoints to assess primary treatment outcomes in nasopharyngeal carcinoma (NPC). We aim to explore the relationship between 24‐month progression‐free survival (PFS24) and subsequent overall survival (sOS) as well as loss of lifetime (LoL) in NPC patients. sOS is defined as survival from the 24‐month point or progression within 24 months leading to mortality. LoL represents the reduction in life expectancy due to NPC, compared to the general population matched by age, sex, and calendar year. The standardized mortality ratio (SMR) is defined as the ratio of observed mortality to expected mortality. The study included 6315 patients from nonendemic and endemic regions of China. Among them, 5301 patients (83.9%) achieved PFS24, with a 5‐year sOS of 90.2% and an SMR of 1.0. Over a 10‐year period following treatment, the mean LoL was only 0.01 months/year. For most subgroups, patients achieving PFS24 exhibited comparable sOS and LoL with the general population. However, patients failing to achieve PFS24 showed significantly worse outcomes, with 5‐year sOS of 21.9%, SMR of 23.7, and LoL of 6.48 months/year. These notable outcome disparities highlight the importance of PFS24 in NPC risk stratification, patient monitoring, and study design.
Functionalized Cerium Oxide Nanoparticles Enhance Penetration into Melanoma Spheroids In Vivo through Angiogenesis
Authors: Lu Fu, Joel M. Yong, Robyn Yeh, Florence Bartlett, John M. Whitelock, Megan S. Lord
Journal: Advanced Healthcare Materials (2025)

Abstract Angiogenesis is a crucial step in tumor progression, including melanoma, making anti‐angiogenic strategies a widely explored treatment approach. However, both innate and acquired resistance to these therapies suggest that this approach may need re‐evaluation. Nanoparticles have gained attention for their potential to enhance drug delivery and retention within tumors via the bloodstream. However, the in vitro screening of nanoparticles is limited by the inability of preclinical models to replicate the complex tumor microenvironment, especially the blood supply. Here, it is demonstrated that melanoma cells embedded in Matrigel spheroids can engraft in and be vascularized by the chorioallantoic membrane (CAM) of fertilized chicken eggs. This model allows for the assessment of nanoparticle toxicity and accumulation in tumor spheroids, as well as functional effects such as angiogenesis. Cerium oxide nanoparticles (nanoceria) and their surface functionalized derivatives are widely explored for biomedical applications due to their ability to modulate oxidative stress and angiogenesis. Here, it is observed that heparin functionalized nanoceria penetrate melanoma spheroids in the CAM and promote spheroid vascularization to a greater extent than nanoceria alone. This study aids in the development of preclinical cancer models for nanoparticle screening and provides new insight into the interplay between nanoparticle surface coatings and biological effects.
GLP-2 prevents antipsychotics-induced metabolic dysfunction in mice
Authors: Yanmin Peng, Chenzhang Feng, Shiyu Peng, Ying Wang, Qian Zhang, Zhuolei Jiao, Huateng Cao, Shajin Huang, Peihuang Tian, Xiujia Sun, Xiaohong Xu, Yu Fu, Ji Hu, Zhe Zhang
Journal: Nature Metabolism (2025)
Intrinsically Pro‐Apoptotic Gold Nanoclusters for Optical Tracing and Inhibition of Solid Tumors
Authors: Priyanka Sharma, Hao Yuan, Ruchi Verma, Nisha Mehla, Hemant Hemant, Poonam Sagar, Clothilde Comby‐Zerbino, Isabelle Russier‐Antoine, Christophe Moulin, Pierre‐François Brevet, Nitin Singhal, Prakash P. Neelakandan, Sonalika Vaidya, Changkui Fu, Md. Ehesan Ali, Rohit Srivastava, Andrew Whittaker, Rodolphe Antoine, Asifkhan Shanavas
Journal: Advanced Healthcare Materials (2025)

Abstract Intrinsically theranostic metal nanoclusters are rare unless the stabilizing ligands exhibit therapeutic properties. A promising class of quasi‐molecular, near‐infrared (NIR) emitting, cytotoxic gold nanoclusters, coined as AXE (Au eXcitable and Eliminable) stabilized through terminal thioester groups on fluorinated, and crosslinked polymers, is presented for simultaneous bioimaging &amp; therapy. Nano Variable Temperature‐Electrospray ionization mass spectrometry analysis of these aqueous stable nanoclusters revealed 5 to 7 core gold atoms, with SAXS measurement confirming average size to be under 1 nm, consistent with the theoretical maximum for few atom planar gold clusters. Despite its small size, AXE exhibits a remarkable Stoke shift of ≈470 nm and emission range spanning 700 to 1100 nm. Fluorination notably enhanced the quantum yield by up to twofold, attributed to charge transfer from the fluorinated monomer to the gold core, as indicated by Löwdin charge distribution analysis. The AXE nanocluster demonstrated dose‐dependent pro‐apoptotic effects on cancer cells while sparing normal cells at lower concentrations. Preclinical evaluation in a breast tumor model confirmed its anticancer efficacy, with intravenous and intraperitoneal administrations significantly inhibiting tumor growth and controlling lung metastasis, surpassing the clinical standard, doxorubicin.
Next-Generation Immunohistochemistry in Thyroid Neoplasm: A Practical Review on the Applications in Diagnosis and Molecular Classification
Authors: Jonathan P. Rivera, Jen-Fan Hang
Journal: Endocrine Pathology (2025)

Abstract An integrative histologic and molecular classification of thyroid tumors has become clinically relevant due to the potential role in risk stratification and selection of targeted therapy. In this review, we discuss the applications of six “next-generation” immunohistochemical markers, namely BRAF V600E (clone VE1), RAS Q61R (clone SP174), pan-TRK (clone EPR 17341), ALK (clones 5A4 or D5F3), PTEN, and β-catenin in the pathologic diagnosis and molecular classification of thyroid tumors. These biomarkers allow the in situ examination of tumor tissue and assist in the diagnosis and pathologic staging by highlighting tumor border and patterns of invasion, identifying isolated tumor cells in lymph nodes, distinguishing lymph node metastasis from benign intranodal thyroid inclusions, and diagnosing multicentric thyroid carcinomas with discordant molecular drivers. Furthermore, it can identify specific thyroid neoplasms that may occur sporadically or may be associated with hereditary syndromes. The next-generation immunohistochemistry provides a novel solution to challenging issues in thyroid pathology and fast turn-around time for accurate molecular classification and further guidance of therapeutic management.