| 1. |
- Svensson, Maria C, et al.
(author)
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High infiltration of CD68+/CD163- macrophages is an adverse prognostic factor after neoadjuvant chemotherapy in esophageal and gastric adenocarcinoma
- 2022
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In: Journal of Innate Immunity. - : S. Karger AG. - 1662-811X .- 1662-8128. ; 14:6, s. 615-628
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Journal article (peer-reviewed)abstract
- Tumor-associated macrophages (TAMs) have emerged as key players in tumor immunology but demonstrate a continuum of functional states being either tumor suppressive or promoting. Moreover, chemotherapeutic agents have been shown to alter the tumor microenvironment. Perioperative chemotherapy is a standard treatment option for resectable esophageal and gastric (EG) adenocarcinoma. The aim of this study was to investigate the influence of neoadjuvant chemotherapy (NAC) on TAMs to improve the prognostication and treatment course for these patients. The study cohort comprised 148 patients, all of whom were diagnosed with resectable EG adenocarcinoma and treated with NAC. Immunohistochemistry was applied to assess the total infiltration and infiltration into tumor nests (TN) of CD68+/CD163−, CD68+/CD163+, and MARCO+ TAMs, on paired biopsies from primary tumors (PT) pre-NAC, and resected PT and lymph node metastases post-NAC. In pre-NAC specimens, high CD68+/CD163+ infiltration into TN was an unfavorable prognostic factor. No association was found between TAM density in PT pre-NAC and histopathological regression. The density of CD68+/CD163+ TAMs was increased in PT post-NAC, while the density of MARCO+ TAMs was decreased. CD68+/CD163− TAM density was not altered. In post-NAC specimens, higher total as well as TN infiltration of CD68+/CD163−TAMs were adverse prognostic factors. In conclusion, these results suggest that NAC may alter certain TAM subsets in EG adenocarcinoma, along with their functional properties and thus their prognostic value.
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| 2. |
- Broberg, Karin, et al.
(author)
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Evaluation of 92 cardiovascular proteins in dried blood spots collected under field-conditions : Off-the-shelf affinity-based multiplexed assays work well, allowing for simplified sample collection
- 2021
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In: BioEssays. - : Wiley. - 0265-9247 .- 1521-1878. ; 43:9
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Journal article (peer-reviewed)abstract
- Workplace-collected blood spots deposited on filter paper were analysed with multiplexed affinity-based protein assays and found to be suitable for proteomics analysis. The protein extension assay (PEA) was used to characterize 92 proteins using 1.2 mm punches in repeated samples collected from 20 workers. Overall, 97.8% of the samples and 91.3% of the analysed proteins passed quality control. Both within and between spot correlations using six replicates from the same individual were above 0.99, suggesting that comparable levels are obtained from multiple punches from the same spot and from consecutive spots. Protein levels from dried blood and wet serum from the same individuals were compared and the majority of the analysed proteins were found to be significantly correlated. These results open up for simplified sample collection of blood in field conditions for proteomic analysis, but also highlight that not all proteins can be robustly measured from dried whole blood.
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| 3. |
- Fhager, Johan, et al.
(author)
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The hairdex quality of life instrument : a translation and psychometric validation in patients with alopecia areata
- 2023
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In: Skin Health and Disease. - : John Wiley & Sons. - 2690-442X. ; 3:3
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Journal article (peer-reviewed)abstract
- Background: The German Hairdex quality of life (QoL) instrument is specific to hair and scalp diseases, developed for self-rating and consists of 48 statements divided into five domains: Symptoms, Functioning, Emotions, Self-confidence and Stigmatisation. There was a need of a Swedish reliability tested, validated hair and scalp specific QoL instrument why the German Hairdex was chosen to be translated and reliability tested in a systematic way.Objectives: To make a translation, a reliability test of stability, and validation of the German Hairdex QoL instrument among 100 Swedish patients with a dermatological ICD-10 diagnosis of alopecia areata (AA).Methods: An eight-step method by Gudmundsson was used as a model with a forward and backward translation and with comments from an expert panel. A statistical test–retest (ICC (2,1)) analysis was made, followed by an internal consistency analysis. A comparison between the German and Swedish Hairdex-S constructs by a principal component analysis was performed.Results: The Hairdex-S was very well accepted by patients. The ICC(2,1) test–retest showed a good to excellent correlation of 0.91 (CI [0.85–0.95]). Internal consistency was α = 0.92. Like the original Hairdex, Hairdex-S showed good factorability with a Kaiser–Meyer–Olkin measure of 0.82 and with one component explaining 70% of the variance: original Hairdex instrument (69%). When tested on patients with AA, the domains Functioning and Emotions had the strongest loadings, followed by Stigmatisation and Self-confidence. Younger AA patients at self-assessment and patients who reported to be younger at the onset of AA, scored statistically significantly higher on the Hairdex-S, indicating an overall lower QoL on domains Emotions and Functioning, respectively.Conclusions: The Hairdex-S is very well accepted by AA patients, shows very good psychometric properties, and a very good agreement with the original Hairdex. The Swedish Hairdex instrument can be recommended for evaluation of patients QoL as well as for research purposes.
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| 4. |
- Glantz, Maria, et al.
(author)
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Impact of protease and lipase activities on quality of Swedish raw milk
- 2020
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In: International Dairy Journal. - : Elsevier BV. - 0958-6946. ; 107
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Journal article (peer-reviewed)abstract
- An increasing demand for dairy products with long shelf-life is foreseen. A limiting factor for maintaining high quality of these products is the activity of spoilage enzymes during storage. Lipase and protease activities in Swedish raw milk at farm and dairy level were investigated, analysing milk samples from three geographical regions and two seasons. Lipase activity in milk at farm level was affected by regional and seasonal variations, whereas at dairy level only season had an effect. Lipase activity was positively correlated with ionic calcium. For protease activity, no effect of either region or season was seen. Degradation products, e.g., free fatty acids, peptides and plasmin proteolysis products, varied differently between season and geographical origin at both farm and dairy level. The results indicate that lipase and protease activities are important for raw milk quality, while ionic calcium might be a future indicator for milk fat stability.
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| 5. |
- Gyllensten, Ulf B., et al.
(author)
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Next Generation Plasma Proteomics Identifies High-Precision Biomarker Candidates for Ovarian Cancer
- 2022
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In: Cancers. - : MDPI AG. - 2072-6694. ; 14:7
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Journal article (peer-reviewed)abstract
- Simple Summary Ovarian cancer is the eighth most common cancer among women and has a 5-year survival of only 30-50%. The survival is close to 90% for patients in stage I but only 20% for patients in stage IV. The presently available biomarkers have insufficient sensitivity and specificity for early detection and there is an urgent need to identify novel biomarkers. The aim of our study was to broadly measure protein biomarkers to find tests for the early detection of ovarian cancer. We found that combinations of 4-7 protein biomarkers can provide highly accurate detection of early- and late-stage ovarian cancer compared to benign conditions. The performance of the tests was then validated in a second independent cohort. Background: Ovarian cancer is the eighth most common cancer among women and has a 5-year survival of only 30-50%. The survival is close to 90% for patients in stage I but only 20% for patients in stage IV. The presently available biomarkers have insufficient sensitivity and specificity for early detection and there is an urgent need to identify novel biomarkers. Methods: We employed the Explore PEA technology for high-precision analysis of 1463 plasma proteins and conducted a discovery and replication study using two clinical cohorts of previously untreated patients with benign or malignant ovarian tumours (N = 111 and N = 37). Results: The discovery analysis identified 32 proteins that had significantly higher levels in malignant cases as compared to benign diagnoses, and for 28 of these, the association was replicated in the second cohort. Multivariate modelling identified three highly accurate models based on 4 to 7 proteins each for separating benign tumours from early-stage and/or late-stage ovarian cancers, all with AUCs above 0.96 in the replication cohort. We also developed a model for separating the early-stage from the late-stage achieving an AUC of 0.81 in the replication cohort. These models were based on eleven proteins in total (ALPP, CXCL8, DPY30, IL6, IL12, KRT19, PAEP, TSPAN1, SIGLEC5, VTCN1, and WFDC2), notably without MUCIN-16. The majority of the associated proteins have been connected to ovarian cancer but not identified as potential biomarkers. Conclusions: The results show the ability of using high-precision proteomics for the identification of novel plasma protein biomarker candidates for the early detection of ovarian cancer.
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| 6. |
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| 7. |
- Jeremiasen, Martin, et al.
(author)
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Tumor-Associated CD68+, CD163+, and MARCO+ Macrophages as Prognostic Biomarkers in Patients With Treatment-Naïve Gastroesophageal Adenocarcinoma
- 2020
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In: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 10
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Journal article (peer-reviewed)abstract
- Background: Despite improvements in surgical methodologies and perioperative chemo- and radiotherapy, the prognosis for patients with esophageal and gastric cancer remains poor. Hence, there is a great need to identify complementary biomarkers for improved treatment stratification. Tumor-infiltrating immune cells have been shown to impact on outcome in many types of cancer, including gastroesophageal cancer. The aim of this present study was to examine the prognostic value of tumor-infiltrating macrophages in gastroesophageal adenocarcinoma. Methods: The density of CD68+, CD163+, and MARCO+ macrophages was assessed by immunohistochemistry on tissue microarrays with primary tumors from a consecutive, retrospective cohort of 174 patients with treatment-naïve gastroesophageal adenocarcinoma. Total densities and infiltration in tumor nest (TN) were denoted as none/sparse (0), intermediate (1), or high (2). The impact on overall survival (OS) was examined by Kaplan–Meier analysis, log-rank test, and Cox proportional hazards modeling. Results: Increased infiltration of both CD68+ and CD163+, but not MARCO+, macrophages in TN was significantly associated with a stepwise reduced survival. Median OS for patients with none/sparse, intermediate, and high CD68+ TN infiltration was 4.4, 2.6, and 1.0 years, respectively. Median OS for patients with none/sparse, intermediate, and high CD163+ TN infiltration was 4.4, 2.2, and 1.1 years, respectively. High infiltration of CD68+ macrophages remained an independent prognostic factor in adjusted analysis (hazard ratio = 1.61, 95% confidence interval = 1.02–2.55, and p = 0.041). Conclusion: Infiltration of CD68+ and CD163+, but not MARCO+, macrophages is prognostic for OS in gastroesophageal adenocarcinoma. The relevance of this finding in clinical practice remains to be elucidated.
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| 8. |
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| 9. |
- Stockfelt, Marit, et al.
(author)
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Activated low-density granulocytes in peripheral and intervillous blood and neutrophil inflammation in placentas from SLE pregnancies
- 2021
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In: Lupus Science and Medicine. - : BMJ. - 2053-8790. ; 8:1
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Journal article (peer-reviewed)abstract
- Objective Women with SLE face an increased risk of adverse pregnancy outcomes compared with healthy women, but the underlying immunological mechanisms are unknown. Given the recognised association of neutrophil activation with SLE pathogenesis, we examined whether there is increased neutrophil activation and inflammation in blood and placenta in SLE relative to healthy pregnancy. Methods At delivery, peripheral blood, maternal-derived intervillous blood and placentas were collected from 12 SLE and 10 healthy control pregnancies. The proportion of low-density granulocytes (LDGs) and the activation status of LDG and normal-density granulocytes were examined with flow cytometry. The chemokines CXCL8 and CXCL1 were quantified with a cytometric bead-based assay and interferon alpha (IFNα) protein levels with a Simoa method. IFNα-stimulated maternal-derived decidual stromal cells were examined for CXCL8 gene expression with qPCR. A pathologist, blinded to the patient background, examined all placentas. Results Women with SLE had significantly higher proportions of LDG in peripheral blood compared with controls (p=0.02), and LDG in both peripheral and intervillous blood were more activated in SLE relative to healthy pregnancies (peripheral blood: p=0.002 and intervillous blood: p=0.05). There were higher levels of CXCL8 and CXCL1 in intervillous compared with peripheral blood in women with SLE (p=0.004 and p=<0.0001, respectively) but not in controls. In SLE pregnancy, IFNα was detectable in 6 out of 10 intervillous blood samples but only in one control. Stimulation with IFNα upregulated CXCL8 gene expression in decidual stromal cells from both SLE and healthy pregnancy. Histological chorioamnionitis was present in 6 out of 12 placentas from women with SLE and in 1 out of 10 controls. Conclusions In women with SLE, locally produced chemokines in the placenta are increased and may attract and activate neutrophils. This in turn could contribute to placental inflammation and dysfunction and increased risk of placenta-related pregnancy complications.
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| 10. |
- Svensson, Maria Christina, et al.
(author)
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T cells, B cells, and PD-L1 expression in esophageal and gastric adenocarcinoma before and after neoadjuvant chemotherapy : relationship with histopathological response and survival
- 2021
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In: OncoImmunology. - 2162-4011. ; 10:1
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Journal article (peer-reviewed)abstract
- Perioperative chemotherapy enhances the survival rates for patients with esophageal and gastric (EG) adenocarcinoma, but not all patients benefit from this additional treatment. Chemotherapeutic agents have been demonstrated to alter the immune cell (IC) composition in the tumor microenvironment. Hence, there is a rationale to investigate the influence of neoadjuvant chemotherapy (NAC) on different IC subsets, to better understand and compare their utility as complementary prognostic or predictive biomarkers in a clinically relevant context. The density of T cells (CD8+ and FoxP3+), B cells (CD20+) and the expression of PD-L1 on ICs and tumor cells (TC) was assessed by immunohistochemistry on paired biopsies from primary tumors (PT) pre-NAC, and resected PT and lymph node metastases post-NAC. The cohort encompasses 148 patients with resectable EG adenocarcinoma, all of whom received NAC. The density of CD8+ cells was decreased and the density of FoxP3+ cells and CD20+ cells was increased in PT post-NAC. PD-L1 expression was not altered following NAC. In pre-NAC specimens, high FoxP3+ density and high PD-L1 expression on ICs were favorable prognostic factors, whereas high CD8+ density was an unfavorable prognostic factor. In post-NAC specimens, however, high FoxP3+ density was an unfavorable prognostic factor, and high PD-L1 expression on TC was associated with a shorter survival. There were no significant associations between IC density or PD-L1 expression in PT pre-NAC and histopathological regression. These findings propose that NAC might alter the density and prognostic impact of some IC subsets in EG adenocarcinoma.
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