{"entity": "label", "iuid": "f1d5497e2f0e4521befaca471f0a8da7", "timestamp": "2026-08-10T20:46:49.628Z", "links": {"self": {"href": "https://publications.scilifelab.se/label/Array%20and%20Analysis%20Facility.json"}, "display": {"href": "https://publications.scilifelab.se/label/Array%20and%20Analysis%20Facility"}}, "value": "Array and Analysis Facility", "started": "2013", "ended": "2016", "created": "2017-05-02T12:09:57.843Z", "modified": "2021-03-15T14:12:31.107Z", "accounts": [{"entity": "account", "iuid": "32a436398938412b93e7ddcef018c708", "timestamp": "2026-08-10T20:46:49.628Z", "links": {"self": {"href": "https://publications.scilifelab.se/account/christopher.erdmann%40scilifelab.uu.se.json"}, "display": {"href": "https://publications.scilifelab.se/account/christopher.erdmann%40scilifelab.uu.se"}}, "email": "christopher.erdmann@scilifelab.uu.se", "name": "Christopher Erdmann", "orcid": "", "role": "curator", "status": "enabled", "login": "2024-08-16T11:56:57.787Z", "created": "2024-08-16T10:01:32.844Z", "modified": "2025-10-17T13:05:06.782Z"}, {"entity": "account", "iuid": "6a38350bd21f4fb6aeeb1530037a99ae", "timestamp": "2026-08-10T20:46:49.628Z", "links": {"self": {"href": "https://publications.scilifelab.se/account/sune.joubert%40scilifelab.uu.se.json"}, "display": {"href": "https://publications.scilifelab.se/account/sune.joubert%40scilifelab.uu.se"}}, "email": "sune.joubert@scilifelab.uu.se", "name": "Sun\u00e9 Joubert", "orcid": "", "role": "curator", "status": "enabled", "login": "2025-10-31T11:15:37.113Z", "created": "2024-08-16T10:01:02.800Z", "modified": "2025-10-31T11:15:37.113Z"}, {"entity": "account", "iuid": "f434f83e33fc45efb3ec0fe30d3e4304", "timestamp": "2026-08-10T20:46:49.628Z", "links": {"self": {"href": "https://publications.scilifelab.se/account/anders.isaksson%40medsci.uu.se.json"}, "display": {"href": "https://publications.scilifelab.se/account/anders.isaksson%40medsci.uu.se"}}, "email": "anders.isaksson@medsci.uu.se", "name": "Anders Isaksson", "orcid": null, "role": "curator", "status": "enabled", "login": null, "created": "2017-05-02T12:10:05.431Z", "modified": "2017-09-18T14:37:19.705Z"}], "publications_count": 67, "publications": [{"entity": "publication", "iuid": "020698099138404ebd24dce553bc56f3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/020698099138404ebd24dce553bc56f3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/020698099138404ebd24dce553bc56f3"}}, "title": "Rawcopy: Improved copy number analysis with Affymetrix arrays.", "authors": [{"family": "Mayrhofer", "given": "Markus", "initials": "M"}, {"family": "Viklund", "given": "Bj\u00f6rn", "initials": "B"}, {"family": "Isaksson", "given": "Anders", "initials": "A"}], "type": "journal article", "published": "2016-10-31", "journal": {"volume": "6", "issn": "2045-2322", "issue": null, "pages": "36158", "title": "Sci Rep", "issn-l": "2045-2322"}, "abstract": "Microarray data is subject to noise and systematic variation that negatively affects the resolution of copy number analysis. We describe Rawcopy, an R package for processing of Affymetrix CytoScan HD, CytoScan 750k and SNP 6.0 microarray raw intensities (CEL files). Noise characteristics of a large number of reference samples are used to estimate log ratio and B-allele frequency for total and allele-specific copy number analysis. Rawcopy achieves better signal-to-noise ratio and higher proportion of validated alterations than commonly used free and proprietary alternatives. In addition, Rawcopy visualizes each microarray sample for assessment of technical quality, patient identity and genome-wide absolute copy number states. Software and instructions are available at http://rawcopy.org.", "doi": "10.1038/srep36158", "pmid": "27796336", "labels": {"Array and Analysis Facility": "Technology development"}, "xrefs": [{"db": "pii", "key": "srep36158"}, {"db": "pmc", "key": "PMC5086940"}], "notes": [], "created": "2017-05-03T13:02:27.306Z", "modified": "2017-06-12T11:40:00.216Z"}, {"entity": "publication", "iuid": "8a3bf6eb1cc84d44b23e9ab88370932e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8a3bf6eb1cc84d44b23e9ab88370932e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8a3bf6eb1cc84d44b23e9ab88370932e"}}, "title": "Targeting Serglycin Prevents Metastasis in Murine Mammary Carcinoma.", "authors": [{"family": "Roy", "given": "Ananya", "initials": "A"}, {"family": "Femel", "given": "Julia", "initials": "J"}, {"family": "Huijbers", "given": "Elisabeth J M", "initials": "EJ"}, {"family": "Spillmann", "given": "Dorothe", "initials": "D"}, {"family": "Larsson", "given": "Erik", "initials": "E"}, {"family": "Ringvall", "given": "Maria", "initials": "M"}, {"family": "Olsson", "given": "Anna-Karin", "initials": "AK"}, {"family": "\u00c5brink", "given": "Magnus", "initials": "M"}], "type": "journal article", "published": "2016-05-25", "journal": {"volume": "11", "issn": "1932-6203", "issue": "5", "pages": "e0156151", "title": "PLoS ONE", "issn-l": "1932-6203"}, "abstract": "In hematopoietic cells, serglycin proteoglycans mainly contribute to proper storage and secretion of inflammatory mediators via their negatively charged glycosaminoglycans. Serglycin proteoglycans are also expressed in cancer cells where increased expression has been linked to poor prognosis. However, the serglycin-dependent mediators promoting cancer progression remain to be determined. In the present study we report that genetic ablation of serglycin proteoglycan completely blocks lung metastasis in the MMTV-PyMT-driven mouse breast cancer model, while serglycin-deficiency did not affect primary tumour growth or number of mammary tumours. Although E-cadherin expression was higher in the serglycin-deficient primary tumour tissue, indicating reduced invasiveness, serglycin-deficient tumour cells were still detected in the circulation. These data suggest that serglycin proteoglycans play a role in extravasation as well as colonization and growth of metastatic cells. A microarray expression analysis and functional annotation of differentially expressed genes identified several biological pathways where serglycin may be important. Our results suggest that serglycin and serglycin-dependent mediators are potential drug targets to prevent metastatic disease/dissemination of cancer.", "doi": "10.1371/journal.pone.0156151", "pmid": "27223472", "labels": {"Array and Analysis Facility": "Service"}, "xrefs": [{"db": "pii", "key": "PONE-D-16-04737"}, {"db": "pmc", "key": "PMC4880347"}, {"db": "GEO", "description": "expression data", "key": "GSE67806"}], "notes": [], "created": "2017-05-03T13:02:27.894Z", "modified": "2021-05-31T17:46:24.942Z"}, {"entity": "publication", "iuid": "2710fb21e358486694f046d63f8bb25b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2710fb21e358486694f046d63f8bb25b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2710fb21e358486694f046d63f8bb25b"}}, "title": "Using an Inbred Horse Breed in a High Density Genome-Wide Scan for Genetic Risk Factors of Insect Bite Hypersensitivity (IBH).", "authors": [{"family": "Velie", "given": "Brandon D", "initials": "BD"}, {"family": "Shrestha", "given": "Merina", "initials": "M"}, {"family": "Fran\u04abois", "given": "Liesbeth", "initials": "L"}, {"family": "Schurink", "given": "Anouk", "initials": "A"}, {"family": "Tesfayonas", "given": "Yohannes G", "initials": "YG"}, {"family": "Stinckens", "given": "Anneleen", "initials": "A"}, {"family": "Blott", "given": "Sarah", "initials": "S"}, {"family": "Ducro", "given": "Bart J", "initials": "BJ"}, {"family": "Mikko", "given": "Sofia", "initials": "S"}, {"family": "Thomas", "given": "Ruth", "initials": "R"}, {"family": "Swinburne", "given": "June E", "initials": "JE"}, {"family": "Sundqvist", "given": "Marie", "initials": "M"}, {"family": "Eriksson", "given": "Susanne", "initials": "S"}, {"family": "Buys", "given": "Nadine", "initials": "N"}, {"family": "Lindgren", "given": "Gabriella", "initials": "G"}], "type": "journal article", "published": "2016-04-12", "journal": {"volume": "11", "issn": "1932-6203", "issue": "4", "pages": "e0152966", "title": "PLoS ONE", "issn-l": "1932-6203"}, "abstract": "While susceptibility to hypersensitive reactions is a common problem amongst humans and animals alike, the population structure of certain animal species and breeds provides a more advantageous route to better understanding the biology underpinning these conditions. The current study uses Exmoor ponies, a highly inbred breed of horse known to frequently suffer from insect bite hypersensitivity, to identify genomic regions associated with a type I and type IV hypersensitive reaction. A total of 110 cases and 170 controls were genotyped on the 670K Axiom Equine Genotyping Array. Quality control resulted in 452,457 SNPs and 268 individuals being tested for association. Genome-wide association analyses were performed using the GenABEL package in R and resulted in the identification of two regions of interest on Chromosome 8. The first region contained the most significant SNP identified, which was located in an intron of the DCC netrin 1 receptor gene. The second region identified contained multiple top SNPs and encompassed the PIGN, KIAA1468, TNFRSF11A, ZCCHC2, and PHLPP1 genes. Although additional studies will be needed to validate the importance of these regions in horses and the relevance of these regions in other species, the knowledge gained from the current study has the potential to be a step forward in unraveling the complex nature of hypersensitive reactions.", "doi": "10.1371/journal.pone.0152966", "pmid": "27070818", "labels": {"Array and Analysis Facility": "Service"}, "xrefs": [{"db": "pii", "key": "PONE-D-15-46048"}, {"db": "pmc", "key": "PMC4829256"}], "notes": [], "created": "2017-05-03T13:02:27.600Z", "modified": "2017-06-12T11:40:00.392Z"}, {"entity": "publication", "iuid": "a269c8a8febc4ef3bb024f2c0f38b1b3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a269c8a8febc4ef3bb024f2c0f38b1b3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a269c8a8febc4ef3bb024f2c0f38b1b3"}}, "title": "Genetic heterogeneity in rhabdomyosarcoma revealed by SNP array analysis.", "authors": [{"family": "Walther", "given": "Charles", "initials": "C"}, {"family": "Mayrhofer", "given": "Markus", "initials": "M"}, {"family": "Nilsson", "given": "Jenny", "initials": "J"}, {"family": "Hofvander", "given": "Jakob", "initials": "J"}, {"family": "Jonson", "given": "Tord", "initials": "T"}, {"family": "Mandahl", "given": "Nils", "initials": "N"}, {"family": "\u00d8ra", "given": "Ingrid", "initials": "I"}, {"family": "Gisselsson", "given": "David", "initials": "D"}, {"family": "Mertens", "given": "Fredrik", "initials": "F"}], "type": "journal article", "published": "2016-01-00", "journal": {"volume": "55", "issn": "1098-2264", "issue": "1", "pages": "3-15", "title": "Genes Chromosomes Cancer", "issn-l": "1045-2257"}, "abstract": "Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and adolescents. Alveolar (ARMS) and embryonal (ERMS) histologies predominate, but rare cases are classified as spindle cell/sclerosing (SRMS). For treatment stratification, RMS is further subclassified as fusion-positive (FP-RMS) or fusion-negative (FN-RMS), depending on whether a gene fusion involving PAX3 or PAX7 is present or not. We investigated 19 cases of pediatric RMS using high resolution single-nucleotide polymorphism (SNP) array. FP-ARMS displayed, on average, more structural rearrangements than ERMS; the single FN-ARMS had a genomic profile similar to ERMS. Apart from previously known amplification (e.g., MYCN, CDK4, and MIR17HG) and deletion (e.g., NF1, CDKN2A, and CDKN2B) targets, amplification of ERBB2 and homozygous loss of ASCC3 or ODZ3 were seen. Combining SNP array with cytogenetic data revealed that most cases were polyploid, with at least one case having started as a near-haploid tumor. Further bioinformatic analysis of the SNP array data disclosed genetic heterogeneity, in the form of subclonal chromosomal imbalances, in five tumors. The outcome was worse for patients with FP-ARMS than ERMS or FN-ARMS (6/8 vs. 1/9 dead of disease), and the only children with ERMS showing intratumor diversity or with MYOD1 mutation-positive SRMS also died of disease. High resolution SNP array can be useful in evaluating genomic imbalances in pediatric RMS.", "doi": "10.1002/gcc.22285", "pmid": "26482321", "labels": {"Array and Analysis Facility": "Collaborative"}, "xrefs": [], "notes": [], "created": "2017-05-02T12:56:43.514Z", "modified": "2017-06-12T11:40:00.040Z"}, {"entity": "publication", "iuid": "9148bf43cc3648498a3e47f7a0d49a79", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9148bf43cc3648498a3e47f7a0d49a79.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9148bf43cc3648498a3e47f7a0d49a79"}}, "title": "Spatiotemporal Heterogeneity Characterizes the Genetic Landscape of Pheochromocytoma and Defines Early Events in Tumorigenesis.", "authors": [{"family": "Crona", "given": "Joakim", "initials": "J"}, {"family": "Backman", "given": "Samuel", "initials": "S"}, {"family": "Maharjan", "given": "Rajani", "initials": "R"}, {"family": "Mayrhofer", "given": "Markus", "initials": "M"}, {"family": "St\u00e5lberg", "given": "Peter", "initials": "P"}, {"family": "Isaksson", "given": "Anders", "initials": "A"}, {"family": "Hellman", "given": "Per", "initials": "P"}, {"family": "Bj\u00f6rklund", "given": "Peyman", "initials": "P"}], "type": "journal article", "published": "2015-10-01", "journal": {"volume": "21", "issn": "1078-0432", "issue": "19", "pages": "4451-4460", "title": "Clin. Cancer Res.", "issn-l": null}, "abstract": "Pheochromocytoma and paraganglioma (PPGL) patients display heterogeneity in the clinical presentation and underlying genetic cause. The degree of inter- and intratumor genetic heterogeneity has not yet been defined.\n\nIn PPGLs from 94 patients, we analyzed LOH, copy-number variations, and mutation status of SDHA, SDHB, SDHC, SDHD, SDHAF2, VHL, EPAS1, NF1, RET, TMEM127, MAX, and HRAS using high-density SNP array and targeted deep sequencing, respectively. Genetic heterogeneity was determined through (i) bioinformatics analysis of individual samples that estimated absolute purity and ploidy from SNP array data and (ii) comparison of paired tumor samples that allowed reconstruction of phylogenetic trees.\n\nMutations were found in 61% of the tumors and correlated with specific patterns of somatic copy-number aberrations (SCNA) and degree of nontumoral cell admixture. Intratumor genetic heterogeneity was observed in 74 of 136 samples using absolute bioinformatics estimations and in 22 of 24 patients by comparison of paired samples. In addition, a low genetic concordance was observed between paired primary tumors and distant metastases. This allowed for reconstructing the life history of individual tumors, identifying somatic mutations as well as copy-number loss of 3p and 11p (VHL subgroup), 1p (Cluster 2), and 17q (NF1 subgroup) as early events in PPGL tumorigenesis.\n\nGenomic landscapes of PPGL are specific to mutation subtype and characterized by genetic heterogeneity both within and between tumor lesions of the same patient.", "doi": "10.1158/1078-0432.CCR-14-2854", "pmid": "25991818", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (SNP&SEQ Technology Platform)": null, "Array and Analysis Facility": null}, "xrefs": [{"db": "pii", "key": "1078-0432.CCR-14-2854"}], "notes": [], "created": "2017-05-02T12:56:47.110Z", "modified": "2020-01-21T13:56:03.728Z"}, {"entity": "publication", "iuid": "d0e54a569ab84188ab4031c834342766", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d0e54a569ab84188ab4031c834342766.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d0e54a569ab84188ab4031c834342766"}}, "title": "The use of gene arrays and corresponding connectivity mapping (Cmap) to identify novel anti-ageing ingredients.", "authors": [{"family": "Gillbro", "given": "J M", "initials": "JM"}, {"family": "Merinville", "given": "E", "initials": "E"}, {"family": "Olsson", "given": "M", "initials": "M"}, {"family": "Al-Bader", "given": "T", "initials": "T"}, {"family": "Klack", "given": "A", "initials": "A"}, {"family": "Visdal-Johnsen", "given": "L", "initials": "L"}, {"family": "Mavon", "given": "A", "initials": "A"}], "type": "journal article", "published": "2015-10-00", "journal": {"volume": "37 Suppl 1", "issn": "1468-2494", "issue": null, "pages": "9-14", "title": "Int J Cosmet Sci", "issn-l": "0142-5463"}, "abstract": "The need for effective 'anti-ageing' treatments, in particular for the management of photodamaged skin, prompted us to develop a novel method to identify new active ingredients. The model utilized a gene profiling study with corresponding connectivity mapping (Cmap) to identify novel anti-ageing compounds using all-trans retinoic acid (RA) as the lead compound due to its beneficial effect on photodamaged skin and skin firmness.\n\nA vehicle-controlled clinical study including nine healthy Caucasian female volunteers aged 57 \u00b1 7 (mean \u00b1 SEM) exhibiting photodamage on their lower outer forearms was conducted. The volunteers applied RA once daily on photodamaged skin for 7 days, and biopsies were subjected to Affymetrix gene arrays. Connectivity mapping (Cmap), examining hundreds of gene expression profiles, was run on the gene signature of RA-treated photodamaged skin to identify small bioactive compounds.\n\nAffymetrix gene array identified 19 genes significantly differentially expressed after application of RA. Corresponding Cmap analysis revealed six natural bioactive compounds including N-acetyl aspartic acid (A-A-A) showing similar activity to RA on the differentially expressed genes identified.\n\nBased on RA mimicking gene array activity, potential use within skincare on molecular size, safety assessment and sourcing, we identified the natural amino acid, A-A-A as a potential candidate to treat ageing skin.", "doi": "10.1111/ics.12251", "pmid": "26112986", "labels": {"Array and Analysis Facility": null}, "xrefs": [], "notes": [], "created": "2017-05-02T12:57:05.798Z", "modified": "2017-05-30T13:05:34.078Z"}, {"entity": "publication", "iuid": "15e72e306a9c420c8af6af87708211d3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/15e72e306a9c420c8af6af87708211d3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/15e72e306a9c420c8af6af87708211d3"}}, "title": "The Human Glioblastoma Cell Culture Resource: Validated Cell Models Representing All Molecular Subtypes.", "authors": [{"family": "Xie", "given": "Yuan", "initials": "Y"}, {"family": "Bergstr\u00f6m", "given": "Tobias", "initials": "T"}, {"family": "Jiang", "given": "Yiwen", "initials": "Y"}, {"family": "Johansson", "given": "Patrik", "initials": "P"}, {"family": "Marinescu", "given": "Voichita Dana", "initials": "VD"}, {"family": "Lindberg", "given": "Nanna", "initials": "N"}, {"family": "Segerman", "given": "Anna", "initials": "A"}, {"family": "Wicher", "given": "Grzegorz", "initials": "G"}, {"family": "Niklasson", "given": "Mia", "initials": "M"}, {"family": "Baskaran", "given": "Sathishkumar", "initials": "S"}, {"family": "Sreedharan", "given": "Smitha", "initials": "S"}, {"family": "Everlien", "given": "Isabelle", "initials": "I"}, {"family": "Kastemar", "given": "Marianne", "initials": "M"}, {"family": "Hermansson", "given": "Annika", "initials": "A"}, {"family": "Elfineh", "given": "Lioudmila", "initials": "L"}, {"family": "Libard", "given": "Sylwia", "initials": "S"}, {"family": "Holland", "given": "Eric Charles", "initials": "EC"}, {"family": "Hesselager", "given": "G\u00f6ran", "initials": "G"}, {"family": "Alafuzoff", "given": "Irina", "initials": "I"}, {"family": "Westermark", "given": "Bengt", "initials": "B"}, {"family": "Nelander", "given": "Sven", "initials": "S"}, {"family": "Forsberg-Nilsson", "given": "Karin", "initials": "K"}, {"family": "Uhrbom", "given": "Lene", "initials": "L"}], "type": "journal article", "published": "2015-10-00", "journal": {"volume": "2", "issn": "2352-3964", "issue": "10", "pages": "1351-1363", "title": "EBioMedicine", "issn-l": "2352-3964"}, "abstract": "Glioblastoma (GBM) is the most frequent and malignant form of primary brain tumor. GBM is essentially incurable and its resistance to therapy is attributed to a subpopulation of cells called glioma stem cells (GSCs). To meet the present shortage of relevant GBM cell (GC) lines we developed a library of annotated and validated cell lines derived from surgical samples of GBM patients, maintained under conditions to preserve GSC characteristics. This collection, which we call the Human Glioblastoma Cell Culture (HGCC) resource, consists of a biobank of 48 GC lines and an associated database containing high-resolution molecular data. We demonstrate that the HGCC lines are tumorigenic, harbor genomic lesions characteristic of GBMs, and represent all four transcriptional subtypes. The HGCC panel provides an open resource for in vitro and in vivo modeling of a large part of GBM diversity useful to both basic and translational GBM research.", "doi": "10.1016/j.ebiom.2015.08.026", "pmid": "26629530", "labels": {"Array and Analysis Facility": null}, "xrefs": [{"db": "pii", "key": "S2352-3964(15)30114-6"}, {"db": "pmc", "key": "PMC4634360"}], "notes": [], "created": "2017-05-02T12:58:58.734Z", "modified": "2017-05-31T07:53:20.950Z"}, {"entity": "publication", "iuid": "b330e96a7bf449b5b90c242a27d27e3f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b330e96a7bf449b5b90c242a27d27e3f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b330e96a7bf449b5b90c242a27d27e3f"}}, "title": "Distinguishing Mast Cell Progenitors from Mature Mast Cells in Mice.", "authors": [{"family": "Dahlin", "given": "Joakim S", "initials": "JS"}, {"family": "Ding", "given": "Zhoujie", "initials": "Z"}, {"family": "Hallgren", "given": "Jenny", "initials": "J"}], "type": "journal article", "published": "2015-07-15", "journal": {"volume": "24", "issn": "1557-8534", "issue": "14", "pages": "1703-1711", "title": "Stem Cells Dev.", "issn-l": "1547-3287"}, "abstract": "Mast cells originate from the bone marrow and develop into c-kit(+) Fc\u025bRI(+) cells. Both mast cell progenitors (MCp) and mature mast cells express these cell surface markers, and ways validated to distinguish between the two maturation forms with flow cytometry have been lacking. Here, we show that primary peritoneal MCp from na\u00efve mice expressed high levels of integrin \u03b27 and had a low side scatter (SSC) light profile; whereas mature mast cells expressed lower levels of integrin \u03b27 and had a high SSC light profile. The maturation statuses of the cells were confirmed using three main strategies: (1) MCp, but not mature mast cells, were shown to be depleted by sublethal whole-body \u03b3-irradiation. (2) The MCp were small and immature in terms of granule formation, whereas the mature mast cells were larger and had fully developed metachromatic granules. (3) The MCp had fewer transcripts of mast cell-specific proteases and the enzyme responsible for sulfation of heparin than mature mast cells. Moreover, isolated peritoneal MCp gave rise to mast cells when cultured in vitro. To summarize, we have defined MCp and mature mast cells in na\u00efve mice by flow cytometry. Using this strategy, mast cell maturation can be studied in vivo.", "doi": "10.1089/scd.2014.0553", "pmid": "25744159", "labels": {"Array and Analysis Facility": null}, "xrefs": [{"db": "pmc", "key": "PMC4499794"}], "notes": [], "created": "2017-05-02T12:56:48.296Z", "modified": "2017-05-30T13:02:11.571Z"}, {"entity": "publication", "iuid": "1ccd294dde83454aac3f82a1398af6d8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1ccd294dde83454aac3f82a1398af6d8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1ccd294dde83454aac3f82a1398af6d8"}}, "title": "Functional loss of I\u03baB\u03b5 leads to NF-\u03baB deregulation in aggressive chronic lymphocytic leukemia.", "authors": [{"family": "Mansouri", "given": "Larry", "initials": "L"}, {"family": "Sutton", "given": "Lesley-Ann", "initials": "LA"}, {"family": "Ljungstr\u00f6m", "given": "Viktor", "initials": "V"}, {"family": "Bondza", "given": "Sina", "initials": "S"}, {"family": "Arng\u00e5rden", "given": "Linda", "initials": "L"}, {"family": "Bhoi", "given": "Sujata", "initials": "S"}, {"family": "Larsson", "given": "Jimmy", "initials": "J"}, {"family": "Cortese", "given": "Diego", "initials": "D"}, {"family": "Kalushkova", "given": "Antonia", "initials": "A"}, {"family": "Plevova", "given": "Karla", "initials": "K"}, {"family": "Young", "given": "Emma", "initials": "E"}, {"family": "Gunnarsson", "given": "Rebeqa", "initials": "R"}, {"family": "Falk-S\u00f6rqvist", "given": "Elin", "initials": "E"}, {"family": "L\u00f6nn", "given": "Peter", "initials": "P"}, {"family": "Muggen", "given": "Alice F", "initials": "AF"}, {"family": "Yan", "given": "Xiao-Jie", "initials": "XJ"}, {"family": "Sander", "given": "Birgitta", "initials": "B"}, {"family": "Enblad", "given": "Gunilla", "initials": "G"}, {"family": "Smedby", "given": "Karin E", "initials": "KE"}, {"family": "Juliusson", "given": "Gunnar", "initials": "G"}, {"family": "Belessi", "given": "Chrysoula", "initials": "C"}, {"family": "Rung", "given": "Johan", "initials": "J"}, {"family": "Chiorazzi", "given": "Nicholas", "initials": "N"}, {"family": "Strefford", "given": "Jonathan C", "initials": "JC"}, {"family": "Langerak", "given": "Anton W", "initials": "AW"}, {"family": "Pospisilova", "given": "Sarka", "initials": "S"}, {"family": "Davi", "given": "Frederic", "initials": "F"}, {"family": "Hellstr\u00f6m", "given": "Mats", "initials": "M"}, {"family": "Jernberg-Wiklund", "given": "Helena", "initials": "H"}, {"family": "Ghia", "given": "Paolo", "initials": "P"}, {"family": "S\u00f6derberg", "given": "Ola", "initials": "O"}, {"family": "Stamatopoulos", "given": "Kostas", "initials": "K"}, {"family": "Nilsson", "given": "Mats", "initials": "M", "orcid": "0000-0001-9985-0387", "researcher": {"href": "https://publications.scilifelab.se/researcher/197cf8ba83ba430f9712b2f4d94dc3e5.json"}}, {"family": "Rosenquist", "given": "Richard", "initials": "R"}], "type": "journal article", "published": "2015-06-01", "journal": {"volume": "212", "issn": "1540-9538", "issue": "6", "pages": "833-843", "title": "J. Exp. Med.", "issn-l": "0022-1007"}, "abstract": "NF-\u03baB is constitutively activated in chronic lymphocytic leukemia (CLL); however, the implicated molecular mechanisms remain largely unknown. Thus, we performed targeted deep sequencing of 18 core complex genes within the NF-\u03baB pathway in a discovery and validation CLL cohort totaling 315 cases. The most frequently mutated gene was NFKBIE (21/315 cases; 7%), which encodes I\u03baB\u03b5, a negative regulator of NF-\u03baB in normal B cells. Strikingly, 13 of these cases carried an identical 4-bp frameshift deletion, resulting in a truncated protein. Screening of an additional 377 CLL cases revealed that NFKBIE aberrations predominated in poor-prognostic patients and were associated with inferior outcome. Minor subclones and/or clonal evolution were also observed, thus potentially linking this recurrent event to disease progression. Compared with wild-type patients, NFKBIE-deleted cases showed reduced I\u03baB\u03b5 protein levels and decreased p65 inhibition, along with increased phosphorylation and nuclear translocation of p65. Considering the central role of B cell receptor (BcR) signaling in CLL pathobiology, it is notable that I\u03baB\u03b5 loss was enriched in aggressive cases with distinctive stereotyped BcR, likely contributing to their poor prognosis, and leading to an altered response to BcR inhibitors. Because NFKBIE deletions were observed in several other B cell lymphomas, our findings suggest a novel common mechanism of NF-\u03baB deregulation during lymphomagenesis.", "doi": "10.1084/jem.20142009", "pmid": "25987724", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (SNP&SEQ Technology Platform)": null, "Array and Analysis Facility": null}, "xrefs": [{"db": "pii", "key": "jem.20142009"}, {"db": "pmc", "key": "PMC4451125"}], "notes": [], "created": "2017-05-02T12:57:58.790Z", "modified": "2021-07-07T13:54:46.048Z"}, {"entity": "publication", "iuid": "712d37d52ba34cf799dc406e5b3bf630", "links": {"self": {"href": "https://publications.scilifelab.se/publication/712d37d52ba34cf799dc406e5b3bf630.json"}, "display": {"href": "https://publications.scilifelab.se/publication/712d37d52ba34cf799dc406e5b3bf630"}}, "title": "Differential Gene Regulation in Fibroblasts in Co-culture with Keratinocytes and Head and Neck SCC Cells.", "authors": [{"family": "Hakelius", "given": "Malin", "initials": "M"}, {"family": "Saiepour", "given": "Daniel", "initials": "D"}, {"family": "G\u00f6ransson", "given": "Hanna", "initials": "H"}, {"family": "Rubin", "given": "Kristofer", "initials": "K"}, {"family": "Gerdin", "given": "Bengt", "initials": "B"}, {"family": "Nowinski", "given": "Daniel", "initials": "D"}], "type": "journal article", "published": "2015-06-00", "journal": {"volume": "35", "issn": "1791-7530", "issue": "6", "pages": "3253-3265", "title": "Anticancer Res.", "issn-l": "0250-7005"}, "abstract": "While carcinoma-associated fibroblasts (CAFs) support tumorigenesis, normal tissue fibroblasts suppress tumor progression. Mechanisms behind conversion of fibroblasts into a CAF phenotype are largely unrevealed.\n\nTranswell co-cultures with fibroblasts in collagen gels and squamous-cell carcinoma (SCC) cells or normal oral keratinocytes (NOKs) in inserts. Differences in fibroblast global gene expression were analyzed using Affymetrix arrays and subsequent functional annotation and cluster analysis, as well as gene set enrichment analysis were performed.\n\nThere were 52 up-regulated and 30 down-regulated transcript IDs (>2-fold, p<0.05) in fibroblasts co-cultured with SCC compared to NOKs. Functional analysis demonstrated an enrichment of collagen-related genes. There were similarities with gene sets reflecting a non-specific, innate-type response with activation of both interferon pathways and connective tissue turnover.\n\nThere were distinct differences in fibroblast gene expression between the co-culture types. Many were in genes related to an innate-type of response and to connective tissue turnover.", "doi": null, "pmid": "26026085", "labels": {"Array and Analysis Facility": null}, "xrefs": [{"db": "pii", "key": "35/6/3253"}], "notes": [], "created": "2017-05-02T12:57:12.822Z", "modified": "2025-12-01T07:52:43.688Z"}, {"entity": "publication", "iuid": "5574a7cc0c2044bf9d9d7afdffd09a4e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5574a7cc0c2044bf9d9d7afdffd09a4e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5574a7cc0c2044bf9d9d7afdffd09a4e"}}, "title": "Site-specific programming of the host epithelial transcriptome by the gut microbiota.", "authors": [{"family": "Sommer", "given": "Felix", "initials": "F"}, {"family": "Nookaew", "given": "Intawat", "initials": "I"}, {"family": "Sommer", "given": "Nina", "initials": "N"}, {"family": "Fogelstrand", "given": "Per", "initials": "P"}, {"family": "B\u00e4ckhed", "given": "Fredrik", "initials": "F"}], "type": "journal article", "published": "2015-03-28", "journal": {"volume": "16", "issn": "1474-760X", "issue": null, "pages": "62", "title": "Genome Biol.", "issn-l": "1474-7596"}, "abstract": "The intestinal epithelium separates us from the microbiota but also interacts with it and thus affects host immune status and physiology. Previous studies investigated microbiota-induced responses in the gut using intact tissues or unfractionated epithelial cells, thereby limiting conclusions about regional differences in the epithelium. Here, we sought to investigate microbiota-induced transcriptional responses in specific fractions of intestinal epithelial cells. To this end, we used microarray analysis of laser capture microdissection (LCM)-harvested ileal and colonic tip and crypt epithelial fractions from germ-free and conventionally raised mice and from mice during the time course of colonization.\n\nWe found that about 10% of the host's transcriptome was microbially regulated, mainly including genes annotated with functions in immunity, cell proliferation, and metabolism. The microbial impact on host gene expression was highly site specific, as epithelial responses to the microbiota differed between cell fractions. Specific transcriptional regulators were enriched in each fraction. In general, the gut microbiota induced a more rapid response in the colon than in the ileum.\n\nOur study indicates that the microbiota engage different regulatory networks to alter host gene expression in a particular niche. Understanding host-microbiota interactions on a cellular level may facilitate signaling pathways that contribute to health and disease and thus provide new therapeutic strategies.", "doi": "10.1186/s13059-015-0614-4", "pmid": "25887251", "labels": {"Array and Analysis Facility": null, "Bioinformatics Support, Infrastructure and Training": null, "Bioinformatics Support and Infrastructure": null, "Bioinformatics (NBIS)": ""}, "xrefs": [{"db": "pii", "key": "10.1186/s13059-015-0614-4"}, {"db": "pmc", "key": "PMC4404278"}], "notes": [], "created": "2017-05-02T12:58:36.919Z", "modified": "2020-01-21T13:53:20.495Z"}, {"entity": "publication", "iuid": "9e58d31bf76440078c7df0a0541e34f0", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9e58d31bf76440078c7df0a0541e34f0.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9e58d31bf76440078c7df0a0541e34f0"}}, "title": "Microsatellite instability and mutations in BRAF and KRAS are significant predictors of disseminated disease in colon cancer.", "authors": [{"family": "Birgisson", "given": "Helgi", "initials": "H"}, {"family": "Edlund", "given": "Karolina", "initials": "K"}, {"family": "Wallin", "given": "Ulrik", "initials": "U"}, {"family": "P\u00e5hlman", "given": "Lars", "initials": "L"}, {"family": "Kultima", "given": "Hanna G\u00f6ransson", "initials": "HG"}, {"family": "Mayrhofer", "given": "Markus", "initials": "M"}, {"family": "Micke", "given": "Patrick", "initials": "P"}, {"family": "Isaksson", "given": "Anders", "initials": "A"}, {"family": "Botling", "given": "Johan", "initials": "J"}, {"family": "Glimelius", "given": "Bengt", "initials": "B"}, {"family": "Sundstr\u00f6m", "given": "Magnus", "initials": "M"}], "type": "journal article", "published": "2015-03-14", "journal": {"volume": "15", "issn": "1471-2407", "issue": null, "pages": "125", "title": "BMC Cancer", "issn-l": "1471-2407"}, "abstract": "Molecular alterations are well studied in colon cancer, however there is still need for an improved understanding of their prognostic impact. This study aims to characterize colon cancer with regard to KRAS, BRAF, and PIK3CA mutations, microsatellite instability (MSI), and average DNA copy number, in connection with tumour dissemination and recurrence in patients with colon cancer.\n\nDisease stage II-IV colon cancer patients (n\u2009=\u2009121) were selected. KRAS, BRAF, and PIK3CA mutation status was assessed by pyrosequencing and MSI was determined by analysis of mononucleotide repeat markers. Genome-wide average DNA copy number and allelic imbalance was evaluated by SNP array analysis.\n\nPatients with mutated KRAS were more likely to experience disease dissemination (OR 2.75; 95% CI 1.28-6.04), whereas the opposite was observed for patients with BRAF mutation (OR 0.34; 95% 0.14-0.81) or MSI (OR 0.24; 95% 0.09-0.64). Also in the subset of patients with stage II-III disease, both MSI (OR 0.29; 95% 0.10-0.86) and BRAF mutation (OR 0.32; 95% 0.16-0.91) were related to lower risk of distant recurrence. However, average DNA copy number and PIK3CA mutations were not associated with disease dissemination.\n\nThe present study revealed that tumour dissemination is less likely to occur in colon cancer patients with MSI and BRAF mutation, whereas the presence of a KRAS mutation increases the likelihood of disseminated disease.", "doi": "10.1186/s12885-015-1144-x", "pmid": "25884297", "labels": {"Array and Analysis Facility": null}, "xrefs": [{"db": "pii", "key": "10.1186/s12885-015-1144-x"}, {"db": "pmc", "key": "PMC4364587"}, {"db": "GEO", "description": "SNP array data", "key": "GSE62875"}], "notes": [], "created": "2017-05-02T12:56:37.304Z", "modified": "2018-11-14T13:42:09.141Z"}, {"entity": "publication", "iuid": "f0030f2c2a5446f0b28876e29f1b16f4", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f0030f2c2a5446f0b28876e29f1b16f4.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f0030f2c2a5446f0b28876e29f1b16f4"}}, "title": "Intratumoral genome diversity parallels progression and predicts outcome in pediatric cancer.", "authors": [{"family": "Mengelbier", "given": "Linda Holmquist", "initials": "LH"}, {"family": "Karlsson", "given": "Jenny", "initials": "J"}, {"family": "Lindgren", "given": "David", "initials": "D"}, {"family": "Valind", "given": "Anders", "initials": "A"}, {"family": "Lilljebj\u00f6rn", "given": "Henrik", "initials": "H"}, {"family": "Jansson", "given": "Caroline", "initials": "C"}, {"family": "Bexell", "given": "Daniel", "initials": "D"}, {"family": "Braekeveldt", "given": "No\u00e9mie", "initials": "N"}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}, {"family": "Jonson", "given": "Tord", "initials": "T"}, {"family": "Kultima", "given": "Hanna G\u00f6ransson", "initials": "HG"}, {"family": "Isaksson", "given": "Anders", "initials": "A"}, {"family": "Asmundsson", "given": "Jurate", "initials": "J"}, {"family": "Versteeg", "given": "Rogier", "initials": "R"}, {"family": "Rissler", "given": "Marianne", "initials": "M"}, {"family": "Fioretos", "given": "Thoas", "initials": "T", "orcid": "0000-0002-3235-6154", "researcher": {"href": "https://publications.scilifelab.se/researcher/35a5c1b6023345c6b1317c590bf80680.json"}}, {"family": "Sandstedt", "given": "Bengt", "initials": "B"}, {"family": "B\u00f6rjesson", "given": "Anna", "initials": "A"}, {"family": "Backman", "given": "Torbj\u00f6rn", "initials": "T"}, {"family": "Pal", "given": "Niklas", "initials": "N"}, {"family": "\u00d8ra", "given": "Ingrid", "initials": "I"}, {"family": "Mayrhofer", "given": "Markus", "initials": "M"}, {"family": "Gisselsson", "given": "David", "initials": "D"}], "type": "journal article", "published": "2015-01-27", "journal": {"volume": "6", "issn": "2041-1723", "issue": null, "pages": "6125", "title": "Nat Commun", "issn-l": "2041-1723"}, "abstract": "Genetic differences among neoplastic cells within the same tumour have been proposed to drive cancer progression and treatment failure. Whether data on intratumoral diversity can be used to predict clinical outcome remains unclear. We here address this issue by quantifying genetic intratumoral diversity in a set of chemotherapy-treated childhood tumours. By analysis of multiple tumour samples from seven patients we demonstrate intratumoral diversity in all patients analysed after chemotherapy, typically presenting as multiple clones within a single millimetre-sized tumour sample (microdiversity). We show that microdiversity often acts as the foundation for further genome evolution in metastases. In addition, we find that microdiversity predicts poor cancer-specific survival (60%; P=0.009), independent of other risk factors, in a cohort of 44 patients with chemotherapy-treated childhood kidney cancer. Survival was 100% for patients lacking microdiversity. Thus, intratumoral genetic diversity is common in childhood cancers after chemotherapy and may be an important factor behind treatment failure.", "doi": "10.1038/ncomms7125", "pmid": "25625758", "labels": {"National Genomics Infrastructure": null, "Array and Analysis Facility": null, "NGI Uppsala (Uppsala Genome Center)": null}, "xrefs": [{"db": "pii", "key": "ncomms7125"}], "notes": [], "created": "2017-05-02T12:57:43.059Z", "modified": "2021-07-07T14:37:06.646Z"}, {"entity": "publication", "iuid": "f5db7e7b9d0c40f58af9b4f98e7caba3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f5db7e7b9d0c40f58af9b4f98e7caba3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f5db7e7b9d0c40f58af9b4f98e7caba3"}}, "title": "1p36 deletion is a marker for tumour dissemination in microsatellite stable stage II-III colon cancer.", "authors": [{"family": "Mayrhofer", "given": "Markus", "initials": "M"}, {"family": "Kultima", "given": "Hanna G\u00f6ransson", "initials": "HG"}, {"family": "Birgisson", "given": "Helgi", "initials": "H"}, {"family": "Sundstr\u00f6m", "given": "Magnus", "initials": "M"}, {"family": "Mathot", "given": "Lucy", "initials": "L"}, {"family": "Edlund", "given": "Karolina", "initials": "K"}, {"family": "Viklund", "given": "Bj\u00f6rn", "initials": "B"}, {"family": "Sj\u00f6blom", "given": "Tobias", "initials": "T"}, {"family": "Botling", "given": "Johan", "initials": "J"}, {"family": "Micke", "given": "Patrick", "initials": "P"}, {"family": "P\u00e5hlman", "given": "Lars", "initials": "L"}, {"family": "Glimelius", "given": "Bengt", "initials": "B"}, {"family": "Isaksson", "given": "Anders", "initials": "A"}], "type": "journal article", "published": "2014-11-24", "journal": {"volume": "14", "issn": "1471-2407", "issue": null, "pages": "872", "title": "BMC Cancer", "issn-l": "1471-2407"}, "abstract": "The clinical behaviour of colon cancer is heterogeneous. Five-year overall survival is 50-65% with all stages included. Recurring somatic chromosomal alterations have been identified and some have shown potential as markers for dissemination of the tumour, which is responsible for most colon cancer deaths. We investigated 115 selected stage II-IV primary colon cancers for associations between chromosomal alterations and tumour dissemination.\n\nFollow-up was at least 5 years for stage II-III patients without distant recurrence. Affymetrix SNP 6.0 microarrays and allele-specific copy number analysis were used to identify chromosomal alterations. Fisher's exact test was used to associate alterations with tumour dissemination, detected at diagnosis (stage IV) or later as recurrent disease (stage II-III).\n\nLoss of 1p36.11-21 was associated with tumour dissemination in microsatellite stable tumours of stage II-IV (odds ratio\u2009=\u20095.5). It was enriched to a similar extent in tumours with distant recurrence within stage II and stage III subgroups, and may therefore be used as a prognostic marker at diagnosis. Loss of 1p36.11-21 relative to average copy number of the genome showed similar prognostic value compared to absolute loss of copies. Therefore, the use of relative loss as a prognostic marker would benefit more patients by applying also to hyperploid cancer genomes. The association with tumour dissemination was supported by independent data from the The Cancer Genome Atlas.\n\nDeletions on 1p36 may be used to guide adjuvant treatment decisions in microsatellite stable colon cancer of stages II and III.", "doi": "10.1186/1471-2407-14-872", "pmid": "25420937", "labels": {"Array and Analysis Facility": null}, "xrefs": [{"db": "pii", "key": "1471-2407-14-872"}, {"db": "pmc", "key": "PMC4251789"}], "notes": [], "created": "2017-05-04T15:03:02.416Z", "modified": "2017-05-30T14:50:06.726Z"}, {"entity": "publication", "iuid": "61168500d6b84e0fb73a7ba0abd8158c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/61168500d6b84e0fb73a7ba0abd8158c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/61168500d6b84e0fb73a7ba0abd8158c"}}, "title": "Synergistic interactions between camptothecin and EGFR or RAC1 inhibitors and between imatinib and Notch signaling or RAC1 inhibitors in glioblastoma cell lines.", "authors": [{"family": "Sooman", "given": "Linda", "initials": "L"}, {"family": "Ekman", "given": "Simon", "initials": "S"}, {"family": "Andersson", "given": "Claes", "initials": "C"}, {"family": "Kultima", "given": "Hanna G\u00f6ransson", "initials": "HG"}, {"family": "Isaksson", "given": "Anders", "initials": "A"}, {"family": "Johansson", "given": "Fredrik", "initials": "F"}, {"family": "Bergqvist", "given": "Michael", "initials": "M"}, {"family": "Blomquist", "given": "Erik", "initials": "E"}, {"family": "Lennartsson", "given": "Johan", "initials": "J"}, {"family": "Gullbo", "given": "Joachim", "initials": "J"}], "type": "journal article", "published": "2013-08-00", "journal": {"volume": "72", "issn": "1432-0843", "issue": "2", "pages": "329-340", "title": "Cancer Chemother. Pharmacol.", "issn-l": "0344-5704"}, "abstract": "The current treatment strategies for glioblastoma have limited health and survival benefits for the patients. A common obstacle in the treatment is chemoresistance. A possible strategy to evade this problem may be to combine chemotherapeutic drugs with agents inhibiting resistance mechanisms. The aim with this study was to identify molecular pathways influencing drug resistance in glioblastoma-derived cells and to evaluate the potential of pharmacological interference with these pathways to identify synergistic drug combinations.\n\nGlobal gene expressions and drug sensitivities to three chemotherapeutic drugs (imatinib, camptothecin and temozolomide) were measured in six human glioblastoma-derived cell lines. Gene expressions that correlated to drug sensitivity or resistance were identified and mapped to specific pathways. Selective inhibitors of these pathways were identified. The effects of six combinations of inhibitors and chemotherapeutic drugs were evaluated in glioblastoma-derived cell lines. Drug combinations with synergistic effects were also evaluated in non-cancerous epithelial cells.\n\nFour drug combinations had synergistic effects in at least one of the tested glioblastoma-derived cell lines; camptothecin combined with gefitinib (epidermal growth factor receptor inhibitor) or NSC 23766 (ras-related C3 botulinum toxin substrate 1 inhibitor) and imatinib combined with DAPT (Notch signaling inhibitor) or NSC 23766. Of these, imatinib combined with DAPT or NSC 23766 did not have synergistic effects in non-cancerous epithelial cells. Two drug combinations had at least additive effects in one of the tested glioblastoma-derived cell lines; temozolomide combined with gefitinib or PF-573228 (focal adhesion kinase inhibitor).\n\nFour synergistic and two at least additive drug combinations were identified in glioblastoma-derived cells. Pathways targeted by these drug combinations may serve as targets for future drug development with the potential to increase efficacy of currently used/evaluated chemotherapy.", "doi": "10.1007/s00280-013-2197-7", "pmid": "23736154", "labels": {"Array and Analysis Facility": null}, "xrefs": [], "notes": [], "created": "2017-05-04T15:03:00.782Z", "modified": "2017-05-30T12:37:50.801Z"}, {"entity": "publication", "iuid": "1b4fd9ae526a4deeb6366d4755d572a1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1b4fd9ae526a4deeb6366d4755d572a1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1b4fd9ae526a4deeb6366d4755d572a1"}}, "title": "Behavioural and Brain Gene Expression Profiling in Pigs during Tail Biting Outbreaks - Evidence of a Tail Biting Resistant Phenotype.", "authors": [{"family": "Brunberg", "given": "Emma", "initials": "E"}, {"family": "Jensen", "given": "Per", "initials": "P"}, {"family": "Isaksson", "given": "Anders", "initials": "A"}, {"family": "Keeling", "given": "Linda J", "initials": "LJ"}], "type": "journal article", "published": "2013-06-18", "journal": {"volume": "8", "issn": "1932-6203", "issue": "6", "pages": "e66513", "title": "PLoS ONE", "issn-l": "1932-6203"}, "abstract": "Abnormal tail biting behaviour is a major welfare problem for pigs receiving the behaviour, as well as an indication of decreased welfare in the pigs performing it. However, not all pigs in a pen perform or receive tail biting behaviour and it has recently been shown that these 'neutral' pigs not only differ in their behaviour, but also in their gene expression compared to performers and receivers of tail biting in the same pen. To investigate whether this difference was linked to the cause or a consequence of them not being involved in the outbreak of tail biting, behaviour and brain gene expression was compared with 'control' pigs housed in pens with no tail biting. It was shown that the pigs housed in control pens performed a wider variety of pig-directed abnormal behaviour (belly nosing 0.95\u00b11.59, tail in mouth 0.31\u00b10.60 and 'other' abnormal 1.53\u00b14.26; mean\u00b1S.D) compared to the neutral pigs (belly nosing 0.30\u00b10.62, tail in mouth 0.13\u00b10.50 and \"other\" abnormal 0.42\u00b11.06). With Affymetrix gene expression arrays, 107 transcripts were identified as differently expressed (p<0.05) between these two categories of pigs. Several of these transcripts had already been shown to be differently expressed in the neutral pigs when they were compared to performers and receivers of tail biting in the same pen in an earlier study. Hence, the different expression of these genes cannot be a consequence of the neutral pigs not being involved in tail biting behaviour, but rather linked to the cause contributing to why they were not involved in tail biting interactions. These neutral pigs seem to have a genetic and behavioural profile that somehow contributes to them being resistant to performing or receiving pig-directed abnormal behaviour, such as tail biting, even when housed in an environment that elicits that behaviour in other pigs.", "doi": "10.1371/journal.pone.0066513", "pmid": "23824700", "labels": {"Array and Analysis Facility": null}, "xrefs": [{"db": "pii", "key": "PONE-D-12-16862"}, {"db": "pmc", "key": "PMC3688911"}], "notes": [], "created": "2017-05-04T15:03:02.113Z", "modified": "2017-05-30T14:50:01.676Z"}, {"entity": "publication", "iuid": "8fafa408f1fa4183a437402e9e8dbb47", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8fafa408f1fa4183a437402e9e8dbb47.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8fafa408f1fa4183a437402e9e8dbb47"}}, "title": "Gambogic acid is cytotoxic to cancer cells through inhibition of the ubiquitin-proteasome system.", "authors": [{"family": "Felth", "given": "Jenny", "initials": "J"}, {"family": "Lesiak-Mieczkowska", "given": "Karolina", "initials": "K"}, {"family": "D'Arcy", "given": "Padraig", "initials": "P"}, {"family": "Haglund", "given": "Caroline", "initials": "C"}, {"family": "Gullbo", "given": "Joachim", "initials": "J"}, {"family": "Larsson", "given": "Rolf", "initials": "R"}, {"family": "Linder", "given": "Stig", "initials": "S"}, {"family": "Bohlin", "given": "Lars", "initials": "L"}, {"family": "Frykn\u00e4s", "given": "M\u00e5rten", "initials": "M"}, {"family": "Rickardson", "given": "Linda", "initials": "L"}], "type": "journal article", "published": "2013-06-00", "journal": {"volume": "31", "issn": "1573-0646", "issue": "3", "pages": "587-598", "title": "Invest New Drugs", "issn-l": "0167-6997"}, "abstract": "Gambogic acid (GA), displays cytotoxicity towards a wide variety of tumor cells and has been shown to affect many important cell-signaling pathways. In the present work, we investigated the mechanism of action of GA by analysis of drug-induced changes in gene expression profiles and identified GA and the derivative dihydro GA as possible inhibitors of the ubiquitin-proteasome system (UPS). Both GA and dihydro GA inhibited proteasome function in cells resulting in the accumulation of polyubiquitin complexes. In vitro experiments showed that both GA and dihydro GA inhibited 20S chymotrypsin activity and the inhibitory effects of GA and dihydro GA on proteasome function corresponded with apoptosis induction and cell death. In conclusion, our results show that GA and dihydro GA exert their cytotoxic activity through inhibition of the UPS, specifically by acting as inhibitors of the chymotrypsin activity of the 20S proteasome.", "doi": "10.1007/s10637-012-9902-y", "pmid": "23179339", "labels": {"Array and Analysis Facility": null}, "xrefs": [], "notes": [], "created": "2017-05-04T15:02:58.925Z", "modified": "2017-05-30T12:37:22.819Z"}, {"entity": "publication", "iuid": "d6ce3456e6b24530998f38d3b86402e5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d6ce3456e6b24530998f38d3b86402e5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d6ce3456e6b24530998f38d3b86402e5"}}, "title": "Patchwork: allele-specific copy number analysis of whole-genome sequenced tumor tissue.", "authors": [{"family": "Mayrhofer", "given": "Markus", "initials": "M"}, {"family": "DiLorenzo", "given": "Sebastian", "initials": "S"}, {"family": "Isaksson", "given": "Anders", "initials": "A"}], "type": "journal article", "published": "2013-03-25", "journal": {"volume": "14", "issn": "1474-760X", "issue": "3", "pages": "R24", "title": "Genome Biol.", "issn-l": "1474-7596"}, "abstract": "Whole-genome sequencing of tumor tissue has the potential to provide comprehensive characterization of genomic alterations in tumor samples. We present Patchwork, a new bioinformatic tool for allele-specific copy number analysis using whole-genome sequencing data. Patchwork can be used to determine the copy number of homologous sequences throughout the genome, even in aneuploid samples with moderate sequence coverage and tumor cell content. No prior knowledge of average ploidy or tumor cell content is required. Patchwork is freely available as an R package, installable via R-Forge (http://patchwork.r-forge.r-project.org/).", "doi": "10.1186/gb-2013-14-3-r24", "pmid": "23531354", "labels": {"Array and Analysis Facility": null}, "xrefs": [{"db": "pii", "key": "gb-2013-14-3-r24"}, {"db": "pmc", "key": "PMC4053982"}], "notes": [], "created": "2017-05-04T15:03:01.598Z", "modified": "2017-05-30T14:49:57.083Z"}, {"entity": "publication", "iuid": "cd503c88e4774b5e85b3eddf807bbdd6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/cd503c88e4774b5e85b3eddf807bbdd6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/cd503c88e4774b5e85b3eddf807bbdd6"}}, "title": "Brain gene expression differences are associated with abnormal tail biting behavior in pigs.", "authors": [{"family": "Brunberg", "given": "E", "initials": "E"}, {"family": "Jensen", "given": "P", "initials": "P"}, {"family": "Isaksson", "given": "A", "initials": "A"}, {"family": "Keeling", "given": "L J", "initials": "LJ"}], "type": "journal article", "published": "2013-03-00", "journal": {"volume": "12", "issn": "1601-183X", "issue": "2", "pages": "275-281", "title": "Genes Brain Behav.", "issn-l": null}, "abstract": "Knowledge about gene expression in animals involved in abnormal behaviors can contribute to the understanding of underlying biological mechanisms. This study aimed to explore the motivational background to tail biting, an abnormal injurious behavior and severe welfare problem in pig production. Affymetrix microarrays were used to investigate gene expression differences in the hypothalamus and prefrontal cortex of pigs performing tail biting, pigs receiving bites to the tail and neutral pigs who were not involved in the behavior. In the hypothalamus, 32 transcripts were differentially expressed (P < 0.05) when tail biters were compared with neutral pigs, 130 when comparing receiver pigs with neutrals, and two when tail biters were compared with receivers. In the prefrontal cortex, seven transcripts were differently expressed in tail biters when compared with neutrals, seven in receivers vs. neutrals and none in the tail biters vs. receivers. In total, 19 genes showed a different expression pattern in neutral pigs when compared with both performers and receivers. This implies that the functions of these may provide knowledge about why the neutral pigs are not involved in tail biting behavior as performers or receivers. Among these 19 transcripts were genes associated with production traits in pigs (PDK4), sociality in humans and mice (GTF2I) and novelty seeking in humans (EGF). These are in line with hypotheses linking tail biting with reduced back fat thickness and explorative behavior.", "doi": "10.1111/gbb.12002", "pmid": "23146156", "labels": {"Array and Analysis Facility": null}, "xrefs": [], "notes": [], "created": "2017-05-04T15:03:01.297Z", "modified": "2017-05-30T12:37:55.391Z"}, {"entity": "publication", "iuid": "7c4249fa03d543eb963d322a8842ba24", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7c4249fa03d543eb963d322a8842ba24.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7c4249fa03d543eb963d322a8842ba24"}}, "title": "A modified Glenn shunt improves haemodynamics in acute right ventricular failure in an experimental model.", "authors": [{"family": "Vikholm", "given": "Per", "initials": "P"}, {"family": "Schiller", "given": "Petter", "initials": "P"}, {"family": "Johansson", "given": "Jakob", "initials": "J"}, {"family": "Hellgren", "given": "Laila", "initials": "L"}], "type": "journal article", "published": "2013-03-00", "journal": {"volume": "43", "issn": "1873-734X", "issue": "3", "pages": "612-618", "title": "Eur J Cardiothorac Surg", "issn-l": "1010-7940"}, "abstract": "Right heart failure is a major cause of morbidity and mortality after left ventricular assist device implantation and is still hard to predict. This study investigated the haemodynamic effect of a modified Glenn shunt on induced right ventricular (RV) failure.\n\nIsolated RV failure was induced by coronary ligation in 11 pigs. A modified Glenn shunt was established by a superior vena cava to pulmonary artery connection. Haemodynamic data were obtained at baseline, RV failure, and RV failure and open shunt. Myocardial biopsies were taken to ascertain established heart failure.\n\nRV failure defined as right atrial pressure \u226520 mmHg was achieved in all 11 animals. A reduction in cardiac output (CO) from 3.7 (3.5-4.2) to 2.3 l/min (2.0-2.6) and mean arterial pressure (MAP) from median 72.7 (70.1-82.2) to 55.9 mmHg (52.6-59.8) was seen during heart failure. The median flow in the shunt was 681 ml. Right atrial pressures decreased from 20.3 (19.6-21.1) to 13.4 mmHg (12.7-14.0), and RV pressures decreased from 18.1 (16.4-20.1) to 13.6 mmHg (13.5-14.2) with open shunt (P = 0.001 for both). CO increased to 2.9 l/min (2.4-3.3) when the shunt was in use. Mixed venous oxygen saturation increased with the shunt from 32 (27-38) to 49% (45-56), P = 0.001. Genes associated with heart failure were upregulated during heart failure.\n\nA modified Glenn shunt improved haemodynamics by reduced right atrial pressure, increased CO, MAP and mixed venous oxygen saturation in an experimental model of induced RV failure.", "doi": "10.1093/ejcts/ezs386", "pmid": "22761503", "labels": {"Array and Analysis Facility": null}, "xrefs": [{"db": "pii", "key": "ezs386"}], "notes": [], "created": "2017-05-04T15:02:57.786Z", "modified": "2017-05-30T12:37:08.560Z"}, {"entity": "publication", "iuid": "3c825df5e171438792031ef930fdba9a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3c825df5e171438792031ef930fdba9a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3c825df5e171438792031ef930fdba9a"}}, "title": "Biomarker discovery in non-small cell lung cancer: integrating gene expression profiling, meta-analysis, and tissue microarray validation.", "authors": [{"family": "Botling", "given": "Johan", "initials": "J"}, {"family": "Edlund", "given": "Karolina", "initials": "K"}, {"family": "Lohr", "given": "Miriam", "initials": "M"}, {"family": "Hellwig", "given": "Birte", "initials": "B"}, {"family": "Holmberg", "given": "Lars", "initials": "L"}, {"family": "Lambe", "given": "Mats", "initials": "M"}, {"family": "Berglund", "given": "Anders", "initials": "A"}, {"family": "Ekman", "given": "Simon", "initials": "S"}, {"family": "Bergqvist", "given": "Michael", "initials": "M"}, {"family": "Pont\u00e9n", "given": "Fredrik", "initials": "F"}, {"family": "K\u00f6nig", "given": "Andr\u00e9", "initials": "A"}, {"family": "Fernandes", "given": "Oswaldo", "initials": "O"}, {"family": "Karlsson", "given": "Mats", "initials": "M"}, {"family": "Helenius", "given": "Gisela", "initials": "G", "orcid": "0000-0003-2317-5738", "researcher": {"href": "https://publications.scilifelab.se/researcher/2994acfdacff45ceb9c6b29aae2148c7.json"}}, {"family": "Karlsson", "given": "Christina", "initials": "C"}, {"family": "Rahnenf\u00fchrer", "given": "J\u00f6rg", "initials": "J"}, {"family": "Hengstler", "given": "Jan G", "initials": "JG"}, {"family": "Micke", "given": "Patrick", "initials": "P"}], "type": "journal article", "published": "2013-01-01", "journal": {"volume": "19", "issn": "1557-3265", "issue": "1", "pages": "194-204", "title": "Clin. Cancer Res.", "issn-l": "1078-0432"}, "abstract": "Global gene expression profiling has been widely used in lung cancer research to identify clinically relevant molecular subtypes as well as to predict prognosis and therapy response. So far, the value of these multigene signatures in clinical practice is unclear, and the biologic importance of individual genes is difficult to assess, as the published signatures virtually do not overlap.\n\nHere, we describe a novel single institute cohort, including 196 non-small lung cancers (NSCLC) with clinical information and long-term follow-up. Gene expression array data were used as a training set to screen for single genes with prognostic impact. The top 450 probe sets identified using a univariate Cox regression model (significance level P < 0.01) were tested in a meta-analysis including five publicly available independent lung cancer cohorts (n = 860).\n\nThe meta-analysis revealed 14 genes that were significantly associated with survival (P < 0.001) with a false discovery rate <1%. The prognostic impact of one of these genes, the cell adhesion molecule 1 (CADM1), was confirmed by use of immunohistochemistry on tissue microarrays from 2 independent NSCLC cohorts, altogether including 617 NSCLC samples. Low CADM1 protein expression was significantly associated with shorter survival, with particular influence in the adenocarcinoma patient subgroup.\n\nUsing a novel NSCLC cohort together with a meta-analysis validation approach, we have identified a set of single genes with independent prognostic impact. One of these genes, CADM1, was further established as an immunohistochemical marker with a potential application in clinical diagnostics.", "doi": "10.1158/1078-0432.CCR-12-1139", "pmid": "23032747", "labels": {"Array and Analysis Facility": null, "Tissue Profiling": null}, "xrefs": [{"db": "pii", "key": "1078-0432.CCR-12-1139"}], "notes": [], "created": "2017-05-04T14:55:56.842Z", "modified": "2021-07-06T16:29:23.776Z"}, {"entity": "publication", "iuid": "46a18a9c8aaf4db1b6effc79fdc3f06a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/46a18a9c8aaf4db1b6effc79fdc3f06a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/46a18a9c8aaf4db1b6effc79fdc3f06a"}}, "title": "450K-array analysis of chronic lymphocytic leukemia cells reveals global DNA methylation to be relatively stable over time and similar in resting and proliferative compartments.", "authors": [{"family": "Cahill", "given": "N", "initials": "N"}, {"family": "Bergh", "given": "A-C", "initials": "AC"}, {"family": "Kanduri", "given": "M", "initials": "M"}, {"family": "G\u00f6ransson-Kultima", "given": "H", "initials": "H"}, {"family": "Mansouri", "given": "L", "initials": "L"}, {"family": "Isaksson", "given": "A", "initials": "A"}, {"family": "Ryan", "given": "F", "initials": "F"}, {"family": "Smedby", "given": "K E", "initials": "KE"}, {"family": "Juliusson", "given": "G", "initials": "G"}, {"family": "Sundstr\u00f6m", "given": "C", "initials": "C"}, {"family": "Ros\u00e9n", "given": "A", "initials": "A"}, {"family": "Rosenquist", "given": "R", "initials": "R"}], "type": "comparative study", "published": "2013-01-00", "journal": {"volume": "27", "issn": "1476-5551", "issue": "1", "pages": "150-158", "title": "Leukemia", "issn-l": "0887-6924"}, "abstract": "In chronic lymphocytic leukemia (CLL), the microenvironment influences gene expression patterns; however, knowledge is limited regarding the extent to which methylation changes with time and exposure to specific microenvironments. Using high-resolution 450K arrays, we provide the most comprehensive DNA methylation study of CLL to date, analyzing paired diagnostic/follow-up samples from IGHV-mutated/untreated and IGHV-unmutated/treated patients (n=36) and patient-matched peripheral blood and lymph node samples (n=20). On an unprecedented scale, we revealed 2239 differentially methylated CpG sites between IGHV-mutated and unmutated patients, with the majority of sites positioned outside annotated CpG islands. Intriguingly, CLL prognostic genes (for example, CLLU1, LPL, ZAP70 and NOTCH1), epigenetic regulator (for example, HDAC9, HDAC4 and DNMT3B), B-cell signaling (for example, IBTK) and numerous TGF-\u03b2 and NF-\u03baB/TNF pathway genes were alternatively methylated between subgroups. Contrary, DNA methylation over time was deemed rather stable with few recurrent changes noted within subgroups. Although a larger number of non-recurrent changes were identified among IGHV-unmutated relative to mutated cases over time, these equated to a low global change. Similarly, few changes were identified between compartment cases. Altogether, we reveal CLL subgroups to display unique methylation profiles and unveil methylation as relatively stable over time and similar within different CLL compartments, implying aberrant methylation as an early leukemogenic event.", "doi": "10.1038/leu.2012.245", "pmid": "22922567", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (SNP&SEQ Technology Platform)": null, "Array and Analysis Facility": null}, "xrefs": [{"db": "pii", "key": "leu2012245"}], "notes": [], "created": "2017-05-04T15:01:21.005Z", "modified": "2020-01-21T13:56:01.993Z"}, {"entity": "publication", "iuid": "b5717e1da4704310b8977f7958d2bf33", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b5717e1da4704310b8977f7958d2bf33.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b5717e1da4704310b8977f7958d2bf33"}}, "title": "Distinct transcriptional control in major immunogenetic subsets of chronic lymphocytic leukemia exhibiting subset-biased global DNA methylation profiles.", "authors": [{"family": "Kanduri", "given": "Meena", "initials": "M"}, {"family": "Marincevic", "given": "Millaray", "initials": "M"}, {"family": "Halld\u00f3rsd\u00f3ttir", "given": "Anna M", "initials": "AM"}, {"family": "Mansouri", "given": "Larry", "initials": "L"}, {"family": "Junevik", "given": "Katarina", "initials": "K"}, {"family": "Ntoufa", "given": "Stavroula", "initials": "S"}, {"family": "Kultima", "given": "Hanna G\u00f6ransson", "initials": "HG"}, {"family": "Isaksson", "given": "Anders", "initials": "A"}, {"family": "Juliusson", "given": "Gunnar", "initials": "G"}, {"family": "Andersson", "given": "Per-Ola", "initials": "PO"}, {"family": "Ehrencrona", "given": "Hans", "initials": "H"}, {"family": "Stamatopoulos", "given": "Kostas", "initials": "K"}, {"family": "Rosenquist", "given": "Richard", "initials": "R"}], "type": "journal article", "published": "2012-12-01", "journal": {"volume": "7", "issn": "1559-2308", "issue": "12", "pages": "1435-1442", "title": "Epigenetics", "issn-l": "1559-2294"}, "abstract": "Chronic lymphocytic leukemia (CLL) can be divided into prognostic subgroups based on the IGHV gene mutational status, and is further characterized by multiple subsets of cases with quasi-identical or stereotyped B cell receptors that also share clinical and biological features. We recently reported differential DNA methylation profiles in IGHV-mutated and IGHV-unmutated CLL subgroups. For the first time, we here explore the global methylation profiles of stereotyped subsets with different prognosis, by applying high-resolution methylation arrays on CLL samples from three major stereotyped subsets: the poor-prognostic subsets #1 (n = 15) and #2 (n = 9) and the favorable-prognostic subset #4 (n = 15). Overall, the three subsets exhibited significantly different methylation profiles, which only partially overlapped with those observed in our previous study according to IGHV gene mutational status. Specifically, gene ontology analysis of the differentially methylated genes revealed a clear enrichment of genes involved in immune response, such as B cell activation (e.g., CD80, CD86 and IL10), with higher methylation levels in subset #1 than subsets #2 and #4. Accordingly, higher expression of the co-stimulatory molecules CD80 and CD86 was demonstrated in subset #4 vs. subset #1, pointing to a key role for these molecules in the crosstalk of CLL subset #4 cells with the microenvironment. In summary, investigation of three prototypic, stereotyped CLL subsets revealed distinct DNA methylation profiles for each subset, which suggests subset-biased patterns of transcriptional control and highlights a key role for epigenetics during leukemogenesis.", "doi": "10.4161/epi.22901", "pmid": "23154584", "labels": {"Array and Analysis Facility": null}, "xrefs": [{"db": "pii", "key": "22901"}, {"db": "pmc", "key": "PMC3528698"}], "notes": [], "created": "2017-05-04T15:02:56.986Z", "modified": "2017-05-30T12:37:03.981Z"}, {"entity": "publication", "iuid": "30181957b2e34c5288e3afd660451d25", "links": {"self": {"href": "https://publications.scilifelab.se/publication/30181957b2e34c5288e3afd660451d25.json"}, "display": {"href": "https://publications.scilifelab.se/publication/30181957b2e34c5288e3afd660451d25"}}, "title": "CD99 is a novel prognostic stromal marker in non-small cell lung cancer.", "authors": [{"family": "Edlund", "given": "Karolina", "initials": "K"}, {"family": "Lindskog", "given": "Cecilia", "initials": "C"}, {"family": "Saito", "given": "Akira", "initials": "A"}, {"family": "Berglund", "given": "Anders", "initials": "A"}, {"family": "Pont\u00e9n", "given": "Fredrik", "initials": "F"}, {"family": "G\u00f6ransson-Kultima", "given": "Hanna", "initials": "H"}, {"family": "Isaksson", "given": "Anders", "initials": "A"}, {"family": "Jirstr\u00f6m", "given": "Karin", "initials": "K"}, {"family": "Planck", "given": "Maria", "initials": "M"}, {"family": "Johansson", "given": "Leif", "initials": "L"}, {"family": "Lambe", "given": "Mats", "initials": "M"}, {"family": "Holmberg", "given": "Lars", "initials": "L"}, {"family": "Nyberg", "given": "Fredrik", "initials": "F"}, {"family": "Ekman", "given": "Simon", "initials": "S"}, {"family": "Bergqvist", "given": "Michael", "initials": "M"}, {"family": "Landelius", "given": "Per", "initials": "P"}, {"family": "Lamberg", "given": "Kristina", "initials": "K"}, {"family": "Botling", "given": "Johan", "initials": "J"}, {"family": "Ostman", "given": "Arne", "initials": "A"}, {"family": "Micke", "given": "Patrick", "initials": "P"}], "type": "journal article", "published": "2012-11-15", "journal": {"volume": "131", "issn": "1097-0215", "issue": "10", "pages": "2264-2273", "title": "Int. J. Cancer", "issn-l": "0020-7136"}, "abstract": "The complex interaction between cancer cells and the microenvironment plays an essential role in all stages of tumourigenesis. Despite the significance of this interplay, alterations in protein composition underlying tumour-stroma interactions are largely unknown. The aim of this study was to identify stromal proteins with clinical relevance in non-small cell lung cancer (NSCLC). A list encompassing 203 stromal candidate genes was compiled based on gene expression array data and available literature. The protein expression of these genes in human NSCLC was screened using the Human Protein Atlas. Twelve proteins were selected that showed a differential stromal staining pattern (BGN, CD99, DCN, EMILIN1, FBN1, PDGFRB, PDLIM5, POSTN, SPARC, TAGLN, TNC and VCAN). The corresponding antibodies were applied on tissue microarrays, including 190 NSCLC samples, and stromal staining was correlated with clinical parameters. Higher stromal expression of CD99 was associated with better prognosis in the univariate (p = 0.037) and multivariate (p = 0.039) analysis. The association was independent from the proportion of tumour stroma, the fraction of inflammatory cells and clinical and pathological parameters like stage, performance status and tumour histology. The prognostic impact of stromal CD99 protein expression was confirmed in an independent cohort of 240 NSCLC patients (p = 0.008). Furthermore, double-staining confocal fluorescence microscopy showed that CD99 was expressed in stromal lymphocytes as well as in cancer-associated fibroblasts. Based on a comprehensive screening strategy the membrane protein CD99 was identified as a novel stromal factor with clinical relevance. The results support the concept that stromal properties have an important impact on tumour progression.", "doi": "10.1002/ijc.27518", "pmid": "22392539", "labels": {"Array and Analysis Facility": null, "Tissue Profiling": null}, "xrefs": [{"db": "GEO", "description": "Expression profiling by array", "key": "GSE33363"}], "notes": [], "created": "2017-05-04T14:55:51.474Z", "modified": "2018-11-14T11:24:08.142Z"}, {"entity": "publication", "iuid": "7276fd82416646febd7940ca3aa08e4c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7276fd82416646febd7940ca3aa08e4c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7276fd82416646febd7940ca3aa08e4c"}}, "title": "Transcriptional profiling of human glioblastoma vessels indicates a key role of VEGF-A and TGF\u03b22 in vascular abnormalization.", "authors": [{"family": "Dieterich", "given": "Lothar C", "initials": "LC"}, {"family": "Mellberg", "given": "Sofie", "initials": "S"}, {"family": "Langenkamp", "given": "Elise", "initials": "E"}, {"family": "Zhang", "given": "Lei", "initials": "L"}, {"family": "Zieba", "given": "Agata", "initials": "A"}, {"family": "Salom\u00e4ki", "given": "Henriikka", "initials": "H"}, {"family": "Teichert", "given": "Martin", "initials": "M"}, {"family": "Huang", "given": "Hua", "initials": "H"}, {"family": "Edqvist", "given": "Per-Henrik", "initials": "PH"}, {"family": "Kraus", "given": "Theo", "initials": "T"}, {"family": "Augustin", "given": "Hellmut G", "initials": "HG"}, {"family": "Olofsson", "given": "Tommie", "initials": "T"}, {"family": "Larsson", "given": "Erik", "initials": "E"}, {"family": "S\u00f6derberg", "given": "Ola", "initials": "O"}, {"family": "Molema", "given": "Grietje", "initials": "G"}, {"family": "Pont\u00e9n", "given": "Fredrik", "initials": "F"}, {"family": "Georgii-Hemming", "given": "Patrik", "initials": "P"}, {"family": "Alafuzoff", "given": "Irina", "initials": "I"}, {"family": "Dimberg", "given": "Anna", "initials": "A"}], "type": "journal article", "published": "2012-11-00", "journal": {"volume": "228", "issn": "1096-9896", "issue": "3", "pages": "378-390", "title": "J. Pathol.", "issn-l": "0022-3417"}, "abstract": "Glioblastoma are aggressive astrocytic brain tumours characterized by microvascular proliferation and an abnormal vasculature, giving rise to brain oedema and increased patient morbidity. Here, we have characterized the transcriptome of tumour-associated blood vessels and describe a gene signature clearly associated with pleomorphic, pathologically altered vessels in human glioblastoma (grade IV glioma). We identified 95 genes differentially expressed in glioblastoma vessels, while no significant differences in gene expression were detected between vessels in non-malignant brain and grade II glioma. Differential vascular expression of ANGPT2, CD93, ESM1, ELTD1, FILIP1L and TENC1 in human glioblastoma was validated by immunohistochemistry, using a tissue microarray. Through qPCR analysis of gene induction in primary endothelial cells, we provide evidence that increased VEGF-A and TGF\u03b22 signalling in the tumour microenvironment is sufficient to invoke many of the changes in gene expression noted in glioblastoma vessels. Notably, we found an enrichment of Smad target genes within the distinct gene signature of glioblastoma vessels and a significant increase of Smad signalling complexes in the vasculature of human glioblastoma in situ. This indicates a key role of TGF\u03b2 signalling in regulating vascular phenotype and suggests that, in addition to VEGF-A, TGF\u03b22 may represent a new target for vascular normalization therapy.", "doi": "10.1002/path.4072", "pmid": "22786655", "labels": {"Array and Analysis Facility": null, "Tissue Profiling": null}, "xrefs": [], "notes": [], "created": "2017-05-04T14:55:52.086Z", "modified": "2017-05-30T12:54:57.271Z"}, {"entity": "publication", "iuid": "60af987d1dab4b67b147feb04b723afe", "links": {"self": {"href": "https://publications.scilifelab.se/publication/60af987d1dab4b67b147feb04b723afe.json"}, "display": {"href": "https://publications.scilifelab.se/publication/60af987d1dab4b67b147feb04b723afe"}}, "title": "Role of sepsis in the development of limb muscle weakness in a porcine intensive care unit model.", "authors": [{"family": "Aare", "given": "Sudhakar", "initials": "S"}, {"family": "Radell", "given": "Peter", "initials": "P"}, {"family": "Eriksson", "given": "Lars I", "initials": "LI"}, {"family": "Chen", "given": "Yi-Wen", "initials": "YW"}, {"family": "Hoffman", "given": "Eric P", "initials": "EP"}, {"family": "Larsson", "given": "Lars", "initials": "L"}], "type": "journal article", "published": "2012-09-18", "journal": {"volume": "44", "issn": "1531-2267", "issue": "18", "pages": "865-877", "title": "Physiol. Genomics", "issn-l": "1094-8341"}, "abstract": "Severe muscle wasting and loss of muscle function in critically ill mechanically ventilated intensive care unit (ICU) patients have significant negative consequences on their recovery and rehabilitation that persist long after their hospital discharge; moreover, the underlying mechanisms are unclear. Mechanical ventilation (MV) and immobilization-induced modifications play an important role in these consequences, including endotoxin-induced sepsis. The present study aims to investigate how sepsis aggravates ventilator and immobilization-related limb muscle dysfunction. Hence, biceps femoris muscle gene expression was investigated in pigs exposed to ICU intervention, i.e., immobilization, sedation, and MV, alone or in combination with sepsis, for 5 days. In previous studies, we have shown that ICU intervention alone or in combination with sepsis did not affect muscle fiber size on day 5, but a significant decrease was observed in single fiber maximal force normalized to cross-sectional area (specific force) when sepsis was added to the ICU intervention. According to microarray data, the addition of sepsis to the ICU intervention induced a deregulation of > 500 genes, such as an increased expression of genes involved in chemokine activity, kinase activity, and transcriptional regulation. Genes involved in the regulation of the oxidative stress response and cytoskeletal/sarcomeric and heat shock proteins were on the other hand downregulated when sepsis was added to the ICU intervention. Thus, sepsis has a significant negative effect on muscle function in critically ill ICU patients, and chemokine activity and heat shock protein genes are forwarded to play an instrumental role in this specific muscle wasting condition.", "doi": "10.1152/physiolgenomics.00031.2012", "pmid": "22851759", "labels": {"Array and Analysis Facility": null}, "xrefs": [{"db": "pii", "key": "physiolgenomics.00031.2012"}], "notes": [], "created": "2017-05-04T15:03:00.265Z", "modified": "2017-05-30T12:37:41.547Z"}, {"entity": "publication", "iuid": "71c62030cc0446d5b86aff2877a1836b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/71c62030cc0446d5b86aff2877a1836b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/71c62030cc0446d5b86aff2877a1836b"}}, "title": "Loss-of-heterozygosity on chromosome 19q in early-stage serous ovarian cancer is associated with recurrent disease.", "authors": [{"family": "Skirnisdottir", "given": "Ingiridur", "initials": "I"}, {"family": "Mayrhofer", "given": "Markus", "initials": "M"}, {"family": "Ryd\u00e5ker", "given": "Maria", "initials": "M"}, {"family": "Akerud", "given": "Helena", "initials": "H"}, {"family": "Isaksson", "given": "Anders", "initials": "A"}], "type": "journal article", "published": "2012-09-12", "journal": {"volume": "12", "issn": "1471-2407", "issue": null, "pages": "407", "title": "BMC Cancer", "issn-l": "1471-2407"}, "abstract": "Ovarian cancer is a heterogeneous disease and prognosis for apparently similar cases of ovarian cancer varies. Recurrence of the disease in early stage (FIGO-stages I-II) serous ovarian cancer results in survival that is comparable to those with recurrent advanced-stage disease. The aim of this study was to investigate if there are specific genomic aberrations that may explain recurrence and clinical outcome.\n\nFifty-one women with early stage serous ovarian cancer were included in the study. DNA was extracted from formalin fixed samples containing tumor cells from ovarian tumors. Tumor samples from thirty-seven patients were analysed for allele-specific copy numbers using OncoScan single nucleotide polymorphism arrays from Affymetrix and the bioinformatic tool Tumor Aberration Prediction Suite. Genomic gains, losses, and loss-of-heterozygosity that associated with recurrent disease were identified.\n\nThe most significant differences (p\u2009<\u20090.01) in Loss-of-heterozygosity (LOH) were identified in two relatively small regions of chromosome 19; 8.0-8,8\u2009Mbp (19 genes) and 51.5-53.0\u2009Mbp (37 genes). Thus, 56 genes on chromosome 19 were potential candidate genes associated with clinical outcome. LOH at 19q (51-56\u2009Mbp) was associated with shorter disease-free survival and was an independent prognostic factor for survival in a multivariate Cox regression analysis. In particular LOH on chromosome 19q (51-56\u2009Mbp) was significantly (p\u2009<\u20090.01) associated with loss of TP53 function.\n\nThe results of our study indicate that presence of two aberrations in TP53 on 17p and LOH on 19q in early stage serous ovarian cancer is associated with recurrent disease. Further studies related to the findings of chromosomes 17 and 19 are needed to elucidate the molecular mechanism behind the recurring genomic aberrations and the poor clinical outcome.", "doi": "10.1186/1471-2407-12-407", "pmid": "22967087", "labels": {"Array and Analysis Facility": null}, "xrefs": [{"db": "pii", "key": "1471-2407-12-407"}, {"db": "pmc", "key": "PMC3495882"}], "notes": [], "created": "2017-05-04T15:02:55.178Z", "modified": "2017-05-30T14:49:43.224Z"}, {"entity": "publication", "iuid": "febbdae8a9934f24b045fce3a12cd7ce", "links": {"self": {"href": "https://publications.scilifelab.se/publication/febbdae8a9934f24b045fce3a12cd7ce.json"}, "display": {"href": "https://publications.scilifelab.se/publication/febbdae8a9934f24b045fce3a12cd7ce"}}, "title": "Global transcriptional response to ISCOM-Matrix adjuvant at the site of administration and in the draining lymph node early after intramuscular injection in pigs.", "authors": [{"family": "Ahlberg", "given": "Viktor", "initials": "V"}, {"family": "L\u00f6vgren Bengtsson", "given": "Karin", "initials": "K"}, {"family": "Wallgren", "given": "Per", "initials": "P"}, {"family": "Fossum", "given": "Caroline", "initials": "C"}], "type": "journal article", "published": "2012-09-00", "journal": {"volume": "38", "issn": "1879-0089", "issue": "1", "pages": "17-26", "title": "Dev. Comp. Immunol.", "issn-l": "0145-305X"}, "abstract": "ISCOM vaccines induce a balanced Th1/Th2 response, long-lasting antibody responses and cytotoxic T lymphocytes. The mode of action for the adjuvant component, the ISCOM-Matrix, is known to some extent but questions remain regarding its mechanism of action. The Affymetrix GeneChip\u00ae Porcine Genome Array was applied to study the global transcriptional response to ISCOM-Matrix in pigs at the injection site and in the draining lymph node 24h after i.m. injection. Gene enrichment analysis revealed inflammation, innate immunity and antigen processing to be central in the ISCOM-Matrix response. At the injection site, 594 genes were differentially expressed, including up-regulation of the cytokines osteopontin (SPP1), IL-10 and IL-18 and the chemokines CCL2, CCL19 and CXCL16. Of the 362 genes differentially expressed in the lymph node, IL-1\u03b2 and CXCL11 were up-regulated whereas IL18, CCL15 and CXCL12 were down-regulated. ISCOM-Matrix also modulated genes for pattern recognition receptors at the injection site (TLR2, TLR4, MRC1, PTX3, LGALS3) and in the lymph node (TLR4, RIG-I, MDA5, OAS1, EIF2AK2, LGALS3). A high proportion of up-regulated interferon-regulated genes indicated an interferon response. Thus, several genes, genetic pathways and biological processes were identified that are likely to shape the early immune response elicited by ISCOM-based vaccines.", "doi": "10.1016/j.dci.2012.03.005", "pmid": "22426325", "labels": {"Array and Analysis Facility": null}, "xrefs": [{"db": "pii", "key": "S0145-305X(12)00043-2"}], "notes": [], "created": "2017-05-04T15:02:56.385Z", "modified": "2017-05-30T12:36:54.617Z"}, {"entity": "publication", "iuid": "679f970f91c14171b9ebc9c804976e4e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/679f970f91c14171b9ebc9c804976e4e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/679f970f91c14171b9ebc9c804976e4e"}}, "title": "Loss of cancer drug activity in colon cancer HCT-116 cells during spheroid formation in a new 3-D spheroid cell culture system.", "authors": [{"family": "Karlsson", "given": "Henning", "initials": "H"}, {"family": "Frykn\u00e4s", "given": "M\u00e5rten", "initials": "M"}, {"family": "Larsson", "given": "Rolf", "initials": "R"}, {"family": "Nygren", "given": "Peter", "initials": "P"}], "type": "journal article", "published": "2012-08-01", "journal": {"volume": "318", "issn": "1090-2422", "issue": "13", "pages": "1577-1585", "title": "Exp. Cell Res.", "issn-l": "0014-4827"}, "abstract": "Clinically relevant in vitro methods are needed to identify new cancer drugs for solid tumors. We report on a new 3-D spheroid cell culture system aimed to mimic the properties of solid tumors in vivo. The colon cancer cell lines HCT-116 wt and HCT-116 wt/GFP were grown as monolayers and for 3 or 6 days on 96-well NanoCulture\u00ae plates to form spheroids. Expression of surface markers, genes and hypoxia were assessed to characterize the spheroids and drug induced cytotoxicity was evaluated based on fluorescein diacetate (FDA) conversion by viable cells to fluorescent fluorescein or by direct measurement of fluorescence of GFP marked cells after a 72 h drug incubation. The cells reproducibly formed spheroids in the NanoCulture\u00ae plates with tight cell-attachment after 6 days. Cells in spheroids showed geno- and phenotypical properties reminiscent of hypoxic stem cells. Monolayer cultured cells were sensitive to standard and investigational drugs, whereas the spheroids gradually turned resistant. Similar results for cytotoxicity were observed using simplified direct measurement of fluorescence of GFP marked cells compared with FDA incubation. In conclusion, this new 3-D spheroid cell culture system provides a convenient and clinically relevant model for the identification and characterization of cancer drugs for solid tumors.", "doi": "10.1016/j.yexcr.2012.03.026", "pmid": "22487097", "labels": {"Array and Analysis Facility": null}, "xrefs": [{"db": "pii", "key": "S0014-4827(12)00162-0"}], "notes": [], "created": "2017-05-04T15:02:58.085Z", "modified": "2017-05-30T12:37:13.364Z"}, {"entity": "publication", "iuid": "cb3714bba2054d88a6db98b25edb4c9c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/cb3714bba2054d88a6db98b25edb4c9c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/cb3714bba2054d88a6db98b25edb4c9c"}}, "title": "Next generation RNA-sequencing in prognostic subsets of chronic lymphocytic leukemia.", "authors": [{"family": "Mansouri", "given": "Larry", "initials": "L"}, {"family": "Gunnarsson", "given": "Rebeqa", "initials": "R"}, {"family": "Sutton", "given": "Lesley-Ann", "initials": "LA"}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}, {"family": "Hooper", "given": "Sean D", "initials": "SD"}, {"family": "Mayrhofer", "given": "Markus", "initials": "M"}, {"family": "Juliusson", "given": "Gunnar", "initials": "G"}, {"family": "Isaksson", "given": "Anders", "initials": "A"}, {"family": "Gyllensten", "given": "Ulf", "initials": "U"}, {"family": "Rosenquist", "given": "Richard", "initials": "R"}], "type": "comparative study", "published": "2012-07-00", "journal": {"volume": "87", "issn": "1096-8652", "issue": "7", "pages": "737-740", "title": "Am. J. Hematol.", "issn-l": "0361-8609"}, "abstract": "Advances in next-generation RNA-sequencing have revealed the complexity of transcriptomes by allowing both coding and noncoding(nc)RNAs to be analyzed. However, limited data exist regarding the whole transcriptional landscape of chronic lymphocytic leukemia(CLL). In this pilot-study, we evaluated RNA-sequencing in CLL by comparing two subsets which carry almost identical or \"stereotyped\" B-cell receptors with distinct clinical outcome, that is the poor-prognostic subset #1 (n 5 4) and the more favorable-prognostic subset #4(n 5 4). Our analysis revealed that 156 genes (e.g. LPL, WNT9A) and 76 ncRNAs, (e.g. SNORD48, SNORD115) were differentially expressed between the subsets. This technology also enabled us to identify numerous subset-specific splice variants (n 5 406), which were predominantly expressed in subset #1, including a splice-isoform of MSI2 with a novel start exon. A further important application of RNA-sequencing was for mutation detection and revealed 16\u201330 missense mutations per sample; notably many of these changes were found in genes with a strong potential for involvement in CLL pathogenesis, e.g., ATM and NOTCH2.This study not only demonstrates the effectiveness of RNA-sequencing for identifying mutations, quantifying gene expression and detecting splicing events, but also highlights the potential such global approaches have to significantly advance our understanding of the molecular mechanisms behind CLL development.", "doi": "10.1002/ajh.23227", "pmid": "22674506", "labels": {"National Genomics Infrastructure": null, "Array and Analysis Facility": null, "NGI Uppsala (Uppsala Genome Center)": null}, "xrefs": [], "notes": [], "created": "2017-05-04T14:57:27.993Z", "modified": "2021-07-07T14:37:06.614Z"}, {"entity": "publication", "iuid": "0d57c18748214d2ebfcfa7819a6aafe6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0d57c18748214d2ebfcfa7819a6aafe6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0d57c18748214d2ebfcfa7819a6aafe6"}}, "title": "1012 Synergistic Effects of PI3K or P38 MAPK Inhibition in Combination With Vandetanib Treatment in Glioblastoma Cells", "authors": [{"family": "Sooman", "given": "L", "initials": "L"}, {"family": "Ekman", "given": "S", "initials": "S"}, {"family": "Andersson", "given": "C", "initials": "C"}, {"family": "Johansson", "given": "F", "initials": "F"}, {"family": "Goransson-Kultima", "given": "H", "initials": "H"}, {"family": "Isaksson", "given": "A", "initials": "A"}, {"family": "Bergqvist", "given": "M", "initials": "M"}, {"family": "Blomquist", "given": "E", "initials": "E"}, {"family": "Lennartsson", "given": "J", "initials": "J"}, {"family": "Gullbo", "given": "J", "initials": "J"}], "type": "journal-article", "published": "2012-07-00", "journal": {"volume": "48", "issn": "0959-8049", "issue": null, "pages": "S244", "title": "European Journal of Cancer", "issn-l": "0959-8049"}, "abstract": null, "doi": "10.1016/s0959-8049(12)71629-5", "pmid": null, "labels": {"Array and Analysis Facility": null}, "xrefs": [], "notes": [], "created": "2017-05-04T15:02:57.525Z", "modified": "2021-06-22T12:06:35.202Z"}, {"entity": "publication", "iuid": "9674d68c923b43cea1ce8b3b2ac0dc9b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9674d68c923b43cea1ce8b3b2ac0dc9b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9674d68c923b43cea1ce8b3b2ac0dc9b"}}, "title": "Digital gene expression profiling of primary acute lymphoblastic leukemia cells.", "authors": [{"family": "Nordlund", "given": "J", "initials": "J", "orcid": "0000-0001-8699-9959", "researcher": {"href": "https://publications.scilifelab.se/researcher/ddf48c9262134821bcc6ce1180049753.json"}}, {"family": "Kiialainen", "given": "A", "initials": "A"}, {"family": "Karlberg", "given": "O", "initials": "O"}, {"family": "Berglund", "given": "E C", "initials": "EC"}, {"family": "G\u00f6ransson-Kultima", "given": "H", "initials": "H"}, {"family": "S\u00f8nderk\u00e6r", "given": "M", "initials": "M"}, {"family": "Nielsen", "given": "K L", "initials": "KL"}, {"family": "Gustafsson", "given": "M G", "initials": "MG"}, {"family": "Behrendtz", "given": "M", "initials": "M"}, {"family": "Forestier", "given": "E", "initials": "E"}, {"family": "Perkki\u00f6", "given": "M", "initials": "M"}, {"family": "S\u00f6derh\u00e4ll", "given": "S", "initials": "S"}, {"family": "L\u00f6nnerholm", "given": "G", "initials": "G"}, {"family": "Syv\u00e4nen", "given": "A-C", "initials": "AC", "orcid": "0000-0002-9681-9146", "researcher": {"href": "https://publications.scilifelab.se/researcher/f7012e35025543379380cb90efd71243.json"}}], "type": "journal article", "published": "2012-06-00", "journal": {"volume": "26", "issn": "1476-5551", "issue": "6", "pages": "1218-1227", "title": "Leukemia", "issn-l": "0887-6924"}, "abstract": "We determined the genome-wide digital gene expression (DGE) profiles of primary acute lymphoblastic leukemia (ALL) cells from 21 patients taking advantage of 'second-generation' sequencing technology. Patients included in this study represent four cytogenetically distinct subtypes of B-cell precursor (BCP) ALL and T-cell lineage ALL (T-ALL). The robustness of DGE combined with supervised classification by nearest shrunken centroids (NSC) was validated experimentally and by comparison with published expression data for large sets of ALL samples. Genes that were differentially expressed between BCP ALL subtypes were enriched to distinct signaling pathways with dic(9;20) enriched to TP53 signaling, t(9;22) to interferon signaling, as well as high hyperdiploidy and t(12;21) to apoptosis signaling. We also observed antisense tags expressed from the non-coding strand of ~50% of annotated genes, many of which were expressed in a subtype-specific pattern. Antisense tags from 17 gene regions unambiguously discriminated between the BCP ALL and T-ALL subtypes, and antisense tags from 76 gene regions discriminated between the 4 BCP subtypes. We observed a significant overlap of gene regions with alternative polyadenylation and antisense transcription (P<1 \u00d7 10(-15)). Our study using DGE profiling provided new insights into the RNA expression patterns in ALL cells.", "doi": "10.1038/leu.2011.358", "pmid": "22173241", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (SNP&SEQ Technology Platform)": null, "Array and Analysis Facility": null}, "xrefs": [{"db": "pii", "key": "leu2011358"}, {"db": "pmc", "key": "PMC3377998"}, {"db": "GEO", "key": "GSE26878"}], "notes": [], "created": "2017-05-04T15:01:02.547Z", "modified": "2021-07-07T15:11:02.260Z"}, {"entity": "publication", "iuid": "f514e4bc75ea468aa19f05ee6aeec896", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f514e4bc75ea468aa19f05ee6aeec896.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f514e4bc75ea468aa19f05ee6aeec896"}}, "title": "Accelerated proliferation and differential global gene expression in pancreatic islets of five-week-old heterozygous Men1 mice: Men1 is a haploinsufficient suppressor.", "authors": [{"family": "Lejonklou", "given": "Margareta H", "initials": "MH"}, {"family": "Barbu", "given": "Andreea", "initials": "A"}, {"family": "St\u00e5lberg", "given": "Peter", "initials": "P"}, {"family": "Skogseid", "given": "Britt", "initials": "B"}], "type": "journal article", "published": "2012-06-00", "journal": {"volume": "153", "issn": "1945-7170", "issue": "6", "pages": "2588-2598", "title": "Endocrinology", "issn-l": "0013-7227"}, "abstract": "Individuals carrying heterozygous (hz) MEN1 (Multiple Endocrine Neoplasia Syndrome Type 1) germ line mutations develop endocrine tumors as a result of somatic loss of the wild-type (wt) allele. However, endocrine cell proliferation has been observed despite wt allele retention, indicating haploinsufficiency. To study downstream molecular effects of the hz haplotype, a germ line Men1 hz mouse model was used to explore differences in global endocrine pancreatic gene expression. Because islet cells of 5-wk-old hz mice express Menin from the retained wt Men1 allele, these were isolated after collagenase digestion of the pancreas, and used for global gene expression array. Wild-type littermates were used for comparison. Array findings were corroborated by quantitative PCR, Western blotting, in situ proximity ligation assay, and immunohistochemistry. The hz islets show increased proliferation: the Ki-67 index was twice as high as in wt islets (3.48 vs. 1.74%; P = 0.024). The microarray results demonstrated that several genes were differentially expressed. Some selected genes were studied on the protein level, e.g. the cytoskeletal regulator myristoylated alanine-rich protein kinase C substrate (Marcks) was significantly less expressed in hz islets, using in situ proximity ligation assay and Western blotting (P < 0.001 and P < 0.01, respectively). Further, gene ontology analysis showed that genes with higher mRNA expression in the hz endocrine pancreas were associated with e.g. chromatin maintenance and apoptosis. Lower mRNA was observed for genes involved in growth factor binding. In conclusion, despite retained Menin expression, proliferation was accelerated, and numerous genes were differentially expressed in the endocrine pancreas of 5-wk-old hz Men1 mice, corroborating the hypothesis that MEN1 is a haploinsufficient suppressor.", "doi": "10.1210/en.2011-1924", "pmid": "22492302", "labels": {"Array and Analysis Facility": null}, "xrefs": [{"db": "pii", "key": "en.2011-1924"}, {"db": "GEO", "key": "GSE29674"}], "notes": [], "created": "2017-05-04T15:02:56.685Z", "modified": "2017-05-30T12:36:59.271Z"}, {"entity": "publication", "iuid": "65f3916f49f14417a25de1d57057d0ef", "links": {"self": {"href": "https://publications.scilifelab.se/publication/65f3916f49f14417a25de1d57057d0ef.json"}, "display": {"href": "https://publications.scilifelab.se/publication/65f3916f49f14417a25de1d57057d0ef"}}, "title": "A comprehensive analysis of human gene expression profiles identifies stromal immunoglobulin \u03ba C as a compatible prognostic marker in human solid tumors.", "authors": [{"family": "Schmidt", "given": "Marcus", "initials": "M"}, {"family": "Hellwig", "given": "Birte", "initials": "B"}, {"family": "Hammad", "given": "Seddik", "initials": "S"}, {"family": "Othman", "given": "Amnah", "initials": "A"}, {"family": "Lohr", "given": "Miriam", "initials": "M"}, {"family": "Chen", "given": "Zonglin", "initials": "Z"}, {"family": "Boehm", "given": "Daniel", "initials": "D"}, {"family": "Gebhard", "given": "Susanne", "initials": "S"}, {"family": "Petry", "given": "Ilka", "initials": "I"}, {"family": "Lebrecht", "given": "Antje", "initials": "A"}, {"family": "Cadenas", "given": "Cristina", "initials": "C"}, {"family": "Marchan", "given": "Rosemarie", "initials": "R"}, {"family": "Stewart", "given": "Joanna D", "initials": "JD"}, {"family": "Solbach", "given": "Christine", "initials": "C"}, {"family": "Holmberg", "given": "Lars", "initials": "L"}, {"family": "Edlund", "given": "Karolina", "initials": "K"}, {"family": "Kultima", "given": "Hanna G\u00f6ransson", "initials": "HG"}, {"family": "Rody", "given": "Achim", "initials": "A"}, {"family": "Berglund", "given": "Anders", "initials": "A"}, {"family": "Lambe", "given": "Mats", "initials": "M"}, {"family": "Isaksson", "given": "Anders", "initials": "A"}, {"family": "Botling", "given": "Johan", "initials": "J"}, {"family": "Karn", "given": "Thomas", "initials": "T"}, {"family": "M\u00fcller", "given": "Volkmar", "initials": "V"}, {"family": "Gerhold-Ay", "given": "Aslihan", "initials": "A"}, {"family": "Cotarelo", "given": "Christina", "initials": "C"}, {"family": "Sebastian", "given": "Martin", "initials": "M"}, {"family": "Kronenwett", "given": "Ralf", "initials": "R"}, {"family": "Bojar", "given": "Hans", "initials": "H"}, {"family": "Lehr", "given": "Hans-Anton", "initials": "HA"}, {"family": "Sahin", "given": "Ugur", "initials": "U"}, {"family": "Koelbl", "given": "Heinz", "initials": "H"}, {"family": "Gehrmann", "given": "Mathias", "initials": "M"}, {"family": "Micke", "given": "Patrick", "initials": "P"}, {"family": "Rahnenf\u00fchrer", "given": "J\u00f6rg", "initials": "J"}, {"family": "Hengstler", "given": "Jan G", "initials": "JG"}], "type": "journal article", "published": "2012-05-01", "journal": {"volume": "18", "issn": "1078-0432", "issue": "9", "pages": "2695-2703", "title": "Clin. Cancer Res.", "issn-l": null}, "abstract": "Although the central role of the immune system for tumor prognosis is generally accepted, a single robust marker is not yet available.\n\nOn the basis of receiver operating characteristic analyses, robust markers were identified from a 60-gene B cell-derived metagene and analyzed in gene expression profiles of 1,810 breast cancer; 1,056 non-small cell lung carcinoma (NSCLC); 513 colorectal; and 426 ovarian cancer patients. Protein and RNA levels were examined in paraffin-embedded tissue of 330 breast cancer patients. The cell types were identified with immunohistochemical costaining and confocal fluorescence microscopy.\n\nWe identified immunoglobulin \u03ba C (IGKC) which as a single marker is similarly predictive and prognostic as the entire B-cell metagene. IGKC was consistently associated with metastasis-free survival across different molecular subtypes in node-negative breast cancer (n = 965) and predicted response to anthracycline-based neoadjuvant chemotherapy (n = 845; P < 0.001). In addition, IGKC gene expression was prognostic in NSCLC and colorectal cancer. No association was observed in ovarian cancer. IGKC protein expression was significantly associated with survival in paraffin-embedded tissues of 330 breast cancer patients. Tumor-infiltrating plasma cells were identified as the source of IGKC expression.\n\nOur findings provide IGKC as a novel diagnostic marker for risk stratification in human cancer and support concepts to exploit the humoral immune response for anticancer therapy. It could be validated in several independent cohorts and carried out similarly well in RNA from fresh frozen as well as from paraffin tissue and on protein level by immunostaining.", "doi": "10.1158/1078-0432.CCR-11-2210", "pmid": "22351685", "labels": {"Array and Analysis Facility": null}, "xrefs": [{"db": "pii", "key": "1078-0432.CCR-11-2210"}], "notes": [], "created": "2017-05-04T15:02:56.079Z", "modified": "2017-05-30T12:36:49.862Z"}, {"entity": "publication", "iuid": "997d4ba8a0914edfa6226639e802cf57", "links": {"self": {"href": "https://publications.scilifelab.se/publication/997d4ba8a0914edfa6226639e802cf57.json"}, "display": {"href": "https://publications.scilifelab.se/publication/997d4ba8a0914edfa6226639e802cf57"}}, "title": "Transgenerational effects of early experience on behavioral, hormonal and gene expression responses to acute stress in the precocial chicken.", "authors": [{"family": "Goerlich", "given": "Vivian C", "initials": "VC"}, {"family": "N\u00e4tt", "given": "Daniel", "initials": "D"}, {"family": "Elfwing", "given": "Magnus", "initials": "M"}, {"family": "Macdonald", "given": "Barry", "initials": "B"}, {"family": "Jensen", "given": "Per", "initials": "P"}], "type": "journal article", "published": "2012-05-00", "journal": {"volume": "61", "issn": "1095-6867", "issue": "5", "pages": "711-718", "title": "Horm Behav", "issn-l": "0018-506X"}, "abstract": "Stress during early life can profoundly influence an individual's phenotype. Effects can manifest in the short-term as well as later in life and even in subsequent generations. Transgenerational effects of stress are potentially mediated via modulation of the hypothalamic-pituitary-adrenal axis (HPA) as well as epigenetic mechanisms causing heritable changes in gene expression. To investigate these pathways we subjected domestic chicken (Gallus gallus) to intermittent social isolation for the first three weeks of life. The early life stress resulted in a dampened corticosterone response to restraint stress in affected birds and in their male offspring. Stress-specific genes, such as early growth response 1 (EGR1) and corticotropin releasing hormone receptor 1 (CRHR1), were upregulated immediately after restraint stress, but not under baseline conditions. Treatment differences in gene expression were also correlated across generations which indicate transgenerational epigenetic inheritance. In an associative learning test early stressed birds made more correct choices suggesting a higher coping ability in stressful situations. This study is the first to show transgenerational effects of early life stress in a precocial species by combining behavioral, endocrinological, and transcriptomic measurements.", "doi": "10.1016/j.yhbeh.2012.03.006", "pmid": "22465454", "labels": {"Array and Analysis Facility": null}, "xrefs": [{"db": "pii", "key": "S0018-506X(12)00083-9"}], "notes": [], "created": "2017-05-04T15:02:58.391Z", "modified": "2017-05-30T12:37:18.223Z"}, {"entity": "publication", "iuid": "10cde2acbb4747dab0b852f5fad4d773", "links": {"self": {"href": "https://publications.scilifelab.se/publication/10cde2acbb4747dab0b852f5fad4d773.json"}, "display": {"href": "https://publications.scilifelab.se/publication/10cde2acbb4747dab0b852f5fad4d773"}}, "title": "Tumor-mast cell interactions: induction of pro-tumorigenic genes and anti-tumorigenic 4-1BB in MCs in response to Lewis Lung Carcinoma.", "authors": [{"family": "Wensman", "given": "Helena", "initials": "H"}, {"family": "Kamgari", "given": "Nona", "initials": "N"}, {"family": "Johansson", "given": "Anna", "initials": "A"}, {"family": "Grujic", "given": "Mirjana", "initials": "M"}, {"family": "Calounova", "given": "Gabriela", "initials": "G"}, {"family": "Lundequist", "given": "Anders", "initials": "A"}, {"family": "R\u00f6nnberg", "given": "Elin", "initials": "E"}, {"family": "Pejler", "given": "Gunnar", "initials": "G"}], "type": "journal article", "published": "2012-04-00", "journal": {"volume": "50", "issn": "1872-9142", "issue": "4", "pages": "210-219", "title": "Mol. Immunol.", "issn-l": "0161-5890"}, "abstract": "Mast cells (MCs) can have either detrimental or beneficial effects on malignant processes but the underlying mechanisms are poorly understood. Here we addressed this issue by examining the interaction between Lewis Lung Carcinoma (LLC) cells and MCs. In vivo, LLC tumors caused a profound accumulation of MCs, suggesting that LLC tumors have the capacity to attract MCs. Indeed, transwell migration assays showed that LLC-conditioned medium had chemotactic activity towards MCs, which was blocked by an antibody towards stem cell factor. In order to gain insight into the molecular mechanisms operative in tumor-MC interactions, the effect of LLC on the MC gene expression pattern was examined. As judged by gene array analysis, conditioned medium from LLC cells caused significant upregulation of numerous cell surface receptors and a pro-angiogenic Runx2/VEGF/Dusp5 axis in MCs, the latter in line with a role for MCs in promoting tumor angiogenesis. Among the genes showing the highest extent of upregulation was Tnfrsf9, encoding the anti-tumorigenic protein 4-1BB, suggesting that also anti-tumorigenic factors are induced. Quantitative RT-PCR analysis showed that 4-1BB was upregulated in a transient manner, and it was also shown that tumor cells induce 4-1BB in human MCs. Immunohistochemical analysis showed that LLC-conditioned medium induced 4-1BB also at the protein level. Together, this study provides novel insight into the molecular events associated with MC-tumor interactions and suggests that tumor cells induce both pro- and anti-tumorigenic responses in MCs.", "doi": "10.1016/j.molimm.2012.01.009", "pmid": "22343053", "labels": {"Array and Analysis Facility": null}, "xrefs": [{"db": "pii", "key": "S0161-5890(12)00010-7"}], "notes": [], "created": "2017-05-04T15:02:59.661Z", "modified": "2017-05-30T12:37:32.226Z"}, {"entity": "publication", "iuid": "b839da82b5ed42dfa4c08eb8f18be674", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b839da82b5ed42dfa4c08eb8f18be674.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b839da82b5ed42dfa4c08eb8f18be674"}}, "title": "Mantle cell lymphoma displays a homogenous methylation profile: a comparative analysis with chronic lymphocytic leukemia.", "authors": [{"family": "Halld\u00f3rsd\u00f3ttir", "given": "Anna Margr\u00e9t", "initials": "AM"}, {"family": "Kanduri", "given": "Meena", "initials": "M"}, {"family": "Marincevic", "given": "Millaray", "initials": "M"}, {"family": "Mansouri", "given": "Larry", "initials": "L"}, {"family": "Isaksson", "given": "Anders", "initials": "A"}, {"family": "G\u00f6ransson", "given": "Hanna", "initials": "H"}, {"family": "Axelsson", "given": "Tomas", "initials": "T"}, {"family": "Agarwal", "given": "Prasoon", "initials": "P"}, {"family": "Jernberg-Wiklund", "given": "Helena", "initials": "H"}, {"family": "Stamatopoulos", "given": "Kostas", "initials": "K"}, {"family": "Sander", "given": "Birgitta", "initials": "B"}, {"family": "Ehrencrona", "given": "Hans", "initials": "H"}, {"family": "Rosenquist", "given": "Richard", "initials": "R"}], "type": "comparative study", "published": "2012-04-00", "journal": {"volume": "87", "issn": "1096-8652", "issue": "4", "pages": "361-367", "title": "Am. J. Hematol.", "issn-l": "0361-8609"}, "abstract": "Mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL) are mature CD5(+) B-cell malignancies with different biological/clinical characteristics. We recently reported an association between different prognostic subgroups of CLL (i.e., IGHV mutated and unmutated) and genomic methylation pattern. However, the relationship between DNA methylation and prognostic markers, such as the proliferation gene expression signature, has not been investigated in MCL. We applied high-resolution methylation microarrays (27,578 CpG sites) to assess the global DNA methylation profiles in 20 MCL (10 each with high/low proliferation signature) and 30 CLL (15 poor-prognostic IGHV unmutated subset #1 and 15 good-prognostic IGHV mutated subset #4) samples. Notably, MCL and each CLL subset displayed distinct genomic methylation profiles. After unsupervised hierarchical clustering, 17/20 MCL cases formed a cluster separate from CLL, while CLL subsets #1 and #4 formed subclusters. Surprisingly, few differentially methylated genes (n = 6) were identified between high vs. low proliferation MCL. In contrast, distinct methylation profiles were demonstrated for MCL and CLL. Importantly, certain functional classes of genes were preferentially methylated in either disease. For instance, developmental genes, in particular homeobox transcription factor genes (e.g., HLXB9, HOXA13), were more highly methylated in MCL, whereas apoptosis-related genes were enriched among targets methylated in CLL (e.g., CYFIP2, NR4A1). Results were validated using pyrosequencing, RQ-PCR and reexpression of specific genes. In summary, the methylation profile of MCL was homogeneous and no correlation with the proliferation signature was observed. Compared to CLL, however, marked differences were discovered such as the preferential methylation of homeobox genes in MCL.", "doi": "10.1002/ajh.23115", "pmid": "22374828", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (SNP&SEQ Technology Platform)": null, "Array and Analysis Facility": null}, "xrefs": [], "notes": [], "created": "2017-05-04T15:00:52.258Z", "modified": "2020-01-21T13:56:04.843Z"}, {"entity": "publication", "iuid": "47589549f1f34f26aaf1da50af5214d1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/47589549f1f34f26aaf1da50af5214d1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/47589549f1f34f26aaf1da50af5214d1"}}, "title": "The transcriptome of the adenovirus infected cell.", "authors": [{"family": "Zhao", "given": "Hongxing", "initials": "H"}, {"family": "Dahl\u00f6", "given": "Martin", "initials": "M"}, {"family": "Isaksson", "given": "Anders", "initials": "A"}, {"family": "Syv\u00e4nen", "given": "Ann-Christine", "initials": "AC", "orcid": "0000-0002-9681-9146", "researcher": {"href": "https://publications.scilifelab.se/researcher/f7012e35025543379380cb90efd71243.json"}}, {"family": "Pettersson", "given": "Ulf", "initials": "U"}], "type": "journal article", "published": "2012-03-15", "journal": {"volume": "424", "issn": "1096-0341", "issue": "2", "pages": "115-128", "title": "Virology", "issn-l": "0042-6822"}, "abstract": "Alternations of cellular gene expression following an adenovirus type 2 infection of human primary cells were studied by using superior sensitive cDNA sequencing. In total, 3791 cellular genes were identified as differentially expressed more than 2-fold. Genes involved in DNA replication, RNA transcription and cell cycle regulation were very abundant among the up-regulated genes. On the other hand, genes involved in various signaling pathways including TGF-\u03b2, Rho, G-protein, Map kinase, STAT and NF-\u03baB stood out among the down-regulated genes. Binding sites for E2F, ATF/CREB and AP2 were prevalent in the up-regulated genes, whereas binding sites for SRF and NF-\u03baB were dominant among the down-regulated genes. It is evident that the adenovirus has gained a control of the host cell cycle, growth, immune response and apoptosis at 24 h after infection. However, efforts from host cell to block the cell cycle progression and activate an antiviral response were also observed.", "doi": "10.1016/j.virol.2011.12.006", "pmid": "22236370", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (SNP&SEQ Technology Platform)": null, "Array and Analysis Facility": null}, "xrefs": [{"db": "pii", "key": "S0042-6822(11)00564-2"}], "notes": [], "created": "2017-05-04T15:01:13.042Z", "modified": "2021-07-07T15:11:02.422Z"}, {"entity": "publication", "iuid": "0cc8e86f74674b16a843ca1093c66d28", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0cc8e86f74674b16a843ca1093c66d28.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0cc8e86f74674b16a843ca1093c66d28"}}, "title": "Microarray profiling of diaphyseal bone of rats suffering from hypervitaminosis A.", "authors": [{"family": "Lind", "given": "Thomas", "initials": "T"}, {"family": "Hu", "given": "Lijuan", "initials": "L"}, {"family": "Lind", "given": "P Monica", "initials": "PM"}, {"family": "Sugars", "given": "Rachael", "initials": "R"}, {"family": "Andersson", "given": "G\u00f6ran", "initials": "G"}, {"family": "Jacobson", "given": "Annica", "initials": "A"}, {"family": "Melhus", "given": "H\u00e5kan", "initials": "H"}], "type": "journal article", "published": "2012-03-00", "journal": {"volume": "90", "issn": "1432-0827", "issue": "3", "pages": "219-229", "title": "Calcif. Tissue Int.", "issn-l": "0171-967X"}, "abstract": "Vitamin A is the only known compound that produces spontaneous fractures in rats. In an effort to resolve the molecular mechanism behind this effect, we fed young male rats high doses of vitamin A and performed microarray analysis of diaphyseal bone with and without marrow after 1 week, i.e., just before the first fractures appeared. Of the differentially expressed genes in cortical bone, including marrow, 98% were upregulated. In contrast, hypervitaminotic cortical bone without marrow showed reduced expression of 37% of differentially expressed genes. Gene ontology (GO) analysis revealed that only samples containing bone marrow were associated with a GO term, which principally represented extracellular matrix. This is consistent with the histological findings of increased endosteal/marrow osteoblast number. Fourteen genes, including Cyp26b1, which is known to be upregulated by vitamin A, were selected and verified by real-time PCR. In addition, immunohistochemical staining of bone sections confirmed that the bone-specific molecule osteoadherin was upregulated. Further analysis of the major gene-expression changes revealed apparent augmented Wnt signaling in the sample containing bone marrow but reduced Wnt signaling in cortical bone. Moreover, induced expression of hypoxia-associated genes was found only in samples containing bone marrow. Together, these results highlight the importance of compartment-specific analysis of bone and corroborate previous observations of compartment-specific effects of vitamin A, with reduced activity in cortical bone but increased activity in the endosteal/marrow compartment. We specifically identify potential key osteoblast-, Wnt signaling-, and hypoxia-associated genes in the processes leading to spontaneous fractures.", "doi": "10.1007/s00223-011-9561-6", "pmid": "22215263", "labels": {"Array and Analysis Facility": null}, "xrefs": [], "notes": [], "created": "2017-05-04T15:02:55.777Z", "modified": "2017-05-30T12:36:45.142Z"}, {"entity": "publication", "iuid": "0ccfaf0b5fba4e478a018931b547b6fb", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0ccfaf0b5fba4e478a018931b547b6fb.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0ccfaf0b5fba4e478a018931b547b6fb"}}, "title": "Heritable genome-wide variation of gene expression and promoter methylation between wild and domesticated chickens.", "authors": [{"family": "N\u00e4tt", "given": "Daniel", "initials": "D"}, {"family": "Rubin", "given": "Carl-Johan", "initials": "CJ"}, {"family": "Wright", "given": "Dominic", "initials": "D"}, {"family": "Johnsson", "given": "Martin", "initials": "M"}, {"family": "Belt\u00e9ky", "given": "Johan", "initials": "J"}, {"family": "Andersson", "given": "Leif", "initials": "L"}, {"family": "Jensen", "given": "Per", "initials": "P"}], "type": "journal article", "published": "2012-02-04", "journal": {"volume": "13", "issn": "1471-2164", "issue": null, "pages": "59", "title": "BMC Genomics", "issn-l": "1471-2164"}, "abstract": "Variations in gene expression, mediated by epigenetic mechanisms, may cause broad phenotypic effects in animals. However, it has been debated to what extent expression variation and epigenetic modifications, such as patterns of DNA methylation, are transferred across generations, and therefore it is uncertain what role epigenetic variation may play in adaptation.\n\nIn Red Junglefowl, ancestor of domestic chickens, gene expression and methylation profiles in thalamus/hypothalamus differed substantially from that of a domesticated egg laying breed. Expression as well as methylation differences were largely maintained in the offspring, demonstrating reliable inheritance of epigenetic variation. Some of the inherited methylation differences were tissue-specific, and the differential methylation at specific loci were little changed after eight generations of intercrossing between Red Junglefowl and domesticated laying hens. There was an over-representation of differentially expressed and methylated genes in selective sweep regions associated with chicken domestication.\n\nOur results show that epigenetic variation is inherited in chickens, and we suggest that selection of favourable epigenomes, either by selection of genotypes affecting epigenetic states, or by selection of methylation states which are inherited independently of sequence differences, may have been an important aspect of chicken domestication.", "doi": "10.1186/1471-2164-13-59", "pmid": "22305654", "labels": {"Array and Analysis Facility": null}, "xrefs": [{"db": "pii", "key": "1471-2164-13-59"}, {"db": "pmc", "key": "PMC3297523"}], "notes": [], "created": "2017-05-04T15:02:55.478Z", "modified": "2017-05-30T14:49:47.817Z"}, {"entity": "publication", "iuid": "d373e71c06094217863b00c08b3b5ee2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d373e71c06094217863b00c08b3b5ee2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d373e71c06094217863b00c08b3b5ee2"}}, "title": "Lymphoblastoid cell line with B1 cell characteristics established from a chronic lymphocytic leukemia clone by in vitro EBV infection.", "authors": [{"family": "Ros\u00e9n", "given": "Anders", "initials": "A"}, {"family": "Bergh", "given": "Ann-Charlotte", "initials": "AC"}, {"family": "Gogok", "given": "Peter", "initials": "P"}, {"family": "Evaldsson", "given": "Chamilly", "initials": "C"}, {"family": "Myhrinder", "given": "Anna Lanemo", "initials": "AL"}, {"family": "Hellqvist", "given": "Eva", "initials": "E"}, {"family": "Rasul", "given": "Abu", "initials": "A"}, {"family": "Bj\u00f6rkholm", "given": "Magnus", "initials": "M"}, {"family": "Jansson", "given": "Mattias", "initials": "M"}, {"family": "Mansouri", "given": "Larry", "initials": "L"}, {"family": "Liu", "given": "Anquan", "initials": "A"}, {"family": "Teh", "given": "Bin Tean", "initials": "BT"}, {"family": "Rosenquist", "given": "Richard", "initials": "R"}, {"family": "Klein", "given": "Eva", "initials": "E"}], "type": "journal article", "published": "2012-01-01", "journal": {"volume": "1", "issn": "2162-4011", "issue": "1", "pages": "18-27", "title": "Oncoimmunology", "issn-l": null}, "abstract": "Chronic lymphocytic leukemia (CLL) cells express the receptor for Epstein-Barr virus (EBV) and can be infected in vitro. Infected cells do not express the growth-promoting set of EBV-encoded genes and therefore they do not yield LCLs, in most experiments. With exceptional clones, lines were obtained however. We describe a new line, HG3, established by in vitro EBV-infection from an IGHV1-2 unmutated CLL patient clone. All cells expressed EBNA-2 and LMP-1, the EBV-encoded genes pivotal for transformation. The karyotype, FISH cytogenetics and SNP-array profile of the line and the patient's ex vivo clone showed biallelic 13q14 deletions with genomic loss of DLEU7, miR15a/miR16-1, the two micro-RNAs that are deleted in 50% of CLL cases. Further features of CLL cells were: expression of CD5/CD20/CD27/CD43 and release of IgM natural antibodies reacting with oxLDL-like epitopes on apoptotic cells (cf. stereotyped subset-1). Comparison with two LCLs established from normal B cells showed 32 genes expressed at higher levels (> 2-fold). Among these were LHX2 and LILRA. These genes may play a role in the development of the disease. LHX2 expression was shown in self-renewing multipotent hematopoietic stem cells, and LILRA4 codes for a receptor for bone marrow stromal cell antigen-2 that contributes to B cell development. Twenty-four genes were expressed at lower levels, among these PARD3 that is essential for asymmetric cell division. These genes may contribute to establish precursors of CLL clones by regulation of cellular phenotype in the hematopoietic compartment. Expression of CD5/CD20/CD27/CD43 and spontaneous production of natural antibodies may identify the CLL cell as a self-renewing B1 lymphocyte.", "doi": "10.4161/onci.1.1.18400", "pmid": "22720208", "labels": {"Array and Analysis Facility": null}, "xrefs": [{"db": "pii", "key": "2011ONCOIMM0075"}, {"db": "pmc", "key": "PMC3376971"}], "notes": [], "created": "2017-05-04T15:02:59.963Z", "modified": "2017-05-31T08:17:05.183Z"}, {"entity": "publication", "iuid": "fcddedebd2f947529567e84610e7b9bf", "links": {"self": {"href": "https://publications.scilifelab.se/publication/fcddedebd2f947529567e84610e7b9bf.json"}, "display": {"href": "https://publications.scilifelab.se/publication/fcddedebd2f947529567e84610e7b9bf"}}, "title": "Mechanisms underlying the sparing of masticatory versus limb muscle function in an experimental critical illness model.", "authors": [{"family": "Aare", "given": "Sudhakar", "initials": "S"}, {"family": "Ochala", "given": "Julien", "initials": "J"}, {"family": "Norman", "given": "Holly S", "initials": "HS"}, {"family": "Radell", "given": "Peter", "initials": "P"}, {"family": "Eriksson", "given": "Lars I", "initials": "LI"}, {"family": "G\u00f6ransson", "given": "Hanna", "initials": "H"}, {"family": "Chen", "given": "Yi-Wen", "initials": "YW"}, {"family": "Hoffman", "given": "Eric P", "initials": "EP"}, {"family": "Larsson", "given": "Lars", "initials": "L"}], "type": "comparative study", "published": "2011-12-16", "journal": {"volume": "43", "issn": "1531-2267", "issue": "24", "pages": "1334-1350", "title": "Physiol. Genomics", "issn-l": "1094-8341"}, "abstract": "Acute quadriplegic myopathy (AQM) is a common debilitating acquired disorder in critically ill intensive care unit (ICU) patients that is characterized by tetraplegia/generalized weakness of limb and trunk muscles. Masticatory muscles, on the other hand, are typically spared or less affected, yet the mechanisms underlying this striking muscle-specific difference remain unknown. This study aims to evaluate physiological parameters and the gene expression profiles of masticatory and limb muscles exposed to factors suggested to trigger AQM, such as mechanical ventilation, immobilization, neuromuscular blocking agents, corticosteroids (CS), and sepsis for 5 days by using a unique porcine model mimicking the ICU conditions. Single muscle fiber cross-sectional area and force-generating capacity, i.e., maximum force normalized to fiber cross-sectional area (specific force), revealed maintained masseter single muscle fiber cross-sectional area and specific-force after 5 days' exposure to all triggering factors. This is in sharp contrast to observations in limb and trunk muscles, showing a dramatic decline in specific force in response to 5 days' exposure to the triggering factors. Significant differences in gene expression were observed between craniofacial and limb muscles, indicating a highly complex and muscle-specific response involving transcription and growth factors, heat shock proteins, matrix metalloproteinase inhibitor, oxidative stress responsive elements, and sarcomeric proteins underlying the relative sparing of cranial vs. spinal nerve innervated muscles during exposure to the ICU intervention.", "doi": "10.1152/physiolgenomics.00116.2011", "pmid": "22010006", "labels": {"Array and Analysis Facility": null}, "xrefs": [{"db": "pii", "key": "physiolgenomics.00116.2011"}], "notes": [], "created": "2017-05-04T15:02:53.851Z", "modified": "2017-05-30T12:36:12.391Z"}, {"entity": "publication", "iuid": "4981f4e297634c109a11f7a33ef378df", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4981f4e297634c109a11f7a33ef378df.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4981f4e297634c109a11f7a33ef378df"}}, "title": "Muscle wasting and the temporal gene expression pattern in a novel rat intensive care unit model.", "authors": [{"family": "Llano-Diez", "given": "Monica", "initials": "M"}, {"family": "Gustafson", "given": "Ann-Marie", "initials": "AM"}, {"family": "Olsson", "given": "Carl", "initials": "C"}, {"family": "Goransson", "given": "Hanna", "initials": "H"}, {"family": "Larsson", "given": "Lars", "initials": "L"}], "type": "journal article", "published": "2011-12-13", "journal": {"volume": "12", "issn": "1471-2164", "issue": null, "pages": "602", "title": "BMC Genomics", "issn-l": "1471-2164"}, "abstract": "Acute quadriplegic myopathy (AQM) or critical illness myopathy (CIM) is frequently observed in intensive care unit (ICU) patients. To elucidate duration-dependent effects of the ICU intervention on molecular and functional networks that control the muscle wasting and weakness associated with AQM, a gene expression profile was analyzed at time points varying from 6 hours to 14 days in a unique experimental rat model mimicking ICU conditions, i.e., post-synaptically paralyzed, mechanically ventilated and extensively monitored animals.\n\nDuring the observation period, 1583 genes were significantly up- or down-regulated by factors of two or greater. A significant temporal gene expression pattern was constructed at short (6 h-4 days), intermediate (5-8 days) and long (9-14 days) durations. A striking early and maintained up-regulation (6 h-14d) of muscle atrogenes (muscle ring-finger 1/tripartite motif-containing 63 and F-box protein 32/atrogin-1) was observed, followed by an up-regulation of the proteolytic systems at intermediate and long durations (5-14d). Oxidative stress response genes and genes that take part in amino acid catabolism, cell cycle arrest, apoptosis, muscle development, and protein synthesis together with myogenic factors were significantly up-regulated from 5 to 14 days. At 9-14 d, genes involved in immune response and the caspase cascade were up-regulated. At 5-14d, genes related to contractile (myosin heavy chain and myosin binding protein C), regulatory (troponin, tropomyosin), developmental, caveolin-3, extracellular matrix, glycolysis/gluconeogenesis, cytoskeleton/sarcomere regulation and mitochondrial proteins were down-regulated. An activation of genes related to muscle growth and new muscle fiber formation (increase of myogenic factors and JunB and down-regulation of myostatin) and up-regulation of genes that code protein synthesis and translation factors were found from 5 to 14 days.\n\nNovel temporal patterns of gene expression have been uncovered, suggesting a unique, coordinated and highly complex mechanism underlying the muscle wasting associated with AQM in ICU patients and providing new target genes and avenues for intervention studies.", "doi": "10.1186/1471-2164-12-602", "pmid": "22165895", "labels": {"Array and Analysis Facility": null}, "xrefs": [{"db": "pii", "key": "1471-2164-12-602"}, {"db": "pmc", "key": "PMC3266306"}], "notes": [], "created": "2017-05-04T15:02:51.187Z", "modified": "2017-05-30T14:49:24.252Z"}, {"entity": "publication", "iuid": "bb261b9837634c8da859d0e1b65915d9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/bb261b9837634c8da859d0e1b65915d9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/bb261b9837634c8da859d0e1b65915d9"}}, "title": "Inhibition of proteasome deubiquitinating activity as a new cancer therapy.", "authors": [{"family": "D'Arcy", "given": "P\u00e1draig", "initials": "P"}, {"family": "Brnjic", "given": "Slavica", "initials": "S"}, {"family": "Olofsson", "given": "Maria H\u00e4gg", "initials": "MH"}, {"family": "Frykn\u00e4s", "given": "M\u00e5rten", "initials": "M"}, {"family": "Lindsten", "given": "Kristina", "initials": "K"}, {"family": "De Cesare", "given": "Michelandrea", "initials": "M"}, {"family": "Perego", "given": "Paola", "initials": "P"}, {"family": "Sadeghi", "given": "Behnam", "initials": "B"}, {"family": "Hassan", "given": "Moustapha", "initials": "M"}, {"family": "Larsson", "given": "Rolf", "initials": "R"}, {"family": "Linder", "given": "Stig", "initials": "S"}], "type": "journal article", "published": "2011-11-06", "journal": {"volume": "17", "issn": "1546-170X", "issue": "12", "pages": "1636-1640", "title": "Nat. Med.", "issn-l": "1078-8956"}, "abstract": "Ubiquitin-tagged substrates are degraded by the 26S proteasome, which is a multisubunit complex comprising a proteolytic 20S core particle capped by 19S regulatory particles. The approval of bortezomib for the treatment of multiple myeloma validated the 20S core particle as an anticancer drug target. Here we describe the small molecule b-AP15 as a previously unidentified class of proteasome inhibitor that abrogates the deubiquitinating activity of the 19S regulatory particle. b-AP15 inhibited the activity of two 19S regulatory-particle-associated deubiquitinases, ubiquitin C-terminal hydrolase 5 (UCHL5) and ubiquitin-specific peptidase 14 (USP14), resulting in accumulation of polyubiquitin. b-AP15 induced tumor cell apoptosis that was insensitive to TP53 status and overexpression of the apoptosis inhibitor BCL2. We show that treatment with b-AP15 inhibited tumor progression in four different in vivo solid tumor models and inhibited organ infiltration in an acute myeloid leukemia model. Our results show that the deubiquitinating activity of the 19S regulatory particle is a new anticancer drug target.", "doi": "10.1038/nm.2536", "pmid": "22057347", "labels": {"Array and Analysis Facility": null}, "xrefs": [{"db": "pii", "key": "nm.2536"}, {"db": "GEO", "key": "GSE24150"}], "notes": [], "created": "2017-05-04T15:02:53.335Z", "modified": "2017-05-30T14:49:33.477Z"}, {"entity": "publication", "iuid": "1e582e233a684cd7ac3a526fdb677dc9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1e582e233a684cd7ac3a526fdb677dc9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1e582e233a684cd7ac3a526fdb677dc9"}}, "title": "Gene copy number aberrations are associated with survival in histologic subgroups of non-small cell lung cancer.", "authors": [{"family": "Micke", "given": "Patrick", "initials": "P"}, {"family": "Edlund", "given": "Karolina", "initials": "K"}, {"family": "Holmberg", "given": "Lars", "initials": "L"}, {"family": "Kultima", "given": "Hanna G\u00f6ransson", "initials": "HG"}, {"family": "Mansouri", "given": "Larry", "initials": "L"}, {"family": "Ekman", "given": "Simon", "initials": "S"}, {"family": "Bergqvist", "given": "Michael", "initials": "M"}, {"family": "Scheibenflug", "given": "Lena", "initials": "L"}, {"family": "Lamberg", "given": "Kristina", "initials": "K"}, {"family": "Myrdal", "given": "Gunnar", "initials": "G"}, {"family": "Berglund", "given": "Anders", "initials": "A"}, {"family": "Andersson", "given": "Annsofie", "initials": "A"}, {"family": "Lambe", "given": "Mats", "initials": "M"}, {"family": "Nyberg", "given": "Fredrik", "initials": "F"}, {"family": "Thomas", "given": "Andrew", "initials": "A"}, {"family": "Isaksson", "given": "Anders", "initials": "A"}, {"family": "Botling", "given": "Johan", "initials": "J"}], "type": "comparative study", "published": "2011-11-00", "journal": {"volume": "6", "issn": "1556-1380", "issue": "11", "pages": "1833-1840", "title": "J Thorac Oncol", "issn-l": "1556-0864"}, "abstract": "Non-small cell lung cancer (NSCLC) is characterized by a multitude of genetic aberrations with unknown clinical impact. In this study, we aimed to identify gene copy number changes that correlate with clinical outcome in NSCLC. To maximize the chance to identify clinically relevant events, we applied a strategy involving two prognostically extreme patient groups.\n\nShort-term (<20 month; n = 53) and long-term survivors (>58 month; n = 47) were selected from a clinically well-characterized NSCLC patient cohort with available fresh frozen tumor specimens. The samples were analyzed using high-resolution single-nucleotide polymorphism array technology to assess gene copy number variations and array-based gene expression profiling. The molecular data were combined with information on clinical parameters.\n\nGenetic aberrations were strongly associated with tumor histology. In adenocarcinoma (n = 50), gene copy number gains on chromosome 8q21-q24.3 (177 genes) were more frequent in long-term than in short-term survivors. In squamous cell carcinoma (n = 28), gains on chromosome 14q23.1-24.3 (133 genes) were associated with shorter survival, whereas losses in a neighboring region, 14q31.1-32.33 (110 genes), correlated with favorable outcome. In accordance with copy number gains and losses, messenger RNA expression levels of corresponding genes were increased or decreased, respectively.\n\nComprehensive tumor profiling permits the integration of genomic, histologic, and clinical data. We identified gene copy number gains and losses, with corresponding changes in messenger RNA levels that were associated with prognosis in adenocarcinoma and squamous cell carcinoma of the lung.", "doi": "10.1097/JTO.0b013e3182295917", "pmid": "22011649", "labels": {"Array and Analysis Facility": null}, "xrefs": [{"db": "pii", "key": "S1556-0864(15)32245-0"}], "notes": [], "created": "2017-05-04T15:02:52.434Z", "modified": "2017-05-30T12:35:49.266Z"}, {"entity": "publication", "iuid": "a8086f9ee6804106831134f4ea762e2d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a8086f9ee6804106831134f4ea762e2d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a8086f9ee6804106831134f4ea762e2d"}}, "title": "Allele-specific copy number analysis of tumor samples with aneuploidy and tumor heterogeneity.", "authors": [{"family": "Rasmussen", "given": "Markus", "initials": "M"}, {"family": "Sundstr\u00f6m", "given": "Magnus", "initials": "M"}, {"family": "G\u00f6ransson Kultima", "given": "Hanna", "initials": "H"}, {"family": "Botling", "given": "Johan", "initials": "J"}, {"family": "Micke", "given": "Patrick", "initials": "P"}, {"family": "Birgisson", "given": "Helgi", "initials": "H"}, {"family": "Glimelius", "given": "Bengt", "initials": "B"}, {"family": "Isaksson", "given": "Anders", "initials": "A"}], "type": "journal article", "published": "2011-10-24", "journal": {"volume": "12", "issn": "1474-760X", "issue": "10", "pages": "R108", "title": "Genome Biol.", "issn-l": "1474-7596"}, "abstract": "We describe a bioinformatic tool, Tumor Aberration Prediction Suite (TAPS), for the identification of allele-specific copy numbers in tumor samples using data from Affymetrix SNP arrays. It includes detailed visualization of genomic segment characteristics and iterative pattern recognition for copy number identification, and does not require patient-matched normal samples. TAPS can be used to identify chromosomal aberrations with high sensitivity even when the proportion of tumor cells is as low as 30%. Analysis of cancer samples indicates that TAPS is well suited to investigate samples with aneuploidy and tumor heterogeneity, which is commonly found in many types of solid tumors.", "doi": "10.1186/gb-2011-12-10-r108", "pmid": "22023820", "labels": {"Array and Analysis Facility": null}, "xrefs": [{"db": "pii", "key": "gb-2011-12-10-r108"}, {"db": "pmc", "key": "PMC3333778"}], "notes": [], "created": "2017-05-04T15:02:51.918Z", "modified": "2017-05-30T14:49:28.836Z"}, {"entity": "publication", "iuid": "28081e743c0d419d98e741189dd798b0", "links": {"self": {"href": "https://publications.scilifelab.se/publication/28081e743c0d419d98e741189dd798b0.json"}, "display": {"href": "https://publications.scilifelab.se/publication/28081e743c0d419d98e741189dd798b0"}}, "title": "Genomic and clinical characteristics of six patients with partially overlapping interstitial deletions at 10p12p11.", "authors": [{"family": "Wentzel", "given": "Christian", "initials": "C"}, {"family": "Rajcan-Separovic", "given": "Evica", "initials": "E"}, {"family": "Ruivenkamp", "given": "Claudia A L", "initials": "CA"}, {"family": "Chantot-Bastaraud", "given": "Sandra", "initials": "S"}, {"family": "Metay", "given": "Corinne", "initials": "C"}, {"family": "Andrieux", "given": "Joris", "initials": "J"}, {"family": "Anner\u00e9n", "given": "G\u00f6ran", "initials": "G"}, {"family": "Gijsbers", "given": "Antoinet C J", "initials": "AC"}, {"family": "Druart", "given": "Luc", "initials": "L"}, {"family": "Hyon", "given": "Capucine", "initials": "C"}, {"family": "Portnoi", "given": "Marie-France", "initials": "MF"}, {"family": "Stattin", "given": "Eva-Lena", "initials": "EL"}, {"family": "Vincent-Delorme", "given": "Catherine", "initials": "C"}, {"family": "Kant", "given": "Sarina G", "initials": "SG"}, {"family": "Steinraths", "given": "Michelle", "initials": "M"}, {"family": "Marlin", "given": "Sandrine", "initials": "S"}, {"family": "Giurgea", "given": "Irina", "initials": "I"}, {"family": "Thuresson", "given": "Ann-Charlotte", "initials": "AC"}], "type": "case reports", "published": "2011-09-00", "journal": {"volume": "19", "issn": "1476-5438", "issue": "9", "pages": "959-964", "title": "Eur. J. Hum. Genet.", "issn-l": "1018-4813"}, "abstract": "With the clinical implementation of genomic microarrays, the detection of cryptic unbalanced rearrangements in patients with syndromic developmental delay has improved considerably. Here we report the molecular karyotyping and phenotypic description of six new unrelated patients with partially overlapping microdeletions at 10p12.31p11.21 ranging from 1.0 to 10.6\u2009Mb. The smallest region of overlap is 306\u2009kb, which includes WAC gene, known to be associated with microtubule function and to have a role in cell division. Another patient has previously been described with a 10\u2009Mb deletion, partially overlapping with our six patients. All seven patients have developmental delay and a majority of the patients have abnormal behaviour and dysmorphic features, including bulbous nasal tip, deep set eyes, synophrys/thick eyebrows and full cheeks, whereas other features varied. All patients also displayed various visual impairments and six out of seven patients had cardiac malformations. Taken together with the previously reported patient, our study suggests that the detected deletions may represent a new contiguous gene syndrome caused by dosage-sensitive genes that predispose to developmental delay.", "doi": "10.1038/ejhg.2011.71", "pmid": "21522184", "labels": {"National Genomics Infrastructure": null, "Array and Analysis Facility": null, "NGI Uppsala (Uppsala Genome Center)": null}, "xrefs": [{"db": "pii", "key": "ejhg201171"}, {"db": "pmc", "key": "PMC3179368"}], "notes": [], "created": "2017-05-04T15:01:57.258Z", "modified": "2020-01-21T13:56:01.163Z"}, {"entity": "publication", "iuid": "29c2577bd03d479a8b23a8a06f02054a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/29c2577bd03d479a8b23a8a06f02054a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/29c2577bd03d479a8b23a8a06f02054a"}}, "title": "Array-based genomic screening at diagnosis and during follow-up in chronic lymphocytic leukemia.", "authors": [{"family": "Gunnarsson", "given": "Rebeqa", "initials": "R"}, {"family": "Mansouri", "given": "Larry", "initials": "L"}, {"family": "Isaksson", "given": "Anders", "initials": "A"}, {"family": "G\u00f6ransson", "given": "Hanna", "initials": "H"}, {"family": "Cahill", "given": "Nicola", "initials": "N"}, {"family": "Jansson", "given": "Mattias", "initials": "M"}, {"family": "Rasmussen", "given": "Markus", "initials": "M"}, {"family": "Lundin", "given": "Jeanette", "initials": "J"}, {"family": "Norin", "given": "Stefan", "initials": "S"}, {"family": "Buhl", "given": "Anne Mette", "initials": "AM"}, {"family": "Smedby", "given": "Karin Ekstr\u00f6m", "initials": "KE"}, {"family": "Hjalgrim", "given": "Henrik", "initials": "H"}, {"family": "Karlsson", "given": "Karin", "initials": "K"}, {"family": "Jurlander", "given": "Jesper", "initials": "J"}, {"family": "Geisler", "given": "Christian", "initials": "C"}, {"family": "Juliusson", "given": "Gunnar", "initials": "G"}, {"family": "Rosenquist", "given": "Richard", "initials": "R"}], "type": "journal article", "published": "2011-08-00", "journal": {"volume": "96", "issn": "1592-8721", "issue": "8", "pages": "1161-1169", "title": "Haematologica", "issn-l": "0390-6078"}, "abstract": "High-resolution genomic microarrays enable simultaneous detection of copy-number aberrations such as the known recurrent aberrations in chronic lymphocytic leukemia [del(11q), del(13q), del(17p) and trisomy 12], and copy-number neutral loss of heterozygosity. Moreover, comparison of genomic profiles from sequential patients' samples allows detection of clonal evolution.\n\nWe screened samples from 369 patients with newly diagnosed chronic lymphocytic leukemia from a population-based cohort using 250K single nucleotide polymorphism-arrays. Clonal evolution was evaluated in 59 follow-up samples obtained after 5-9 years.\n\nAt diagnosis, copy-number aberrations were identified in 90% of patients; 70% carried known recurrent alterations, including del(13q) (55%), trisomy 12 (10.5%), del(11q) (10%), and del(17p) (4%). Additional recurrent aberrations were detected on chromosomes 2 (1.9%), 4 (1.4%), 8 (1.6%) and 14 (1.6%). Thirteen patients (3.5%) displayed recurrent copy-number neutral loss of heterozygosity on 13q, of whom 11 had concurrent homozygous del(13q). Genomic complexity and large 13q deletions correlated with inferior outcome, while the former was linked to poor-prognostic aberrations. In the follow-up study, clonal evolution developed in 8/24 (33%) patients with unmutated IGHV, and in 4/25 (16%) IGHV-mutated and treated patients. In contrast, untreated patients with mutated IGHV (n=10) did not acquire additional aberrations. The most common secondary event, del(13q), was detected in 6/12 (50%) of all patients with acquired alterations. Interestingly, aberrations on, for example, chromosome 6q, 8p, 9p and 10q developed exclusively in patients with unmutated IGHV.\n\nWhole-genome screening revealed a high frequency of genomic aberrations in newly diagnosed chronic lymphocytic leukemia. Clonal evolution was associated with other markers of aggressive disease and commonly included the known recurrent aberrations.", "doi": "10.3324/haematol.2010.039768", "pmid": "21546498", "labels": {"National Genomics Infrastructure": null, "Array and Analysis Facility": null, "NGI Stockholm (Genomics Applications)": null, "NGI Stockholm (Genomics Production)": null}, "xrefs": [{"db": "pii", "key": "haematol.2010.039768"}, {"db": "pmc", "key": "PMC3148910"}], "notes": [], "created": "2017-05-04T14:57:19.184Z", "modified": "2020-01-21T13:56:01.198Z"}, {"entity": "publication", "iuid": "e98203dd8dca4e79a329c847888f656d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e98203dd8dca4e79a329c847888f656d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e98203dd8dca4e79a329c847888f656d"}}, "title": "Prostasomal DNA characterization and transfer into human sperm.", "authors": [{"family": "Ronquist", "given": "G\u00f6ran K", "initials": "GK"}, {"family": "Larsson", "given": "Anders", "initials": "A"}, {"family": "Ronquist", "given": "Gunnar", "initials": "G"}, {"family": "Isaksson", "given": "Anders", "initials": "A"}, {"family": "Hreinsson", "given": "Julius", "initials": "J"}, {"family": "Carlsson", "given": "Lena", "initials": "L"}, {"family": "Stavreus-Evers", "given": "Anneli", "initials": "A"}], "type": "journal article", "published": "2011-07-00", "journal": {"volume": "78", "issn": "1098-2795", "issue": "7", "pages": "467-476", "title": "Mol. Reprod. Dev.", "issn-l": "1040-452X"}, "abstract": "Human prostasomes, exosome-like microvesicles secreted by acinar cells of the prostate gland, contain chromosomal DNA. Agarose gel electrophoresis of DNA from seminal prostasomes displayed fragments of over 12 kb and smaller, with a distinct band around 1 kb that was excised, cloned, and sequenced. The sequences showed 8 out of 25 clones (32%) originating from genes. We elaborated the concept further by carrying out a genome-wide DNA copy number analysis of prostasomal DNA, hypothesizing that human prostasomes contain fragments of DNA randomly selected from the entire genome. Acridine orange-stained prostasomes were incubated with freshly prepared sperm for different times, and a transfer of acridine orange-stained prostasomal DNA to sperm (preferentially the head region) was observed. Fluorescence microscopy of slices in the center of 14 optical slides of the sperm head displayed an even fluorescence rather than a halo-like one, indicating DNA-uptake rather than just binding along the sperm head membrane.", "doi": "10.1002/mrd.21327", "pmid": "21638509", "labels": {"Array and Analysis Facility": null}, "xrefs": [], "notes": [], "created": "2017-05-04T15:02:53.033Z", "modified": "2017-05-30T12:35:58.608Z"}, {"entity": "publication", "iuid": "a0ffab842d724c6389fe4f2bdb882398", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a0ffab842d724c6389fe4f2bdb882398.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a0ffab842d724c6389fe4f2bdb882398"}}, "title": "Feather pecking behavior in laying hens: hypothalamic gene expression in birds performing and receiving pecks.", "authors": [{"family": "Brunberg", "given": "E", "initials": "E"}, {"family": "Jensen", "given": "P", "initials": "P"}, {"family": "Isaksson", "given": "A", "initials": "A"}, {"family": "Keeling", "given": "L", "initials": "L"}], "type": "journal article", "published": "2011-06-00", "journal": {"volume": "90", "issn": "0032-5791", "issue": "6", "pages": "1145-1152", "title": "Poult. Sci.", "issn-l": null}, "abstract": "Feather pecking (FP) is a welfare and economic problem in the egg production sector. Beak trimming, the current method used to reduce FP, is also criticized. The present study used gene expression to explore the biological mechanisms underlying this behavior, which could lead to a greater understanding of the cause and a tool to mitigate the problem. White Leghorn hens performing and receiving FP, as well as neutral control birds, were identified on a commercial farm. Hypothalamic RNA from 11 peckers, 10 victims, and 10 controls was hybridized onto GeneChip Chicken Genome Arrays (Affymetrix Inc., Santa Clara, CA) to compare gene expression profiles in the different groups. Eleven transcripts corresponding to 10 genes differed significantly between the 3 groups (adjusted P < 0.05). Eight of these transcripts differed in the peckers compared with the controls, 1 was upregulated in the victims compared with the controls, and 6 differed significantly in the peckers compared with the victims. Additionally, 5 transcripts showed a trend (adjusted P < 0.1) to differ in the pecker-victim comparison. Some of the products of the differently expressed genes are involved in disorders, such as intestinal inflammation and insulin resistance, which fit well with the previously proposed hypothesis that FP is an abnormal foraging behavior. Other findings may also support the proposal that FP is linked to immune mechanisms and may serve as an animal model for obsessive compulsive disorder in humans. In conclusion, this study provides a gene list that may be useful in further research on the mechanisms behind FP.", "doi": "10.3382/ps.2010-00961", "pmid": "21597052", "labels": {"Array and Analysis Facility": null}, "xrefs": [{"db": "pii", "key": "90/6/1145"}], "notes": [], "created": "2017-05-04T15:02:54.148Z", "modified": "2017-05-30T12:36:17.012Z"}, {"entity": "publication", "iuid": "b53086961f1e45b0b13944910d3c1dc4", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b53086961f1e45b0b13944910d3c1dc4.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b53086961f1e45b0b13944910d3c1dc4"}}, "title": "Experimental evidence supports a sex-specific selective sieve in mitochondrial genome evolution.", "authors": [{"family": "Innocenti", "given": "Paolo", "initials": "P"}, {"family": "Morrow", "given": "Edward H", "initials": "EH"}, {"family": "Dowling", "given": "Damian K", "initials": "DK"}], "type": "journal article", "published": "2011-05-13", "journal": {"volume": "332", "issn": "1095-9203", "issue": "6031", "pages": "845-848", "title": "Science", "issn-l": "0036-8075"}, "abstract": "Mitochondria are maternally transmitted; hence, their genome can only make a direct and adaptive response to selection through females, whereas males represent an evolutionary dead end. In theory, this creates a sex-specific selective sieve, enabling deleterious mutations to accumulate in mitochondrial genomes if they exert male-specific effects. We tested this hypothesis, expressing five mitochondrial variants alongside a standard nuclear genome in Drosophila melanogaster, and found striking sexual asymmetry in patterns of nuclear gene expression. Mitochondrial polymorphism had few effects on nuclear gene expression in females but major effects in males, modifying nearly 10% of transcripts. These were mostly male-biased in expression, with enrichment hotspots in the testes and accessory glands. Our results suggest an evolutionary mechanism that results in mitochondrial genomes harboring male-specific mutation loads.", "doi": "10.1126/science.1201157", "pmid": "21566193", "labels": {"Array and Analysis Facility": null}, "xrefs": [{"db": "pii", "key": "332/6031/845"}, {"db": "GEO", "key": "GSE24729"}], "notes": [], "created": "2017-05-04T15:02:54.449Z", "modified": "2017-05-31T08:17:00.513Z"}, {"entity": "publication", "iuid": "3c311d033f2f4e079d7daf1f85bbb354", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3c311d033f2f4e079d7daf1f85bbb354.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3c311d033f2f4e079d7daf1f85bbb354"}}, "title": "The 12q14 microdeletion syndrome: six new cases confirming the role of HMGA2 in growth.", "authors": [{"family": "Lynch", "given": "Sally Ann", "initials": "SA"}, {"family": "Foulds", "given": "Nicola", "initials": "N"}, {"family": "Thuresson", "given": "Ann-Charlotte", "initials": "AC"}, {"family": "Collins", "given": "Amanda L", "initials": "AL"}, {"family": "Anner\u00e9n", "given": "G\u00f6ran", "initials": "G"}, {"family": "Hedberg", "given": "Bernt-Oves", "initials": "BO"}, {"family": "Delaney", "given": "Carol A", "initials": "CA"}, {"family": "Iremonger", "given": "James", "initials": "J"}, {"family": "Murray", "given": "Caroline M", "initials": "CM"}, {"family": "Crolla", "given": "John A", "initials": "JA"}, {"family": "Costigan", "given": "Colm", "initials": "C"}, {"family": "Lam", "given": "Wayne", "initials": "W"}, {"family": "Fitzpatrick", "given": "David R", "initials": "DR"}, {"family": "Regan", "given": "Regina", "initials": "R"}, {"family": "Ennis", "given": "Sean", "initials": "S"}, {"family": "Sharkey", "given": "Freddie", "initials": "F"}], "type": "journal article", "published": "2011-05-00", "journal": {"volume": "19", "issn": "1476-5438", "issue": "5", "pages": "534-539", "title": "Eur. J. Hum. Genet.", "issn-l": "1018-4813"}, "abstract": "We report six patients with array deletions encompassing 12q14. Out of a total of 2538 array investigations carried out on children with developmental delay and dysmorphism in three diagnostic testing centres, six positive cases yielded a frequency of 1 in 423 for this deletion syndrome. The deleted region in each of the six cases overlaps significantly with previously reported cases with microdeletions of this region. The chromosomal range of the deletions extends from 12q13.3q15. In the current study, we report overlapping deletions of variable extent and size but primarily comprising chromosomal bands 12q13.3q14.1. Four of the six deletions were confirmed as de novo events. Two cases had deletions that included HMGA2, and both children had significant short stature. Neither case had osteopoikilosis despite both being deleted for LEMD3. Four cases had deletions that ended proximal to HMGA2 and all of these had much better growth. Five cases had congenital heart defects, including two with atrial septal defects, one each with pulmonary stenosis, sub-aortic stenosis and a patent ductus. Four cases had moderate delay, two had severe developmental delay and a further two had a diagnosis of autism. All six cases had significant speech delay with subtle facial dysmorphism.", "doi": "10.1038/ejhg.2010.215", "pmid": "21267005", "labels": {"National Genomics Infrastructure": null, "Array and Analysis Facility": null, "NGI Uppsala (Uppsala Genome Center)": null}, "xrefs": [{"db": "pii", "key": "ejhg2010215"}, {"db": "pmc", "key": "PMC3083609"}], "notes": [], "created": "2017-05-04T15:01:56.658Z", "modified": "2020-01-21T13:56:01.699Z"}, {"entity": "publication", "iuid": "ef0fa515e7784205b0174e14717300cd", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ef0fa515e7784205b0174e14717300cd.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ef0fa515e7784205b0174e14717300cd"}}, "title": "High-resolution genomic screening in mantle cell lymphoma--specific changes correlate with genomic complexity, the proliferation signature and survival.", "authors": [{"family": "Halld\u00f3rsd\u00f3ttir", "given": "Anna M", "initials": "AM"}, {"family": "Sander", "given": "Birgitta", "initials": "B"}, {"family": "G\u00f6ransson", "given": "Hanna", "initials": "H"}, {"family": "Isaksson", "given": "Anders", "initials": "A"}, {"family": "Kimby", "given": "Eva", "initials": "E"}, {"family": "Mansouri", "given": "Mahmoud", "initials": "M"}, {"family": "Rosenquist", "given": "Richard", "initials": "R"}, {"family": "Ehrencrona", "given": "Hans", "initials": "H"}], "type": "comparative study", "published": "2011-02-00", "journal": {"volume": "50", "issn": "1098-2264", "issue": "2", "pages": "113-121", "title": "Genes Chromosomes Cancer", "issn-l": "1045-2257"}, "abstract": "Mantle cell lymphoma (MCL) is characterized by the t(11;14)(q13;q32) and numerous copy number aberrations (CNAs). Recently, gene expression profiling defined a proliferation gene expression signature in MCL where high scores predict shorter survival. We investigated 31 MCL cases using high-density single nucleotide polymorphism arrays and correlated CNA patterns with the proliferation signature and with clinical data. Many recurrent CNAs typical of MCL were detected, including losses at 1p (55%), 8p (29%), 9q (29%), 11q (55%), 13q (42%) and 17p (32%), and gains at 3q (39%), 8q (26%), 15q (23%) and 18q (23%). A novel deleted region at 20q (16%) contained only one candidate gene, ZFP64, a putative tumor suppressor. Unsupervised clustering identified subgroups with different patterns of CNAs, including a subset (19%) characterized by the presence of 11q loss in all cases and by the absence of 13q loss, and 3q and 7p gains. Losses at 1p, 8p, 13q and 17p were associated with increased genomic complexity. High proliferation signature scores correlated with increased number of large (>15 Mbp) CNAs (P = 0.03) as well as copy number gains at 7p (P = 0.02) and losses at 9q (P = 0.04). Furthermore, large/complex 13q losses were associated with improved survival (P < 0.05) as were losses/copy number neutral LOH at 19p13 (P = 0.01). In summary, this high-resolution genomic analysis identified novel aberrations and revealed that several CNAs correlated with genomic complexity, the proliferation status and survival.", "doi": "10.1002/gcc.20836", "pmid": "21117067", "labels": {"National Genomics Infrastructure": null, "Array and Analysis Facility": null, "NGI Stockholm (Genomics Applications)": null, "NGI Stockholm (Genomics Production)": null}, "xrefs": [], "notes": [], "created": "2017-05-04T14:57:18.877Z", "modified": "2020-01-21T13:56:06.110Z"}, {"entity": "publication", "iuid": "c078a6e6ac5a41028569854b10862c18", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c078a6e6ac5a41028569854b10862c18.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c078a6e6ac5a41028569854b10862c18"}}, "title": "Targeted resequencing of candidate genes using selector probes.", "authors": [{"family": "Johansson", "given": "H", "initials": "H"}, {"family": "Isaksson", "given": "M", "initials": "M"}, {"family": "S\u00f6rqvist", "given": "E Falk", "initials": "EF"}, {"family": "Roos", "given": "F", "initials": "F"}, {"family": "Stenberg", "given": "J", "initials": "J"}, {"family": "Sj\u00f6blom", "given": "T", "initials": "T"}, {"family": "Botling", "given": "J", "initials": "J"}, {"family": "Micke", "given": "P", "initials": "P"}, {"family": "Edlund", "given": "K", "initials": "K"}, {"family": "Fredriksson", "given": "S", "initials": "S"}, {"family": "Kultima", "given": "H G\u00f6ransson", "initials": "HG"}, {"family": "Ericsson", "given": "Olle", "initials": "O"}, {"family": "Nilsson", "given": "Mats", "initials": "M", "orcid": "0000-0001-9985-0387", "researcher": {"href": "https://publications.scilifelab.se/researcher/197cf8ba83ba430f9712b2f4d94dc3e5.json"}}], "type": "evaluation study", "published": "2011-01-00", "journal": {"volume": "39", "issn": "1362-4962", "issue": "2", "pages": "e8", "title": "Nucleic Acids Res.", "issn-l": "0305-1048"}, "abstract": "Targeted genome enrichment is a powerful tool for making use of the massive throughput of novel DNA-sequencing instruments. We herein present a simple and scalable protocol for multiplex amplification of target regions based on the Selector technique. The updated version exhibits improved coverage and compatibility with next-generation-sequencing (NGS) library-construction procedures for shotgun sequencing with NGS platforms. To demonstrate the performance of the technique, all 501 exons from 28 genes frequently involved in cancer were enriched for and sequenced in specimens derived from cell lines and tumor biopsies. DNA from both fresh frozen and formalin-fixed paraffin-embedded biopsies were analyzed and 94% specificity and 98% coverage of the targeted region was achieved. Reproducibility between replicates was high (R(2) = 0, 98) and readily enabled detection of copy-number variations. The procedure can be carried out in <24 h and does not require any dedicated instrumentation.", "doi": "10.1093/nar/gkq1005", "pmid": "21059679", "labels": {"National Genomics Infrastructure": null, "Array and Analysis Facility": null, "NGI Uppsala (Uppsala Genome Center)": null}, "xrefs": [{"db": "pii", "key": "gkq1005"}, {"db": "pmc", "key": "PMC3025563"}], "notes": [], "created": "2017-05-04T14:57:23.142Z", "modified": "2021-07-07T13:54:46.136Z"}, {"entity": "publication", "iuid": "49de0859712c408eabd80917a59f2310", "links": {"self": {"href": "https://publications.scilifelab.se/publication/49de0859712c408eabd80917a59f2310.json"}, "display": {"href": "https://publications.scilifelab.se/publication/49de0859712c408eabd80917a59f2310"}}, "title": "Distinct gene expression profiles in subsets of chronic lymphocytic leukemia expressing stereotyped IGHV4-34 B-cell receptors.", "authors": [{"family": "Marincevic", "given": "Millaray", "initials": "M"}, {"family": "Mansouri", "given": "Mahmoud", "initials": "M"}, {"family": "Kanduri", "given": "Meena", "initials": "M"}, {"family": "Isaksson", "given": "Anders", "initials": "A"}, {"family": "G\u00f6ransson", "given": "Hanna", "initials": "H"}, {"family": "Smedby", "given": "Karin Ekstr\u00f6m", "initials": "KE"}, {"family": "Jurlander", "given": "Jesper", "initials": "J"}, {"family": "Juliusson", "given": "Gunnar", "initials": "G"}, {"family": "Davi", "given": "Fred", "initials": "F"}, {"family": "Stamatopoulos", "given": "Kostas", "initials": "K"}, {"family": "Rosenquist", "given": "Richard", "initials": "R"}], "type": "journal article", "published": "2010-12-00", "journal": {"volume": "95", "issn": "1592-8721", "issue": "12", "pages": "2072-2079", "title": "Haematologica", "issn-l": "0390-6078"}, "abstract": "Numerous subsets of patients with chronic lymphocytic leukemia display similar immunoglobulin gene usage with almost identical complementarity determining region 3 sequences. Among IGHV4-34 cases, two such subsets with \"stereotyped\" B-cell receptors were recently identified, i.e. subset #4 (IGHV4-34/IGKV2-30) and subset #16 (IGHV4-34/IGKV3-20). Subset #4 patients appear to share biological and clinical features, e.g. young age at diagnosis and indolent disease, whereas little is known about subset #16 at a clinical level.\r\n\r\nWe investigated the global gene expression pattern in sorted chronic lymphocytic leukemia cells from 25 subset/non-subset IGHV4-34 patients using Affymetrix gene expression arrays.\r\n\r\nAlthough generally few differences were found when comparing subset to non-subset 4/16 IGHV4-34 cases, distinct gene expression profiles were revealed for subset #4 versus subset #16. The differentially expressed genes, predominantly with lower expression in subset #4 patients, are involved in important cell regulatory pathways including cell-cycle control, proliferation and immune response, which may partly explain the low-proliferative disease observed in subset #4 patients.\r\n\r\nOur novel data demonstrate distinct gene expression profiles among patients with stereotyped IGHV4-34 B-cell receptors, providing further evidence for biological differences in the pathogenesis of these subsets and underscoring the functional relevance of subset assignment based on B-cell receptor sequence features.", "doi": "10.3324/haematol.2010.028639", "pmid": "20801898", "labels": {"National Genomics Infrastructure": null, "Array and Analysis Facility": null, "NGI Uppsala (Uppsala Genome Center)": null}, "xrefs": [{"db": "pii", "key": "haematol.2010.028639"}, {"db": "pmc", "key": "PMC2995565"}], "notes": [], "created": "2017-05-04T14:57:11.356Z", "modified": "2020-01-21T13:56:10.375Z"}, {"entity": "publication", "iuid": "a343b5d7ca1f49f7a9dad4764c15835f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a343b5d7ca1f49f7a9dad4764c15835f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a343b5d7ca1f49f7a9dad4764c15835f"}}, "title": "High-density screening reveals a different spectrum of genomic aberrations in chronic lymphocytic leukemia patients with 'stereotyped' IGHV3-21 and IGHV4-34 B-cell receptors.", "authors": [{"family": "Marincevic", "given": "Millaray", "initials": "M"}, {"family": "Cahill", "given": "Nicola", "initials": "N"}, {"family": "Gunnarsson", "given": "Rebeqa", "initials": "R"}, {"family": "Isaksson", "given": "Anders", "initials": "A"}, {"family": "Mansouri", "given": "Mahmoud", "initials": "M"}, {"family": "G\u00f6ransson", "given": "Hanna", "initials": "H"}, {"family": "Rasmussen", "given": "Markus", "initials": "M"}, {"family": "Jansson", "given": "Mattias", "initials": "M"}, {"family": "Ryan", "given": "Fergus", "initials": "F"}, {"family": "Karlsson", "given": "Karin", "initials": "K"}, {"family": "Adami", "given": "Hans-Olov", "initials": "HO"}, {"family": "Davi", "given": "Fred", "initials": "F"}, {"family": "Jurlander", "given": "Jesper", "initials": "J"}, {"family": "Juliusson", "given": "Gunnar", "initials": "G"}, {"family": "Stamatopoulos", "given": "Kostas", "initials": "K"}, {"family": "Rosenquist", "given": "Richard", "initials": "R"}], "type": "journal article", "published": "2010-09-00", "journal": {"volume": "95", "issn": "1592-8721", "issue": "9", "pages": "1519-1525", "title": "Haematologica", "issn-l": "0390-6078"}, "abstract": "The existence of multiple subsets of chronic lymphocytic leukemia expressing 'stereotyped' B-cell receptors implies the involvement of antigen(s) in leukemogenesis. Studies also indicate that 'stereotypy' may influence the clinical course of patients with chronic lymphocytic leukemia, for example, in subsets with stereotyped IGHV3-21 and IGHV4-34 B-cell receptors; however, little is known regarding the genomic profile of patients in these subsets.\n\nWe applied 250K single nucleotide polymorphism-arrays to study copy-number aberrations and copy-number neutral loss-of-heterozygosity in patients with stereotyped IGHV3-21 (subset #2, n=29), stereotyped IGHV4-34 (subset #4, n=17; subset #16, n=8) and non-subset #2 IGHV3-21 (n=13) and non-subset #4/16 IGHV4-34 (n=34) patients.\n\nOver 90% of patients in subset #2 and non-subset #2 carried copy-number aberrations, whereas 75-76% of patients in subset #4 and subset #16 showed copy-number aberrations. Subset #2 and non-subset #2 patients also displayed a higher average number of aberrations compared to patients in subset #4. Deletion of 13q was the only known recurrent aberration detected in subset #4 (35%); this aberration was even more frequent in subset #2 (79%). del(11q) was more frequent in subset #2 and non-subset #2 (31% and 23%) patients than in subset #4 and non-subset #4/16 patients. Recurrent copy-number neutral loss-of-heterozygosity was mainly detected on chromosome 13q, independently of B-cell receptor stereotypy.\n\nGenomic aberrations were more common in subset #2 and non-subset #2 than in subset #4. The particularly high frequency of del(11q) in subset #2 may be linked to the adverse outcome reported for patients in this subset. Conversely, the lower prevalence of copy-number aberrations and the absence of poor-prognostic aberrations in subset #4 may reflect an inherently low-proliferative disease, which would prevent accumulation of genomic alterations.", "doi": "10.3324/haematol.2009.021014", "pmid": "20421269", "labels": {"Array and Analysis Facility": null}, "xrefs": [{"db": "pii", "key": "haematol.2009.021014"}, {"db": "pmc", "key": "PMC2930953"}], "notes": [], "created": "2017-05-04T15:02:49.751Z", "modified": "2017-05-30T12:35:02.795Z"}, {"entity": "publication", "iuid": "c6a2bbd1be584e2fb21c88a01174d803", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c6a2bbd1be584e2fb21c88a01174d803.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c6a2bbd1be584e2fb21c88a01174d803"}}, "title": "Ontogenetic complexity of sexual dimorphism and sex-specific selection.", "authors": [{"family": "Mank", "given": "Judith E", "initials": "JE"}, {"family": "Nam", "given": "Kiwoong", "initials": "K"}, {"family": "Brunstr\u00f6m", "given": "Bj\u00f6rn", "initials": "B"}, {"family": "Ellegren", "given": "Hans", "initials": "H"}], "type": "journal article", "published": "2010-07-00", "journal": {"volume": "27", "issn": "1537-1719", "issue": "7", "pages": "1570-1578", "title": "Mol. Biol. Evol.", "issn-l": "0737-4038"}, "abstract": "Sex-biased gene expression is becoming an increasingly important way to study sexual selection at the molecular genetic level. However, little is known about the timing, persistence, and continuity of gene expression required in the creation of distinct male and female phenotypes, and even less about how sex-specific selection pressures shift over the life cycle. Here, we present a time-series global transcription profile for autosomal genes in male and female chicken, beginning with embryonic development and spanning to reproductive maturity, for the gonad. Overall, the amount and magnitude of sex-biased expression increased as a function of age, though sex-biased gene expression was surprisingly ephemeral, with very few genes exhibiting continuous sex bias in both embryonic and adult tissues. Despite a large predicted role of the sex chromosomes in sexual dimorphism, our study indicates that the autosomes house the majority of genes with sex-biased expression. Most interestingly, sex-specific evolutionary pressures shifted over the course of the life cycle, acting equally strongly on female-biased genes and male-biased genes but at different ages. Female-biased genes exhibited high rates of divergence late in embryonic development, shortly before arrested meiosis halts oogenesis. The level of divergence on female-biased late embryonic genes is similar to that seen in male-biased genes expressed in adult gonads, which correlates with the onset of spermatogenesis. These analyses reveal that sex-specific selection pressure varies over the life cycle as a function of male and female biology.", "doi": "10.1093/molbev/msq042", "pmid": "20142440", "labels": {"Array and Analysis Facility": null}, "xrefs": [{"db": "pii", "key": "msq042"}], "notes": [], "created": "2017-05-04T15:02:52.737Z", "modified": "2017-05-30T12:35:53.873Z"}, {"entity": "publication", "iuid": "ba656281ab624babbca5bfd810453f8a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ba656281ab624babbca5bfd810453f8a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ba656281ab624babbca5bfd810453f8a"}}, "title": "Characterization of the RNA content of chromatin.", "authors": [{"family": "Mondal", "given": "Tanmoy", "initials": "T"}, {"family": "Rasmussen", "given": "Markus", "initials": "M"}, {"family": "Pandey", "given": "Gaurav Kumar", "initials": "GK"}, {"family": "Isaksson", "given": "Anders", "initials": "A"}, {"family": "Kanduri", "given": "Chandrasekhar", "initials": "C"}], "type": "journal article", "published": "2010-07-00", "journal": {"volume": "20", "issn": "1549-5469", "issue": "7", "pages": "899-907", "title": "Genome Res.", "issn-l": "1088-9051"}, "abstract": "Noncoding RNA (ncRNA) constitutes a significant portion of the mammalian transcriptome. Emerging evidence suggests that it regulates gene expression in cis or trans by modulating the chromatin structure. To uncover the functional role of ncRNA in chromatin organization, we deep sequenced chromatin-associated RNAs (CARs) from human fibroblast (HF) cells. This resulted in the identification of 141 intronic regions and 74 intergenic regions harboring CARs. The intronic and intergenic CARs show significant conservation across 44 species of placental mammals. Functional characterization of one of the intergenic CARs, Intergenic10, revealed that it regulates gene expression of neighboring genes through modulating the chromatin structure in cis. Our data suggest that ncRNA is an integral component of chromatin and that it may regulate various biological functions through fine-tuning of the chromatin architecture.", "doi": "10.1101/gr.103473.109", "pmid": "20404130", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (SNP&SEQ Technology Platform)": null, "Array and Analysis Facility": null}, "xrefs": [{"db": "pii", "key": "gr.103473.109"}, {"db": "pmc", "key": "PMC2892091"}, {"db": "GEO", "key": "GSE21227"}], "notes": [], "created": "2017-05-04T15:00:31.276Z", "modified": "2020-01-21T13:56:04.877Z"}, {"entity": "publication", "iuid": "e9e2e9d5ed3149cab65af7954a5ba54a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e9e2e9d5ed3149cab65af7954a5ba54a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e9e2e9d5ed3149cab65af7954a5ba54a"}}, "title": "Interstitial Deletions at 6q14.1-q15 Associated with Obesity, Developmental Delay and a Distinct Clinical Phenotype.", "authors": [{"family": "Wentzel", "given": "C", "initials": "C"}, {"family": "Lynch", "given": "S A", "initials": "SA"}, {"family": "Stattin", "given": "E-L", "initials": "EL"}, {"family": "Sharkey", "given": "F H", "initials": "FH"}, {"family": "Anner\u00e9n", "given": "G", "initials": "G"}, {"family": "Thuresson", "given": "A-C", "initials": "AC"}], "type": "journal article", "published": "2010-06-09", "journal": {"volume": "1", "issn": "1661-8769", "issue": "2", "pages": "75-81", "title": "Mol Syndromol", "issn-l": null}, "abstract": "BACKGROUND: Interstitial deletions of the long arm of chromosome 6 have been described in several patients with obesity and a Prader-Willi-like phenotype. Haploinsufficiency of the SIM1 gene located at 6q16.3 is suggested as being responsible for the regulation of body weight. Here we report on 2 patients with interstitial deletions at 6q14.1-q15 presenting with obesity and symptoms strikingly similar to those reported for deletions involving the SIM1 gene despite not having a deletion of this gene. METHODS: Array comparative genomic hybridisation was used to diagnose 2 children with obesity and developmental delay, revealing 2 interstitial deletions at 6q14.1-q15 of 8.73 and 4.50 Mb, respectively, and a region of overlap of 4.2-Mb. RESULTS: The similar phenotype in the 2 patients was most likely due to a 4.2-Mb common microdeletion at 6q14.1-q15. Another patient has previously been described with an overlapping deletion. The 3 patients share several features, such as developmental delay, obesity, hernia, rounded face with full cheeks, epicanthal folds, short palpebral fissures, bulbous nose, large ears, and syndactyly between toes II and III. CONCLUSIONS: Together with a previously reported patient, our study suggests that the detected deletions may represent a novel clinically recognisable microdeletion syndrome caused by haploinsufficiency of dosage-sensitive genes in the 6q14.1-q15 region.", "doi": "10.1159/000314025", "pmid": "21045960", "labels": {"National Genomics Infrastructure": null, "Array and Analysis Facility": null, "NGI Uppsala (Uppsala Genome Center)": null}, "xrefs": [{"db": "pmc", "key": "PMC2941842"}, {"db": "pii", "key": "314025"}], "notes": [], "created": "2017-05-04T15:01:52.587Z", "modified": "2020-01-21T13:56:05.960Z"}, {"entity": "publication", "iuid": "1b91c55735414fdc8cc0f72e9f37b548", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1b91c55735414fdc8cc0f72e9f37b548.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1b91c55735414fdc8cc0f72e9f37b548"}}, "title": "Improving Bayesian credibility intervals for classifier error rates using maximum entropy empirical priors.", "authors": [{"family": "Gustafsson", "given": "Mats G", "initials": "MG"}, {"family": "Wallman", "given": "Mikael", "initials": "M"}, {"family": "Wickenberg Bolin", "given": "Ulrika", "initials": "U"}, {"family": "G\u00f6ransson", "given": "Hanna", "initials": "H"}, {"family": "Frykn\u00e4s", "given": "M", "initials": "M"}, {"family": "Andersson", "given": "Claes R", "initials": "CR"}, {"family": "Isaksson", "given": "Anders", "initials": "A"}], "type": "journal article", "published": "2010-06-00", "journal": {"volume": "49", "issn": "1873-2860", "issue": "2", "pages": "93-104", "title": "Artif Intell Med", "issn-l": "0933-3657"}, "abstract": "Successful use of classifiers that learn to make decisions from a set of patient examples require robust methods for performance estimation. Recently many promising approaches for determination of an upper bound for the error rate of a single classifier have been reported but the Bayesian credibility interval (CI) obtained from a conventional holdout test still delivers one of the tightest bounds. The conventional Bayesian CI becomes unacceptably large in real world applications where the test set sizes are less than a few hundred. The source of this problem is that fact that the CI is determined exclusively by the result on the test examples. In other words, there is no information at all provided by the uniform prior density distribution employed which reflects complete lack of prior knowledge about the unknown error rate. Therefore, the aim of the study reported here was to study a maximum entropy (ME) based approach to improved prior knowledge and Bayesian CIs, demonstrating its relevance for biomedical research and clinical practice.\n\nIt is demonstrated how a refined non-uniform prior density distribution can be obtained by means of the ME principle using empirical results from a few designs and tests using non-overlapping sets of examples.\n\nExperimental results show that ME based priors improve the CIs when employed to four quite different simulated and two real world data sets.\n\nAn empirically derived ME prior seems promising for improving the Bayesian CI for the unknown error rate of a designed classifier.", "doi": "10.1016/j.artmed.2010.02.004", "pmid": "20347582", "labels": {"Array and Analysis Facility": null}, "xrefs": [{"db": "pii", "key": "S0933-3657(10)00025-4"}], "notes": [], "created": "2017-05-04T15:02:48.282Z", "modified": "2018-11-14T14:24:36.251Z"}, {"entity": "publication", "iuid": "1b906cd95a43425dae9ba7270d1e5338", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1b906cd95a43425dae9ba7270d1e5338.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1b906cd95a43425dae9ba7270d1e5338"}}, "title": "Alpha terpineol: a potential anticancer agent which acts through suppressing NF-kappaB signalling.", "authors": [{"family": "Hassan", "given": "Saadia Bashir", "initials": "SB"}, {"family": "Gali-Muhtasib", "given": "Hala", "initials": "H"}, {"family": "G\u00f6ransson", "given": "Hanna", "initials": "H"}, {"family": "Larsson", "given": "Rolf", "initials": "R", "orcid": "0000-0002-5261-7390", "researcher": {"href": "https://publications.scilifelab.se/researcher/b2fab759f00549cfaf3417d98e691323.json"}}], "type": "journal article", "published": "2010-06-00", "journal": {"volume": "30", "issn": "1791-7530", "issue": "6", "pages": "1911-1919", "title": "Anticancer Res.", "issn-l": "0250-7005"}, "abstract": "Alpha terpineol is a bioactive component of Salvia libanotica essential oil extract and has shown antitumour activity.\n\nThe cytotoxicity of alpha terpineol towards different tumour cell lines was evaluated in vitro. Mechanistic characterization was performed using analysis of drug activity in a cell line panel and drug-induced gene expression perturbation using the connectivity map approach.\n\nThe small cell lung carcinoma was the cell line most sensitive to alpha terpineol. The results proposed alpha terpineol as an NF-kappaB inhibitor, which was confirmed by the observed dose-dependent inhibition of NF-kappaB translocation and activity using two NF-kappaB assays, and by the down-regulation of the expression of several NF-kappaB-related genes such as IL-1 beta and IL1R1.\n\nThe results suggest that alpha terpineol inhibits the growth of tumour cells through a mechanism that involves inhibition of the NF-kappaB pathway.", "doi": null, "pmid": "20651334", "labels": {"Array and Analysis Facility": null}, "xrefs": [{"db": "pii", "key": "30/6/1911"}], "notes": [], "created": "2017-05-04T15:02:47.977Z", "modified": "2025-11-17T10:02:57.365Z"}, {"entity": "publication", "iuid": "33d8bc4f851d44bab399bb25c345b0c5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/33d8bc4f851d44bab399bb25c345b0c5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/33d8bc4f851d44bab399bb25c345b0c5"}}, "title": "The sexually antagonistic genes of Drosophila melanogaster.", "authors": [{"family": "Innocenti", "given": "Paolo", "initials": "P"}, {"family": "Morrow", "given": "Edward H", "initials": "EH"}], "type": "journal article", "published": "2010-03-16", "journal": {"volume": "8", "issn": "1545-7885", "issue": "3", "pages": "e1000335", "title": "PLoS Biol.", "issn-l": "1544-9173"}, "abstract": "When selective pressures differ between males and females, the genes experiencing these conflicting evolutionary forces are said to be sexually antagonistic. Although the phenotypic effect of these genes has been documented in both wild and laboratory populations, their identity, number, and location remains unknown. Here, by combining data on sex-specific fitness and genome-wide transcript abundance in a quantitative genetic framework, we identified a group of candidate genes experiencing sexually antagonistic selection in the adult, which correspond to 8% of Drosophila melanogaster genes. As predicted, the X chromosome is enriched for these genes, but surprisingly they represent only a small proportion of the total number of sex-biased transcripts, indicating that the latter is a poor predictor of sexual antagonism. Furthermore, the majority of genes whose expression profiles showed a significant relationship with either male or female adult fitness are also sexually antagonistic. These results provide a first insight into the genetic basis of intralocus sexual conflict and indicate that genetic variation for fitness is dominated and maintained by sexual antagonism, potentially neutralizing any indirect genetic benefits of sexual selection.", "doi": "10.1371/journal.pbio.1000335", "pmid": "20305719", "labels": {"Array and Analysis Facility": null}, "xrefs": [{"db": "pmc", "key": "PMC2838750"}], "notes": [], "created": "2017-05-04T15:02:50.889Z", "modified": "2018-11-14T14:25:11.656Z"}, {"entity": "publication", "iuid": "761dcca202684ddd85283ce9be32b8c6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/761dcca202684ddd85283ce9be32b8c6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/761dcca202684ddd85283ce9be32b8c6"}}, "title": "Appearance of Cxcl10-expressing cell clusters is common for traumatic brain injury and neurodegenerative disorders.", "authors": [{"family": "Israelsson", "given": "Charlotte", "initials": "C"}, {"family": "Bengtsson", "given": "Henrik", "initials": "H"}, {"family": "Lobell", "given": "Anna", "initials": "A"}, {"family": "Nilsson", "given": "Lars N G", "initials": "LN"}, {"family": "Kylberg", "given": "Annika", "initials": "A"}, {"family": "Isaksson", "given": "Magnus", "initials": "M"}, {"family": "Wootz", "given": "Hanna", "initials": "H"}, {"family": "Lannfelt", "given": "Lars", "initials": "L"}, {"family": "Kullander", "given": "Klas", "initials": "K"}, {"family": "Hillered", "given": "Lars", "initials": "L"}, {"family": "Ebendal", "given": "Ted", "initials": "T"}], "type": "journal article", "published": "2010-03-00", "journal": {"volume": "31", "issn": "1460-9568", "issue": "5", "pages": "852-863", "title": "Eur. J. Neurosci.", "issn-l": "0953-816X"}, "abstract": "Traumatic brain injury (TBI) in the mouse results in the rapid appearance of scattered clusters of cells expressing the chemokine Cxcl10 in cortical and subcortical areas. To extend the observation of this unique pattern, we used neuropathological mouse models using quantitative reverse transcriptase-polymerase chain reaction, gene array analysis, in-situ hybridization and flow cytometry. As for TBI, cell clusters of 150-200 mum expressing Cxcl10 characterize the cerebral cortex of mice carrying a transgene encoding the Swedish mutation of amyloid precursor protein, a model of amyloid Alzheimer pathology. The same pattern was found in experimental autoimmune encephalomyelitis in mice modelling multiple sclerosis. In contrast, mice carrying a SOD1(G93A) mutant mimicking amyotrophic lateral sclerosis pathology lacked such cell clusters in the cerebral cortex, whereas clusters appeared in the brainstem and spinal cord. Mice homozygous for a null mutation of the Cxcl10 gene did not show detectable levels of Cxcl10 transcript after TBI, confirming the quantitative reverse transcriptase-polymerase chain reaction and in-situ hybridization signals. Moreover, unbiased microarray expression analysis showed that Cxcl10 was among 112 transcripts in the neocortex upregulated at least threefold in both TBI and ageing TgSwe mice, many of them involved in inflammation. The identity of the Cxcl10(+) cells remains unclear but flow cytometry showed increased numbers of activated microglia/macrophages as well as myeloid dendritic cells in the TBI and experimental autoimmune encephalomyelitis models. It is concluded that the Cxcl10(+) cells appear in the inflamed central nervous system and may represent a novel population of cells that it may be possible to target pharmacologically in a broad range of neurodegenerative conditions.", "doi": "10.1111/j.1460-9568.2010.07105.x", "pmid": "20374285", "labels": {"Array and Analysis Facility": null}, "xrefs": [{"db": "pii", "key": "EJN7105"}], "notes": [], "created": "2017-05-04T15:02:48.802Z", "modified": "2018-11-14T14:29:39.539Z"}, {"entity": "publication", "iuid": "ebcd0009f3a841cf85ed682bb9d32f78", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ebcd0009f3a841cf85ed682bb9d32f78.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ebcd0009f3a841cf85ed682bb9d32f78"}}, "title": "Infection of mast cells with live streptococci causes a toll-like receptor 2- and cell-cell contact-dependent cytokine and chemokine response.", "authors": [{"family": "R\u00f6nnberg", "given": "Elin", "initials": "E"}, {"family": "Guss", "given": "Bengt", "initials": "B"}, {"family": "Pejler", "given": "Gunnar", "initials": "G"}], "type": "journal article", "published": "2010-02-00", "journal": {"volume": "78", "issn": "1098-5522", "issue": "2", "pages": "854-864", "title": "Infect. Immun.", "issn-l": "0019-9567"}, "abstract": "Mast cells (MCs) are strongly implicated in immunity toward bacterial infection, but the molecular mechanisms by which MCs contribute to the host response are only partially understood. We addressed this issue by examining the direct effects of a Gram-positive pathogen, Streptococcus equi, on bone marrow-derived MCs (BMMCs). Ultrastructural analysis revealed extensive formation of dilated rough endoplasmic reticulum in response to bacterial infection, indicating strong induction of protein synthesis. However, the BMMCs did not show signs of extensive degranulation, and this was supported by only slow release of histamine in response to infection. Coculture of live bacteria with BMMCs caused a profound secretion of CCL2/MCP-1, CCL7/MCP-3, CXCL2/MIP-2, CCL5/RANTES, interleukin-4 (IL-4), IL-6, IL-12, IL-13, and tumor necrosis factor alpha, as shown by antibody-based cytokine/chemokine arrays and/or enzyme-linked immunosorbent assay. In contrast, heat-inactivated bacteria caused only minimal cytokine/chemokine release. The cytokine/chemokine responses were substantially attenuated in Toll-like receptor 2-deficient BMMCs and were strongly dependent on cell-cell contacts between bacteria and BMMCs. Gene chip microarray analysis confirmed a massively upregulated expression of the genes coding for the secreted cytokines and chemokines and also identified a pronounced upregulation of numerous additional genes, including transcription factors, signaling molecules, and proteases. Together, the present study outlines MC-dependent molecular events associated with Gram-positive infection and thus provides an advancement in our understanding of how MCs may contribute to host defense toward bacterial insults.", "doi": "10.1128/IAI.01004-09", "pmid": "19933827", "labels": {"Array and Analysis Facility": null}, "xrefs": [{"db": "pii", "key": "IAI.01004-09"}, {"db": "pmc", "key": "PMC2812202"}], "notes": [], "created": "2017-05-04T15:02:50.056Z", "modified": "2018-11-14T14:07:27.086Z"}, {"entity": "publication", "iuid": "a5dfb0f136e4469e92b29eeff0b619cb", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a5dfb0f136e4469e92b29eeff0b619cb.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a5dfb0f136e4469e92b29eeff0b619cb"}}, "title": "Differential genome-wide array-based methylation profiles in prognostic subsets of chronic lymphocytic leukemia.", "authors": [{"family": "Kanduri", "given": "Meena", "initials": "M"}, {"family": "Cahill", "given": "Nicola", "initials": "N"}, {"family": "G\u00f6ransson", "given": "Hanna", "initials": "H"}, {"family": "Enstr\u00f6m", "given": "Camilla", "initials": "C"}, {"family": "Ryan", "given": "Fergus", "initials": "F"}, {"family": "Isaksson", "given": "Anders", "initials": "A"}, {"family": "Rosenquist", "given": "Richard", "initials": "R"}], "type": "journal article", "published": "2010-01-14", "journal": {"volume": "115", "issn": "1528-0020", "issue": "2", "pages": "296-305", "title": "Blood", "issn-l": "0006-4971"}, "abstract": "Global hypomethylation and regional hypermethylation are well-known epigenetic features of cancer; however, in chronic lymphocytic leukemia (CLL), studies on genome-wide epigenetic modifications are limited. Here, we analyzed the global methylation profiles in CLL, by applying high-resolution methylation microarrays (27,578 CpG sites) to 23 CLL samples, belonging to the immunoglobulin heavy-chain variable (IGHV) mutated (favorable) and IGHV unmutated/IGHV3-21 (poor-prognostic) subsets. Overall, results demonstrated significant differences in methylation patterns between these subgroups. Specifically, in IGHV unmutated CLL, we identified methylation of 7 known or candidate tumor suppressor genes (eg, VHL, ABI3, and IGSF4) as well as 8 unmethylated genes involved in cell proliferation and tumor progression (eg, ADORA3 and PRF1 enhancing the nuclear factor-kappaB and mitogen-activated protein kinase pathways, respectively). In contrast, these latter genes were silenced by methylation in IGHV mutated patients. The array data were validated for selected genes using methylation-specific polymerase chain reaction, quantitative reverse transcriptase-polymerase chain reaction, and bisulfite sequencing. Finally, the significance of DNA methylation in regulating gene promoters was shown by reinducing 4 methylated tumor suppressor genes (eg, VHL and ABI3) in IGHV unmutated samples using the methyl-inhibitor 5-aza-2'-deoxycytidine. Taken together, our data for the first time reveal differences in global methylation profiles between prognostic subsets of CLL, which may unfold epigenetic silencing mechanisms involved in CLL pathogenesis.", "doi": "10.1182/blood-2009-07-232868", "pmid": "19897574", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (SNP&SEQ Technology Platform)": null, "Array and Analysis Facility": null}, "xrefs": [{"db": "pii", "key": "blood-2009-07-232868"}], "notes": [], "created": "2017-05-04T15:00:27.663Z", "modified": "2020-01-21T13:56:11.374Z"}, {"entity": "publication", "iuid": "1da7009322084dd19cdb9230f1f7bace", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1da7009322084dd19cdb9230f1f7bace.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1da7009322084dd19cdb9230f1f7bace"}}, "title": "Large but not small copy-number alterations correlate to high-risk genomic aberrations and survival in chronic lymphocytic leukemia: a high-resolution genomic screening of newly diagnosed patients.", "authors": [{"family": "Gunnarsson", "given": "R", "initials": "R"}, {"family": "Isaksson", "given": "A", "initials": "A"}, {"family": "Mansouri", "given": "M", "initials": "M"}, {"family": "G\u00f6ransson", "given": "H", "initials": "H"}, {"family": "Jansson", "given": "M", "initials": "M"}, {"family": "Cahill", "given": "N", "initials": "N"}, {"family": "Rasmussen", "given": "M", "initials": "M"}, {"family": "Staaf", "given": "J", "initials": "J"}, {"family": "Lundin", "given": "J", "initials": "J"}, {"family": "Norin", "given": "S", "initials": "S"}, {"family": "Buhl", "given": "A M", "initials": "AM"}, {"family": "Smedby", "given": "K E", "initials": "KE"}, {"family": "Hjalgrim", "given": "H", "initials": "H"}, {"family": "Karlsson", "given": "K", "initials": "K"}, {"family": "Jurlander", "given": "J", "initials": "J"}, {"family": "Juliusson", "given": "G", "initials": "G"}, {"family": "Rosenquist", "given": "R", "initials": "R"}], "type": "letter", "published": "2010-01-00", "journal": {"volume": "24", "issn": "1476-5551", "issue": "1", "pages": "211-215", "title": "Leukemia", "issn-l": "0887-6924"}, "abstract": null, "doi": "10.1038/leu.2009.187", "pmid": "19741724", "labels": {"Array and Analysis Facility": null}, "xrefs": [{"db": "pii", "key": "leu2009187"}, {"db": "GEO", "description": "Genome variation profiling by SNP array", "key": "GSE16406"}], "notes": [], "created": "2017-05-04T15:02:50.357Z", "modified": "2018-11-14T14:16:15.622Z"}, {"entity": "publication", "iuid": "6390ec72923c41d59b4190f3dbf9493e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6390ec72923c41d59b4190f3dbf9493e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6390ec72923c41d59b4190f3dbf9493e"}}, "title": "Characterization of the cytotoxic properties of the benzimidazole fungicides, benomyl and carbendazim, in human tumour cell lines and primary cultures of patient tumour cells.", "authors": [{"family": "Laryea", "given": "Daniel", "initials": "D"}, {"family": "Gullbo", "given": "Joachim", "initials": "J"}, {"family": "Isaksson", "given": "Anders", "initials": "A"}, {"family": "Larsson", "given": "Rolf", "initials": "R"}, {"family": "Nygren", "given": "Peter", "initials": "P"}], "type": "journal article", "published": "2010-01-00", "journal": {"volume": "21", "issn": "1473-5741", "issue": "1", "pages": "33-42", "title": "Anticancer Drugs", "issn-l": "0959-4973"}, "abstract": "The benzimidazoles, benomyl and carbendazim, are fungicides suggested to target microtubules. Benomyl is metabolized to carbendazim, which has already been explored as an anticancer drug in phase 1 clinical trials. We further characterized the cytotoxic properties of benomyl and carbendazim in 12 human cell lines and in primary cultures of patient tumour cells with the overall aims of elucidating mechanisms of action and anticancer activity spectrum. Cytotoxicity was assessed in the short-term fluorometric microculture cytotoxicity assay and was correlated with the activity of other anticancer drugs and gene expression assessed by cDNA microarray analysis. Benomyl was generally more potent than its metabolite, carbendazim. Both showed high drug activity correlations with several established and experimental anticancer drugs, but modest association with established mechanisms of drug resistance. Furthermore, these benzimidazoles showed high correlations with genes considered relevant for the activity of several mechanistically different standard and experimental anticancer drugs, indicating multiple and broad mechanisms of action. In patient tumour samples, benomyl tended to be more active in haematological compared with solid tumour malignancies, whereas the opposite was observed for carbendazim. In conclusion, benomyl and carbendazim show interesting and diverse cytotoxic mechanisms of action and seem suitable as lead compounds for the development of new anticancer drugs.", "doi": "10.1097/CAD.0b013e328330e74e", "pmid": "19786863", "labels": {"Array and Analysis Facility": null}, "xrefs": [], "notes": [], "created": "2017-05-04T15:02:47.652Z", "modified": "2018-11-14T14:21:05.005Z"}]}