| 1. |
- Munksgaard Persson, Matilda, et al.
(författare)
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HIF-2 alpha Expression Is Suppressed in SCLC Cells, Which Survive in Moderate and Severe Hypoxia When HIF-1 alpha Is Repressed
- 2012
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Ingår i: American Journal of Pathology. - : Elsevier. - 0002-9440 .- 1525-2191. ; 180:2, s. 494-504
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Tidskriftsartikel (refereegranskat)abstract
- Small cell lung carcinoma (SCLC) is extremely aggressive and frequently metastasizes widely in its early stage. Because tumor hypoxia is related to aggressive tumor behavior and the hypoxic adaptation of SCLC is poorly documented, we stained SCLC tumors arranged in a tissue microarray for hypoxia-inducible factor (HIF)-1 alpha and HIF-2 alpha proteins. We found an overall lack of HIF-2 alpha protein expression, which was confirmed in large tumor sections. HIF-1 alpha protein was strongly expressed in most tumors, frequently adjacent to necrotic regions. In concordance, cultured SCLC but not non-small cell lung carcinoma cells showed no or extremely low levels of HIF-2 alpha mRNA and no HIF-2 alpha protein at hypoxia. HIF-1 alpha was stabilized after 4 hours at hypoxia, and its accumulation increased up to 96 hours. SCLC cells survived well and showed net proliferation and low cell death in modest (1% oxygen) and severe (0.1% oxygen) hypoxia. HIF-1 alpha repression virtually did not influence cell death or viability despite reduced levels of hypoxia-inducible genes, such as BNIP3 and BNIP3L. At 1% oxygen no increased autophagy (LC3B-II activation) or NF-kappa B signaling were detected, whereas the unfolded protein response was activated at severe hypoxia. Our data indicate that HIFs are not exclusively required for SCLC cell survival at modest or severe hypoxia and that additional, yet uncharacterized, hypoxia-driven adaptation pathways may become activated.
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| 2. |
- Ovaskainen, Louise, 1981-
(författare)
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Superhydrophobic coatings of wax and polymers sprayed from supercritical solutions
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The possibility of using supercritical carbon dioxide (scCO2) as the primary solvent in a spray process for producing superhydrophobic surfaces have been examined in this work. Using scCO2 as solvent will have considerably lower environmental impact compared to an organic solvent since scCO2 is considered a green solvent as it is non-toxic, non-flammable and recyclable. To be able to work at the pressures needed to reach the supercritical state of carbon dioxide, a high-pressure technique called rapid expansion of supercritical solutions (RESS) has been used to produce the coatings. Fluorinated compounds are often used when producing superhydrophobic coatings due to their intrinsic water repellent properties, but generally these compound do not degrade in nature. Due to this, a wax and a biodegradable polymer have been used as the coating materials in this work.Two RESS set-ups were used to spray a polymer from solutions of scCO2 and acetone. The first system was based on a continuous flow of the solvent mixture and the polymer particles were collected on silica surfaces. Some of the coatings had superhydrophobic properties and the limitation with this technique was the loss of particles between the nozzle and the surface. In the second set-up, RESS was combined with electrostatic deposition (ED) to improve the particle collection. Different processing parameters were examined and most of the RESS-ED sprayed surfaces were superhydrophobic. This was demonstrated by high contact angles against water, low contact angle hysteresis and low tilt angles at which a water droplet rolls off the surface. It was also shown that the surface structures created when spraying using RESS-ED induced the important two-level roughness that was needed to achieve superhydrophobicity. A semi-continuous process for scaling-up the RESS system when spraying the wax has been developed. Temperature and pressure was investigated to find the highest solubility of the wax in scCO2, and 250 bar and 67 °C resulted in the largest amount of sprayed wax. It was also shown that the system is suitable for spray-coating the wax on different substrates such as glass, paper, aluminium etc. since all of these surfaces showed superhydrophobic properties. The wear resistance of the coatings were examined by different methods. Scratch resistance, vertical compression and the friction between the surface and a finger were analysed. The polymer coated surfaces showed a larger robustness compared with the wax surfaces in the scratch tests. The superhydrophobicity was lost for the wax coatings exposed to compression loads above 59 kPa and in the frictions test, one finger stroke over the coating destroyed the surface roughness. Finally, the wax surfaces were investigated as coating barriers to protect steel from corrosion. The superhydrophobic coating was stable up to 10 days before corrosion of the steel started.
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| 3. |
- Skogh, Ann-Charlott Docherty, et al.
(författare)
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Variation in Calvarial Bone Healing Capacity : A Clinical Study on the Effects of BMP-2-Hydrogel or Bone Autograft Treatments at Different Cranial Locations
- 2013
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Ingår i: The Journal of craniofacial surgery (Print). - 1049-2275 .- 1536-3732. ; 24:2, s. 339-343
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Tidskriftsartikel (refereegranskat)abstract
- Background: Bone morphogenetic protein-2 (BMP-2) together with a suitable carrier is an attractive option that may be used for craniofacial bone reconstruction. In this prospective randomized study, a hyaluronan-based hydrogel with BMP-2 was used to achieve bone healing in standardized critical-size cranial defects in humans after neurosurgery. Methods: Twelve patients were randomized into the treatment group (N = 6) or control group (N = 6). In the treatment group, holes made during craniotomy were treated with hydrogel with BMP-2, 250 mu g/mL, or hydrogel without BMP-2. In the remaining hole/s in the same patient, Spongostan (Ethicon) alone or Tisseel (Baxter) mixed with autologous bone matrix were used as negative and positive controls, respectively. In the control group, the holes were treated with Spongostan or Tisseel mixed with bone autograft. Bone healing was assessed with CT scans after 3 and 6 months. Bone areas in treated defects were measured and statistical analysis was performed. Results: Independent of location, bone healing in defects treated with Tisseel with autograft, hydrogel alone, or hydrogel with BMP-2 was significantly increased compared to negative control (P < 0.001, P = 0.002, and P = 0.005, respectively). In general, all defects healed significantly better in the frontal bone as compared to parietal-temporal location, except for defects treated with Tisseel and autograft, which healed well independently of location. No local or systemic side effects, including excessive bone overgrowth or inflammatory reaction, were seen in treated patients. Conclusions: Tissue engineering of bone with hyaluronan-based hydrogel shows good healing of cranial defects, comparable with bone autografts. The hydrogel itself may represent a novel alternative to autologous bone transplants in craniofacial bone repair. The study also reveals a general superior healing capacity in the frontal bone as compared to parietal/temporal bones.
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