tbuckley/cabot-search huggingface dataset:
NAD<sup>+</sup>metabolism enzyme NNMT in cancer-associated fibroblasts drives tumor progression and resistance to immunotherapy by modulating macrophages in urothelial bladder cancer
Authors: Meihua Yang, Bo Wang, Weibin Hou, Honghui Zeng, Wang He, Xin-Ke Zhang, Dong Yan, Hao Yu, Long Huang, Lu Pei, Kaiwen Li, Haide Qin, Tianxin Lin, Jian Huang
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background This study comprehensively investigates the association between the expression of nicotinamide N-methyltransferase (NNMT) and clinical outcomes of urothelial bladder cancer (UBC), as well as the molecular mechanisms by which NNMT in cancer-associated fibroblast (CAF) modulates tumor progression and immunotherapy resistance in UBC. Methods Single-cell transcriptomic analyses, immunohistochemical and immunofluorescence assays were performed on bladder cancer samples to validate the relationship between NNMT expression and clinical outcomes. A series of experiments, including chromatin immunoprecipitation assay, liquid chromatography tandem mass spectrometry assay, and CRISPR‒Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated protein 9) knockout, together with in vivo models, have been established to determine the molecular functions of NNMT in CAFs in UBC. Results We demonstrated that elevated expression of the nicotinamide adenine dinucleotide (NAD + ) metabolism enzyme NNMT in CAFs (NNMT + CAFs) was significantly associated with non-response to programmed death-ligand 1 (PD-L1) blockade immunotherapy in patients with UBC and predicted the unfavorable prognosis of UBC in two independent large cohorts. Targeting NNMT using the inhibitor 5-Amino-1-methylquinolinium iodide significantly reduced tumor growth and enhanced the apoptotic effects of the anti-PD-L1 antibody in UBC mouse models. Mechanistically, NNMT + CAFs recruit tumor-associated macrophages via epigenetic reprogramming of serum amyloid A (SAA) to drive tumor cell proliferation and confer resistance to programmed death-1/PD-L1 blockade immunotherapy. Conclusions NNMT + CAFs were significantly associated with non-response to PD-L1 blockade immunotherapy in patients with UBC. Elevated NNMT, specifically in CAFs, upregulates SAA expression and enhances the recruitment and differentiation of macrophages in the tumor microenvironment, thereby directly or indirectly promoting tumor progression and conferring resistance to immunotherapies in bladder cancer.
VEXAS syndrome was in front of us for decades
Authors: Nicolas Giachetti, Valentin Lacombe
Journal: British Journal of Dermatology (2024)

Journal Article Corrected proof VEXAS syndrome was in front of us for decades Get access Nicolas Giachetti, Nicolas Giachetti Formal analysis, Investigation, Writing - original draft Department of Internal Medicine and Clinical Immunology, Angers University Hospital, Angers, FranceUniversité Angers, MitoLab, Unité MITOVASC, UMR CNRS 6015, INSERM U1083, SFR ICAT, Angers, France Search for other works by this author on: Oxford Academic Google Scholar Valentin Lacombe Valentin Lacombe Conceptualization, Methodology, Supervision, Writing - review & editing Department of Internal Medicine and Clinical Immunology, Angers University Hospital, Angers, FranceUniversité Angers, MitoLab, Unité MITOVASC, UMR CNRS 6015, INSERM U1083, SFR ICAT, Angers, France Correspondence: Valentin Lacombe. Email: lacombe.valentin31@gmail.com Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljae309, https://doi.org/10.1093/bjd/ljae309 Published: 27 July 2024 Article history Received: 25 June 2024 Revision received: 19 July 2024 Accepted: 23 July 2024 Published: 27 July 2024 Corrected and typeset: 27 August 2024
Phase II basket trial of Dual Anti-CTLA-4 and Anti-PD-1 blockade in Rare Tumors (DART) SWOG S1609: adrenocortical carcinoma cohort
Authors: Sandip P Patel, Megan Othus, Young Kwang Chae, Tridu Huynh, Benjamin Tan, Timothy Kuzel, Christine McLeod, Gabby Lopez, Helen X Chen, Elad Sharon, Howard Streicher, Christopher W Ryan, Charles Blanke, Razelle Kurzrock
Journal: Journal for ImmunoTherapy of Cancer (2024)

Objectives Multiple common cancers benefit from immunotherapy; however, less is known about efficacy in rare tumors. We report the results of the adrenocortical carcinoma cohort of NCI/SWOG S1609 Dual Anti-CTLA-4 and Anti-PD-1 blockade in Rare Tumors. Design/setting A prospective, phase 2 clinical trial of ipilimumab plus nivolumab was conducted by the SWOG Early Therapeutics and Rare Cancers Committee for multiple rare tumor cohorts across &gt;1,000 National Clinical Trial Network sites. Participants 21 eligible patients were registered. Median age was 53 years (range 26–69); 16 (76%) were women. Interventions Ipilimumab 1 mg/kg intravenously every 6 weeks with nivolumab 240 mg intravenously every 2 weeks was administered until disease progression, symptomatic deterioration, treatment delay for any reason &gt;56 days, unacceptable or immune-related toxicity with inability to decrease prednisone to &lt;10 mg daily, or per patient request. Main outcome measures The primary endpoint was the overall response rate (ORR) (RECIST V.1.1). Secondary endpoints include clinical benefit rate (CBR) (includes stable disease (SD)&gt;6 months), progression-free survival (PFS), overall survival (OS), and toxicity. Immune-related outcomes included immune ORR (iORR), immune CBR (iCBR), and immune PFS (iPFS). A two-stage design was used assuming: null=5% alternative=30%, n=6 in the first stage, 16 max, one-sided alpha=13%. Results The median number of prior therapy lines was 2 (range: 1–9). 3 of 21 patients attained confirmed partial response (PR) (ORR=14%). In addition, one patient had an unconfirmed PR; one, stable disease (SD)&gt;6 months; one, immune-related RECIST (iRECIST) PR (iPR); and one patient attained iSD&gt;6 months: clinical benefit rate (response or SD&gt;6 months)=5/21 (24%), iORR=4/21 (19%), iCBR=7/21 (33%). The 6-month PFS was 24%; 6-month iPFS, 33%. The PFS for patients (N=7) with iRECIST clinical benefit were 57, 52, 18, 15, 13, 7, and 7 months. The 6-month OS was 76%; the median OS, was 15.8 months. The most common toxicities were fatigue (62%) and rash (38%), and the most common grade 3/4 immune-related adverse events were hepatic dysfunction (9.5%) and adrenal insufficiency (9.5%). Treatment-related adverse events leading to discontinuation of therapy in four patients (21%). There were no grade 5 adverse events. Conclusions Ipilimumab plus nivolumab is active in refractory metastatic adrenocortical cancer meeting the primary endpoint of the study, with a 19% iORR and 33% iCBR (includes SD/iSD&gt;6 months) and with the longest PFS/iPFS of 52 and 57 months. Trial registration number NCT02834013 (registered 15 July, 2016; https://clinicaltrials.gov/ct2/show/NCT02834013 ).
Density of tertiary lymphoid structures predicts clinical outcome in breast cancer brain metastasis
Authors: Yuan-Yuan Zhao, Zhen Fan, Bao-Rui Tao, Zun-Guo Du, Zhi-Feng Shi
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Patients with breast cancer brain metastases (BCBM) experience a rapid decline in their quality of life. Recently, tertiary lymphoid structures (TLSs), analogs of secondary lymphoid organs, have attracted extensive attention. However, the potential clinical implications of TLSs in BCBMs are poorly understood. In this study, we evaluated the density and composition of TLSs in BCBMs and described their prognostic value. Methods Clinicopathological data were collected from 98 patients (2015–2021). TLSs were evaluated, and a TLS scoring system was constructed. Differences in progression-free survival (PFS) and overall survival (OS) between groups were calculated using the Kaplan-Meier method. Immunohistochemistry and multiplex immunofluorescence (mIF) were used to assess TLSs heterogeneity. Results TLSs were identified in 47 patients with BCBM. High TLSs density indicated favorable survival (OS, p=0.003; PFS, p&lt;0.001). TLS was positively associated with OS (p=0.0172) and PFS (p=0.0161) in the human epidermal growth factor receptor type 2-positive subtype, and with prolonged OS (p=0.0482) in the triple-negative breast cancer subtype. The mIF results showed significant differences in the percentages of T follicular helper (Tfh) cells, M2 macrophages, cytotoxic T lymphocytes, and CD8 + TIM-3 + T lymphocytes between the groups of TLS scores 0–3 (cytotoxic T lymphocytes, p=0.044; Tfh, p=0.021; M2 macrophages, p=0.033; CD8 + TIM-3 + T lymphocytes, p=0.018). Furthermore, novel nomograms incorporating the TLS scores and other clinicopathological predictors demonstrated prominent predictability of the 1-year, 3-year, and 5-year outcomes of BCBMs (area under the curve &gt;0.800). Conclusion Our results highlight the impact of TLSs abundance on the OS and PFS of patients with BCBM. Additionally, we described the immune composition of TLSs and proposed novel nomograms to predict the prognosis of patients with BCBM.
POSTN<sup>+</sup>cancer-associated fibroblasts determine the efficacy of immunotherapy in hepatocellular carcinoma
Authors: Hao Wang, Yuan Liang, Zheng Liu, Rui Zhang, Jiashuo Chao, Mingming Wang, Mu Liu, Lei Qiao, Zhengfeng Xuan, Haitao Zhao, Ling Lu
Journal: Journal for ImmunoTherapy of Cancer (2024)

Objective Hepatocellular carcinoma (HCC) poses a significant clinical challenge because the long-term benefits of immune checkpoint blockade therapy are limited. A comprehensive understanding of the mechanisms underlying immunotherapy resistance in HCC is imperative for improving patient prognosis. Design In this study, to systematically investigate the characteristics of cancer-associated fibroblast (CAF) subsets and the dynamic communication among the tumor microenvironment (TME) components regulated by CAF subsets, we generated an HCC atlas by compiling single-cell RNA sequencing (scRNA-seq) datasets on 220 samples from six datasets. We combined spatial transcriptomics with scRNA-seq and multiplexed immunofluorescence to identify the specific CAF subsets in the TME that determine the efficacy of immunotherapy in HCC patients. Results Our findings highlight the pivotal role of POSTN + CAFs as potent immune response barriers at specific tumor locations, as they hinder effective T-cell infiltration and decrease the efficacy of immunotherapy. Additionally, we elucidated the interplay between POSTN + CAFs and SPP1 + macrophages, whereby the former recruits the latter and triggers increased SPP1 expression via the IL-6/STAT3 signaling pathway. Moreover, we demonstrated a spatial correlation between POSTN + CAFs and SPP1 + macrophages, revealing an immunosuppressive microenvironment that limits the immunotherapy response. Notably, we found that patients with elevated expression levels of both POSTN + CAFs and SPP1 + macrophages achieved less therapeutic benefit in an immunotherapy cohort. Conclusion Our research elucidates light on the role of a particular subset of CAFs in immunotherapy resistance, emphasizing the potential benefits of targeting specific CAF subpopulations to improve clinical responses to immunotherapy.
Decoding the spatiotemporal heterogeneity of tumor-associated macrophages
Authors: Xiangyuan Chu, Yu Tian, Chao Lv
Journal: Molecular Cancer (2024)

Abstract Tumor-associated macrophages (TAMs) are pivotal in cancer progression, influencing tumor growth, angiogenesis, and immune evasion. This review explores the spatial and temporal heterogeneity of TAMs within the tumor microenvironment (TME), highlighting their diverse subtypes, origins, and functions. Advanced technologies such as single-cell sequencing and spatial multi-omics have elucidated the intricate interactions between TAMs and other TME components, revealing the mechanisms behind their recruitment, polarization, and distribution. Key findings demonstrate that TAMs support tumor vascularization, promote epithelial-mesenchymal transition (EMT), and modulate extracellular matrix (ECM) remodeling, etc., thereby enhancing tumor invasiveness and metastasis. Understanding these complex dynamics offers new therapeutic targets for disrupting TAM-mediated pathways and overcoming drug resistance. This review underscores the potential of targeting TAMs to develop innovative cancer therapies, emphasizing the need for further research into their spatial characteristics and functional roles within the TME.
Author Correction: DNA methylation remodeling and the functional implication during male gametogenesis in rice
Authors: Xue Li, Bo Zhu, Yue Lu, Feng Zhao, Qian Liu, Jiahao Wang, Miaomiao Ye, Siyuan Chen, Junwei Nie, Lizhong Xiong, Yu Zhao, Changyin Wu, Dao-Xiu Zhou
Journal: Genome biology (2024)
Bedaquiline: what might the future hold?
Authors: Emily S Shaw, Neil G Stoker, Jessica L Potter, Helgard Claassen, Alasdair Leslie, Conor D Tweed, Chen-Yuan Chiang, Francesca Conradie, Hanif Esmail, Christoph Lange, Lancelot Pinto, Oxana Rucsineanu, Derek J Sloan, Grant Theron, Phumeza Tisile, Teck Chuan Voo, Robin M Warren, Limakatso Lebina, Marc Lipman
Journal: The Lancet Microbe (2024)

Tuberculosis drug development has stagnated for decades, so the recent availability of bedaquiline is welcome. Bedaquiline-containing regimens, now the first-line therapy recommended by WHO, have transformed the treatment of drug-resistant tuberculosis, offering safer and more effective oral treatment options. However, key obstacles need to be overcome to ensure global access and prevent the rapid development of resistance against this promising class of drugs. In this Personal View, building on an international workshop held in 2023, we evaluate the current evidence and suggest possible ways forward, recognising the tension between increasing use and slowing the rise of resistance. We also discuss problems in accessing bedaquiline-containing regimens, the potential widening of their use beyond drug-resistant tuberculosis, and lessons for utilising new drugs as they are developed.
Answering the call: co-designing a global trials network for cerebral palsy
Authors: Iona Novak, Michael Fahey, Bernard Dan, Simon Craig, Alexandra Griffin, Paul Gross, Mikkel Damgaard Justiniano, Annabel Webb, Maria Mc Namara, Jens Bo Nielsen, Thomas Snelling, Anina Ritterband-Rosenbaum, M. Wade Shrader, Lars Adde, Catherine Arnaud, Marina Brandao, Sylvain Brochard, Annemieke Buizer, Simon Craig, Bernard Dan, Michael Fahey, Charlie Fairhurst, Darcy Fehlings, Kathleen Friel, Paul Gross, Andrea Guzzetta, Ann-Christin Eliasson, Christina Høi-Hansen, Reidun Birgitta Jahnsen, Mette Johansen, Angelina Kakooza Mwesige, Marjolijn Ketelaar, Karin Lind, Egmar Longo, Bente Maimann, Maria Mc Namara, Ronit Mesterman, Jenna Mitchell, Elegast Monbaliu, Catherine Morgan, Christopher J. Newman, Jens Bo Nielsen, Iona Novak, Els Ortibus, Gija Rackauskaite, Anina Ritterband-Rosenbaum, Solveig Sigurdardottir, Tom Snelling, M. Wade Shrader
Journal: The Lancet Regional Health - Europe (2024)
γ-Secretase activity, clinical features, and biomarkers of autosomal dominant Alzheimer's disease: cross-sectional and longitudinal analysis of the Dominantly Inherited Alzheimer Network observational study (DIAN-OBS)
Authors: Stephanie A Schultz, Lei Liu, Aaron P Schultz, Colleen D Fitzpatrick, Raina Levin, Jean-Pierre Bellier, Zahra Shirzadi, Nelly Joseph-Mathurin, Charles D Chen, Tammie L S Benzinger, Gregory S Day, Martin R Farlow, Brian A Gordon, Jason J Hassenstab, Clifford R Jack, Mathias Jucker, Celeste M Karch, Jae-Hong Lee, Johannes Levin, Richard J Perrin, Peter R Schofield, Chengjie Xiong, Keith A Johnson, Eric McDade, Randall J Bateman, Reisa A Sperling, Dennis J Selkoe, Jasmeer P Chhatwal
Journal: The Lancet Neurology (2024)
Oxygen-Defect Bismuth Oxychloride Nanosheets for Ultrasonic Cavitation Effect Enhanced Sonodynamic and Second Near-Infrared Photo-induced Therapy of Breast Cancer
Authors: Chengyuan Hong, Zhusheng Liu, Quanliang Mao, Jianjun Zheng, Yanzi Sun, Yagui Lv, Pengyu Wang, Manxiang Wu, Jie Lin, Changyong Gao, Xuehua Ma, Yuning Pan, Jingfeng Zhang, Tianxiang Chen, Xiaogang Yang, Aiguo Wu
Journal: Biomaterials (2024)
An anti-senescence hydrogel with pH-responsive drug release for mitigating intervertebral disc degeneration and low back pain
Authors: Wantao Wang, Lei Liu, Wenzheng Ma, Lei Zhao, Lin Huang, Dan Zhou, Jinghao Fan, Jianru Wang, Hongmei Liu, Decheng Wu, Zhaomin Zheng
Journal: Bioactive Materials (2024)
Prospective evaluation of blood pressure, heart rate, and side effects in hypertensive patients using low-dose oral minoxidil for hair loss
Authors: Paulo Müller Ramos, Daniel Fernandes Melo, Bevin Bhoyrul, Baltazar Dias Sanabria, Juan Jimenez-Cauhe, David Saceda-Corralo, Prateek Sharma, Monica Ramos, Hélio Amante Miot, Sergio Vaño-Galvan
Journal: Journal of the American Academy of Dermatology (2024)
Physicochemical and structural insights into lyophilized mRNA-LNP from lyoprotectant and buffer screenings
Authors: Yuchen Fan, Diamanda Rigas, Lee Joon Kim, Feng-Peng Chang, Nanzhi Zang, Kristina McKee, Christopher C Kemball, Zhixin Yu, Pascal Winkler, Wan-Chih Su, Pierce Jessen, Greg L Hura, Tao Chen, Stefan G Koenig, Karthik Nagapudi, Dennis Leung, Chun-Wan Yen
Journal: Journal of Controlled Release (2024)
Molecular Developments in Parasellar Tumors and Potential Therapeutic Implications
Authors: Paraskevi Xekouki, Vasiliki Venetsanaki, Georgios Kyriakopoulos, Krystallenia Alexandraki, Anna Angelousi, Gregory Kaltsas
Journal: Endocrine Reviews (2024)

Abstract The parasellar region is the anatomical area around the sella turcica that represents a crucial crossroad for important adjacent structures. Several distinct tumors can primarily originate from this area, the most common being meningiomas, gliomas, embryonal cell tumors, germ cell tumors, and craniopharyngiomas. In addition, a number of systemic and inflammatory disorders can also affect the parasellar region, most commonly involving the pituitary. These lesions have different pathologic characteristics and malignant potential according to the new World Health Organization CNS5 2021 classification. Signs and symptoms may be nonspecific and are mostly related to a mass effect on the surrounding anatomical structures and/or impairment of endocrine function, whereas the vast majority lack a secretory component. The mutational signature analysis based on advances in molecular techniques has recently enabled the identification of specific gene mutations or signaling pathway aberrations. These developments may serve as a powerful means to delineate the pathophysiology of these lesions and serve as a diagnostic, prognostic, and therapeutic tool, particularly for high-risk populations. Treatment options include surgery alone or in combination with radiotherapy, chemotherapy, and disease-specific medical therapy, in order to prevent recurrence or further tumor growth along with replacement of coexistent pituitary hormonal deficiencies. In this comprehensive review, we present the current state-of-the-art developments in the histopathology and molecular biology of parasellar lesions, which often represent a diagnostic and therapeutic challenge, that may be utilized by a dedicated multidisciplinary team for the diagnosis, monitoring, and treatment of these lesions.
Nitroxide radical conjugated ovalbumin theranostic nanosystem for enhanced dendritic cell-based immunotherapy and T1-magnetic resonance imaging
Authors: Yike Hou, Fei Kong, Zhe Tang, Rui Zhang, Dan Li, Jian Ge, Zhangsen Yu, Abdul Wahab, Yunyang Zhang, M Zubair Iqbal, Xiangdong Kong
Journal: Journal of Controlled Release (2024)
Interleukin 23 versus interleukin 12/23 inhibitors on preventing incidental psoriatic arthritis in patients with psoriasis? A real-world comparison from the TriNetX Global Collaborative Network
Authors: Sung Huang Laurent Tsai, Chi-Ya Yang, An-Ping Huo, James Cheng-Chung Wei
Journal: Journal of the American Academy of Dermatology (2024)
Are Blood Tests for Alzheimer Disease Ready for Prime Time?
Authors: Stephen Salloway, Christopher Rowe, Jeffrey M. Burns
Journal: JAMA (2024)

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AUF1-mediated inhibition of autophagic lysosomal degradation contributes to CagA stability and <i>Helicobacter pylori</i> -induced inflammation
Authors: Huiling Zheng, Ting Zhang, Jing Zhang, Jing Ning, Weiwei Fu, Ye Wang, Yanyan Shi, Guochao Wei, Jing Zhang, Xiangmei Chen, Shigang Ding
Journal: Gut Microbes (2024)

CagA, a virulence factor of Helicobacter pylori (H. pylori), is known to drive inflammation in gastric epithelial cells and is typically degraded through autophagy. However, the molecular mechanism by which CagA evades autophagy-mediated degradation remains elusive. This study found that H. pylori inhibits autophagic flux by upregulating the expression of AU-rich element RNA-binding factor 1 (AUF1). We confirmed that AUF1 does not affect autophagy initiation but instead hampers lysosomal clearance, as evidenced by treatments with 3-MA, CQ and BafA1. Upregulated AUF1 stabilizes CagA protein levels by inhibiting the autolysosomal degradation of intracellular CagA in H. pylori-infected gastric epithelial cells. Knocking down AUF1 promotes CagA degradation, an effect that can be reversed by the lysosome inhibitor BafA1 and CQ. Transcriptome analysis of AUF1-knockdown gastric epithelial cells infected with H. pylori indicated that AUF1 regulates the expression of lysosomal-associated hydrolase genes, specifically CTSD, to inhibit autolysosomal degradation. Moreover, we observed that knockdown of AUF1 enhanced the stability of CTSD mRNA and identified AUF1 binding to the 3'UTR region of CTSD mRNA. AUF1-mediated downregulation of CTSD expression contributes to CagA stability, and AUF1 overexpression leads to an increase in CagA levels in exosomes, thus promoting extracellular inflammation. In clinical gastric mucosa, the expression of AUF1 and its cytoplasmic translocation are associated with H. pylori-associated gastritis, with CagA being necessary for the translocation of AUF1 into the cytoplasm. Our findings suggest that AUF1 is a novel host-positive regulator of CagA, and dysregulation of AUF1 expression increases the risk of H. pylori-associated gastritis.