| 1. |
- Ferrari, Raffaele, et al.
(author)
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Frontotemporal dementia and its subtypes: a genome-wide association study.
- 2014
-
In: Lancet Neurology. - 1474-4465. ; 13:7, s. 686-699
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Journal article (peer-reviewed)abstract
- Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes-MAPT, GRN, and C9orf72-have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder.
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| 2. |
- Lindgren, David, et al.
(author)
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Isolation and characterization of progenitor-like cells from human renal proximal tubules.
- 2011
-
In: American Journal of Pathology. - : Elsevier BV. - 1525-2191 .- 0002-9440. ; 178:2, s. 828-837
-
Journal article (peer-reviewed)abstract
- The tubules of the kidney display a remarkable capacity for self-renewal on damage. Whether this regeneration is mediated by dedifferentiating surviving cells or, as recently suggested, by stem cells has not been unequivocally settled. Herein, we demonstrate that aldehyde dehydrogenase (ALDH) activity may be used for isolation of cells with progenitor characteristics from adult human renal cortical tissue. Gene expression profiling of the isolated ALDH(high) and ALDH(low) cell fractions followed by immunohistochemical interrogation of renal tissues enabled us to delineate a tentative progenitor cell population scattered through the proximal tubules (PTs). These cells expressed CD24 and CD133, previously described markers for renal progenitors of Bowman's capsule. Furthermore, we show that the PT cells, and the glomerular progenitors, are positive for KRT7, KRT19, BCL2, and vimentin. In addition, tubular epithelium regenerating on acute tubular necrosis displayed long stretches of CD133(+)/VIM(+) cells, further substantiating that these cells may represent a progenitor cell population. Furthermore, a potential association of these progenitor cells with papillary renal cell carcinoma was discovered. Taken together, our data demonstrate the presence of a previously unappreciated subset of the PT cells that may be endowed with a more robust phenotype, allowing increased resistance to acute renal injury, enabling rapid repopulation of the tubules.
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| 3. |
- Bayani, Jane, et al.
(author)
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Evaluation of multiple transcriptomic gene risk signatures in male breast cancer
- 2021
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In: npj Breast Cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 7:1
-
Journal article (peer-reviewed)abstract
- Male breast cancer (BCa) is a rare disease accounting for less than 1% of all breast cancers and 1% of all cancers in males. The clinical management is largely extrapolated from female BCa. Several multigene assays are increasingly used to guide clinical treatment decisions in female BCa, however, there are limited data on the utility of these tests in male BCa. Here we present the gene expression results of 381 M0, ER+ve, HER2-ve male BCa patients enrolled in the Part 1 (retrospective analysis) of the International Male Breast Cancer Program. Using a custom NanoString™ panel comprised of the genes from the commercial risk tests Prosigna®, OncotypeDX®, and MammaPrint®, risk scores and intrinsic subtyping data were generated to recapitulate the commercial tests as described by us previously. We also examined the prognostic value of other risk scores such as the Genomic Grade Index (GGI), IHC4-mRNA and our prognostic 95-gene signature. In this sample set of male BCa, we demonstrated prognostic utility on univariate analysis. Across all signatures, patients whose samples were identified as low-risk experienced better outcomes than intermediate-risk, with those classed as high risk experiencing the poorest outcomes. As seen with female BCa, the concordance between tests was poor, with C-index values ranging from 40.3% to 78.2% and Kappa values ranging from 0.17 to 0.58. To our knowledge, this is the largest study of male breast cancers assayed to generate risk scores of the current commercial and academic risk tests demonstrating comparable clinical utility to female BCa.
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| 4. |
- Belle, Simon, et al.
(author)
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Use of sedimentary algal pigment analyses to infer past lake-water total phosphorus concentrations
- 2022
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In: Journal of Paleolimnology. - : Springer Science and Business Media LLC. - 0921-2728 .- 1573-0417. ; 68, s. 415-426
-
Journal article (peer-reviewed)abstract
- We tested the feasibility of using sedimentary algal pigment analyses by spectral deconvolution to infer past lake-water total phosphorus concentrations. We established equations that link lake-water nutrient concentrations and sediment pigment concentrations, using a combination of calibration in both space and time, with a training set of 31 Swedish lakes. The calibration dataset yielded a significant positive relationship between total carotenoid concentrations and lake-water total phosphorus concentrations. We also compared sediment-pigment-based nutrient inferences with time series of water column monitoring data to evaluate whether temporal changes in total phosphorus concentrations are well captured by analysis of sedimentary pigments. We found that changes in pigment preservation through time can alter the relationship between concentrations of lake-water nutrients and sedimentary pigments, thus limiting the reliability of historical ecological conditions inferred from pigments in the sediment. Our data suggested that ratios of Chlorophyll derivatives to total carotenoids (CD/TC ratio) and Chlorophyll a to Chlorophyll derivatives (CPI) can be used as proxies for pigment preservation. Using our approach, inferred temporal changes in water-column total phosphorus concentrations in lakes are promising, but require further development, specifically with respect to the influence of pigment degradation in both the water column and sediments, as well as the factors that control such degradation.
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| 5. |
- Bjartell, Anders, et al.
(author)
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Time-resolved fluorescence in immunocytochemical detection of prostate-specific antigen in prostatic tissue sections
- 1999
-
In: Histochemical Journal. - 0018-2214. ; 31:1, s. 45-52
-
Journal article (peer-reviewed)abstract
- Chelates with fluorescent lanthanides such as europium and terbium are widely used in immunofluorometric assays, e.g. for the measurement of different molecular forms of prostate-specific antigen (PSA) in serum for detection and monitoring of prostate cancer. These chelates have also been introduced as non-radioactive labels in immunocytochemistry and in situ hybridization. In the present study, sections of non-malignant prostate were investigated using monoclonal IgGs against PSA. Detection of specific immunostaining employing time-resolved fluorescence with europium-labeled streptavidin was compared with conventional detection by streptavidin conjugated to horse-radish peroxidase. The high PSA concentration in the tissue produced high intensity, specific time-resolved fluorescence signals in the epithelial cells of the prostate gland without disturbance from non-specific tissue autofluorescence. This allowed short exposure times to be used which resulted in insignificant photobleaching. Two of the three europium-chelates evaluated yielded high signal intensities. Counterstaining was found to be optimal with Gill No. 1-Haematoxylin solution and Merckoglas(TM) was the best mounting medium for the europium chelates tested. In conclusion, time-resolved fluorescence imaging is an attractive alternative to conventional detection of streptavidin conjugated to horse-radish peroxidase, as it provides linear, high intensity, specific signals subsequent to the decay of non-specific tissue autofluorescence.
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| 6. |
- Boström, Anna-Karin, et al.
(author)
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Sarcomatoid conversion of clear cell renal cell carcinoma in relation to epithelial-to-mesenchymal transition.
- 2012
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In: Human Pathology. - : Elsevier BV. - 1532-8392 .- 0046-8177. ; 43, s. 708-719
-
Journal article (peer-reviewed)abstract
- Approximately 8% of clear cell renal cell carcinoma cases contain regions of radically different morphology, demonstrating a mesenchymal appearance histologically resembling sarcomas. These biphasic neoplasms are called sarcomatoid clear cell renal cell carcinoma. Patients diagnosed with sarcomatoid clear cell renal cell carcinoma face a considerably worse prognosis due to an increased propensity for metastasis. In the present study we investigate whether the sarcomatoid conversion of clear cell renal cell carcinoma could be interpreted as linked to the process of epithelial-mesenchymal transition. Using 6 biphasic clear cell renal cell carcinoma cases we show that sarcomatoid clear cell renal cell carcinoma shares characteristic markers associated with loss of von Hippel-Lindau tumor suppressor with conventional clear cell renal cell carcinoma and also exhibits a markedly higher proliferative index. Furthermore the sarcomatoid elements demonstrate an enhanced expression of epithelial-mesenchymal transition related mesenchymal markers as compared with the clear cell renal cell carcinoma counterparts. We further selected a representative case, clinically demonstrating direct overgrowth of the sarcomatoid component into the liver and colon, for extended immunohistochemical characterization, resulting in a further set of positive and negative epithelial-mesenchymal transition markers as well as pronounced transforming growth factor β positivity, indicating that sarcomatoid clear cell renal cell carcinoma may be associated to epithelial-mesenchymal transition. Transforming growth factor β1 exposure of in vitro cultured primary clear cell renal cell carcinoma cells resulted in cells adopting a mesenchymal morphology similar to sarcomatoid clear cell renal cell carcinoma. Corresponding changes in RNA levels for key epithelial-mesenchymal transition markers were also seen. We therefore suggest that sarcomatoid clear cell renal cell carcinoma morphologically and immunohistochemically may represent a completed epithelial-mesenchymal transition and that transforming growth factor β1 could be an important driving force during the sarcomatoid transdifferentiation of clear cell renal cell carcinoma.
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| 7. |
- Clark, Charlotte, et al.
(author)
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Psychological restoration, coping strategies and children’s cognitive performance in the RANCH study
- 2006
-
In: Proceedings of Inter-Noise 2006, Honolulu, Hawaii, USA, 3-6 December, 2006, Paper no in06_090 (Available on CD). ; :Paper no in06_090
-
Conference paper (peer-reviewed)abstract
- The RANCH study found a linear exposure effect association between chronic aircraft noise exposure at primary school and the impairment of children’s reading comprehension, in the Netherlands, Spain and the United Kingdom. This paper presents multilevel modelling analyses, exploring psychological mechanisms, which may moderate the effect of aircraft noise on children’s cognition. Psychological restoration – the process whereby places which afford tranquility and relaxation are utilized to reduce stress and promote well being – has been shown to reduce the adverse effect of noise on children’s annoyance responses. This paper examines whether having places for psychological restoration at home, moderates the adverse effects of chronic aircraft noise exposure at school on children’s cognition. In addition, the effectiveness of coping strategies in relation to noise exposure at school are examined – are specific coping strategies associated with less impairment of cognition? Multi-level models examining the role of psychological restoration and coping strategies, as part of a broader model of environmental risk and protective factors for children’s cognition are presented. The implication of the findings for interventions for children attending noise exposed schools are discussed.
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| 8. |
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| 9. |
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| 10. |
- Ehlén, Åsa, et al.
(author)
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Tumors with non-functional RB1 are killed by reduced gamma-tubulin levels.
- 2012
-
In: Journal of Biological Chemistry. - 1083-351X. ; 287:21, s. 17241-17247
-
Journal article (peer-reviewed)abstract
- In various tumors inactivation of growth control is achieved by interfering with the RB1 signaling pathway. Here, we describe that RB1 and γ tubulin proteins moderate each other's expression by binding to their respective gene promoters. Simultaneous reduction of RB1 and γ tubulin protein levels result in an E2F1-dependent upregulation of apoptotic genes such as caspase 3. We report that in various tumors types, there is an inverse correlation between the expression levels of γ tubulin and RB1 and that in tumor cell lines with a non-functioning RB1, reduction of γ tubulin protein levels leads to induction of apoptosis. Thus, the RB1/γ tubulin signal network can be considered as a new target for cancer treatment.
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| 11. |
- Gaber, Alexander, et al.
(author)
-
Increased serum levels of tumour-associated trypsin inhibitor independently predict a poor prognosis in colorectal cancer patients
- 2010
-
In: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 10, s. 498-
-
Journal article (peer-reviewed)abstract
- Background: There is an insufficient number of reliable prognostic and response predictive biomarkers in colorectal cancer (CRC) management. In a previous study, we found that high tumour tissue expression of tumour-associated trypsin inhibitor (TATI) correlated with liver metastasis and an impaired prognosis in CRC. The aim of this study was to investigate the prognostic validity of serum TATI (s-TATI) in CRC. We further assessed the prognostic value of carcino-embryonic antigen in serum (s-CEA) and the interrelationship between s-TATI and TATI in tissue (t-TATI). Methods: Using an immunofluorometric assay, s-TATI levels were analysed in 334 preoperatively collected serum samples from patients with CRC. Spearman's Rho and Chi-square test were used for analysis of correlations between s-TATI and clinicopathological parameters, s-CEA and t-TATI. Kaplan-Meier analysis and Cox uni-and multivariate regression analysis were used to estimate disease free survival (DFS) and overall survival (OS) according to quartiles of s-TATI and cut-offs derived from ROC-analysis of s-TATI and s-CEA. Results: Increased levels of s-TATI were associated with a reduced DFS (HR = 2.00; 95% CI 1.40-2.84, P < 0.001) and OS (HR = 2.40; 95% CI 1.74-3.33, P < 0.001). (HR = 2.89; 95% CI 1.96-4.25). This association remained significant in multivariate analysis. The association for OS remained significant in multivariate analysis (HR = 1.51; 95% CI 1.032.22, P = 0.034 for DFS and HR = 1.78; 95% CI 1.25-2.53, P = 0.001 for OS). There was no significant association between s-TATI and t-TATI. The prognostic value of s-CEA was also evident, but somewhat weaker than for s-TATI. Conclusions: High preoperative s-TATI levels predict a poor prognosis in patients with CRC, and the prognostic value is independent of established prognostic parameters and t-TATI expression. These data suggest that s-TATI might be a useful marker for prognostic stratification in CRC.
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| 12. |
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| 13. |
- Jensen, Kim Steen, et al.
(author)
-
FoxO3A promotes metabolic adaptation to hypoxia by antagonizing Myc function
- 2011
-
In: EMBO Journal. - : Wiley. - 1460-2075 .- 0261-4189. ; 30:22, s. 4554-4570
-
Journal article (peer-reviewed)abstract
- Exposure of metazoan organisms to hypoxia engages a metabolic switch orchestrated by the hypoxia-inducible factor 1 (HIF-1). HIF-1 mediates induction of glycolysis and active repression of mitochondrial respiration that reduces oxygen consumption and inhibits the production of potentially harmful reactive oxygen species (ROS). Here, we show that FoxO3A is activated in hypoxia downstream of HIF-1 and mediates the hypoxic repression of a set of nuclear-encoded mitochondrial genes. FoxO3A is required for hypoxic suppression of mitochondrial mass, oxygen consumption, and ROS production and promotes cell survival in hypoxia. FoxO3A is recruited to the promoters of nuclear-encoded mitochondrial genes where it directly antagonizes c-Myc function via a mechanism that does not require binding to the consensus FoxO recognition element. Furthermore, we show that FoxO3A is activated in human hypoxic tumour tissue in vivo and that FoxO3A shor-thairpin RNA (shRNA)-expressing xenograft tumours are decreased in size and metabolically changed. Our findings define a novel mechanism by which FoxO3A promotes metabolic adaptation and stress resistance in hypoxia. The EMBO Journal (2011) 30, 4554-4570. doi:10.1038/emboj.2011.323; Published online 13 September 2011
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| 14. |
- Khazaei, Somayeh, et al.
(author)
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Research Paper Impact of combining vitamin C with radiation therapy in human breast cancer : Does it matter?
- 2022
-
In: Oncotarget. - 1949-2553. ; 13:1, s. 439-453
-
Journal article (peer-reviewed)abstract
- Vitamin C may impact the efficiency of radiation therapy (RT) in breast cancer. The effects of RT alone or in combination with vitamin C in SKBR3, MDA-MB-231, and MCF7 cells were compared using clonogenic assay, proliferation assay (MTT), cell cycle analysis, and Western blot. Vitamin C use was assessed in 1803 breast cancer patients 2002–2017 in relation to clinicopathological features and recurrences after RT. Vitamin C combined with RT resulted in non-significant increases in colony formation and minor differences in cell cycle arrest and expression of studied proteins, compared to RT alone. Lower vitamin C doses alone or in combination with RT, resulted in higher proliferation with MTT than higher vitamin C doses in a cell line-dependent manner. Vitamin C use was associated with lower histological grade and BMI but not recurrence risk in RT-treated patients (LogRank P = 0.54). Vitamin C impacted RT efficiency differently depending on breast cancer subtype and vitamin C concentration. Lower doses of vitamin C, achievable with oral administration, might increase breast cancer cell proliferation and decrease radiosensitivity. Despite vitamin C users having less aggressive tumors than non-users, the recurrence risk in RT-treated patients was similar in vitamin C users and non-users.
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| 15. |
- Kronblad, Åsa, et al.
(author)
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ERK1/2 inhibition increases antiestrogen treatment efficacy by interfering with hypoxia-induced downregulation of ERalpha: a combination therapy potentially targeting hypoxic and dormant tumor cells.
- 2005
-
In: Oncogene. - : Springer Science and Business Media LLC. - 1476-5594 .- 0950-9232. ; 24:45, s. 6835-6841
-
Journal article (peer-reviewed)abstract
- Tumor hypoxia is associated with cancer invasiveness, metastasis and treatment failure. Recent data suggest that the major target for endocrine treatment in breast cancer, ER alpha, is downregulated during hypoxia, but the mechanism behind this remains unknown. MAPK signaling as well as ER alpha regulation has earlier been independently linked to hypoxia and we now demonstrate HIF-1 alpha and ERK1/2-activation in vivo towards the necrotic zone in DCIS of the breast, parallel with ER alpha downregulation. Hypoxia further caused transcriptional downregulation of ER alpha via activation of ERK1/2 in cell lines and, importantly, MEK1/2 inhibitors (U0126 or PD184352) or ERK1/2 suppression by siRNA partially restored the ERa expression. U0126 combined with tamoxifen accordingly produced an increased efficacy of the anti-estrogens during hypoxia. Base don these findings, we suggest a promising novel therapy for ER alpha-positive breast cancer where a combination of endocrine treatment and ERK1/2 inhibitors may increase treatment response by improved targeting of dormant hypoxic tumor cells.
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| 16. |
- Lindström, Lisa, et al.
(author)
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Therapeutic Targeting of Nuclear Gamma-Tubulin in RB1-negative Tumors.
- 2015
-
In: Molecular Cancer Research. - 1557-3125. ; 13:7, s. 1073-1082
-
Journal article (peer-reviewed)abstract
- In addition to its cytosolic function, gamma-tubulin is a chromatin-associated protein. Reduced levels of nuclear gamma-tubulin increase the activity of E2 promoter-binding factors (E2F) and raise the levels of retinoblastoma (RB1) tumor suppressor protein. In tumor cells lacking RB1 expression, decreased gamma-tubulin levels induce cell death. Consequently, impairment of the nuclear activity of gamma-tubulin has been suggested as a strategy for targeted chemotherapy of RB1-deficient tumors; thus, tubulin inhibitors were tested to identify compounds that interfere with gamma-tubulin. Interestingly, citral increased E2F activity but impaired microtubule dynamics while citral analogs, like citral dimethyl acetal (CDA), increased E2F activity without affecting microtubules. The cytotoxic effect of CDA on tumor cells was attenuated by increased expression of either RB1 or gamma-tubulin, and increased by reduced levels of either RB1 or gamma-tubulin. Mechanistic study, in silico and in vitro, demonstrated that CDA prevents GTP binding to gamma-tubulin and suggested that the FDA approved drug dimethyl fumarate is also a gamma-tubulin inhibitor. Finally, in vivo growth of xenograft tumors carrying defects in the RB1 signaling pathway were inhibited by CDA treatment. These results demonstrate that inhibition of gamma-tubulin has the potential to specifically target tumor cells and may aid in the design of safer and more efficient chemotherapeutic regimes.
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| 17. |
- Löfberg, Helge, et al.
(author)
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The prevalence of renal amyloidosis of the AA-type in a series of 1,158 consecutive autopsies
- 1987
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In: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - : Wiley. - 0108-0164. ; 95A:1-6, s. 297-302
-
Journal article (peer-reviewed)abstract
- To determine the prevalence of renal amyloidosis of the AA-type in a defined population, formalin-fixed specimens from the kidneys of all the cases autopsied in 1983 at The General Hospital of Malmö, Sweden, were investigated using immunohistochemical techniques. Amyloid deposits of protein AA were found in 10 of 1,158 investigated cases and the calculated prevalence was 0.86 per cent. The mean age at death of the individuals with the AA-type of amyloidosis was 79 years. Six of the cases with amyloidosis had rheumatoid arthritis. The avidin-biotin-peroxidase complex technique was found to be superior to the immunofluorescence method and a high sensitivity and specificity was achieved when sequence-specific antibodies against a synthetized nonapeptide corresponding to a hydrophilic segment of the polypeptide chain of protein AA were used in the assay. Nine cases with other types of amyloid deposits in the kidneys were also detected. None of these cases showed any AA immunoreactivity but all of them demonstrated Congophilic deposits which were immunohistochemically stained by antibodies against the amyloid P-component. The prevalence of renal amyloidosis comprising all types of amyloid protein deposits was 1.64 per cent.
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| 18. |
- Manzoni, Claudia, et al.
(author)
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Genome-wide analyses reveal a potential role for the MAPT, MOBP, and APOE loci in sporadic frontotemporal dementia
- 2024
-
In: American Journal of Human Genetics. - 0002-9297. ; 111:7, s. 1316-1329
-
Journal article (peer-reviewed)abstract
- Frontotemporal dementia (FTD) is the second most common cause of early-onset dementia after Alzheimer disease (AD). Efforts in the field mainly focus on familial forms of disease (fFTDs), while studies of the genetic etiology of sporadic FTD (sFTD) have been less common. In the current work, we analyzed 4,685 sFTD cases and 15,308 controls looking for common genetic determinants for sFTD. We found a cluster of variants at the MAPT (rs199443; p = 2.5 × 10−12, OR = 1.27) and APOE (rs6857; p = 1.31 × 10−12, OR = 1.27) loci and a candidate locus on chromosome 3 (rs1009966; p = 2.41 × 10−8, OR = 1.16) in the intergenic region between RPSA and MOBP, contributing to increased risk for sFTD through effects on expression and/or splicing in brain cortex of functionally relevant in-cis genes at the MAPT and RPSA-MOBP loci. The association with the MAPT (H1c clade) and RPSA-MOBP loci may suggest common genetic pleiotropy across FTD and progressive supranuclear palsy (PSP) (MAPT and RPSA-MOBP loci) and across FTD, AD, Parkinson disease (PD), and cortico-basal degeneration (CBD) (MAPT locus). Our data also suggest population specificity of the risk signals, with MAPT and APOE loci associations mainly driven by Central/Nordic and Mediterranean Europeans, respectively. This study lays the foundations for future work aimed at further characterizing population-specific features of potential FTD-discriminant APOE haplotype(s) and the functional involvement and contribution of the MAPT H1c haplotype and RPSA-MOBP loci to pathogenesis of sporadic forms of FTD in brain cortex.
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| 19. |
- Marsh, Timothy, et al.
(author)
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Hematopoietic age at onset of triple-negative breast cancer dictates disease aggressiveness and progression
- 2016
-
In: Cancer Research. - 0008-5472. ; 76:10, s. 2932-2943
-
Journal article (peer-reviewed)abstract
- Triple-negative breast cancer (TNBC) is considered an early onset subtype of breast cancer that carries with it a poorer prognosis in young rather than older women for reasons that remain poorly understood. Hematopoiesis in the bone marrow becomes altered with age and may therefore affect the composition of tumor-infiltrating hematopoietic cells and subsequent tumor progression. In this study, we investigated how age- and tumor-dependent changes to bone marrow-derived hematopoietic cells impact TNBC progression. Using multiple mouse models of TNBC tumorigenesis and metastasis, we found that a specific population of bone marrow cells (BMC) upregulated CSF-1R and secreted the growth factor granulin to support stromal activation and robust tumor growth in young mice. However, the same cell population in old mice expressed low levels of CSF1R and granulin and failed to promote tumor outgrowth, suggesting that age influences the tumorigenic capacity of BMCs in response to tumor-associated signals. Importantly, BMCs from young mice were sufficient to activate a tumor-supportive microenvironment and induce tumor progression in old mice. These results indicate that hematopoietic age is an important determinant of TNBC aggressiveness and provide rationale for investigating age-stratified therapies designed to prevent the protumorigenic effects of activated BMCs.
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| 20. |
- Natsch, Andreas, et al.
(author)
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Interlaboratory evaluation of methods to quantify skin sensitizing hydroperoxides potentially formed from linalool and limonene in perfumes
- 2017
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In: Flavour and fragrance journal. - : Wiley. - 0882-5734 .- 1099-1026. ; 32:4, s. 277-285
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Journal article (peer-reviewed)abstract
- The fragrant terpenes limonene and linalool can form skin sensitizing hydroperoxides upon prolonged exposure to air. Recently, high frequencies of positive patch tests to oxidized linalool and limonene were reported from multiple dermatological centres. However, there is a lack of data indicating potential sources of consumer exposure to sensitizing doses of terpene hydroperoxides which explains this frequent contact allergy. Within the IDEA project ( International Dialogue for the Evaluation of Allergens; http://ideaproject.info/), a taskforce was formed to drive analytical method development and evaluation. In an inter-laboratory study in five laboratories, a method based on hydroperoxide reduction combined with GC-MS was tested for reproducibility. Blinded samples of commercial fine fragrances were spiked with four different hydroperoxides. In samples spiked with 100-200 mu g/ml, an average recovery of 86-105% with a relative standard deviation between laboratories of 7.4-22% was found. In samples spiked with 2050 mu g/ml, the recovery was 85-91%. The reduction approach offers a transferable and reproducible method to indirectly detect low levels of hydroperoxides, at least in fine fragrances. Ideally, one would prefer to directly detect the parent hydroperoxide. Therefore the same samples were further tested with three LC-based methods directly detecting the parent hydroperoxide. LC coupled to chemiluminescence, LC-Q-TOF-MS or LC-orbitrap-MS were used. Results indicate that with specific gradients a separation of the four analytes and quantification in the fragrance matrix can be achieved. Results of this method evaluation study present a toolbox of methods to detect terpene hydroperoxides to further investigate consumer exposure.
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| 21. |
- Nodin, Björn, et al.
(author)
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Increased androgen receptor expression in serous carcinoma of the ovary is associated with an improved survival
- 2010
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In: Journal of Ovarian Research. - : Springer Science and Business Media LLC. - 1757-2215. ; 3
-
Journal article (peer-reviewed)abstract
- Background: Altered androgen hormone homeostasis and androgen receptor (AR) activity have been implicated in ovarian carcinogenesis but the relationship between AR expression in ovarian cancer and clinical outcome remains unclear. Methods: In this study, the prognostic impact of AR expression was investigated using immunohistochemistry in tissue microarrays from 154 incident cases of epithelial ovarian cancer (EOC) in the prospective, population-based cohorts Malmo Diet and Cancer Study and Malmo Preventive Project. A subset of corresponding fallopian tubes (n = 36) with no histopathological evidence of disease was also analysed. Results: While abundantly expressed in the majority of fallopian tubes with more than 75% positive nuclei in 16/36 (44%) cases, AR was absent in 108/154 (70%) of EOC cases. AR expression was not related to prognosis in the entire cohort, but in the serous subtype (n = 90), AR positivity (> 10% positive nuclei) was associated with a prolonged disease specific survival in univariate (HR= 0.49; 95% CI 0.25- 0.96; p= 0.038) and multivariate (HR= 0.46; 95% CI 0.22-0.97; p= 0.042) analysis, adjusted for age, grade and clinical stage. Conclusions: AR expression is considerably reduced in EOC as compared to fallopian tubes, and in EOC of the serous subtype, high AR expression is a favourable prognostic factor. These results indicate that assessment of AR expression might be of value for treatment stratification of EOC patients with serous ovarian carcinoma.
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| 22. |
- Okroj, Marcin, et al.
(author)
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Local expression of complement factor I in breast cancer cells correlates with poor survival and recurrence.
- 2015
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In: Cancer Immunology and Immunotherapy. - : Springer Science and Business Media LLC. - 1432-0851 .- 0340-7004. ; 64:4, s. 467-478
-
Journal article (peer-reviewed)abstract
- Tumor cells often evade killing by the complement system by overexpressing membrane-bound complement inhibitors. However, production of soluble complement inhibitors in cells other than hepatocytes was rarely reported. We screened several breast cancer cell lines for expression of soluble complement inhibitor, complement factor I (FI). We also analyzed local production of FI in tissue microarrays with tumors from 130 breast cancer patients by in situ hybridization and immunohistochemistry. We found expression of FI in breast adenocarcinoma cell line MDA-MB-468 and confirmed its functional activity. Expression of FI at mRNA and protein levels was also confirmed in tumor cells and tumor stroma, both in fibroblasts and infiltrating immune cells. Multivariate Cox regression analyses revealed that high expression of FI protein in tumor cells was correlated with significantly shorter cancer-specific survival (HR 2.8; 95 % CI 1.0-7.5; p = 0.048) and recurrence-free survival (HR 3.4; 95 % CI 1.5-7.4; p = 0.002). High FI expression was positively correlated with tumor size (p < 0.001), and Nottingham histological grade (p = 0.015) and associated with estrogen and progesterone receptor status (p = 0.03 and p = 0.009, respectively). Our data show that FI is expressed in breast cancer and is associated with unfavorable clinical outcome.
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| 23. |
- Persdotter Hedlund, Gabriella, et al.
(author)
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Fetal antigen 1 (FA1) in the adult rat adrenal gland, ovary and pituitary gland
- 2003
-
In: In Vivo. - 0258-851X .- 1791-7549. ; 17:1, s. 1-4
-
Journal article (peer-reviewed)abstract
- Fetal antigen 1 (FA1) is a circulating glycoprotein containing six epidermal growth factor (EGF)-like repeats. FA1's larger membrane-bound precursor is defined by the cDNAs referred to as either human delta-like (dlk) or human adrenal specific cDNA, pG2. In rodents FA1 has also been studied under the names of preadipocyte factor 1 (Pref-1), and zona glomerulosa-specific factor (ZOG). FA1 is abundantly expressed in fetal tissues, but in the mature cells of the adult organism the tissue presence of the protein seems to be restricted to neuroendocrine tissues. The present study demonstrates FA1 localisation in endocrine tissues of the adult female rat in which the protein was found present in the medulla and the zona glomerulosa of the cortex of the adrenal glands, in the pars distalis of the adenohypophysis, and in the ovarian granulosa lutein cells. No staining was found in the pancreas, which is in contrast to what has been described in the human.
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| 24. |
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| 25. |
- Stenberg, Leisa, et al.
(author)
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A functional prothrombin gene product is synthesized by human kidney cells
- 2001
-
In: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 280:4, s. 1036-1041
-
Journal article (peer-reviewed)abstract
- gamma -carboxylated polypeptides were detected in the human kidney by immunohistochemistry with a monoclonal antibody (M3B) specific for gamma -carboxyglutamyl residues. An similar to 70-kDa gamma -carboxylated protein, subsequently identified as prothrombin, was isolated from the intracellular compartment of cultured human embryonic kidney (HEK293) cells by immunoaffinity chromatography on M3B-coupled resin. Immunohistochemical analyses demonstrated that prothrombin and another vitamin K-dependent protein, the growth arrest-specific protein 6, were detectable in human kidney. As in the liver, the kidney synthesizes prothrombin as a zymogen that can be cleaved by ecarin to an amidolytically active serine protease that is inhibited by hirudin, This demonstrates for the first time the de novo synthesis of a full-length, gamma -carboxylated, and functional prothrombin gene product by human kidney cells.
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| 26. |
- Stenberg, Leisa, et al.
(author)
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Synthesis of gamma-carboxylated polypeptides by alpha-cells of the pancreatic islets
- 2001
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In: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 283:2, s. 454-459
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Journal article (peer-reviewed)abstract
- gamma -Carboxylated proteins were detected in normal human pancreas by immunohistochemistry with a monoclonal antibody (M3B) specific for gamma -carboxyglutamyl residues, Staining appeared to be localized to the glucagon-secreting alpha -cells in the islets of Langerhans, Consistent with this, sections from a glucagonoma were stained much more intensely with the M3B antibody than those from an insulinoma. A murine alpha -cell line (alpha TC1 Clone 9) was cultured and gamma -carboxylated polypeptides, identified immunologically as prothrombin, protein S and (tentatively) Gas6, were isolated from the intracellular compartment by chromatography on an M3B-coupled resin, As in liver, prothrombin is synthesized by alpha -cells as a gamma -carboxylated zymogen that can be cleaved by ecarin to form an active serine protease that is inhibited by hirudin, The pancreas thus appears to be a novel site of synthesis for certain vitamin K-dependent proteins.
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| 27. |
- Tillander, Bo, et al.
(author)
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Carrageenan-induced subacromial bursitis caused changes in the rat's rotator cuff
- 2001
-
In: Journal of Orthopaedic Research. - 0736-0266. ; 19:3, s. 441-447
-
Journal article (peer-reviewed)abstract
- This study was designed to investigate the histologic expression of the rat's supra- and infraspinatus tendons in carrageenan-induced subacromial bursitis. Thirty-two rats received subacromial injections with carrageenan (n = 28) or saline (n = 4). The tendons were analysed microscopically after staining with hematoxyline eosin, Van Giesons hematoxyline and immunofluorescent staining of fibronectin and fibrinogen. In the controls (saline × 10) and group A (carrageenan × 5) there were no changes in the tendons. In group B (carrageenan × 10) 3/8 rats showed macrophages between the collagen fibres and an increased staining of fibronectin. In group C (double dosis carrageenan) all rats had signs of fibrocartilaginous metaplasia in the supraspinatus tendon. In eight of these specimens even bony metaplasia was seen. The infraspinatus tendon showed fibrosis but no fibro-cartilaginous metaplasia. The results showed that iatrogenic bursitis after carrageenan subacromial injections was associated with marked changes of the supraspinatus tendon.
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| 28. |
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| 29. |
- Ulrich, Jason D., et al.
(author)
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ApoE facilitates the microglial response to amyloid plaque pathology
- 2018
-
In: Journal of Experimental Medicine. - : ROCKEFELLER UNIV PRESS. - 0022-1007 .- 1540-9538. ; 215:4, s. 1047-1058
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Journal article (peer-reviewed)abstract
- One of the hallmarks of Alzheimers disease is the presence of extracellular diffuse and fibrillar plaques predominantly consisting of the amyloid-beta (A beta) peptide. Apolipoprotein E (ApoE) influences the deposition of amyloid pathology through affecting the clearance and aggregation of monomeric A beta in the brain. In addition to influencing A beta metabolism, increasing evidence suggests that apoE influences microglial function in neurodegenerative diseases. Here, we characterize the impact that apoE has on amyloid pathology and the innate immune response in APPPS1 Delta E9 and APPPS1-21 transgenic mice. We report that Apoe deficiency reduced fibrillar plaque deposition, consistent with previous studies. However, fibrillar plaques in Apoe-deficient mice exhibited a striking reduction in plaque compaction. Hyperspectral fluorescent imaging using luminescent conjugated oligothiophenes identified distinct A beta morphotypes in Apoe-deficient mice. We also observed a significant reduction in fibrillar plaque-associated microgliosis and activated microglial gene expression in Apoe-deficient mice, along with significant increases in dystrophic neurites around fibrillar plaques. Our results suggest that apoE is critical in stimulating the innate immune response to amyloid pathology.
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| 30. |
- van Kempen, Elise E.M.M., et al.
(author)
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Children's annoyance reactions to aircraft and road traffic noise
- 2009
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In: Journal of the Acoustical Society of America. - : Acoustical Society of America. - 0001-4966 .- 1520-8524. ; 125:2, s. 895-904
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Journal article (peer-reviewed)abstract
- Since annoyance reactions of children to environmental noise have rarely been investigated, no source specific exposure-response relations are available. The aim of this paper is to investigate children’s reactions to aircraft and road traffic noise and to derive exposure-response relations. To this end, children’s annoyance reactions to aircraft and road traffic noise in both the home and the school setting were investigated using the data gathered in a cross-sectional multicenter study, carried out among 2844 children age 9–11 years attending 89 primary schools around three European airports. An exposure-response relation was demonstrated between exposure to aircraft noise at school LAeq, 7–23 h and severe annoyance in children: after adjustment for confounders, the percentage severely annoyed children was predicted to increase from about 5.1% at 50 dB to about 12.1% at 60 dB. The findings were consistent across the three samples. Aircraft noise at home LAeq,7–23 h demonstrated a similar relation with severe annoyance. Children attending schools with higher road traffic noise LAeq,7–23 h were more annoyed. Although children were less annoyed at levels above 55 dB, the shapes of the exposure-response relations found among children were comparable to those found in their parents.
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| 31. |
- van Kempen, Elise, et al.
(author)
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The role of annoyance in the relation between transportation noise and children's health and cognition
- 2010
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In: Journal of the Acoustical Society of America. - : Acoustical Society of America (ASA). - 0001-4966 .- 1520-8524. ; 128:5, s. 2817-2828
-
Journal article (peer-reviewed)abstract
- Onthe basis of this study it cannot be ruled outthat the appraisal of the noise affects the association betweenair and road traffic noise exposure and children's health andcognition. However, the conclusion is limited due to the relativelysmall group of annoyed children, which may have influenced ourgroup comparisons. Furthermore, the observed relation between annoyance and perceivedhealth is possibly biased due to the fact that bothwere measured within the same questionnaire. These are the mainconclusions of a cross-sectional multi-center study carried out among 2,844schoolchildren (age 9–11 years) attending 89 primary schools around threeEuropean airports. The aim was to investigate how annoyance affectsthe relation between air and road traffic noise exposure andchildren's health and cognition. Different, sometimes competing, working mechanisms ofhow noise affects children's health are suggested. Some effects aresupposed to be precipitated through (chronic) stress, while others mayarise directly. There is still no theory that can adequatelyaccount for the circumstances in which noise will affect cognitiveperformance.
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| 32. |
- Vasdal, Guro, et al.
(author)
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Description of Light Environment in Broiler Breeder Houses with Different Light Sources—And How It Differs from Natural Forest Light
- 2022
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In: Animals. - : MDPI AG. - 2076-2615. ; 12:23
-
Journal article (peer-reviewed)abstract
- Light is a key factor in poultry production; however, there is still a lack of knowledge as to describing the light quality, how to measure the light environment as perceived by birds, and how artificial light compares with the light in the natural forest habitats of their wild ancestors. The aim of this study was to describe the light environment in broiler breeder houses with three different light sources, using two different methods of light assessment. We also aimed to compare an artificial light environment with the light in a range of relevant natural forest habitats. A total of 9 commercial broiler breeder houses with one of three different light sources—Lumilux 830 CFL (n = 3), Biolux 965 CFL (n = 3) or LED Evolys with UVA (n = 3) were visited. Assessments of the light environment in the breeder houses were conducted using both a spectrometer and the environmental light field (ELF) method. ELF measurements from three forest types in south India (Kerala) were also included. We found that most aspects of the light environment were similar between the nine breeder houses and were not dependent on the type of light sources. The only clear difference related to the light source was the spectral balance, wherein 830 CFL had the most red-dominated light, 965 CFL had the most blue-dominated light and Evolys was intermediate but with more UV than the latter two. Plumage color had minimal effect on the light environment. Both the spectrometer and the ELF method provided valuable information. The spectrometer gave detailed values about certain aspects of the light environment, while the ELF described the light more in line with human and avian visual perception. We also found that the light environment in the investigated broiler breeder houses differs dramatically in all measured aspects from the natural light habitats of wild junglefowl, suggesting improvement possibilities in artificial lighting systems.
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| 33. |
- Vasiljevic, Natasa, et al.
(author)
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The Bcl-xL inhibitor of apoptosis is preferentially expressed in cutaneous squamous cell carcinoma compared with that in keratoacanthoma.
- 2009
-
In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 124, s. 2361-2366
-
Journal article (peer-reviewed)abstract
- Keratoacanthoma (KA) is difficult to histologically distinguish from squamous cell carcinoma (SCC). Therefore, although KA is a benign self-resolving skin lesion, KA is commonly treated as SCC. Biomarkers to distinguish KA and SCC would thus be desirable. In search for specific markers, paraffin-embedded tissue samples from 25 SCC and 64 KA were arranged in a tissue microarray (TMA) and stained for immunologic cell-markers CD3, CD20 and CD68 as well as for proteins considered of relevance in tumorgenesis, namely NFkappaB/p65, IkappaB-alpha, STAT3, p53, TRAP-1, pRB, phosphorylated pRb, Cyld, p21, p16(INK4), Survivin, Bcl-xL, Caspase 3, Bak, FLK-1/VEGF-r2 and Ki-67. In addition, the tumors were tested for presence of human papillomavirus by PCR. We detected that the two lesions differed significantly in expression of Bcl-xL which was present in 84% of the SCC compared with only 15% in the KA (p < 0.001). The lower expression of the antiapoptotic protein Bcl-xL in KA is consistent with a possible role of apoptosis in the regression of KA. (c) 2008 Wiley-Liss, Inc.
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| 34. |
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| 35. |
- Wegiel, Barbara, et al.
(author)
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Multiple cellular mechanisms related to cyclin A1 in prostate cancer invasion and metastasis
- 2008
-
In: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 100:14, s. 1022-1036
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Cyclin A1 is a cell cycle regulator that has been implicated in the progression of prostate cancer. Its role in invasion and metastasis of this disease has not been characterized.METHODS: Immunohistochemistry and cDNA microarray analyses were used to assess protein and mRNA expression of cyclin A1 and proteins with roles in metastasis, including vascular endothelial growth factor (VEGF), metalloproteinase 2 (MMP2), and MMP9, in human prostate cancer. Transient transfection and infection with viral vectors expressing cyclin A1 and short hairpin RNA (shRNA) targeting cyclin A1 were used to study the effects of altered cyclin A1 expression in PC3 prostate cancer cells. The BrdU assay, annexin V staining, and invasion chambers were used to examine cyclin A1 effects on proliferation, apoptosis, and invasion, respectively. The role of cyclin A1 and androgen receptor (AR) in transcription of VEGF and MMP2 was assessed by promoter mutation and chromatin immunoprecipitation. The effect of cyclin A1 expression on tumor growth and metastasis was analyzed in a mouse model of metastasis. All statistical tests were two-sided.RESULTS: Cyclin A1 protein and mRNA expression were statistically significantly higher in prostate cancers than in adjacent benign tissues. A statistically significant correlation between expression of cyclin A1 and of MMP2, MMP9, and VEGF was observed in prostate tumors from 482 patients (P values from Spearman rank correlation tests < .001). PC3 cells that overexpressed cyclin A1 showed increased invasiveness, and inhibition of cyclin A1 expression via shRNA expression reduced invasiveness of these cells. Eight of 10 mice (80%) bearing PC3 cells overexpressing cyclin A1 had infiltration of tumor cells in lymph node, liver, and lung, but all 10 mice bearing tumors expressing control vector were free of liver and lung metastases and only one mouse from this group had lymph node metastasis (P values from Fisher exact tests < .001). Cyclin A1, in concert with AR, bound to and increased expression from the VEGF and MMP2 promoters.CONCLUSIONS: Cyclin A1 contributes to prostate cancer invasion by modulating the expression of MMPs and VEGF and by interacting with AR.
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