| 1. |
- Allaoui, Roni, et al.
(författare)
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Cancer-associated fibroblast-secreted CXCL16 attracts monocytes to promote stroma activation in triple-negative breast cancers
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Triple-negative (TN) breast cancers (ER â ' PR â ' HER2 â ') are highly metastatic and associated with poor prognosis. Within this subtype, invasive, stroma-rich tumours with infiltration of inflammatory cells are even more aggressive. The effect of myeloid cells on reactive stroma formation in TN breast cancer is largely unknown. Here, we show that primary human monocytes have a survival advantage, proliferate in vivo and develop into immunosuppressive myeloid cells expressing the myeloid-derived suppressor cell marker S100A9 only in a TN breast cancer environment. This results in activation of cancer-associated fibroblasts and expression of CXCL16, which we show to be a monocyte chemoattractant. We propose that this migratory feedback loop amplifies the formation of a reactive stroma, contributing to the aggressive phenotype of TN breast tumours. These insights could help select more suitable therapies targeting the stromal component of these tumours, and could aid prediction of drug resistance.
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| 2. |
- Gunnarsdóttir, Frida Björk, et al.
(författare)
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Inflammatory macrophage derived TNFα downregulates estrogen receptor α via FOXO3a inactivation in human breast cancer cells
- 2020
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Ingår i: Experimental Cell Research. - : Elsevier BV. - 0014-4827. ; 390:1
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Tidskriftsartikel (refereegranskat)abstract
- Patients with estrogen receptor α positive (ERα+) breast cancer can respond to endocrine therapy, but treatment resistance is common and associated with downregulation of ERα expression in the dormant residual cells. Here we show, using long-term NSG xenograft models of human breast cancer and primary human monocytes, in vitro primary cell cultures and tumors from breast cancer patients, that macrophage derived tumor necrosis factor alpha (TNFα) downregulates ERα in breast cancer cells via inactivation of the transcription factor Forkhead box O transcription factor 3a (FOXO3a). Moreover, presence of tumor associated macrophages in the primary tumor of breast cancer patients, was associated with ERα negativity, and with worse prognosis in patients with ERα+ tumors. We propose that pro-inflammatory macrophages, despite being tumoricidal, may have direct effects on tumor progression and endocrine resistance in breast cancer patients. Our findings suggest that TNFα antagonists should be evaluated for treatment of ERα+ breast cancer.
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| 3. |
- Elbing, Karin, 1974, et al.
(författare)
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Role of hexose transport in control of glycolytic flux in Saccharomyces cerevisiae
- 2004
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Ingår i: Applied and Environmental Microbiology. - 0099-2240 .- 1098-5336. ; 70:9, s. 5323-5330
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Tidskriftsartikel (refereegranskat)abstract
- The yeast Saccharomyces cerevisiae predominantly ferments glucose to ethanol at high external glucose concentrations, irrespective of the presence of oxygen. In contrast, at low external glucose concentrations and in the presence of oxygen, as in a glucose-limited chemostat, no ethanol is produced. The importance of the external glucose concentration suggests a central role for the affinity and maximal transport rates of yeast's glucose transporters in the control of ethanol production. Here we present a series of strains producing functional chimeras between the hexose transporters Hxt1 and Hxt7, each of which has distinct glucose transport characteristics. The strains display a range of decreasing glycollytic rates resulting in a proportional decrease in ethanol production. Using these strains, we show for the first time that at high glucose levels, the glucose uptake capacity of wild-type S. cerevisiae does not control glycolytic flux during exponential batch growth. In contrast, our chimeric Hxt transporters control the rate of glycollysis to a high degree. Strains whose glucose uptake is mediated by these chimeric transporters will undoubtedly provide a powerful tool with which to examine in detail the mechanism underlying the switch between fermentation and respiration in S. cerevisiae and will provide new tools for the control of industrial fermentations.
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| 4. |
- Fredrikson, Karin, et al.
(författare)
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Isolation and polypeptide composition of 1,3-ß-glucan synthase from plasma membranes of Brassica oleracea
- 1991
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Ingår i: Physiologia Plantarum. - : Wiley. - 0031-9317 .- 1399-3054. ; 81:3, s. 289-294
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Tidskriftsartikel (refereegranskat)abstract
- The l,3‐ß‐glucan synthase (callose synthase, EC 2.4.1.34) was solubilized from cauliflower (Brassica oleracea L.) plasma membranes with digitonin, and partially purified by ion exchange chromatography and gel filtration [fast protein liquid chromatography (FPLC)] using 3‐[(cholamidopropyl)dimethylammonio]‐1‐propane‐sulfonate (CHAPS) in the elution buffers. These initial steps were necessary to obtain specific precipitation of the enzyme during product entrapment, the final purification step. Five polypeptides of 32, 35, 57, 65 and 66 kDa were highly enriched in the final preparation and are thus likely components of the callose synthase complex. The purified enzyme was activated by Ca2+, spermine and cellobiose in the same way as the enzyme in situ, indicating that no essential subunits were missing. The polyglucan produced by the purified enzyme contained mainly 1,3‐linked glucose.
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| 5. |
- Henricsson, Cecilia, 1975, et al.
(författare)
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Engineering of a novel Saccharomyces cerevisiae wine strain with a respiratory phenotype at high external glucose concentrations
- 2005
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Ingår i: Applied and Environmental Microbiology. - 0099-2240 .- 1098-5336. ; 71:10, s. 6185-6192
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Tidskriftsartikel (refereegranskat)abstract
- The recently described respiratory strain Saccharomyces cerevisiae KOY.TM6*P is, to our knowledge, the only reported strain of S. cerevisiae which completely redirects the flux of glucose from ethanol fermentation to respiration, even at high external glucose concentrations (27). In the KOY.TM6*P strain, portions of the genes encoding the predominant hexose transporter proteins, Hxt1 and Hxt7, were fused within the regions encoding transmembrane (TM) domain 6. The resulting chimeric gene, TM6*, encoded a chimera composed of the amino-terminal half of Hxt1 and the carboxy-terminal half of Hxt7. It was subsequently integrated into the genome of an hxt null strain. In this study, we have demonstrated the transferability of this respiratory phenotype to the V5 hxt1-7 strain, a derivative of a strain used in enology. We also show by using this mutant that it is not necessary to transform a complete hxt null strain with the TM6* construct to obtain a nonethanol- producing phenotype. The resulting V5.TM6*P strain, obtained by transformation of the V5 hxt1-7 strain with the TM6* chimeric gene, produced only minor amounts of ethanol when cultured on external glucose concentrations as high as 5%. Despite the fact that glucose flux was reduced to 30% in the V5.TM6*P strain compared with that of its parental strain, the V5.TM6*P strain produced biomass at a specific rate as high as 85% that of the V5 wild-type strain. Even more relevant for the potential use of such a strain for the production of heterologous proteins and also of low-alcohol beverages is the observation that the biomass yield increased 50% with the mutant compared to its parental strain.
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| 6. |
- Kalstad Lönne, Gry, et al.
(författare)
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PKCalpha expression is a marker for breast cancer aggressiveness.
- 2010
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Ingår i: Molecular cancer. - : Springer Science and Business Media LLC. - 1476-4598. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Protein kinase C (PKC) isoforms are potential targets for breast cancer therapy. This study was designed to evaluate which PKC isoforms might be optimal targets for different breast cancer subtypes.
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| 7. |
- Larsson, Christer, et al.
(författare)
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Prognostic implications of the expression levels of different immunoglobulin heavy chain-encoding RNAs in early breast cancer
- 2020
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Ingår i: npj Breast Cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- The extent and composition of the immune response in a breast cancer is one important prognostic factor for the disease. The aim of the current work was to refine the analysis of the humoral component of an immune response in breast tumors by quantifying mRNA expression of different immunoglobulin classes and study their association with prognosis. We used RNA-Seq data from two local population-based breast cancer cohorts to determine the expression of IGJ and immunoglobulin heavy (IGH) chain-encoding RNAs. The association with prognosis was investigated and public data sets were used to corroborate the findings. Except for IGHE and IGHD, mRNAs encoding heavy chains were generally detected at substantial levels and correlated with other immune-related genes. High IGHG1 mRNA was associated with factors related to poor prognosis such as estrogen receptor negativity, HER2 amplification, and high grade, whereas high IGHA2 mRNA levels were primarily associated with lower age at diagnosis. High IGHA2 and IGJ mRNA levels were associated with a more favorable prognosis both in univariable and multivariable Cox models. When adjusting for other prognostic factors, high IGHG1 mRNA levels were positively associated with improved prognosis. To our knowledge, these results are the first to demonstrate that expression of individual Ig class types has prognostic implications in breast cancer.
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| 8. |
- Otterstedt, Karin, et al.
(författare)
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Switching the mode of metabolism in the yeast Saccharomyces cerevisiae.
- 2004
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Ingår i: Embro reports. - : EMBO. - 1469-221X .- 1469-3178. ; 5:5, s. 532-537
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Tidskriftsartikel (refereegranskat)abstract
- The biochemistry of most metabolic pathways is conserved from bacteria to humans, although the control mechanisms are adapted to the needs of each cell type. Oxygen depletion commonly controls the switch from respiration to fermentation. However, Saccharomyces cerevisiae also controls that switch in response to the external glucose level. We have generated an S. cerevisiae strain in which glucose uptake is dependent on a chimeric hexose transporter mediating reduced sugar uptake. This strain shows a fully respiratory metabolism also at high glucose levels as seen for aerobic organisms, and switches to fermentation only when oxygen is lacking. These observations illustrate that manipulating a single step can alter the mode of metabolism. The novel yeast strain is an excellent tool to study the mechanisms underlying glucose-induced signal transduction.
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| 9. |
- Palmgren, Michael Gjedde, et al.
(författare)
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Sealed Inside-Out and Right-Side-Out Plasma Membrane Vesicles : Optimal Conditions for Formation and Separation
- 1990
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Ingår i: Plant Physiology. - 0032-0889 .- 1532-2548. ; 92:4, s. 871-880
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Tidskriftsartikel (refereegranskat)abstract
- Plasma membrane preparations of high purity (about 95%) are easily obtained by partitioning in aqueous polymer two-phase systems. These preparations, however, mainly contain sealed right-side-out (apoplastic side out) vesicles. Part of these vesicles have been turned inside-out by freezing and thawing, and sealed inside-out and right-side-out vesicles subsequently separated by repeating the phase partition step. Increasing the KCI concentration in the freeze/thaw medium as well as increasing the number of freeze/thaw cycles significantly increased the yield of inside-out vesicles. At optimal conditions, 15 to 25% of total plasma membrane protein was recovered as inside-out vesicles, corresponding to 5 to 10 milligrams of protein from 500 grams of sugar beet (Beta vulgaris L.) leaves. Based on enzyme latency, trypsin inhibition of NADH-cytochrome c reductase, and H+ pumping capacity, a cross-contamination of about 20% between the two fractions of oppositely oriented vesicles was estimated. Thus, preparations containing about 80% inside-out and 80% right-side-out vesicles, respectively, were obtained. ATPase activity and H+ pumping were both completely inhibited by vanadate (Ki ≈ 10 micromolar), indicating that the fractions were completely free from nonplasma membrane ATPases. Furthermore, the polypeptide patterns of the two fractions were close to identical, which shows that the vesicles differed in sidedness only. Thus, preparations of both inside-out and right-side-out plasma membrane vesicles are now available. This permits studies on transport, signal transduction mechanisms, enzyme topology, etc., using plasma membrane vesicles of either orientation.
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| 10. |
- Sotoudeh, Omid, et al.
(författare)
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ISAR measurements at Saab
- 2013
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Ingår i: [Host publication title missing]. - 9781467321877 ; , s. 2934-2935
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Konferensbidrag (refereegranskat)abstract
- The ISAR measurement technique and analysis at Saab is discussed. The traditional criterion for far-field distance is not satisfied as the scattering measurements often are conducted for aircraft at 100 m measurement distance. The considerable phase variation over the target that results leads to near-field measurements. We have therefore adapted a fast image based compensation method which transforms the ISAR image into the far-field region and in essence renders accurate RCS determinations for the targets. RCS measurements at Saab can be dated back to 1986. We will in this paper give an overview of our activities and methodology.
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