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| 2. |
- Bjellerup, Mats, et al.
(författare)
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The role of vascular surgery in chronic leg ulcers: report from a specialized ulcer clinic.
- 2002
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Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 1651-2057 .- 0001-5555. ; 82:4, s. 266-269
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Tidskriftsartikel (refereegranskat)abstract
- Experience gained from cooperation between dermatologists and vascular surgeons in 177 patients evaluated at a joint leg ulcer clinic is reported. Patients were divided into two subgroups: (i) 86 patients with healed ulcers and (ii) 91 patients with ongoing therapy-resistant ulcers. Venous insufficiency was the most common etiology in both subgroups (87% and 55%, respectively). Of previous therapy-resistant ulcers, 71% were healed after the combined effort. The pattern of venous incompetence differed between the two subgroups; patients with isolated superficial disease constituting 68% and 26% of patients, respectively. In patients with therapy-resistant ulcers, those with isolated superficial venous insufficiency were found to have a better prognosis than those with deep venous insufficiency. Cooperation between the dermatologist and vascular surgeon is a mainstay in order to take advantage of the possibilities offered by modern vascular surgery.
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| 3. |
- Blixt, Maria, et al.
(författare)
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MYCN induces cell-specific tumorigenic growth in RB1-proficient human retinal organoid and chicken retina models of retinoblastoma
- 2022
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Ingår i: Oncogenesis. - : Springer Science and Business Media LLC. - 2157-9024. ; 11:1, s. 34-
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Tidskriftsartikel (refereegranskat)abstract
- Retinoblastoma is a rare, intraocular paediatric cancer that originates in the neural retina and is most frequently caused by bi-allelic loss of RB1 gene function. Other oncogenic mutations, such as amplification and increased expression of the MYCN gene, have been found even with proficient RB1 function. In this study, we investigated whether MYCN over-expression can drive carcinogenesis independently of RB1 loss-of-function mutations. The aim was to elucidate the events that result in carcinogenesis and identify the cancer cell-of-origin. We used the chicken retina, a well-established model for studying retinal neurogenesis, and established human embryonic stem cell-derived retinal organoids as model systems. We over-expressed MYCN by electroporation of piggyBac genome-integrating expression vectors. We found that over-expression of MYCN induced tumorigenic growth with high frequency in RB1-proficient chicken retinas and human organoids. In both systems, the tumorigenic cells expressed markers for undifferentiated cone photoreceptor/horizontal cell progenitors. The over-expression resulted in metastatic retinoblastoma within 7–9 weeks in chicken. Cells expressing MYCN could be grown in vitro and, when orthotopically injected, formed tumours that infiltrated the sclera and optic nerve and expressed markers for cone progenitors. Investigation of the tumour cell phenotype determined that the potential for neoplastic growth was embryonic stage-dependent and featured a cell-specific resistance to apoptosis in the cone/horizontal cell lineage, but not in ganglion or amacrine cells. We conclude that MYCN over-expression is sufficient to drive tumorigenesis and that a cell-specific resistance to apoptosis in the cone/horizontal cell lineage mediates the cancer phenotype.
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| 5. |
- Wallman, Lars, et al.
(författare)
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Biogrid-a microfluidic device for large-scale enzyme-free dissociation of stem cell aggregates.
- 2011
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Ingår i: Lab on a Chip. - : Royal Society of Chemistry (RSC). - 1473-0189 .- 1473-0197. ; 11, s. 3241-3248
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Tidskriftsartikel (refereegranskat)abstract
- Culturing stem cells as free-floating aggregates in suspension facilitates large-scale production of cells in closed systems, for clinical use. To comply with GMP standards, the use of substances such as proteolytic enzymes should be avoided. Instead of enzymatic dissociation, the growing cell aggregates may be mechanically cut at passage, but available methods are not compatible with large-scale cell production and hence translation into the clinic becomes a severe bottle-neck. We have developed the Biogrid device, which consists of an array of micrometerscale knife edges, micro-fabricated in silicon, and a manifold in which the microgrid is placed across the central fluid channel. By connecting one side of the Biogrid to a syringe or a pump and the other side to the cell culture, the culture medium with suspended cell aggregates can be aspirated, forcing the aggregates through the microgrid, and ejected back to the cell culture container. Large aggregates are thereby dissociated into smaller fragments while small aggregates pass through the microgrid unaffected. As proof-of-concept, we demonstrate that the Biogrid device can be successfully used for repeated passage of human neural stem/progenitor cells cultured as so-called neurospheres, as well as for passage of suspension cultures of human embryonic stem cells. We also show that human neural stem/progenitor cells tolerate transient pressure changes far exceeding those that will occur in a fluidic system incorporating the Biogrid microgrids. Thus, by using the Biogrid device it is possible to mechanically passage large quantities of cells in suspension cultures in closed fluidic systems, without the use of proteolytic enzymes.
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