| 1. |
- Erlandsson, Rikard
(författare)
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Molecular genetics of kidney cancer : chromosomal regions of importance in the development of renal cell carcinoma
- 1996
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Renal cell carcinoma (RCC) is a malignancy of the human kidney, occurring most commonly during the seventh and eighth decades of life. The incidence is high in the Nordic countries and the five year survival is 40-50%. Smoking is a risk factor inferring a minor increase in risk. The best established risk factor is obesity. It is usually sporadic and unilateral but can also occur in hereditary forms characterized by an earlier age of onset, multiple primary, bilateral tumors. The best established prognostic factor for RCC is stage. Other factors like cell type, age at diagnosis, and tumor size, have been implicated to affect survival. We wanted to establish, what chromosomal abnormalities are associated with the development of RCC. Tumor and normal kidney tissues were examined from sporadic, non-hereditary RCC cases. 86% of the examined patients had a detectable anomaly of chromosome 3p, manifested as a deletion, distal to band 3pl 1.2-pl3 combined with the non reciprocal translocation of a segment from another chromosome or monosomy 3. Restriction fragment length polymorphism (RFLP) analysis showed loss of D3F15S2 heterozygosity in 76%. D3S2 hetaozygosity was lost in 18%. The variability of the breakpoint between 3pl 1.2 and 3pl3 and the absence of a consistently translocated segment from another chromosome suggested a genetic loss mechanism. With the previously demonstrated involvement of the 3pl4.2 region in a familial case, these findings suggested that RCCs arise by the deletion of a tumor suppressor gene located at the short arm of chromosome 3. Physical maps were constructed around loci D3F15S2, D3S2 and c-rafl on the short arm of human chromosome 3 using pulsed field gradient gel electrophoresis. The normal restriction pattern was not altered by the t(3;8)(pl4.2;q24.1) characteristic for a hereditary form of renal cell carcinoma, indicating that the breakpoint itself is not included in any of the mapped areas. We found a CpG island within the D3F 15S2 locus, suggesting, the presence of a functional gene in the region. The screening of a human placenta cDNA library with DNA probes derived from D3F15S2 led to the isolation of several cDNA clones. They identified a 2.9 Kb long message in human placenta and kidney. A DNA homology search in GENBANK revealed that the gene encoded human acylpeptidehydrolase (APEH). The nucleotide identity between the rat and the human genes was 88%. We found an APEH expression below 20%, compared to normal kidney, in 73% of the studied primary RCCs. No tumor had an expression above half of that in normal kidney. It was expressed in all cell lines and normal tissues examined, except in one Burkitt's Iymphoma cell line (DG75). RCC appearsto be associated with a decrease of this enzyme activity. This reduction may reflect the existence of a small, acetylated growth factor of importance in renal tumors. Since tumors in animal models are easier to manipulate we wanted to determine the chromosomal location of APEH in rat and mouse. It is localized at mouse chromosome 9 and rat chromosome 8. This increases the number of conserved genes in this region. Other regions, beside chromosome 3, have also been found to harbour non-random losses in RCC. They might be associated with the progression of the tumor. Tumor and constitutional DNA pairs were analysed with RFLP markers from all chromosomal arms and compared with clinical classifications and survival. Allelic imbalance (Al) for loci on 5q was found to be a negative prognostic factor for RCC. Grade correlated with fractional allelic loss, loss of 14q and 17p Al but not with specific aberrations on other chromosomes.
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| 2. |
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| 3. |
- Jochems, Caroline, 1973, et al.
(författare)
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Effects of oestradiol and raloxifene on the induction and effector phases of experimental postmenopausal arthritis and secondary osteoporosis
- 2011
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Ingår i: Clinical and Experimental Immunology. - Chichester : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 165:1, s. 121-129
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Tidskriftsartikel (refereegranskat)abstract
- Oestradiol and the selective oestrogen receptor modulator (SERM) raloxifene have been shown to ameliorate collagen-induced arthritis (CIA) in rats and in mice. One aim was to investigate if raloxifene exerts its anti-arthritic and anti-osteoporotic effects during the induction or effector phase of arthritis. A second aim was to analyse if raloxifene activates the oestrogen response element (ERE) to produce its immune-modulator effects. CIA or collagen-antibody-induced arthritis (CAIA) was induced in ovariectomized DBA/1-mice. CIA was used for evaluation of treatment during the induction, and CAIA for the effector phase of arthritis and osteoporosis development. Raloxifene, oestradiol or vehicle was administered 5 days/week. The clinical disease was evaluated continuously. Bone marrow density (BMD) was analysed with peripheral quantitative computer tomography, paws were collected for histological examination, and sera were analysed for markers of bone and cartilage turnover and proinflammatory cytokines. Transgenic luciferase (Luc)-ERE mice were immunized with collagen (CII), and after 10 days injected once with raloxifene, oestradiol or vehicle before termination. Spleens were analysed for luciferase activity to measure ERE activation. Treatment with oestradiol or raloxifene during the induction phase of CIA failed to affect arthritis. Raloxifene did not hamper disease activity in CAIA, whereas oestradiol delayed the onset and ameliorated the severity. Both raloxifene and oestradiol preserved BMD in CAIA. CII-immunization increased the oestradiol-induced ERE activation in spleen, and raloxifene activated the ERE at about 25% the intensity of oestradiol. Further experiments are needed to elucidate the exact mechanisms behind this finding.
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| 4. |
- Jochems, Caroline, 1973, et al.
(författare)
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Role of endogenous and exogenous female sex hormones in arthritis and osteoporosis development in B10.Q-ncf1*/* mice with collagen-induced chronic arthritis.
- 2010
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Ingår i: BMC musculoskeletal disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 16:11
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Tidskriftsartikel (refereegranskat)abstract
- Collagen-induced arthritis (CIA) is an often-used murine model for human rheumatoid arthritis (RA). Earlier studies have shown potent anti-arthritic effects with the female sex hormone estradiol and the selective estrogen receptor modulator (SERM) raloxifene in CIA in DBA/1-mice. B10.Q-ncf1*/*mice are B10.Q mice with a mutated Ncf1 gene. In B10.Q-ncf1*/*mice, CIA develops as a chronic relapsing disease, which more accurately mimics human RA. We investigated the role of endogenous and exogenous sex steroids and raloxifene in the course of this model of chronic arthritis. We also examined whether treatment would prevent the development of inflammation-triggered generalized osteoporosis.
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| 5. |
- Johansson, Tomas, et al.
(författare)
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Transcriptional responses of Paxillus involutus and Betula pendula during formation of ectomycorrhizal root tissue
- 2004
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Ingår i: Molecular Plant-Microbe Interactions. - 0894-0282 .- 1943-7706. ; 17:2, s. 202-215
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Tidskriftsartikel (refereegranskat)abstract
- In order to obtain information on genes specifically expressed in the ectomycorrhizal symbiosis, 3,555 expressed sequence tags (ESTs) were analyzed from a cDNA library constructed from ectomycorrhiza formed between the basidiomycete Paxillus involutus and birch (Betula pendula). cDNA libraries from saprophytically growing fungus (3,964 ESTs) and from axenic plants (2,532 ESTs) were analyzed in parallel. By clustering all the EST obtained, a nonredundant set of 2,284 unique transcripts of either fungal or plant origin were identified. The expression pattern of these genes was analyzed using cDNA microarrays. The analyses showed that the plant and fungus responded to the symbiosis by altering the expression levels of a number of enzymes involved in carbon metabolism. Several plant transcripts with sequence similarities to genes encoding enzymes in the tricarboxylic cycle and electron transport chain were down regulated as compared with the levels in free-living roots. In the fungal partner, a number of genes encoding enzymes in the lipid and secondary metabolism were down regulated in mycorrhiza as compared with the saprophytically growing mycelium. A substantial number of the ESTs analyzed displayed significant sequence similarities to proteins involved in biotic stress responses, but only a few of them showed differential expression in the mycorrhizal tissue, including plant and fungal metallothioneins and a plant defensin homologue. Several of the genes that were differentially expressed in the mycorrhizal root tissue displayed sequence similarity to genes that are known to regulate growth and development of plant roots and fungal hyphae, including transcription factors and Rho-like GTPases.
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| 6. |
- Lagerquist, Marie, et al.
(författare)
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17Beta-estradiol expands IgA-producing B cells in mice deficient for the mu chain.
- 2008
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Ingår i: Scandinavian journal of immunology. - : Wiley. - 1365-3083 .- 0300-9475. ; 67:1, s. 12-7
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Tidskriftsartikel (refereegranskat)abstract
- Oestrogen is not only a sex hormone but also an important regulator of the immune system. Expression of the heavy chain of IgM (mu) is essential for B-cell differentiation. However, a small number of IgA-positive B cells can be found in mice lacking the mu chain (muMT-/-). The aim of this study was to investigate the effects of oestrogen on this alternative B-cell pathway in muMT-/- mice. Our results clearly demonstrate that oestrogen increases the frequency of IgA-producing B cells in muMT-/- mice in both bone marrow and spleen cells. We also show that mature IgM-producing B cells are not required for oestrogen-mediated suppression of granulocyte-mediated inflammation or thymic involution. In conclusion, we demonstrate that 17beta-estradiol benzoate increases the frequency of IgA-producing B cells in muMT-/- mice, suggesting that oestrogen can influence the alternative B-cell pathway found in muMT-/- mice.
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| 7. |
- Lysenkova Wiklander, Mariya, et al.
(författare)
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Genomic, transcriptomic and epigenomic sequencing data of the B-cell leukemia cell line REH
- 2023
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Ingår i: BMC Research Notes. - : BioMed Central (BMC). - 1756-0500. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesThe aim of this data paper is to describe a collection of 33 genomic, transcriptomic and epigenomic sequencing datasets of the B-cell acute lymphoblastic leukemia (ALL) cell line REH. REH is one of the most frequently used cell lines for functional studies of pediatric ALL, and these data provide a multi-faceted characterization of its molecular features. The datasets described herein, generated with short- and long-read sequencing technologies, can both provide insights into the complex aberrant karyotype of REH, and be used as reference datasets for sequencing data quality assessment or for methods development.Data descriptionThis paper describes 33 datasets corresponding to 867 gigabases of raw sequencing data generated from the REH cell line. These datasets include five different approaches for whole genome sequencing (WGS) on four sequencing platforms, two RNA sequencing (RNA-seq) techniques on two different sequencing platforms, DNA methylation sequencing, and single-cell ATAC-sequencing.
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| 8. |
- Sievertzon, Maria, et al.
(författare)
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Transcriptome analysis in primary neural stem cells using a tag cDNA amplification method
- 2005
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Ingår i: BMC Neuroscience. - : Springer Science and Business Media LLC. - 1471-2202. ; 6:28, s. 13-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Neural stem cells ( NSCs) can be isolated from the adult mammalian brain and expanded in culture, in the form of cellular aggregates called neurospheres. Neurospheres provide an in vitro model for studying NSC behaviour and give information on the factors and mechanisms that govern their proliferation and differentiation. They are also a promising source for cell replacement therapies of the central nervous system. Neurospheres are complex structures consisting of several cell types of varying degrees of differentiation. One way of characterising neurospheres is to analyse their gene expression profiles. The value of such studies is however uncertain since they are heterogeneous structures and different populations of neurospheres may vary significantly in their gene expression. Results: To address this issue, we have used cDNA microarrays and a recently reported tag cDNA amplification method to analyse the gene expression profiles of neurospheres originating from separate isolations of the lateral ventricle wall of adult mice and passaged to varying degrees. Separate isolations as well as consecutive passages yield a high variability in gene expression while parallel cultures yield the lowest variability. Conclusions: We demonstrate a low technical amplification variability using the employed amplification strategy and conclude that neurospheres from the same isolation and passage are sufficiently similar to be used for comparative gene expression analysis.
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| 9. |
- Woll, Petter S, et al.
(författare)
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Myelodysplastic Syndromes Are Propagated by Rare and Distinct Human Cancer Stem Cells In Vivo.
- 2014
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Ingår i: Cancer Cell. - : Elsevier BV. - 1878-3686 .- 1535-6108. ; 25:6, s. 794-808
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Tidskriftsartikel (refereegranskat)abstract
- Evidence for distinct human cancer stem cells (CSCs) remains contentious and the degree to which different cancer cells contribute to propagating malignancies in patients remains unexplored. In low- to intermediate-risk myelodysplastic syndromes (MDS), we establish the existence of rare multipotent MDS stem cells (MDS-SCs), and their hierarchical relationship to lineage-restricted MDS progenitors. All identified somatically acquired genetic lesions were backtracked to distinct MDS-SCs, establishing their distinct MDS-propagating function in vivo. In isolated del(5q)-MDS, acquisition of del(5q) preceded diverse recurrent driver mutations. Sequential analysis in del(5q)-MDS revealed genetic evolution in MDS-SCs and MDS-progenitors prior to leukemic transformation. These findings provide definitive evidence for rare human MDS-SCs in vivo, with extensive implications for the targeting of the cells required and sufficient for MDS-propagation.
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