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Stigbrand, Torgny
Publications (10 of 49) Show all publications
Stigbrand, T. (2017). The rapidly changing landscape of scientific publishing.
Open this publication in new window or tab >>The rapidly changing landscape of scientific publishing
2017 (English)Other (Other (popular science, discussion, etc.))
Keywords
Scientific publishing
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-143266 (URN)10.1177/1010428316687894 (DOI)
Note

tub.com/home/tej

Available from: 2017-12-19 Created: 2017-12-19 Last updated: 2018-06-09
Lindgren, T., Stigbrand, T., Råberg, A., Riklund, K., Johansson, L. & Eriksson, D. (2015). Genome wide expression analysis of radiation induced DNA damage responses in isogenic HCT116 p53 +/+ and HCT116 p53 -/- colorectal carcinoma cell lines. International Journal of Radiation Biology, 91(1), 99-111
Open this publication in new window or tab >>Genome wide expression analysis of radiation induced DNA damage responses in isogenic HCT116 p53 +/+ and HCT116 p53 -/- colorectal carcinoma cell lines
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2015 (English)In: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 91, no 1, p. 99-111Article in journal (Refereed) Published
Abstract [en]

Purpose : To study the kinetics of gene expression alterations following radiation exposure of isogenic HCT116 p53+/+ and HCT116 p53-/- cell lines. Materials and methods : Cells were exposed to 5 Gy of irradiation (Cs-137) and genome-wide temporal expression analysis using Illumina bead chip arrays was performed. Signalling pathways were explored using Metacore (Genego). Biological responses including cell cycle checkpoint activation, centrosome amplification and senescence induction were analyzed. Results : Significant differences in the radiation response were observed between the p53+/+ and the p53-/- cell lines. In p53+/+ cells concurrent G1- and G2-arrests were activated followed by senescence induction. Increased expression of genes associated with senescence, senescence associated secretory phenotype (SASP) and repression of genes essential for G2-M transition were detected. P53-/- cells arrested mainly in G2 followed by centrosome amplification, mitotic slippage and a subsequent increase of polyploid cells. Furthermore, changes in expression correlated well with these signs of mitotic catastrophe. Conclusions : The presence or absence of p53 triggers different signalling cascades with different endpoints. Elucidating these differences is important as it enables improvement of radiation treatment and could be used to develop new combination treatments with specific inhibitors of key regulators of these cell death modalities.

Keywords
radiation, gene expression, senescence, p53, mitotic catastrophe, cell cycle checkpoint
National Category
Cell and Molecular Biology
Research subject
Immunology; radiofysik
Identifiers
urn:nbn:se:umu:diva-80231 (URN)10.3109/09553002.2015.959668 (DOI)000349557900011 ()25219679 (PubMedID)
Note

Originally published in manuscript form.

Available from: 2013-09-12 Created: 2013-09-12 Last updated: 2018-06-08Bibliographically approved
Lindgren, T., Stigbrand, T., Johansson, L., Riklund, K. & Eriksson, D. (2014). Alterations in Gene Expression During Radiation-Induced Mitotic Catastrophe in He La Hep2 Cells. Anticancer Research, 34(8), 3875-3880
Open this publication in new window or tab >>Alterations in Gene Expression During Radiation-Induced Mitotic Catastrophe in He La Hep2 Cells
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2014 (English)In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 34, no 8, p. 3875-3880Article in journal (Refereed) Published
Abstract [en]

Aim: To explore kinetic changes in the gene expression profile during radiation-induced mitotic catastrophes. Materials and Methods: Gene expression changes were measured in HPV-infected HeLa Hep2 tumor cells following exposure to 5 Gy of ionizing radiation (Co-60). Signaling pathways were explored and correlated to the biological responses linked to mitotic catastrophe. Results: Following irradiation a transient G(2)-arrest was induced. Anaphase bridge formation and centrosome hyperamplification was observed. These phenotypical changes correlated well with the observed gene expression changes. Genes with altered expression were found to be involved in mitotic processes as well as G(2)- and spindle assembly checkpoints. Also centrosome-associated genes displayed an increased expression. Conclusion: This study elucidates specific characteristics in the altered gene expression pattern induced by irradiation, which can be correlated to the events of mitotic catastrophe in HeLa Hep2 cells. Therapeutic strategies modulating these alterations might potentiate future therapy and enhance tumor cell killing.

Place, publisher, year, edition, pages
INT INST ANTICANCER RESEARCH, 2014
Keywords
Radiation, cell cycle checkpoint, cell death, mitotic catastrophe, gene expression
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-92927 (URN)000339773400002 ()
Available from: 2014-09-18 Created: 2014-09-09 Last updated: 2018-06-07Bibliographically approved
Stigbrand, T. & Lejon, K. (2013). Välkomna till 2013 års Forskningens dag! (1ed.). In: Mattias Grundström Mitz och Lena Åminne (Ed.), Cancerforskning på nya vägar: en bok från Forskningens dag 2013, Medicinska fakulteten vid Umeå universitet (pp. 7-14). Umeå: Umeå universitet
Open this publication in new window or tab >>Välkomna till 2013 års Forskningens dag!
2013 (Swedish)In: Cancerforskning på nya vägar: en bok från Forskningens dag 2013, Medicinska fakulteten vid Umeå universitet / [ed] Mattias Grundström Mitz och Lena Åminne, Umeå: Umeå universitet , 2013, 1, p. 7-14Chapter in book (Other (popular science, discussion, etc.))
Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2013 Edition: 1
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-87780 (URN)978-91-7459-805-6 (ISBN)
Note

Available from: 2014-04-09 Created: 2014-04-09 Last updated: 2018-06-08Bibliographically approved
Lindgren, T., Stigbrand, T., Riklund, K., Johansson, L. & Eriksson, D. (2012). Gene expression profiling in MOLT-4 cells during gamma-radiation-induced apoptosis. Tumor Biology, 33(3), 689-700
Open this publication in new window or tab >>Gene expression profiling in MOLT-4 cells during gamma-radiation-induced apoptosis
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2012 (English)In: Tumor Biology, ISSN 1010-4283, E-ISSN 1423-0380, Vol. 33, no 3, p. 689-700Article in journal (Refereed) Published
Abstract [en]

This study aims to identify the temporal changes in gene expression in MOLT-4, a leukemia cell line, in response to radiation and to present a comprehensive description of the pathways and processes that most significantly relate to the cellular biological responses. A global gene expression profile of 24,500 genes was performed on MOLT-4 tumor cells following exposure to 5 Gy of ionizing radiation (Co-60) using a bead chip array (Illumina). Signaling pathways and processes significantly altered following irradiation were explored using MetaCore. Cellular viability [3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide], activation of cell cycle checkpoints [fluorescence activated cell sorting (FACS)], and induction of apoptosis (FACS, caspase assays) were evaluated to correlate these biological responses to the gene expression changes. Totally, 698 different genes displayed a significantly altered expression following radiation, and out of these transcripts, all but one showed increased expression. One hour following irradiation, the expression was changed only for a few genes. Striking changes appeared at later time-points. From 3 to 24 h post-irradiation, a significant fraction of the genes with altered expression were found to be involved in cell cycle checkpoints and their regulation (CDKN1A), DNA repair (GADD45A, DDB2, XPC), apoptosis induction (DR5, FasR, Apo-2L, Bax), and T-cell activation/proliferation (CD70, OX40L). Irradiated MOLT-4 cells were arrested at the G2-checkpoint, followed by a decrease in cell viability, most pronounced 48 h after exposure. The cell death was executed by induced apoptosis and was visualized by an increase in subG1 cells and an increased activation of initiator (caspase-8 and caspase-9) and execution (caspase-3) caspases. Activation of cell cycle arrest and apoptosis correlated well in time with the changes in gene expression of those genes important for these biological processes. Activation of the apoptotic signaling pathways in MOLT-4 cells following irradiation includes components from the intrinsic as well as the extrinsic apoptotic pathways. This study indicates that the altered gene expression pattern induced by irradiation is important for the sequential steps observed in MOLT-4 cells during apoptosis induction.

Keywords
Apoptosis, Radiation, Gene expression, Leukemia, Microarray
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-56209 (URN)10.1007/s13277-012-0329-z (DOI)000303530200013 ()
Available from: 2012-06-12 Created: 2012-06-12 Last updated: 2018-06-08Bibliographically approved
Lindgren, T., Stigbrand, T., Raberg, A., Riklund, K., Johansson, L. & Eriksson, D. (2012). Genome wide expression analysis of radiation induced DNA damage responses in isogenic HCT 116 cell lines. Paper presented at 40th Congress of the International-Society-of-Oncology-and-Biomarkers, OCT 13-17, 2012, Jerusalem, ISRAEL. Tumor Biology, 33(Suppl. 1), 76-76
Open this publication in new window or tab >>Genome wide expression analysis of radiation induced DNA damage responses in isogenic HCT 116 cell lines
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2012 (English)In: Tumor Biology, ISSN 1010-4283, E-ISSN 1423-0380, Vol. 33, no Suppl. 1, p. 76-76Article in journal, Meeting abstract (Other academic) Published
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-61570 (URN)000309547800115 ()
Conference
40th Congress of the International-Society-of-Oncology-and-Biomarkers, OCT 13-17, 2012, Jerusalem, ISRAEL
Available from: 2012-11-28 Created: 2012-11-20 Last updated: 2018-06-08Bibliographically approved
Paus, E., Haugen, M. H., Olsen, K. H., Flatmark, K., Maelandsmo, G. M., Nilsson, O., . . . Stigbrand, T. (2011). TD-11 workshop report: characterization of monoclonal antibodies to S100 proteins. Tumor Biology, 32(1), 1-12
Open this publication in new window or tab >>TD-11 workshop report: characterization of monoclonal antibodies to S100 proteins
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2011 (English)In: Tumor Biology, ISSN 1010-4283, E-ISSN 1423-0380, Vol. 32, no 1, p. 1-12Article in journal (Refereed) Published
Abstract [en]

Fourteen monoclonal antibodies with specificity against native or recombinant antigens within the S100 family were investigated with regard to immunoreactivity. The specificities of the antibodies were studied using ELISA tests, Western blotting epitope mapping using competitive assays, and QCM technology. The mimotopes of antibodies against S100A4 were determined by random peptide phage display libraries. Antibody specificity was also tested by IHC and pair combinations evaluated for construction of immunoradiometric assays for S100B. Out of the 14 antibodies included in this report eight demonstrated specificity to S100B, namely MAbs 4E3, 4D2, S23, S53, 6G1, S21, S36, and 8B10. This reactivity could be classified into four different epitope groups using competing studies. Several of these MAbs did display minor reactivity to other S100 proteins when they were presented in denatured form. Only one of the antibodies, MAb 3B10, displayed preferential reactivity to S100A1; however, it also showed partial cross-reactivity with S100A10 and S100A13. Three antibodies, MAbs 20.1, 22.3, and S195, were specific for recombinant S100A4 in solution. Western blot revealed that MAb 20.1 and 22.3 recognized linear epitopes of S100A4, while MAb S195 reacted with a conformational dependent epitope. Surprisingly, MAb 14B3 did not demonstrate any reactivity to the panel of antigens used in this study.

Keywords
S100 proteins, Monoclonal antibodies, Antibody specificities
Identifiers
urn:nbn:se:umu:diva-41988 (URN)10.1007/s13277-010-0073-1 (DOI)20652782 (PubMedID)
Available from: 2011-04-04 Created: 2011-04-04 Last updated: 2018-06-08Bibliographically approved
Erlandsson, A., Holm, P., Jafari, R., Stigbrand, T. & Sundström, B. E. (2010). Functional mapping of the anti-idiotypic antibody anti-TS1 scFv using site-directed mutagenesis and kinetic analysis. mAbs, 2(6), 662-669
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 1942-0870, Vol. 2, no 6, p. 662-669Article in journal (Refereed) Published
Abstract [en]

Recombinant antibodies may be engineered to obtain improved functional properties. Functional mapping of the residues in the binding surfaces is of importance for predicting alterations needed to yield the desired properties. In this investigation, 17 single mutation mutant single-chain variable fragments (scFvs) of the anti-idiotypic antibody anti-TS1 were generated in order to functionally map amino acid residues important for the interaction with its idiotype TS1. Residues in anti-TS1 determined to be very important for the interaction were identified, Y32L, K50L, K33H, and Y52H, and they were distributed adjacent to a centrally located hydrophobic area, and contributed extensively to the interaction energy (≥2.5 kcal/mol) in the interaction. Quantitative ELISA assays, BIAcore technologies and three-dimensional surface analysis by modeling were employed to visualize the consequences of the mutations. The expression levels varied between 2 - 1,800 nM as determined by ELISA. All the 17 scFvs displayed higher dissociation rates (60 - 1,300 times) and all but two of them also faster association rates (1.3 - 56 times). The decrease in affinity was determined to be 1.6 - 12,200 times. Two of the mutants displayed almost identical affinity with the wild type anti-TS1, but with a change in both association and dissociation rates. The present investigation demonstrates that it is possible to generate a large panorama of anti-idiotypic antibodies, and single out a few that might be of potential use for future clearing and pre-targeting purposes of idiotypic-anti-idiotypic interactions.

Identifiers
urn:nbn:se:umu:diva-41993 (URN)10.4161/mabs.2.6.13275 (DOI)000286088300008 ()21124071 (PubMedID)
Available from: 2011-04-04 Created: 2011-04-04 Last updated: 2018-06-08Bibliographically 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
Abstract [en]

Recombinant single-chain fragment variable (scFv) antibodies with specificity to tumor antigens can be used to target tumors in vivo. The approach to use administration of complexes of idiotypic-anti-idiotypic scFvs when targeting tumors has not been tested earlier, and from a theoretical point it could contribute to longer in vivo circulation and improved targeting efficiency by dissociation, when in contact with the target antigen. In this study two models to evaluate the targeting efficiency of such complexes were used. HeLa HEp-2 tumor cells were grown as multicellular tumor spheroids (MCTS) and exposed to the antibody constructs in vitro. The behavior in vivo was tested in an in vivo tumor xenograft model. To increase the size of the anticytokeratin 8 scFv, TS1-218, complexes were formed between TS1-218 and its anti-idiotype, alphaTS1 scFv. The functionality of (125)I-labeled TS1-218 alone and in complex was studied in both models. The uptake patterns were similar in both models. The idiotypic TS1-218 was able to localize to the MCTS and xenografted tumors, both alone and in complex with alphaTS1 scFv. TS1-218 in complex, however, demonstrated a significantly higher uptake than the monomeric TS1-218 in both models (p < 0.0005 and p < 0.0089, respectively). When complexes were administered in vivo, a slower clearance and an increased tumor half-life could be observed. The present investigation indicates that administration of targeting antibodies, with initially blocked antigen-binding sites by complex formation with their anti-idiotypes, may improve targeting efficiency.

Keywords
CK 8, HeLa HEp-2 tumors, immunotargeting, MCTS, scFv/scFv immune complexes, TS1-218, αTS1 scFv
Identifiers
urn:nbn:se:umu:diva-41989 (URN)10.1089/cbr.2010.0785 (DOI)000281255100010 ()20707717 (PubMedID)
Available from: 2011-04-04 Created: 2011-04-04 Last updated: 2018-06-08Bibliographically approved
Petzold, A., Altintas, A., Andreoni, L., Bartos, A., Berthele, A., Blankenstein, M. A., . . . Teunissen, C. E. (2010). Neurofilament ELISA validation. JIM - Journal of Immunological Methods, 352(1-2), 23-31
Open this publication in new window or tab >>Neurofilament ELISA validation
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2010 (English)In: JIM - Journal of Immunological Methods, ISSN 0022-1759, E-ISSN 1872-7905, Vol. 352, no 1-2, p. 23-31Article in journal (Refereed) Published
Abstract [en]

This multi-center validation study identified the lack of preparation of accurate and consistent protein standards as the main reason for a poor inter-laboratory CV. This issue is also relevant to other protein biomarkers based on this type of assay and will need to be solved in order to achieve an acceptable level of analytical accuracy. The raw data of this study is available online.

Keywords
Neurofilament; NfL; NF-L; NEFL; Biomarker; Validation
Identifiers
urn:nbn:se:umu:diva-41961 (URN)10.1016/j.jim.2009.09.014 (DOI)000274102000003 ()19857497 (PubMedID)
Available from: 2011-04-04 Created: 2011-04-04 Last updated: 2018-06-08Bibliographically approved
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