| 1. |
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| 2. |
- Bryhn, Andreas, et al.
(författare)
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Kunskapsunderlag om möjliga icke-torskfiskerelaterade åtgärder för att torskbestånd ska bevaras och återhämta sig i svenska vatten
- 2020
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Rapport (refereegranskat)abstract
- Torsk (Gadus morhua) är en viktig art för marina ekosystem i Sverige, där den har en strukturerande och reglerande funktion i relation till andra arter. Torsken har under historiens gång även spelat en viktig roll för samhället i Sverige inom dess nuvarande gränsers område (Bohuslän har t.ex. inte alltid tillhört Sverige), som en målart för fiske. Samtliga torskbestånd som återfinns i havsområdena runt Sverige har nu dålig status och det internationella havsforskningsrådet ICES rekommenderar låg eller ingen fångst, beroende på bestånd. Utöver riktat fiske påverkas dock torsken av en rad andra faktorer som exempelvis bifångster i annat fiske, syrebrist, klimatförändringar, predatorer, parasiter, bottenpåverkan av trålning, förlust av uppväxtmiljöer, födobrist, tiaminbrist och giftiga ämnen. Denna rapport diskuterar möjligheter att skydda och bevara torsken på sätt som kan komplettera begränsningar i det riktade torskfisket. Torskens situation är komplex och rapporten är därför skriven utifrån ett ekosystemperspektiv för att möjliggöra en bredare ansats i förvaltningen av torskbestånd i svenska vatten, där alla relevanta påverkansfaktorer bör beaktas. Det bör poängteras att denna rapport inte har gjort någon ny utredning av påverkansfaktorernas effekter, utan har istället gjort en litteratursammanställning och en kvalitativ analys. Vi har ändå valt att lyfta fram vissa åtgärder som särskilt potentiellt betydelsefulla - en samlad kvalitativ expertbedömning som rangordnar olika åtgärders effektivitet för återuppbyggnad per bestånd, se avsnitt 6 i rapporten.
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| 3. |
- Bryhn, Andreas, et al.
(författare)
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Which factors can affect the productivity and dynamics of cod stocks in the Baltic Sea, Kattegat and Skagerrak?
- 2022
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Ingår i: Ocean and Coastal Management. - : Elsevier BV. - 0964-5691 .- 1873-524X. ; 223
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Forskningsöversikt (refereegranskat)abstract
- Stocks of Atlantic cod (Gadus morhua) in the Baltic Sea, Kattegat and Skagerrak (N. Europe) have been strongly exploited for decades bringing them into an enduringly depleted status. Scientific cod stock related advice for targeted and mixed fisheries is provided on an annual basis by the International Council for Exploration of the Sea. This advice forms a basis for ministerial decisions on, e.g., the total allowable catch and management plans. Despite measures to reduce fishing-induced mortality of cod, such as catch and effort restrictions, increased gear selectivity, closed areas and seasons, clear signs of recovery are yet to be seen. Thus, traditional advice for the management of these stocks may have to be complemented by advice on supporting measures focusing on other pressures hampering the recovery of cod. The present study elaborates on potential supportive measures for cod stock recovery in the Baltic Sea, Kattegat, and Skagerrak (including local populations where applicable), based on current knowledge. The list of measures presented here is the outcome of in-depth discussions on the state-of-the-art knowledge, among cod experts and further with stakeholders with the aim to follow principles of ecosystem-based fisheries management. Following the identification of different pressures on and prerequisites for the separate stocks, the listed measures differ between stocks and include cod bycatch mortality reduction, alterations in fisheries affecting food sources for cod, restocking, protection of juvenile habitats, and reduced predation. The literature review and the list of measures are intended to provide decision-support for managers and policymakers aiming to provide conditions for the cod stocks to recover.
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| 4. |
- Decaesteker, Bieke, et al.
(författare)
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SOX11 regulates SWI/SNF complex components as member of the adrenergic neuroblastoma core regulatory circuitry
- 2023
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- The pediatric extra-cranial tumor neuroblastoma displays a low mutational burden while recurrent copy number alterations are present in most high-risk cases. Here, we identify SOX11 as a dependency transcription factor in adrenergic neuroblastoma based on recurrent chromosome 2p focal gains and amplifications, specific expression in the normal sympatho-adrenal lineage and adrenergic neuroblastoma, regulation by multiple adrenergic specific (super-)enhancers and strong dependency on high SOX11 expression in adrenergic neuroblastomas. SOX11 regulated direct targets include genes implicated in epigenetic control, cytoskeleton and neurodevelopment. Most notably, SOX11 controls chromatin regulatory complexes, including 10 SWI/SNF core components among which SMARCC1, SMARCA4/BRG1 and ARID1A. Additionally, the histone deacetylase HDAC2, PRC1 complex component CBX2, chromatin-modifying enzyme KDM1A/LSD1 and pioneer factor c-MYB are regulated by SOX11. Finally, SOX11 is identified as a core transcription factor of the core regulatory circuitry (CRC) in adrenergic high-risk neuroblastoma with a potential role as epigenetic master regulator upstream of the CRC.
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| 5. |
- Ek, Hanna, et al.
(författare)
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Transitioning from conventional photon therapy to proton therapy for primary brain tumors
- 2023
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Ingår i: Acta oncologica (Stockholm, Sweden). - 1651-226X. ; 62:4, s. 391-399
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Proton radiation therapy (PT) has become a treatment option alongside photon therapy (XRT) for lower-grade gliomas (LGG). In this single-institution retrospective study, we investigate the patient characteristics and treatment outcomes, including pseudo-progression (PsP), for LGG patients selected for PT. Method: Adult patients with grade 2–3 glioma consecutively treated with radiotherapy (RT) from May 2012 to December 2019 were retrospectively included in this cohort study. Tumor characteristics and treatment data were collected. The groups treated with PT and XRT were compared regarding treatment characteristics, side effects, occurrence of PsP, and survival outcomes. PsP was defined as new or growing lesions followed by either decrease or stabilization during a 12 month-period with no treatment. Results: Out of 143 patients meeting the inclusion criteria, 44 were treated with PT, 98 with XRT and one with mixed PT + XRT. The patients receiving PT were younger, had a lower tumor grade, more oligodendrogliomas and received a lower mean brain and brainstem dose. PsP was observed in 21 out of 126 patients, with no difference between XRT and PT (p =.38). The rate of fatigue in immediate connection to RT (zero to three months after) was higher for XRT than for PT (p =.016). The PT patients had a significantly better PFS and OS than the XRT patients (p =.025 and.035), but in multivariate analysis radiation modality was non-significant. Higher average dose to both brain and brainstem was associated with inferior PFS and OS (p <.001). Median follow-up time were 69 months and 26 months for XRT and PT patients, respectively. Conclusion: Contrary to previous studies, there was no difference in risk of PsP for XRT and PT. PT was associated with lower rates of fatigue <3 months after RT. The superior survival outcomes for PT indicates that the patients with the best prognosis were referred to PT.
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| 6. |
- Emruli, Venera Kuci, et al.
(författare)
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Identification of V-ATPase as a molecular sensor of SOX11-levels and potential therapeutic target for mantle cell lymphoma
- 2016
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mantle cell lymphoma (MCL) is an aggressive disease with short median survival. Molecularly, MCL is defined by the t(11;14) translocation leading to overexpression of the CCND1 gene. However, recent data show that the neural transcription factor SOX11 is a disease defining antigen and several involved signaling pathways have been pin-pointed, among others the Wnt/β-catenin pathway that is of importance for proliferation in MCL. Therefore, we evaluated a compound library focused on the Wnt pathway with the aim of identifying Wnt-related targets that regulate growth and survival in MCL, with particular focus on SOX11-dependent growth regulation. Methods: An inducible SOX11 knock-down system was used to functionally screen a library of compounds (n = 75) targeting the Wnt signaling pathway. A functionally interesting target, vacuolar-type H+-ATPase (V-ATPase), was further evaluated by western blot, siRNA-mediated gene silencing, immunofluorescence, and flow cytometry. Results: We show that 15 out of 75 compounds targeting the Wnt pathway reduce proliferation in all three MCL cell lines tested. Furthermore, three substances targeting two different targets (V-ATPase and Dkk1) showed SOX11-dependent activity. Further validation analyses were focused on V-ATPase and showed that two independent V-ATPase inhibitors (bafilomycin A1 and concanamycin A) are sensitive to SOX11 levels, causing reduced anti-proliferative response in SOX11 low cells. We further show, using fluorescence imaging and flow cytometry, that V-ATPase is mainly localized to the plasma membrane in primary and MCL cell lines. Conclusions: We show that SOX11 status affect V-ATPase dependent pathways, and thus may be involved in regulating pH in intracellular and extracellular compartments. The plasma membrane localization of V-ATPase indicates that pH regulation of the immediate extracellular compartment may be of importance for receptor functionality and potentially invasiveness in vivo.
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| 7. |
- Freiburghaus, Catja, et al.
(författare)
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Bortezomib prevents cytarabine resistance in MCL, which is characterized by down-regulation of dCK and up-regulation of SPIB resulting in high NF-κB activity
- 2018
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The addition of high-dose cytarabine to the treatment of mantle cell lymphoma (MCL) has significantly prolonged survival of patients, but relapses are common and are normally associated with increased resistance. To elucidate the mechanisms responsible for cytarabine resistance, and to create a tool for drug discovery investigations, we established a unique and molecularly reproducible cytarabine resistant model from the Z138 MCL cell line.METHODS: Effects of different substances on cytarabine-sensitive and resistant cells were evaluated by assessment of cell proliferation using [methyl-14C]-thymidine incorporation and molecular changes were investigated by protein and gene expression analyses.RESULTS: Gene expression profiling revealed that major transcriptional changes occur during the initial phase of adaptation to cellular growth in cytarabine containing media, and only few key genes, including SPIB, are deregulated upon the later development of resistance. Resistance was shown to be mediated by down-regulation of the deoxycytidine kinase (dCK) protein, responsible for activation of nucleoside analogue prodrugs. This key event, emphasized by cross-resistance to other nucleoside analogues, did not only effect resistance but also levels of SPIB and NF-κB, as assessed through forced overexpression in resistant cells. Thus, for the first time we show that regulation of drug resistance through prevention of conversion of pro-drug into active drug are closely linked to increased proliferation and resistance to apoptosis in MCL. Using drug libraries, we identify several substances with growth reducing effect on cytarabine resistant cells. We further hypothesized that co-treatment with bortezomib could prevent resistance development. This was confirmed and show that the dCK levels are retained upon co-treatment, indicating a clinical use for bortezomib treatment in combination with cytarabine to avoid development of resistance. The possibility to predict cytarabine resistance in diagnostic samples was assessed, but analysis show that a majority of patients have moderate to high expression of dCK at diagnosis, corresponding well to the initial clinical response to cytarabine treatment.CONCLUSION: We show that cytarabine resistance potentially can be avoided or at least delayed through co-treatment with bortezomib, and that down-regulation of dCK and up-regulation of SPIB and NF-κB are the main molecular events driving cytarabine resistance development.
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| 8. |
- Afanasyeva, Elena A., et al.
(författare)
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Kalirin-RAC controls nucleokinetic migration in ADRN-type neuroblastoma
- 2021
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Ingår i: Life Science Alliance. - : Life Science Alliance, LLC. - 2575-1077. ; 4:5
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Tidskriftsartikel (refereegranskat)abstract
- The migrational propensity of neuroblastoma is affected by cell identity, but the mechanisms behind the divergence remain unknown. Using RNAi and time-lapse imaging, we show that ADRN-type NB cells exhibit RAC1- and kalirin-dependent nucleokinetic (NUC) migration that relies on several integral components of neuronal migration. Inhibition of NUC migration by RAC1 and kalirin-GEF1 inhibitors occurs without hampering cell proliferation and ADRN identity. Using three clinically relevant expression dichotomies, we reveal that most of up-regulated mRNAs in RAC1- and kalirin-GEF1-suppressed ADRN-type NB cells are associated with low-risk characteristics. The computational analysis shows that, in a context of overall gene set poverty, the upregulomes in RAC1- and kalirin-GEF1-suppressed ADRN-type cells are a batch of AU-rich element-containing mRNAs, which suggests a link between NUC migration and mRNA stability. Gene set enrichment analysis-based search for vulnerabilities reveals prospective weak points in RAC1- and kalirin-GEF1-suppressed ADRN-type NB cells, including activities of H3K27- and DNA methyltransferases. Altogether, these data support the introduction of NUC inhibitors into cancer treatment research.
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| 9. |
- Albertsson-Lindblad, Alexandra, et al.
(författare)
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Ibrutinib inhibits antibody dependent cellular cytotoxicity induced by rituximab or obinutuzumab in MCL cell lines, not overcome by addition of lenalidomide
- 2019
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Ingår i: Experimental Hematology and Oncology. - : Springer Science and Business Media LLC. - 2162-3619. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Bruton's Tyrosine Kinase (BTK)-inhibitor ibrutinib is highly active in mantle cell lymphoma (MCL) but may inhibit response to anti-CD20 antibody as previously shown in CLL models. We investigated how antibody-dependent cellular cytotoxicity (ADCC) induced by type I/II anti-CD20 antibodies was affected by treatment with ibrutinib in MCL. Furthermore, we investigated if lenalidomide, a potential sensitizer to anti-CD20 treatment, could prevent an inhibitory effect of ibrutinib. Methods: Anti-CD20 (rituximab/obinutuzumab) opsonized MCL cell lines were co-cultured with ibrutinib (± lenalidomide) - exposed effector cells, and analyzed for evaluation of cell death. Results: Cell death induced by rituximab was reduced with 75% at 0.5 μM ibrutinib and with 52% at 0.1 μM ibrutinib when induced by obinutuzumab, even by addition of lenalidomide. Moreover, obinutuzumab was associated with higher rate of cell death compared to rituximab. Conclusion: Ibrutinib negatively affects anti-CD20 induced cell death in MCL, not reversed by lenalidomide. Explorations of sequential administration and selective BTK-inhibitors may reveal the optimal combination of novel agents in MCL.
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| 10. |
- Amer-Wåhlin, Isis, et al.
(författare)
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Slutrapport för EVIDIGVO
- 2024
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Den här texten presenterar resultat från tre aktiviteter för kunskapsinsamling om implementering av digitala verktyg inom vård- och omsorg: en litteratursammanställning, en workshopserie i två delar och en enkätundersökning. Den primära målgruppen har varit verksamhetsutvecklare och projektledare i regioner och kommuner. Antalet svarande i enkätstudien var för lågt för att kunna dra några statistiska slutsatser, men resultatet kan, tillsammans med workshopserien, ändå användas för att identifiera områden där det verkar finnas utmaningar. Både litteratursammanställningen och enkätundersökningen pekar på ett behov av att utveckla strukturerade utvärderingsmodeller för implementering. Även under workshoppen diskuterades den bristande förmågan att ”samla in evidens under projektens gång”, och det fanns en önskan om att ett sådant arbetssätt skulle utvecklas. Enkäten och workshoppen pekar även på flera återkommande problem under implementeringsprojekts olika faser. I den inledande fasen efterfrågas bättre analyser och förankringsarbete. Analyser med användarfokus missas speciellt ofta, så som användarresa, hållbarhetsanalys och intressent- och behovsanalys. Även i andra ändan av processen, då system och arbetssätt ska avvecklas, finns utmaningar och förbättringsförslag, t.ex. saknas ofta beslut om utfasning av gamla lösningar, och ett förslag är att man redan när man skriver kontakt med en leverantör ska säkerställa att leverantören hjälper till med migrering vid utfasning. En annan genomgående problematik är osäkerhet, och ibland avsaknad, av roller, ansvar och kommunikation. Detta handlar om att man inte riktigt vet varför man ska göra saker, eller att verksamheten och personerna som ska göra förändringen inte är tillräckligt inblandade. Det kan också handla om att support och förvaltning inte är tillräckligt väl utvecklat, och om att man inte vet hur man kan samarbeta med leverantörer. Här identifieras även förändringsledning som ett viktigt verktyg för att underlätta en god implementering.
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| 11. |
- Andreasson, Ulrika, et al.
(författare)
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B cell lymphomas express CX(3)CR1 a non-B cell lineage adhesion molecule
- 2008
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Ingår i: Cancer Letters. - : Elsevier BV. - 0304-3835 .- 1872-7980. ; 259:2, s. 138-145
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Tidskriftsartikel (refereegranskat)abstract
- To study the differential expression of cell membrane-bound receptors and their potential role in growth and/or survival of the tumor cells, highly purified follicular lymphoma cells were analyzed, using gene expression analysis, and compared to non-malignant B cell populations. Filtering the genome for overexpressed genes coding for cell membrane-bound proteins/receptors resulted in a hit list of 27 identified genes. Among these, we have focused on the aberrant over expression of CX3CR1, in different types of B cell lymphoma, as compared to non-malignant B cells. We show that CX3CR1, which normally is not expressed on B cells, is expressed both at the mRNA and protein level in several subtypes of lymphoma. CX3CR1 has also shown to be involved in the homing to specific tissues that express the ligand, CX3CL1, in breast and prostate cancer and may thus be involved in dissemination of lymphoma.
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| 12. |
- Andreasson, Ulrika, et al.
(författare)
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Identification of molecular targets associated with transformed diffuse large B cell lymphoma using highly purified tumor cells
- 2009
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Ingår i: American Journal of Hematology. - : Wiley. - 0361-8609 .- 1096-8652. ; 84:12, s. 803-808
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Tidskriftsartikel (refereegranskat)abstract
- Follicular lymphoma (FL) frequently transforms into the more aggressive diffuse large B cell lymphoma (DLBCL-tr), but no protein biomarkers have been identified for predictive or early diagnosis. Gene expression analyses have identified genes changing on transformation but have failed to be reproducible in different studies, reflecting the heterogeneity within the tumor tissue and between tumor samples. Gene expression analyses on Affymetrix Human Genome U133 Plus 2.0 arrays were performed, using flow cytometry sorted tumor cells derived from FL and transformed DLBCL. To identify molecular targets associated with the transformation, subsequent immunohistochemistry (IHC) analyses of the corresponding proteins were performed. Using highly purified cells, this study identified 163 genes, which were significantly deregulated during the transformation in a majority of cases. Among the upregulated transcripts, 13 genes were selected for validation using IHC, based on the availability of commercial antibodies, and galectin-3 and NEK2 proteins specifically identify DLBCL-tr, when compared with FL. We demonstrate that by purifying tumor cells through cell sorting, thereby reducing the heterogeneity due to infiltrating cells, it was possible to identify distinct differences between tumor entities rather than variations due to cellular composition. Galectin-3 and NEK2 both identified a subgroup of DLBCL-tr, and the function of these protein markers also suggests a biological role in the transformation process.
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| 13. |
- Andreasson, Ulrika, et al.
(författare)
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Identification of uniquely expressed transcription factors in highly purified B-cell lymphoma samples.
- 2010
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Ingår i: American Journal of Hematology. - : Wiley. - 0361-8609 .- 1096-8652. ; 85:6, s. 418-425
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Tidskriftsartikel (refereegranskat)abstract
- Transcription factors (TFs) are critical for B-cell differentiation, affecting gene expression both by repression and transcriptional activation. Still, this information is not used for classification of B-cell lymphomas (BCLs). Traditionally, BCLs are diagnosed based on a phenotypic resemblance to normal B-cells; assessed by immunohistochemistry or flow cytometry, by using a handful of phenotypic markers. In the last decade, diagnostic and prognostic evaluation has been facilitated by global gene expression profiling (GEP), providing a new powerful means for the classification, prediction of survival, and response to treatment of lymphomas. However, most GEP studies have typically been performed on whole tissue samples, containing varying degrees of tumor cell content, which results in uncertainties in data analysis. In this study, global GEP analyses were performed on highly purified, flow-cytometry sorted tumor-cells from eight subgroups of BCLs. This enabled identification of TFs that can be uniquely associated to the tumor cells of chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), hairy cell leukemia (HCL), and mantle cell lymphoma (MCL). The identified transcription factors influence both the global and specific gene expression of the BCLs and have possible implications for diagnosis and treatment.
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| 14. |
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| 15. |
- Baresel, Christian, et al.
(författare)
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Läkemedelsrester och andra skadliga ämnen i avloppsreningsverk - koncentrationer, kvantifiering, beteende och reningsalternativ
- 2015
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Många läkemedelsrester och andra prioriterade substanser passerar igenom dagens avloppsreningsverk (ARV) och hamnar antingen i slammet eller i recipienten, ibland i nivåer som kan påverka vattenlevande organismer. Substanser som släpps ut via avlopps-reningsverk kan också anrikas i den akvatiska näringskedjan och orsaka effekter i högre organismer såsom fiskätande fåglar eller däggdjur, inklusive människor. Studier har också visat att antibiotika som hamnar i miljön kan bidra till uppkomsten av antibiotikaresistenta gener i bakterier, vilket är ett allvarligt globalt hot mot möjligheten att bota livshotande sjukdomar. Eftersom nuvarande vattenreningstekniker har utvecklats främst för att avlägsna partikulärt material samt kväve och fosfor är de oftast inte anpassade för att rena bort mikrobiellt stabila kemiska föroreningar. Utvärderingar av effektiviteten hos olika behandlingstekniker för avlägsnande av sådana ämnen baseras vanligtvis på analyser av förekomst av ett ämne i inkommande och utgående vatten från reningsverket. Det finns dock problem med detta tillvägagångssätt eftersom vissa ämnen metaboliseras till potentiellt mer skadliga substanser, som då inte automatiskt fångas i analysen. Dessutom kan vissa ämnen spontant bildas i reningsverken, vilket kan resultera i högre nivåer i utgående än i inkommande vatten. Ett ytterligare problem är att de utgående koncentrationerna ibland kan vara lägre än detektions-gränserna, men trots det ändå vara högre än eller nära etablerade risknivåer. This report is only available in Swedish.
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| 16. |
- Baresel, Christian, et al.
(författare)
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Pharmaceutical residues and other emerging substances in the effluent of sewage treatment plants
- 2015
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Pharmaceutical residues and other emerging substances pass through modern sewage treatment plants (STPs) and end up in the receiving waters and sludge. In several studies, recipient concentrations have been detected with expected effects on aquatic organisms. Chemicals released via STPs may also enter the aquatic food-web and cause effects in higher organisms such as fish-eating birds or mammals including humans. Studies have also shown that antibiotics in the environment may contribute to the increase of antibiotic resistant genes in bacteria, which is a serious threat to our possibility to cure life-threatening diseases on the global scale. Current STP treatment technologies are usually not fit to remove microbial stable chemical pollutants and the evaluation of the removal efficiency of the STP systems applied today, is not complete. The evaluation of the removal efficiency of the substances in the STP systems is usually based on chemical analysis of the presence of certain substances in influent and effluent waters. However, there are difficulties associated with this approach, e.g. since some substances are metabolized into potentially more harmful substances which are not captured in the analysis unless they are actively sought for. Furthermore, some substances are formed in the STPs, resulting in higher levels in effluents than in influents. In addition, effluent concentrations may sometimes be lower than the analytical detection limits, yet still higher than or close to established risk concentrations emphasizing the need for developments of the analytical methods.
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| 17. |
- Belfrage, Emma, et al.
(författare)
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Predictive and Prognostic Biomarkers in Patients With Mycosis Fungoides and Sézary Syndrome (BIO-MUSE) : Protocol for a Translational Study
- 2024
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Ingår i: JMIR Research Protocols. - 1929-0748. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cutaneous T-cell lymphoma (CTCL) is a rare group of lymphomas that primarily affects the skin. Mycosis fungoides (MF) is the most common form of CTCL and Sézary syndrome (SS) is more infrequent. Early stages (IA-IIA) have a favorable prognosis, while advanced stages (IIB-IVB) have a worse prognosis. Around 25% of patients with early stages of the disease will progress to advanced stages. Malignant skin-infiltrating T-cells in CTCL are accompanied by infiltrates of nonmalignant T-cells and other immune cells that produce cytokines that modulate the inflammation. Skin infection, often with Staphylococcus aureus, is frequent in advanced stages and can lead to sepsis and death. S. aureus has also been reported to contribute to the progression of the disease. Previous reports indicate a shift from Th1 to Th2 cytokine production and dysfunction of the skin barrier in CTCL. Treatment response is highly variable and often unpredictable, and there is a need for new predictive and prognostic biomarkers.OBJECTIVE: This prospective translational study aims to identify prognostic biomarkers in the blood and skin of patients with MF and SS.METHODS: The Predictive and Prognostic Biomarkers in Patients With MF and SS (BIO-MUSE) study aims to recruit 120 adult patients with MF or SS and a control group of 20 healthy volunteers. The treatments will be given according to clinical routine. The sampling of each patient will be performed every 3 months for 3 years. The blood samples will be analyzed for lactate dehydrogenase, immunoglobulin E, interleukins, thymus and activation-regulated chemokine, and lymphocyte subpopulations. The lymphoma microenvironment will be investigated through digital spatial profiling and single-cell RNA sequencing. Microbiological sampling and analysis of skin barrier function will be performed. The life quality parameters will be evaluated. The results will be evaluated by the stage of the disease.RESULTS: Patient inclusion started in 2021 and is still ongoing in 2023, with 18 patients and 20 healthy controls enrolled. The publication of selected translational findings before the publication of the main results of the trial is accepted.CONCLUSIONS: This study aims to investigate blood and skin with a focus on immune cells and the microbiological environment to identify potential new prognostic biomarkers in MF and SS.TRIAL REGISTRATION: ClinicalTrials.gov NCT04904146; https://www.clinicaltrials.gov/study/NCT04904146.INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/55723.
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| 18. |
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| 19. |
- Bergstrand, Sara, et al.
(författare)
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Blood flow measurements at different depths using photoplethysmography and laser Doppler techniques
- 2009
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Ingår i: Skin research and technology. - : Wiley-Blackwell. - 0909-752X .- 1600-0846. ; 15:2, s. 139-147
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Tidskriftsartikel (refereegranskat)abstract
- Background/purpose: This study has evaluated a multi-parametric system combining laser Doppler flowmetry and photoplethysmography in a single probe for the simultaneous measurement of blood flow at different depths in the tissue. This system will be used to facilitate the understanding of pressure ulcer formation and in the evaluation of pressure ulcer mattresses.Methods: The blood flow in the tissue over the sacrum was measured before, during and after loading with 37.5 mmHg, respectively, 50.0 mmHg. The evaluation of the system consisted of one clinical part, and the other part focusing on the technicalities of the probe prototype.Results: An increase in blood flow while loading was the most common response, but when the blood flow decreased during loading it was most affected at the skin surface and the blood flow responses may be different due to depths of measurement. Reactive hyperaemia may occur more frequently in the superficial layers of the tissue.Conclusion: The study showed that the new system is satisfactory for measuring tissue blood flow at different depths. The laser Doppler complements the photoplethysmography, and further development of the system into a thin flexible probe with the ability to measure a larger area is required.
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| 20. |
- Bergstrand, Sara, et al.
(författare)
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Existence of Tissue Blood Flow in Response to External Pressure in the Sacral Region of Elderly Individuals - Using an Optical Probe Prototype
- 2010
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Ingår i: MICROCIRCULATION. - : Taylor and Francis. - 1073-9688 .- 1549-8719. ; 17:4, s. 311-319
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Tidskriftsartikel (refereegranskat)abstract
- Pandgt;Objective: The aim was to investigate the existence of sacral tissue blood flow at different depths in response to external pressure and compression in elderly individuals using a newly developed optical probe prototype. Methods: The tissue blood flow and tissue thickness in the sacral area were measured during load in 17 individuals using laser Doppler flowmetry and photoplethysmography in a combined probe, and digital ultrasound. Results: The mean age was 68.6 +/- 7.0 years. While loading, the mean compression was 60.3 +/- 11.9%. The number of participants with existing blood flow while loading increased with increased measurement depth. None had enclosed blood flow deep in the tissue and at the same time an existing more superficial blood flow. Correlation between tissue thickness and BMI in unloaded and loaded sacral tissue was shown: r = 0.68 (P = 0.003) and r = 0.68 (P = 0.003). Conclusions: Sacral tissue is highly compressed by external load. There seems to be a difference in responses to load in the different tissue layers, as occluded blood flow in deeper tissue layers do not occur unless the blood flow in the superficial tissue layers is occluded.
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| 21. |
- Bergstrand, Sara, et al.
(författare)
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Microcirculatory responses of sacral tissue in healthy individuals and in patients on different pressure-redistribution mattresses
- 2015
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Ingår i: Journal of Wound Care. - : Mark Allen Group. - 0969-0700 .- 2052-2916. ; 24:8, s. 346-358
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to explore the interaction between interface pressure and pressure-induced vasodilation and reactive hyperemia with different pressureredistribution mattresses.Method: A cross-sectional study was performed with a convenience sample of 42 healthy individuals between 18 and 64 years of age, 38 healthy individuals 65 years or older, and 35 inpatients 65 years or older at a university hospital in Sweden. Blood flow was measured at depths of 1 mm, 2 mm, and 10 mm using a combined system of laser Doppler flowmetry and photoplethysmography. The blood flow, interface pressure and skin temperature were measured in the sacral tissue before, during, and after load while lying on one standard hospital mattress and three different pressure-redistribution mattresses.Results: There were significant differences between the three foam mattresses with regard to average sacral pressure, peak sacral pressure, and local probe pressure with the lowest values at the visco-elastic foam/air mattress (23.5 ± 2.5 mmHg, 49.3 ± 11.1 mmHg, 29.2 ± 14.0 mmHg respectively). A greater proportion of subjects had affected blood flow in terms of lack of pressure-induced vasodilation on the visco-elastic foam/air mattress compared to the alternating pressure mattress at tissue depths of 2 mm (39.0% vs. 20.0%, respectively) and 10 mm (56.9 % vs. 35.1%, respectively). Eleven individuals, including subjects in all three subject groups were identified with no pressure-induced vasodilation or reactive hyperemia in any mattress, and this was considered a high-risk blood flow response.Conclusion: Interface pressure magnitudes considered not harmful during pressure-exposure lying on different pressure-redistribution mattresses can affect the microcirculation in different tissue structures. Despite having the lowest pressure values compared to the other mattresses, the visco-elastic foam/air mattress had the highest proportion of subjects with decreased blood flow indicating a more affected blood flow. Three young healthy individuals were identified with the high-risk blood flow response, indicating an innate vulnerability to pressure exposure and may not benefit from pressure-redistribution mattresses. Finally it was shown that the evaluation of pressure-redistribution support surfaces in terms of mean blood flow during and after tissue exposure is not feasible but assessment of pressure-induced vasodilation and reactive hyperemia could be a new possibility to assess individualized physiological measurements of mechanisms known to be related to pressure ulcer development.
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| 22. |
- Bergstrand, Sara, et al.
(författare)
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Pressure-induced vasodilation and reactive hyperemia at different depths in sacral tissue under clinically relevant conditions
- 2014
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Ingår i: Microcirculation. - : John Wiley & Sons. - 1073-9688 .- 1549-8719. ; 21:8, s. 761-771
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To characterize pressure-induced vasodilatation and reactive hyperemia at different sacral tissue depths in different populations under clinically relevant pressure exposure.METHODS: Forty-two subjects (< 65 years), 38 subjects (≥ 65 years), and 35 patients (≥ 65 years) participated. Interface pressure, skin temperature, and blood flow at tissue depths of 1 mm, 2 mm, and 10 mm (using laser Doppler flowmetry and photoplethysmography) were measured in the sacral tissue before, during, and after load in a supine position.RESULTS: pressure-induced vasodilatation and reactive hyperemia were observed at three tissue depths. At 10 mm depth, the proportion of subjects with a lack of pressure-induced vasodilatation was higher compared to superficial depths. The patients had higher interface pressure during load than the healthy individuals, but there were no significant differences in blood flow. Twenty-nine subjects in all three study groups were identified with a lack of pressure-induced vasodilatation and reactive hyperemia.CONCLUSIONS: pressure-induced vasodilatation and reactive hyperemia can be measured at different tissue depths. A lack of these responses was found in healthy individuals as well as in patients indicating an innate susceptibility in some individuals, and are potential important factors to evaluate in order to better understand the etiology of pressure ulcers.
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| 23. |
- Bergstrand, Sara, 1978-
(författare)
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Preventing pressure ulcers by assessment of the microcirculation in tissue exposed to pressure
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall aim of this thesis was to combine optical methods into a system with the ability to simultaneously measure blood flow changes at different tissue depths. The goal of such a system was to reveal vascular mechanisms relevant to pressure ulcer etiology under clinically relevant conditions and in relation to the evaluation of pressure-redistribution support surfaces.This thesis consists of four quantitative, cross-sectional studies measuring blood flow responses before, during, and after pressure exposure of the sacral tissue. Two optical methods – photoplethysmography and laser Doppler flowmetry – were combined in a newly developed system that has the ability to discriminate blood flows at different tissue depths. Studies I and II explored blood flow responses at different depths in 17 individuals. In Study I the blood flow was related to tissue thickness and tissue compression during pressure exposure of ≥ 220 mmHg. In Study II, the sacral tissue was loaded with 37.5 mmHg and 50.0 mmHg, and the variation in blood flow was measured. Studies III and IV included 42 healthy individuals < 65 years, 38 healthy individuals ≥ 65 years, and 35 patients ≥ 65 years. Study III included between-subject comparisons of blood flow and pressure between individuals in the three study groups lying in supine positions on a standard hospital mattress. Study IV added within-subject comparisons while the individual was lying on four different types of mattress. The studies explored the vascular phenomena pressure-induced vasodilation (PIV) and reactive hyperemia (RH).The most common blood flow response to tissue exposure in this thesis was PIV, although a decrease in blood flow (a lack of PIV) was observed in some individuals. The patients tended to have higher interface pressure during pressure exposure than the healthy groups but no differences in blood flow responses were seen. Our results showed that pressure levels that are normally considered to be harmless could have a significant effect on the microcirculation in different tissue structures. Differences in individual blood flow responses in terms of PIV and RH were seen, and a larger proportion of individuals lacked these responses in the deeper tissue structures compared to more superficial tissue structures.This thesis identified PIV and RH that are important vascular mechanisms for pressure ulcer development and revealed for the first time that PIV and RH are present at different depths under clinically relevant conditions. The thesis also identified a population of individuals not previously identified who lack both PIV and RH and seem to be particularly vulnerable to pressure exposure. Further, this thesis has added a new perspective to the microcirculation in pressure ulcer etiology in terms of blood flow regulation and endothelial function that are anchored in clinically relevant studies. Finally, the evaluation of pressureredistribution support surfaces in terms of mean blood flow during and after tissue exposure was shown to be unfeasible, but the assessment of PIV and RH could provide a new possibility for measuring individual physiological responses that are known to be related to pressure ulcer development.
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| 24. |
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| 25. |
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| 26. |
- Bergstrand, Sara, 1978-
(författare)
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Tissue Blood Flow Responses to External Pressure Using LDF and PPG : Testing a System Developed for Pressure Ulcer Research
- 2009
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Pressure ulcers are a problem for immobile individuals, and having pressure ulcers impact and restrict the daily and are often associated with pain. Pressure ulcers occur frequently and cause high costs for the health care system. The prevention of pressure ulcers by focussing on different mattresses and overlays aimed to reduce the interface pressure or the pressure exposure of the tissue. The problem is the poor evaluation of this type of equipment. There are important factors regarding pressure ulcer development, pressure, shear, temperature and humidity. People are affected by external pressure in different ways and therefore it is preferable to measure the effect of pressure as a complement to the pressure measurement and thus we consider blood flow measurements to be a suitable method.Aims: The aim of Study I, the first part in this thesis was to investigate the existence of sacral tissue blood flow at different depths in response to external pressure in elderly individuals as a part of evaluation of a. newly developed system. The aim of Study II, the second part was to evaluate a multiparametric system combining LDF and photoplethysmography into a single probe, for the simultaneous measurement of blood flow at different depths in the sacral tissue when the tissue is exposed to external load. This new system will be used to facilitate the understanding of pressure ulcer formation.Methods: To be able to observe tissue blood flow, the non-invasive optical methods laser Doppler flowmetry and photoplethysmography were used. In this thesis a newly developed prototype probe was used, combining the two methods. Green light and infrared light were used in the PPG instrument for penetrating the depths of approximately 2 mm, 8 mm and 20 mm depths. A HeNe laser was used to measure the superficial skin blood flow, <1 mm depth. The prototype probe, made of silicone was fixed in a stiff 10×10 cm plate.Seventeen active individuals over the age of 60 were recruited for the two studies. In Study I, the subject´s sacral blood flow and tissue thickness (using ultrasound) were measured in unloaded position and in supine position loading the area with their own body weight. In Study II, the sacral area was provoked with external load at 37.5 mmHg and 50.0 mmHg and the relative change in blood flow at different depths was observed before, during and after load.Results: Study I showed that the sacral tissue in elderly individuals is highly affected by load and is compressed by 60.3 ± 11.9%. The mean sacral tissue thickness was 26 ± 13 mm in unloaded tissue and 10 ± 6 mm in loaded tissue. Correlations were found between BMI and tissue thickness: both TTunload r=0.68 (p=0.003) and TTload r=0.68 (p=0.003). Almost all subjects had affected blood flow superficially but only occasionally deeper in the tissue and findings may indicate that the blood flow is occluded in the superficial layer before it is occluded deeper in the tissue structure. The most common response in Study II was an increase in blood flow while loading. In those occasions when the blood flow decreased, it was mostly affected at the skin surface and the reactive hyperaemia occurred more frequently in the superficial tissue structures. The blood flow responses may be different in the different tissue layers.Conclusions: The newly developed system was found to be suitable for measuring tissue blood flow at different depths; however the prototype probe had some limitations that will be solved in the further development of the system into a thin flexible probe with ability to measure a larger area.
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| 27. |
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| 28. |
- Bignert, Anders, et al.
(författare)
-
Comments Concerning the National Swedish Contaminant Monitoring Programme in Marine Biota, 2017 : Övervakning av metaller och organiska miljögifter i marin biota, 2017
- 2017
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The report summarises the monitoring activities within the National Swedish Contaminant Programme in marine biota. Time series of analysed contaminants (heavy metals, organochlorines, brominated flame retardants, perfluorinated substances and polycyclic aromatic hydrocarbons) in biota are presented together with summaries of the results from the statistical analyses. The data represent the bioavailable portion of the investigated contaminants i.e. the portion that has effectively passed through biological membranes and may cause toxic effects. The report does not in general give background or explanations to significant changes found in the time series. Thus, increasing concentrations highlight the need for intensified studies. - There was no general trend in heavy metal concentrations except for lead that is generally decreasing over the study period (in time series of sufficient length), supposedly due to the elimination of lead in gasoline. - Generally, decreasing concentrations were observed for organochlorines (DDT’s, PCB’s, HCH’s, HCB), also including TCDD-equivalents over the whole study period, but not during the last decades. The chlorinated compounds generally show higher concentrations in the Bothnian Sea and/or Baltic Proper when compared to the Bothnian Bay and the Swedish west coast. - Increasing trends of brominated flame retardants in guillemot eggs from late 1960s until early 1990s for polybrominated diphenyl ethers such as BDE-47, -99 and -100 and until mid-2000s for HBCDD, but with decreasing concentrations during the more recent time period. The PBDEs and HBCDD show higher concentrations in the Baltic Sea compared to the Swedish west coast. - A consistently increasing concentration of PFOS in guillemot eggs has been observed throughout the whole time period, however, during the most recent ten years a change of direction is seen.
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| 29. |
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| 30. |
- Bignert, Anders, et al.
(författare)
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Comments Concerning the National Swedish Contaminant Monitoring Programme in Marine Biota, 2017 (2016 years data)
- 2017
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The report summarises the monitoring activities within the National Swedish Contaminant Programme in marine biota.Time series of analysed contaminants (heavy metals, organochlorines, brominated flame retardants, perfluorinated substances and polycyclic aromatic hydrocarbons) in biota are presented together with summaries of the results from the statistical analyses. The data represent the bioavailable portion of the investigated contaminants i.e. the portion that has effectively passed through biological membranes and may cause toxic effects. The report does not in general give background or explanations to significant changes found in the time series. Thus, increasing concentrations highlight the need for intensified studies.- There was no general trend in heavy metal concentrations except for lead that is generally decreasing over the study period (in time series of sufficient length), supposedly due to the elimination of lead in gasoline.- Generally, decreasing concentrations were observed for organochlorines (DDT’s, PCB’s, HCH’s, HCB), also including TCDD-equivalents over the whole study period, but not during the last decades. The chlorinated compounds generally show higher concentrations in the Bothnian Sea and/or Baltic Proper when compared to the Bothnian Bay and the Swedish west coast.- Increasing trends of brominated flame retardants in guillemot eggs from late 1960s until early 1990s for polybrominated diphenyl ethers such as BDE-47, -99 and -100 and until mid-2000s for HBCDD, but with decreasing concentrations during the more recent time period. The PBDEs and HBCDD show higher concentrations in the Baltic Sea compared to the Swedish west coast.- A consistently increasing concentration of PFOS in guillemot eggs has been observed throughout the whole time period, however, during the most recent ten years a change of direction is seen.
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| 31. |
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| 32. |
- Bjorck, E, et al.
(författare)
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High expression of cyclin B1 predicts a favorable outcome in patients with follicular lymphoma
- 2005
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 105:7, s. 2908-2915
-
Tidskriftsartikel (refereegranskat)abstract
- Substantial research has been dedicated to the study of the relationship between genetic mechanisms regulating cell functions in tumors and how those tumors respond to various treatment regimens. Because these mechanisms are still not well understood, we have chosen to study the genetic makeup of 57 tumor samples from patients with follicular lymphoma (FL). Our goal was to develop a prognostic tool, which can be used as an aid in determining FL patients with tumors genetically predisposed to a successful treatment with the CHOP (cyclophosphamide, vincristine, doxorubicin, prednisone) regimen. To select relevant genes, high-density oligonucleotide arrays were used. There were 14 genes highly expressed in FL patients that responded well to CHOP chemotherapy, and 11 of these were involved in G(2)/M transition of the cell cycle, in mitosis, or in DNA modulation. A high expression of CCNB1 (cyclin B1), CDC2, CDKN3A, CKS1B, ANP32E, and KIAA0101, but not of the proliferation-related antigen Ki-67, was associated with better survival rate in a univariate analysis. CCNB1 expression had an independent prognostic value when included in a multivariate analysis together with the 5 parameters of the follicular lymphoma international prognostic index.
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| 33. |
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| 34. |
- Brennan, Donal, et al.
(författare)
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The transcription factor Sox11 is a prognostic factor for improved recurrence-free survival in epithelial ovarian cancer
- 2009
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 45:8, s. 1510-1517
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Background: Current prognostic molecular markers for epithelial ovarian cancer (EOC) are insufficient. The aim of the current study was to investigate the role of Sox11 in EOC Methods: Using an in silico transcriptomic screen Sox11 was identified as a potential EOC biomarker. Sox11 protein expression was evaluated using immunohistochemistry (IHC) in 76 EOC cases, which were analyzed using automated algorithms to develop a quantitative scoring model. Results: Sox11 mRNA expression was up-regulated in EOC compared to normal tissues. Automated analysis of Sox11 in the EOC cohort revealed high expression of Sox11, in 40% of tumours, who had an improved recurrence free survival (RFS) (p= 0.002). Multivariate analysis confirmed Sox11 was an independent predictor of improved RFS after controlling for stage and grade. Conclusions: These data suggest that Sox11 is a new prognostic marker in EOC. Loss of SOX 11 is associated with a decreased RFS and a more aggressive phenotype.
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| 35. |
- Carlsson, Anders, et al.
(författare)
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Molecular serum portraits in patients with primary breast cancer predict the development of distant metastases.
- 2011
-
Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 108:34, s. 14252-14257
-
Tidskriftsartikel (refereegranskat)abstract
- The risk of distant recurrence in breast cancer patients is difficult to assess with current clinical and histopathological parameters, and no validated serum biomarkers currently exist. Using a recently developed recombinant antibody microarray platform containing 135 antibodies against 65 mainly immunoregulatory proteins, we screened 240 sera from 64 patients with primary breast cancer. This unique longitudinal sample material was collected from each patient between 0 and 36 mo after the primary operation. The velocity for each serum protein was determined by comparing the samples collected at the primary operation and then 3-6 mo later. A 21-protein signature was identified, using leave-one-out cross-validation together with a backward elimination strategy in a training cohort. This signature was tested and evaluated subsequently in an independent test cohort (prevalidation). The risk of developing distant recurrence after primary operation could be assessed for each patient, using her molecular portraits. The results from this prevalidation study showed that patients could be classified into high- versus low-risk groups for developing metastatic breast cancer with a receiver operating characteristic area under the curve of 0.85. This risk assessment was not dependent on the type of adjuvant therapy received by the patients. Even more importantly, we demonstrated that this protein signature provided an added value compared with conventional clinical parameters. Consequently, we present here a candidate serum biomarker signature able to classify patients with primary breast cancer according to their risk of developing distant recurrence, with an accuracy outperforming current procedures.
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| 36. |
- Conrotto, Paolo, et al.
(författare)
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Knock-down of SOX11 induces autotaxin-dependent increase in proliferation in vitro and more aggressive tumors in vivo
- 2011
-
Ingår i: Molecular Oncology. - : Wiley. - 1574-7891. ; 5, s. 527-537
-
Tidskriftsartikel (refereegranskat)abstract
- Abstract in UndeterminedThe transcription factor SOX11 is a novel diagnostic marker for mantle cell lymphoma (MCL), distinguishing this aggressive tumor from potential simulators. Recent data also show that the level of SOX11 correlates to in vitro growth properties in MCL, as well as the clinical progression. We have previously shown that MCL-associated pathways, such as Rb-E2F, are dysregulated leading to decreased proliferation upon overexpression of SOX11, emphasizing the impact of SOX11 on MCL-specific gene expression and growth control. However, it remains to be determined which growth regulatory pathways that are induced upon SOX11 knock-down, leading to an increased cellular growth. Consequently, we established a model cell line with constitutive down-regulation of SOX11. The highly proliferative features of this cell line were investigated by gene expression analysis, proliferation assay, cell cycle distribution and potential to induce tumors in NOD-SCID mice. Our in vitro studies demonstrated a SOX11-dependent regulation of MCL-specific gene expression. In addition, we identified autotaxin (ATX) to be regulated by SOX11. Our results clearly showed a correlation between SOX11 level and cellular growth rate, which was dependent on ATX, as well as a direct relation between the level of SOX11 in tumorigenic cells and the growth rate of these tumors in NOD-SCID mice.
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| 37. |
- Dahl, Mette, et al.
(författare)
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Expression patterns and prognostic potential of circular RNAs in mantle cell lymphoma : a study of younger patients from the MCL2 and MCL3 clinical trials
- 2022
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 36:1, s. 177-188
-
Tidskriftsartikel (refereegranskat)abstract
- Mantle cell lymphoma (MCL) is characterized by marked differences in outcome, emphasizing the need for strong prognostic biomarkers. Here, we explore expression patterns and prognostic relevance of circular RNAs (circRNAs), a group of endogenous non-coding RNA molecules, in MCL. We profiled the circRNA expression landscape using RNA-sequencing and explored the prognostic potential of 40 abundant circRNAs in samples from the Nordic MCL2 and MCL3 clinical trials, using NanoString nCounter Technology. We report a circRNA-based signature (circSCORE) developed in the training cohort MCL2 that is highly predictive of time to progression (TTP) and lymphoma-specific survival (LSS). The dismal outcome observed in the large proportion of patients assigned to the circSCORE high-risk group was confirmed in the independent validation cohort MCL3, both in terms of TTP (HR 3.0; P = 0.0004) and LSS (HR 3.6; P = 0.001). In Cox multiple regression analysis incorporating MIPI, Ki67 index, blastoid morphology and presence of TP53 mutations, circSCORE retained prognostic significance for TTP (HR 3.2; P = 0.01) and LSS (HR 4.6; P = 0.01). In conclusion, circRNAs are promising prognostic biomarkers in MCL and circSCORE improves identification of high-risk disease among younger patients treated with cytarabine-containing chemoimmunotherapy and autologous stem cell transplant.
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| 38. |
- Danielsson, Sara, et al.
(författare)
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Det svenska nationella miljöövervakningsprogrammet för miljögifter i marin biota (fram till 2017 års data) - Temporal- och spatial variation
- 2018
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The report summarises the monitoring activities within the National Swedish Contaminant Programme in marine biota. In this report, we present time series and maps of most contaminants in various species but we only comment results that shows large differences compared to the previous year. Results show that herring from Holmöarna had elevated concentrations during the last two years of the time series for approximately half of the analysed metals, most chlorinated pesticides, polychlorinated biphenyls (PCBs) and brominated flame retardants (BFRs). The last two years’ Herring is on average one year older than the previous years’, heavier and the last years’ fat percentage is ca. 2 % higher compared to the year before. These differences in biological variables may have had an influence on the elevated contaminant concentrations. Also, herring from Väderöarna shows increasing concentrations for several chlorinated pesticides, PCBs, dioxins, and BFRs during the ten most recent years. A reason for this might be that the included fish were older during the seven most recent years, although their size was similar or smaller than previous years. Additionally, the fat percentage of the tissue has also decreased over time and might influence the results.This year’s report is also the first to show PFAS concentrations in Cod, Perch and Eelpout where Perch has the highest concentrations of most PFASs within the Baltic Proper sampling sites.This report is also the first report within the Swedish National Monitoring Programme of Contaminants in marine biota presenting environmental contaminant data in eggs of Common tern and Eurasian oystercatcher. In general, many of the compounds could be detected in Common tern and Eurasian oystercatcher.Concentrations of several of the contaminants are similar in the two species, but there are exceptions among each contaminant class and even opposing time trends for some contaminants. There are clear differences in contaminant concentrations between species for PCDD/Fs and BFRs; for most PCDD/Fs, concentrations are higher in Eurasian oystercatcher compared to Common tern, while for the BFRs concentrations are higher in Common tern, with the exception of HBCDD.
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| 39. |
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| 40. |
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| 41. |
- Dictor, Michael, et al.
(författare)
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Strong lymphoid nuclear expression of SOX11 transcription factor defines lymphoblastic neoplasms, mantle cell lymphoma and Burkitt's lymphoma.
- 2009
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 94:11, s. 1563-1568
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We surveyed lymphomas to determine the range of expression of the mantle cell lymphoma-associated SOX11 transcription factor and its relation to cyclin D1. DESIGN AND METHODS: On hundred and seventy-two specimens were immunostained for the SOX11 N and C termini. Cyclin D1 was detected by immunohistochemistry and quantitative reverse transcriptase polymerase chain reaction; in situ hybridization for t(11;14) was applied when needed. RESULTS: Nuclear SOX11 was strongly expressed in most B and T-lymphoblastic leukemia/lymphomas and half of childhood Burkitt's lymphomas, but only weakly expressed in some hairy cell leukemias. Chronic lymphocytic leukemia/lymphoma, marginal zone, follicular and diffuse large B-cell lymphomas were negative for SOX11, as were all cases of intermediate Burkitt's lymphomas/diffuse large B-cell lymphoma, myeloma, Hodgkin's lymphomas and mature T-cell and NK/T-cell lymphomas. CONCLUSIONS: In addition to mantle cell lymphoma, SOX11 is strongly expressed only in lymphoblastic malignancies and Burkitt's lymphomas. Its expression is independent of cyclin D1 (except for weak expression in hairy cell leukemias) and unlikely to be due to translocations in lymphoid neoplasia.
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| 42. |
- Ek, Anders, et al.
(författare)
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Slaughterhouse waste co-digestion - Experiences from 15 years of full-scale operation
- 2011
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Ingår i: World Renewable Energy Congress - Sweden 8-13 May, 2011. - Linköping : Linköping University Electronic Press. - 9789173930703 ; , s. 64-71
-
Konferensbidrag (refereegranskat)abstract
- At Tekniska Verken in Linköping AB (TVAB) there is a long time experience of handling and producing biogas from large volumes of slaughterhouse waste. Experiences from research and development and plant operations have lead to the implementation of several process improving technological/biological solutions. We can in this paper describe how the improvements have had several positive effects on the process, including energy savings, better odor control, higher gas quality, increased organic loading rates and higher biogas production with maintained process stability. In addition, it is described how much of the process stability in anaerobic digestion of slaughter house waste relates to the plant operation, which allow the microbiological consortia to adapt to the substrate. Since digestion of proteinaceous substrates like slaughterhouse waste lead to high ammonia loads, special requirements in ammonia tolerance are placed on the microbiota of the anaerobic digestion. Biochemical assays revealed that the main route for methane production proceed through syntrophic acetate oxidation, which require longer retention times than methane production by acetoclastic methanogens. Thus, the long retention time of the plant, accomplished by a low dilution of the substrate, is a vital component of the process stability when treating high protein substrates like slaughterhouse waste.
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| 43. |
- Ek, Caroline, et al.
(författare)
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Evaluation of different stable isotope methods to estimate trophic position of perch (Perca fluviatilis) in Swedish lakes
- 2019
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The Water Framework Directive (WFD) requires member states to implement a strategy to meet the environmental quality standards (EQS) set by the WFD for a number of priority substances. Since the EQSs listed in the WFD are derived to protect the most sensitive species in the ecosystem, often top predators or humans, it has been decided that for certain priority substances the quality standards should be compared to a monitoring species with a trophic position (TP) similar to the diet of the most sensitive species. To enable such adjustment require both knowledge about the monitoring species TP in the food web as well as the relationship between contaminant concentration and trophic position. In this study, we focus on finding a suitable method for TP estimates of perch in Swedish lakes by evaluating both traditional stable isotope analysis in bulk samples (BSIA) using different baseline matrices and the more recent development of compound-specific stable isotope analysis in amino acids (CSIA-AA). For this, three representative monitoring lakes were selected in which perch together with potential baseline matrices (bivalves, gastropods and sediment) were sampled. We applied triple-isotope analyses, d15N, d13C and d34S, of bulk material of all sampled matrices, and in addition d15N in perch using CSIA-AA. Results showed that TP estimates derived from CSIA-AA were significantly (p<0.001) lower compared to all the BSIA-derived methods and further that the BSIA-derived TP estimates using gastropods as a baseline were significantly higher (p<0.001) than all other TP estimates. Since no statistical differences could be detected between TP estimates based on bivalves, sediment or a ‘mixture’ baseline these were assumed to produce similar results and therefore all valid baseline matrices for TP estimates of perch in these three lakes. In the present study we also attempted to adjust mercury contaminant data to a specific TP of 3.5 according to the WFD. The adjustment resulted in significantly different concentration for one of the two tested lakes but did not influence the chemical status classification as all lakes were well above the threshold for mercury in freshwater lakes.
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| 44. |
- Ek, Caroline, et al.
(författare)
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Screening for pharmaceuticals, phthalates and polycyclic aromatic hydrocarbons (PAHs) in bivalves sampled along the Swedish coast
- 2019
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Within the Swedish National Monitoring Programme for Contaminants in marine biota, a selection of the wide array of contaminants that can be found in the environment is analysed. Analysing the samples for all possible contaminants would hardly be feasible, however, screening for different substance groups is a way to investigate if and where new substances arise and may pose a threat to wildlife and humans. In this report, data from a spatial screening study is presented, which aimed to densify the ongoing Swedish National Monitoring Programme for Contaminants in marine biota with regard to pharmaceuticals, phthalates and polycyclic aromatic hydrocarbons (PAHs). The study includes 16 sampling sites along the Swedish coast, from where two different species of bivalves, Limecola balthica and Mytilus edulis, were collected. All applied sampling material in this screening study originates from the Swedish Environmental Specimen Bank of the Swedish Museum of Natural History. The screening included a total of 100 pharmaceuticals, out of which 17 were detected and quantified in at least one sampling site. Risperidone was the pharmaceutical detected at most sites (10 of 13). The only detected phthalate was di(2-ethylhexyl) phthalate (DEHP), which was found in the samples from 3 of 13 sampling sites. Among the PAHs, Benzo(a)pyrene was the substance quantified at most sites (14 out of 16). No geographical patterns could be identified for the detected contaminants, besides for the PAHs. However, this pattern could also be due to a difference in species rather than due to location. PAHs could be detected in the Bothnian Sea and the Sea of Åland, where to date no mussel sampling sites exist within the Swedish National Monitoring Programme for Contaminants in marine biota. The Baltic clam might be a good additional monitoring species besides the Blue mussel, due to their difference in feeding strategy and the potential higher PAH uptake from contaminated sediments rather than the water phase.
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| 45. |
- Ek, caroline, et al.
(författare)
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Utvärdering av stabila isotoper som metod för att uppskatta trofinivå i abborre (Perca fluviatilis) från Svenska sjöar
- 2022
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The Water Framework Directive (WFD) requires member states to implement a strategy to meet the environmental quality standards (EQS) set by the WFD for a number of priority substances. Since the EQSs listed in the WFD are derived to protect the most sensitive species in the ecosystem, often top predators or humans, it has been decided that for certain priority substances the quality standards should be compared to a monitoring species with a trophic position (TP) similar to the diet of the most sensitive species. To enable such adjustment require both knowledge about the monitoring species TP in the food web as well as the relationship between contaminant concentration and trophic position. In this study, we focus on finding a suitable method for TP estimates of perch in Swedish lakes by evaluating both traditional stable isotope analysis in bulk samples (BSIA) using different baseline matrices and the more recent development of compound-specific stable isotope analysis in amino acids (CSIA-AA). For this, three representative monitoring lakes were selected in which perch together with potential baseline matrices (bivalves, gastropods and sediment) were sampled. We applied triple-isotope analyses, δ15N, δ13C and δ34S, of bulk material of all sampled matrices, and in addition δ15N in perch using CSIA-AA. Results showed that TP estimates derived from CSIA-AA were significantly (p<0.001) lower compared to all the BSIA-derived methods and further that the BSIA-derived TP estimates using gastropods as a baseline were significantly higher (p<0.001) than all other TP estimates. Since no statistical differences could be detected between TP estimates based on bivalves, sediment or a ‘mixture’ baseline these were assumed to produce similar results and therefore all valid baseline matrices for TP estimates of perch in these three lakes. In the present study we also attempted to adjust mercury contaminant data to a specific TP of 3.5 according to the WFD. The adjustment resulted in significantly different concentration for one of the two tested lakes but did not influence the chemical status classification as all lakes were well above the threshold for mercury in freshwater lakes.
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| 46. |
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| 47. |
- Ek, Sara, et al.
(författare)
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Compact fiber-optic fluorosensor employing light-emitting ultraviolet diodes as excitation sources
- 2008
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Ingår i: Spectrochimica Acta, Part B: Atomic Spectroscopy. - : Elsevier BV. - 0584-8547. ; 63, s. 349-353
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Tidskriftsartikel (refereegranskat)abstract
- A compact fluorosensor using three different ultraviolet light-emission diodes as excitation sources for fiber-optic recording of fluorescence 10 spectra from samples is described. A compact integrated spectrometer with linear array wavelength recording is used, yielding a spectral resolution 11 of about 8 nm. In two system implementations ultraviolet light-emitting diodes at 300, 340 and 395 nm, or at 360, 385 and 410 nm were used as 12 excitation sources with typical emission halfwidths of 12 nm, each combined with a matching long-path colored-glass filter automatically brought 13 into the fluorescence light flow for suppression of reflected light. Spectra from measurements on vegetation, human skin tumors and a rare-earth 14 ion-based thermographic phosphor were recorded to illustrate the system performance. 15 © 2007 Published by Elsevier B.V.
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| 48. |
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| 49. |
- Ek, Sara, et al.
(författare)
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Gene expression profiling of mantle cell lymphonas
- 2003
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Ingår i: Immunology Letters (Abstracts of the 15th European Immunology Congress (EFIS 2003)). - 0165-2478 .- 1879-0542. ; 87:1-3, s. 01-24
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 50. |
- Ek, Sara, et al.
(författare)
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Increased expression of Ki-67 in mantle cell lymphoma is associated with de-regulation of several cell cycle regulatory components, as identified by global gene expression analysis
- 2004
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Ingår i: Haematologica. - 1592-8721. ; 89:6, s. 686-695
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives. Mantle cell lymphoma (MCL) is an aggressive disease. Patients with this malignancy have a median survival of 3 years. To better understand disease progression, which is characterized by increased proliferation, we analyzed the gene expression of MCL with different proliferative indices, as determined by immunohistochemical staining for Ki-67. Furthermore, primary and relapsed tumors were compared to identify the possible growth advantages possessed by cells which persist after therapy and which might evolve into a tumor relapse. Design and Methods. Twenty-one samples of MCL were analyzed, using the Affymetrix U95Av2 chip, containing probes for approximately 12,000 transcripts. Samples with a high versus low fraction of Ki-67(+) cells were compared as were relapsed versus primary tumors. Immunohistochemistry was used to confirm the expression of some gene products. Results. A distinct genetic signature, consisting of 32 genes, was found when comparing Ki-67(high) with Ki-67(low) MCL. The signature consisted of genes involved in cellular processes, such as mitotic spindle formation, gene transcription and cell cycle regulation, e.g. components of the p53 and retinoblastoma protein (pRb) pathways. Of note, cyclin D1, the hallmark of MCL, as well as Ki-67 were up-regulated in the samples with a high proliferative index. Comparing primary vs. relapsed tumors, 26 individual genes were found, several involved in cell adhesion. Furthermore, increased expression of transferrin receptor was found in the relapsed tumors. Interpretation and Conclusions. A genetic signature distinguishing Ki-67(high) MCL from Ki-67(low) was established. The generated signature was used to assign new MCL samples to the high proliferative group, validating the association between these genes and proliferation in MCL.
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