检索结果-内蒙古大学图书馆

The exposome and pancreatic cancer, lifestyle and environmental risk factors for PDAC

Seminars in cancer Biology 2025年 113卷 100-129页

作者： Peduzzi, Giulia Archibugi, Livia Farinella, Riccardo de Leon Pisani, Ruggero Ponz Vodickova, Ludmila Vodicka, Pavel Kraja, Bledar Sainz, Juan Bars-Cortina, David Daniel, Neil Silvestri, Roberto Uysal-Onganer, Pinar Landi, Stefano Dulińska-Litewka, Joanna Comandatore, Annalisa Campa, Daniele Hughes, David J. Rizzato, Cosmeri Department of Biology University of Pisa Pisa Italy Pancreato-Biliary Endoscopy and Endosonography Division Pancreas Translational and Clinical Research Center IRCCS Ospedale San Raffaele Milan Italy Biomedical Center Martin Bioinformatic Center Comenius University in Bratislava Jessenius Faculty of Medicine in Martin Slovakia Faculty of Medicine and Biomedical Center in Pilsen Charles University Pilsen Czech Republic University Clinic of Gastrohepatology University Hospital Center Mother Teresa Tirana Albania Department of Biochemistry and Molecular Biology University of Granada Granada Spain Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP) Madrid 28029 Spain GENYO. Centre for Genomics and Oncological Research. Genomic Oncology department Granada Spain Instituto de Investigación Biosanitaria Ibs.Granada Granada Spain Institut Català d'Oncologia (ICO) IDIBELL Unit of Biomarkers and Susceptibility (UBS) Oncology Data Analytics Program (ODAP) Catalan Institute of Oncology (ICO) L′Hospitalet del Llobregat Barcelona Spain Institut Català d'Oncologia (ICO) IDIBELL ONCOBELL Program Bellvitge Biomedical Research Institute (IDIBELL) L′Hospitalet de Llobregat Barcelona Spain Molecular Epidemiology of Cancer Group UCD Conway Institute School of Biomolecular and Biomedical Science University College Dublin Dublin Ireland Cancer Mechanisms and Biomarkers Research Group School of Life Sciences University of Westminster London United Kingdom Chair of Medical Biochemistry Medical College Jagiellonian University Krakow Poland General Surgery Unit Department of Translational Research and New Technologies in Medicine and Surgery University of Pisa Italy

Pancreatic cancer (PC), particularly pancreatic ductal adenocarcinoma (PDAC), is a significant global health issue with high mortality rates. PDAC, though only 3 % of cancer diagnoses, causes 7 % of cancer deaths due to its severity and asymptomatic early stages. Risk factors include lifestyle choices, environmental exposures, and genetic predispositions. Conditions like new-onset type 2 diabetes and chronic pancreatitis also contribute significantly. Modifiable risk factors include smoking, alcohol consumption, non-alcoholic fatty pancreatic disease (NAFPD), and obesity. Smoking and heavy alcohol consumption increase PC risk, while NAFPD and obesity, particularly central adiposity, contribute through chronic inflammation and insulin resistance. Refined sugar and sugar-sweetened beverages (SSBs) are also linked to increased PC risk, especially among younger individuals. Hormonal treatments and medications like statins, aspirin, and metformin have mixed results on PC risk, with some showing protective effects. The gut microbiome influences PC through the gut-pancreas axis, with disruptions leading to inflammation and carcinogenesis. Exposure to toxic substances, including heavy metals and chemicals, is associated with increased PC risk. Glycome changes, such as abnormal glycosylation patterns, are significant in PDAC development and offer potential for early diagnosis. Interactions between environmental and genetic factors are crucial in PDAC susceptibility. Genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) linked to PDAC, but gene-environment interactions remain largely unexplored. Future research should focus on polygenic risk scores (PRS) and large-scale studies to better understand these interactions and their impact on PDAC risk. © 2025 The Authors

关键词： Exposome Pancreatic cancer Risk factors

来源：评论

学校读者我要写书评

暂无评论

AI-driven 3D Spatial Transcriptomics

arXiv

引用

arXiv 2025年

作者： Almagro-Pérez, Cristina Song, Andrew H. Weishaupt, Luca Kim, Ahrong Jaume, Guillaume Williamson, Drew F.K. Hemker, Konstantin Lu, Ming Y. Singh, Kritika Chen, Bowen Le, Long Phi Baras, Alexander S. Jiang, Sizun Bashashati, Ali Liu, Jonathan T.C. Mahmood, Faisal Department of Pathology Mass General Brigham Harvard Medical School BostonMA United States Cancer Program Broad Institute of Harvard and MIT CambridgeMA United States Data Science Program Dana-Farber Cancer Institute BostonMA United States Harvard-MIT Division of Health Sciences and Technology Massachusetts Institute of Technology CambridgeMA United States Department of Pathology Pusan National University Busan Korea Republic of Department of Pathology and Laboratory Medicine Emory University School of Medicine AtlantaGA United States Department of Computer Science & Technology University of Cambridge Cambridge United Kingdom Department of Electrical Engineering and Computer Science Massachusetts Institute of Technology CambridgeMA United States Rutgers Robert Wood Johnson Medical School New BrunswickNJ United States Department of Pathology Johns Hopkins Hospital BaltimoreMD United States Department of Biomedical Engineering Johns Hopkins Hospital BaltimoreMD United States Broad Institute of Harvard and MIT CambridgeMA United States Center for Virology and Vaccine Research Beth Israel Deaconess Medical Center Harvard Medical School BostonMA United States Department of Pathology Dana Farber Cancer Institute BostonMA United States Department of Pathology and Laboratory Medicine University of British Columbia VancouverBC Canada School of Biomedical Engineering University of British Columbia VancouverBC Canada Department of Mechanical Engineering Bioengineering Laboratory Medicine & Pathology University of Washington SeattleWA United States Harvard Data Science Initiative Harvard University CambridgeMA United States

A comprehensive three-dimensional (3D) map of tissue architecture and gene expression is crucial for illuminating the complexity and heterogeneity of tissues across diverse biomedical applications1. However, most spatial transcriptomics (ST) approaches remain limited to two-dimensional (2D) sections of tissue2–4. Although current 3D ST methods hold promise, they typically require extensive tissue sectioning, are complex, are not compatible with non-destructive 3D tissue imaging technologies, and often lack scalability5–8. Here, we present VOlumetrically Resolved Transcriptomics EXpression (VORTEX), an AI framework that leverages 3D tissue morphology and minimal 2D ST to predict volumetric 3D ST. By pretraining on diverse 3D morphology–transcriptomic pairs from heterogeneous tissue samples and then fine-tuning on minimal 2D ST data from a specific volume of interest, VORTEX learns both generic tissue-related and sample-specific morphological correlates of gene expression. This approach enables dense, high-throughput, and fast 3D ST, scaling seamlessly to large tissue volumes far beyond the reach of existing 3D ST techniques. By offering a cost-effective and minimally destructive route to obtaining volumetric molecular insights, we anticipate that VORTEX will accelerate biomarker discovery and our understanding of morphomolecular associations and cell states in complex tissues. Interactive 3D ST volumes can be viewed at https://***/. © 2025, CC BY-NC-ND.

关键词： Vortex flow

来源：评论

学校读者我要写书评

暂无评论

Tumor Immunophenotypic Correlates in Patients Aged 80 Years or Older With Non-Small Cell Lung cancer and Outcomes to First-Line Pembrolizumab in PD-L1 High (≥50%) Patients

引用

Clinical Lung cancer 2025年第4期26卷 288-298.e8页

作者： Barrichello, Adriana P.C. Elkrief, Arielle Ricciuti, Biagio Ganta, Teja Marron, Thomas U. Wang, Xinan Lotter, William Lindsay, James Santo, Valentina Cortellini, Alessio Sharma, Bijaya Felt, Kristen Pfaff, Kathleen Lamberti, Giuseppe Pecci, Federica Federico, Alessandro Di Makarem, Maisam Gandhi, Malini M. Nguyen, Tom Haradon, Danielle Vaz, Victor R. Johnson, Bruce E. Debnath, Neha Wang, Yinghong Kuang, Andrew G. Saeed, Anwaar Radford, Maluki Lovly, Christine M. Nebhan, Caroline A. Pinato, David J. Rodig, Scott J. Schoenfeld, Adam J. Awad, Mark M. Alessi, Joao V. Naqash, Abdul Rafeh Lowe Center for Thoracic Oncology Dana-Farber Cancer Institute Boston MA United States Thoracic Oncology Center Memorial Sloan Kettering Cancer Center New York NY United States Tisch Cancer Institute Icahn School of Medicine at Mount Sinai New York NY United States Department of Environmental Health Harvard T.H. Chan School of Public Health Harvard University Boston MA United States Department of Data Science Dana-Farber Cancer Institute Boston MA United States Department of Surgery and Cancer Imperial College London Faculty of Medicine Hammersmith Hospital London United Kingdom ImmunoProfile Brigham and Women's Hospital and Dana-Farber Cancer Institute Boston MA United States Center for Immuno-oncology Dana-Farber Cancer Institute Boston MA United States Department of Gastroenterology Hepatology & Nutrition University of Texas MD Anderson Cancer Center Houston TX United States Department of Internal Medicine Baylor College of Medicine Houston TX United States Division of Medical Oncology Department of Medicine Kansas University Medical Center Westwood KS United States Department of Medicine and Vanderbilt-Ingram Cancer Center Vanderbilt University Nashville TN United States Department of Pathology Brigham and Women's Hospital Boston MA United States Medical Oncology/TSET Phase 1 Program Stephenson Cancer Center University of Oklahoma Oklahoma City OK United States

Background: Non-small cell lung cancer (NSCLC) patients aged ≥80 years [y] are underrepresented in clinical trials. We evaluated whether age correlates with a distinct immunophenotype or impacts outcomes to first-line pembrolizumab in patients with advanced NSCLC, PD-L1 Tumor Proportion Score (TPS) of ≥50%, and aged ≥80y. Methods: Three NSCLC cohorts were retrospectively analyzed to assess the impact of age (<80y versus ≥80y) on pembrolizumab efficacy and the tumor microenvironment (TME). Cohort A encompassed patients receiving first-line pembrolizumab for advanced NSCLC with PD-L1 ≥50%. Cohort B comprised patients with tumor profiling using multiplexed immunofluorescence (ImmunoPROFILE). Cohort C included The cancer Genome Atlas (TCGA) and Stand Up to cancer (SU2C) databases for gene expression analysis. Results: In Cohort A (N = 669), patients ≥80y (N = 111) showed no significant differences in objective response rate or median progression-free survival compared to younger patients (N = 558), but had shorter median overall survival and were less likely to receive second-line therapy after progression on pembrolizumab. In Cohort B (N = 567), tumors from patients ≥80y (N = 45) exhibited higher intratumoral FOXP3+ T cells and closer vicinity of PD-1+ immune cells to tumor cells compared to <80y (N = 522). Cohort C revealed a distinct immunophenotype in samples from patients ≥ 80y, with elevated specific immune cell subsets and up-regulated immune checkpoint proteins. Conclusion: Patients ≥80y with PD-L1-high NSCLC displayed a distinct immunophenotype in the TME but achieved similar ORR and mPFS with first-line pembrolizumab compared to younger patients. OS was shorter in older patients, who were less likely to receive second-line therapy. © 2025 Elsevier Inc.

关键词： Immune cells Immunotherapy Older adults Thoracic tumors Tumor microenvironment

来源：评论

学校读者我要写书评

暂无评论

Expression of HLA-B35 Is Associated with an Increased Risk of CMV Viremia and Clinically Significant CMV Infection in Patients Receiving Ptcy-Based Hematopoietic Cell Transplantation

引用

Transplantation and Cellular Therapy 2025年第2期31卷 S519-S519页

作者： Little, Jessica S., MD Hebert, Kyle, MS Neuberg, Donna, ScD Nikiforow, Sarah, MD, PhD Gooptu, Mahasweta, MD Shapiro, Roman M., MD Koreth, John, MBBS, DPhil Antin, Joseph H., MD Cutler, Corey S., MD MPH Soiffer, Robert J., MD Ritz, Jerome, MD Romee, Rizwan, MD Ho, Dr. Vincent T., MD Issa, Nicolas, M.D. Baden, Lindsey, MD Dulery, Remy, MD, PhD Prockop, Susan E., MD Division of Stem Cell Transplantation and Cellular Therapy Dana-Farber Cancer Institute and Harvard Medical School Boston MA Division of Infectious Diseases Brigham and Women's Hospital Boston MA Department of Data Science Dana-Farber Cancer Institute Boston MA Department of Data Science Dana Farber Cancer Institute Boston MA Department of Medical Oncology Dana-Farber Cancer Institute Boston MA Department of Medical Oncology Dana-Farber Cancer Institute and Harvard Medical School Boston MA Dana-Farber Cancer Institute Boston MA Division of Stem Cell Transplant and Cellular Therapy Dana-Farber Cancer Institute and Harvard Medical School Boston MA Hematopoietic Stem Cell Transplant Program Dana Farber Cancer Institute Boston Children's Hospital and Harvard Medical School Boston MA

IntroductionHematopoietic cell transplant (HCT) with post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GvHD) prophylaxis carries a higher risk of cytomegalovirus (CMV) infections despite letermovir prophylaxis. T cell immune responses are crucial for controlling viral infections like CMV, but PTCy may reduce TCR repertoire diversity. A prior study (Hasan A, et al. Blood Adv 2022) showed impaired CMV control by CMVpp65 CTLs restricted by HLA-B35 alleles. We hypothesized that HLA-B35 expression could be a risk factor for CMV infections post-PTCy-based HCT with in-vivo T cell depletion. MethodsIn this single-center retrospective study, we included consecutive adults at risk for CMV reactivation (recipient and/or donor seropositive) undergoing HCT with PTCy from February 2015 to February 2022. CMV viremia and clinically significant CMV infection (CS-CMVi; CMV viremia/disease requiring CMV therapy) were assessed. Letermovir prophylaxis through D100 was used for CMV-seropositive recipients after 2017. Fine-Gray sub-distribution hazards models identified risk factors for CS-CMVi and CMV viremia, with disease relapse, repeat HCT, or death as competing risks. Cytokine release syndrome (CRS), neutrophil recovery, and acute/chronic GVHD were included as time-varying covariates. The Dana-Farber Harvard cancer Center (DF/HCC) Institutional Review Board approved the study. ResultsOf 211 patients included, 59% were male, with a median age of 60 years (19.4 – 78.3). Acute myeloid leukemia (39%) and myelodysplastic syndrome/myeloproliferative neoplasms (29%) were the most common diseases. Donor were haploidentical (55%), HLA-mismatched unrelated (26%), and HLA-matched unrelated (19%). The majority of recipients were CMV seropositive (78%) and 60% received letermovir prophylaxis. HLA-B35 was carried by 18% patients. Transplant-related complications included CRS (47%), acute GVHD (42%), and chronic GVHD (27%). The one-year cumulative incidence of CS-CMVi was 29.9%

关键词：

来源：评论

学校读者我要写书评

暂无评论

Targeting the intracellular immune checkpoint CISH with CRISPR-Cas9-edited T cells in patients with metastatic colorectal cancer: a first-in-human, single-centre, phase 1 trial

引用

The Lancet Oncology 2025年第5期26卷 559-570页

作者： Lou, Emil Choudhry, Modassir S Starr, Timothy K Folsom, Timothy D Bell, Jason Rathmann, Blaine DeFeo, Anthony P Kim, Jihyun Slipek, Nicholas Jin, Zhaohui Sumstad, Darin Klebanoff, Christopher A Ladner, Katherine Sarkari, Akshat McIvor, R Scott Murray, Thomas A Miller, Jeffrey S Rao, Madhuri Jensen, Eric Ankeny, Jacob Khalifa, Mahmoud A Chauhan, Anil Spilseth, Benjamin Dixit, Ajay Provenzano, Paolo P Pan, Wenjing Weber, Daniel Byrne-Steele, Miranda Henley, Tom McKenna, David H Johnson, Matthew J Webber, Beau R Moriarity, Branden S Department of Medicine Division of Hematology Oncology and Transplantation University of Minnesota Minneapolis MN United States Department of Obstetrics Gynecology and Women's Health University of Minnesota Minneapolis MN United States Department of Pediatrics University of Minnesota Minneapolis MN United States Masonic Cancer Center University of Minnesota Minneapolis MN United States Center for Genome Engineering University of Minnesota Minneapolis MN United States Department of Genetics Cell Biology and Development University of Minnesota Minneapolis MN United States Department of Biomedical Engineering University of Minnesota Minneapolis MN United States Center for Multiparametric Imaging of Tumor Immune Microenvironments University of Minnesota Minneapolis MN United States Stem Cell Institute University of Minnesota Minneapolis MN United States Intima Bioscience New York NY United States Deparment of Medical Oncology Mayo Clinic Rochester MN United States Cell Therapy Clinical Laboratory University of Minnesota Medical School Minneapolis MN United States Division of Biostatistics and Health Data Science University of Minnesota Medical School Minneapolis MN United States Department of Surgery University of Minnesota Medical School Minneapolis MN United States Department of Laboratory Medicine and Pathology University of Minnesota Medical School Minneapolis MN United States Department of Radiology University of Minnesota Medical School Minneapolis MN United States Department of Medicine Human Oncology and Pathogenesis Program and Parker Institute for Cancer Immunotherapy Memorial Sloan Kettering Cancer Center New York NY United States Department of Radiology University of Kansas Medical Center Kansas City KS United States Division of Gastroenterology Hepatology and Nutrition Cincinnati Children's Hospital Medical Center Cincinnati OH United States iRepertoire Huntsville AL United States

Background: Over the past decade, immunotherapeutic strategies—mainly targeting the PD-1–PD-L1 immune checkpoint axis—have altered cancer treatment for many solid tumours, but few patients with gastrointestinal forms of cancer have benefited to date. There remains an urgent need to extend immunotherapy efficacy to more patients while addressing resistance to current immune checkpoint inhibitors. The aim of this study was to determine the safety and anti-tumour activity of knockout of CISH, which encodes cytokine-inducible SH2-containing protein, a novel intracellular immune checkpoint target and a founding member of the SOCS family of E3-ligases, using tumour infiltrating lymphocyte (TILs) genetically edited with CRISPR-Cas9 in patients with metastatic gastrointestinal epithelial cancers. Methods: For this first-in-human, single-centre, phase 1 trial, patients aged 18–70 years with a diagnosis of metastatic gastrointestinal epithelial cancer with progressive disease following at least one first line standard therapy, measurable disease with at least one lesion identified as resectable for TIL generation and at least one other lesion meeting RECIST criteria as measurable to serve as an indicator of disease response, and an ECOG performance status of 0 or 1 were screened and enrolled if meeting these and all other eligibility criteria. TILs procured from tumour biopsies were expanded on the basis of neoantigen reactivity, subjected to CRISPR-Cas9-mediated CISH knockout, and infused intravenously into 12 patients after non-myeloablative lymphocyte depleting chemotherapy (cyclophosphamide 60 mg/kg per dose on study days –6 and –5, and fludarabine 25 mg/m² per dose on days –7 to –3) followed by high-dose IL-2 (aldesleukin;720 000 IU/kg per dose). The primary endpoint was safety of administration of neoantigen-reactive TILs with knockout of the CISH gene, and a key secondary endpoint was anti-tumour activity measured as objective radiographic response and progr

关键词：

来源：评论

学校读者我要写书评

暂无评论

Correction to: Multiplexed inhibition of immunosuppressive genes with Cas13d for combinatorial cancer immunotherapy (Nature Biotechnology, (2025), 10.1038/s41587-024-02535-2)

引用

Nature Biotechnology 2025年

作者： Zhang, Feifei Chow, Ryan D. He, Emily Dong, Chuanpeng Xin, Shan Mirza, Daniyal Feng, Yanzhi Tian, Xiaolong Verma, Nipun Majety, Medha Zhang, Yueqi Wang, Guangchuan Chen, Sidi Department of Genetics Yale University School of Medicine New HavenCT United States System Biology Institute Yale University West HavenCT United States Center for Cancer Systems Biology Yale University West HavenCT United States M.D.–Ph.D. Program Yale University West HavenCT United States Molecular Cell Biology Genetics and Development Program Yale University New HavenCT United States Yale College New HavenCT United States Immunobiology Program Yale University New HavenCT United States Department of Therapeutic Radiology Yale University School of Medicine New HavenCT United States Department of Neurosurgery Yale University School of Medicine New HavenCT United States Yale Comprehensive Cancer Center Yale University School of Medicine New HavenCT United States Yale Stem Cell Center Yale University School of Medicine New HavenCT United States Yale Center for Biomedical Data Science Yale University School of Medicine New HavenCT United States Key Laboratory of Multi-Cell Systems Shanghai Institute of Biochemistry and Cell Biology Center for Excellence in Molecular Cell Science Chinese Academy of Sciences Shanghai China

Correction to: Nature Biotechnologyhttps://***/10.1038/s41587-024-02535-2, published online 16 January 2025. In the version of the article initially published, Sidi Chen was incorrectly associated with a present address. This has now been corrected in the HTML and PDF versions of the article. © The Author(s), under exclusive licence to Springer Nature America, Inc. 2025.

关键词：

来源：评论

学校读者我要写书评

暂无评论

High-resolution dynamic imaging of chromatin DNA communication using Oligo-LiveFISH

引用

Cell 2025年

作者： Zhu, Yanyu Balaji, Ashwin Han, Mengting Andronov, Leonid Roy, Anish R. Wei, Zheng Chen, Crystal Miles, Leanne Cai, Sa Gu, Zhengxi Tse, Ariana Yu, Betty Chentzu Uenaka, Takeshi Lin, Xueqiu Spakowitz, Andrew J. Moerner, W.E. Qi, Lei S. Department of Bioengineering Stanford University Stanford 94305 CA United States Department of Chemistry Stanford University Stanford 94305 CA United States Biophysics PhD Program Stanford University Stanford 94305 CA United States Computational Biology Program Public Health Sciences Division and Translational Data Science IRC Fred Hutchinson Cancer Center Seattle 98109 WA United States Department of Chemical Engineering Stanford University Stanford 94305 CA United States Department of Materials Science and Engineering Stanford University Stanford 94305 CA United States Institute for Stem Cell Biology & Regenerative Medicine and Department of Pathology Stanford University School of Medicine Stanford 94305 CA United States Sarafan ChEM-H Stanford University Stanford 94305 CA United States Chan Zuckerberg Biohub San Francisco 94080 CA United States

Three-dimensional (3D) genome dynamics are crucial for cellular functions and disease. However, real-time, live-cell DNA visualization remains challenging, as existing methods are often confined to repetitive regions, suffer from low resolution, or require complex genome engineering. Here, we present Oligo-LiveFISH, a high-resolution, reagent-based platform for dynamically tracking non-repetitive genomic loci in diverse cell types, including primary cells. Oligo-LiveFISH utilizes fluorescent guide RNA (gRNA) oligo pools generated by computational design, in vitro transcription, and chemical labeling, delivered as ribonucleoproteins. Utilizing machine learning, we characterized the impact of gRNA design and chromatin features on imaging efficiency. Multi-color Oligo-LiveFISH achieved 20-nm spatial resolution and 50-ms temporal resolution in 3D, capturing real-time enhancer and promoter dynamics. Our measurements and dynamic modeling revealed two distinct modes of chromatin communication, and active transcription slows enhancer-promoter dynamics at endogenous genes like FOS. Oligo-LiveFISH offers a versatile platform for studying 3D genome dynamics and their links to cellular processes and disease. © 2025 Elsevier Inc.

关键词： CRISPR imaging DNA communication dynamic tracking enhancer-promoter interaction high-resolution imaging live DNA imaging non-repetitive genome imaging Oligo-LiveFISH polymer modeling primary cell

来源：评论

学校读者我要写书评

暂无评论

The dynamic immune behavior of primary and metastatic ovarian carcinoma

引用

npj Precision Oncology 2025年第1期9卷 1-12页

作者： Stur, Elaine Peng, Fuduan Teng, Pang-Ning Bayraktar, Emine Hu, Min Corvigno, Sara Brown, David J. Lee, Sanghoon Moore, Kathleen N. Bateman, Nicholas W. Darcy, Kathleen M. Maxwell, George L. P. Conrads, Thomas Sahni, Nidhi Vázquez-García, Ignacio Shah, Sohrab P. Celestino, Joseph D. Fleming, Nicole Navin, Nicholas E. Wang, Linghua Sood, Anil K. Department of Gynecologic Oncology and Reproductive Medicine The University of Texas MD Anderson Cancer Center Houston TX United States Department of Genomic Medicine The University of Texas MD Anderson Cancer Center Houston TX United States Gynecologic Cancer Center of Excellence The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc. Walter Reed National Military Medical Center Bethesda 20889 MD United States Department of Gynecologic Surgery and Obstetrics Uniformed Services University of the Health Sciences Walter Reed National Military Medical Center Bethesda MD United States Department of Genetics The University of Texas MD Anderson Cancer Center Houston TX United States Obstetrics and Gynecology Stephenson Cancer Center Stephenson Cancer Center at the University of Oklahoma Health Sciences Center/Sarah Cannon Research Institute Oklahoma City OK United States Women’s Health Integrated Research Center Women’s Service Line Inova Health System Falls Church VA United States Department of Epigenetics and Molecular Carcinogenesis The University of Texas MD Anderson Cancer Center Baylor College of Medicine Houston TX United States Department of Bioinformatics and Computational Biology The University of Texas MD Anderson Cancer Center Houston TX United States Quantitative and Computational Biosciences Program Baylor College of Medicine Houston TX United States Computational Oncology Department of Epidemiology and Biostatistics Memorial Sloan Kettering Cancer Center New York NY United States The Halvorsen Center for Computational Oncology Memorial Sloan Kettering Cancer Center Boston MA United States Irving Institute for Cancer Dynamics Columbia University Cambridge 10027 MA United States Department of Systems Biology The University of Texas MD Anderson Cancer Center Houston MA United States The James P. Allison Institute The University of Texas MD Anderson Cancer Center Houston 77030 TX United States The Institute for Data Sc

Patients with high-grade serous ovarian carcinoma (HGSC) are usually diagnosed with advanced-stage disease, and the tumors often have immunosuppressive characteristics. Together, these factors are important for disease progression, drug resistance, and mortality. In this study, we used a combination of single-cell sequencing and spatial transcriptomics to identify the molecular mechanisms that lead to immunosuppression in HGSC. Primary tumors consistently showed a more active immune microenvironment than did omental tumors. In addition, we found that untreated primary tumors were mostly populated by dysfunctional CD4 and CD8 T cells in later stages of differentiation;this, in turn, was correlated with expression changes in the interferon α and γ pathways in epithelial cells, showing that cross-communication between the epithelial and immune compartments is important for immune suppression in HGSC. These findings could have implications for the design of clinical trials with immune-modulating drugs. © The Author(s) 2025.

关键词：

来源：评论

学校读者我要写书评

暂无评论

A decomposition of Fisher’s information to inform sample size for developing fair and precise clinical prediction models - Part 2: time-to-event outcomes

arXiv

引用

arXiv 2025年

作者： Riley, Richard D. Collins, Gary S. Archer, Lucinda While, Rebecca Legha, Amardeep Kirton, Laura Dhiman, Paula Sadatsafavi, Mohsen Adderley, Nicola J. Alderman, Joseph MarGn, Glen P. Ensor, Joie Department of Applied Health Sciences School of Health Sciences College of Medicine and Health University of Birmingham Birmingham United Kingdom Birmingham Biomedical Research Centre Birmingham United Kingdom Centre for Sta?s?cs in Medicine Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal Sciences University of Oxford OxfordOX3 7LD United Kingdom Cancer Research UK Clinical Trials Unit Ins?tute of Cancer and Genomic Sciences College of Medical and Dental Sciences University of Birmingham Birmingham United Kingdom Respiratory Evalua?on Sciences Program Faculty of Pharmaceu?cal Sciences The University of Bri?sh Columbia Vancouver Canada Ins?tute of Inflamma?on and Ageing College of Medicine and Health University of Birmingham Birmingham United Kingdom Queen Elizabeth Hospital University Hospitals Birmingham NHS Founda?on Trust Birmingham United Kingdom Division of Informatics Imaging and Data Science Faculty of Biology Medicine and Health University of Manchester Manchester Academic Health Science Centre Manchester United Kingdom

Background When developing a clinical predicGon model using Gme-to-event data (i.e., with censoring and different lengths of follow-up), previous research focuses on the sample size needed to minimise overfifng and precisely esGmaGng the overall risk. However, instability of individual-level risk esGmates may sGll be large. Methods We propose using a decomposiGon of Fisher’s informaGon matrix to help examine and calculate the sample size required for developing a model that aims for precise and fair risk esGmates. We propose a six-step process which can be used before data collecGon or when an exisGng dataset is available. Steps (1) to (5) require researchers to specify the overall risk in the target populaGon at a key Gme-point of interest;an assumed pragmaGc ‘core model’ in the form of an exponenGal regression model;the (anGcipated) joint distribuGon of core predictors included in that model;and the distribuGon of any censoring. The ‘core model’ can be specified directly or based on a specified C-index and relaGve effects of (standardised) predictors. The joint distribuGon of predictors may be available directly in an exisGng dataset, in a pilot study, or in a syntheGc dataset provided by other researchers. Results We derive closed-form soluGons that decompose the variance of an individual’s esGmated event rate into Fisher’s unit informaGon matrix, predictor values and total sample size;this allows researchers to calculate and examine uncertainty distribuGons around individual risk esGmates and misclassificaGon probabiliGes for specified sample sizes. We provide an illustraGve example in breast cancer and emphasise the importance of clinical context, including any risk thresholds for decision making, and examine fairness concerns for pre- and post-menopausal women. Lastly, in two empirical evaluaGons, we provide reassurance that uncertainty interval widths based on our exponenGal approach are close to using more flexible parametric models. Conclusions Our approach

关键词： Fisher information matrix

来源：评论

学校读者我要写书评

暂无评论

Lsh, chromatin remodeling family member, modulates genome-wide cytosine methylation patterns at nonrepeat sequences (vol 108, pg 5626, 2011)

引用

PROCEEDINGS OF THE NATIONAL ACADEMY OF scienceS OF THE UNITED STATES OF AMERICA 2011年第37期108卷 15535-15535页

作者： Tao, Yongguang Xi, Sichuan Shan, Jigui Maunakea, Alika Che, Anney Briones, Victorino Lee, Eunice Y. Geiman, Theresa Huang, Jiaqiang Stephens, Robert Leighty, Robert M. Zhao, Keji Muegge, Kathrin [a]Basic Science Program Laboratory of Cancer Prevention [b]Advanced Biomedical Computing Center and [d]Data Management Services Science Applications International Corporation Frederick Inc. National Cancer Institute Frederick Frederick MD 21702 and [c]Laboratory of Molecular Immunology National Heart Lung and Blood Institute National Institutes of Health Bethesda MD 20817

DNA methylation is critical for normal development and plays important roles in genome organization and transcriptional regulation. Although DNA methyltransferases have been identified, the factors that establish and contribute to genome-wide methylation patterns remain elusive. Here, we report a high-resolution cytosine methylation map of the murine genome modulated by Lsh, a chromatin remodeling family member that has previously been shown to regulate CpG methylation at repetitive sequences. We provide evidence that Lsh also controls genome-wide cytosine methylation at nonrepeat sequences and relate those changes to alterations in H4K4me3 modification and gene expression. Deletion of Lsh alters the allocation of cytosine methylation in chromosomal regions of 50 kb to 2 Mb and, in addition, leads to changes in the methylation profile at the 5' end of genes. Furthermore, we demonstrate that loss of Lsh promotes--as well as prevents--cytosine methylation. Our data indicate that Lsh is an epigenetic modulator that is critical for normal distribution of cytosine methylation throughout the murine genome.

关键词： methylated DNA immunoprecipitation chIP-sequencing epigenetics

来源：评论

学校读者我要写书评

暂无评论

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案：

请选择收藏分类：

通借通还

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：