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Sundström, Birgitta E.ORCID iD iconorcid.org/0000-0001-9302-2396
Alternative names
Publications (10 of 40) Show all publications
Rendel, F., Fjaeraa Alfredsson, C., Bornehag, C.-G., Sundström, B. E. & Nånberg, E. (2017). Effects of Di-Isononyl Phthalate on Neuropeptide Y Expression in Differentiating Human Neuronal Cells. Basic & Clinical Pharmacology & Toxicology, 120(3), 218-323
Open this publication in new window or tab >>Effects of Di-Isononyl Phthalate on Neuropeptide Y Expression in Differentiating Human Neuronal Cells
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2017 (English)In: Basic & Clinical Pharmacology & Toxicology, ISSN 1742-7835, E-ISSN 1742-7843, Vol. 120, no 3, p. 218-323Article in journal (Refereed) Published
Place, publisher, year, edition, pages
Wiley-Blackwell, 2017
Keywords
phthlate, DiNP, MiNP, NPY, SH-SY5Y neuroblastoma cells
National Category
Medical and Health Sciences Cell and Molecular Biology
Research subject
Biomedical Sciences; Biomedical Sciences
Identifiers
urn:nbn:se:kau:diva-45720 (URN)10.1111/bcpt.12670 (DOI)000394538600016 ()27625336 (PubMedID)
Available from: 2016-09-05 Created: 2016-09-05 Last updated: 2019-06-10Bibliographically approved
Fjæraa Alfredsson, C., Rendel, F., Liang, Q.-L., Sundström, B. E. & Nånberg, E. (2015). Altered sensitivity to ellagic acid in neuroblastoma cells undergoing differentiation with 12-0-tetradecanoylphorbol-13-acetate and all-trans retinoic acid. Biomedicine and Pharmacotherapy, 76, 39-45
Open this publication in new window or tab >>Altered sensitivity to ellagic acid in neuroblastoma cells undergoing differentiation with 12-0-tetradecanoylphorbol-13-acetate and all-trans retinoic acid
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2015 (English)In: Biomedicine and Pharmacotherapy, ISSN 0753-3322, E-ISSN 1950-6007, Vol. 76, p. 39-45Article in journal (Refereed) Published
Abstract [en]

Ellagic acid has previously been reported to induce reduced proliferation and activation of apoptosis in several tumor cell lines including our own previous data from non-differentiated human neuroblastoma SH-SY5Y cells. The aim of this study was now to investigate if in vitro differentiation with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate or the vitamin A derivative all-trans retinoic acid altered the sensitivity to ellagic acid in SH-SY5Y cells. The methods used were cell counting and LDH-assay for evaluation of cell number and cell death, flow cytometric analysis of SubG(1)-and TUNEL-analysis for apoptosis and western blot for expression of apoptosis-associated proteins. In vitro differentiation was shown to reduce the sensitivity to ellagic acid with respect to cell detachment, loss of viability and activation of apoptosis. The protective effect was phenotype-specific and most prominent in all-trans retinoic acid-differentiated cultures. Differentiation-dependent up-regulation of Bcl-2 and integrin expression is introduced as possible protective mechanisms. The presented data also point to a positive correlation between proliferative activity and sensitivity to ellagic-acid-induced cell detachment. In conclusion, the presented data emphasize the need to consider degree of neuronal differentiation and phenotype of neuroblastoma cells when discussing a potential pharmaceutical application of ellagic acid in tumor treatment.

Keywords
Ellagic acid, Cell adhesion, Apoptosis, Neuroblastoma, Differentiation
National Category
Basic Medicine
Research subject
Biomedical Sciences
Identifiers
urn:nbn:se:kau:diva-29903 (URN)10.1016/j.biopha.2015.10.008 (DOI)000367541500007 ()
Available from: 2013-10-24 Created: 2013-10-24 Last updated: 2019-07-09Bibliographically approved
Fjæraa Alfredsson, C., Ding, M., Liang, Q.-L., Sundström, B. & Nånberg, E. (2014). Ellagic acid induces a dose- and time-dependent depolarization of mitochondria and activation of caspase-9 and -3 in human neuroblastoma cells. Biomedicine and Pharmacotherapy, 68(1), 129-135
Open this publication in new window or tab >>Ellagic acid induces a dose- and time-dependent depolarization of mitochondria and activation of caspase-9 and -3 in human neuroblastoma cells
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2014 (English)In: Biomedicine and Pharmacotherapy, ISSN 0753-3322, E-ISSN 1950-6007, Vol. 68, no 1, p. 129-135Article in journal (Refereed) Published
Abstract [en]

The polyphenol ellagic acid is found in many natural food sources and has been proposed as a candidate compound for clinical applications due to its anti-oxidative capacity and as a potential anti-tumorigenic compound. The objective of the present study was to evaluate the sensitivity to and possible apoptosis mechanism induced by ellagic acid in neuronal tumor cells. As a model the human neuroblastoma SH-SY5Y cell line was used. The methods applied were bright field and phase contrast microscopy, XTT- and LDH-assays, western blot, and flow cytometric analysis of DNA degradation and mitochondrial membrane potential. Ellagic acid treatment was found to induce a reduction in cell number preceded by alterations of the mitochondrial membrane potential and activation of caspase-9 and -3, DNA-fragmentation and cell death by apoptosis. The apoptotic cell death studied was not due to anoikis since it was significant in the adherent fraction of the cells. We conclude that ellagic acid induces dose- and time-dependent apoptosis, at least partly by the mitochondrial pathway, in an embryonal neuronal tumor cell system. This finding is in agreement with previously reported data on adult carcinoma cells thus suggesting a more general effect of ellagic acid on tumor cells.

Place, publisher, year, edition, pages
Elsevier, 2014
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:kau:diva-29599 (URN)10.1016/j.biopha.2013.08.010 (DOI)000332448400019 ()24051122 (PubMedID)
Available from: 2013-10-17 Created: 2013-10-17 Last updated: 2020-04-03Bibliographically approved
Jafari, R., Holm, P., Piercecchi, M. & Sundström, B. E. (2011). Construction of divalent anti-keratin 8 single-chain antibodies (sc(FV)2), expression in Pichia Pastoris and their reactivity with multicellular tumor spheroids. JIM - Journal of Immunological Methods, 364(1-2), 65-76
Open this publication in new window or tab >>Construction of divalent anti-keratin 8 single-chain antibodies (sc(FV)2), expression in Pichia Pastoris and their reactivity with multicellular tumor spheroids
2011 (English)In: JIM - Journal of Immunological Methods, ISSN 0022-1759, E-ISSN 1872-7905, Vol. 364, no 1-2, p. 65-76Article in journal (Refereed) Published
Abstract [en]

Single-chain variable fragments (scFvs) are small monovalent recombinant antibody fragments that retain the specificity of their parent immunoglobulins. ScFvs are excellent building blocks for new and improved immunodiagnostic and therapeutic proteins. However, the monovalency and the rapid renal elimination of scFvs result in poor tumor accumulation and retention. Engineering divalent antibody fragments is an excellent way to address these shortcomings. In this study, covalent divalent single-chain variable fragments (sc(Fv)2s), were constructed from the monovalent anti-keratin 8 scFvs, TS1-218 and its mutant, HE1-Q. The scFvs and sc(Fv)2s were expressed in the methylotrophic yeast Pichia pastoris, utilizing the alpha-factor secretion signal (α-factor) for extracellular secretion. The immunoreactivity and specificity of the antibody fragments were analyzed with enzyme-linked immunosorbent assay (ELISA) and the uptake and retention of the 125I labeled antibody fragments were evaluated using HeLa HEp-2 multicellular tumor spheroids (MCTSs). Analysis of the antibody fragments demonstrated that parts of the α-factor remained at the N-terminal of the antibody fragments. Despite incomplete processing of the α-factor, the antibody fragments were functional where the sc(Fv)2s gave a three-fold stronger signal in ELISA compared to their scFv counterparts and the mutant antibodies demonstrated a stronger signal than their initial wild types. In addition, the sc(Fv)2s DiTS1-218 and DiHE1-Q displayed an approximately two-fold higher uptake and were retained to a larger extent in the MCTS, demonstrating a 3.9 and 9.4-fold increase in half-life respectively compared to their corresponding scFvs. In conclusion, expression in P. pastoris improved the yield 20-fold and facilitated the purification of the antibody fragments. Furthermore, the sc(Fv)2s presented a higher functional affinity to K 8 both in ELISA and MCTS compared to the scFvs with DiHE1-Q being the best candidate for further studies.

Keywords
Anti-keratin 8 antibodies, Divalent single-chain Fv, Pichia pastoris, Immunotargeting, ELISA, Multicellular tumor spheroids
National Category
Biomedical Laboratory Science/Technology
Research subject
Biomedical Sciences
Identifiers
urn:nbn:se:kau:diva-6639 (URN)10.1016/j.jim.2010.11.003 (DOI)000287062700007 ()
Available from: 2010-11-30 Created: 2010-11-30 Last updated: 2019-07-09Bibliographically approved
Jafari, R., Sundström, B. E. & Holm, P. (2011). Optimization of production of the anti-keratin 8 single-chain Fv TS1-218 in Pichia Pastoris using design of experiments. Microbial Cell Factories, 10, 34
Open this publication in new window or tab >>Optimization of production of the anti-keratin 8 single-chain Fv TS1-218 in Pichia Pastoris using design of experiments
2011 (English)In: Microbial Cell Factories, ISSN 1475-2859, E-ISSN 1475-2859, Vol. 10, p. 34-Article in journal (Refereed) Published
National Category
Medical Biotechnology
Identifiers
urn:nbn:se:kau:diva-6640 (URN)10.1186/1475-2859-10-34 (DOI)000291855800001 ()
Available from: 2010-11-30 Created: 2010-11-30 Last updated: 2019-07-09Bibliographically approved
Sundström, B., Holm, P., Jafari, R. & Stigbrand, T. (2010). Anti-keratin 8 single-chain antibody fragments and their evaluation using multicellular tumor spheroids. Paper presented at Cancerfondens planeringsgrupp för onkologisk nuklidterapi.
Open this publication in new window or tab >>Anti-keratin 8 single-chain antibody fragments and their evaluation using multicellular tumor spheroids
2010 (English)Conference paper, Published paper (Other (popular science, discussion, etc.))
National Category
Biological Sciences Biological Sciences
Research subject
Biomedical Sciences
Identifiers
urn:nbn:se:kau:diva-10807 (URN)
Conference
Cancerfondens planeringsgrupp för onkologisk nuklidterapi
Available from: 2012-02-08 Created: 2012-02-08 Last updated: 2019-07-09Bibliographically approved
Sundström, B., Holm, P., Jafari, R. & Stigbrand, T. (2010). Evaluating targeting efficiency of anti-keratin 8 antibody fragments using multicellular tumor spheroids. Paper presented at 38th International Society for Oncology and Biomarkers Munich, Germany 2010.
Open this publication in new window or tab >>Evaluating targeting efficiency of anti-keratin 8 antibody fragments using multicellular tumor spheroids
2010 (English)Conference paper, Published paper (Refereed)
National Category
Biological Sciences Biological Sciences
Research subject
Biomedical Sciences
Identifiers
urn:nbn:se:kau:diva-10316 (URN)
Conference
38th International Society for Oncology and Biomarkers Munich, Germany 2010
Available from: 2012-02-08 Created: 2012-02-08 Last updated: 2019-07-09Bibliographically approved
Erlandsson, A., Holm, P., Jafari, R., Stigbrand, T. & Sundström, B. (2010). Functional mapping of the anti-idiotypic antibody anti-TS1 scFv using site-directed mutagenesis and kinetic analysis. mAbs, 2(6), 663-669
Open this publication in new window or tab >>Functional mapping of the anti-idiotypic antibody anti-TS1 scFv using site-directed mutagenesis and kinetic analysis
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2010 (English)In: mAbs, ISSN 1942-0862, Vol. 2, no 6, p. 663-669Article in journal (Refereed) Published
Place, publisher, year, edition, pages
Taylor & Francis, 2010
National Category
Biological Sciences Biological Sciences
Research subject
Biomedical Sciences
Identifiers
urn:nbn:se:kau:diva-10027 (URN)10.4161/mabs.2.6.13275 (DOI)
Available from: 2012-02-08 Created: 2012-02-08 Last updated: 2019-07-09Bibliographically approved
Jafari, R., Holm, P., Sandegren, J., Stigbrand, T. & Sundström, B. E. (2010). Localization of Complexed Anticytokeratin 8 scFv TS1-218 to HeLa HEp-2 Multicellular Tumor Spheroids and Experimental Tumors. Cancer Biotherapy and Radiopharmaceuticals, 25(4), 455-463
Open this publication in new window or tab >>Localization of Complexed Anticytokeratin 8 scFv TS1-218 to HeLa HEp-2 Multicellular Tumor Spheroids and Experimental Tumors
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2010 (English)In: Cancer Biotherapy and Radiopharmaceuticals, ISSN 1084-9785, E-ISSN 1557-8852, Vol. 25, no 4, p. 455-463Article in journal (Refereed) Published
National Category
Medical Biotechnology
Research subject
Biomedical Sciences
Identifiers
urn:nbn:se:kau:diva-6635 (URN)10.1089/cbr.2010.0785 (DOI)
Available from: 2010-11-29 Created: 2010-11-29 Last updated: 2019-07-09Bibliographically approved
Holm, P., Jafari, R. & Sundström, B. (2007). Functional mapping and single chain construction of the anti-cytokeratin 8 monoclonal antibody TS1. Molecular Immunology, 44(6), 1075-1084
Open this publication in new window or tab >>Functional mapping and single chain construction of the anti-cytokeratin 8 monoclonal antibody TS1
2007 (English)In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 44, no 6, p. 1075-1084Article in journal (Refereed) Published
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:kau:diva-2083 (URN)10.1016/j.molimm.2006.08.001 (DOI)
Available from: 2007-03-14 Created: 2007-03-14 Last updated: 2019-07-09Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0001-9302-2396

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