| 1. |
- Adolfsson, Karl, et al.
(författare)
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Fluorescent Nanowire Heterostructures as a Versatile Tool for Biology Applications
- 2013
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Ingår i: Nano Letters. - : American Chemical Society (ACS). - 1530-6992 .- 1530-6984. ; 13:10, s. 4728-4732
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Tidskriftsartikel (refereegranskat)abstract
- Nanowires are increasingly used in biology, as sensors, as injection devices, and us model systems for toxicity studies. Currently, in situ visualization of nanowires in biological media is done using organic dyes, which a;:e prone to photobleaching, or using microscopy methods which either yield poor resolution or require a sophisticated setup. Here we show that inherently fluorescent nanowire axial heterostructnies c:an be used to localize and identify nanowires in cells and tissue; By synthesizing GaP GaInP nanowire heterostructures, with nonfluorescent GaP segments and fluorescent GaInP segments, we created a barcode labeling system enabling the distinction of the nanowire morphological and chemical properties using fluorescence microscopy. The GaInP photoluminescence stability, combined with the fact that the nanowires can be coated with different materials while retaining their fluorescence, make these nanowires promising tools for biological and nanotoxicological studies.
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| 2. |
- Alm, Kersti, et al.
(författare)
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Cells and holograms : holograms and digital holographic microscopy as a tool to study the morphology of living cells
- 2013
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Ingår i: Holography. - : INTECH. - 9789535111177 ; , s. 335-351
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- We present a method to study the morphology of living, dividing and dying cells using DHM. DHM is a non-invasive, non-destructive and non-phototoxic method which allows the user to perform both qualitative and quantitative measurements of living cells over time. We show here our results on cell division and cell death in single cells. The morphological analyses performed here show changes caused by cell death and cell division, and indicate the possibilities to discriminate between different types of cell death. Cells dying in an apoptosis-like manner display different cell area and cell thickness profiles over time compared to cells dying in a necrosis-like manner, although their volume profiles are very similar. Dividing cells show a characteristic dip in the volume profile, which makes them easily distinguishable. Also, several previous studies show the versatile abilities of DHM. Different cell types have been studied and the morphology has been used to determine cell functionality as well as changes in morphology related to the environment. Cell morphology parameters can be very useful when following the effects of different treatments, the process of differentiation as well as cell growth and cell death. Cell morphology studied by DHM can be useful in toxicology, stem cell and cancer research.
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| 3. |
- Alm, Kersti, et al.
(författare)
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Cells and polyamines do it cyclically
- 2009
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Ingår i: Essays in Biochemistry. - : Portland Press Ltd.. - 0071-1365 .- 1744-1358. ; 46, s. 63-76
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Tidskriftsartikel (refereegranskat)abstract
- Cell-cycle progression is a one-way journey where the cell grows in size to be able to divide into two equally sized daughter cells. The cell cycle is divided into distinct consecutive phases defined as G(1) (first gap), S (synthesis), G(2) (second gap) and M (mitosis). A non-proliferating cell, which has retained the ability to enter the cell cycle when it receives appropriate signals, is in G(0) phase, and cycling cells that do not receive proper signals leave the cell cycle from G(1) into G(0). One of the major events of the cell cycle is the duplication of DNA during S-phase. A group of molecules that are important for proper cell-cycle progression is the polyamines. Polyamine biosynthesis occurs cyclically during the cell cycle with peaks in activity in conjunction with the G(1)/S transition and at the end of S-phase and during G(2)-phase. The negative regulator of polyamine biosynthesis, antizyme, shows an inverse activity compared with the polyamine biosynthetic activity. The levels of the polyamines, putrescine, spermidine and spermine, double during the cell cycle and show a certain degree of cyclic variation in accordance with the biosynthetic activity. When cells in G(0)/G(1) -phase are seeded in the presence of compounds that prevent the cell-cycle-related increases in the polyamine pools, the S-phase of the first cell cycle is prolonged, whereas the other phases are initially unaffected. The results point to an important role for polyamines with regard to the ability of the cell to attain optimal rates of DNA replication.
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| 4. |
- Alm, Kersti, et al.
(författare)
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Digital holography and cell studies
- 2011
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Ingår i: Holography, Research and Technologies. - : DKV - Deutscher Kälte- und Klimatechnischer Verein. - 9789533072272 ; , s. 237-252
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Digital holography microscopy (DHM) has developed into a broad field, and one of all the interesting applications is to study cells without staining, labeling or in any other way affecting them. Both fixed and living, dying or dead cells can be studied. The first DHM images showing living cells were published in 2004 and 2005 (Carl et al. 2004, Marquet et al. 2005), making this field of research rather new. Digital holography makes it possible to easily measure cell properties that previously have been very difficult to study, such as cell thickness and volume (Marquet et al. 2005, Mölder et al. 2008). Two of the major advantages of DHM is the 3-D imaging possibility and measurements over time. Digital holography has ben used to study several types of cells, such as nerve cells, red blood cells, stem cells and cancer cells (Emery et al. 2007, Kemper et al. 2006, Langehanenberg et al. 2009) . It has also been applied for studies of cell proliferation, cell movement, sub-cellular structures and cell morphology (Kemper et al. 2009, Yu et al. 2009). Both 2-D and 3-D cell movement can be determined ( Langehanenberg et al. 2009). Even cell viability status can be determined using DHM. Interestingly, it is possible to study both single cells and entire populations simultaneously, allowing for very nuanced studies. Older, well known techniques often require some degree of cell disturbance such as the fluorescent antibody labeling required for fluorescense or confocal microscopy studies. In this paper we will present some of the studies made possible by DHM. We will compare DHM with previously used techniques and discuss the benefits and drawbacks of digital holography cell measurements.
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| 5. |
- Antoszczak, Michał, et al.
(författare)
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Bivalent polyether ionophores : Synthesis and biological evaluation of C2-symmetric salinomycin dimers
- 2017
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Ingår i: Tetrahedron Letters. - : Elsevier BV. - 0040-4039. ; 58:24, s. 2396-2399
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Tidskriftsartikel (refereegranskat)abstract
- Efficient methods for the synthesis of C2-symmetric dimers of salinomycin joined at either the C1 or C20 positions are reported. Similarly to the native structure, the C20-O-terephthalate dimer displayed activity in the low μM range against a series of cancer cell lines, while dimers joined at the C1 position were essentially inactive.
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| 6. |
- Borgström, Björn, et al.
(författare)
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Salinomycin Hydroxamic Acids: Synthesis, Structure, and Biological Activity of Polyether Ionophore Hybrids
- 2016
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Ingår i: ACS Medicinal Chemistry Letters. - : American Chemical Society (ACS). - 1948-5875. ; 7:6, s. 635-640
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Tidskriftsartikel (refereegranskat)abstract
- The polyether ionophore salinomycin has recently gained attention due to its exceptional ability to selectively reduce the proportion of cancer stem cells within a number of cancer cell lines. Efficient single step strategies for the preparation of hydroxamic acid hybrids of this compound varying in N- and O-alkylation are presented. The parent hydroxamic acid, salinomycin-NHOH, forms both inclusion complexes and well-defined electroneutral complexes with potassium and sodium cations via 1,3-coordination by the hydroxamic acid moiety to the metal ion. A crystal structure of an cationic sodium complex with a noncoordinating anion corroborates this finding and, moreover, reveals a novel type of hydrogen bond network that stabilizes the head-to-tail conformation that encapsulates the cation analogously to the native structure. The hydroxamic acid derivatives display down to single digit micromolar activity against cancer cells but unlike salinomycin selective reduction of ALDH+ cells, a phenotype associated
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| 7. |
- Borgström, Björn, et al.
(författare)
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Structure–Activity Relationships in Salinomycin : Cytotoxicity and Phenotype Selectivity of Semi-synthetic Derivatives
- 2017
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Ingår i: Chemistry - A European Journal. - : Wiley. - 0947-6539. ; 23:9, s. 2077-2083
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Tidskriftsartikel (refereegranskat)abstract
- The ionophore salinomycin has attracted attention for its exceptional ability to selectively reduce the proportion of cells with stem-like properties in cancer cell populations of varying origin. Targeting the tumorigenicity of such cells is of interest as they are implicated in recurrence, metastasis, and drug resistance. Structural derivatives of salinomycin are thus sought after, both as tools for probing the molecular mechanism(s) underlying the observed phenotype effects, and for improving selectivity and activity against cancer stem cells. Synthetic strategies for modification of each of the directly accessible functional groups of salinomycin are presented and the resulting library of analogues was investigated to establish structure–activity relationships, both with respect to cytotoxicity and phenotype selectivity in breast cancer cells. 20-O-Acylated derivatives stand out by exhibiting both improved selectivity and activity. Mechanistically, the importance of the ionophore properties of salinomycin is highlighted by a significant loss of activity by modifications directly interfering with either of the two primary ion coordinating motifs in salinomycin, the C11 ketone and the C1 carboxylate.
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| 8. |
- Borgström, Björn, et al.
(författare)
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Synthetic modification of salinomycin: selective O-acylation and biological evaluation
- 2013
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Ingår i: Chemical Communications. - : Royal Society of Chemistry (RSC). - 1364-548X .- 1359-7345. ; 49:85, s. 9944-9946
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Tidskriftsartikel (refereegranskat)abstract
- Salinomycin has found renewed interest as an agent for prevention of cancer recurrence through selectively targeting cancer stem cells. Strategies for generation of improved salinomycin analogs by individual modification of its hydroxyl groups are presented. An evaluation of the dose-response effects of the resulting library on breast cancer cell lines shows that acylation of the C20 hydroxyl can be used to improve IC50 values down to one fifth that of salinomycin.
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| 9. |
- Cirenajwis, Helena, et al.
(författare)
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Reduction of the putative CD44+CD24- breast cancer stem cell population by targeting the polyamine metabolic pathway with PG11047.
- 2010
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Ingår i: Anti-Cancer Drugs. - 0959-4973. ; 21:10, s. 897-906
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Tidskriftsartikel (refereegranskat)abstract
- Cancer stem cells (CSCs) are considered to be of particular concern in cancer as they possess inherent properties of self-renewal and differentiation, along with expressing certain genes related to a mesenchymal phenotype. These features favour the promotion of tumour recurrence and metastasis in cancer patients. Thus, the optimal chemotherapeutic treatment should target the CSC population, either by killing these cells and/or by inducing their transition to a more differentiated epithelial-like phenotype. Experiments were carried out on the trastuzumab-resistant human epidermal growth factor receptor 2-overexpressing breast cancer cell line JIMT-1 to unravel the chemotherapeutic effects of the polyamine analogue [N,N]bis(ethyl)-cis-6,7-dehydrospermine (PG11047) and of the polyamine biosynthetic inhibitor 2-difluoromethylornithine (DFMO) on the CD44CD24 CSC population. Furthermore, effects on the properties of self-renewal and epithelial/mesenchymal markers were also investigated. Treatment with PG11047 reduced the CD44CD24 subpopulation of JIMT-1 cells by approximately 50%, inhibited and/or reduced self-renewal capability of the CSC population, decreased cell motility and induced expression of mesenchymal to epithelial transition-associated proteins that are involved in promoting an epithelial phenotype. By contrast, DFMO slightly increased the CD44CD24 subpopulation, increased cell motility and the level of mesenchymal-related proteins. DFMO treatment reduced the self-renewal capability of the CSC population. Both PG11047 and DFMO reduced the expression of the human epidermal growth factor receptor 2 protein, which is correlated to malignancy and resistance to trastuzumab in JIMT-1 cells. Our findings indicate that treatment with PG11047 targeted the CSC population by interfering with several stem cell-related properties, such as self-renewal, differentiation, motility and the mesenchymal phenotype.
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| 10. |
- Delaine, Tamara, et al.
(författare)
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Galectin-3-Binding Glycomimetics that Strongly Reduce Bleomycin-Induced Lung Fibrosis and Modulate Intracellular Glycan Recognition
- 2016
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Ingår i: ChemBioChem. - : Wiley. - 1439-4227. ; 17:18, s. 1759-1770
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Tidskriftsartikel (refereegranskat)abstract
- Discovery of glycan-competitive galectin-3-binding compounds that attenuate lung fibrosis in a murine model and that block intracellular galectin-3 accumulation at damaged vesicles, hence revealing galectin-3-glycan interactions involved in fibrosis progression and in intracellular galectin-3 activities, is reported. 3,3'-Bis-(4-aryltriazol-1-yl)thiodigalactosides were synthesized and evaluated as antagonists of galectin-1, -2, -3, and -4 N-terminal, -4 C-terminal, -7 and -8 N-terminal, -9 N-terminal, and -9 C-terminal domains. Compounds displaying low-nanomolar affinities for galectins-1 and -3 were identified in a competitive fluorescence anisotropy assay. X-ray structural analysis of selected compounds in complex with galectin-3, together with galectin-3 mutant binding experiments, revealed that both the aryltriazolyl moieties and fluoro substituents on the compounds are involved in key interactions responsible for exceptional affinities towards galectin-3. The most potent galectin-3 antagonist was demonstrated to act in an assay monitoring galectin-3 accumulation upon amitriptyline-induced vesicle damage, visualizing a biochemically/medically relevant intracellular lectin-carbohydrate binding event and that it can be blocked by a small molecule. The same antagonist administered intratracheally attenuated bleomycin-induced pulmonary fibrosis in a mouse model with a dose/response profile comparing favorably with that of oral administration of the marketed antifibrotic compound pirfenidone.
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