| 1. |
- Cheng, Wei Kang, et al.
(författare)
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Nuclear and stromal expression of Manic fringe in renal cell carcinoma
- 2021
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Ingår i: Experimental and molecular pathology (Print). - : Elsevier. - 0014-4800 .- 1096-0945. ; 122
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Tidskriftsartikel (refereegranskat)abstract
- Renal cell carcinoma (RCC) is the most common type of kidney cancer and has the highest mortality rate among genitourinary cancers. Despite the advances in molecular targeted therapies to treat RCC, the inevitable emergence of resistance has delineated the need to uncover biomarkers to prospectively identify patient response to treatment and more accurately predict patient prognosis. Fringe is a fucose specific beta 1, 3N-acetylglucosaminyltransferase that modifies the Notch receptors. Given the link between its function and aberrant Notch activation in RCC, Fringe may be implicated in this disease. The Fringe homologs comprise of Lunatic fringe (LFng), Manic fringe (MFng) and Radical fringe (RFng). MFng has been reported to play a role in cancer. MFng is also essential in the development of B cells. However, the expression profile and clinical significance of MFng, and its association with B cells in RCC are unknown. CD20 is a clinically employed biomarker for B cells. This pilot study aimed to determine if MFng protein expression can be utilized as a prospective biomarker for therapeutics and prognosis in RCC, as well as to determine its association with CD20+ B cells. Analysis of publicly available MFng gene expression datasets on The Cancer Genome Atlas Netlwork (TCGA) identified MFng gene expression to be up-regulated in Kidney Clear Cell Renal Carcinoma (KIRC) patients. However there was no significant association between the patient survival probability and the level of MFng expression in this cohort. Immunohistochemistry performed on a tissue microarray containing cores from 64 patients revealed an elevated MFng protein expression in the epithelial and stromal tissues of RCC compared to the normal kidney, suggesting a possible role in tumorigenesis. Our study describes for the first time to our knowledge, the protein expression of MFng in the nuclear compartment of normal kidney and RCC, implicating a prospective involvement in gene transcription. At the cellular level, cytoplasmic MFng was also abundant in the normal kidney and RCC. However, MFng protein expression in the malignant epithelial and stromal tissue of RCC had no positive correlation with the patients' overall survival, progression-free survival and time to metastasis, as well as the gender, age, tumor stage and RCC subtype, indicating that MFng may not be an appropriate prognostic marker. The association between CD20+ B cells and epithelial MFng was found to approach borderline insignificance. Nonetheless, these preliminary findings may provide valuable information on the suitability of MFng as a potential therapeutic molecular marker for RCC, thus warrants further investigation using a larger cohort.
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| 2. |
- Ericsson, Elin, et al.
(författare)
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Effect of Electrode Belt and Body Positions on Regional Pulmonary Ventilation- and Perfusion-Related Impedance Changes Measured by Electric Impedance Tomography
- 2016
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 11:6, s. e0155913-
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Tidskriftsartikel (refereegranskat)abstract
- Ventilator-induced or ventilator-associated lung injury (VILI/VALI) is common and there is an increasing demand for a tool that can optimize ventilator settings. Electrical impedance tomography (EIT) can detect changes in impedance caused by pulmonary ventilation and perfusion, but the effect of changes in the position of the body and in the placing of the electrode belt on the impedance signal have not to our knowledge been thoroughly evaluated. We therefore studied ventilation-related and perfusion-related changes in impedance during spontaneous breathing in 10 healthy subjects in five different body positions and with the electrode belt placed at three different thoracic positions using a 32-electrode EIT system. We found differences between regions of interest that could be attributed to changes in the position of the body, and differences in impedance amplitudes when the position of the electrode belt was changed. Ventilation-related changes in impedance could therefore be related to changes in the position of both the body and the electrode belt. Perfusion-related changes in impedance were probably related to the interference of major vessels. While these findings give us some insight into the sources of variation in impedance signals as a result of changes in the positions of both the body and the electrode belt, further studies on the origin of the perfusion-related impedance signal are needed to improve EIT further as a tool for the monitoring of pulmonary ventilation and perfusion.
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| 3. |
- Guo, Min, et al.
(författare)
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SFRP2 induces a mesenchymal subtype transition by suppression of SOX2 in glioblastoma
- 2021
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Ingår i: Oncogene. - : Springer Nature. - 0950-9232 .- 1476-5594. ; 40:32, s. 5066-5080
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Tidskriftsartikel (refereegranskat)abstract
- Intratumoral heterogeneity is a characteristic of glioblastomas that contain an intermixture of cell populations displaying different glioblastoma subtype gene expression signatures. Proportions of these populations change during tumor evolution, but the occurrence and regulation of glioblastoma subtype transition is not well described. To identify regulators of glioblastoma subtypes we utilized a combination of in vitro experiments and in silico analyses, using experimentally generated as well as publicly available data. Through this combined approach SOX2 was identified to confer a proneural glioblastoma subtype gene expression signature. SFRP2 was subsequently identified as a SOX2-antagonist, able to induce a mesenchymal glioblastoma subtype signature. A subset of patient glioblastoma samples with high SFRP2 and low SOX2 expression was particularly enriched with mesenchymal subtype samples. Phenotypically, SFRP2 decreased tumor sphere formation, stemness as assessed by limiting dilution assay, and overall cell proliferation but increased cell motility, whereas SOX2 induced the opposite effects. Furthermore, an SFRP2/non-canonical-WNT/KLF4/PDGFR/phospho-AKT/SOX2 signaling axis was found to be involved in the mesenchymal transition. Analysis of human tumor tissue spatial gene expression patterns showed distinct expression of SFRP2- and SOX2-correlated genes in vascular and cellular areas, respectively. Finally, conditioned media from SFRP2 overexpressing cells increased CD206 on macrophages. Together, these findings present SFRP2 as a SOX2-antagonist with the capacity to induce a mesenchymal subtype transition in glioma cells located in vascular tumor areas, highlighting its role in glioblastoma tumor evolution and intratumoral heterogeneity.
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| 4. |
- Hultman, Elin
(författare)
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Bristande vattenföring förbi Gävleborgs regleringsdammar
- 2010
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Gävleborgs regionala miljömål8.6 Godtagbar minimivattenföring,lyder”2010 ska 50 % av alla kraftverk och regleringsdammar ha en, ur biologiskmångfald, godtagbar minimivattenföring genom eller förbi respektive anläggning”.Måletsyftar till att främja den biologiska mångfalden genom att förbättra vandringsmöjligheter ochlivsmiljöer för fisk och övriga vattenlevande växter och djur.Vattenkraft är en ren och förnybar energikälla med låga utsläpp och mycket litenklimatpåverkan men konsekvenserna för landskapet och organismerna i och kring ett utbyggtvattendrag är stora. Vissa områden torrläggs, medan andra överdäms, forsar försvinner ochdet blir svårare för fiskar och andra djur och växter att överleva. De flesta stora svenskakraftverken byggdes under en tid då samhället inte prioriterade naturvårdsfrågor.Länsstyrelsens uppföljning av miljömålet visar att situationen för länets vattendrag är mycketallvarlig. Resultatet visar att det vid endast 16 av 142 kraftverksdammar finns en godtagbarminimivattenföring. Det motsvarar 11 % vilket är långt ifrån det uppsatta målet om 50 %.Vi har i den här studien definierat att en damm har en biologiskt godtagbarminimivattenföring när dammens minimitappning är större än eller lika stor som vattendragetslågvattenföring. För att urskilja de dammar som har en godtagbar minimivattenföring, harstudien gjorts i två steg utifrån länets 142 regleringsdammar. I det första steget bedömdes dedammar som har nolltappninginte ha en biologiskt godtagbar vattenföring. Nolltappningbetyder att inget vatten alls behöver tappas förbi anläggningen. De 65 urskiljdaregleringsdammarna bedömdes sedan utifrån dess minimitappning i jämförelse medvattendragets normala lågvattenföring. Minimitappning är den minsta vattenföring somregleringsdammen måste släppa förbi.För att på sikt nå målet krävs ett aktivt arbete från Länsstyrelsen, kommuner ochKammarkollegiet för att ta fram underlag och att driva omprövningar av gamla vattendomar isyfte att få till stånd ökade minimitappningar förbi dammar och kraftverk. Arbetet bör ske idialog med kraftbolagen. Berörda myndigheter bör också tillsammans med kraftbolagenidentifiera de dammar som idag inte ger någon större nytta för kraftproduktion och åtgärdadessa, t.ex. genom utrivning, så att vattenföringen kan återgå till det ursprungliga flödet.
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| 5. |
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| 6. |
- Johansson, Robert, et al.
(författare)
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Tailored vs. Standardized Internet-Based Cognitive Behavior Therapy for Depression and Comorbid Symptoms: A Randomized Controlled Trial
- 2012
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Ingår i: PLOS ONE. - San Francisco : Public Library of Science. - 1932-6203. ; 7:5
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: Major depression can be treated by means of cognitive behavior therapy, delivered via the Internet as guided self-help. Individually tailored guided self-help treatments have shown promising results in the treatment of anxiety disorders. This randomized controlled trial tested the efficacy of an Internet-based individually tailored guided self-help treatment which specifically targeted depression with comorbid symptoms. The treatment was compared both to standardized (non-tailored) Internet-based treatment and to an active control group in the form of a monitored online discussion group. Both guided self-help treatments were based on cognitive behavior therapy and lasted for 10 weeks. The discussion group consisted of weekly discussion themes related to depression and the treatment of depression. Methods: A total of 121 participants with diagnosed major depressive disorder and with a range of comorbid symptoms were randomized to three groups. The tailored treatment consisted of a prescribed set of modules targeting depression as well as comorbid problems. The standardized treatment was a previously tested guided self-help program for depression. Results: From pre-treatment to post-treatment, both treatment groups improved on measures of depression, anxiety and quality of life. The results were maintained at a 6-month follow-up. Subgroup analyses showed that the tailored treatment was more effective than the standardized treatment among participants with higher levels of depression at baseline and more comorbidity, both in terms of reduction of depressive symptoms and on recovery rates. In the subgroup with lower baseline scores of depression, few differences were seen between treatments and the discussion group. Conclusions: This study shows that tailored Internet-based treatment for depression is effective and that addressing comorbidity by tailoring may be one way of making guided self-help treatments more effective than standardized approaches in the treatment of more severe depression.
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| 7. |
- Krona, Cecilia, 1976, et al.
(författare)
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Screening for gene mutations in a 500 kb neuroblastoma tumor suppressor candidate region in chromosome 1p; mutation and stage-specific expression in UBE4B/UFD2.
- 2003
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 0950-9232 .- 1476-5594. ; 22:15, s. 2343-51
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Tidskriftsartikel (refereegranskat)abstract
- Deletion of a part of the short arm of chromosome 1 is one of the most common chromosomal rearrangements observed in neuroblastoma (NBL) tumors and it is associated with a poor prognosis. No NBL tumor suppressor gene has yet been identified in the region. Our shortest region of overlap of deletions, ranging from marker D1S80 to D1S244, was shown to partly overlap a 500 kb region that was homozygously deleted in a NBL cell line. We have screened seven genes known to reside in or very close to this overlap consensus region, UBE4B/UFD2, KIF1B, DFFA, PGD, CORT, PEX14, and ICAT, for coding mutations in NBL tumor DNA. A few deviations from the reference sequences were identified; most interestingly being a splice site mutation that was detected in UBE4B/UFD2 in a stage 3 NBL with a fatal outcome. This mutation was neither present in the patients constitutional DNA nor in any of 192 control chromosomes analysed. Also, the expression of UBE4B/UFD2 was markedly diminished in the high-stage/poor-outcome tumors as compared to the low-stage/favorable-outcome tumors. Overall, the number of amino-acid changes in the genes of the region was low, which shows that mutations in these genes are rare events in NBL development. Given the data presented here, UBE4B/UFD2 stands out as the strongest candidate NBL tumor suppressor gene in the region at this stage.
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| 8. |
- Malmer, Elin, 1963-
(författare)
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Hemmet vid nationens skola : Väckelsekristendom, värnplikt och soldatmission, ca 1900-1920
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis is set within a framework of the revivalist Christians’ Inner Mission, and presents as a case-study their mission to conscripts stationed in military exercise areas and garrison towns across Sweden. The revivalists’ evangelical zeal is given special attention. This is in contrast to much of the earlier research, which worked with the secularization paradigm formulated by the founders of sociology.Conscription in the early 20th century was regarded in various civilian and military circles as a platform for social and national integration, although these attitudes remain largely unstudied in Sweden’s case. Those engaged in missionizing the army were also drawn to this ‘School of the Nation’. The thesis shows that the motives of those involved in this home mission to soldiers were grounded in religion. However, the expansive missionary work was strengthened by the positions held by its male protagonists in the power structures of society. The mission was maintained by social contacts between an informal alliance of upper-class officers from among the mission’s military members, and by civilian missionaries from lower social classes.A decisive contextual factor for the army-mission as an educational project was that Sweden remained at peace. The civilian contribution to the mission grew as it spread more widely through the country. It is argued in this thesis that the soldiers’ homes were dominated by a discourse of domesticity. This discourse designated a place, a relationship, and a state of mind for the conscript during his free time at the military base. The missionaries were convinced that contact with the domestic and family values of civilian society should be preserved by the soldiers’ homes. The discourse of domesticity also looked ahead to the conscript’s subsequent life in civilian society: the missionaries wished to train up conscripts to be sober, moral family breadwinners.
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| 9. |
- Morin, Eric, et al.
(författare)
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Perivascular Neuropilin-1 expression is an independent marker of improved survival in renal cell carcinoma
- 2020
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Ingår i: Journal of Pathology. - : Wiley. - 0022-3417 .- 1096-9896. ; 250:4, s. 387-396
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Tidskriftsartikel (refereegranskat)abstract
- Renal cell carcinoma (RCC) treatment has improved in the last decade with the introduction of drugs targeting tumor angiogenesis. However, the 5-year survival of metastatic disease is still only 10–15%. Here, we explored the prognostic significance of compartment-specific expression of Neuropilin 1 (NRP1), a co-receptor for vascular endothelial growth factor (VEGF). NRP1 expression was analyzed in RCC tumor vessels, in perivascular tumor cells, and generally in the tumor cell compartment. Moreover, complex formation between NRP1 and the main VEGF receptor, VEGFR2, was determined. Two RCC tissue microarrays were used; a discovery cohort consisting of 64 patients and a validation cohort of 314 patients. VEGFR2/NRP1 complex formation in cis (on the same cell) and trans (between cells) configurations was determined by in situ proximity ligation assay (PLA), and NRP1 protein expression in three compartments (endothelial cells, perivascular tumor cells, and general tumor cell expression) was determined by immunofluorescent staining. Expression of NRP1 in perivascular tumor cells was explored as a marker for RCC survival in the two RCC cohorts. Results were further validated using a publicly available gene expression dataset of clear cell RCC (ccRCC). We found that VEGFR2/NRP1 trans complexes were detected in 75% of the patient samples. The presence of trans VEGFR2/NRP1 complexes or perivascular NRP1 expression was associated with a reduced tumor vessel density and size. When exploring NRP1 as a biomarker for RCC prognosis, perivascular NRP1 and general tumor cell NRP1 protein expression correlated with improved survival in the two independent cohorts, and significant results were obtained also at the mRNA level using the publicly available ccRCC gene expression dataset. Only perivascular NRP1 expression remained significant in multivariable analysis. Our work shows that perivascular NRP1 expression is an independent marker of improved survival in RCC patients, and reduces tumor vascularization by forming complexes in trans with VEGFR2 in the tumor endothelium.
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| 10. |
- Morin, Eric, et al.
(författare)
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VEGF receptor-2/neuropilin 1 trans-complex formation between endothelial and tumor cells is an independent predictor of pancreatic cancer survival
- 2018
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Ingår i: Journal of Pathology. - : John Wiley & Sons. - 0022-3417 .- 1096-9896. ; 246:3, s. 311-322
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Tidskriftsartikel (refereegranskat)abstract
- Unstable and dysfunctional tumor vasculature promotes cancer progression and spread. Signal transduction by the pro-angiogenic vascular endothelial growth factor (VEGF) receptor-2 (VEGFR2) is modulated by VEGFA-dependent complex formation with neuropilin 1 (NRP1). NRP1 expressed on tumor cells can form VEGFR2/NRP1 trans-complexes between tumor cells and endothelial cells which arrests VEGFR2 on the endothelial surface, thus interfering with productive VEGFR2 signaling. In mouse fibrosarcoma, VEGFR2/NRP1 trans-complexes correlated with reduced tumor vessel branching and reduced tumor cell proliferation. Pancreatic ductal adenocarcinoma (PDAC) strongly expressed NRP1 on both tumor cells and endothelial cells, in contrast to other common cancer forms. Using proximity ligation assay, VEGFR2/NRP1 trans-complexes were identified in human PDAC tumor tissue, and its presence was associated with reduced tumor vessel branching, reduced tumor cell proliferation, and improved patient survival after adjusting for other known survival predictors. We conclude that VEGFR2/NRP1 trans-complex formation is an independent predictor of PDAC patient survival.
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