Opposing roles of hepatic stellate cell subpopulations in hepatocarcinogenesis.


Journal

Nature
ISSN: 1476-4687
Titre abrégé: Nature
Pays: England
ID NLM: 0410462

Informations de publication

Date de publication:
10 2022
Historique:
received: 26 04 2021
accepted: 30 08 2022
pubmed: 6 10 2022
medline: 15 10 2022
entrez: 5 10 2022
Statut: ppublish

Résumé

Hepatocellular carcinoma (HCC), the fourth leading cause of cancer mortality worldwide, develops almost exclusively in patients with chronic liver disease and advanced fibrosis

Identifiants

pubmed: 36198802
doi: 10.1038/s41586-022-05289-6
pii: 10.1038/s41586-022-05289-6
pmc: PMC9949942
mid: NIHMS1867159
doi:

Substances chimiques

Collagen Type I 0
Hepatocyte Growth Factor 67256-21-7
Discoidin Domain Receptor 1 EC 2.7.10.1

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

356-365

Subventions

Organisme : NIDDK NIH HHS
ID : R01 DK128955
Pays : United States
Organisme : Medical Research Council
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 219542/Z/19/Z
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : R01 CA190844
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK116620
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA228483
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK132710
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA211794
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA274295
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA262424
Pays : United States

Informations de copyright

© 2022. The Author(s), under exclusive licence to Springer Nature Limited.

Références

Villanueva, A. Hepatocellular carcinoma. N. Engl. J. Med. 380, 1450–1462 (2019).
pubmed: 30970190 doi: 10.1056/NEJMra1713263
Affo, S., Yu, L. X. & Schwabe, R. F. The role of cancer-associated fibroblasts and fibrosis in liver cancer. Annu. Rev. Pathol. 12, 153–186 (2017).
pubmed: 27959632 doi: 10.1146/annurev-pathol-052016-100322
Mederacke, I. et al. Fate tracing reveals hepatic stellate cells as dominant contributors to liver fibrosis independent of its aetiology. Nat. Commun. 4, 2823 (2013).
pubmed: 24264436 doi: 10.1038/ncomms3823
Ryerson, A. B. et al. Annual report to the nation on the status of cancer, 1975–2012, featuring the increasing incidence of liver cancer. Cancer 122, 1312–1337 (2016).
pubmed: 26959385 doi: 10.1002/cncr.29936
Jemal, A. et al. Annual report to the nation on the status of cancer, 1975–2014, featuring survival. J. Natl Cancer Inst. 109, djx030 (2017).
pmcid: 5409140 doi: 10.1093/jnci/djx030
Llovet, J. M. et al. Immunotherapies for hepatocellular carcinoma. Nat. Rev. Clin. Oncol. 19, 151–172 (2022).
pubmed: 34764464 doi: 10.1038/s41571-021-00573-2
Schwabe, R. F. & Luedde, T. Apoptosis and necroptosis in the liver: a matter of life and death. Nat. Rev. Gastroenterol. Hepatol. 15, 738–752 (2018).
pubmed: 30250076 pmcid: 6490680 doi: 10.1038/s41575-018-0065-y
Dvorak, H. F. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N. Engl. J. Med. 315, 1650–1659 (1986).
Paradis, V. et al. Hepatocellular carcinomas in patients with metabolic syndrome often develop without significant liver fibrosis: a pathological analysis. Hepatology 49, 851–859 (2009).
pubmed: 19115377 doi: 10.1002/hep.22734
Lujambio, A. et al. Non-cell-autonomous tumor suppression by p53. Cell 153, 449–460 (2013).
pubmed: 23562644 pmcid: 3702034 doi: 10.1016/j.cell.2013.03.020
Kocabayoglu, P. et al. β-PDGF receptor expressed by hepatic stellate cells regulates fibrosis in murine liver injury, but not carcinogenesis. J. Hepatol. 63, 141–147 (2015).
pubmed: 25678385 pmcid: 4475471 doi: 10.1016/j.jhep.2015.01.036
Duran, A. et al. p62/SQSTM1 by binding to vitamin D receptor inhibits hepatic stellate cell activity, fibrosis, and liver cancer. Cancer Cell 30, 595–609 (2016).
pubmed: 27728806 pmcid: 5081228 doi: 10.1016/j.ccell.2016.09.004
Yoshimoto, S. et al. Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature 499, 97–101 (2013).
pubmed: 23803760 doi: 10.1038/nature12347
Krizhanovsky, V. et al. Senescence of activated stellate cells limits liver fibrosis. Cell 134, 657–667 (2008).
pubmed: 18724938 pmcid: 3073300 doi: 10.1016/j.cell.2008.06.049
Loo, T. M. et al. Gut microbiota promotes obesity-associated liver cancer through PGE2-mediated suppression of antitumor immunity. Cancer Discov. 7, 522–538 (2017).
pubmed: 28202625 doi: 10.1158/2159-8290.CD-16-0932
Omori, S. et al. Generation of a p16 reporter mouse and its use to characterize and target p16
pubmed: 32949498 doi: 10.1016/j.cmet.2020.09.006
Wandzioch, E., Kolterud, A., Jacobsson, M., Friedman, S. L. & Carlsson, L. Lhx2
pubmed: 15536133 pmcid: 526277 doi: 10.1073/pnas.0404678101
Anstee, Q. M., Reeves, H. L., Kotsiliti, E., Govaere, O. & Heikenwalder, M. From NASH to HCC: current concepts and future challenges. Nat. Rev. Gastroenterol. Hepatol. 16, 411–428 (2019).
pubmed: 31028350 doi: 10.1038/s41575-019-0145-7
Wang, X. et al. Hepatocyte TAZ/WWTR1 promotes inflammation and fibrosis in nonalcoholic steatohepatitis. Cell Metab. 24, 848–862 (2016).
pubmed: 28068223 pmcid: 5226184 doi: 10.1016/j.cmet.2016.09.016
Hoshida, Y. et al. Gene expression in fixed tissues and outcome in hepatocellular carcinoma. N. Engl. J. Med. 359, 1995–2004 (2008).
pubmed: 18923165 pmcid: 2963075 doi: 10.1056/NEJMoa0804525
Ji, J. et al. Hepatic stellate cell and monocyte interaction contributes to poor prognosis in hepatocellular carcinoma. Hepatology 62, 481–495 (2015).
pubmed: 25833323 doi: 10.1002/hep.27822
Mu, X. et al. Hepatocellular carcinoma originates from hepatocytes and not from the progenitor/biliary compartment. J. Clin. Invest. 125, 3891–3903 (2015).
pubmed: 26348897 pmcid: 4607132 doi: 10.1172/JCI77995
Puche, J. E. et al. A novel murine model to deplete hepatic stellate cells uncovers their role in amplifying liver damage in mice. Hepatology 57, 339–350 (2013).
pubmed: 22961591 doi: 10.1002/hep.26053
Affo, S. et al. Promotion of cholangiocarcinoma growth by diverse cancer-associated fibroblast subpopulations. Cancer Cell 39, 866–882.e11 (2021).
pubmed: 33930309 pmcid: 8241235 doi: 10.1016/j.ccell.2021.03.012
Bhattacharjee, S. et al. Tumor restriction by type I collagen opposes tumor-promoting effects of cancer-associated fibroblasts. J. Clin. Invest. 131, e146987 (2021).
pmcid: 8159701 doi: 10.1172/JCI146987
Xiong, X. et al. Landscape of intercellular crosstalk in healthy and NASH liver revealed by single-cell secretome gene analysis. Mol. Cell 75, 644–660.e5 (2019).
pubmed: 31398325 pmcid: 7262680 doi: 10.1016/j.molcel.2019.07.028
Hayward, M. K., Muncie, J. M. & Weaver, V. M. Tissue mechanics in stem cell fate, development, and cancer. Dev. Cell 56, 1833–1847 (2021).
pubmed: 34107299 pmcid: 9056158 doi: 10.1016/j.devcel.2021.05.011
Masuzaki, R. et al. Prospective risk assessment for hepatocellular carcinoma development in patients with chronic hepatitis C by transient elastography. Hepatology 49, 1954–1961 (2009).
pubmed: 19434742 doi: 10.1002/hep.22870
Poynard, T. et al. Staging chronic hepatitis C in seven categories using fibrosis biomarker (FibroTest) and transient elastography (FibroScan(R)). J. Hepatol. 60, 706–714 (2014).
pubmed: 24291240 doi: 10.1016/j.jhep.2013.11.016
Wang, H. M. et al. Liver stiffness measurement as an alternative to fibrotic stage in risk assessment of hepatocellular carcinoma incidence for chronic hepatitis C patients. Liver Int. 33, 756–761 (2013).
pubmed: 23405889 doi: 10.1111/liv.12118
Baglieri, J. et al. Nondegradable collagen increases liver fibrosis but not hepatocellular carcinoma in mice. Am. J. Pathol. 191, 1564–1579 (2021).
pubmed: 34119473 pmcid: 8406794 doi: 10.1016/j.ajpath.2021.05.019
Su, H. et al. Collagenolysis-dependent DDR1 signalling dictates pancreatic cancer outcome. Nature https://doi.org/10.1038/s41586-022-05169-z (2022).
Dhar, D. et al. Liver cancer initiation requires p53 inhibition by CD44-enhanced growth factor signaling. Cancer Cell 33, 1061–1077.e6 (2018).
pubmed: 29894692 pmcid: 6005359 doi: 10.1016/j.ccell.2018.05.003
Goyal, L., Muzumdar, M. D. & Zhu, A. X. Targeting the HGF/c-MET pathway in hepatocellular carcinoma. Clin. Cancer Res. 19, 2310–2318 (2013).
pubmed: 23388504 pmcid: 4583193 doi: 10.1158/1078-0432.CCR-12-2791
Takami, T. et al. Loss of hepatocyte growth factor/c-Met signaling pathway accelerates early stages of N-nitrosodiethylamine induced hepatocarcinogenesis. Cancer Res. 67, 9844–9851 (2007).
pubmed: 17942915 doi: 10.1158/0008-5472.CAN-07-1905
Ueki, T. et al. Hepatocyte growth factor gene therapy of liver cirrhosis in rats. Nat. Med. 5, 226–230 (1999).
pubmed: 9930873 doi: 10.1038/5593
Santoni-Rugiu, E. et al. Inhibition of neoplastic development in the liver by hepatocyte growth factor in a transgenic mouse model. Proc. Natl Acad. Sci. USA 93, 9577–9582 (1996).
pubmed: 8790372 pmcid: 38470 doi: 10.1073/pnas.93.18.9577
Suzuki, A. et al. Hepatocyte growth factor promotes cell survival from Fas-mediated cell death in hepatocellular carcinoma cells via Akt activation and Fas-death-inducing signaling complex suppression. Hepatology 32, 796–802 (2000).
pubmed: 11003625 doi: 10.1053/jhep.2000.17738
Stoker, M. G., Shearer, M. & O'Neill, C. Growth inhibition of polyoma-transformed cells by contact with static normal fibroblasts. J. Cell Sci. 1, 297–310 (1966).
pubmed: 4291022 doi: 10.1242/jcs.1.3.297
Alkasalias, T. et al. Inhibition of tumor cell proliferation and motility by fibroblasts is both contact and soluble factor dependent. Proc. Natl Acad. Sci. USA 111, 17188–17193 (2014).
pubmed: 25404301 pmcid: 4260581 doi: 10.1073/pnas.1419554111
Sun, X. et al. Tumour DDR1 promotes collagen fibre alignment to instigate immune exclusion. Nature 599, 673–678 (2021).
pubmed: 34732895 pmcid: 8839149 doi: 10.1038/s41586-021-04057-2
Chen, Y. et al. Type I collagen deletion in αSMA
pubmed: 33667385 pmcid: 8423173 doi: 10.1016/j.ccell.2021.02.007
Nault, J. C. et al. Clinical impact of genomic diversity from early to advanced hepatocellular carcinoma. Hepatology 71, 164–182 (2020).
pubmed: 31206197 doi: 10.1002/hep.30811
Krempen, K. et al. Far upstream regulatory elements enhance position-independent and uterus-specific expression of the murine α1(I) collagen promoter in transgenic mice. Gene Expr. 8, 151–163 (1999).
pubmed: 10634317
Mangale, V. S. et al. Lhx2 selector activity specifies cortical identity and suppresses hippocampal organizer fate. Science 319, 304–309 (2008).
pubmed: 18202285 pmcid: 2494603 doi: 10.1126/science.1151695
Geisler, F., Algul, H., Paxian, S. & Schmid, R. M. Genetic inactivation of RelA/p65 sensitizes adult mouse hepatocytes to TNF-induced apoptosis in vivo and in vitro. Gastroenterology 132, 2489–2503 (2007).
pubmed: 17570221 doi: 10.1053/j.gastro.2007.03.033
Buchtler, S. et al. Cellular origin and functional relevance of collagen I production in the kidney. J. Am. Soc. Nephrol. 29, 1859–1873 (2018).
pubmed: 29777019 pmcid: 6050926 doi: 10.1681/ASN.2018020138
Affo, S. et al. Promotion of cholangiocarcinoma growth by diverse cancer-associated fibroblast subpopulations. Cancer Cell 39, 866–882.e11 (2021).
pubmed: 33930309 pmcid: 8241235 doi: 10.1016/j.ccell.2021.03.012
Phaneuf, D., Moscioni, A. D., LeClair, C., Raper, S. E. & Wilson, J. M. Generation of a mouse expressing a conditional knockout of the hepatocyte growth factor gene: demonstration of impaired liver regeneration. DNA Cell Biol. 23, 592–603 (2004).
pubmed: 15383179 doi: 10.1089/dna.2004.23.592
Matsumoto, K. et al. Conditional inactivation of Has2 reveals a crucial role for hyaluronan in skeletal growth, patterning, chondrocyte maturation and joint formation in the developing limb. Development 136, 2825–2835 (2009).
pubmed: 19633173 pmcid: 2730409 doi: 10.1242/dev.038505
Murtaugh, L. C., Stanger, B. Z., Kwan, K. M. & Melton, D. A. Notch signaling controls multiple steps of pancreatic differentiation. Proc. Natl Acad. Sci. USA 100, 14920–14925 (2003).
pubmed: 14657333 pmcid: 299853 doi: 10.1073/pnas.2436557100
Ozdemir, B. C. et al. Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival. Cancer Cell 25, 719–734 (2014).
pubmed: 24856586 pmcid: 4180632 doi: 10.1016/j.ccr.2014.04.005
Mitchell, C. & Willenbring, H. A reproducible and well-tolerated method for 2/3 partial hepatectomy in mice. Nat. Protoc. 3, 1167–1170 (2008).
pubmed: 18600221 doi: 10.1038/nprot.2008.80
Zhang, S. et al. The Hippo effector transcriptional coactivator with PDZ-binding motif cooperates with oncogenic β-catenin to induce hepatoblastoma development in mice and humans. Am. J. Pathol. 190, 1397–1413 (2020).
pubmed: 32283103 pmcid: 7322365 doi: 10.1016/j.ajpath.2020.03.011
Tao, J. et al. Modeling a human hepatocellular carcinoma subset in mice through coexpression of met and point-mutant β-catenin. Hepatology 64, 1587–1605 (2016).
pubmed: 27097116 doi: 10.1002/hep.28601
Mederacke, I., Dapito, D. H., Affo, S., Uchinami, H. & Schwabe, R. F. High-yield and high-purity isolation of hepatic stellate cells from normal and fibrotic mouse livers. Nat. Protoc. 10, 305–315 (2015).
pubmed: 25612230 pmcid: 4681437 doi: 10.1038/nprot.2015.017
Pradere, J. P. et al. Hepatic macrophages but not dendritic cells contribute to liver fibrosis by promoting the survival of activated hepatic stellate cells in mice. Hepatology 58, 1461–1473 (2013).
pubmed: 23553591 doi: 10.1002/hep.26429
Chung, A. S. et al. Immune checkpoint inhibition is safe and effective for liver cancer prevention in a mouse model of hepatocellular carcinoma. Cancer Prev. Res. 13, 911–922 (2020).
doi: 10.1158/1940-6207.CAPR-20-0200
Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).
pubmed: 25516281 pmcid: 4302049 doi: 10.1186/s13059-014-0550-8
Zhou, Y. et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat. Commun. 10, 1523 (2019).
pubmed: 30944313 pmcid: 6447622 doi: 10.1038/s41467-019-09234-6
Hao, Y. et al. Integrated analysis of multimodal single-cell data. Cell 184, 3573–3587.e29 (2021).
Slyper, M. et al. A single-cell and single-nucleus RNA-seq toolbox for fresh and frozen human tumors. Nat. Med. 26, 792–802 (2020).
pubmed: 32405060 pmcid: 7220853 doi: 10.1038/s41591-020-0844-1
Andrews, T. S. et al. Single-cell, single-nucleus, and spatial RNA sequencing of the human liver identifies cholangiocyte and mesenchymal heterogeneity. Hepatol. Commun. 6, 821–840 (2022).
pubmed: 34792289 doi: 10.1002/hep4.1854
Fleming, S. J., Marioni, J. C. & Babadi, M. CellBender remove-background: a deep generative model for unsupervised removal of background noise from scRNA-seq datasets. Preprint at bioRxiv https://doi.org/10.1101/791699 (2022).
Franzen, O., Gan, L. M. & Bjorkegren, J. L. M. PanglaoDB: a web server for exploration of mouse and human single-cell RNA sequencing data. Database 2019, baz046 (2019).
pubmed: 30951143 pmcid: 6450036 doi: 10.1093/database/baz046
Cao, J. et al. The single-cell transcriptional landscape of mammalian organogenesis. Nature 566, 496–502 (2019).
pubmed: 30787437 pmcid: 6434952 doi: 10.1038/s41586-019-0969-x
Hoshida, Y. Nearest template prediction: a single-sample-based flexible class prediction with confidence assessment. PLoS ONE 5, e15543 (2010).
pubmed: 21124904 pmcid: 2990751 doi: 10.1371/journal.pone.0015543
Kuleshov, M. V. et al. Enrichr: a comprehensive gene set enrichment analysis web server 2016 update. Nucleic Acids Res. 44, W90–W97 (2016).
pubmed: 27141961 pmcid: 4987924 doi: 10.1093/nar/gkw377
Vento-Tormo, R. et al. Single-cell reconstruction of the early maternal–fetal interface in humans. Nature 563, 347–353 (2018).
pubmed: 30429548 pmcid: 7612850 doi: 10.1038/s41586-018-0698-6
Efremova, M., Vento-Tormo, M., Teichmann, S. A. & Vento-Tormo, R. CellPhoneDB: inferring cell–cell communication from combined expression of multi-subunit ligand–receptor complexes. Nat. Protoc. 15, 1484–1506 (2020).
pubmed: 32103204 doi: 10.1038/s41596-020-0292-x

Auteurs

Aveline Filliol (A)

Department of Medicine, Columbia University, New York, NY, USA.

Yoshinobu Saito (Y)

Department of Medicine, Columbia University, New York, NY, USA.

Ajay Nair (A)

Department of Medicine, Columbia University, New York, NY, USA.
Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA.

Dianne H Dapito (DH)

Department of Medicine, Columbia University, New York, NY, USA.

Le-Xing Yu (LX)

Department of Medicine, Columbia University, New York, NY, USA.

Aashreya Ravichandra (A)

Department of Medicine, Columbia University, New York, NY, USA.
Klinikum Rechts der Isar, Technical University of Munich (TUM), Munich, Germany.

Sonakshi Bhattacharjee (S)

Department of Medicine, Columbia University, New York, NY, USA.

Silvia Affo (S)

Department of Medicine, Columbia University, New York, NY, USA.
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.

Naoto Fujiwara (N)

Liver Tumor Translational Research Program, Harold C. Simmons Comprehensive Cancer Center, Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Hua Su (H)

Department of Pharmacology, School of Medicine, University of California, San Diego, San Diego, CA, USA.

Qiuyan Sun (Q)

Department of Medicine, Columbia University, New York, NY, USA.

Thomas M Savage (TM)

Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, USA.

John R Wilson-Kanamori (JR)

Centre for Inflammation Research, The Queen's Medical Research Institute, Edinburgh BioQuarter, University of Edinburgh, Edinburgh, UK.

Jorge M Caviglia (JM)

Department of Medicine, Columbia University, New York, NY, USA.
Department of Health and Nutrition Sciences, Brooklyn College, City University of New York, New York, NY, USA.

LiKang Chin (L)

Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Department of Biomedical Engineering, Widener University, Chester, PA, USA.

Dongning Chen (D)

Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Xiaobo Wang (X)

Department of Medicine, Columbia University, New York, NY, USA.

Stefano Caruso (S)

Functional Genomics of Solid Tumors Laboratory, Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, Paris, France.

Jin Ku Kang (JK)

Department of Medicine, Columbia University, New York, NY, USA.
Institute of Human Nutrition, Columbia University, New York, NY, USA.

Amit Dipak Amin (AD)

Department of Medicine, Columbia University, New York, NY, USA.

Sebastian Wallace (S)

Centre for Inflammation Research, The Queen's Medical Research Institute, Edinburgh BioQuarter, University of Edinburgh, Edinburgh, UK.

Ross Dobie (R)

Centre for Inflammation Research, The Queen's Medical Research Institute, Edinburgh BioQuarter, University of Edinburgh, Edinburgh, UK.

Deqi Yin (D)

Department of Medicine, Columbia University, New York, NY, USA.

Oscar M Rodriguez-Fiallos (OM)

Department of Medicine, Columbia University, New York, NY, USA.

Chuan Yin (C)

Department of Medicine, Columbia University, New York, NY, USA.
Department of Gastroenterology, Changzheng Hospital, Shanghai, China.

Adam Mehal (A)

Department of Medicine, Columbia University, New York, NY, USA.

Benjamin Izar (B)

Department of Medicine, Columbia University, New York, NY, USA.

Richard A Friedman (RA)

Biomedical Informatics Shared Resource, Herbert Irving Comprehensive Cancer Center, and Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, NY, USA.

Rebecca G Wells (RG)

Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Utpal B Pajvani (UB)

Department of Medicine, Columbia University, New York, NY, USA.
Institute of Human Nutrition, Columbia University, New York, NY, USA.

Yujin Hoshida (Y)

Liver Tumor Translational Research Program, Harold C. Simmons Comprehensive Cancer Center, Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Helen E Remotti (HE)

Department of Pathology, Columbia University Irving Medical Center, New York, NY, USA.

Nicholas Arpaia (N)

Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, USA.

Jessica Zucman-Rossi (J)

Functional Genomics of Solid Tumors Laboratory, Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, Paris, France.

Michael Karin (M)

Department of Pharmacology, School of Medicine, University of California, San Diego, San Diego, CA, USA.

Neil C Henderson (NC)

Centre for Inflammation Research, The Queen's Medical Research Institute, Edinburgh BioQuarter, University of Edinburgh, Edinburgh, UK.
MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.

Ira Tabas (I)

Department of Medicine, Columbia University, New York, NY, USA.
Institute of Human Nutrition, Columbia University, New York, NY, USA.
Department of Pathology, Columbia University Irving Medical Center, New York, NY, USA.
Department of Physiology, Columbia University, New York, NY, USA.

Robert F Schwabe (RF)

Department of Medicine, Columbia University, New York, NY, USA. rfs2102@cumc.columbia.edu.
Institute of Human Nutrition, Columbia University, New York, NY, USA. rfs2102@cumc.columbia.edu.

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