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A flexible liposomal polymer complex as a platform of specific and regulable immune regulation for individual cancer immunotherapy

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Journal of Experimental and Clinical Cancer Research 2023年第1期42卷 29-29页

作者： Chen, Chia-Hung Weng, Tzu-Han Huang, Hsiao-Hsuan Huang, Ling-Ya Huang, Kai-Yao Chen, Pin-Rong Yeh, Kuang-Yu Huang, Chi-Ting Chien, Yu-Tzu Chuang, Po-Ya Lin, Yu-Ling Tsai, Nu-Man Liu, Shih-Jen Su, Yu-Cheng Weng, Shun-Long Liao, Kuang-Wen Department of Medical Research Hsinchu MacKay Memorial Hospital Hsinchu City 30071 Taiwan Department of Dermatology MacKay Memorial Hospital Taipei City 10449 Taiwan Industrial Development Graduate Program of College of Biological Science and Technology National Yang Ming Chiao Tung University Hsinchu City 30068 Taiwan Institute of Bioinformatics and Systems Biology National Yang Ming Chiao Tung University Hsinchu City 30068 Taiwan Department of Medicine MacKay Medical College New Taipei City 25245 Taiwan Institute of Molecular Medicine and Bioengineering National Yang Ming Chiao Tung University Hsinchu City 30068 Taiwan Department of Biological Science and Technology National Yang Ming Chiao Tung University Hsinchu City 30068 Taiwan Agricultural Biotechnology Research Center Academia Sinica Taipei 11529 Taiwan Department of Medical Laboratory and Biotechnology Chung Shan Medical University Taichung City 40201 Taiwan Department of Pathology and Clinical Laboratory Chung Shan Medical University Hospital Taichung City 40201 Taiwan National Institute of Infectious Diseases and Vaccinology National Health Research Institutes Miaoli 350401 Taiwan Department of Obstetrics and Gynecology Hsinchu MacKay Memorial Hospital Hsinchu City 30071 Taiwan MacKay Junior College of Medicine Nursing and Management Taipei City 11260 Taiwan Graduate Institute of Medicine College of Medicine Kaohsiung Medical University Kaohsiung City 80708 Taiwan College of Dental Medicine Kaohsiung Medical University School of Dentistry Kaohsiung City 80708 Taiwan Department of Biotechnology and Bioindustry Sciences National Cheng Kung University Tainan City 70101 Taiwan Center for Intelligent Drug Systems and Smart Bio-Devices National Yang Ming Chiao Tung University Hsinchu City 30068 Taiwan

Background: The applicability and therapeutic efficacy of specific personalized immunotherapy for cancer patients is limited by the genetic diversity of the host or the tumor. Side-effects such as immune-related adverse events (IRAEs) derived from the administration of immunotherapy have also been observed. Therefore, regulatory immunotherapy is required for cancer patients and should be developed. Methods: The cationic lipo-PEG-PEI complex (LPPC) can stably and irreplaceably adsorb various proteins on its surface without covalent linkage, and the bound proteins maintain their original functions. In this study, LPPC was developed as an immunoregulatory platform for personalized immunotherapy for tumors to address the barriers related to the heterogenetic characteristics of MHC molecules or tumor associated antigens (TAAs) in the patient population. Here, the immune-suppressive and highly metastatic melanoma, B16F10 cells were used to examine the effects of this platform. Adsorption of anti-CD3 antibodies, HLA-A2/peptide, or dendritic cells’ membrane proteins (MP) could flexibly provide pan-T-cell responses, specific Th1 responses, or specific Th1 and Th2 responses, depending on the host needs. Furthermore, with regulatory antibodies, the immuno-LPPC complex properly mediated immune responses by adsorbing positive or negative antibodies, such as anti-CD28 or anti-CTLA4 antibodies. Results: The results clearly showed that treatment with LPPC/MP/CD28 complexes activated specific Th1 and Th2 responses, including cytokine release, CTL and prevented T-cell apoptosis. Moreover, LPPC/MP/CD28 complexes could eliminate metastatic B16F10 melanoma cells in the lung more efficiently than LPPC/MP. Interestingly, the melanoma resistance of mice treated with LPPC/MP/CD28 complexes would be reversed to susceptible after administration with LPPC/MP/CTLA4 complexes. NGS data revealed that LPPC/MP/CD28 complexes could enhance the gene expression of cytokine and chemokine pathways to st

关键词： Costimulatory molecules Immunotherapy LPPC personalized cancer therapy Tumor heterogenicity

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Publisher Correction: MEMOTE for standardized genome-scale metabolic model testing

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Nature biotechnology 2020年第4期38卷 504页

作者： Christian Lieven Moritz E Beber Brett G Olivier Frank T Bergmann Meric Ataman Parizad Babaei Jennifer A Bartell Lars M Blank Siddharth Chauhan Kevin Correia Christian Diener Andreas Dräger Birgitta E Ebert Janaka N Edirisinghe José P Faria Adam M Feist Georgios Fengos Ronan M T Fleming Beatriz García-Jiménez Vassily Hatzimanikatis Wout van Helvoirt Christopher S Henry Henning Hermjakob Markus J Herrgård Ali Kaafarani Hyun Uk Kim Zachary King Steffen Klamt Edda Klipp Jasper J Koehorst Matthias König Meiyappan Lakshmanan Dong-Yup Lee Sang Yup Lee Sunjae Lee Nathan E Lewis Filipe Liu Hongwu Ma Daniel Machado Radhakrishnan Mahadevan Paulo Maia Adil Mardinoglu Gregory L Medlock Jonathan M Monk Jens Nielsen Lars Keld Nielsen Juan Nogales Intawat Nookaew Bernhard O Palsson Jason A Papin Kiran R Patil Mark Poolman Nathan D Price Osbaldo Resendis-Antonio Anne Richelle Isabel Rocha Benjamín J Sánchez Peter J Schaap Rahuman S Malik Sheriff Saeed Shoaie Nikolaus Sonnenschein Bas Teusink Paulo Vilaça Jon Olav Vik Judith A H Wodke Joana C Xavier Qianqian Yuan Maksim Zakhartsev Cheng Zhang Novo Nordisk Foundation Center for Biosustainability Technical University of Denmark Lyngby Denmark. Systems Biology Lab Amsterdam Institute of Molecular and Life Sciences (AIMMS) Vrije Universiteit Amsterdam Amsterdam the Netherlands. BioQUANT/COS Heidelberg University Heidelberg Germany. Ecole Polytechnique Fédérale de Lausanne Laboratory of Computational Systems Biotechnology Lausanne Switzerland. iAMB-Institute of Applied Microbiology ABBt-Aachen Biology and Biotechnology RWTH Aachen University Aachen Germany. Department of Bioengineering University of California La Jolla CA USA. Department of Chemical Engineering and Applied Chemistry University of Toronto Toronto Ontario Canada. Human Systems Biology Laboratory Instituto Nacional de Medicina Genomica & Coordinación de la Investigación Científica-Red de Apoyo a la Investigación UNAM Mexico City Mexico. Institute for Systems Biology Seattle WA USA. Computational Systems Biology of Infection and Antimicrobial-Resistant Pathogens Institute for Biomedical Informatics (IBMI) Tübingen Germany. Department of Computer Science University of Tübingen Tübingen Germany. German Center for Infection Research (DZIF) partner site Tübingen Tübingen Germany. Australian Institute for Bioengineering and Nanotechnology The University of Queensland Brisbane Queensland Australia. Argonne National Laboratory Lemont IL USA. Analytical Biosciences Division of Systems Biomedicine and Pharmacology Leiden Academic Centre for Drug Research Leiden University Leiden the Netherlands. Department of Systems Biology Centro Nacional de Biotecnología Consejo Superior de Investigaciones Científicas (CNB-CSIC) Madrid Spain. Centro de Biotecnología y Genómica de Plantas (CBGP UPM-INIA) Universidad Politécnica de Madrid (UPM) - Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA) Madrid Spain. Department of Animal and Aquacultural Sciences Faculty of Biosciences Norwegian University of Life Sciences Oslo Norway

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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Genome wide conditional mouse knockout resources

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Drug Discovery Today: Disease Models 2016年 20卷 3-12页

作者： Kaloff, C. Anastassiadis, K. Ayadi, A. Baldock, R. Beig, J. Birling, M.-C. Bradley, A. Brown, S.D.M. Bürger, A. Bushell, W. Chiani, F. Collins, F.S. Doe, B. Eppig, J.T. Finnell, R.H. Fletcher, C. Flicek, P. Fray, M. Friedel, R.H. Gambadoro, A. Gates, H. Hansen, J. Herault, Y. Hicks, G.G. Hörlein, A. Hrabé de Angelis, M. Iyer, V. de Jong, P.J. Koscielny, G. Kühn, R. Liu, P. Lloyd, K.C.K. Lopez, R.G. Marschall, S. Martínez, S. McKerlie, C. Meehan, T. von Melchner, H. Moore, M. Murray, S.A. Nagy, A. Nutter, L.M.J. Pavlovic, G. Pombero, A. Prosser, H. Ramirez-Solis, R. Ringwald, M. Rosen, B. Rosenthal, N. Rossant, J. Ruiz Noppinger, P. Ryder, E. Skarnes, W.C. Schick, J. Schnütgen, F. Schofield, P. Seisenberger, C. Selloum, M. Smedley, D. Simpson, E.M. Stewart, A.F. Teboul, L. Tocchini Valentini, G.P. Valenzuela, D. West, A.P. Wurst, W. Institute of Developmental Genetics Helmholtz Zentrum Muenchen Neuherberg D-85764 Germany Biotechnology Center (BIOTEC) of the Technische Universität Dresden Dresden 01307 Germany CELPHEDIA PHENOMIN Institut Clinique de la Souris (ICS) CNRS INSERM University of Strasbourg 1 rue Laurent Fries Illkirch-Graffenstaden F-67404 France MRC Human Genetics Unit Institute of Genetics and Molecular Medicine University of Edinburgh College of Medicine and Veterinary Medicine Edinburgh EH4 2XU Scotland United Kingdom The Wellcome Trust Sanger Institute Wellcome Trust Genome Campus Hinxton Cambridge CB101HH United Kingdom Mammalian Genetics Unit and Mary Lyon Centre MRC Harwell Harwell Science and Innovation Campus Oxfordshire OX110RD United Kingdom Monterotondo Mouse Clinic Italian National Research Council (CNR) Institute of Cell Biology and Neurobiology Monterotondo-Scalo Rome I-00015 Italy National Human Genome Research Institute National Institutes of Health Bethesda 20892 MD United States The Jackson Laboratory Bar Harbor 04609 ME United States Dell Pediatric Research Institute The University of Texas at Austin Austin 78712 TX United States University of Texas at Austin Austin 78712 TX United States National Institutes of Health Bethesda 20205 MD United States European Bioinformatics Institute (EBI) Hinxton Cambridge CB101ST United Kingdom Fishberg Department of Neuroscience Friedman Brain Institute Icahn School of Medicine at Mount Sinai New York 10029 New York United States Institut de Génétique et de Biologie Moléculaire et Cellulaire Université de Strasbourg 1 rue Laurent Fries Illkirch 67404 France Centre National de la Recherche Scientifique UMR7104 Illkirch France Institut National de la Santé et de la Recherche Médicale U964 Illkirch France Université de Strasbourg 1 rue Laurent Fries Illkirch 67404 France University of Manitoba Manitoba Institute of Cell Biology Winnipeg R3EOV9 MB Canada Institute of Epidemiology II Helmh

The International Knockout Mouse Consortium (IKMC) developed high throughput gene trapping and gene targeting pipelines that produced mostly conditional mutations of more than 18,500 genes in C57BL/6N mouse embryonic stem (ES) cells which have been archived and are freely available to the research community as a frozen resource. From this unprecedented resource more than 6000 mutant mouse strains have been generated by the IKMC in collaboration with the International Mouse Phenotyping Consortium (IMPC). In addition, a cre-driver resource was established including 250 C57BL/6 cre-inducible mouse strains. Complementing the cre-driver resource, a collection comprising 27 rAAVs expressing cre in a tissue-specific manner has also been produced. All resources are easily accessible from the IKMC/IMPC web portal (***). The IKMC/IMPC resource is a standardized reference library of mouse models with defined genetic backgrounds enabling the analysis of gene-disease associations in mice of different genetic makeup and should therefore have a major impact on biomedical research. © 2017 Elsevier Ltd

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11th German Conference on Chemoinformatics (GCC 2015) Abstracts

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JOURNAL OF CHEMINFORMATICS 2016年第SUPPL 1期8卷 1-27页

作者： [Anonymous] GDCh-CIC Division Associated Board Member Beilstein-Institut zur Förderung der Chemischen Wissenschaften Trakehner Str. 7-9 60487 Frankfurt Germany. ufechner@beilstein-institut.de. Division Medicinal Chemistry Amsterdam Institute for Molecules Medicines and Systems (AIMMS) VU University Amsterdam The Netherlands. Centre for Bioinformatics Uni Hamburg Bundesstr. 43 20146 Hamburg Germany. Sanofi-Aventis Deutschland GmbH 65926 Frankfurt am Main Germany. stefan.guessregen@***. Sanofi-Aventis Deutschland GmbH 65926 Frankfurt am Main Germany. GlaxoSmithKline Stevenage SG1 2NY UK. nicola.j.richmond@***. Discngine Paris 75011 France. Organisch-Chemisches Institut Westfälische Wilhelms-Universität Münster Germany. marwin.segler@wwu.de. Organisch-Chemisches Institut Westfälische Wilhelms-Universität Münster Germany. Bundeskriminalamt Wiesbaden Central Analytics II 65173 Wiesbaden Germany. Department of Chemistry and Biochemistry University of California Santa Barbara CA 93111 USA. shea@chem.ucsb.edu. Department of Chemistry and Biochemistry University of California Santa Barbara CA 93111 USA. Chemistry Department Ludwig-Maximilians-Universität München Butenandtstr. 7 81377 Munich Germany. Inorganic Chemistry and Center for Nanointegration University of Duisburg-Essen Essen Germany. CAM-D Technologies Essen Germany. Institute for Bioinformatics and Chemoinformatics Westphalian University of Applied Sciences Recklinghausen Germany. Institute for Bioinformatics and Chemoinformatics Westphalian University of Applied Sciences Recklinghausen Germany. achim.zielesny@w-hs.de. Leiden University Leiden Netherlands. j.fraaije@chem.leidenuniv.nl. Culgi BV Berlin Germany. Physikalische Chemie III TU Dortmund 44227 Dortmund Germany. stefan.kast@tu-dortmund.de. Centre for Molecular Informatics Department of Chemistry University of Cambridge Lensfield Road Cambridge CB2 1EW United Kingdom. kcb27@cam.ac.uk. Centre for Molecular Informatics Department of Chemistry

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Kidney multiome-based genetic scorecard reveals convergent coding and regulatory variants

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Science (New York, N.Y.) 2025年第6734期387卷 eadp4753页

作者： Liu, Hongbo Abedini, Amin Ha, Eunji Ma, Ziyuan Sheng, Xin Dumoulin, Bernhard Qiu, Chengxiang Aranyi, Tamas Li, Shen Dittrich, Nicole Chen, Hua-Chang Tao, Ran Tarng, Der-Cherng Hsieh, Feng-Jen Chen, Shih-Ann Yang, Shun-Fa Lee, Mei-Yueh Kwok, Pui-Yan Wu, Jer-Yuarn Chen, Chien-Hsiun Khan, Atlas Limdi, Nita A. Wei, Wei-Qi Walunas, Theresa L. Karlson, Elizabeth W. Kenny, Eimear E. Luo, Yuan Kottyan, Leah Connolly, John J. Jarvik, Gail P. Weng, Chunhua Shang, Ning Cole, Joanne B. Mercader, Josep M. Mandla, Ravi Majarian, Timothy D. Florez, Jose C. Haas, Mary E. Lotta, Luca A. Drivas, Theodore G. Vy, Ha My T Nadkarni, Girish N. Wiley, Laura K. Wilson, Melissa P. Gignoux, Christopher R. Rasheed, Humaira Thomas, Laurent F. Åsvold, Bjørn Olav Brumpton, Ben M. Hallan, Stein I. Hveem, Kristian Zheng, Jie Hellwege, Jacklyn N. Zawistowski, Matthew Zöllner, Sebastian Franceschini, Nora Hu, Hailong Zhou, Jianfu Kiryluk, Krzysztof Ritchie, Marylyn D. Palmer, Matthew Edwards, Todd L. Voight, Benjamin F. Hung, Adriana M. Susztak, Katalin Department of Medicine Renal Electrolyte and Hypertension Division University of Pennsylvania Philadelphia PA United States Institute of Diabetes Obesity and Metabolism University of Pennsylvania Philadelphia PA United States Department of Genetics University of Pennsylvania Philadelphia PA United States Penn-CHOP Kidney Innovation Center University of Pennsylvania Philadelphia PA United States Liangzhu Laboratory Zhejiang University 1369 West Wenyi Road Hangzhou Zhejiang China Department of Nephrology Children' Hospital Zhejiang University School of Medicine National Clinical Research Center for Child Health Hangzhou Zhejiang China Institute of Molecular Life Sciences HUN-REN Research Center for Natural Sciences Budapest Hungary Department of Molecular Biology Semmelweis University Budapest Hungary Department of Medicine Federal University of São Paulo São Paulo Brazil Department of Biostatistics Vanderbilt University Medical Center Nashville TN United States Vanderbilt Genetics Institute Vanderbilt University Medical Center Nashville TN United States Institute of Clinical Medicine School of Medicine National Yang Ming Chiao Tung University ROC Taipei Taiwan Division of Nephrology Department of Medicine Taipei Veterans General Hospital ROC Taipei Taiwan Institute of Biomedical Sciences Academia Sinica ROC Taipei Taiwan Cardiovascular Center Taichung Veterans General Hospital Taichung Taiwan ROC National Chung Hsing University Taichung Taiwan ROC Heart Rhythm Center Division of Cardiology Department of Medicine Taipei Veterans General Hospital ROC Taipei Taiwan Department of Internal Medicine College of Medicine National Yang Ming Chiao Tung University ROC Taipei Taiwan Institute of Medicine Chung Shan Medical University Taichung Taiwan ROC Department of Medical Research Chung Shan Medical University Hospital Taichung Taiwan ROC Division of Endocrinology and Metabolism Department of Internal Medicine Kaohsiung Medical Universit

Kidney dysfunction is a major cause of mortality, but its genetic architecture remains elusive. In this study, we conducted a multiancestry genome-wide association study in 2.2 million individuals and identified 1026 (97 previously unknown) independent loci. Ancestry-specific analysis indicated an attenuation of newly identified signals on common variants in European ancestry populations and the power of population diversity for further discoveries. We defined genotype effects on allele-specific gene expression and regulatory circuitries in more than 700 human kidneys and 237,000 cells. We found 1363 coding variants disrupting 782 genes, with 601 genes also targeted by regulatory variants and convergence in 161 genes. Integrating 32 types of genetic information, we present the "Kidney Disease Genetic Scorecard" for prioritizing potentially causal genes, cell types, and druggable targets for kidney disease.

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Author Correction: Expanded encyclopaedias of DNA elements in the human and mouse genomes

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Nature 2022年第7909期605卷 E3页

作者： Jill E Moore Michael J Purcaro Henry E Pratt Charles B Epstein Noam Shoresh Jessika Adrian Trupti Kawli Carrie A Davis Alexander Dobin Rajinder Kaul Jessica Halow Eric L Van Nostrand Peter Freese David U Gorkin Yin Shen Yupeng He Mark Mackiewicz Florencia Pauli-Behn Brian A Williams Ali Mortazavi Cheryl A Keller Xiao-Ou Zhang Shaimae I Elhajjajy Jack Huey Diane E Dickel Valentina Snetkova Xintao Wei Xiaofeng Wang Juan Carlos Rivera-Mulia Joel Rozowsky Jing Zhang Surya B Chhetri Jialing Zhang Alec Victorsen Kevin P White Axel Visel Gene W Yeo Christopher B Burge Eric Lécuyer David M Gilbert Job Dekker John Rinn Eric M Mendenhall Joseph R Ecker Manolis Kellis Robert J Klein William S Noble Anshul Kundaje Roderic Guigó Peggy J Farnham J Michael Cherry Richard M Myers Bing Ren Brenton R Graveley Mark B Gerstein Len A Pennacchio Michael P Snyder Bradley E Bernstein Barbara Wold Ross C Hardison Thomas R Gingeras John A Stamatoyannopoulos Zhiping Weng University of Massachusetts Medical School Program in Bioinformatics and Integrative Biology Worcester MA USA. The Broad Institute of Harvard and MIT Cambridge MA USA. Department of Genetics School of Medicine Stanford University Palo Alto CA USA. Cold Spring Harbor Laboratory Functional Genomics Cold Spring Harbor NY USA. Altius Institute for Biomedical Sciences Seattle WA USA. Department of Medicine University of Washington School of Medicine Seattle WA USA. Department of Cellular and Molecular Medicine Institute for Genomic Medicine Stem Cell Program Sanford Consortium for Regenerative Medicine University of California San Diego La Jolla CA USA. Program in Computational and Systems Biology Massachusetts Institute of Technology Cambridge MA USA. Center for Epigenomics Department of Cellular and Molecular Medicine University of California San Diego La Jolla CA USA. Ludwig Institute for Cancer Research University of California San Diego La Jolla CA USA. Institute for Human Genetics Department of Neurology University of California San Francisco San Francisco CA USA. Genomics Analysis Laboratory The Salk Institute for Biological Studies La Jolla CA USA. HudsonAlpha Institute for Biotechnology Huntsville AL USA. Division of Biology and Biological Engineering California Institute of Technology Pasadena CA USA. Department of Developmental and Cell Biology University of California Irvine Irvine CA USA. Department of Biochemistry and Molecular Biology The Pennsylvania State University University Park PA USA. Environmental Genomics and Systems Biology Division Lawrence Berkeley National Laboratory Berkeley CA USA. Department of Genetics and Genome Sciences Institute for Systems Genomics UConn Health Farmington CT USA. Département de Biochimie et Médecine Moléculaire Université de Montréal Montréal Quebec Canada. Division of Experimental Medicine McGill University Montreal Quebec Canada. Institut de Recherches Cliniques de Montréal (IR

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The Huanan Seafood Wholesale Market in Wuhan was the early epicenter of the COVID-19 pandemic

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四川生理科学杂志 2022年第7期44卷 1246-1246页

作者： Michael Worobey Department of Ecology and Evolutionary Biology University of Arizona Tucson AZ 85721 USA Department of Immunology and Microbiology The Scripps Research Institute La Jolla CA 92037 USA W. Harry Feinstone Department of Molecular Microbiology and Immunology Johns Hopkins Bloomberg School of Public Health Baltimore MD 21205 USA Bioinformatics and Systems Biology Graduate Program University of California San Diego La Jolla CA 92093 USA Department of Biomedical Informatics University of California San Diego La Jolla CA 92093 USA Department of Human Genetics University of Utah School of Medicine Salt Lake City UT 84112 USA Vaccine and Infectious Disease Organization University of Saskatchewan Saskatoon SK S7N 5E3 Canada Center for Global Health Science and Security Georgetown University Washington DC 20057 USA Department of Zoology University of Oxford Oxford OX1 3SZ UK Wildlife Conservation Research Unit Department of Zoology The Recanati-Kaplan Centre University of Oxford Oxford OX13 5QL UK Pandemic and Disaster Preparedness Centre Erasmus University Medical Center 3015 CE Rotterdam Netherlands Department of Viroscience Erasmus University Medical Center 3015 CE Rotterdam Netherlands Department of Biostatistics Fielding School of Public Health University of California Los Angeles Los Angeles CA 90095 USA Department of Human Genetics David Geffen School of Medicine University of California Los Angeles Los Angeles CA 90095 USA Department of Computational Medicine David Geffen School of Medicine University of California Los Angeles Los Angeles CA 90095 USA Department of Medicine University of California San Diego La Jolla CA 92093 USA Department of Microbiology Immunology and Transplantation Rega Institute for Medical Research KU Leuven 3000 Leuven Belgium Global Virus Network (GVN) Baltimore MD 21201 USA MRC-University of Glasgow Center for Virus Research Glasgow G61 1QH UK Tulane University School of Medicine Department of Microbiology and Immu

Understanding how severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)emerged in 2019 is critical to preventing zoonotic outbreaks before they become the next *** Huanan Seafood Wholesale Market in Wuhan,China,was identified as a likely source of cases in early reports but later this conclusion became *** show the earliest known COVID-19 cases from December 2019,including those without reported direct links,were geographically centered on this *** report that live SARS-CoV-2 susceptible mammals were sold at the market in late 2019 and,within the market,SARS-CoV-2-positive environmental samples were spatially associated with vendors selling live mammals.

关键词： Market likely Wuhan

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Tumor-selective activity of RAS-GTP inhibition in pancreatic cancer

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Nature 2024年第8013期629卷 927-936页

作者： Urszula N Wasko Jingjing Jiang Tanner C Dalton Alvaro Curiel-Garcia A Cole Edwards Yingyun Wang Bianca Lee Margo Orlen Sha Tian Clint A Stalnecker Kristina Drizyte-Miller Marie Menard Julien Dilly Stephen A Sastra Carmine F Palermo Marie C Hasselluhn Amanda R Decker-Farrell Stephanie Chang Lingyan Jiang Xing Wei Yu C Yang Ciara Helland Haley Courtney Yevgeniy Gindin Karl Muonio Ruiping Zhao Samantha B Kemp Cynthia Clendenin Rina Sor William P Vostrejs Priya S Hibshman Amber M Amparo Connor Hennessey Matthew G Rees Melissa M Ronan Jennifer A Roth Jens Brodbeck Lorenzo Tomassoni Basil Bakir Nicholas D Socci Laura E Herring Natalie K Barker Junning Wang James M Cleary Brian M Wolpin John A Chabot Michael D Kluger Gulam A Manji Kenneth Y Tsai Miroslav Sekulic Stephen M Lagana Andrea Califano Elsa Quintana Zhengping Wang Jacqueline A M Smith Matthew Holderfield David Wildes Scott W Lowe Michael A Badgley Andrew J Aguirre Robert H Vonderheide Ben Z Stanger Timour Baslan Channing J Der Mallika Singh Kenneth P Olive Department of Medicine Vagelos College of Physicians and Surgeons Columbia University Irving Medical Center New York NY USA. Herbert Irving Comprehensive Cancer Center Columbia University Irving Medical Center New York NY USA. Revolution Medicines Redwood City CA USA. Department of Cell Biology and Physiology University of North Carolina at Chapel Hill Chapel Hill NC USA. University of Pennsylvania Perelman School of Medicine Department of Medicine Philadelphia PA USA. Cancer Biology and Genetics Program Sloan Kettering Institute Memorial Sloan Kettering Cancer Center New York NY USA. Lineberger Comprehensive Cancer Center University of North Carolina at Chapel Hill Chapel Hill NC USA. Department of Pharmacology University of North Carolina at Chapel Hill Chapel Hill NC USA. Department of Medical Oncology Dana-Farber Cancer Institute Boston MA USA. Harvard Medical School Boston MA USA. University of Pennsylvania Perelman School of Medicine Abramson Cancer Center Philadelphia PA USA. The Broad Institute of Harvard and MIT Cambridge MA USA. Department of Systems Biology Columbia University Irving Medical Center New York NY USA. Bioinformatics Core Memorial Sloan Kettering Cancer Center New York NY USA. UNC Michael Hooker Proteomics Center University of North Carolina at Chapel Hill Chapel Hill NC USA. Department of Surgery Vagelos College of Physicians and Surgeons Columbia University Irving Medical Center New York NY USA. Department of Pathology H. Lee Moffitt Cancer Center and Research Institute Tampa FL USA. Department of Tumor Microenvironment and Metastasis H. Lee Moffitt Cancer Center and Research Institute Tampa FL USA. Department of Pathology and Cell Biology Columbia University Irving Medical Center New York NY USA. Department of Oncology The Johns Hopkins University School of Medicine Baltimore MD USA. J. P. Sulzberger Columbia Genome Center Columbia University New York NY USA. Department of Biochemistry and Molecular Biop

Broad-spectrum RAS inhibition has the potential to benefit roughly a quarter of human patients with cancer whose tumours are driven by RAS mutations. RMC-7977 is a highly selective inhibitor of the active GTP-bound forms of KRAS, HRAS and NRAS, with affinity for both mutant and wild-type variants. More than 90% of cases of human pancreatic ductal adenocarcinoma (PDAC) are driven by activating mutations in KRAS. Here we assessed the therapeutic potential of RMC-7977 in a comprehensive range of PDAC models. We observed broad and pronounced anti-tumour activity across models following direct RAS inhibition at exposures that were well-tolerated in vivo. Pharmacological analyses revealed divergent responses to RMC-7977 in tumour versus normal tissues. Treated tumours exhibited waves of apoptosis along with sustained proliferative arrest, whereas normal tissues underwent only transient decreases in proliferation, with no evidence of apoptosis. In the autochthonous KPC mouse model, RMC-7977 treatment resulted in a profound extension of survival followed by on-treatment relapse. Analysis of relapsed tumours identified Myc copy number gain as a prevalent candidate resistance mechanism, which could be overcome by combinatorial TEAD inhibition in vitro. Together, these data establish a strong preclinical rationale for the use of broad-spectrum RAS-GTP inhibition in the setting of PDAC and identify a promising candidate combination therapeutic regimen to overcome monotherapy resistance.

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Author Correction: Comprehensive molecular characterization of mitochondrial genomes in human cancers

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Nature genetics 2023年第6期55卷 1078页

作者： Yuan Yuan Young Seok Ju Youngwook Kim Jun Li Yumeng Wang Christopher J Yoon Yang Yang Inigo Martincorena Chad J Creighton John N Weinstein Yanxun Xu Leng Han Hyung-Lae Kim Hidewaki Nakagawa Keunchil Park Peter J Campbell Han Liang Department of Bioinformatics and Computational Biology The University of Texas MD Anderson Cancer Center Houston TX USA. Cancer Genome Project Wellcome Trust Sanger Institute Hinxton UK. Graduate School of Medical Science and Engineering Korea Advanced Institute of Science and Technology Daejeon Korea. Department of Health Science and Technology Samsung Advanced Institute for Health Science and Technology Sungkyunkwan University School of Medicine Seoul Korea. Samsung Genome Institute Samsung Medical Center Seoul Korea. Quantitative and Computational Biosciences Graduate Program Baylor College of Medicine Houston TX USA. Division of Biostatistics The University of Texas Health Science Center at Houston School of Public Health Houston TX USA. Department of Medicine and Dan L. Duncan Cancer Center Division of Biostatistics Baylor College of Medicine Houston TX USA. Department of Systems Biology The University of Texas MD Anderson Cancer Center Houston TX USA. Department of Applied Mathematics and Statistics Johns Hopkins University Baltimore MD USA. Department of Biochemistry and Molecular Biology The University of Texas Health Science Center at Houston McGovern Medical School Houston TX USA. Department of Biochemistry Ewha Womans University School of Medicine Seoul Korea. Laboratory for Cancer Genomics RIKEN Center for Integrative Medical Sciences Yokohama Japan. Division of Hematology/Oncology Samsung Medical Center Sungkyunkwan University School of Medicine Seoul Korea. kpark@skku.edu. Samsung Advanced Institute for Health Sciences and Technology Sungkyunkwan University School of Medicine Seoul South Korea. kpark@skku.edu. Cancer Genome Project Wellcome Trust Sanger Institute Hinxton UK. pc8@sanger.ac.uk. Department of Haematology University of Cambridge Cambridge UK. pc8@sanger.ac.uk. Department of Bioinformatics and Computational Biology The University of Texas MD Anderson Cancer Center Houston TX USA. hliang1@mdanderson.org. Quantitative and Comp

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Author Correction: Cellular deconvolution of GTEx tissues powers discovery of disease and cell-type associated regulatory variants

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Nature communications 2020年第1期11卷 4426页

作者： Margaret K R Donovan Agnieszka D'Antonio-Chronowska Matteo D'Antonio Kelly A Frazer Bioinformatics and Systems Biology Graduate Program University of California San Diego La Jolla CA 92093 USA. Department of Biomedical Informatics University of California San Diego La Jolla CA 92093 USA. Department of Pediatrics and Rady Children's Hospital University of California San Diego La Jolla CA 92093 USA. Department of Pediatrics and Rady Children's Hospital University of California San Diego La Jolla CA 92093 USA. madantonio@health.ucsd.edu. Department of Pediatrics and Rady Children's Hospital University of California San Diego La Jolla CA 92093 USA. kafrazer@health.ucsd.edu. Institute for Genomic Medicine University of California San Diego La Jolla CA 92093 USA. kafrazer@health.ucsd.edu.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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