1. |
- Arne, Gabriella, et al.
(author)
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Expression profiling of GIST: CD133 is associated with KIT exon 11 mutations, gastric location, and poor prognosis.
- 2011
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In: International journal of cancer. Journal international du cancer. - : Wiley. - 1097-0215 .- 0020-7136. ; 129:5, s. 1149-1161
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Journal article (peer-reviewed)abstract
- In gastrointestinal stromal tumors (GISTs), KIT exon 11 deletions are associated with poor prognosis. The aim of this study was to determine the gene expression profiles of GISTs carrying KIT exon 11 deletions and to identify genes associated with poor prognosis. Expression profiling was performed on 9 tumors with KIT exon 11 deletions and 7 without KIT exon 11 mutations using oligonucleotide microarrays. In addition, gene expression profiles for 35 GISTs were analyzed by meta-analysis. Expression of CD133 (prominin-1) protein was examined by tissue microarray (TMA) analysis of 204 GISTs from a population-based study in western Sweden. Survival analysis was performed on patients subjected to R0 resection (n=180) using the Cox proportional hazards model. Gene expression profiling, meta-analysis, and qPCR showed up regulation of CD133 in GISTs carrying KIT exon 11 deletions. Immunohistochemical analysis on TMA confirmed CD133 expression in 28% of all tumors. CD133 positivity was more frequent in gastric GISTs (48%) than in small intestinal GISTs (4%). CD133 positivity was also more frequent in GISTs with KIT exon 11 mutations (41%) than in tumors with mutations in KIT exon 9, PDGFRA, or wild-type tumors (0-17%). Univariate survival analysis showed a significant correlation between the presence of CD133 protein and shorter overall survival (hazard ratio=2.23, P=0.027). Multivariate analysis showed that CD133 provided additional information on patient survival compared to age, sex, NIH risk group and mutational status. CD133 is expressed in a subset of predominantly gastric GISTs with KIT exon 11 mutations and poor prognosis.
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2. |
- Arne, Gabriella, et al.
(author)
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Gastrointestinal stromal tumors (GISTs) express somatostatin receptors and bind radiolabeled somatostatin analogs.
- 2013
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In: Acta oncologica (Stockholm, Sweden). - 1651-226X .- 0284-186X. ; 52:4, s. 783-792
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Journal article (peer-reviewed)abstract
- Background. Gastrointestinal stromal tumors (GISTs) can be effectively treated with tyrosine kinase inhibitors (TKIs). However, some patients with GIST develop drug resistance, and alternative treatment strategies are therefore needed. The aim of this study was to analyze the expression of somatostatin receptors (SSTR) in GIST as a target for peptide receptor-mediated radiotherapy (PRRT). Material and methods. Expression profiling of SSTR1-5 was performed on biopsies from 34 GISTs (16 gastric tumors, 15 small intestinal tumors, and three rectal tumors). SSTR scintigraphy ((111)In-octreotide) and measurement of (111)In activity in tumor specimens was performed in seven patients. Uptake and internalization of (177)Lu- octreotate was studied in primary cell cultures from two patients. Results. Quantitative PCR analysis showed expression of SSTR1 and SSTR2 in the majority of tumors, while SSTR3-5 were expressed at low levels. Immunohistochemical analysis confirmed the presence of SSTR1 and SSTR2 proteins in all GISTs, and SSTR3-5 in a subset of tumors. Diagnostic imaging by SSTR scintigraphy, using (111)In-octreotide, demonstrated tumor uptake of (111)In in three of six GIST patients. Measurement of (111)In activity in excised tumor specimens from five patients gave tumor-to-blood (T/B) activity ratios of between eight and 96. Tumor cells in primary culture (gastric and small intestinal GIST) specifically bound and internalized (177)Lu when incubated with the therapeutic compound (177)Lu-octreotate for 4-48 hours (p < 0.05). Conclusion. Peptide receptor-mediated radiotherapy via SSTR may provide a novel treatment strategy in carefully selected GIST patients with TKI-resistant tumors.
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3. |
- Caronna, Edoardo, et al.
(author)
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Redefining migraine prevention: early treatment with anti-CGRP monoclonal antibodies enhances response in the real world
- 2024
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In: JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY. - 0022-3050 .- 1468-330X.
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Journal article (peer-reviewed)abstract
- Background Anti-CGRP monoclonal antibodies (anti-CGRP MAbs) are approved and available treatments for migraine prevention. Patients do not respond alike and many countries have reimbursement policies, which hinder treatments to those who might respond. This study aimed to investigate clinical factors associated with good and excellent response to anti-CGRP MAbs at 6 months. Methods European multicentre, prospective, real-world study, including high-frequency episodic or chronic migraine (CM) patients treated since March 2018 with anti-CGRP MAbs. We defined good and excellent responses as >= 50% and >= 75% reduction in monthly headache days (MHD) at 6 months, respectively. Generalised mixed-effect regression models (GLMMs) were used to identify variables independently associated with treatment response. Results Of the 5818 included patients, 82.3% were females and the median age was 48.0 (40.0-55.0) years. At baseline, the median of MHD was 20.0 (14.0-28.0) days/months and 72.2% had a diagnosis of CM. At 6 months (n=4963), 56.5% (2804/4963) were good responders and 26.7% (1324/4963) were excellent responders. In the GLMM model, older age (1.08 (95% CI 1.02 to 1.15), p=0.016), the presence of unilateral pain (1.39 (95% CI 1.21 to 1.60), p<0.001), the absence of depression (0.840 (95% CI 0.731 to 0.966), p=0.014), less monthly migraine days (0.923 (95% CI 0.862 to 0.989), p=0.023) and lower Migraine Disability Assessment at baseline (0.874 (95% CI 0.819 to 0.932), p<0.001) were predictors of good response (AUC of 0.648 (95% CI 0.616 to 0.680)). These variables were also significant predictors of excellent response (AUC of 0.691 (95% CI 0.651 to 0.731)). Sex was not significant in the GLMM models. Conclusions This is the largest real-world study of migraine patients treated with anti-CGRP MAbs. It provides evidence that higher migraine frequency and greater disability at baseline reduce the likelihood of responding to anti-CGRP MAbs, informing physicians and policy-makers on the need for an earlier treatment in order to offer the best chance of treatment success.
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5. |
- Kim, Dae-Kyum, et al.
(author)
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EVpedia: A Community Web Portal for Extracellular Vesicles Research
- 2015
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In: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 31:6, s. 933-939
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Journal article (peer-reviewed)abstract
- Motivation: Extracellular vesicles (EVs) are spherical bilayered proteolipids, harboring various bioactive molecules. Due to the complexity of the vesicular nomenclatures and components, online searches for EV-related publications and vesicular components are currently challenging. Results: We present an improved version of EVpedia, a public database for EVs research. This community web portal contains a database of publications and vesicular components, identification of orthologous vesicular components, bioinformatic tools and a personalized function. EVpedia includes 6879 publications, 172 080 vesicular components from 263 high-throughput datasets, and has been accessed more than 65 000 times from more than 750 cities. In addition, about 350 members from 73 international research groups have participated in developing EVpedia. This free web-based database might serve as a useful resource to stimulate the emerging field of EV research.
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6. |
- Kristiansson, Erik, 1978, et al.
(author)
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A novel method for cross-species gene expression analysis
- 2013
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In: BMC Bioinformatics. - : Springer Science and Business Media LLC. - 1471-2105. ; 14
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Journal article (peer-reviewed)abstract
- Background Analysis of gene expression from different species is a powerful way to identify evolutionarily conserved transcriptional responses. However, due to evolutionary events such as gene duplication, there is no one-to-one correspondence between genes from different species which makes comparison of their expression profiles complex. Results In this paper we describe a new method for cross-species meta-analysis of gene expression. The method takes the homology structure between compared species into account and can therefore compare expression data from genes with any number of orthologs and paralogs. A simulation study shows that the proposed method results in a substantial increase in statistical power compared to previously suggested procedures. As a proof of concept, we analyzed microarray data from heat stress experiments performed in eight species and identified several well-known evolutionarily conserved transcriptional responses. The method was also applied to gene expression profiles from five studies of estrogen exposed fish and both known and potentially novel responses were identified. Conclusions The method described in this paper will further increase the potential and reliability of meta-analysis of gene expression profiles from evolutionarily distant species. The method has been implemented in R and is freely available at http://bioinformatics.math.chalmers.se/Xspecies/ webcite.
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7. |
- Magnus, Fridrik, et al.
(author)
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Tunable giant magnetic anisotropy in amorphous SmCo thin films
- 2013
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In: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 102:16, s. 162402-
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Journal article (peer-reviewed)abstract
- SmCo thin films have been grown by magnetron sputtering at room temperature with a composition of 2-35 at.% Sm. Films with 5 at.% or higher Sm are amorphous and smooth. A giant tunable uniaxial in-plane magnetic anisotropy is induced in the films which peaks in the composition range 11-22 at.% Sm. This cross-over behavior is not due to changes in the atomic moments but rather the local configuration changes. The excellent layer perfection combined with highly tunable magnetic properties make these films important for spintronics applications.
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8. |
- Nåbo, Arne, 1958-, et al.
(author)
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Elvägar i körsimulator : design, test, utvärdering och demonstration av elvägstekniker och elfordon med virtuella metoder
- 2015
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Reports (other academic/artistic)abstract
- Elvägar, där el överförs kontinuerligt till fordon på vägen, kan vara ett sätt att nå målet om en fossiloberoende transportsektor. För att testa och utvärdera elvägar och elfordon på elvägar i ett tidigt stadium utvecklades en demonstrationsmiljö i körsimulator. En studie genomfördes med 25 förare där varje förare fick köra en 40 kilometer lång vägsträcka, dels med en hybridlastbil på elväg, dels med en konventionell lastbil utan elväg. Körning på elväg uppvisade inga anmärkningsvärda skillnader på förarens upplevelser vad gäller säkerhet och estetik eller körbeteende jämfört med körning utan elväg. Undantaget var medelhastigheten vilken var cirka 2 kilometer/timme högre på elväg. Energianvändningen var cirka 35 procent lägre på elväg. För att sprida projektresultatet till aktörer och intressenter av elvägar har ett stort antal demonstrationer genomförts, samt kommunikation via pressreleaser och tidningsartiklar. Det har även tagits fram en mindre, mobil körsimulator för elvägar som ett led i att nå ut till en större målgrupp.
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9. |
- Nåbo, Arne, 1958-, et al.
(author)
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Regeringsuppdrag om elektrifieringen av transporter : rekommendationer för att underlätta datadelning och nyttiggörande av data för planering, utveckling och drift av laddinfrastruktur och affärsmodeller
- 2023
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Reports (other academic/artistic)abstract
- Regeringen har uppdragit åt Statens väg- och transportforskningsinstitut (VTI) att ”bidra till kunskapsuppbyggnaden kring en snabb, smart och samhällsekonomiskt effektiv elektrifiering av transportsektorn”. Den här rapporten redovisar den del av uppdraget som handlar om att genomföra pilotprojekt och ta fram modeller för hur data i praktiken på bästa sätt kan tillgängliggöras, delas och nyttiggöras för att optimera planering, utveckling, drift samt affärsmodeller för laddinfrastruktur. I rapporten ges en beskrivning av förekommande tekniker för laddning av elfordon, viktiga användarperspektiv, och hur affärsmodeller och system för laddinfrastruktur kan modelleras. Rapporten fokuserar på datadelning och beskriver hur aktörer idag delar data samt vilka svårigheter de ser med datadelning. Detta omfattar bland annat datatillgänglighet, delning och nyttiggörande, samt hur aktörerna vill att det ska fungera framåt. En stor utmaning handlar om datatillgänglighet, där aktörer dels ser problem med att få tillgång till data och dels är avvaktande till att vilja dela med sig av egna data. Ofta handlar det om integritetsfrågor och reglering enligt GDPR. Betydelsen av en väl fungerande samverkan mellan energi- och transportsektorn har lyfts i tidigare rapporteringar från det här uppdraget. Vikten av en digitalisering och digital infrastruktur som kopplar samman dessa sektorer betonas speciellt i detta arbete. Digitalisering behövs för att effektivisera planering, utveckling och drift av den infrastruktur som ett elektrifierat transportsystem kräver. De modelleringar som gjorts i den här delen av uppdraget handlar om transportmodellering och energimodellering samt utveckling för att få modellerna att samspela.
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10. |
- Olofsson, Sven-Erik, et al.
(author)
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Population-Based Study of Treatment Guided by Tumor Marker Decline in Patients With Metastatic Nonseminomatous Germ Cell Tumor : A Report From the Swedish-Norwegian Testicular Cancer Group
- 2011
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In: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 29:15, s. 2032-2039
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Journal article (peer-reviewed)abstract
- Purpose From 1995 to 2003, 603 adult patients from Sweden and Norway with metastatic testicular nonseminomatous germ cell tumor (NSGCT) were included prospectively in a population-based protocol with strict guidelines for staging, treatment, and follow-up. Patients with extragonadal primary tumor or previous treatment for contralateral testicular tumor were excluded. The basic strategy was to individualize treatment according to initial tumor marker response. Methods Initial treatment for all patients was two courses of standard bleomycin, etoposide, and cisplatin (BEP), with tumor markers analyzed weekly. Good response was defined as a half-life (t(1/2)) for alpha-fetoprotein (AFP) of <= 7 days and/or for beta-human chorionic gonadotropin (beta-HCG) of <= 3 days. Patients with prolonged marker t(1/2) (ie, poor response) received intensification with addition of ifosfamide (BEP-if/PEI) in step 1. If poor response continued, the treatment was intensified with high-dose chemotherapy with stem-cell rescue as step 2. Results Overall, 99% of all patients with metastatic testicular NSGCT in the population were included in the protocol. Median follow-up was 8.2 years. Seventy-seven percent of the patients were treated with BEP alone; 18% received intensification step 1%, and 5% received intensification step 2. Grouped according to International Germ Cell Consensus Classification, 10-year overall survival was 94.7% in good-prognosis patients, 90.0% in intermediate-prognosis patients, and 67.4% in poor-prognosis patients. Conclusion With detailed treatment protocols and a dedicated collaborative group of specialists, treatment results comparable to those reported from large single institutions can be achieved at national level. With the treatment principles used in Swedish-Norwegian Testicular Cancer Group study SWENOTECA IV, the survival of intermediate-prognosis patients is remarkable and close to that of good-prognosis patients.
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