{"entity": "journal", "iuid": "ee83acb267174fd8a1e7bff41835d17b", "timestamp": "2026-07-19T18:34:52.980Z", "links": {"self": {"href": "https://publications.scilifelab.se/journal/Ann.%20Oncol..json"}, "display": {"href": "https://publications.scilifelab.se/journal/Ann.%20Oncol."}}, "title": "Ann. Oncol.", "issn": "1569-8041", "issn-l": "0923-7534", "publications_count": 2, "publications": [{"entity": "publication", "iuid": "a1d03fcc7fa3461e9650387c7304fbdc", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a1d03fcc7fa3461e9650387c7304fbdc.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a1d03fcc7fa3461e9650387c7304fbdc"}}, "title": "Improved breast cancer histological grading using deep learning.", "authors": [{"family": "Wang", "given": "Y", "initials": "Y"}, {"family": "Acs", "given": "B", "initials": "B"}, {"family": "Robertson", "given": "S", "initials": "S"}, {"family": "Liu", "given": "B", "initials": "B"}, {"family": "Solorzano", "given": "L", "initials": "L"}, {"family": "W\u00e4hlby", "given": "C", "initials": "C"}, {"family": "Hartman", "given": "J", "initials": "J"}, {"family": "Rantalainen", "given": "M", "initials": "M"}], "type": "journal article", "published": "2022-01-00", "journal": {"title": "Ann. Oncol.", "issn": "1569-8041", "issn-l": "0923-7534", "volume": "33", "issue": "1", "pages": "89-98"}, "abstract": "The Nottingham histological grade (NHG) is a well-established prognostic factor for breast cancer that is broadly used in clinical decision making. However, \u223c50% of patients are classified as grade 2, an intermediate risk group with low clinical value. To improve risk stratification of NHG 2 breast cancer patients, we developed and validated a novel histological grade model (DeepGrade) based on digital whole-slide histopathology images (WSIs) and deep learning.\n\nIn this observational retrospective study, routine WSIs stained with haematoxylin and eosin from 1567 patients were utilised for model optimisation and validation. Model generalisability was further evaluated in an external test set with 1262 patients. NHG 2 cases were stratified into two groups, DG2-high and DG2-low, and the prognostic value was assessed. The main outcome was recurrence-free survival.\n\nDeepGrade provides independent prognostic information for stratification of NHG 2 cases in the internal test set, where DG2-high showed an increased risk for recurrence (hazard ratio [HR] 2.94, 95% confidence interval [CI] 1.24-6.97, P = 0.015) compared with the DG2-low group after adjusting for established risk factors (independent test data). DG2-low also shared phenotypic similarities with NHG 1, and DG2-high with NHG 3, suggesting that the model identifies morphological patterns in NHG 2 that are associated with more aggressive tumours. The prognostic value of DeepGrade was further assessed in the external test set, confirming an increased risk for recurrence in DG2-high (HR 1.91, 95% CI 1.11-3.29, P = 0.019).\n\nThe proposed model-based stratification of patients with NHG 2 tumours is prognostic and adds clinically relevant information over routine histological grading. The methodology offers a cost-effective alternative to molecular profiling to extract information relevant for clinical decisions.", "doi": "10.1016/j.annonc.2021.09.007", "pmid": "34756513", "labels": {"BioImage Informatics": "Collaborative", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S0923-7534(21)04486-0"}], "notes": [], "created": "2022-11-02T06:22:59.287Z", "modified": "2024-01-16T13:48:37.913Z"}, {"entity": "publication", "iuid": "f0189e06f40849b6aa396efe9d60aad1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f0189e06f40849b6aa396efe9d60aad1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f0189e06f40849b6aa396efe9d60aad1"}}, "title": "Validation and development of MTH1 inhibitors for treatment of cancer.", "authors": [{"family": "Warpman Berglund", "given": "U", "initials": "U"}, {"family": "Sanjiv", "given": "K", "initials": "K"}, {"family": "Gad", "given": "H", "initials": "H"}, {"family": "Kalder\u00e9n", "given": "C", "initials": "C"}, {"family": "Koolmeister", "given": "T", "initials": "T"}, {"family": "Pham", "given": "T", "initials": "T"}, {"family": "Gokturk", "given": "C", "initials": "C"}, {"family": "Jafari", "given": "R", "initials": "R"}, {"family": "Maddalo", "given": "G", "initials": "G"}, {"family": "Seashore-Ludlow", "given": "B", "initials": "B"}, {"family": "Chernobrovkin", "given": "A", "initials": "A"}, {"family": "Manoilov", "given": "A", "initials": "A"}, {"family": "Pateras", "given": "I S", "initials": "IS"}, {"family": "Rasti", "given": "A", "initials": "A"}, {"family": "Jemth", "given": "A-S", "initials": "AS"}, {"family": "Alml\u00f6f", "given": "I", "initials": "I"}, {"family": "Loseva", "given": "O", "initials": "O"}, {"family": "Visnes", "given": "T", "initials": "T"}, {"family": "Einarsdottir", "given": "B O", "initials": "BO"}, {"family": "Gaugaz", "given": "F Z", "initials": "FZ"}, {"family": "Saleh", "given": "A", "initials": "A"}, {"family": "Platzack", "given": "B", "initials": "B"}, {"family": "Wallner", "given": "O A", "initials": "OA"}, {"family": "Vallin", "given": "K S A", "initials": "KS"}, {"family": "Henriksson", "given": "M", "initials": "M"}, {"family": "Wakchaure", "given": "P", "initials": "P"}, {"family": "Borhade", "given": "S", "initials": "S"}, {"family": "Herr", "given": "P", "initials": "P"}, {"family": "Kallberg", "given": "Y", "initials": "Y"}, {"family": "Baranczewski", "given": "P", "initials": "P"}, {"family": "Homan", "given": "E J", "initials": "EJ"}, {"family": "Wiita", "given": "E", "initials": "E"}, {"family": "Nagpal", "given": "V", "initials": "V"}, {"family": "Meijer", "given": "T", "initials": "T"}, {"family": "Schipper", "given": "N", "initials": "N"}, {"family": "Rudd", "given": "S G", "initials": "SG"}, {"family": "Br\u00e4utigam", "given": "L", "initials": "L"}, {"family": "Lindqvist", "given": "A", "initials": "A"}, {"family": "Filppula", "given": "A", "initials": "A"}, {"family": "Lee", "given": "T-C", "initials": "TC"}, {"family": "Artursson", "given": "P", "initials": "P"}, {"family": "Nilsson", "given": "J A", "initials": "JA"}, {"family": "Gorgoulis", "given": "V G", "initials": "VG"}, {"family": "Lehti\u00f6", "given": "J", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Zubarev", "given": "R A", "initials": "RA", "orcid": "0000-0001-9839-2089", "researcher": {"href": "https://publications.scilifelab.se/researcher/e971b9cdec2b4411934f9c5d535da8b4.json"}}, {"family": "Scobie", "given": "M", "initials": "M"}, {"family": "Helleday", "given": "T", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d7256c271ea4adea404d4ff355f804e.json"}}], "type": "journal article", "published": "2016-12-00", "journal": {"volume": "27", "issn": "1569-8041", "issue": "12", "pages": "2275-2283", "title": "Ann. Oncol.", "issn-l": "0923-7534"}, "abstract": "Previously, we showed cancer cells rely on the MTH1 protein to prevent incorporation of otherwise deadly oxidised nucleotides into DNA and we developed MTH1 inhibitors which selectively kill cancer cells. Recently, several new and potent inhibitors of MTH1 were demonstrated to be non-toxic to cancer cells, challenging the utility of MTH1 inhibition as a target for cancer treatment.\n\nHuman cancer cell lines were exposed in vitro to MTH1 inhibitors or depleted of MTH1 by siRNA or shRNA. 8-oxodG was measured by immunostaining and modified comet assay. Thermal Proteome profiling, proteomics, cellular thermal shift assays, kinase and CEREP panel were used for target engagement, mode of action and selectivity investigations of MTH1 inhibitors. Effect of MTH1 inhibition on tumour growth was explored in BRAF V600E-mutated malignant melanoma patient derived xenograft and human colon cancer SW480 and HCT116 xenograft models.\n\nHere, we demonstrate that recently described MTH1 inhibitors, which fail to kill cancer cells, also fail to introduce the toxic oxidized nucleotides into DNA. We also describe a new MTH1 inhibitor TH1579, (Karonudib), an analogue of TH588, which is a potent, selective MTH1 inhibitor with good oral availability and demonstrates excellent pharmacokinetic and anti-cancer properties in vivo.\n\nWe demonstrate that in order to kill cancer cells MTH1 inhibitors must also introduce oxidized nucleotides into DNA. Furthermore, we describe TH1579 as a best-in-class MTH1 inhibitor, which we expect to be useful in order to further validate the MTH1 inhibitor concept.", "doi": "10.1093/annonc/mdw429", "pmid": "27827301", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Clinical Proteomics Mass spectrometry": "Collaborative", "Chemical Proteomics": "Service", "Advanced Mass Spectrometry Proteomics": "Collaborative", "Bioinformatics Support and Infrastructure": "Collaborative", "Bioinformatics (NBIS)": "Collaborative", "Chemical Biology Consortium Sweden": "Collaborative", "Drug Discovery and Development": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S0923-7534(19)36552-4"}], "notes": "Laboratories for Chemical Biology at Karolinska Institutet (LCBKI)\r\nADME of Therapeutics (UDOPP)", "created": "2017-05-03T12:58:49.192Z", "modified": "2025-10-17T13:05:09.110Z"}], "created": "2017-05-09T09:12:08.941Z", "modified": "2020-11-27T13:14:05.679Z"}