| 221. |
- Roggen, EL, et al.
(författare)
-
Interactions between dendritic cells and epithelial cells in allergic disease
- 2006
-
Ingår i: Proceedings of the 42nd Congress of the European Societies of Toxicology - EUROTOX 2005 (Toxicology Letters). - : Elsevier BV. - 0378-4274. ; 162:1, s. 71-82
-
Konferensbidrag (refereegranskat)abstract
- Dendritic cells (DCs) play a crucial role in the sensitisation process. Upon encounter with an allergen, DCs require interactions with other cells and factors for triggering a primary or secondary immune response. Epithelial cells (ECs) express features of accessory cells, Such as expression of HLA-DR, co-stimulatory molecules, functional Fc gamma R, molecules of the antigen-processing machinery, and display an ability to internalise antigen. These features may authorize them to function as immunomodulators (e.g. amplification of memory T cells during secondary immune responses). ECs may increase chemokine (e.g. CCL20) secretion thereby attracting DCs. Epithelial human TSLP activates DC, which allow them to prime naive T cell, for the production of pro-inflammatory cytokines, while down-regulating IFN-gamma and IL-10. ECs may also influence the local polarization of types 1 and 2 antigen-presenting cells via PGE(2) by impairing the ability of maturing DC to produce bioactive IL-12 p70. PGE(2) is synergistic with IL-1 beta and TNF-alpha in the induction of functional and phenotypic maturation of DC and induce IL12 p40 production. Sensitisation via the respiratory route may be Th-2 skewed, possibly because the antigen recognition by DC occurs in an environment rich of airway EC-product such its PGE(2). (c) 2005 Elsevier Ireland Ltd. All rights reserved.
|
|
| 222. |
|
|
| 223. |
|
|
| 224. |
- Sandström Gerdtsson, Anna, et al.
(författare)
-
A Multicenter Trial Defining a Serum Protein Signature Associated with Pancreatic Ductal Adenocarcinoma.
- 2015
-
Ingår i: International Journal of Proteomics. - : Hindawi Limited. - 2090-2174 .- 2090-2166. ; 2015
-
Tidskriftsartikel (refereegranskat)abstract
- Background. Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with rapid tumor progression and poor prognosis. This study was motivated by the lack of sensitive and specific PDAC biomarkers and aimed to identify a diagnostic, serum protein signature for PDAC. Methods. To mimic a real life test situation, a multicenter trial comprising a serum sample cohort, including 338 patients with either PDAC or other pancreatic diseases (OPD) and controls with nonpancreatic conditions (NPC), was analyzed on 293-plex recombinant antibody microarrays targeting immunoregulatory and cancer-associated antigens. Results. Serum samples collected from different hospitals were analyzed and showed that (i) sampling from five different hospitals could not be identified as a preanalytical variable and (ii) a multiplexed biomarker signature could be identified, utilizing up to 10 serum markers that could discriminate PDAC from controls, with sensitivities and specificities in the 91-100% range. The first protein profiles associated with the location of the primary tumor in the pancreas could also be identified. Conclusions. The results demonstrate that robust enough serum signatures could be identified in a multicenter trial, potentially contributing to the development of a multiplexed biomarker immunoassay for improved PDAC diagnosis.
|
|
| 225. |
- Sandström Gerdtsson, Anna, et al.
(författare)
-
Serum proteome profiling of pancreatitis using recombinant antibody microarrays reveals disease-associated biomarker signatures
- 2012
-
Ingår i: Proteomics Clinical Applications. - : Wiley. - 1862-8354 .- 1862-8346. ; 6:9-10, s. 96-486
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Pancreatitis is an inflammatory state of the pancreas, for which high-performing serological biomarkers are lacking. The aim of the present study was to evaluate the use of affinity proteomics for identifying potential markers of disease and stratifying pancreatitis subtypes. EXPERIMENTAL DESIGN: High-content, recombinant antibody microarrays were applied for serum protein expression profiling of 113 serum samples from patients with chronic, acute, and autoimmune pancreatitis, as well as healthy controls. The sample groups were compared using supervised classification based on support vector machine analysis. RESULTS: This discovery study showed that pancreatitis subtypes could be discriminated with high accuracy. Using unfiltered data, the individual subtypes, as well as the combined pancreatitis cohort, were distinguished from healthy controls with high AUC values (0.96-1.00). Moreover, characteristic protein patterns and AUC values in the range of 0.69-0.95 were observed for the individual pancreatitis entities when compared to each other, and to all other samples combined. CONCLUSIONS AND CLINICAL RELEVANCE: This study demonstrated the potential of the antibody microarray approach for stratification of pancreatitis. Distinct candidate multiplex serum biomarker signatures for chronic, acute, and autoimmune pancreatitis were defined, which could enhance our fundamental knowledge of the underlying molecular mechanisms, and potentially lead to improved diagnosis.
|
|
| 226. |
- Santegoets, Saskia J A M, et al.
(författare)
-
Transcriptional profiling of human skin-resident Langerhans cells and CD1a+ dermal dendritic cells: differential activation states suggest distinct functions.
- 2008
-
Ingår i: Journal of Leukocyte Biology. - : Oxford University Press (OUP). - 1938-3673 .- 0741-5400. ; 84, s. 143-151
-
Tidskriftsartikel (refereegranskat)abstract
- In human skin, two main populations of dendritic cells (DC) can be discriminated: dermal DC (DDC) and epidermal Langerhans cells (LC). Although extensively studied, most of the knowledge about DDC and LC phenotype and function is obtained from studying DDC and LC cultured in vitro or DDC and LC migrated from skin explants. These studies have left the exact relationship between steady-state human LC and DDC unclear: in particular, whether CD1a(+) DDC represent migrated LC or whether they constitute a separate subset. To gain further insight in the kinship between skin-resident CD1a(+) DDC and LC, we analyzed CD1a(+) DDC and LC, isolated from steady-state skin samples, by high-density microarray analysis. Results show that the CD1a(+) DDC specifically express markers associated with DDC phenotype, such as the macrophage mannose receptor, DC-specific ICAM-grabbing nonintegrin, the scavenger receptor CD36, coagulation factor XIIIa, and chemokine receptor CCR5, whereas LC specifically express Langerin, membrane ATPase (CD39), and CCR6, all hallmarks of the LC lineage. In addition, under steady-state conditions, both DC subsets display a strikingly different activation status, indicative of distinct functional properties. CD1a(+) DDC exhibit a more activated, proinflammatory, migratory, and T cell-stimulatory profile, as compared with LC, whereas LC mainly express molecules involved in cell adhesion and DC retention in the epidermis. In conclusion, transcriptional profiling is consistent with the notion that CD1a(+) DDC and LC represent two distinct DC subsets but also that under steady-state conditions, CD1a(+) DDC and epidermal LC represent opposites of the DC activation spectrum.
|
|
| 227. |
- Schiött, Åsa, et al.
(författare)
-
CD27- CD4+ memory T cells define a differentiated memory population at both the functional and transcriptional levels
- 2004
-
Ingår i: Immunology. - : Wiley. - 0019-2805 .- 1365-2567. ; 113:3, s. 363-370
-
Tidskriftsartikel (refereegranskat)abstract
- The memory T-cell population is a heterogeneous population, including both effector cells, which exert a direct secondary immune response, and resting or intermediate cells, which serve as a reservoir and exert a possible regulatory role. To further dissect the T-cell memory population residing in the CD4 +CD45RO+ T-cell pool, we studied the functional properties of memory populations identified by the CD27 marker. This marker clearly divides the memory population into two groups. One group consists of effector cells lacking CD27 and displaying a high antigen recall response. The other group consists of an intermediate memory population, displaying CD27. This latter group lacks an antigen recall response and requires costimulation for T-cell receptor triggering. To evaluate the function of the CD27+ memory pool, we analysed the transcriptional profile, using high-density microarray technology. These gene data strongly support the different functional profiles of CD27+ and CD27+ memory populations, in terms of protein expression and the capacity to respond to antigen.
|
|
| 228. |
- Sekula, Sylwia, et al.
(författare)
-
Multiplexed Lipid Dip-Pen Nanolithography on Subcellular Scales for the Templating of Functional Proteins and Cell Culture
- 2008
-
Ingår i: Small. - : Wiley. - 1613-6829 .- 1613-6810. ; 4:10, s. 1785-1793
-
Tidskriftsartikel (refereegranskat)abstract
- Molecular patterning processes taking place in biological systems are challenging to study in vivo because of their dynamic behavior, subcellular size, and high degree of complexity. In vitro patterning of biomolecules using nanolithography allows simplification of the processes and detailed study of the dynamic interactions. Parallel dip-pen nanolithography (DPN) is uniquely capable of integrating functional biomolecules on subcellular length scales due to its constructive nature, high resolution, and high throughput. Phospholipids are particularly well suited as inks for DPN since a variety of different functional lipids can be readily patterned in parallel. Here DPN is used to spatially pattern multicomponent micro- and nano-structured supported lipid membranes and multilayers that are fluid and contain various amounts of biotin and/or nitrilotriacetic acid functional groups. The patterns are characterized by fluorescence microscopy and photoemission electron microscopy. Selective adsorption of functionalized or recombinant proteins based on streptavidin or histidine-tag coupling enables the semisynthetic fabrication of model peripheral membrane bound proteins. The biomimetic membrane patterns formed in this way are then used as substrates for cell culture, as demonstrated by the selective adhesion and activation of T-cells.
|
|
| 229. |
- Sernbo, Sandra, et al.
(författare)
-
Nuclear T-STAR Protein Expression Correlates with HER2 Status, Hormone Receptor Negativity and Prolonged Recurrence Free Survival in Primary Breast Cancer and Decreased Cancer Cell Growth In Vitro
- 2013
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:7, s. e70596-
-
Tidskriftsartikel (refereegranskat)abstract
- T-STAR (testis-signal transduction and activation of RNA) is an RNA binding protein, containing an SH3-binding domain and thus potentially playing a role in integration of cell signaling and RNA metabolism. The specific function of T-STAR is unknown and its implication in cancer is poorly characterized. Expression of T-STAR has been reported in human testis, muscle and brain tissues, and is associated with a growth-inhibitory role in immortalized fibroblasts. The aim of this paper was to investigate the functional role of T-STAR through (i) survival analysis of patients with primary invasive breast cancer and (ii) experimental evaluation of the effect of T-STAR on breast cancer cell growth. T-STAR protein expression was analysed by immunohistochemistry (IHC) in tissue microarrays with tumors from 289 patients with primary invasive breast cancer, and correlations to clinicopathological characteristics, recurrence-free and overall survival (RFS and OS) and established tumor markers such as HER2 and ER status were evaluated. In addition, the function of T-STAR was investigated using siRNA-mediated knock-down and overexpression of the gene in six breast cancer cell lines. Of the tumors analysed, 86% showed nuclear T-STAR expression, which was significantly associated with an improved RFS and strongly associated with positive HER2 status and negative hormone receptor status. Furthermore, experimental data showed that overexpression of T-STAR decreased cellular growth while knock-down increased it, as shown both by thymidine incorporation and metabolic activity. In summary, we demonstrate that T-STAR protein expression correlates with an improved RFS in primary breast cancer. This is supported by functional data, indicating that T-STAR regulation is of importance both for breast cancer biology and clinical outcome but future studies are needed to determine a potential role in patient stratification.
|
|
| 230. |
- Sernbo, Sandra, et al.
(författare)
-
The tumour suppressor SOX11 is associated with improved survival among high grade epithelial ovarian cancers and is regulated by reversible promoter methylation
- 2011
-
Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The neural transcription factor SOX11 has been described as a prognostic marker in epithelial ovarian cancers (EOC), however its role in individual histological subtypes and tumour grade requires further clarification. Furthermore, methylation-dependent silencing of SOX11 has been reported for B cell lymphomas and indicates that epigenetic drugs may be used to re-express this tumour suppressor, but information on SOX11 promoter methylation in EOC is still lacking. Methods: SOX11 expression and clinicopathological data was compared using chi(2) test in a cohort of 154 cases of primary invasive EOC. Kaplan-Meier analysis and the log rank test were applied to evaluate ovarian cancer-specific survival (OCSS) and overall survival (OS) in strata, according to SOX11 expression. Also, the methylation status of the SOX11 promoter was determined by sodium bisulfite sequencing and methylation specific PCR (MSP). Furthermore, the effect of ectopic overexpression of SOX11 on proliferation was studied through [3H]-thymidine incorporation. Results: SOX11 expression was associated with an improved survival of patients with high grade EOC, although not independent of stage. Further analyses of EOC cell lines showed that SOX11 mRNA and protein were expressed in two of five cell lines, correlating with promoter methylation status. Demethylation was successfully performed using 5'-Aza-2'deoxycytidine (5-Aza-dC) resulting in SOX11 mRNA and protein expression in a previously negative EOC cell line. Furthermore, overexpression of SOX11 in EOC cell lines confirmed the growth regulatory role of SOX11. Conclusions: SOX11 is a functionally associated protein in EOC with prognostic value for high-grade tumours. Re-expression of SOX11 in EOC indicates a potential use of epigenetic drugs to affect cellular growth in SOX11-negative tumours.
|
|
