SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "WFRF:(Fryknäs Mårten) "

Sökning: WFRF:(Fryknäs Mårten)

  • Resultat 1-10 av 47
  • [1]2345Nästa
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • Aftab, Obaid, 1984-, et al. (författare)
  • Detection of cell aggregation and altered cell viability by automated label-free video microscopy : A promising alternative to endpoint viability assays in high throughput screening
  • ????
  • Annan publikation (övrigt vetenskapligt)abstract
    • Automated phase-contrast video microscopy now makes it feasible to monitor a high throughput (HT) screening experiment in a 384-well microtiter plate format by collecting one timelapse video per well. Being a very cost effective and label free monitoring method, its potential as an alternative to cell viability assays was evaluated. Three simple morphology feature extraction and comparison algorithms were developed and implemented for analysis of differentially time-evolving morphologies (DTEM) monitored in phase-contrast microscopy videos. The most promising layout, pixel histogram hierarchy comparison (PHHC), was able to detect several compounds that did not induce any significant change in cell viability, but made the cell population appear as spheroidal cell aggregates. According to recent reports, all these compounds seem to be involved in inhibition of platelet derived growth factor receptor (PDGFR) signalling. Thus, automated quantification of DTEM (AQDTEM) holds strong promise as an alternative or compliment to viability assays in HT in vitro screening of chemical compounds. 
  •  
2.
  • Aftab, Obaid, 1984-, et al. (författare)
  • Label-free detection and dynamic monitoring of drug-induced intracellular vesicle formation enabled using a 2-dimensional matched filter
  • 2014
  • Ingår i: Autophagy. - 1554-8627. ; 10:1, s. 57-69
  • Tidskriftsartikel (refereegranskat)abstract
    • Analysis of vesicle formation and degradation is a central issue in autophagy research and microscopy imaging is revolutionizing the study of such dynamic events inside living cells. A limiting factor is the need for labeling techniques that are labor intensive, expensive, and not always completely reliable. To enable label-free analyses we introduced a generic computational algorithm, the label-free vesicle detector (LFVD), which relies on a matched filter designed to identify circular vesicles within cells using only phase-contrast microscopy images. First, the usefulness of the LFVD is illustrated by presenting successful detections of autophagy modulating drugs found by analyzing the human colorectal carcinoma cell line HCT116 exposed to each substance among 1266 pharmacologically active compounds. Some top hits were characterized with respect to their activity as autophagy modulators using independent in vitro labeling of acidic organelles, detection of LC3-II protein, and analysis of the autophagic flux. Selected detection results for 2 additional cell lines (DLD1 and RKO) demonstrate the generality of the method. In a second experiment, label-free monitoring of dose-dependent vesicle formation kinetics is demonstrated by recorded detection of vesicles over time at different drug concentrations. In conclusion, label-free detection and dynamic monitoring of vesicle formation during autophagy is enabled using the LFVD approach introduced.
  •  
3.
  • Aftab, Obaid, 1984-, et al. (författare)
  • Label free high throughput screening for apoptosis inducing chemicals using time-lapse microscopy signal processing
  • 2014
  • Ingår i: Apoptosis (London). - 1360-8185. ; 19:9, s. 1411-1418
  • Tidskriftsartikel (refereegranskat)abstract
    • Label free time-lapse microscopy has opened a new avenue to the study of time evolving events in living cells. When combined with automated image analysis it provides a powerful tool that enables automated large-scale spatiotemporal quantification at the cell population level. Very few attempts, however, have been reported regarding the design of image analysis algorithms dedicated to the detection of apoptotic cells in such time-lapse microscopy images. In particular, none of the reported attempts is based on sufficiently fast signal processing algorithms to enable large-scale detection of apoptosis within hours/days without access to high-end computers. Here we show that it is indeed possible to successfully detect chemically induced apoptosis by applying a two-dimensional linear matched filter tailored to the detection of objects with the typical features of an apoptotic cell in phase-contrast images. First a set of recorded computational detections of apoptosis was validated by comparison with apoptosis specific caspase activity readouts obtained via a fluorescence based assay. Then a large screen encompassing 2,866 drug like compounds was performed using the human colorectal carcinoma cell line HCT116. In addition to many well known inducers (positive controls) the screening resulted in the detection of two compounds here reported for the first time to induce apoptosis.
  •  
4.
  • Aftab, Obaid, 1984-, et al. (författare)
  • Label free quantification of time evolving morphologies using time-lapse video microscopy enables identity control of cell lines and discovery of chemically induced differential activity in iso-genic cell line pairs
  • ????
  • Annan publikation (övrigt vetenskapligt)abstract
    • Background: Label free time-lapse video microscopy based monitoring of time evolving cell population morphology has potential to offer a simple and cost effective method for identity control of cell lines. An identity control method of this kind would be useful in any cell biology lab to ensure that new batches of cell lines and clones are not contaminated or simply assigned the wrong label. Such morphology monitoring also has potential to offer discovery of chemically induced differential changes between pairs of cell lines of interest, for example where one of the two cell lines is normal/sensitive and the other is malignant/resistant. A discovery tool of this kind would be useful in cancer as well as toxicological research where a key question is to identify individual chemicals/drugs, or mixtures, having outstanding differential biochemical effects in carefully selected pairs of in vitro cell line models.Results: A new simple algorithm for comparison of time evolving morphologies (TEM) in phase contrast time-lapse microscopy movies was applied to a set of 11 different cell lines as well as to three different iso-genic colon cancer cell line pairs, each pair being genetically identical except for one single mutation. The new algorithm, here called pixel histogram hierarchy comparison (PHHC), quantifies differences in morphology by comparing pixel histogram intensities at six different resolutions. Unsupervised clustering as well as machine learning based classification methods were employed and found to quite accurately identify cell lines based on their recorded time-evolving morphology. In the same way, drugs with differential activity in iso-genic cell line pairs were identified.Conclusions: Automated analysis of TEMs enables simple control of cell line identity as well as the finding of differential drug activity in iso-genic cell line pairs. Thus, this is a cost effective and simple alternative to conventional molecular profiling techniques and might be useful as part of the quality control in research based on cell line models and in any anti-cancer or toxicology project with interest in finding drug differential activity in pairs of cell line models of interest.
  •  
5.
  • Andersson, Claes R., et al. (författare)
  • In vitro drug sensitivity-gene expression correlations involve a tissue of origin dependency
  • 2007
  • Ingår i: Journal of chemical information and modeling. - 1549-9596. ; 47:1, s. 239-248
  • Tidskriftsartikel (refereegranskat)abstract
    • A major concern of chemogenomics is to associate drug activity with biological variables. Several reports have clustered cell line drug activity profiles as well as drug activity-gene expression correlation profiles and noted that the resulting groupings differ but still reflect mechanism of action. The present paper shows that these discrepancies can be viewed as a weighting of drug-drug distances, the weights depending on which cell lines the two drugs differ in.
  •  
6.
  • Björklund, Peyman, et al. (författare)
  • Stathmin as a Marker for Malignancy in Pheochromocytomas
  • 2010
  • Ingår i: Experimental and clinical endocrinology & diabetes. - 0947-7349. ; 118:1, s. 27-30
  • Tidskriftsartikel (refereegranskat)abstract
    • Pheochromocytomas of the adrenal medulla may be life-threatening catecholamine-producing tumors which are malignant in about 10% of cases. Differential diagnosis between malignant and benign tumors is dependent on the development of metastasis or extensive local invasion. A number of genetic aberrations have been described in pheochromocytomas, but no marker associated to malignancy has been reported. We applied an expression microarray containing 7770 cDNA clones and analysed the expression profiles in eleven tumors compared to normal adrenal medulla. Stathmin (STMN1, Op18) was most conspiciously overexpressed among the differentially expressed genes. RT-PCR analysis further confirmed mRNA overexpression, 6 to 8-fold for benign and malignant tumors, and 16-fold for metastases. Stathmin protein overexpression was observed by immunohistochemistry, and distinct differential protein expression between benign and malignant/metastasis specimens was confirmed by Western blot analysis. The results introduce stathmin as a possible diagnostic marker for malignant pheochromocytomas, and further evaluations are warranted.
  •  
7.
  • D'Arcy, Padraig, et al. (författare)
  • Inhibition of proteasome deubiquitinating activity as a new cancer therapy
  • 2011
  • Ingår i: Nature Medicine. - 1078-8956. ; 17:12, s. 1636-1640
  • Tidskriftsartikel (refereegranskat)abstract
    • Ubiquitin-tagged substrates are degraded by the 26S proteasome, which is a multisubunit complex comprising a proteolytic 20S core particle capped by 19S regulatory particles. The approval of bortezomib for the treatment of multiple myeloma validated the 20S core particle as an anticancer drug target. Here we describe the small molecule b-AP15 as a previously unidentified class of proteasome inhibitor that abrogates the deubiquitinating activity of the 19S regulatory particle. b-AP15 inhibited the activity of two 19S regulatory-particle-associated deubiquitinases, ubiquitin C-terminal hydrolase 5 (UCHL5) and ubiquitin-specific peptidase 14 (USP14), resulting in accumulation of polyubiquitin. b-AP15 induced tumor cell apoptosis that was insensitive to TP53 status and overexpression of the apoptosis inhibitor BCL2. We show that treatment with b-AP15 inhibited tumor progression in four different in vivo solid tumor models and inhibited organ infiltration in an acute myeloid leukemia model. Our results show that the deubiquitinating activity of the 19S regulatory particle is a new anticancer drug target.
8.
  • Dimberg, Lina Y., et al. (författare)
  • Stat1 activation attenuates IL-6 induced Stat3 activity but does not alter apoptosis sensitivity in multiple myeloma
  • 2012
  • Ingår i: BMC Cancer. - 1471-2407. ; 12, s. 318
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Multiple myeloma (MM) is at present an incurable malignancy, characterized by apoptosis-resistant tumor cells. Interferon (IFN) treatment sensitizes MM cells to Fas-induced apoptosis and is associated with an increased activation of Signal transducer and activator of transcription (Stat)1. The role of Stat1 in MM has not been elucidated, but Stat1 has in several studies been ascribed a pro-apoptotic role. Conversely, IL-6 induction of Stat3 is known to confer resistance to apoptosis in MM. Methods: To delineate the role of Stat1 in IFN mediated sensitization to apoptosis, sub-lines of the U-266-1970 MM cell line with a stable expression of the active mutant Stat1C were utilized. The influence of Stat1C constitutive transcriptional activation on endogenous Stat3 expression and activation, and the expression of apoptosis-related genes were analyzed. To determine whether Stat1 alone would be an important determinant in sensitizing MM cells to apoptosis, the U-266-1970-Stat1C cell line and control cells were exposed to high throughput compound screening (HTS). Results: To explore the role of Stat1 in IFN mediated apoptosis sensitization of MM, we established sublines of the MM cell line U-266-1970 constitutively expressing the active mutant Stat1C. We found that constitutive nuclear localization and transcriptional activity of Stat1 was associated with an attenuation of IL-6-induced Stat3 activation and up-regulation of mRNA for the pro-apoptotic Bcl-2 protein family genes Harakiri, the short form of Mcl-1 and Noxa. However, Stat1 activation alone was not sufficient to sensitize cells to Fas-induced apoptosis. In a screening of > 3000 compounds including bortezomib, dexamethasone, etoposide, suberoylanilide hydroxamic acid (SAHA), geldanamycin (17-AAG), doxorubicin and thalidomide, we found that the drug response and IC50 in cells constitutively expressing active Stat1 was mainly unaltered. Conclusion: We conclude that Stat1 alters IL-6 induced Stat3 activity and the expression of pro-apoptotic genes. However, this shift alone is not sufficient to alter apoptosis sensitivity in MM cells, suggesting that Stat1 independent pathways are operative in IFN mediated apoptosis sensitization.
9.
  • Eriksson, Anna, 1977-, et al. (författare)
  • AKN-028 induces cell cycle arrest, downregulation of Myc associated genes and a dose dependent reduction of kinase activity in acute myeloid leukemia
  • 2014
  • Ingår i: Biochemical Pharmacology. - Elsevier. - 0006-2952. ; 87:2, s. 284-291
  • Tidskriftsartikel (refereegranskat)abstract
    • AKN-028 is a novel tyrosine kinase inhibitor with preclinical activity in acute myeloid leukemia (AML), presently undergoing investigation in a phase I/II study. It is a potent inhibitor of the FMS-like kinase 3 (FLT3) but shows in vitro activity in a wide range of AML samples. In the present study, we have characterized the effects of AKN-028 on AML cells in more detail. AKN-028 induced a dose-dependent G(0)/arrest in AML cell line MV4-11. Treatment with AKN-028 caused significantly altered gene expression in all AML cell types tested (430 downregulated, 280 upregulated transcripts). Subsequent gene set enrichment analysis revealed enrichment of genes associated with the proto-oncogene and cell cycle regulator c-Myc among the downregulated genes in both AKN-028 and midostaurin treated cells. Kinase activity profiling in AML cell lines and primary AML samples showed that tyrosine kinase activity, but not serine/threonine kinase activity, was inhibited by AKN-028 in a dose dependent manner in all samples tested, reaching approximately the same level of kinase activity. Cells sensitive to AKN-028 showed a higher overall tyrosine kinase activity than more resistant ones, whereas serine/threonine kinase activity was similar for all primary AML samples. In summary, AKN-028 induces cell cycle arrest in AML cells, downregulates Myc-associated genes and affect several signaling pathways. AML cells with high global tyrosine kinase activity seem to be more sensitive to the cytotoxic effect of AKN-028 in vitro.
10.
  • Fayad, Walid, et al. (författare)
  • Identification of a novel topoisomerase inhibitor effective in cells overexpressing drug efflux transporters
  • 2009
  • Ingår i: PLoS ONE. - 1932-6203. ; 4:10, s. e7238
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND:Natural product structures have high chemical diversity and are attractive as lead structures for discovery of new drugs. One of the disease areas where natural products are most frequently used as therapeutics is oncology.METHOD AND FINDINGS:A library of natural products (NCI Natural Product set) was screened for compounds that induce apoptosis of HCT116 colon carcinoma cells using an assay that measures an endogenous caspase-cleavage product. One of the apoptosis-inducing compounds identified in the screen was thaspine (taspine), an alkaloid from the South American tree Croton lechleri. The cortex of this tree is used for medicinal purposes by tribes in the Amazonas basin. Thaspine was found to induce conformational activation of the pro-apoptotic proteins Bak and Bax, mitochondrial cytochrome c release and mitochondrial membrane permeabilization in HCT116 cells. Analysis of the gene expression signature of thaspine-treated cells suggested that thaspine is a topoisomerase inhibitor. Inhibition of both topoisomerase I and II was observed using in vitro assays, and thaspine was found to have a reduced cytotoxic effect on a cell line with a mutated topoisomerase II enzyme. Interestingly, in contrast to the topoisomerase II inhibitors doxorubicin, etoposide and mitoxantrone, thaspine was cytotoxic to cell lines overexpressing the PgP or MRP drug efflux transporters. We finally show that thaspine induces wide-spread apoptosis in colon carcinoma multicellular spheroids and that apoptosis is induced in two xenograft mouse models in vivo.CONCLUSIONS:The alkaloid thaspine from the cortex of Croton lechleri is a dual topoisomerase inhibitor effective in cells overexpressing drug efflux transporters and induces wide-spread apoptosis in multicellular spheroids.
  •  
Skapa referenser, mejla, bekava och länka
  • Resultat 1-10 av 47
  • [1]2345Nästa
Åtkomst
fritt online (9)
Typ av publikation
tidskriftsartikel (41)
annan publikation (5)
doktorsavhandling (1)
Typ av innehåll
refereegranskat (38)
övrigt vetenskapligt (9)
Författare/redaktör
Fryknäs, Mårten, (46)
Larsson, Rolf, (35)
Rickardson, Linda, (18)
Linder, Stig (14)
Gullbo, Joachim, (14)
Nygren, Peter, (12)
visa fler...
Isaksson, Anders (11)
Wickström, Malin, (10)
Gustafsson, Mats G., (8)
D'Arcy, Padraig (8)
Haglund, Caroline, (6)
Göransson, Hanna, (5)
Brnjic, Slavica (5)
Fayad, Walid (5)
Aftab, Obaid, 1984-, (4)
Hammerling, Ulf, (4)
Gustafsson, Mats, (4)
Zhang, Xiaonan (4)
De Milito, Angelo (4)
Öberg, Fredrik, (4)
Dhar, Sumeer, (4)
Lövborg, Henrik (4)
Hassan, Saadia, (3)
Bohlin, Lars, (3)
Felth, Jenny, (3)
Olofsson, Maria Hägg (3)
Jarvius, Malin, (3)
Fryknas, M. (3)
Wickstrom, M. (3)
Wickenberg Bolin, Ul ... (3)
Landegren, Ulf (2)
Kalushkova, Antonia, (2)
Nilsson, Kenneth, (2)
Jernberg-Wiklund, He ... (2)
Larsson, Catharina (2)
Grander, Dan (2)
Pettersson, Ulf, (2)
Johnsson, Per (2)
Andersson, Claes R., (2)
Hägg Olofsson, Maria (2)
Gullbo, J, (2)
Lesiak-Mieczkowska, ... (2)
Rydåker, Maria, (2)
Hernlund, Emma (2)
Kolosenko, Iryna (2)
Strese, Sara, (2)
Österborg, Anders (1)
Hassan, Moustapha (1)
Gustafsson, M. (1)
Wang, Xin, (1)
visa färre...
Lärosäte
Uppsala universitet (47)
Lunds universitet (2)
Chalmers tekniska högskola (2)
Göteborgs universitet (1)
Karolinska institutet (1)
Kungliga Tekniska Högskolan (1)
Språk
Engelska (42)
Ämne (HSV)
Medicin och hälsovetenskap (2)
Naturvetenskap (1)

År

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy