| 1. |
- Bignert, Anders, et al.
(författare)
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Övervakning av metaller och organiska miljögifter i marin biota, 2011
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The environmental toxicants examined in this report can be classified into five groups –heavy metals, chlorinated compounds, brominated flame retardants, polyaromatichydrocarbons and perfluorinated compounds. Each of these contaminants has beenexamined from various sites for up to six different fish species, in blue mussels, and inguillemot eggs, for varying lengths of time. The following summary examines overalltrends, spatial and temporal, for the five groups.Condition and Fat ContentCondition and fat content in different species tended to follow the same pattern at the samesites, with a few exceptions. Most of the fish species generally displayed a decreasing trendin both condition and fat content at most sites examined. Exceptions to this were increasesin fat content seen in herring (the last ten years) and cod at Fladen; an increase in conditionfor herring at Ängskärsklubb in spring; and in perch, a decrease in fat content atKvädöfjärden but no trend in condition for the same site.Heavy MetalsDue to a change in methods for metal analysis (not Hg) in 2004, values between 2003 and2007 should be interpreted with care. From 2009 metals are analyzed at ITM, Stockholmuniversity.The longer time series in guillemot egg and spring-caught herring from the southernBothnian Sea and southern Baltic Proper show significant decreases of mercury. Theherring site in the southern Bothnain Sea indicates a local Hg-source. The rest of the timeseries show varying concentrations over the study period, and even increasing trends in e.g.cod muscle and blue mussels, but the concentrations are fairly low compared to measuredconcentrations in perch from fresh water and coastal sites. However, in most cases, theseconcentrations are above the newly suggested EU-target level of 20 ng/g wet weight.Lead is generally decreasing over the study period (in time series of sufficient length),supposedly due to the elimination of lead in gasoline. Elevated lead concentrations between2003 and 2007 (e.g. Harufjärden) should be viewed with caution (see above regardingchange in analysis methods).Cadmium concentrations show varying non-linear trends over the monitored period. It isworth noting that despite several measures taken to reduce discharges of cadmium,generally the most recent concentrations are similar to concentrations measured 30 yearsago in the longer time series.The reported nickel concentrations show no consistent decreasing trends. Some series beginwith two elevated values that exert a strong leverage effect on the regression line and maygive a false impression of decreasing trends. Chromium generally shows decreasing trends,possibly explained by a shift in analytical method. The essential trace metals, copper andzinc, show no consistent trends during the monitored period.
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| 2. |
- Hedegaard, Jakob, et al.
(författare)
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Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma
- 2016
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Ingår i: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 30:1, s. 27-42
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Tidskriftsartikel (refereegranskat)abstract
- Non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease with widely different outcomes. We performed a comprehensive transcriptional analysis of 460 early-stage urothelial carcinomas and showed that NMIBC can be subgrouped into three major classes with basal-and luminal-like characteristics and different clinical outcomes. Large differences in biological processes such as the cell cycle, epithelial-mesenchymal transition, and differentiation were observed. Analysis of transcript variants revealed frequent mutations in genes encoding proteins involved in chromatin organization and cytoskeletal functions. Furthermore, mutations in well-known cancer driver genes (e.g., TP53 and ERBB2) were primarily found in high-risk tumors, together with APOBEC-related mutational signatures. The identification of subclasses in NMIBC may offer better prognostication and treatment selection based on subclass assignment.
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| 3. |
- Jeremiasen, Martin, et al.
(författare)
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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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Ingår i: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 10
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Tidskriftsartikel (refereegranskat)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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| 4. |
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| 5. |
- Lindquist, Kajsa Ericson, et al.
(författare)
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Clinical framework for next generation sequencing based analysis of treatment predictive mutations and multiplexed gene fusion detection in non-small cell lung cancer
- 2017
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 8:21, s. 34796-34810
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Tidskriftsartikel (refereegranskat)abstract
- Precision medicine requires accurate multi-gene clinical diagnostics. We describe the implementation of an Illumina TruSight Tumor (TST) clinical NGS diagnostic framework and parallel validation of a NanoString RNA-based ALK, RET, and ROS1 gene fusion assay for combined analysis of treatment predictive alterations in non-small cell lung cancer (NSCLC) in a regional healthcare region of Sweden (Scandinavia). The TST panel was clinically validated in 81 tumors (99% hotspot mutation concordance), after which 533 consecutive NSCLCs were collected during one-year of routine clinical analysis in the healthcare region (~90% advanced stage patients). The NanoString assay was evaluated in 169 of 533 cases. In the 533-sample cohort 79% had 1-2 variants, 12% >2 variants and 9% no detected variants. Ten gene fusions (five ALK, three RET, two ROS1) were detected in 135 successfully analyzed cases (80% analysis success rate). No ALK or ROS1 FISH fusion positive case was missed by the NanoString assay. Stratification of the 533-sample cohort based on actionable alterations in 11 oncogenes revealed that 66% of adenocarcinomas, 13% of squamous carcinoma (SqCC) and 56% of NSCLC not otherwise specified harbored ≥1 alteration. In adenocarcinoma, 10.6% of patients (50.3% if including KRAS) could potentially be eligible for emerging therapeutics, in addition to the 15.3% of patients eligible for standard EGFR or ALK inhibitors. For squamous carcinoma corresponding proportions were 4.4% (11.1% with KRAS) vs 2.2%. In conclusion, multiplexed NGS and gene fusion analyses are feasible in NSCLC for clinical diagnostics, identifying notable proportions of patients potentially eligible for emerging molecular therapeutics.
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| 6. |
- Mezheyeuski, Artur, et al.
(författare)
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An immune score reflecting pro- and anti-tumoural balance of tumour microenvironment has major prognostic impact and predicts immunotherapy response in solid cancers
- 2023
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 88
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cancer immunity is based on the interaction of a multitude of cells in the spatial context of the tumour tissue. Clinically relevant immune signatures are therefore anticipated to fundamentally improve the accuracy in predicting disease progression.Methods: Through a multiplex in situ analysis we evaluated 15 immune cell classes in 1481 tumour samples. Single-cell and bulk RNAseq data sets were used for functional analysis and validation of prognostic and predictive associations.Findings: By combining the prognostic information of anti-tumoural CD8+ lymphocytes and tumour supportive CD68+CD163+ macrophages in colorectal cancer we generated a signature of immune activation (SIA). The prognostic impact of SIA was independent of conventional parameters and comparable with the state-of-art immune score. The SIA was also associated with patient survival in oesophageal adenocarcinoma, bladder cancer, lung adenocarcinoma and melanoma, but not in endometrial, ovarian and squamous cell lung carcinoma. We identified CD68+CD163+ macrophages as the major producers of complement C1q, which could serve as a surrogate marker of this macrophage subset. Consequently, the RNA-based version of SIA (ratio of CD8A to C1QA) was predictive for survival in independent RNAseq data sets from these six cancer types. Finally, the CD8A/C1QA mRNA ratio was also predictive for the response to checkpoint inhibitor therapy.Interpretation: Our findings extend current concepts to procure prognostic information from the tumour immune microenvironment and provide an immune activation signature with high clinical potential in common human cancer types.
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| 7. |
- Mezheyeuski, Artur, et al.
(författare)
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The ratio of CD8+ lymphocytes to CD68+CD163+ macrophages is prognostic in immunogenic tumors and predicts immunotherapy response
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Immune cells in the microenvironment shape tumor development and progression. Through in situ analyses we assessed 15 immune cell classes in 352 colorectal cancers and identified a simpleprognostic signature based on the ratio of anti-tumoral CD8+ lymphocytes to tumor-supportiveCD68+CD163+ macrophages in the tumor microenvironment. The prognostic ability of this signature was superior to the state-of-art immune score and was also demonstrated in four other tumor types. Single-cell analyses identified these CD68+CD163+ macrophages as the source of complement C1q, and the ratio of CD8A to C1QA gene expression levels in bulk RNA predicted survival in five tumor types. In single cell analyses, RNA-based versions of the signature also predicted response to checkpoint inhibitor therapy. This supports broad clinical applicability of immune scores considering CD68+CD163+ macrophages as prognostic and predictive biomarkers in common cancers.
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| 8. |
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| 9. |
- Ringsberg, Karin, et al.
(författare)
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The health-line : a method for collecting data on self-rated health over time: a pilot study
- 2001
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Ingår i: Scandinavian Journal of Public Health. - : SAGE Publications. - 1403-4948. ; 29:3, s. 233-239
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is a need for an instrument to record a life-course perspective of self-rated health. Aim: To test the ''health-line'', a simple, comprehensive method of collecting data on self-rated health over time. Method: In 1996, a questionnaire was mailed to people who in 1985 were aged between 25 and 34 years old and had a sick-leave spell >28 days with ''back diagnoses''. They were asked to rate their global health graphically with a ''health-line'' for the years 1985-95. Official data on sick leave and disability pension were obtained for the same period. In all, 37 out of 52 men and 60 out of 83 women answered; that is, they drew a health-line. Result: A statistically significant negative correlation between the mean number of absence days due to ill health and the health-line data was found for every year (r = -0.35 to -0.53; p < 0.001 ) and for the whole period 1985-95 (r = -0.546; p < 0.001) respectively. Conclusion: The method worked well and is well worth further development and testing.
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| 10. |
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