Studentbloggens i sitt sammanhang – En studie av tio studentbloggar, deras tema och utformning på tre olika universitet

Titel: Studentbloggens i sitt sammanhang – En studie av tio studentbloggar, deras tema och utformning på tre olika universitet Författare: Lisa Bergenfelz Uppdragsgivare: Institutionen för journalistik, medier och kommunikation vid Göteborgs Universitet (JMG) Kurs: Examensarbete i medie- och kommunikationsvetenskap. Institutionen för journalistik, medier och kommunikation, Göteborgs universitet Termin: Vårterminen 2012 Handledare: Ulrika Andersson Sidantal/Antal ord: 44 sidor/15 487 ord inklusive källförteckning samt bilagor. Syfte: Syftet med studien är att göra en genomlysning av olika former av studentbloggar som återfinns på universitet i Sverige för att skapa förståelse hur det fungerar då ett personligt medium används inom en organisatorisk kontext. Metod: Kvalitativ innehållsanalys av studentbloggar med hjälp av Ethnographic Content Analysis (ECA). Material: Tio utvalda studentbloggar ifrån Linköpings Universitet, Karlstad Universitet och Uppsala Universitet. Huvudresultat: Arbetet med studentbloggar skilde sig åt mellan de tre universiteten. De hade olika former av avtal med studenterna som bloggade, publiceringsplattform skilde sig åt och presentationen av studentbloggen på hemsidan varierade. Detta påverkade studentbloggens sammanhang och hur anknuten studentbloggen var till universitetet. Detta påverkade vilket tema som bloggen behandlade. De studentbloggar som hade en närmare anknytning till universitetet behandlade i större grad universitetsrelaterade ämnen i sina bloggar än de studentbloggar som hade en svagare anknytning till sitt universitet. Detta påvisar att bloggen är beroende av dess sammanhang. Däremot visade det sig även att det fanns en likhet i hur de tio studentbloggarna utformades på de tre universiteten. Studentbloggarna användande sig av olika tekniska funktioner på liknande vis. Det kom till uttryck i en liknande hantering av bilder och länkar i blogginlägg och liknande användning av kategorier, arkiv och länkar i marginalen på bloggen. Resultaten visar på att studentbloggens tema och utformning påverkas av sin anknytning till universitetet men även av hur studenten är bunden av rollen som bloggare vilket tar sig i uttryck i anpassningen efter en gemensam bloggpraktik hos studentbloggarna. Tillsammans påverkar detta hur studentbloggen utformas

Gene expression in metastatic breast cancer—patterns in primary tumors and metastatic tissue with prognostic potential

Background: Metastatic breast cancer (MBC) is the main cause of breast cancer-related death. The outcome of MBC varies, and there is a lack of biomarkers to aid in prognostication. The primary aim of this study was to evaluate the prognostic value of gene expression (GEX) signatures in the primary tumor (PT) and distant metastasis (DM) for progression-free survival (PFS) and overall survival (OS). The secondary aim was to describe GEX changes through MBC evolution and to identify MBC subtypes.Methods: RNA was extracted from the PT, lymph node metastasis (LNM), and DM from MBC patients in a prospective observational study (n = 142; CTC-MBC NCT01322893) and was subjected to GEX analysis retrospectively using the NanoString Breast Cancer 360™ panel. 31 continuous GEX variables in DMs and PTs were analyzed for PFS and OS by Cox regression analysis and Kaplan-Meier estimates. Multivariable Cox regressions were adjusted for number of DM sites and CTCs, visceral metastasis, ECOG status, age at MBC diagnosis and, in additional analyses, PAM50 subtype. Differential GEX analyses and Euclidean distances were used to describe subgroup differences and visualize within-patient heterogeneity.Results: Compared to DM GEX, GEX of the PT was at least equally useful for predicting MBC outcome. The strongest marker for a favorable PFS, both when expressed in the PT and the DM was AR, even after adjustment for prognostic markers including PAM50. GEX signatures related to hormone responsiveness, including ESR1, FOXA1, PGR, and AR were favorable prognostic markers, and the p53 signature was unfavorable for PFS when expressed in PT or DM. The previously published PAM50MET signature was prognostic for both PFS and OS. We established five distinct DM GEX profiles where two associated with liver and bone metastases, respectively. Finally, we identified four DM GEX profiles able to identify MBCs with poor OS in this cohort.Conclusion: GEX of both DM and PT are useful in MBC prognostication. GEX of AR adds prognostic information for MBC. Our descriptive analyses illuminate the biological differences between MBCs in relation to outcome and metastatic site

Peripheral Blood Mononuclear Cell Populations Correlate with Outcome in Patients with Metastatic Breast Cancer

Local tumor-associated immune cells hold prognostic and predictive value in various forms of malignancy. The role of systemic, circulating leukocytes is, however, not well-characterized. In this prospective and explorative study, we aim to delineate the clinical relevance of a broad panel of circulating immune cells in 32 patients with newly diagnosed metastatic breast cancer (MBC) before the start of systemic treatment. Freshly isolated peripheral blood mononuclear cells (PBMCs) were analyzed by flow cytometry and evaluated for potential associations to clinicopathological variables and patient outcome. We show that the levels of specific circulating leukocyte populations are associated with clinical parameters such as hormone receptor status, histological subtype, number of circulating tumor cells (CTCs) and metastatic burden. Importantly, high levels of CD8+ cytotoxic T lymphocytes (CTLs) are significantly linked to improved overall survival (OS). In patients with estrogen receptor (ER)-positive primary tumors, high levels of circulating CTLs and non-classical (CD14+CD16++) monocytes were associated with improved OS, whereas in patients with ER-negative tumors low levels of circulating natural killer (NK) cells potentially associate with improved OS. We propose that the levels of specific circulating immune cell populations, such as CD8+ CTLs, may be used to predict clinical outcomes in MBC patients. Thus, larger studies are warranted to validate these findings

Serum immuno-oncology markers carry independent prognostic information in patients with newly diagnosed metastatic breast cancer, from a prospective observational study

Background: Metastatic breast cancer (MBC) is a challenging disease, and despite new therapies, prognosis is still poor for a majority of patients. There is a clinical need for improved prognostication where immuno-oncology markers can provide important information. The aim of this study was to evaluate serum immuno-oncology markers in MBC patients and their respective relevance for prediction of survival. Patients and methods: We investigated a broad panel of 92 immuno-oncology proteins in serum from 136 MBC patients included in a prospective observational study (NCT01322893) with long-term follow-up. Serum samples were collected before start of systemic therapy and analyzed using multiplex proximity extension assay (Olink Target 96 Immuno-Oncology panel). Multiple machine learning techniques were used to identify serum markers with highest importance for prediction of overall and progression-free survival (OS and PFS), and associations to survival were further evaluated using Cox regression analyses. False discovery rate was then used to adjust for multiple comparisons. Results: Using random forest and random survival forest analyses, we identified the top nine and ten variables of highest predictive importance for OS and PFS, respectively. Cox regression analyses revealed significant associations (P < 0.005) of higher serum levels of IL-8, IL-10 and CAIX with worse OS in multivariable analyses, adjusted for established clinical prognostic factors including circulating tumor cells (CTCs). Similarly, high serum levels of IL-8, IL-10, ADA and CASP8 significantly associated with worse PFS. Interestingly, high serum levels of FasL significantly associated with improved OS and PFS. In addition, CSF-1, IL-6, MUC16, TFNSFR4 and CD244 showed suggestive evidence (P < 0.05) for an association to survival in multivariable analyses. After correction for multiple comparisons, IL-8 still showed strong evidence for correlation to survival. Conclusion: To conclude, we found six serum immuno-oncology markers that were significantly associated with OS and/or PFS in MBC patients, independently of other established prognostic factors including CTCs. Furthermore, an additional five serum immuno-oncology markers provided suggestive evidence for an independent association to survival. These findings highlight the relevance of immuno-oncology serum markers in MBC patients and support their usefulness for improved prognostication. Trial registration Clinical Trials (NCT01322893), registered March 25, 2011

A high frequency of MDSCs in sepsis patients, with the granulocytic subtype dominating in gram-positive cases.

The causative microorganisms dictate the type of MDSC generated in sepsis patients, and a large proportion of PMN-MDSCs in gram-positive sepsis includes immunosuppressive myeloid blasts. MDSCs constitute a heterogeneous population of immature myeloid cells that potently suppress immune responses. They were identified originally in cancer patients and have since been reported to occur also in chronic inflammation, autoimmunity, and even bacterial infections. Human MDSCs are commonly divided into Mo-MDSCs and granulocytic (PMN-MDSCs) subtypes. To what extent the bona fide cancer MDSCs are representative of the proposed MDSCs found in other diseases is not well known. PMN-MDSCs have been found previously to be enriched among LDGs in density gradient-centrifuged blood. In this study, we analyzed potential MDSCs in sepsis patients with different causative microorganisms, using total peripheral blood compared with density gradient-centrifuged blood. We found a high frequency of typical CD14(+)HLA-DR(low) Mo-MDSCs in all sepsis patients, whereas the typical PMN-MDSCs, as well as a prominent CD14(low) PMN-MDSC-like population, appeared preferentially in gram-positive cases. The CD14(low) PMN-MDSC variant was demonstrated to suppress T cell proliferation in vitro via a ROS-dependent mechanism, to display an increased IL-10:TNF-α ratio, and to present with signs of immaturity: blast morphology and low cytokine levels. We conclude that a spectrum of cells with MDSC features is enriched in sepsis and that the microbial origin of sepsis contributes to the substantial interindividual patient variation in the MDSC pattern

Systemic Monocytic-MDSCs Are Generated from Monocytes and Correlate with Disease Progression in Breast Cancer Patients.

Myeloid-derived suppressor cells (MDSCs) are highly immunosuppressive myeloid cells, which increase in cancer patients. The molecular mechanism behind their generation and function is unclear. Whereas granulocytic-MDSCs correlate with poor overall survival in breast cancer, the presence and relevance of monocytic-MDSCs (Mo-MDSCs) is unknown. Here we report for the first time an enrichment of functional blood Mo-MDSCs in breast cancer patients before they acquire a typical Mo-MDSC surface phenotype. A clear population of Mo-MDSCs with the typical cell surface phenotype (CD14+HLA-DRlow/-CD86low/-CD80low/-CD163low/-) increased significantly first during disease progression and correlated to metastasis to lymph nodes and visceral organs. Furthermore, monocytes, comprising the Mo-MDSC population, from patients with metastatic breast cancer resemble the reprogrammed immunosuppressive monocytes in patients with severe infections, both by their surface and functional phenotype but also at their molecular gene expression profile. Our data suggest that monitoring the Mo-MDSC levels in breast cancer patients may represent a novel and simple biomarker for assessing disease progression

Increased frequency of Mo-MDSCs (CD14⁺HLA-DR^low/-Co-receptor^low/-) in patients with advanced breast cancer.

<p>Flow cytometric analyzes of freshly isolated PBMCs from healthy controls (HC), patients with early breast cancer (BC), patients with advanced breast cancer (LRR/MBC) and patients with sepsis. (<b>A</b>) The box plots represent the percentage of CD14⁺HLA-DR^low/- Mo-MDSC of PBMCs or (<b>B</b>) within total CD14⁺ monocyte population, HC <i>n</i> = 13, Early BC <i>n</i> = 10, LRR/MBC <i>n</i> = 25 and sepsis <i>n</i> = 18. Statistics were performed using Mann-Whitney Wilcoxon test. * p < 0.05, ** p < 0.01, *** p < 0.001. (<b>C</b>) Relative expression (mean fluorescence intensity; MFI) of co-receptors on CD14⁺HLA-DR^low/- monocytes from patients with LRR/MBC (grey) or sepsis (white) compared to CD14⁺HLA-DR⁺⁺monocytes. Co-receptor expression on CD14⁺HLA-DR⁺⁺ cells put to 1. Columns, mean; bars, SEM. Students t-test ** p < 0.01, *** p < 0.001. (<b>D</b>) T cell proliferation (CPM) <i>in vitro</i> at stimulator:responder ratio 0.01:1 correlates inversely with the percentage of Mo-MDSC within total CD14⁺ monocyte population. LRR/MBC <i>n</i> = 9, Spearman’s rho correlation.</p

Mo-MDSCs are enriched in a subpopulation of patients with locoregional recurrence or metastatic breast cancer.

<p>(<b>A-C</b>) Flow cytometric analyzes of freshly isolated PBMCs from healthy controls (HC), patients with locoregional recurrence or metastatic breast cancer (LRR/MBC) or sepsis. The box plots represents the variation in respective cell population as percentage (%) of PBMCs. Cutoff into “normal” or “high” levels of Mo-MDSCs were based on the highest healthy control value. (A) Percentage of CD14+HLA-DRlow/- monocytes of PBMCs (HC <i>n</i> = 13, LRR/MBC “normal” <i>n</i> = 13, LRR/MBC “high” <i>n</i> = 12, Sepsis <i>n</i> = 18) or (B) within total CD14+ monocyte population (HC <i>n</i> = 13, LRR/MBC “normal” <i>n</i> = 13, LRR/MBC “high” <i>n</i> = 12, Sepsis <i>n</i> = 18). (C) Percentage of total CD14+ monocyte of PBMCs. HC <i>n</i> = 13, LRR/MBC “normal” <i>n</i> = 17, LRR/MBC “high” <i>n</i> = 8, Sepsis <i>n</i> = 18. (<b>D</b>) Cartoon presenting proposed frequencies of relevant systemic myeloid cell populations with disease progression. Abbreviations: Monocytes, Mo; Monocytic-MDSC, Mo-MDSC; granulocytic-MDSC, G-MDSC.</p