{"entity": "journal", "iuid": "12a18231f2924749970d277830672b2e", "timestamp": "2026-08-11T07:49:24.098Z", "links": {"self": {"href": "https://publications.scilifelab.se/journal/J%20Transl%20Med.json"}, "display": {"href": "https://publications.scilifelab.se/journal/J%20Transl%20Med"}}, "title": "J Transl Med", "issn": "1479-5876", "issn-l": "1479-5876", "publications_count": 14, "publications": [{"entity": "publication", "iuid": "e423aa4f3d3743ffa8ead1c41ea5a808", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e423aa4f3d3743ffa8ead1c41ea5a808.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e423aa4f3d3743ffa8ead1c41ea5a808"}}, "title": "Beta-blockers prolong response to androgen deprivation therapy in prostate cancer through modulation of the neuro-immuno-oncology axis.", "authors": [{"family": "Thulin", "given": "Malin Hagberg", "initials": "MH"}, {"family": "Ramberg", "given": "H\u00e5kon", "initials": "H"}, {"family": "Nielsen", "given": "Heidi Kristin", "initials": "HK"}, {"family": "Grytli", "given": "Helene Hartvedt", "initials": "HH"}, {"family": "Sivanesan", "given": "Shivanthe", "initials": "S"}, {"family": "Pandya", "given": "Abhilash D", "initials": "AD"}, {"family": "Seip", "given": "Kotryna", "initials": "K"}, {"family": "Andressen", "given": "Kjetil Wessel", "initials": "KW"}, {"family": "Linder", "given": "Anna", "initials": "A", "orcid": "0000-0002-9444-1346", "researcher": {"href": "https://publications.scilifelab.se/researcher/38b4f1c441ff49b891db4d7fb8163491.json"}}, {"family": "\u00d8ijordsbakken", "given": "Miriam", "initials": "M"}, {"family": "Poutanen", "given": "Matti", "initials": "M"}, {"family": "Katz", "given": "Betina", "initials": "B"}, {"family": "Halvorsen", "given": "Bente", "initials": "B", "orcid": "0000-0002-6529-6485", "researcher": {"href": "https://publications.scilifelab.se/researcher/83218278a90c41609ea44fcd6315d395.json"}}, {"family": "M\u00e6landsmo", "given": "Gunhild Mari", "initials": "GM"}, {"family": "Task\u00e9n", "given": "Kristin Austlid", "initials": "KA", "orcid": "0000-0001-5530-4915", "researcher": {"href": "https://publications.scilifelab.se/researcher/0c58b6542626483697216077c630309a.json"}}], "type": "journal article", "published": "2025-06-17", "journal": {"title": "J Transl Med", "issn": "1479-5876", "volume": "23", "issue": "1", "pages": "672", "issn-l": "1479-5876"}, "abstract": "The therapeutic impact of beta-blockers (BB), beta-adrenergic receptor antagonists, on prostate cancer remains controversial. The underlying health conditions of BB users complicate the ability to isolate and evaluate the specific effects of these drugs on the tumour cells. This study investigated whether BBs, by inhibiting sympathetic nerve signalling, extended the duration of androgen deprivation therapy (ADT) effectiveness in patients with de novo metastatic hormone sensitive prostate cancer and in prostate cancer xenograft models, while also uncovering the molecular mechanisms involved.\n\nAn analysis was conducted on prospectively collected data from the Cancer Registry of Norway, Norwegian Prescription Database, and Norwegian Cause of Death Registry focusing on patients with de novo metastatic prostate cancer undergoing ADT using the commencement of second-line treatment as the endpoint. In addition, the causal effect of BB treatment was studied in two different hormone-sensitive prostate cancer xenograft mouse models. Prior to treatment, mice were surgically castrated, to mimic ADT, and tumour progression was tracked by measuring serum PSA levels. RNA sequencing was performed on xenografted orthotopic tumours to investigate the underlying mechanisms, utilizing annotation based on human data and protein levels were validated by the Protein Simple Immunoassay. Immune-related effects were evaluated using immunohistochemistry on tumour tissue and measuring neopterin levels, along with 92 analytes, using the OLINK proximity extension assay on serum samples from xenografted mice and prostate cancer patients, both BB users and non-users.\n\nA competitive risk analysis indicated that BB treatment postponed the initiation of second-line treatment in prostate cancer patients on ADT. Additionally, in both prostate cancer xenograft models, BB treatment reduced tumour burden and delayed progression to castration-resistant prostate cancer. Mechanistically, BB treatment suppressed androgen receptor signalling and induced a metabolic shift by up-regulating oxidative phosphorylation transcripts and down-regulating those involved in fatty acid synthesis and the PI3K/AKT/mTOR pathway. Additionally, BB treatment increased serum pro-inflammatory cytokines, such as the IL23/IL17 axis, in both xenografted mice and in patient samples. Enhanced intra-tumoral CD68+ immune cell infiltration was also observed in the tumours.\n\nThe data suggest that BB combined with ADT delay the progression to castration-resistant prostate cancer. This may be achieved by influencing androgen receptor activity, adjusting energy metabolism and fostering a pro-inflammatory antitumoral microenvironment.", "doi": "10.1186/s12967-025-06644-7", "pmid": "40528241", "labels": {"Clinical Genomics": "Service", "Clinical Genomics Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12175445"}, {"db": "pii", "key": "10.1186/s12967-025-06644-7"}], "notes": [], "created": "2025-07-08T13:57:28.735Z", "modified": "2025-11-04T11:53:28.029Z"}, {"entity": "publication", "iuid": "6c6cbdbfe7064dcfb2e87e001b74625e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6c6cbdbfe7064dcfb2e87e001b74625e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6c6cbdbfe7064dcfb2e87e001b74625e"}}, "title": "Proteomic analysis of human kidney biopsies unveils emerging acute kidney injury very early after liver graft reperfusion.", "authors": [{"family": "Nor\u00e9n", "given": "\u00c5sa", "initials": "\u00c5"}, {"family": "Boi", "given": "Roberto", "initials": "R"}, {"family": "Pullerits", "given": "Rille", "initials": "R"}, {"family": "M\u00f6lne", "given": "Johan", "initials": "J"}, {"family": "Ebefors", "given": "Kerstin", "initials": "K"}, {"family": "Friman", "given": "Styrbj\u00f6rn", "initials": "S"}, {"family": "Sihlbom", "given": "Carina", "initials": "C"}, {"family": "Herlenius", "given": "Gustaf", "initials": "G"}, {"family": "Nystr\u00f6m", "given": "Jenny", "initials": "J"}, {"family": "Oltean", "given": "Mihai", "initials": "M", "orcid": "0000-0003-3783-5207", "researcher": {"href": "https://publications.scilifelab.se/researcher/60a46e232d2644afbe9a4f3d89316a7a.json"}}], "type": "journal article", "published": "2025-06-16", "journal": {"title": "J Transl Med", "issn": "1479-5876", "volume": "23", "issue": "1", "pages": "658", "issn-l": "1479-5876"}, "abstract": "Acute kidney injury (AKI) is a frequent complication after liver transplantation (LT) and is associated with morbidity, mortality, and late development of chronic kidney disease. Risk factors for AKI after LT include patient, perioperative and graft-related factors. The exact renal molecular mechanisms behind AKI in LT are unclear.\n\nAlterations in the proteome were investigated in kidney biopsies from 21 patients undergoing LT using quantitative proteomics. The most upregulated protein was validated using immunohistochemistry. In addition, serum levels of interleukin (IL)-33, insulin-like growth factor binding protein (IGFBP)-7 and high-mobility group box (HMGB)-1 were analyzed. In silico data validation was performed using 14 recently published proteomics and transcriptomics datasets.\n\nIn post-reperfusion biopsies, we identified 731 differentially regulated proteins between patients with and without AKI. The most upregulated pathways were related to inflammation, integrin signaling and extracellular matrix (ECM) remodeling. The most downregulated pathways were traceable to a mitochondrial origin. HMGB-1 was found to be already upregulated (15%) 2 h after LT in patients who later developed AKI. The AKI group also showed upregulation of the alarmin IGFBP-7, caspases 1, 4 and 8, nuclear factor kappa B subunits, and the inflammasome adaptor protein PYCARD. Circulating IL-33 and HMGB-1 (but not IGFBP-7) increased during LT but returned to normal levels within 24 h. Altogether, these findings indicate ongoing inflammatory signaling activity in the kidneys of LT recipients who ultimately develop moderate or severe AKI shortly after liver graft reperfusion.\n\nLT induces extensive alarmin signaling and ECM remodeling in the kidneys of recipients who develop postoperative AKI. Further strategies to curtail this phenomenon are mandated. Trial registration https://www.researchweb.org/is/en/vgr/project/278585 , Registered 24 May 2022 (Retrospectively registered).", "doi": "10.1186/s12967-025-06695-w", "pmid": "40524147", "labels": {"Glycoproteomics and MS Proteomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12172208"}, {"db": "pii", "key": "10.1186/s12967-025-06695-w"}], "notes": [], "created": "2025-10-23T09:39:17.958Z", "modified": "2025-10-23T09:39:18.049Z"}, {"entity": "publication", "iuid": "b4d27c0d48ac4143a49b87b646b8f03d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b4d27c0d48ac4143a49b87b646b8f03d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b4d27c0d48ac4143a49b87b646b8f03d"}}, "title": "Indole-3-propionic acid promotes hepatic stellate cells inactivation.", "authors": [{"family": "Ilha", "given": "Mariana", "initials": "M"}, {"family": "Sehgal", "given": "Ratika", "initials": "R"}, {"family": "Matilainen", "given": "Johanna", "initials": "J"}, {"family": "Rilla", "given": "Kirsi", "initials": "K"}, {"family": "Kaminska", "given": "Dorota", "initials": "D"}, {"family": "Gandhi", "given": "Shrey", "initials": "S"}, {"family": "M\u00e4nnist\u00f6", "given": "Ville", "initials": "V"}, {"family": "Ling", "given": "Charlotte", "initials": "C"}, {"family": "Romeo", "given": "Stefano", "initials": "S"}, {"family": "Pajukanta", "given": "P\u00e4ivi", "initials": "P"}, {"family": "Pirinen", "given": "Eija", "initials": "E"}, {"family": "Virtanen", "given": "Kirsi A", "initials": "KA"}, {"family": "Pietil\u00e4inen", "given": "Kirsi H", "initials": "KH"}, {"family": "Vaittinen", "given": "Maija", "initials": "M", "orcid": "0000-0002-7423-557X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f4df504651a54e8bae68022d8ce7f89a.json"}}, {"family": "Pihlajam\u00e4ki", "given": "Jussi", "initials": "J"}], "type": "journal article", "published": "2025-03-01", "journal": {"title": "J Transl Med", "issn": "1479-5876", "volume": "23", "issue": "1", "pages": "253", "issn-l": "1479-5876"}, "abstract": "We have previously reported that the serum levels of gut-derived tryptophan metabolite indole-3-propionic acid (IPA) are lower in individuals with liver fibrosis. Now, we explored the transcriptome and DNA methylome associated with serum IPA levels in human liver from obese individuals together with IPA effects on shifting the hepatic stellate cell (HSC) phenotype to inactivation in vitro.\n\nA total of 116 obese individuals without type 2 diabetes (T2D) (age 46.8 \u00b1 9.3 years; BMI: 42.7 \u00b1 5.0 kg/m2) from the Kuopio OBesity Surgery (KOBS) study undergoing bariatric surgery were included. Circulating IPA levels were measured using LC-MS, liver transcriptomics with total RNA-sequencing and DNA methylation with Infinium HumanMethylation450 BeadChip. Human hepatic stellate cells (LX-2) where used for in vitro experiments.\n\nSerum IPA levels were associated with the expression of liver genes enriched for apoptosis, mitophagy and longevity pathways in the liver. AKT serine/threonine kinase 1 (AKT1) was the shared and topmost interactive gene from the liver transcript and DNA methylation profile. IPA treatment induced apoptosis, reduced mitochondrial respiration as well as modified cell morphology, and mitochondrial dynamics by modulating the expression of genes known to regulate fibrosis, apoptosis, and survival in LX-2 cells.\n\nIn conclusion, these data support that IPA has a plausible therapeutic effect and may induce apoptosis and the HSC phenotype towards the inactivation state, extending the possibilities to suppress hepatic fibrogenesis by interfering with HSC activation and mitochondrial metabolism.", "doi": "10.1186/s12967-025-06266-z", "pmid": "40025530", "labels": {"Clinical Genomics Lund": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11871697"}, {"db": "pii", "key": "10.1186/s12967-025-06266-z"}], "notes": [], "created": "2025-10-30T13:30:46.601Z", "modified": "2025-10-30T13:30:46.745Z"}, {"entity": "publication", "iuid": "e04df0fa941a476eb99c34ad3c1febab", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e04df0fa941a476eb99c34ad3c1febab.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e04df0fa941a476eb99c34ad3c1febab"}}, "title": "Shedding of membrane complement inhibitors CD59 and CD46 into the circulation is associated with poor prognosis in acute coronary syndrome patients: a cohort study.", "authors": [{"family": "Zhong", "given": "Baojun", "initials": "B", "orcid": "0000-0001-9612-4507", "researcher": {"href": "https://publications.scilifelab.se/researcher/2f6adf8f586b4f29a1bc490e4ce98758.json"}}, {"family": "King", "given": "Ben", "initials": "B"}, {"family": "Waziri", "given": "Homa", "initials": "H"}, {"family": "Yndigegn", "given": "Troels", "initials": "T"}, {"family": "Engelbertsen", "given": "Daniel", "initials": "D"}, {"family": "Bj\u00f6rkbacka", "given": "Harry", "initials": "H"}, {"family": "Nilsson", "given": "Jan", "initials": "J"}, {"family": "Goncalves", "given": "Isabel", "initials": "I"}, {"family": "Blom", "given": "Anna M", "initials": "AM"}, {"family": "Schiopu", "given": "Alexandru", "initials": "A"}], "type": "journal article", "published": "2024-11-10", "journal": {"title": "J Transl Med", "issn": "1479-5876", "volume": "22", "issue": "1", "pages": "1011", "issn-l": "1479-5876"}, "abstract": "The role of the complement inhibitory proteins CD46 and CD59 in the immune response to an acute coronary syndrome (ACS) is unknown. We investigated the relationships between the shedding of CD46 and CD59 into the circulation, reflected by plasma levels of soluble CD46 and CD59, and the risk for post-ACS complications.\n\nWe measured plasma sCD46 and sCD59 in a cohort of 546 ACS patients within 24 h after hospital admission, and after 6-weeks in a subgroup of 114 patients. Study outcomes were incident heart failure (HF), major adverse cardiovascular events (MACE) and mortality during a median follow-up period of up to 3.3 years. Echocardiography at 1-year was performed in the follow-up subgroup.\n\nElevated sCD46 and sCD59 were correlated with increased levels of inflammatory mediators and metalloproteinases in plasma, and were associated with increased risk for MACE in Cox proportional hazard models adjusted for cardiovascular risk factors and revascularization [HR 95% CI 1.24 (1.02-1.52), p = 0.034 for sCD46 and 1.18 (1.00-1.38), p = 0.049 for sCD59]. Elevated sCD59 was also associated with higher incidence of HF [HR 95% CI 1.41 (1.15-1.74), p = 0.001], and with lower left ventricular ejection fraction at 1-year post-ACS (Spearman r = - 0.234, p = 0.020). We found no associations between plasma levels of the proteins at 6 weeks and outcomes.\n\nShedding of the complement regulators CD46 and CD59 in plasma in the acute phase of ACS is associated with a negative prognosis. Plasma sCD46 and sCD59 could reflect the degree of local immune activation and serve as prognostic biomarkers in ACS patients.", "doi": "10.1186/s12967-024-05781-9", "pmid": "39523332", "labels": {"Affinity Proteomics Uppsala": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11550518"}, {"db": "pii", "key": "10.1186/s12967-024-05781-9"}], "notes": [], "created": "2025-11-25T19:20:31.650Z", "modified": "2025-11-25T19:20:31.714Z"}, {"entity": "publication", "iuid": "aa2a7d975fb74315acad6d0064c484ee", "links": {"self": {"href": "https://publications.scilifelab.se/publication/aa2a7d975fb74315acad6d0064c484ee.json"}, "display": {"href": "https://publications.scilifelab.se/publication/aa2a7d975fb74315acad6d0064c484ee"}}, "title": "Parvimonas micra forms a distinct bacterial network with oral pathobionts in colorectal cancer patients.", "authors": [{"family": "L\u00f6wenmark", "given": "Thyra", "initials": "T"}, {"family": "K\u00f6hn", "given": "Linda", "initials": "L"}, {"family": "Kellgren", "given": "Therese", "initials": "T"}, {"family": "Rosenbaum", "given": "William", "initials": "W"}, {"family": "Bronnec", "given": "Vicky", "initials": "V"}, {"family": "L\u00f6fgren-Burstr\u00f6m", "given": "Anna", "initials": "A"}, {"family": "Zingmark", "given": "Carl", "initials": "C"}, {"family": "Larsson", "given": "P\u00e4r", "initials": "P"}, {"family": "Dahlberg", "given": "Michael", "initials": "M"}, {"family": "Schroeder", "given": "Bjoern O", "initials": "BO"}, {"family": "Wai", "given": "Sun Nyunt", "initials": "SN"}, {"family": "Ljuslinder", "given": "Ingrid", "initials": "I"}, {"family": "Edin", "given": "Sofia", "initials": "S"}, {"family": "Palmqvist", "given": "Richard", "initials": "R", "orcid": "0000-0002-9933-2843", "researcher": {"href": "https://publications.scilifelab.se/researcher/40ae823e5364458b8f957a65a82c741f.json"}}], "type": "journal article", "published": "2024-10-17", "journal": {"title": "J Transl Med", "issn": "1479-5876", "volume": "22", "issue": "1", "pages": "947", "issn-l": "1479-5876"}, "abstract": "Mounting evidence suggests a significant role of the gut microbiota in the development and progression of colorectal cancer (CRC). In particular, an over-representation of oral pathogens has been linked to CRC. The aim of this study was to further investigate the faecal microbial landscape of CRC patients, with a focus on the oral pathogens Parvimonas micra and Fusobacterium nucleatum.\n\nIn this study, 16S rRNA sequencing was conducted using faecal samples from CRC patients (n = 275) and controls without pathological findings (n = 95).\n\nWe discovered a significant difference in microbial composition depending on tumour location and microsatellite instability (MSI) status, with P. micra, F. nucleatum, and Peptostreptococcus stomatis found to be more abundant in patients with MSI tumours. Moreover, P. micra and F. nucleatum were associated with a cluster of CRC-related bacteria including Bacteroides fragilis as well as with other oral pathogens such as P. stomatis and various Porphyromonas species. This cluster was distinctly different in the control group, suggesting its potential linkage with CRC.\n\nOur results suggest a similar distribution of several CRC-associated bacteria within CRC patients, underscoring the importance of considering the concomitant presence of bacterial species in studies investigating the mechanisms of CRC development and progression.", "doi": "10.1186/s12967-024-05720-8", "pmid": "39420333", "labels": {"Clinical Genomics Ume\u00e5": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC11487773"}, {"db": "pii", "key": "10.1186/s12967-024-05720-8"}], "notes": [], "created": "2024-11-28T07:54:58.747Z", "modified": "2024-11-28T07:54:58.927Z"}, {"entity": "publication", "iuid": "1d3b7fea5cfd4176bf02dbfee8c38279", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1d3b7fea5cfd4176bf02dbfee8c38279.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1d3b7fea5cfd4176bf02dbfee8c38279"}}, "title": "Deciphering the role of FUS::DDIT3 expression and tumor microenvironment in myxoid liposarcoma development.", "authors": [{"family": "Ranji", "given": "Parmida", "initials": "P"}, {"family": "Jonasson", "given": "Emma", "initials": "E"}, {"family": "Andersson", "given": "Lisa", "initials": "L"}, {"family": "Filges", "given": "Stefan", "initials": "S"}, {"family": "Luna Santamar\u00eda", "given": "Manuel", "initials": "M"}, {"family": "Vannas", "given": "Christoffer", "initials": "C"}, {"family": "Dolatabadi", "given": "Soheila", "initials": "S"}, {"family": "Gustafsson", "given": "Anna", "initials": "A"}, {"family": "Myklebost", "given": "Ola", "initials": "O"}, {"family": "H\u00e5kansson", "given": "Joakim", "initials": "J"}, {"family": "Fagman", "given": "Henrik", "initials": "H"}, {"family": "Landberg", "given": "G\u00f6ran", "initials": "G"}, {"family": "\u00c5man", "given": "Pierre", "initials": "P"}, {"family": "St\u00e5hlberg", "given": "Anders", "initials": "A", "orcid": "0000-0003-4243-0191", "researcher": {"href": "https://publications.scilifelab.se/researcher/05306b130d6543eea88a4f518085981e.json"}}], "type": "journal article", "published": "2024-04-26", "journal": {"title": "J Transl Med", "issn": "1479-5876", "volume": "22", "issue": "1", "pages": "389", "issn-l": "1479-5876"}, "abstract": "Myxoid liposarcoma (MLS) displays a distinctive tumor microenvironment and is characterized by the FUS::DDIT3 fusion oncogene, however, the precise functional contributions of these two elements remain enigmatic in tumor development.\n\nTo study the cell-free microenvironment in MLS, we developed an experimental model system based on decellularized patient-derived xenograft tumors. We characterized the cell-free scaffold using mass spectrometry. Subsequently, scaffolds were repopulated using sarcoma cells with or without FUS::DDIT3 expression that were analyzed with histology and RNA sequencing.\n\nCharacterization of cell-free MLS scaffolds revealed intact structure and a large variation of protein types remaining after decellularization. We demonstrated an optimal culture time of 3 weeks and showed that FUS::DDIT3 expression decreased cell proliferation and scaffold invasiveness. The cell-free MLS microenvironment and FUS::DDIT3 expression both induced biological processes related to cell-to-cell and cell-to-extracellular matrix interactions, as well as chromatin remodeling, immune response, and metabolism. Data indicated that FUS::DDIT3 expression more than the microenvironment determined the pre-adipocytic phenotype that is typical for MLS.\n\nOur experimental approach opens new means to study the tumor microenvironment in detail and our findings suggest that FUS::DDIT3-expressing tumor cells can create their own extracellular niche.", "doi": "10.1186/s12967-024-05211-w", "pmid": "38671504", "labels": {"Clinical Genomics Gothenburg": "Service", "Glycoproteomics and MS Proteomics": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11046918"}, {"db": "pii", "key": "10.1186/s12967-024-05211-w"}], "notes": [], "created": "2024-11-01T08:25:55.237Z", "modified": "2024-11-27T15:40:32.134Z"}, {"entity": "publication", "iuid": "abf59e6dbadf4871b930cf0a39f5f661", "links": {"self": {"href": "https://publications.scilifelab.se/publication/abf59e6dbadf4871b930cf0a39f5f661.json"}, "display": {"href": "https://publications.scilifelab.se/publication/abf59e6dbadf4871b930cf0a39f5f661"}}, "title": "Metabolomic profiles of intact tissues reflect clinically relevant prostate cancer subtypes.", "authors": [{"family": "Dudka", "given": "Ilona", "initials": "I"}, {"family": "Lundquist", "given": "Kristina", "initials": "K"}, {"family": "Wikstr\u00f6m", "given": "Pernilla", "initials": "P"}, {"family": "Bergh", "given": "Anders", "initials": "A"}, {"family": "Gr\u00f6bner", "given": "Gerhard", "initials": "G", "orcid": "0000-0001-7380-8797", "researcher": {"href": "https://publications.scilifelab.se/researcher/85bd86ebc85d4653bc880bc9be25bc80.json"}}], "type": "journal article", "published": "2023-11-27", "journal": {"title": "J Transl Med", "issn": "1479-5876", "volume": "21", "issue": "1", "pages": "860", "issn-l": "1479-5876"}, "abstract": "Prostate cancer (PC) is a heterogenous multifocal disease ranging from indolent to lethal states. For improved treatment-stratification, reliable approaches are needed to faithfully differentiate between high- and low-risk tumors and to predict therapy response at diagnosis.\n\nA metabolomic approach based on high resolution magic angle spinning nuclear magnetic resonance (HR MAS NMR) analysis was applied on intact biopsies samples (n = 111) obtained from patients (n = 31) treated by prostatectomy, and combined with advanced multi- and univariate statistical analysis methods to identify metabolomic profiles reflecting tumor differentiation (Gleason scores and the International Society of Urological Pathology (ISUP) grade) and subtypes based on tumor immunoreactivity for Ki67 (cell proliferation) and prostate specific antigen (PSA, marker for androgen receptor activity).\n\nValidated metabolic profiles were obtained that clearly distinguished cancer tissues from benign prostate tissues. Subsequently, metabolic signatures were identified that further divided cancer tissues into two clinically relevant groups, namely ISUP Grade 2 (n = 29) and ISUP Grade 3 (n = 17) tumors. Furthermore, metabolic profiles associated with different tumor subtypes were identified. Tumors with low Ki67 and high PSA (subtype A, n = 21) displayed metabolite patterns significantly different from tumors with high Ki67 and low PSA (subtype B, n = 28). In total, seven metabolites; choline, peak for combined phosphocholine/glycerophosphocholine metabolites (PC + GPC), glycine, creatine, combined signal of glutamate/glutamine (Glx), taurine and lactate, showed significant alterations between PC subtypes A and B.\n\nThe metabolic profiles of intact biopsies obtained by our non-invasive HR MAS NMR approach together with advanced chemometric tools reliably identified PC and specifically differentiated highly aggressive tumors from less aggressive ones. Thus, this approach has proven the potential of exploiting cancer-specific metabolites in clinical settings for obtaining personalized treatment strategies in PC.", "doi": "10.1186/s12967-023-04747-7", "pmid": "38012666", "labels": {"Swedish NMR Centre": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC10683247"}, {"db": "pii", "key": "10.1186/s12967-023-04747-7"}], "notes": [], "created": "2023-12-01T21:40:45.536Z", "modified": "2025-10-17T13:03:53.305Z"}, {"entity": "publication", "iuid": "29909db19bd74064be97cd0a000ef1a7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/29909db19bd74064be97cd0a000ef1a7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/29909db19bd74064be97cd0a000ef1a7"}}, "title": "Mitochondrial heteroplasmic shifts reveal a positive selection of breast cancer.", "authors": [{"family": "Li", "given": "Yanni", "initials": "Y", "orcid": "0000-0003-4550-8935", "researcher": {"href": "https://publications.scilifelab.se/researcher/29f30b9be82b470ea5123ddf3329c0f0.json"}}, {"family": "Sundquist", "given": "Kristina", "initials": "K"}, {"family": "Vats", "given": "Sakshi", "initials": "S"}, {"family": "Hong", "given": "Mun-Gwan", "initials": "MG"}, {"family": "Wang", "given": "Xiao", "initials": "X"}, {"family": "Chen", "given": "Yilun", "initials": "Y"}, {"family": "Hedelius", "given": "Anna", "initials": "A"}, {"family": "Saal", "given": "Lao H", "initials": "LH"}, {"family": "Sundquist", "given": "Jan", "initials": "J"}, {"family": "Memon", "given": "Ashfaque A", "initials": "AA"}], "type": "journal article", "published": "2023-10-05", "journal": {"title": "J Transl Med", "issn": "1479-5876", "volume": "21", "issue": "1", "pages": "696", "issn-l": "1479-5876"}, "abstract": "Breast cancer is, despite screening, not always detected early enough and is together with other tumor types known to shed genetic information in circulation. Unlike single-copy nuclear DNA, mitochondrial DNA (mtDNA) copies range from 100s to 10,000s per cell, thus providing a potentially alternative to identify potential missing cancer information in circulation at an early stage.\n\nTo characterize mitochondrial mutation landscapes in breast cancer, whole mtDNA sequencing and bioinformatics analyses were performed on 86 breast cancer biopsies and 50 available matched baseline cancer-free whole blood samples from the same individuals, selected from a cohort of middle-aged women in Sweden. To determine whether the mutations can be detected in blood plasma prior to cancer diagnosis, we further designed a nested case-control study (n = 663) and validated the shortlisted mutations using droplet digital PCR.\n\nWe detected different mutation landscapes between biopsies and matched whole blood samples. Compared to whole blood samples, mtDNA from biopsies had higher heteroplasmic mutations in the D-loop region (P = 0.02), RNR2 (P = 0.005), COX1 (P = 0.037) and CYTB (P = 0.006). Furthermore, the germline mtDNA mutations had higher heteroplasmy level than the lost (P = 0.002) and de novo mutations (P = 0.04). The nonsynonymous to synonymous substitution ratio (dN/dS) was higher for the heteroplasmic mutations (P = 7.25 \u00d7 10-12) than that for the homoplasmic mutations, but the de novo (P = 0.06) and lost mutations (P = 0.03) had lower dN/dS than the germline mutations. Interestingly, we found that the critical regions for mitochondrial transcription: MT-HSP1 (odds ratio [OR]: 21.41), MT-TFH (OR: 7.70) and MT-TAS2 (OR: 3.62), had significantly higher heteroplasmic mutations than the rest of the D-loop sub-regions. Finally, we found that the presence of mt.16093T > C mutation increases 67% risk of developing breast cancer.\n\nOur findings show that mitochondrial genetic landscape changes during cancer pathogenesis and positive selection of mtDNA heteroplasmic mutations in breast cancer. Most importantly, the mitochondrial mutations identified in biopsies can be traced back in matched plasma samples and could potentially be used as early breast cancer diagnostic biomarkers.", "doi": "10.1186/s12967-023-04534-4", "pmid": "37798736", "labels": {"Bioinformatics Support and Infrastructure": "Collaborative", "Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC10557196"}, {"db": "pii", "key": "10.1186/s12967-023-04534-4"}], "notes": [], "created": "2023-11-16T12:29:55.895Z", "modified": "2023-11-16T12:29:55.935Z"}, {"entity": "publication", "iuid": "2ace00d184224d9a8da1fe7ded82ae91", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2ace00d184224d9a8da1fe7ded82ae91.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2ace00d184224d9a8da1fe7ded82ae91"}}, "title": "The Swedish childhood tumor biobank: systematic collection and molecular characterization of all pediatric CNS and other solid tumors in Sweden.", "authors": [{"family": "D\u00edaz de St\u00e5hl", "given": "Teresita", "initials": "T", "orcid": "0000-0001-5933-6623", "researcher": {"href": "https://publications.scilifelab.se/researcher/2f51158ce6e14f3b96bf16a214689d1d.json"}}, {"family": "Shamikh", "given": "Alia", "initials": "A"}, {"family": "Mayrhofer", "given": "Markus", "initials": "M"}, {"family": "Juhos", "given": "Szilvester", "initials": "S"}, {"family": "Basmaci", "given": "Elisa", "initials": "E"}, {"family": "Prochazka", "given": "Gabriela", "initials": "G"}, {"family": "Garcia", "given": "Maxime", "initials": "M"}, {"family": "Somarajan", "given": "Praveen Raj", "initials": "PR"}, {"family": "Zielinska-Chomej", "given": "Katarzyna", "initials": "K"}, {"family": "Illies", "given": "Christopher", "initials": "C"}, {"family": "\u00d8ra", "given": "Ingrid", "initials": "I"}, {"family": "Siesj\u00f6", "given": "Peter", "initials": "P"}, {"family": "Sandstr\u00f6m", "given": "Per-Erik", "initials": "P"}, {"family": "Stenman", "given": "Jakob", "initials": "J"}, {"family": "Sabel", "given": "Magnus", "initials": "M"}, {"family": "Gustavsson", "given": "Bengt", "initials": "B"}, {"family": "Kogner", "given": "Per", "initials": "P"}, {"family": "Pfeifer", "given": "Susan", "initials": "S"}, {"family": "Ljungman", "given": "Gustaf", "initials": "G"}, {"family": "Sandgren", "given": "Johanna", "initials": "J"}, {"family": "Nist\u00e9r", "given": "Monica", "initials": "M"}], "type": "journal article", "published": "2023-05-23", "journal": {"title": "J Transl Med", "issn": "1479-5876", "issn-l": "1479-5876", "volume": "21", "issue": "1", "pages": "342"}, "abstract": "The Swedish Childhood Tumor Biobank (BTB) is a nonprofit national infrastructure for collecting tissue samples and genomic data from pediatric patients diagnosed with central nervous system (CNS) and other solid tumors. The BTB is built on a multidisciplinary network established to provide the scientific community with standardized biospecimens and genomic data, thereby improving knowledge of the biology, treatment and outcome of childhood tumors. As of 2022, over 1100 fresh-frozen tumor samples are available for researchers. We present the workflow of the BTB from sample collection and processing to the generation of genomic data and services offered. To determine the research and clinical utility of the data, we performed bioinformatics analyses on next-generation sequencing (NGS) data obtained from a subset of 82 brain tumors and patient blood-derived DNA combined with methylation profiling to enhance the diagnostic accuracy and identified germline and somatic alterations with potential biological or clinical significance. The BTB procedures for collection, processing, sequencing, and bioinformatics deliver high-quality data. We observed that the findings could impact patient management by confirming or clarifying the diagnosis in 79 of the 82 tumors and detecting known or likely driver mutations in 68 of 79 patients. In addition to revealing known mutations in a broad spectrum of genes implicated in pediatric cancer, we discovered numerous alterations that may represent novel driver events and specific tumor entities. In summary, these examples reveal the power of NGS to identify a wide number of actionable gene alterations. Making the power of NGS available in healthcare is a challenging task requiring the integration of the work of clinical specialists and cancer biologists; this approach requires a dedicated infrastructure, as exemplified here by the BTB.", "doi": "10.1186/s12967-023-04178-4", "pmid": "37221626", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Long-term Support WABI": "Collaborative", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Collaborative", "NGI Short read": "Collaborative", "NGI Stockholm (Genomics Production)": "Collaborative", "NGI SNP genotyping": "Service", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC10204274"}, {"db": "pii", "key": "10.1186/s12967-023-04178-4"}], "notes": [], "created": "2023-07-07T10:40:17.052Z", "modified": "2024-01-16T13:48:33.377Z"}, {"entity": "publication", "iuid": "64858245a8d64a6392e5c0222e60544e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/64858245a8d64a6392e5c0222e60544e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/64858245a8d64a6392e5c0222e60544e"}}, "title": "Short term starvation potentiates the efficacy of chemotherapy in triple negative breast cancer via metabolic reprogramming.", "authors": [{"family": "Pateras", "given": "Ioannis S", "initials": "IS"}, {"family": "Williams", "given": "Chloe", "initials": "C"}, {"family": "Gianniou", "given": "Despoina D", "initials": "DD"}, {"family": "Margetis", "given": "Aggelos T", "initials": "AT"}, {"family": "Avgeris", "given": "Margaritis", "initials": "M"}, {"family": "Rousakis", "given": "Pantelis", "initials": "P"}, {"family": "Legaki", "given": "Aigli-Ioanna", "initials": "AI"}, {"family": "Mirtschink", "given": "Peter", "initials": "P"}, {"family": "Zhang", "given": "Wei", "initials": "W"}, {"family": "Panoutsopoulou", "given": "Konstantina", "initials": "K"}, {"family": "Delis", "given": "Anastasios D", "initials": "AD"}, {"family": "Pagakis", "given": "Stamatis N", "initials": "SN"}, {"family": "Tang", "given": "Wei", "initials": "W"}, {"family": "Ambs", "given": "Stefan", "initials": "S"}, {"family": "Warpman Berglund", "given": "Ulrika", "initials": "U"}, {"family": "Helleday", "given": "Thomas", "initials": "T"}, {"family": "Varvarigou", "given": "Anastasia", "initials": "A"}, {"family": "Chatzigeorgiou", "given": "Antonios", "initials": "A"}, {"family": "Nordstr\u00f6m", "given": "Anders", "initials": "A"}, {"family": "Tsitsilonis", "given": "Ourania E", "initials": "OE"}, {"family": "Trougakos", "given": "Ioannis P", "initials": "IP"}, {"family": "Gilthorpe", "given": "Jonathan D", "initials": "JD"}, {"family": "Frisan", "given": "Teresa", "initials": "T"}], "type": "journal article", "published": "2023-03-03", "journal": {"title": "J Transl Med", "issn": "1479-5876", "volume": "21", "issue": "1", "pages": "169", "issn-l": "1479-5876"}, "abstract": "Chemotherapy (CT) is central to the treatment of triple negative breast cancer (TNBC), but drug toxicity and resistance place strong restrictions on treatment regimes. Fasting sensitizes cancer cells to a range of chemotherapeutic agents and also ameliorates CT-associated adverse effects. However, the molecular mechanism(s) by which fasting, or short-term starvation (STS), improves the efficacy of CT is poorly characterized.\n\nThe differential responses of breast cancer or near normal cell lines to combined STS and CT were assessed by cellular viability and integrity assays (Hoechst and PI staining, MTT or H2DCFDA staining, immunofluorescence), metabolic profiling (Seahorse analysis, metabolomics), gene expression (quantitative real-time PCR) and iRNA-mediated silencing. The clinical significance of the in vitro data was evaluated by bioinformatical integration of transcriptomic data from patient data bases: The Cancer Genome Atlas (TCGA), European Genome-phenome Archive (EGA), Gene Expression Omnibus (GEO) and a TNBC cohort. We further examined the translatability of our findings in vivo by establishing a murine syngeneic orthotopic mammary tumor-bearing model.\n\nWe provide mechanistic insights into how preconditioning with STS enhances the susceptibility of breast cancer cells to CT. We showed that combined STS and CT enhanced cell death and increased reactive oxygen species (ROS) levels, in association with higher levels of DNA damage and decreased mRNA levels for the NRF2 targets genes NQO1 and TXNRD1 in TNBC cells compared to near normal cells. ROS enhancement was associated with compromised mitochondrial respiration and changes in the metabolic profile, which have a significant clinical prognostic and predictive value. Furthermore, we validate the safety and efficacy of combined periodic hypocaloric diet and CT in a TNBC mouse model.\n\nOur in vitro, in vivo and clinical findings provide a robust rationale for clinical trials on the therapeutic benefit of short-term caloric restriction as an adjuvant to CT in triple breast cancer treatment.", "doi": "10.1186/s12967-023-03935-9", "pmid": "36869333", "labels": {"Swedish Metabolomics Centre": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9983166"}, {"db": "pii", "key": "10.1186/s12967-023-03935-9"}], "notes": [], "created": "2023-08-30T07:08:41.408Z", "modified": "2025-10-17T13:03:14.109Z"}, {"entity": "publication", "iuid": "6b96a366c06542319f176c1ff67cf59a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6b96a366c06542319f176c1ff67cf59a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6b96a366c06542319f176c1ff67cf59a"}}, "title": "Whole blood gene expression in adolescent chronic fatigue syndrome: an exploratory cross-sectional study suggesting altered B cell differentiation and survival.", "authors": [{"family": "Nguyen", "given": "Chinh Bkrong", "initials": "CB"}, {"family": "Als\u00f8e", "given": "Lene", "initials": "L"}, {"family": "Lindvall", "given": "Jessica M", "initials": "JM", "orcid": "0000-0002-5042-8481", "researcher": {"href": "https://publications.scilifelab.se/researcher/78debae1bc714b11a97ecf9e9656f1eb.json"}}, {"family": "Sulheim", "given": "Dag", "initials": "D"}, {"family": "Fagermoen", "given": "Even", "initials": "E"}, {"family": "Winger", "given": "Anette", "initials": "A"}, {"family": "Kaarb\u00f8", "given": "Mari", "initials": "M"}, {"family": "Nilsen", "given": "Hilde", "initials": "H"}, {"family": "Wyller", "given": "Vegard Bruun", "initials": "VB"}], "type": "journal article", "published": "2017-05-11", "journal": {"volume": "15", "issn": "1479-5876", "issue": "1", "pages": "102", "title": "J Transl Med", "issn-l": "1479-5876"}, "abstract": "Chronic fatigue syndrome (CFS) is a prevalent and disabling condition affecting adolescents. The pathophysiology is poorly understood, but immune alterations might be an important component. This study compared whole blood gene expression in adolescent CFS patients and healthy controls, and explored associations between gene expression and neuroendocrine markers, immune markers and clinical markers within the CFS group.\n\nCFS patients (12-18\u00a0years old) were recruited nation-wide to a single referral center as part of the NorCAPITAL project. A broad case definition of CFS was applied, requiring 3\u00a0months of unexplained, disabling chronic/relapsing fatigue of new onset, whereas no accompanying symptoms were necessary. Healthy controls having comparable distribution of gender and age were recruited from local schools. Whole blood samples were subjected to RNA sequencing. Immune markers were blood leukocyte counts, plasma cytokines, serum C-reactive protein and immunoglobulins. Neuroendocrine markers encompassed plasma and urine levels of catecholamines and cortisol, as well as heart rate variability indices. Clinical markers consisted of questionnaire scores for symptoms of post-exertional malaise, inflammation, fatigue, depression and trait anxiety, as well as activity recordings.\n\nA total of 29 CFS patients and 18 healthy controls were included. We identified 176 genes as differentially expressed in patients compared to controls, adjusting for age and gender factors. Gene set enrichment analyses suggested impairment of B cell differentiation and survival, as well as enhancement of innate antiviral responses and inflammation in the CFS group. A pattern of co-expression could be identified, and this pattern, as well as single gene transcripts, was significantly associated with indices of autonomic nervous activity, plasma cortisol, and blood monocyte and eosinophil counts. Also, an association with symptoms of post-exertional malaise was demonstrated.\n\nAdolescent CFS is characterized by differential gene expression pattern in whole blood suggestive of impaired B cell differentiation and survival, and enhanced innate antiviral responses and inflammation. This expression pattern is associated with neuroendocrine markers of altered HPA axis and autonomic nervous activity, and with symptoms of post-exertional malaise. Trial registration Clinical Trials NCT01040429.", "doi": "10.1186/s12967-017-1201-0", "pmid": "28494812", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Support and Infrastructure": "Collaborative", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1186/s12967-017-1201-0"}, {"db": "pmc", "key": "PMC5426002"}, {"db": "ClinicalTrials.gov", "key": "NCT01040429"}, {"db": "ClinicalTrials.gov", "key": "NCT01040429"}], "notes": [], "created": "2019-01-15T07:56:54.940Z", "modified": "2021-07-05T12:48:15.991Z"}, {"entity": "publication", "iuid": "21c76b86d39f445bbe0e41910513b2e3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/21c76b86d39f445bbe0e41910513b2e3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/21c76b86d39f445bbe0e41910513b2e3"}}, "title": "Adenovirus-mediated CD40L gene transfer increases Teffector/Tregulatory cell ratio and upregulates death receptors in metastatic melanoma patients.", "authors": [{"family": "Schiza", "given": "A", "initials": "A"}, {"family": "Wenthe", "given": "J", "initials": "J"}, {"family": "Mangsbo", "given": "S", "initials": "S"}, {"family": "Eriksson", "given": "E", "initials": "E"}, {"family": "Nilsson", "given": "Anders", "initials": "A"}, {"family": "T\u00f6tterman", "given": "T H", "initials": "TH"}, {"family": "Loskog", "given": "A", "initials": "A"}, {"family": "Ullenhag", "given": "G", "initials": "G", "orcid": "0000-0003-4949-3267", "researcher": {"href": "https://publications.scilifelab.se/researcher/c500b5e092af439fb28a7ec1d26fe53d.json"}}], "type": "clinical trial, phase i", "published": "2017-04-20", "journal": {"title": "J Transl Med", "issn": "1479-5876", "issn-l": "1479-5876", "volume": "15", "issue": "1", "pages": "79"}, "abstract": "Malignant melanoma is an aggressive tumor sensitive for immunotherapy such as checkpoint blockade antibodies. Still, most patients with late stage disease do not respond, and the side effects can be severe. Stimulation of the CD40 pathway to initiate anti-tumor immunity is a promising alternative. Herein, we demonstrate immune profiling data from melanoma patients treated with an adenovirus-based CD40 ligand gene therapy (AdCD40L).\n\nPeripheral blood mononuclear cells and plasma were collected from malignant melanoma patients (n = 15) enrolled in a phase I/IIa study investigating intratumoral delivery of AdCD40L with or without low dose cyclophosphamide. Cells were analyzed by flow cytometry while plasma samples were analyzed by a multi-array proteomics.\n\nAll patients had an increased Teffector/Tregulatory cell ratio post therapy. Simultaneously, the death receptors TNFR1 and TRAIL-R2 were significantly up-regulated post treatment. Stem cell factor (SCF), E-selectin, and CD6 correlated to enhanced overall survival while a high level of granulocytic myeloid-derived suppressor cells (gMDSCs), IL8, IL10, TGFb1, CCL4, PlGF and Fl3t ligand was highest in patients with short survival.\n\nAdCD40L intratumoral injection induced desirable systemic immune effects that correlated to prolonged survival. Further studies using CD40 stimulation in malignant melanoma are warranted. Trial registration The 002:CD40L trial \"Phase I/IIa AdCD40L Immunogene Therapy for Malignant Melanoma and Other Solid Tumors\" (clinicalTrials.gov identifier: NCT01455259) was registered at September 2011.", "doi": "10.1186/s12967-017-1182-z", "pmid": "28427434", "labels": {"Clinical Biomarkers": "Service", "PLA and Single Cell Proteomics": "Service", "Affinity Proteomics Uppsala": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s12967-017-1182-z"}, {"db": "pmc", "key": "PMC5399418"}, {"db": "ClinicalTrials.gov", "key": "NCT01455259"}, {"db": "ClinicalTrials.gov", "key": "NCT01455259"}], "notes": [], "created": "2020-01-23T15:08:30.707Z", "modified": "2023-04-14T13:56:15.463Z"}, {"entity": "publication", "iuid": "884ba280b10244048de9dd250b7257b9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/884ba280b10244048de9dd250b7257b9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/884ba280b10244048de9dd250b7257b9"}}, "title": "Low RBM3 protein expression correlates with tumour progression and poor prognosis in malignant melanoma: an analysis of 215 cases from the Malm\u00f6 Diet and Cancer Study.", "authors": [{"family": "Jonsson", "given": "Liv", "initials": "L"}, {"family": "Bergman", "given": "Julia", "initials": "J"}, {"family": "Nodin", "given": "Bj\u00f6rn", "initials": "B"}, {"family": "Manjer", "given": "Jonas", "initials": "J"}, {"family": "Pont\u00e9n", "given": "Fredrik", "initials": "F"}, {"family": "Uhl\u00e9n", "given": "Mathias", "initials": "M", "orcid": "0000-0002-4858-8056", "researcher": {"href": "https://publications.scilifelab.se/researcher/ff81da3cb0cf4262873b993a1b06798c.json"}}, {"family": "Jirstr\u00f6m", "given": "Karin", "initials": "K"}], "type": "journal article", "published": "2011-07-21", "journal": {"volume": "9", "issn": "1479-5876", "issue": null, "pages": "114", "title": "J Transl Med", "issn-l": "1479-5876"}, "abstract": "We have previously reported that expression of the RNA- and DNA-binding protein RBM3 is associated with a good prognosis in breast cancer and ovarian cancer. In this study, the prognostic value of immunohistochemical RBM3 expression was assessed in incident cases of malignant melanoma from a prospective population-based cohort study.\n\nUntil Dec 31st 2008, 264 incident cases of primary invasive melanoma had been registered in the Malm\u00f6 Diet and Cancer Study. Histopathological and clinical information was obtained for available cases and tissue microarrays (TMAs) constructed from 226 (85.6%) suitable paraffin-embedded tumours and 31 metastases. RBM3 expression was analysed by immunohistochemistry on the TMAs and a subset of full-face sections. Chi-square and Mann-Whitney U tests were used for comparison of RBM3 expression and relevant clinicopathological characteristics. Kaplan Meier analysis and Cox proportional hazards modelling were used to assess the relationship between RBM3 and recurrence free survival (RFS) and overall survival (OS).\n\nRBM3 could be assessed in 215/226 (95.1%) of primary tumours and all metastases. Longitudinal analysis revealed that 16/31 (51.6%) of metastases lacked RBM3 expression, in contrast to the primary tumours in which RBM3 was absent in 3/215 (1.4%) cases and strongly expressed in 120/215 (55.8%) cases. Strong nuclear RBM3 expression in the primary tumour was significantly associated with favourable clinicopathological parameters; i.e. non-ulcerated tumours, lower depth of invasion, lower Clark level, less advanced clinical stage, low mitotic activity and non-nodular histological type, and a prolonged RFS (RR = 0.50; 95% CI = 0.27-0.91) and OS (RR = 0.36, 95%CI = 0.20-0.64). Multivariate analysis demonstrated that the beneficial prognostic value of RBM3 remained significant for OS (RR = 0.33; 95%CI = 0.18-0.61).\n\nIn line with previous in vitro data, we here show that RBM3 is down-regulated in metastatic melanoma and high nuclear RBM3 expression in the primary tumour is an independent marker of a prolonged OS. The potential utility of RBM3 in treatment stratification of patients with melanoma should be pursued in future studies.", "doi": "10.1186/1479-5876-9-114", "pmid": "21777469", "labels": {"Tissue Profiling": null}, "xrefs": [{"db": "pii", "key": "1479-5876-9-114"}, {"db": "pmc", "key": "PMC3156749"}], "notes": [], "created": "2017-05-04T14:55:48.238Z", "modified": "2021-07-08T13:44:33.391Z"}, {"entity": "publication", "iuid": "48f20361419045e3bacde5fd8576433b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/48f20361419045e3bacde5fd8576433b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/48f20361419045e3bacde5fd8576433b"}}, "title": "Expression of the RNA-binding protein RBM3 is associated with a favourable prognosis and cisplatin sensitivity in epithelial ovarian cancer.", "authors": [{"family": "Ehl\u00e9n", "given": "Asa", "initials": "A"}, {"family": "Brennan", "given": "Donal J", "initials": "DJ"}, {"family": "Nodin", "given": "Bj\u00f6rn", "initials": "B"}, {"family": "O'Connor", "given": "Darran P", "initials": "DP"}, {"family": "Eberhard", "given": "Jakob", "initials": "J"}, {"family": "Alvarado-Kristensson", "given": "Maria", "initials": "M"}, {"family": "Jeffrey", "given": "Ian B", "initials": "IB"}, {"family": "Manjer", "given": "Jonas", "initials": "J"}, {"family": "Br\u00e4ndstedt", "given": "Jenny", "initials": "J"}, {"family": "Uhl\u00e9n", "given": "Mathias", "initials": "M", "orcid": "0000-0002-4858-8056", "researcher": {"href": "https://publications.scilifelab.se/researcher/ff81da3cb0cf4262873b993a1b06798c.json"}}, {"family": "Pont\u00e9n", "given": "Fredrik", "initials": "F"}, {"family": "Jirstr\u00f6m", "given": "Karin", "initials": "K"}], "type": "journal article", "published": "2010-08-20", "journal": {"volume": "8", "issn": "1479-5876", "issue": null, "pages": "78", "title": "J Transl Med", "issn-l": "1479-5876"}, "abstract": "We recently demonstrated that increased expression of the RNA-binding protein RBM3 is associated with a favourable prognosis in breast cancer. The aim of this study was to examine the prognostic value of RBM3 mRNA and protein expression in epithelial ovarian cancer (EOC) and the cisplatin response upon RBM3 depletion in a cisplatin-sensitive ovarian cancer cell line.\n\nRBM3 mRNA expression was analysed in tumors from a cohort of 267 EOC cases (Cohort I) and RBM3 protein expression was analysed using immunohistochemistry (IHC) in an independent cohort of 154 prospectively collected EOC cases (Cohort II). Kaplan Meier analysis and Cox proportional hazards modelling were applied to assess the relationship between RBM3 and recurrence free survival (RFS) and overall survival (OS). Immunoblotting and IHC were used to examine the expression of RBM3 in a cisplatin-resistant ovarian cancer cell line A2780-Cp70 and its cisplatin-responsive parental cell line A2780. The impact of RBM3 on cisplatin response in EOC was assessed using siRNA-mediated silencing of RBM3 in A2780 cells followed by cell viability assay and cell cycle analysis.\n\nIncreased RBM3 mRNA expression was associated with a prolonged RFS (HR = 0.64, 95% CI = 0.47-0.86, p = 0.003) and OS (HR = 0.64, 95% CI = 0.44-0.95, p = 0.024) in Cohort I. Multivariate analysis confirmed that RBM3 mRNA expression was an independent predictor of a prolonged RFS, (HR = 0.61, 95% CI = 0.44-0.84, p = 0.003) and OS (HR = 0.62, 95% CI = 0.41-0.95; p = 0.028) in Cohort I. In Cohort II, RBM3 protein expression was associated with a prolonged OS (HR = 0.53, 95% CI = 0.35-0.79, p = 0.002) confirmed by multivariate analysis (HR = 0.61, 95% CI = 0.40-0.92, p = 0.017). RBM3 mRNA and protein expression levels were significantly higher in the cisplatin sensitive A2780 cell line compared to the cisplatin resistant A2780-Cp70 derivative. siRNA-mediated silencing of RBM3 expression in the A2780 cells resulted in a decreased sensitivity to cisplatin as demonstrated by increased cell viability and reduced proportion of cells arrested in the G2/M-phase.\n\nThese data demonstrate that RBM3 expression is associated with cisplatin sensitivity in vitro and with a good prognosis in EOC. Taken together these findings suggest that RBM3 may be a useful prognostic and treatment predictive marker in EOC.", "doi": "10.1186/1479-5876-8-78", "pmid": "20727170", "labels": {"Tissue Profiling": null}, "xrefs": [{"db": "pii", "key": "1479-5876-8-78"}, {"db": "pmc", "key": "PMC2936876"}], "notes": [], "created": "2017-05-04T14:55:44.411Z", "modified": "2021-07-08T13:44:33.212Z"}], "created": "2017-05-09T09:12:14.265Z", "modified": "2020-11-27T13:14:04.117Z"}