BRAF


Journal

Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179

Informations de publication

Date de publication:
21 09 2023
Historique:
received: 23 03 2023
accepted: 07 09 2023
medline: 25 9 2023
pubmed: 22 9 2023
entrez: 22 9 2023
Statut: epublish

Résumé

BRAF mutations occur early in serrated colorectal cancers, but their long-term influence on tissue homeostasis is poorly characterized. We investigated the impact of short-term (3 days) and long-term (6 months) expression of Braf

Identifiants

pubmed: 37735514
doi: 10.1038/s42003-023-05331-x
pii: 10.1038/s42003-023-05331-x
pmc: PMC10514332
doi:

Substances chimiques

BRAF protein, human EC 2.7.11.1
Cholesterol 97C5T2UQ7J
Proto-Oncogene Proteins B-raf EC 2.7.11.1
Braf protein, mouse EC 2.7.11.1

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

962

Subventions

Organisme : Cancer Research UK
ID : C325/A15575
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 210911/Z/18/Z
Pays : United Kingdom

Informations de copyright

© 2023. Springer Nature Limited.

Références

Santos, A. J. M., Lo, Y. H., Mah, A. T. & Kuo, C. J. The intestinal stem cell niche: homeostasis and adaptations. Trends Cell Biol. 28, 1062–1078 (2018).
pubmed: 30195922 pmcid: 6338454 doi: 10.1016/j.tcb.2018.08.001
van der Flier, L. G., Haegebarth, A., Stange, D. E., van de Wetering, M. & Clevers, H. OLFM4 is a robust marker for stem cells in human intestine and marks a subset of colorectal cancer cells. Gastroenterology 137, 15–17 (2009).
pubmed: 19450592 doi: 10.1053/j.gastro.2009.05.035
Barker, N. et al. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 449, 1003–1007 (2007).
pubmed: 17934449 doi: 10.1038/nature06196
Minoo, P., Zlobec, I., Peterson, M., Terracciano, L. & Lugli, A. Characterization of rectal, proximal and distal colon cancers based on clinicopathological, molecular and protein profiles. Int. J. Oncol. 37, 707–718 (2010).
pubmed: 20664940 doi: 10.3892/ijo_00000720
Stintzing, S., Tejpar, S., Gibbs, P., Thiebach, L. & Lenz, H. J. Understanding the role of primary tumour localisation in colorectal cancer treatment and outcomes. Eur. J. Cancer 84, 69–80 (2017).
pubmed: 28787661 pmcid: 7505124 doi: 10.1016/j.ejca.2017.07.016
Chen, B. et al. Differential pre-malignant programs and microenvironment chart distinct paths to malignancy in human colorectal polyps. Cell 184, 6262–6280.e6226 (2021).
pubmed: 34910928 pmcid: 8941949 doi: 10.1016/j.cell.2021.11.031
Joanito, I. et al. Single-cell and bulk transcriptome sequencing identifies two epithelial tumor cell states and refines the consensus molecular classification of colorectal cancer. Nat. Genet. 54, 963–975 (2022).
pubmed: 35773407 pmcid: 9279158 doi: 10.1038/s41588-022-01100-4
Muzny, D. M. et al. Comprehensive molecular characterization of human colon and rectal cancer. Nature 487, 330–337 (2012).
doi: 10.1038/nature11252
Fearon, E. R. & Vogelstein, B. A genetic model for colorectal tumorigenesis. Cell 61, 759–767 (1990).
pubmed: 2188735 doi: 10.1016/0092-8674(90)90186-I
Missiaglia, E. et al. Distal and proximal colon cancers differ in terms of molecular, pathological, and clinical features. Ann. Oncol. 25, 1995–2001 (2014).
pubmed: 25057166 doi: 10.1093/annonc/mdu275
Leach, J. D. G. et al. Oncogenic BRAF, unrestrained by TGFβ-receptor signalling, drives right-sided colonic tumorigenesis. Nat. Commun. 12, 3464 (2021).
pubmed: 34103493 pmcid: 8187652 doi: 10.1038/s41467-021-23717-5
Weisenberger, D. J. et al. CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer. Nat. Genet. 38, 787–793 (2006).
pubmed: 16804544 doi: 10.1038/ng1834
Davies, H. et al. Mutations of the BRAF gene in human cancer. Nature 417, 949–954 (2002).
pubmed: 12068308 doi: 10.1038/nature00766
Rajagopalan, H. et al. RAF/RAS oncogenes and mismatch-repair status. Nature 418, 934–934 (2002).
pubmed: 12198537 doi: 10.1038/418934a
Dhillon, A. S., Hagan, S., Rath, O. & Kolch, W. MAP kinase signalling pathways in cancer. Oncogene 26, 3279–3290 (2007).
pubmed: 17496922 doi: 10.1038/sj.onc.1210421
Parsons, R. et al. Microsatellite instability and mutations of the transforming growth factor beta type II receptor gene in colorectal cancer. Cancer Res. 55, 5548–5550 (1995).
pubmed: 7585632
Barras, D. et al. BRAF V600E mutant colorectal cancer subtypes based on gene expression. Clin. Cancer Res. 23, 104–115 (2017).
pubmed: 27354468 doi: 10.1158/1078-0432.CCR-16-0140
Tong, K. et al. Degree of tissue differentiation dictates susceptibility to BRAF-driven colorectal cancer. Cell Rep. 21, 3833–3845 (2017).
pubmed: 29281831 pmcid: 5747303 doi: 10.1016/j.celrep.2017.11.104
Rad, R. et al. A genetic progression model of Braf(V600E)-induced intestinal tumorigenesis reveals targets for therapeutic intervention. Cancer Cell 24, 15–29 (2013).
pubmed: 23845441 pmcid: 3706745 doi: 10.1016/j.ccr.2013.05.014
Carragher, L. A. et al. V600EBraf induces gastrointestinal crypt senescence and promotes tumour progression through enhanced CpG methylation of p16INK4a. EMBO Mol. Med. 2, 458–471 (2010).
pubmed: 20941790 pmcid: 3394506 doi: 10.1002/emmm.201000099
Jänne, P. A. & Mayer, R. J. Chemoprevention of colorectal cancer. N. Engl. J. Med. 342, 1960–1968 (2000).
pubmed: 10874065 doi: 10.1056/NEJM200006293422606
Riemer, P. et al. Transgenic expression of oncogenic BRAF induces loss of stem cells in the mouse intestine, which is antagonized by β-catenin activity. Oncogene 34, 3164–3175 (2015).
pubmed: 25109331 doi: 10.1038/onc.2014.247
Feng, Y. et al. Mutant KRAS promotes hyperplasia and alters differentiation in the colon epithelium but does not expand the presumptive stem cell pool. Gastroenterology 141, 1003–1013.e1010 (2011).
pubmed: 21699772 doi: 10.1053/j.gastro.2011.05.007
Liberzon, A. et al. Molecular signatures database (MSigDB) 3.0. Bioinformatics 27, 1739–1740 (2011).
pubmed: 21546393 pmcid: 3106198 doi: 10.1093/bioinformatics/btr260
Popovici, V. et al. Identification of a poor-prognosis BRAF-mutant-like population of patients with colon cancer. J. Clin. Oncol. 30, 1288–1295 (2012).
pubmed: 22393095 doi: 10.1200/JCO.2011.39.5814
Tsai, J.-H. et al. Aberrant expression of annexin A10 is closely related to gastric phenotype in serrated pathway to colorectal carcinoma. Mod. Pathol. 28, 268–278 (2015).
pubmed: 25081749 doi: 10.1038/modpathol.2014.96
Gonzalo, D. H. et al. Gene expression profiling of serrated polyps identifies annexin A10 as a marker of a sessile serrated adenoma/polyp. J. Pathol. 230, 420–429 (2013).
pubmed: 23595865 doi: 10.1002/path.4200
Lytras, T., Nikolopoulos, G. & Bonovas, S. Statins and the risk of colorectal cancer: an updated systematic review and meta-analysis of 40 studies. World J. Gastroenterol. 20, 1858–1870 (2014).
pubmed: 24587664 pmcid: 3930985 doi: 10.3748/wjg.v20.i7.1858
Mullen, P. J., Yu, R., Longo, J., Archer, M. C. & Penn, L. Z. The interplay between cell signalling and the mevalonate pathway in cancer. Nat. Rev. Cancer 16, 718–731 (2016).
pubmed: 27562463 doi: 10.1038/nrc.2016.76
De Sousa, E. M. F. et al. Poor-prognosis colon cancer is defined by a molecularly distinct subtype and develops from serrated precursor lesions. Nat. Med. 19, 614–618 (2013).
doi: 10.1038/nm.3174
Delker, D. A. et al. RNA sequencing of sessile serrated colon polyps identifies differentially expressed genes and immunohistochemical markers. PLoS ONE 9, e88367 (2014).
pubmed: 24533081 pmcid: 3922809 doi: 10.1371/journal.pone.0088367
Parker, H. R. et al. The proto CpG island methylator phenotype of sessile serrated adenomas/polyps. Epigenetics 13, 1088–1105 (2018).
pubmed: 30398409 pmcid: 6342079 doi: 10.1080/15592294.2018.1543504
Andreatta, M. & Carmona, S. J. UCell: Robust and scalable single-cell gene signature scoring. Comput. Struct. Biotechnol. J. 19, 3796–3798 (2021).
pubmed: 34285779 pmcid: 8271111 doi: 10.1016/j.csbj.2021.06.043
Aibar, S. et al. SCENIC: single-cell regulatory network inference and clustering. Nat. Methods 14, 1083–1086 (2017).
pubmed: 28991892 pmcid: 5937676 doi: 10.1038/nmeth.4463
Suo, S. et al. Revealing the critical regulators of cell identity in the mouse cell atlas. Cell Rep. 25, 1436–1445.e1433 (2018).
pubmed: 30404000 pmcid: 6281296 doi: 10.1016/j.celrep.2018.10.045
Janky, R. et al. iRegulon: from a gene list to a gene regulatory network using large motif and track collections. PLoS Comput. Biol. 10, e1003731 (2014).
pubmed: 25058159 pmcid: 4109854 doi: 10.1371/journal.pcbi.1003731
Beumer, J. & Clevers, H. Regulation and plasticity of intestinal stem cells during homeostasis and regeneration. Development 143, 3639–3649 (2016).
pubmed: 27802133 doi: 10.1242/dev.133132
de Jong, P. R. et al. ERK5 signalling rescues intestinal epithelial turnover and tumour cell proliferation upon ERK1/2 abrogation. Nat. Commun. 7, 11551 (2016).
pubmed: 27187615 pmcid: 4873670 doi: 10.1038/ncomms11551
Miller, S. A. et al. LSD1 and aberrant DNA methylation mediate persistence of enteroendocrine progenitors that support BRAF-mutant colorectal cancer. Cancer Res. 81, 3791–3805 (2021).
pubmed: 34035083 pmcid: 8513805 doi: 10.1158/0008-5472.CAN-20-3562
Herr, R. et al. B-Raf inhibitors induce epithelial differentiation in BRAF-mutant colorectal cancer cells. Cancer Res. 75, 216–229 (2015).
pubmed: 25381152 doi: 10.1158/0008-5472.CAN-13-3686
Giannakis, M. et al. RNF43 is frequently mutated in colorectal and endometrial cancers. Nat. Genet. 46, 1264–1266 (2014).
pubmed: 25344691 pmcid: 4283570 doi: 10.1038/ng.3127
Borowsky, J. et al. The role of APC in WNT pathway activation in serrated neoplasia. Mod. Pathol. 31, 495–504 (2018).
pubmed: 29148535 doi: 10.1038/modpathol.2017.150
Panarelli, N. C., Vaughn, C. P., Samowitz, W. S. & Yantiss, R. K. Sporadic microsatellite instability-high colon cancers rarely display immunohistochemical evidence of Wnt signaling activation. Am. J. Surg. Pathol. 39, 313–317 (2015).
pubmed: 25602793 doi: 10.1097/PAS.0000000000000380
Yachida, S., Mudali, S., Martin, S. A., Montgomery, E. A. & Iacobuzio-Donahue, C. A. Beta-catenin nuclear labeling is a common feature of sessile serrated adenomas and correlates with early neoplastic progression after BRAF activation. Am. J. Surg. Pathol. 33, 1823–1832 (2009).
pubmed: 19745699 pmcid: 2788075 doi: 10.1097/PAS.0b013e3181b6da19
Cairns, R. A., Harris, I. S. & Mak, T. W. Regulation of cancer cell metabolism. Nat. Rev. Cancer 11, 85–95 (2011).
pubmed: 21258394 doi: 10.1038/nrc2981
Vander Heiden, M. G. et al. Metabolic pathway alterations that support cell proliferation. Cold Spring Harb. Symp. Quant. Biol. 76, 325–334 (2011).
doi: 10.1101/sqb.2012.76.010900
Satoh, K. et al. Global metabolic reprogramming of colorectal cancer occurs at adenoma stage and is induced by MYC. Proc. Natl. Acad. Sci. USA 114, E7697–e7706 (2017).
pubmed: 28847964 pmcid: 5604037 doi: 10.1073/pnas.1710366114
Alaqbi, S. S. et al. Increased mitochondrial proline metabolism sustains proliferation and survival of colorectal cancer cells. PLoS ONE 17, e0262364 (2022).
pubmed: 35130302 pmcid: 8820619 doi: 10.1371/journal.pone.0262364
Alexandrou, C. et al. Sensitivity of colorectal cancer to arginine deprivation therapy is shaped by differential expression of urea cycle enzymes. Sci. Rep. 8, 12096 (2018).
pubmed: 30108309 pmcid: 6092409 doi: 10.1038/s41598-018-30591-7
Ying, Z. et al. The unfolded protein response and cholesterol biosynthesis link luman/CREB3 to regenerative axon growth in sensory neurons. J. Neurosci. 35, 14557–14570 (2015).
pubmed: 26511246 pmcid: 6605466 doi: 10.1523/JNEUROSCI.0012-15.2015
Myers, S. A., Wang, S. C. & Muscat, G. E. The chicken ovalbumin upstream promoter-transcription factors modulate genes and pathways involved in skeletal muscle cell metabolism. J. Biol. Chem. 281, 24149–24160 (2006).
pubmed: 16803904 doi: 10.1074/jbc.M601941200
Rodríguez, J. C., Ortiz, J. A., Hegardt, F. G. & Haro, D. Chicken ovalbumin upstream-promoter transcription factor (COUP-TF) could act as a transcriptional activator or repressor of the mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase gene. Biochem. J. 326, 587–592 (1997).
pubmed: 9291136 pmcid: 1218709 doi: 10.1042/bj3260587
Yamazaki, T. et al. The COUP-TFII variant lacking a DNA-binding domain inhibits the activation of the Cyp7a1 promoter through physical interaction with COUP-TFII. Biochem. J. 452, 345–357 (2013).
pubmed: 23458092 doi: 10.1042/BJ20121200
Vallejo, A. et al. FOSL1 promotes cholangiocarcinoma via transcriptional effectors that could be therapeutically targeted. J. Hepatol. 75, 363–376 (2021).
pubmed: 33887357 doi: 10.1016/j.jhep.2021.03.028
Bardou, M., Barkun, A. & Martel, M. Effect of statin therapy on colorectal cancer. Gut 59, 1572 (2010).
pubmed: 20660702 doi: 10.1136/gut.2009.190900
Jung, Y. S., Park, C. H., Eun, C. S., Park, D. I. & Han, D. S. Statin use and the risk of colorectal adenoma: A meta-analysis. J. Gastroenterol. Hepatol. 31, 1823–1830 (2016).
pubmed: 27043957 doi: 10.1111/jgh.13393
Wei, J. T., Mott, L. A., Baron, J. A. & Sandler, R. S. Reported use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors was not associated with reduced recurrence of colorectal adenomas. Cancer Epidemiol. Biomark. Prev. 14, 1026–1027 (2005).
doi: 10.1158/1055-9965.EPI-03-0080
Lee, J. E. et al. Statin use and colorectal cancer risk according to molecular subtypes in two large prospective cohort studies. Cancer Prev. Res. 4, 1808–1815 (2011).
doi: 10.1158/1940-6207.CAPR-11-0113
Mo, H. & Elson, C. E. Studies of the isoprenoid-mediated inhibition of mevalonate synthesis applied to cancer chemotherapy and chemoprevention. Exp. Biol. Med. 229, 567–585 (2004).
doi: 10.1177/153537020422900701
Wong, W. W., Dimitroulakos, J., Minden, M. D. & Penn, L. Z. HMG-CoA reductase inhibitors and the malignant cell: the statin family of drugs as triggers of tumor-specific apoptosis. Leukemia 16, 508–519 (2002).
pubmed: 11960327 doi: 10.1038/sj.leu.2402476
Kodach, L. L. et al. The effect of statins in colorectal cancer is mediated through the bone morphogenetic protein pathway. Gastroenterology 133, 1272–1281 (2007).
pubmed: 17919499 doi: 10.1053/j.gastro.2007.08.021
Amirkhah, R. et al. MmCMS: mouse models’ consensus molecular subtypes of colorectal cancer. Br. J. Cancer 128, 1333–1343 (2023).
pubmed: 36717674 pmcid: 10050155 doi: 10.1038/s41416-023-02157-6
Ouahoud, S. et al. Statin use is associated with a reduced incidence of colorectal cancer expressing SMAD4. Br. J. Cancer 126, 297–301 (2022).
pubmed: 34703008 doi: 10.1038/s41416-021-01604-6
DeStefano Shields, C. E. et al. Bacterial-driven inflammation and mutant BRAF expression combine to promote murine colon tumorigenesis that is sensitive to immune checkpoint therapy. Cancer Discov. 11, 1792–1807 (2021).
pubmed: 33632774 pmcid: 8295175 doi: 10.1158/2159-8290.CD-20-0770
Andersen, C. L., Jensen, J. L. & Ørntoft, T. F. Normalization of real-time quantitative reverse transcription-PCR data: a model-based variance estimation approach to identify genes suited for normalization, applied to bladder and colon cancer data sets. Cancer Res. 64, 5245–5250 (2004).
pubmed: 15289330 doi: 10.1158/0008-5472.CAN-04-0496
Bustin, S. A. et al. The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. Clin. Chem. 55, 611–622 (2009).
pubmed: 19246619 doi: 10.1373/clinchem.2008.112797
Chen, S., Zhou, Y., Chen, Y. & Gu, J. fastp: an ultra-fast all-in-one FASTQ preprocessor. Bioinformatics 34, i884–i890 (2018).
pubmed: 30423086 pmcid: 6129281 doi: 10.1093/bioinformatics/bty560
Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15–21 (2013).
pubmed: 23104886 doi: 10.1093/bioinformatics/bts635
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
Smedley, D. et al. BioMart—biological queries made easy. BMC Genomics 10, 22 (2009).
pubmed: 19144180 pmcid: 2649164 doi: 10.1186/1471-2164-10-22
Yu, G., Wang, L. G., Han, Y. & He, Q. Y. clusterProfiler: an R package for comparing biological themes among gene clusters. Omics 16, 284–287 (2012).
pubmed: 22455463 pmcid: 3339379 doi: 10.1089/omi.2011.0118
Liberzon, A. et al. The Molecular Signatures Database (MSigDB) hallmark gene set collection. Cell Syst. 1, 417–425 (2015).
pubmed: 26771021 pmcid: 4707969 doi: 10.1016/j.cels.2015.12.004
Gautier, L., Cope, L., Bolstad, B. M. & Irizarry, R. A. affy-analysis of Affymetrix GeneChip data at the probe level. Bioinformatics 20, 307–315 (2004).
pubmed: 14960456 doi: 10.1093/bioinformatics/btg405
Grossman, R. L. et al. Toward a shared vision for cancer genomic data. New Engl. J. Med. 375, 1109–1112 (2016).
pubmed: 27653561 doi: 10.1056/NEJMp1607591
Colaprico, A. et al. TCGAbiolinks: an R/Bioconductor package for integrative analysis of TCGA data. Nucleic Acids Res. 44, e71 (2016).
pubmed: 26704973 doi: 10.1093/nar/gkv1507
Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl. Acad. Sci. USA 102, 15545–15550 (2005).
pubmed: 16199517 pmcid: 1239896 doi: 10.1073/pnas.0506580102
Wolf, F. A., Angerer, P. & Theis, F. J. SCANPY: large-scale single-cell gene expression data analysis. Genome Biol. 19, 15 (2018).
pubmed: 29409532 pmcid: 5802054 doi: 10.1186/s13059-017-1382-0
Reback, J. et al. pandas-dev/pandas: Pandas 1.3.1 (v1.3.1). Zenodo. https://doi.org/10.5281/zenodo.5136416 . (2021).
Stuart, T. et al. Comprehensive integration of single-cell data. Cell 177, 1888–1902.e1821 (2019).
pubmed: 31178118 pmcid: 6687398 doi: 10.1016/j.cell.2019.05.031
Hao, Y. et al. Integrated analysis of multimodal single-cell data. Cell 184, 3573–3587.e3529 (2021).
pubmed: 34062119 pmcid: 8238499 doi: 10.1016/j.cell.2021.04.048
Kassambara A ggpubr: ‘ggplot2’ Based Publication Ready Plots. R package version 0.4.0, https://rpkgs.datanovia.com/ggpubr/ . (2020).
Shannon, P. et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 13, 2498–2504 (2003).
pubmed: 14597658 pmcid: 403769 doi: 10.1101/gr.1239303

Auteurs

Paulina Rzasa (P)

Leicester Cancer Research Centre, University of Leicester, Leicester, UK.

Sarah Whelan (S)

Leicester Cancer Research Centre, University of Leicester, Leicester, UK.

Pooyeh Farahmand (P)

Leicester Cancer Research Centre, University of Leicester, Leicester, UK.

Hong Cai (H)

Leicester Cancer Research Centre, University of Leicester, Leicester, UK.

Inna Guterman (I)

Leicester Cancer Research Centre, University of Leicester, Leicester, UK.

Raquel Palacios-Gallego (R)

Leicester Cancer Research Centre, University of Leicester, Leicester, UK.

Shanthi S Undru (SS)

Leicester Cancer Research Centre, University of Leicester, Leicester, UK.

Lauren Sandford (L)

Leicester Cancer Research Centre, University of Leicester, Leicester, UK.
Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.

Caleb Green (C)

Leicester Cancer Research Centre, University of Leicester, Leicester, UK.

Catherine Andreadi (C)

Leicester Cancer Research Centre, University of Leicester, Leicester, UK.

Maria Mintseva (M)

Leicester Cancer Research Centre, University of Leicester, Leicester, UK.
Area of Neuroscience, International School for Advanced Studies (SISSA), Trieste, Italy.

Emma Parrott (E)

Leicester Cancer Research Centre, University of Leicester, Leicester, UK.

Hong Jin (H)

Leicester Cancer Research Centre, University of Leicester, Leicester, UK.

Fiona Hey (F)

Leicester Cancer Research Centre, University of Leicester, Leicester, UK.

Susan Giblett (S)

Leicester Cancer Research Centre, University of Leicester, Leicester, UK.

Nicolas B Sylvius (NB)

NUCLEUS Genomics, Core Biotechnology Services, University of Leicester, Leicester, UK.

Natalie S Allcock (NS)

University of Leicester Core Biotechnology Services Electron Microscopy Facility, Leicester, UK.

Anna Straatman-Iwanowska (A)

University of Leicester Core Biotechnology Services Electron Microscopy Facility, Leicester, UK.

Roberto Feuda (R)

Department of Genetics and Genome Biology, University of Leicester, Leicester, UK.

Cristina Tufarelli (C)

Leicester Cancer Research Centre, University of Leicester, Leicester, UK.

Karen Brown (K)

Leicester Cancer Research Centre, University of Leicester, Leicester, UK.

Catrin Pritchard (C)

Leicester Cancer Research Centre, University of Leicester, Leicester, UK.

Alessandro Rufini (A)

Leicester Cancer Research Centre, University of Leicester, Leicester, UK. Alessandro.Rufini@unimi.it.
Dipartimento di Bioscienze, University of Milan, Milan, Italy. Alessandro.Rufini@unimi.it.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH