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| 2. |
- Jiang, Yiwen, et al.
(författare)
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Glioblastoma Cell Malignancy and Drug Sensitivity Are Affected by the Cell of Origin
- 2017
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 18:4, s. 977-990
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Tidskriftsartikel (refereegranskat)abstract
- The identity of the glioblastoma (GBM) cell of origin and its contributions to disease progression and treatment response remain largely unknown. We have analyzed how the phenotypic state of the initially transformed cell affects mouse GBM development and essential GBM cell (GC) properties. We find that GBM induced in neural stem-cell-like glial fibrillary acidic protein (GFAP)-expressing cells in the subventricular zone of adult mice shows accelerated tumor development and produces more malignant GCs (mGC1GFAP) that are less resistant to cancer drugs, compared with those originating from more differentiated nestin- (mGC2NES) or 2,'3'-cyclic nucleotide 3'-phosphodiesterase (mGC3CNP)-expressing cells. Transcriptome analysis of mouse GCs identified a 196 mouse cell origin (MCO) gene signature that was used to partition 61 patient-derived GC lines. Human GC lines that clustered with the mGC1GFAP cells were also significantly more self-renewing, tumorigenic, and sensitive to cancer drugs compared with those that clustered with mouse GCs of more differentiated origin.
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| 3. |
- Ossman, Lisa, et al.
(författare)
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Nulägesanalys för satsning på NNE byggnader : slutrapport etapp 1
- 2012
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Det övergripande syftet med uppdraget är att få en detaljerad bild över byggnaders energiprestanda i Sverige. Den första etappen, förstudien, går ut på att beskriva metoden för hur denna analys ska göras. Som etapp 2 genomförs själva nulägesanalysen och slut¬ligen i etapp 3 analyseras resultat och slutsatser presenteras. I denna rapport redogörs för etapp 1, dvs metodbeskrivningen för nulägesanalysen. Nulägesanalysen ska senare kunna användas för att följa upp hur satsningar på Näranoll¬energibyggnader (NNE) påverkar energianvändningen i hela byggnadsbeståndet, inte bara i de faktiska demonstrationsprojekt som beviljas stöd och där uppföljning är betydligt enklare. Resultatet av nulägesanalysen, och den uppföljande analysen (planerad till 2015), ska i förlängningen kunna vara ett stöd när de nationella målnivåerna för näranollenergi-byggnader bestäms. I denna rapport redogörs för etapp 1, dvs metodbeskrivningen för nulägesanalysen. Rapporten beskriver vilka statistikkällor som finns idag samt en metod för hur dessa kan bidra till en mer detaljerad bild av byggnaders energiprestanda under ett valt referensår.
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| 4. |
- Bergh, Caroline, 1980-
(författare)
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Organophosphates and phthalates in air and dust from indoor environments : Method development and applied measurements
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Organophosphate and phthalate esters are polymer additives that are frequently found in air and dust in indoor environments. This thesis describes the development and application of air sampling and selective mass spectrometric (MS) determination of these two compound groups. It also describes the sampling and screening of these compounds in indoor air and dust from different environments and the development and evaluation of a method for the extraction and determination of these compounds in indoor dust.An air sampling method previously used for air sampling of only organophosphate esters, is here demonstrated to be applicable for simultaneous sampling of both phthalate and organophosphate esters. Selective detection using tandem mass spectrometry (MS/MS) showed good results for simultaneous determination of organophosphate and phthalate esters in air. The high selectivity of this technique was especially advantageous when analyzing dust.Comparison of chemical profiles of the organophosphate ester between indoor environments including daycare centers, offices and private homes differed between the types of locations while the phthalate profiles were rather similar. Comparison of concentration levels of these compounds in multi-storey apartment buildings classified as either high or low risk “sick” buildings could not differentiate the two classes of buildings. Further, the studies also points out some potential sources of organophosphate and phthalate esters in these indoor environments.In general the levels of phthalate esters were consistently higher than the levels of organophosphate esters both in air and in dust. Phthalate and organophosphate esters were also determined in a dust standard reference material; seventeen of the targeted compounds were quantified out of which ten had not previously been reported for this reference material.
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| 5. |
- Boss, Annika, et al.
(författare)
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Uppvärmning och kylning av lokaler ur energi- och miljömässigt samt ekonomiskt perspektiv
- 2009
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Rapport (refereegranskat)abstract
- Demand for cooling of commercial buildings is increasing and there is a potential for expanding district cooling systems, especially in district heating areas. Using district heating and district cooling has been compared to heat pump techniques. Primary energy, environmental influence and economy have been evaluated. Four buildings in Gothenburg have been included in the study and certain differences have been found depending on demands of heating and cooling, which vary according to design and activity. The results are specific for Gothenburg due to the combination of production methods for district heating and cooling and the pricing, which differ compared to other places. Different perspectives on production of electricity, district heating and district cooling, e.g. average or marginal production, is of vital importance when comparing environmental influence. In most of the case studies the demand of primary energy is lower for district heating and cooling compared to heat pump systems. With a marginal perspective district heating and cooling will lead to lower emissions of greenhouse gases. Using the perspective of average production will on the other hand rate heat pump systems to have a lower influence on the greenhouse effect in most of the cases. Which technique is the most cost efficient depends mainly upon relation of heating and cooling demands. Where there is a greater demand for cooling than for heating, district heating and cooling is more advantageous. It is a need for improved data in commercial buildings from reliable field measurements. The quality of the evaluation is very much dependent on reliable measured data from real installations.
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| 6. |
- de Flon, Caroline Haglund, et al.
(författare)
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High Levels of FGF11 Correlate with Poor Survival in Patients with Human Papillomavirus (HPV)-Positive Oropharyngeal Squamous Cell Carcinoma
- 2023
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Ingår i: Cancers. - : MDPI. - 2072-6694. ; 15:7
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Tidskriftsartikel (refereegranskat)abstract
- To better identify patients with human papillomavirus (HPV)-positive oropharyngeal cancer (OPSCC) and a poor prognosis after treatment, we compared the gene expression in tumours from patients with a poor or a favourable prognosis in a case-control setting. The results were thereafter validated in two separate cohorts on the RNA and protein levels. High RNA or protein expression of FGF11 was correlated with a poor patient survival in all three cohorts. Taken together, the data imply that FGF11 may play a major role in the prognosis of patients and that FGF11 could serve as a prognostic marker in HPV-positive oropharyngeal cancer.Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) is associated with a favourable prognosis. It has therefore been suggested that treatment should be individualized and separated by HPV status. However, additional prognostic markers are still needed before treatment can be individualized for this patient group. For this purpose, all patients diagnosed with HPV and p16-positive OPSCC in Stockholm 2000-2009, identified as having a partial/nonresponse to treatment and having viable tumour cells in their neck specimen with material available were categorized as cases. These were matched to controls (complete responders), and the differences in the gene expression were analysed. Two separate verification cohorts were identified including patients with HPV- and p16-positive OPSCC, and the data from the case-control study were verified by qPCR and immunohistochemistry (IHC) in the respective cohorts. A separation of gene expression in correlation with survival was observed in the case-control study, and FGF11 expression was identified as significantly differently expressed between the two groups. The prognostic role of FGF11 was validated in the two cohorts on the RNA and protein levels, respectively. Taken together, our findings suggest that FGF11 may indicate a poor prognosis in HPV-positive OPSCC and may serve as a prognostic biomarker.
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| 7. |
- Fayad, Walid, et al.
(författare)
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Identification of Agents that Induce Apoptosis of Multicellular Tumour Spheroids : Enrichment for Mitotic Inhibitors with Hydrophobic Properties
- 2011
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Ingår i: Chemical Biology and Drug Design. - : Wiley. - 1747-0277 .- 1747-0285. ; 78:4, s. 547-557
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Tidskriftsartikel (refereegranskat)abstract
- Cell-based anticancer drug screening generally utilizes rapidly proliferating tumour cells grown as monolayer cultures. Hit compounds from such screens are not necessarily effective on hypoxic and slowly proliferating cells in 3-D tumour tissue. The aim of this study was to examine the potential usefulness of 3-D cultured tumour cells for anticancer drug screening. We used colon carcinoma multicellular spheroids containing hypoxic and quiescent cells in core areas for this purpose. Three libraries (similar to 11 000 compounds) were screened using antiproliferative activity and/or apoptosis as end-points. Screening of monolayer and spheroid cultures was found to identify different sets of hit compounds. Spheroid screening enriched for hydrophobic compounds: median XLogP values of 4.3 and 4.4 were observed for the hits in two independent screening campaigns. Mechanistic analysis revealed that the majority of spheroid screening hits were microtubuli inhibitors. One of these inhibitors was examined in detail and found to be effective against non-dividing cells in the hypoxic centres of spheroids. Spheroid screening represents a conceptually new strategy for anticancer drug discovery. Our findings have implications for drug library design and hit selection in projects aimed to develop drugs for the treatment of solid tumours.
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| 8. |
- Felth, Jenny, 1979-, et al.
(författare)
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Gambogic acid is cytotoxic to cancer cells through inhibition of the ubiquitin-proteasome system
- 2013
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Ingår i: Investigational new drugs. - : Springer Science and Business Media LLC. - 0167-6997 .- 1573-0646. ; 31:3, s. 587-598
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Gambogic acid (GA), displays cytotoxicity towards a wide variety of tumor cells and has been shown to affect many important cell-signaling pathways. In the present work, we investigated the mechanism of action of GA by analysis of drug-induced changes in gene expression profiles and identified GA and the derivative dihydro GA as possible inhibitors of the ubiquitin-proteasome system (UPS). Both GA and dihydro GA inhibited proteasome function in cells resulting in the accumulation of polyubiquitin complexes. In vitro experiments showed that both GA and dihydro GA inhibited 20S chymotrypsin activity and the inhibitory effects of GA and dihydro GA on proteasome function corresponded with apoptosis induction and cell death. In conclusion, our results show that GA and dihydro GA exert their cytotoxic activity through inhibition of the UPS, specifically by acting as inhibitors of the chymotrypsin activity of the 20S proteasome.
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