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- Munthe, Christian, 1962
(författare)
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Etiska aspekter på regenerativ medicin : Ethical aspects on regenerative medicine
- 2003
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Ingår i: SNIB-konferensen 2003, Chalmers tekniska högskola, Göteborg, 16-18 maj 2003.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Inom den regenerativa medicinen strävar man efter att ersätta skadat eller sjukligt biologiskt mänskligt material (celler, organ, kroppsdelar) med nya biologiska komponenter. Området aktualiserar en rad etiska frågeställningar vad gäller (1) produktionen av ersättningsmaterialet (t.ex. embryonala stamceller eller införskaffande av transplantationsvävnad från donatorer), (2) risker i samband med försök på människa (genmodifierat material, material från djur), samt (3) gränserna för hur långt man bör gå i denna slags försök att förlänga människans livsspann. Föredraget ger en kort översikt över dessa frågeställningar, ståndpunkter och argument i debatten kring dem.
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| 2. |
- Montelius, Mikael, 1979, et al.
(författare)
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Multiparametric MRI with spatiotemporal evaluation reveals potential therapy response biomarkers for 177Lu-octreotate therapy of mice with human neuroendocrine tumor
- 2017
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Ingår i: ISMRM 25th Annual Meeting. 22-27 April 2017, Honolulu, Hawaii, USA.
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Konferensbidrag (refereegranskat)abstract
- Tissue parameters derived from multiparametric MRI were evaluated as potential imaging biomarkers for therapy response assessment in mice with human neuroendocrine tumor treated with 177Lu-octreotate. Animals were imaged before and repeatedly after 177Lu-octreotate treatment, using T2w, IVIM-DWI, DCE-MRI, T1- and T2*-mapping techniques. MR-parameters were evaluated regionally and longitudinally, and quantitative proteomics was used to evaluate underlying biological response in central and peripheral tumor separately. Several MR-parameters showed strong correlation with tumor response, as verified by MRI-based tumor volume measurements, but also with proteins associated with radiobiological effects on tumor tissue. Spatial and temporal evaluation increased sensitivity of the methods.
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| 3. |
- Spetz, Johan, et al.
(författare)
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Effects of internal irradiation from 177Lu-octreotate on transcriptional expression in GOT1 midgut carcinoid in nude mice
- 2014
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Ingår i: SweRays Workshop, Malmö, Sweden, Aug 20-22.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Neuroendocrine (NE) tumors expressing somatostatin receptors (SSTR) are often treated with 177Lu-octreotate. The treatment is highly successful in animal models, but low cure rates in clinical studies suggests optimization of treatment protocol is needed. Little is known about which cellular responses play a crucial role in neuroendocrine tumors after irradiation. It is therefore important to identify the effects of 177Lu-octreotate on biological functions for future optimization of treatment parameters and the identification of biomarkers predicting treatment response. The aim of this study was to investigate the transcriptional response of GOT1 midgut carcinoid in nude mice following 177Lu-octreotate treatment. Methods: GOT1 bearing BALB/c nude mice were i.v. injected with 15 MBq 177Lu-octreotate and tumor size was measured twice a week using calipers. Animals were killed after 1, 3, 7 or 41 days and tumor samples excised and snap frozen in liquid nitrogen. Total RNA was extracted from tumor samples and subjected to Illumina microarray expression analysis. Differential transcriptional profiles were identified by comparing treated and untreated tumor samples using Nexus Expression 3.0 software. Associated biological functions and biological pathways (according to Gene Ontology terms) were compared using Nexus Expression 3.0 and Ingenuity IPA. Results: The mean tumor volume was clearly reduced after 177Lu-octreotate treatment. Microarray analysis showed clear difference in regulation pattern between the time points. The analysis of associated biological functions revealed clear effect on cell death and survival, and cell cycle after 1, 3, and 7 days, while cellular movement and cellular development were clearly influenced after 41 days. Cellular growth and proliferation was also affected after 1 day but not at the other time points studied. Conclusions: : Analysis of the transcriptional regulation in GOT1 tumors in nude mice following 177Lu-octreotate treatment revealed responses in different cellular functions that were distinct for each time point. These findings indicate potential venues for increasing clinical effectiveness of midgut carcinoid therapy with 177Lu-octreotate.
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| 5. |
- Hamngren Blomqvist, Charlotte, 1984, et al.
(författare)
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Design and evaluation of a microfluidic system for inhibition studies of yeast cell signaling
- 2012
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Ingår i: Proceedings of SPIE. - : SPIE. - 0277-786X .- 1996-756X. - 9780819491756 ; , s. 84582K-
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Konferensbidrag (refereegranskat)abstract
- In cell signaling, different perturbations lead to different responses and using traditional biological techniques that result in averaged data may obscure important cell-to-cell variations. The aim of this study was to develop and evaluate a four-inlet microfluidic system that enables single-cell analysis by investigating the effect on Hog1 localization post a selective Hog1 inhibitor treatment during osmotic stress. Optical tweezers was used to position yeast cells in an array of desired size and density inside the microfluidic system. By changing the flow rates through the inlet channels, controlled and rapid introduction of two different perturbations over the cell array was enabled. The placement of the cells was determined by diffusion rates flow simulations. The system was evaluated by monitoring the subcellular localization of a fluorescently tagged kinase of the yeast "High Osmolarity Glycerol" (HOG) pathway, Hog1-GFP. By sequential treatment of the yeast cells with a selective Hog1 kinase inhibitor and sorbitol, the subcellular localization of Hog1-GFP was analysed on a single-cell level. The results showed impaired Hog1-GFP nuclear localization, providing evidence of a congenial design. The setup made it possible to remove and add an agent within 2 seconds, which is valuable for investigating the dynamic signal transduction pathways and cannot be done using traditional methods. We are confident that the features of the four-inlet microfluidic system will be a valuable tool and hence contribute significantly to unravel the mechanisms of the HOG pathway and similar dynamic signal transduction pathways.
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| 6. |
- Abbas, Abdul-Karim, 1959, et al.
(författare)
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Long-term potentiation and insult conditioning in hippocampal slices from young rats: a role for protein synthesis under chemical stress?
- 2010
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Ingår i: The 10th Biennial Meeting of the Asia-Pacific Society for Neurochemistry (APSN), October 17-20, 2010, Phuket, Thailand.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- We have previously demonstrated that in young rats (12-20-day-old) a sustained long-term potentiation (LTP) can still be induced under conditions of protein synthesis inhibition. It was therefore suggested that sufficient and necessary proteins were already available at the induction time to accomplish LTP maintenance for several hours. Against this background, we have questioned whether hippocampal slices subjected to certain insult conditions might be more sensitive to protein synthesis inhibitors. High K+ concentration has previously been reported to cause an amnesic effect in vivo as well as increasing protein turnover in vitro. We have here employed a K+ insult model under conditions when protein synthesis was inhibited. Recordings were obtained from hippocampal slices for up to 9 h, with or without a cocktail of protein synthesis inhibitors, containing cycloheximide (60 µM) and anisomycin (25 µM). High potassium (50 mM) was transiently applied (5-15 min) shortly after inducing LTP in one of two separate pathways stimulated alternatively. Additionally, an NMDA-receptor antagonist AP5 was supplied after LTP induction to minimize effects related to depolarization-induced glutamate release. Following elimination of all responses for about 30 min, both test and control responses partly recovered. The degree of remaining LTP, defined as test/control ratio, was reduced in both groups of slices (NMDA-independent depotentiation) but was significantly smaller in the drug-treated ones. We are also running an insult model based on oxidative stress, applying hydrogen peroxide (4-5 mM) before or after LTP induction; however, the results are still insufficient for a final conclusion. The potency of cycloheximide, anisomycin or cocktail of the drugs was verified by measurement of incorporation of [3H]-leucine into trichloracetic acid (TCA) precipitable macromolecules. Cycloheximide, anisomycin or cocktail, at concentrations used here caused 95%, 97% and 95% blocking effect, respectively. Our data confirm the idea that sufficient and necessary constitutive proteins are available in the young hippocampus to maintain LTP under conditions of protein synthesis inhibition. They also reveal that LTP in slices subjected to certain insult conditions early after the induction is sensitive to protein synthesis inhibition, probably due to increase in constitutive proteins turnover.
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| 7. |
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| 8. |
- Spetz, Johan, et al.
(författare)
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Spatial proteomic analysis of GOT1 human small intestine neuroendocrine tumor in nude mice following 177Lu-octreotate therapy
- 2016
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Ingår i: 62nd Annual International Meeting Radiation Research Society, Waikoloa, HI, USA, October 16-19, 2016.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: 177Lu-octreotate can be used for therapy of somatostatin receptor expressing neuroendocrine tumors (NET). 177Lu-octreotate therapy has achieved high cure rates in GOT1 (human small intestine NET) transplanted to nude mice. However, clinical studies result in moderate response, and complete tumor remission is rarely seen. Solid tumors often develop necrotic cores during growth due to e.g. insufficient vascularization, which may account for the different uptake kinetics and varying therapeutic success seen after 177Lu-octreotate treatment. It is therefore important to explore the cellular effects of 177Lu-octreotate to further optimize treatment parameters and identify biomarkers for treatment response assessment. Aim: To detect significant changes in protein profiles from peripheral and central samples of GOT1 tumor after 177Lu-octreotate therapy. Methods: GOT1 bearing BALB/c nude mice were i.v. injected with 15 MBq 177Lu-octreotate (corresponding to 4 Gy tumor absorbed dose) and killed after 13 days. Total cellular proteins were extracted from the peripheral and central parts of surgically excised tumor samples. Proteomic profiling was generated using liquid chromatography tandem-mass spectrometry (LC-MS/MS), followed by database-based protein identification and relative quantification. Functional annotation of proteins was performed using the DAVID bioinformatics resource tool. Results: The LC-MS/MS analysis identified 58 differentially expressed proteins (p<0.05, Fold Change>1.2) between the peripheral and central parts of tumor samples. Forty of these showed higher levels in the peripheral compared with the central samples, and among them were proteins associated with blood vessel/vasculature development (e.g. FAK1, H6ST1, LMA4, and SYWM), regulation of cell cycle and apoptosis (e.g. FAK1 and MK01), and cellular integrity (e.g. PDLI5, CALD1, FERM2, and NEB2). Conclusions: Taken together, these findings suggest spatial differences in tumor response to 177Lu-octreotate, mainly constituted by differences in vascularization and cellular integrity. These findings indicate potential venues for prognostic evaluation of NET therapy using 177Lu-octreotate. However, further studies are needed to determine whether these effects are time- and/or dose-dependent.
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| 9. |
- Calon, Tim, et al.
(författare)
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Multimodal analysis of the tissue response to a bone-anchored hearing implant. : 11. Calon TGA, Johansson ML, Omar O, Shah FA, Budding D, Trobos M, Thomsen P, Stokroos RJ, Palmquist
- 2019
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Ingår i: 2nd Politzer Society Meeting/2nd World Congress of Otology, 28 May - 1 June, 2019, Warsaw, Poland..
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 10. |
- Henry, Ewan, et al.
(författare)
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Sorting red blood cells by their dynamical properties
- 2016
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Ingår i: 20th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2016. - 9780979806490 ; , s. 786-787
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Konferensbidrag (refereegranskat)abstract
- A combination of mesoscale hydrodynamic simulations and microfluidic experiments are used to explore the use of cells' mechanical and dynamical properties as biomarkers for separation. Dynamic behaviour of red blood cells (RBCs) within deterministic lateral displacement (DLD) devices is investigated within various array geometries and for different viscosity contrasts between the intra- and extra-cellular fluid. We find that the viscosity contrast and associated cell dynamics clearly determine RBC trajectories through DLD devices. Simulation results compare well to experiments and provide new insights into the physical mechanisms which govern the sorting of non-spherical and deformable cells in DLD devices.
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