| 1. |
- Andersson-Evelönn, Emma, 1983-
(författare)
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DNA methylation as a prognostic marker in clear cell Renal Cell Carcinoma
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cell carcinoma worldwide. Metastatic ccRCC is correlated to poor prognosis whereas non-metastatic disease has a 5-year survival rate up to 90%. Due to increased accessibility to different types of diagnostic imaging the frequency of metastatic ccRCC at diagnosis has decreased since the beginning of the 21st century. This has led to an earlier detection of primary tumors before patients present symptoms. However, 20-30% of the non-metastatic patients at diagnosis will progress and metastasize within five years of primary nephrectomy. Identifying patients at high risk of tumor progression at an early stage after diagnosis is of importance to improve outcome and survival. Currently, in Sweden, the Mayo scoring system is used to divide tumors into low, intermediate or high risk for tumor progression.DNA methylation has been associated with tumor development and progression in different malignancies. In this thesis, Illumina Infinium HumanMeth27 BeadChip Arrays and Human Meth450K BeadChip Arrays have been used to evaluate the relationship between methylation and clinicopathological variables as well as ccRCC outcome in 45 and 115 patients.Our studies identified an association between higher level of promoter-associated DNA methylation and clinicopathological variables in ccRCC. There was a significant stepwise increase of average methylation from tumor-free tissue, via non-metastatic tumors to metastatic disease. Cluster analysis divided patients into two distinct groups that differed in average methylation levels, TNM stage, Fuhrman nuclear grade, tumor size, survival and tumor progression. We also presented two prognostic classifiers for non-metastatic tumors; the promoter methylation classifier (PMC) panel and the triple classifier. The PMC panel divided tumors depending on the methylation level, PMC low or PMC high, with significantly worse prognosis in the PMC high group. This data was verified in an independent, publically available cohort. The triple classifier was created using a combination of clinicopathological variables, previously identified CpGs biomarkers and a novel cluster analysis approach (Directed Cluster Analysis). The triple classifier had a higher specificity compared to the clinically used Mayo scoring system and predicted tumor progression with higher accuracy at a fixed sensitivity.The identification of two epigenetic classifiers that predicted outcome in non-metastatic ccRCC further establishes the role of DNA methylation as a prognostic marker. This knowledge can contribute to identification of patients with a high risk of tumor progression and can be of importance in the decision regarding adjuvant treatment post-nephrectomy.
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| 2. |
- Engfeldt, Johnny D., et al.
(författare)
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GLAZING FOR ENERGY EFFICIENT BUILDINGS: : The Almost Forgotten Role of Angular-Dependent Solar Transmittance
- 2020
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Ingår i: Society of Vacuum Coaters Bulletin. - : Society of Vacuum Coaters. ; :spring, s. 72-78
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Tidskriftsartikel (refereegranskat)abstract
- Glazing for energy efficient buildings comprises multi-pane units with surface coated glass. According to today’s standards, glazing is characterized by optical measurements at normal light incidence. Here we show that this prerequisite is grossly inadequate for common vertical glazing, in particular regarding solar transmittance and total energy transmittance (g-value). We present data on spectral and angular-dependent transmittance in the 300–2500-nm wavelength range for several types of glass samples with hard (tin-oxide-based) and soft (silver-based) coatings. Furthermore, we use standard procedures to compute g-values for triple-pane glazing embodying such glass and find that the g-value at 60° off-normal angle typically is as low as 65–68% of the g-value for normal incidence. This difference is essential for assessing the energy efficiency of modern buildings and highlights that the glazing’s angularity must be accounted for.
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| 3. |
- Lindqvist, Maria
(författare)
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Promised Soils : Senses of Place Among Yezidis in Dalarna and Sheikhan
- 2021
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This is an ethnographic study that focuses on Zahmanê Êzîdîa Li Dalarna, the Yezidi cemetery, in Borlänge. The Swedish town of Borlänge has one of the largest Yezidi diaspora communities in Western Europe; a majority emigrated from the Northern Iraqi region of Sheikhan during the 1990s and early 2000s. The overall aim of this project is to investigate how the Yezidi community in Borlänge puts Zahmanê Êzîdîa Li Dalarna into use, the meanings ascribed to the site by individual interviewees, and how these relate to ritual places and practices in Sheikhan.The empirical material stems from observations and interviews among members of three extended Yezidi families in Borlänge and in Sheikhan, and archival material from the Church of Sweden. Fieldwork in Sheikhan focused on the valley of Lalish and the cemetery sites in the Yezidi villages in Sheikhan. The empirical material is presented, analysed and discussed through a theoretical framework of place, creation and maintenance of social memory through ritual practice, and the concept of transfer of ritual.The empirical material reveals that salient ritual actions and elements from ceremonies in Lalish and the Yezidi villages in Sheikhan are transferred to Borlänge, and there put into use for ritual practices and for creating and maintaining a collective identity outside of Iraq.
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| 4. |
- Tumkur Sitaram, Raviprakash, 1974-, et al.
(författare)
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Role of Wnt Signaling Pathways in Clear Cell Renal Cell Carcinoma Pathogenesis in Relation to VHL and HIF Status
- 2020
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Ingår i: Clinical Oncology and Research. - 2613-4942. ; 3:3
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Forskningsöversikt (refereegranskat)abstract
- Renal cell carcinoma (RCC) encompasses various tumor types characterized by a variety of genetic abnormalities. The genetic changes, like mutations, deletions, and epigenetic alterations, can affect the signaling components and signaling networks, causing the modification of tumor pathogenesis and prognosis of RCC. The most prevalent RCC, clear cell RCC (ccRCC), is asymptomatic in the early stages, refractory to chemotherapy and radiation therapy, and has a poorer prognosis compared with the papillary and chromophobe ccRCC types. Loss of the VHL gene and upregulation of oxygen sensors, hypoxia-inducible factor alphas (HIF-α), which promote different growth factors, is a signature of sporadic ccRCC. The VHL-HIF-α and Wnt/β-catenin pathways are closely connected and contribute to the ontogeny of ccRCC. This review confines to ccRCC and the role of the Wnt/β-catenin signaling pathways and its crosstalk with VHL/HIF.
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| 5. |
- Tumkur Sitaram, Raviprakash, 1974-, et al.
(författare)
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Significance of PI3K Signalling pathway in clear cell renal cell carcinoma in relation to VHL and HIF status
- 2021
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Ingår i: Journal of Clinical Pathology. - : BMJ Publishing Group Ltd. - 0021-9746 .- 1472-4146. ; 74:4, s. 216-222
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Forskningsöversikt (refereegranskat)abstract
- Renal cell carcinoma (RCC) includes diverse tumor types characterized by various genetic abnormalities. The genetic changes, like mutations, deletions, and epigenetic alterations, play a crucial role in the modification of signaling networks, tumor pathogenesis, and prognosis. The most prevalent RCC type, clear cell RCC (ccRCC), is asymptomatic in the early stages and has a poorer prognosis compared with the papillary and the chromophobe typesRCCs. Generally, ccRCC is refractory to chemotherapy and radiation therapy. Loss of VHL gene and upregulation of hypoxia-inducible factors (HIF), the signature of most sporadic ccRCC, promote multiple growth factors. Hence, VHL/HIF and a variety of pathways, including PTEN/PI3K/AKT, are closely connected and contribute to the ontogeny of ccRCC. In the recent decade, multiple targeting agents have been developed based on blocking major signaling pathways directly or indirectly involved in ccRCC tumor progression, metastasis, angiogenesis, and survival. However, most of these drugs have limitations; either metastatic ccRCC develops resistance to these agents, or despite blocking receptors, tumor cells utilize alternate signaling pathways. This review compiles the state of knowledge about the PI3K/AKT signaling pathway confined to ccRCC and their cross-talks with VHL/HIF pathways.
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