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- Erdtman, Edvin, et al.
(författare)
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Modelling the behavior of 5-aminolevulinic acid and its alkyl esters in a lipid bilayer
- 2008
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Ingår i: Chemical Physics Letters. - Amsterdam : North-Holland Publishing Co. - 0009-2614 .- 1873-4448. ; 463:1-3, s. 178-182
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Tidskriftsartikel (refereegranskat)abstract
- 5-Aminolevulinic acid (5ALA) and ester derivates thereof are used as prodrugs in photodynamic therapy (PDT). The behavior of 5ALA and three esters of 5ALA in a DPPC lipid bilayer is investigated. In particular, the methyl ester displays a very different free energy profile, where the highest barrier is located in the region with highest lipid density, while the others have their peak in the middle of the membrane, and also displays a considerably lower permeability coefficient than neutral 5ALA and the ethyl ester. The zwitterion of 5ALA has the highest permeability constant, but a significant free energy minimum in the polar head-group region renders an accumulation in this region.
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| 3. |
- Landström, Fredrik, 1966-, et al.
(författare)
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Electrochemotherapy - possible benefits and limitations to its use in the head and neck region
- 2015
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Ingår i: Acta Oto-Laryngologica. - : Informa Healthcare. - 0001-6489 .- 1651-2251. ; 135:1, s. 90-95
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Tidskriftsartikel (refereegranskat)abstract
- Conclusion: Electrochemotherapy (ECT) is an efficacious treatment. It should, however, be used with some caution in the treatment of head and neck cancer.Objectives: To assess local tumor control, safety, survival, and functional outcome after treatment of cancer in the head and neck region with ECT.Methods: Four patients with primary T2 cancer of the oral cavity or oropharynx and one patient with a metastasis of renal cancer in the masseter muscle were treated with ECT with intratumorally administered bleomycin. Control biopsies were carried out 2 months after treatment. Postoperative radiotherapy was performed based on tumor T-stage and the depth of tumor infiltration. Serious adverse events and treatment malfunctions were recorded. The follow-up time was 24 months for the surviving patients and 20 months overall. The PSS-HN scale was used to assess the functional outcome.Results: No local recurrence was recorded in any patient during the follow-up. However, only one patient was treated with ECT alone. There were four serious adverse events: one nearly lethal bleeding, two cases of osteoradionecrosis, and a fistula. One patient died from distant metastasis. The other patients were tumor-free both locally and overall at 24 months. The median functional outcome in all parameters was worse 1 year after treatment.
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| 4. |
- Landström, Fredrik J., 1966-, et al.
(författare)
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Electroporation therapy for T1 and T2 oral tongue cancer
- 2011
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Ingår i: Acta Oto-Laryngologica. - : Informa Healthcare. - 0001-6489 .- 1651-2251. ; 131:6, s. 660-664
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Tidskriftsartikel (refereegranskat)abstract
- Conclusion: Electroporation therapy appears to be a safe treatment achieving excellent local tumor control and very good functional results in our study and it should be further clinically evaluated.Objectives: The objectives of this study were to assess local tumor control, survival, and effects on speech and eating after treatment of tongue cancer with electroporation therapy, a new local therapeutic modality. In this approach intracellular accumulation of a chemotherapeutic agent is achieved by using a locally applied electrical field.Methods: Fifteen patients with primary T1 and T2 oral tongue cancer were treated with electroporation therapy with intratumorally administered bleomycin. Postoperative radiotherapy was performed when the tumor infiltration was 5 mm or more. The follow-up time was 24 months for the surviving patients and 20.4 months overall. The effects on eating and speech were assessed using the PSS-HN scale and voice recordings.Results: No local recurrence was recorded in any patient during the follow-up. Three patients died, two from progressive regional disease. Of the 12 surviving patients, 2 patients had regional recurrence and 10 patients including the 5 patients treated with EPT alone were tumor-free both locally and regionally at the last follow-up. The functional outcome for speech and eating were very good.
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| 5. |
- Landström, Fredrik J, et al.
(författare)
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Electroporation therapy of skin cancer in the head and neck area.
- 2010
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Ingår i: Dermatologic Surgery. - : Ovid Technologies (Wolters Kluwer Health). - 1076-0512 .- 1524-4725. ; 36:8, s. 1245-50
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Electroporation therapy is a new cancer treatment modality in which a locally applied electrical field enhances cell membrane permeability, allowing greater intracellular accumulation of a chemotherapeutic agent.OBJECTIVE: To evaluate the efficacy of electroporation therapy in treating basal cell and squamous cell carcinomas of the skin.MATERIALS AND METHODS: Six patients with skin cancer of the head and neck were treated using electroporation therapy with intratumorally injected bleomycin. Orbital growth, facial nerve proximity, or proximity to cartilage of the external meatus complicated four of these tumors. The intention was curative. The follow-up period was 24 months and included biopsies after 8 weeks.RESULTS: In four of the six patients, one treatment was enough to eradicate the tumor. In one patient, the tumor persisted even after a second treatment with electroporation therapy. A septal cartilage perforation was the only major complication. The cosmetic results were very satisfactory. One additional recurrence was recorded 6 months after the follow-up periodCONCLUSION: Electroporation therapy is a promising new cancer treatment that should be further evaluated as an alternative to surgery, especially in complicated skin cancer.
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| 9. |
- Löfgren, Sara E., et al.
(författare)
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A 3 '-Untranslated Region Variant Is Associated With Impaired Expression of CD226 in T and Natural Killer T Cells and Is Associated With Susceptibility to Systemic Lupus Erythematosus
- 2010
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 62:11, s. 3404-3414
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Costimulatory receptor CD226 plays an important role in T cell activation, differentiation, and cytotoxicity. This study was undertaken to investigate the genetic association of CD226 with susceptibility to systemic lupus erythematosus (SLE) and to assess the functional implications of this association. Methods. Twelve tag single-nucleotide polymorphisms (SNPs) in CD226 were typed in 1,163 SLE patients and 1,482 healthy control subjects from Europe or of European ancestry. Analyses of association were performed by single-marker Cochran-Mantel-Haenszel meta-analysis, followed by haplotype analysis. Gene expression was analyzed by quantitative real-time polymerase chain reaction analyses of RNA from peripheral blood mononuclear cells, and by fluorescence-activated cell sorter analysis. To study the functional impact of the associated variants, luciferase reporter constructs containing different portions of the 3'-untranslated region (3'-UTR) of the gene were prepared and used in transfection experiments. Results. A 3-variant haplotype, rs763361; rs34794968; rs727088 (ATC), in the last exon of CD226 was associated with SLE (P = 1.3 x 10(-4), odds ratio 1.24, 95% confidence interval 1.11-1.38). This risk haplotype correlated with low CD226 transcript expression and low CD226 protein levels on the surface of CD4+ and CD8+ T cells and natural killer T (NKT) cells. NK cells expressed high levels of CD226, but this expression was independent of the haplotype. Reporter assays with deletion constructs indicated that only the presence of rs727088 could account for the differences in the levels of luciferase transcripts. Conclusion. This study identified an association of CD226 with SLE in individuals of European ancestry. These data support the importance of the 3'-UTR SNP rs727088 in the regulation of CD226 transcription both in T cells and in NKT cells.
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| 10. |
- Löfgren, Sara E, et al.
(författare)
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Genetic association of miRNA-146a with systemic lupus erythematosus in Europeans through decreased expression of the gene
- 2012
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Ingår i: Genes and Immunity. - : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 13:3, s. 268-274
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Tidskriftsartikel (refereegranskat)abstract
- A recent genome-wide association study revealed a variant (rs2431697) in an intergenic region, between the pituitary tumor-transforming 1 (PTTG1) and microRNA (miR-146a) genes, associated with systemic lupus erythematosus (SLE) susceptibility. Here, we analyzed with a case-control design this variant and other candidate polymorphisms in this region together with expression analysis in order to clarify to which gene this association is related. The single-nucleotide polymorphisms (SNPs) rs2431697, rs2910164 and rs2277920 were genotyped by TaqMan assays in 1324 SLE patients and 1453 healthy controls of European ancestry. Genetic association was statistically analyzed using Unphased. Gene expression of PTTG1, the miRNAs miR-3142 and primary and mature forms of miR-146a in peripheral blood mononuclear cells (PBMCs) were assessed by quantitative real-time PCR. Of the three variants analyzed, only rs2431697 was genetically associated with SLE in Europeans. Gene expression analysis revealed that this SNP was not associated with PTTG1 expression levels, but with the microRNA-146a, where the risk allele correlates with lower expression of the miRNA. We replicated the genetic association of rs2341697 with SLE in a case-control study in Europeans and demonstrated that the risk allele of this SNP correlates with a downregulation of the miRNA 146a, potentially important in SLE etiology.
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