| 51. |
- Schmidt, L., et al.
(författare)
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Comparative drug pair screening across multiple glioblastoma cell lines reveals novel drug-drug interactions
- 2013
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Ingår i: Neuro-Oncology. - : Oxford University Press (OUP). - 1522-8517 .- 1523-5866. ; 15:11, s. 1469-1478
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Tidskriftsartikel (refereegranskat)abstract
- Glioblastoma multiforme (GBM) is the most aggressive brain tumor in adults, and despite state-of-the-art treatment, survival remains poor and novel therapeutics are sorely needed. The aim of the present study was to identify new synergistic drug pairs for GBM. In addition, we aimed to explore differences in drug-drug interactions across multiple GBM-derived cell cultures and predict such differences by use of transcriptional biomarkers. We performed a screen in which we quantified drug-drug interactions for 465 drug pairs in each of the 5 GBM cell lines U87MG, U343MG, U373MG, A172, and T98G. Selected interactions were further tested using isobole-based analysis and validated in 5 glioma-initiating cell cultures. Furthermore, drug interactions were predicted using microarray-based transcriptional profiling in combination with statistical modeling. Of the 5 465 drug pairs, we could define a subset of drug pairs with strong interaction in both standard cell lines and glioma-initiating cell cultures. In particular, a subset of pairs involving the pharmaceutical compounds rimcazole, sertraline, pterostilbene, and gefitinib showed a strong interaction in a majority of the cell cultures tested. Statistical modeling of microarray and interaction data using sparse canonical correlation analysis revealed several predictive biomarkers, which we propose could be of importance in regulating drug pair responses. We identify novel candidate drug pairs for GBM and suggest possibilities to prospectively use transcriptional biomarkers to predict drug interactions in individual cases.
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| 52. |
- Stenseke, Marie, et al.
(författare)
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Kris i naturen – vår existens har blivit sårbar
- 2019
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Ingår i: Svenska Dagbladet, Stockholm. - 1101-2412.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Fler arter än någonsin i mänsklighetens historia hotas av utrotning och den biologiska mångfalden lokalt har förändrats kraftigt i en stor del av världens ekosystem. Grundläggande förändringar behövs både i samhället och för individer, för att bromsa den negativa trenden, skriver en rad debattörer.
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| 53. |
- Sundqvist, Jan, et al.
(författare)
-
Cooperation in the building sector between building - material manufacturers and contractors to develop products
- 2007
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Ingår i: The Australian Journal of Construction Economics and Building. - Deakin West : The Australian Institute of Quantity Surveyors and The Australian Institute of Building. - 1445-2634. ; 7:2, s. 46-54
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Tidskriftsartikel (refereegranskat)abstract
- Previous research has indicated that poor cooperation has dominated the relationship between building-material manufacturers and contractors in Europe for more than a century. The purpose of this study, based on earlier research by the authors, analysis of data and reference to other studies, is to ascertain whether the previous indication of poor cooperation still applies and whether this, subsequently, affects the development of new construction products, based on the premise that development demands product ideas in order to know what to develop as well as cooperation in order to facilitate this development. Semi structured interviews with ten Swedish and two Danish building-material manufacturers were carried out to investigate the extent to which they cooperate with contractors to develop new products. None of the twelve building-material manufactures were found to cooperate with contractors, but rather with other manufac-turers. Cooperation in the building industry still seems to be poor. The findings show that there is a need for further studies in this area to explore ways in which cooperation can be improved or increased.
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| 54. |
- Sundqvist, Jan, 1949-, et al.
(författare)
-
Cooperation in the building sector between building-material manufacturers and contractors to develop products
- 2007
-
Ingår i: Australian Journal of Construction Economics and Building. - 1837-9133. ; 7:2, s. 45-53
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Tidskriftsartikel (refereegranskat)abstract
- The Australian Construction Industry is now facing skills shortages in all trades. As an industry focused on the skill of its workforce, there is now concern the Australian standard in quality, workmanship, and productivity will inhibit both at national and international level.This research paper addresses the underlying, influential factors concerning skills shortages in the Australian construction industry. The influential factors addressed include funding, training statistics, employer expectations, financial limitations, Industrial Relations and immigration. Given the reference to skills shortages within the industry, and documented in related literature, if skills shortages are to continue to exist, their effect will impact upon the overall performance of construction companies throughout Australia.
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| 55. |
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| 56. |
- Svedberg, Marie M., et al.
(författare)
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[C-11]PIB-amyloid binding and levels of A beta 40 and A beta 42 in postmortem brain tissue from Alzheimer patients
- 2009
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Ingår i: Neurochemistry International. - : Elsevier BV. - 0197-0186 .- 1872-9754. ; 54:5-6, s. 347-357
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Tidskriftsartikel (refereegranskat)abstract
- beta-Amyloid (A beta) deposits are one of the major histopathological hallmarks of Alzheimer's disease (AD). The amyloid-imaging positron emission tomography (PET) tracer [C-11]PIB (N-methyl[C-11]2-(4'-methylaminophenyl)-6-hydroxy-benzothiazole) is used in the assessment of A beta deposits in the human brain. [C-11]PIB-amyloid interaction and insoluble A beta 40 and A beta 42 peptide levels in the brain were quantified in postmortem tissue from nine AD patients and nine age-matched control subjects in the temporal, frontal and parietal cortices and the cerebellum. Autoradiographical studies showed significantly higher densities of specific [C-11]PIB-amyloid binding in gray matter in the temporal and parietal cortex (62 fmol/mg tissue) in AD patients as compared to control subjects, whereas the density was somewhat lower in the frontal cortex (56 fmol/mg tissue). No specific binding could be detected in the AD cerebellum or in the tissues from the control subjects (<= 5 fmol/mg tissue). Insoluble A beta 40 and total A beta levels (i.e. sum of A beta 40 and A beta 42) were significantly higher in patients than in controls in all measured cortical regions as determined using ELISA, which was confirmed using immunohistochemistry. The present findings show a more regional selective distribution of [C-11]PIB amyloid binding than previously reported. Moreover, it is suggested that some of the [C-11]PIB binding and insoluble A beta seen in control subjects may be amyloid in the blood vessels. (C) 2009 Elsevier Ltd. All rights reserved.
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| 57. |
- Vernersson Lindahl, Emma, 1980-
(författare)
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Investigating the function of Anaplastic Lymphoma Kinase
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Anaplastic Lymphoma Kinase (ALK) was discovered in 1994, as a chromosomal translocation, t(2;5)(p23;q35), often seen in Anaplastic Large Cell Lymphomas (ALCL). Since then ALK has been extensively studied in this disease as well as in different model organisms. Due to its expression pattern within the central and peripheral nervous system ALK has been implicated in neuronal development. This hypothesis has been further strengthened by studies from Drosophila which have shown Alk to have an important role in optic lobe development. A recently described ALK mouse knockout model do not indicate an essential role for ALK in development, although a potential role within the central nervous system was strengthened. This since ALK-/- animals has an increased number of progenitor cells in the hippocampus and display altered behavior. The overall aim of the studies included in this thesis was to elucidate the function of ALK in the mouse. As a first step toward this goal we conducted an analysis of ALK mRNA and protein expression patterns during development. The strong expression of ALK in neuronal structures supports a role for ALK in neuronal development during embryogenesis. To further investigate the function of ALK in a physiological context we have developed two different ALK knockout strains, the ALK Kinase knockout (KO) and the ALK exon1 KO. The only visible phenotype in these strains is a reduction of total body weight which is apparent in the ALK-/- population when compared to wild type littermates. This size difference seems to take place after birth and is not due to an alteration in food consumption. We have also extensively studied the ALK Kinase KO with respect to gross development, the gastrointestinal canal and the olfactory system. ALK displays a very distinct expression pattern within the gastrointestinal canal being confined to enteric neuron precursors during embryogenesis and enteric nerves in the adult tissue. From these studies we conclude that ALK is not needed for development and viability in mice although it does play a role in regulation of body weight via a presently unknown mechanism. In addition, we have investigated the relationship between the Drosophila and mouse ALK receptor by examining the ability of the Drosophila Alk ligand Jelly-Belly, Jeb, to activate mouse ALK. Using different in vivo and in vitro techniques, we have shown that activation of mouse ALK cannot be accomplished by Drosophila Jeb. From this study we draw the conclusion that during development ligands for the Drosophila and mouse ALK has diverged to a level at which they can no longer substitute for each other.
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| 58. |
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| 59. |
- Wasteson, Per, 1974, et al.
(författare)
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Developmental origin of smooth muscle cells in the descending aorta in mice.
- 2008
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Ingår i: Development (Cambridge, England). - : The Company of Biologists. - 0950-1991 .- 1477-9129. ; 135:10, s. 1823-32
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Tidskriftsartikel (refereegranskat)abstract
- Aortic smooth muscle cells (SMCs) have been proposed to derive from lateral plate mesoderm. It has further been suggested that induction of SMC differentiation is confined to the ventral side of the aorta, and that SMCs later migrate to the dorsal side. In this study, we investigate the origin of SMCs in the descending aorta using recombination-based lineage tracing in mice. Hoxb6-cre transgenic mice were crossed with Rosa 26 reporter mice to track cells of lateral plate mesoderm origin. The contribution of lateral plate mesoderm to SMCs in the descending aorta was determined at different stages of development. SMC differentiation was induced in lateral plate mesoderm-derived cells on the ventral side of the aorta at embryonic day (E) 9.0-9.5, as indicated by expression of the SMC-specific reporter gene SM22alpha-lacZ. There was, however, no migration of SMCs from the ventral to the dorsal side of the vessel. Moreover, the lateral plate mesoderm-derived cells in the ventral wall of the aorta were replaced by somite-derived cells at E10.5, as indicated by reporter gene expression in Meox1-cre/Rosa 26 double transgenic mice. Examination of reporter gene expression in adult aortas from Hoxb6-cre/Rosa 26 and Meox1-cre/Rosa 26 double transgenic mice suggested that all SMCs in the adult descending aorta derive from the somites, whereas no contribution was recorded from lateral plate mesoderm.
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| 60. |
- Willen, R, et al.
(författare)
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Similarity of uterine mucosa changes in patients treated by Raloxifen and Tamoxifen
- 2002
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Ingår i: Anticancer research. - 1791-7530. ; 22:2B, s. 1121-1125
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Tidskriftsartikel (refereegranskat)abstract
- Background: Selective estrogen receptor modulators (SERMS) like Tamoxifen and Raloxifen are used for menopausal symptoms, prevention of cardio-vascular diseases, osteoporosis and mammary carcinoma. Tamoxifen acts as an estrogen inhibitor on the mammary gland, but stimulates postmenopausal uterine mucosa in about 25% of cases while decreasing the risk of osteoporosis. Materials, Methods and Results: In three menopausal women, 56, 79 and 62 years of age, we found uterine mucosal changes similar to what is found in Tamoxifen-treated patients. Using light microscopy and immuno-histopathological techniques, partly cystic mucosa with both atrophic and proliferating glands was found. Strong stromal proliferation was also seen with the typical sharp-edged form of stromal cells and mitoses. A strong ostrogen and progesterone reaction was revealed with immuno-histopathological techniques in both gland and stromal parts. Conclusion: Taking into account the variable amount of different estrogen-receptor types in the uterine mucosa, we can not in the long run expect that no patient will react with estrogen-stimulation features on SERMs like Raloxifen. Further studies and thorough observations are needed to elucidate the true frequency of Raloxifen impact on the uterine mucosa.
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