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Simonsson, Martin
Publications (10 of 10) Show all publications
Azar, J., Simonsson, M., Bengtsson, E. & Hast, A. (2015). Automated Classification of Glandular Tissue by Statistical Proximity Sampling. International Journal of Biomedical Imaging, Article ID 943104.
Open this publication in new window or tab >>Automated Classification of Glandular Tissue by Statistical Proximity Sampling
2015 (English)In: International Journal of Biomedical Imaging, ISSN 1687-4188, E-ISSN 1687-4196, article id 943104Article in journal (Refereed) Published
Abstract [en]

Due to the complexity of biological tissue and variations in staining procedures, features that are based on the explicit extraction of properties from subglandular structures in tissue images may have difficulty generalizing well over an unrestricted set of images and staining variations. We circumvent this problem by an implicit representation that is both robust and highly descriptive, especially when combined with a multiple instance learning approach to image classification. The new feature method is able to describe tissue architecture based on glandular structure. It is based on statistically representing the relative distribution of tissue components around lumen regions, while preserving spatial and quantitative information, as a basis for diagnosing and analyzing different areas within an image. We demonstrate the efficacy of the method in extracting discriminative features for obtaining high classification rates for tubular formation in both healthy and cancerous tissue, which is an important component in Gleason and tubule-based Elston grading. The proposed method may be used for glandular classification, also in other tissue types, in addition to general applicability as a region-based feature descriptor in image analysis where the image represents a bag with a certain label (or grade) and the region-based feature vectors represent instances.

National Category
Medical Image Processing
Identifiers
urn:nbn:se:uu:diva-230871 (URN)10.1155/2015/943104 (DOI)000362067400001 ()
Available from: 2014-09-01 Created: 2014-09-01 Last updated: 2017-12-05Bibliographically approved
Issac Niwas, S., Kårsnäs, A., Uhlmann, V., Ponnusamy, P., Kampf, C., Simonsson, M., . . . Strand, R. (2013). Automated classification of immunostaining patterns in breast tissue from the Human Protein Atlas. Journal of Pathology Informatics, 4(14)
Open this publication in new window or tab >>Automated classification of immunostaining patterns in breast tissue from the Human Protein Atlas
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2013 (English)In: Journal of Pathology Informatics, ISSN 2229-5089, E-ISSN 2153-3539, Vol. 4, no 14Article in journal (Refereed) Published
Abstract [en]

Background:

The Human Protein Atlas (HPA) is an effort to map the location of all human proteins (http://www.proteinatlas.org/). It contains a large number of histological images of sections from human tissue. Tissue micro arrays (TMA) are imaged by a slide scanning microscope, and each image represents a thin slice of a tissue core with a dark brown antibody specific stain and a blue counter stain. When generating antibodies for protein profiling of the human proteome, an important step in the quality control is to compare staining patterns of different antibodies directed towards the same protein. This comparison is an ultimate control that the antibody recognizes the right protein. In this paper, we propose and evaluate different approaches for classifying sub-cellular antibody staining patterns in breast tissue samples.

Materials and Methods:

The proposed methods include the computation of various features including gray level co-occurrence matrix (GLCM) features, complex wavelet co-occurrence matrix (CWCM) features, and weighted neighbor distance using compound hierarchy of algorithms representing morphology (WND-CHARM)-inspired features. The extracted features are used into two different multivariate classifiers (support vector machine (SVM) and linear discriminant analysis (LDA) classifier). Before extracting features, we use color deconvolution to separate different tissue components, such as the brownly stained positive regions and the blue cellular regions, in the immuno-stained TMA images of breast tissue.

Results:

We present classification results based on combinations of feature measurements. The proposed complex wavelet features and the WND-CHARM features have accuracy similar to that of a human expert.

Conclusions:

Both human experts and the proposed automated methods have difficulties discriminating between nuclear and cytoplasmic staining patterns. This is to a large extent due to mixed staining of nucleus and cytoplasm. Methods for quantification of staining patterns in histopathology have many applications, ranging from antibody quality control to tumor grading.

National Category
Medical Image Processing
Research subject
Behavioural Neuroscience; Computerized Image Processing
Identifiers
urn:nbn:se:uu:diva-212564 (URN)10.4103/2153-3539.109881 (DOI)
Available from: 2013-12-11 Created: 2013-12-11 Last updated: 2017-12-06Bibliographically approved
Hedström, G., Thunberg, U., Berglund, M., Simonsson, M., Amini, R.-M. & Enblad, G. (2013). Low expression of microRNA-129-5p predicts poor clinical outcome in diffuse large B cell lymphoma (DLBCL). International Journal of Hematology, 97(4), 465-471
Open this publication in new window or tab >>Low expression of microRNA-129-5p predicts poor clinical outcome in diffuse large B cell lymphoma (DLBCL)
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2013 (English)In: International Journal of Hematology, ISSN 0925-5710, E-ISSN 1865-3774, Vol. 97, no 4, p. 465-471Article in journal (Refereed) Published
Abstract [en]

Diffuse large B cell lymphoma (DLBCL) is a heterogeneous group of B cell lymphomas. MicroRNA expression provides a new and interesting tool for understanding the biology and clinical course of DLBCL. The present study presents microRNA-129-5p expression data from DLBCL patients treated with CHOP or R-CHOP. Patients with low microRNA-129-5p expression had a median survival of 23 months and a significantly shorter overall survival (P = 0.0042) compared to patients with high microRNA-129-5p expression, who had a median survival of 58 months. We also found that patients treated with R-CHOP only and displaying low microRNA-129-5p expression had a significantly shorter overall survival compared to patients with high microRNA-129-5p expression; all such patients were still alive at the time of last follow-up (P = 0.043). No significant difference was found among microRNA-129-5p expression in tumor tissue, the tissue surrounding the tumor, and normal controls. To our knowledge, this is the first report to show that the expression of microRNA-129-5p can affect the clinical outcome of DLBCL patients and that microRNA-129-5p may be involved in the biology of DLBCL development, although larger studies are necessary to confirm this. Further investigations may also help to elucidate the biological role of microRNA-129-5p in DLBCL.

Keywords
DLBCL, microRNA-129-5p, Prognosis
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-200079 (URN)10.1007/s12185-013-1303-2 (DOI)000317475500005 ()
Available from: 2013-05-23 Created: 2013-05-20 Last updated: 2017-12-06Bibliographically approved
Seppänen, H., Rauhala, T., Kiprich, S., Ukkonen, J., Simonsson, M., Kurppa, R., . . . Hæggström, E. (2013). One kilometer (1 km) electric solar wind sail tether produced automatically. Review of Scientific Instruments, 84(9), Article ID 095102.
Open this publication in new window or tab >>One kilometer (1 km) electric solar wind sail tether produced automatically
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2013 (English)In: Review of Scientific Instruments, ISSN 0034-6748, E-ISSN 1089-7623, Vol. 84, no 9, article id 095102Article in journal (Refereed) Published
Abstract [en]

We produced a 1 km continuous piece of multifilament electric solar wind sail tether of μm-diameter aluminum wires using a custom made automatic tether factory. The tether comprising 90 704 bonds between 25 and 50 μm diameter wires is reeled onto a metal reel. The total mass of 1 km tether is 10 g. We reached a production rate of 70 m/24 h and a quality level of 1‰ loose bonds and 2‰ rebonded ones. We thus demonstrated that production of long electric solar wind sail tethers is possible and practical.

National Category
Energy Engineering
Identifiers
urn:nbn:se:uu:diva-212504 (URN)10.1063/1.4819795 (DOI)000325402000053 ()24089861 (PubMedID)
Available from: 2013-09-03 Created: 2013-12-11 Last updated: 2017-12-06Bibliographically approved
Issac Niwas, S., Kårsnäs, A., Uhlmann, V., Palanisamy, P., Kampf, C., Simonsson, M., . . . Strand, R. (2012). Automated classification of immunostaining patterns in breast tissue from the Human Protein Atlas. In: Histopathology Image Analysis (HIMA): a MICCAI 2012 workshop. Paper presented at Histopathology Image Analysis (HIMA), a MICCAI 2012 workshop, 5 October, 2012, Nice, France.
Open this publication in new window or tab >>Automated classification of immunostaining patterns in breast tissue from the Human Protein Atlas
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2012 (English)In: Histopathology Image Analysis (HIMA): a MICCAI 2012 workshop, 2012Conference paper, Poster (with or without abstract) (Refereed)
Abstract [en]

Background:

The Human Protein Atlas (HPA) is an effort to map the location of all human proteins (http://www.proteinatlas.org/ ). It contains a large number of histological images of sections from human tissue. Tissue micro arrays are imaged by a slide scanning microscope, and each image represents a thin slice of a tissue core with a dark brown antibody specific stain and a blue counter stain. When generating antibodies for protein profiling of the human proteome, an important step in the quality control is to compare staining patterns of different antibodies directed towards the same protein. This comparison is an ultimate control that the antibody recognizes the right protein. In this paper, we propose and evaluate different approaches for classifying sub-cellular antibody staining patterns in breast tissue samples.

Methods and Material:

The proposed methods include the computation of various features including gray level co-occurrence matrix (GLCM) features, complex wavelet co-occurrence matrix (CWCM) features and WND-CHARM-inspired features. The extracted features are used into two different multivariate classifiers (SVM and LDA classifier). Before extracting features, we use color deconvolution to separate different tissue components, such as the brownly stained positive regions and the blue cellular regions, in the immuno-stained TMA images of breast tissue.

Results:

Good results have been obtained by using the combinations of GLCM and wavelets and texture features, edge features, histograms, transforms, etc. (WND-CHARM). The proposed complex wavelet features and the WND-CHARM features have accuracy similar to that of a human expert.

Conclusions:

Both human experts and the proposed automated methods have difficulties discriminating between nuclear and cytoplasmic staining patterns. This is to a large extent due to mixed staining of nucleus and cytoplasm. Methods for quantification of staining patterns in histopathology have many applications, ranging from antibody quality control to tumour grading.

National Category
Medical Image Processing
Identifiers
urn:nbn:se:uu:diva-188447 (URN)
Conference
Histopathology Image Analysis (HIMA), a MICCAI 2012 workshop, 5 October, 2012, Nice, France
Available from: 2012-12-17 Created: 2012-12-17 Last updated: 2013-07-05Bibliographically approved
Wu, X., Smavadati, S., Nordfjäll, K., Karlsson, K., Qvarnström, F., Simonsson, M., . . . Paulsson-Karlsson, Y. (2012). Telomerase antagonist imetelstat inhibits esophageal cancer cell growth and increases radiation-induced DNA breaks. Biochimica et Biophysica Acta. Molecular Cell Research, 1823(12), 2130-2135
Open this publication in new window or tab >>Telomerase antagonist imetelstat inhibits esophageal cancer cell growth and increases radiation-induced DNA breaks
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2012 (English)In: Biochimica et Biophysica Acta. Molecular Cell Research, ISSN 0167-4889, E-ISSN 1879-2596, Vol. 1823, no 12, p. 2130-2135Article in journal (Refereed) Published
Abstract [en]

Telomerase is mainly active in human tumor cells, which provides an opportunity for a therapeutic window on telomerase targeting. We sought to evaluate the potential of the thio-phosphoramidate oligonucleotide inhibitor of telomerase, imetelstat, as a drug candidate for treatment of esophageal cancer. Our results showed that imetelstat inhibited telomerase activity in a dose-dependent manner in esophageal cancer cells. After only 1. week of imetelstat treatment, a reduction of colony formation ability of esophageal cancer cells was observed. Furthermore, long-term treatment with imetelstat decreased cell growth of esophageal cancer cells with different kinetics regarding telomere lengths. Short-term imetelstat treatment also increased γ-H2AX and 53BP1 foci staining in the esophageal cancer cell lines indicating a possible induction of DNA double strand breaks (DSBs). We also found that pre-treatment with imetelstat led to increased number and size of 53BP1 foci after ionizing radiation. The increase of 53BP1 foci number was especially pronounced during the first 1 h of repair whereas the increase of foci size was prominent later on. This study supports the potential of imetelstat as a therapeutic agent for the treatment of esophageal cancer.

Keywords
γ-H2AX and 53BP1 foci, DNA double strand break, Esophageal cancer, Imetelstat, Telomerase
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-184884 (URN)10.1016/j.bbamcr.2012.08.003 (DOI)000312629200004 ()
Available from: 2012-11-21 Created: 2012-11-15 Last updated: 2017-12-07Bibliographically approved
Glimelius, I., Qvarnström, F., Simonsson, M., Ekwall, A., Smedby, K. E., Molin, D. & Amini, R.-M. (2012). Tissue microarray and digital image analysis: a methodological study with special reference to the microenvironment in Hodgkin lymphoma. Histopathology, 61(1), 26-32
Open this publication in new window or tab >>Tissue microarray and digital image analysis: a methodological study with special reference to the microenvironment in Hodgkin lymphoma
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2012 (English)In: Histopathology, ISSN 0309-0167, E-ISSN 1365-2559, Vol. 61, no 1, p. 26-32Article in journal (Refereed) Published
Abstract [en]

Aim:  Cancer research has moved from solely investigating the tumour cells to also including analysis of the tumour microenvironment; however, the methods utilized have not been evaluated for this change. The aim of this study was to compare tissue microarrays (TMA) to whole tissue sections (WS) with regard to cells in the tumour microenvironment. Manual evaluation and digital image analyses (DIA) were utilized and also compared.

Methods and results:  TMA slides from 117 Hodgkin lymphoma patients were immunostained for forkhead box protein 3 (FoxP3) [identifying regulatory T cells (T(reg) )], and 39 corresponding WS were also analysed. Manual evaluation and DIA were utilized for all patients on both the TMA and the WS. A correlation coefficient of 0.83 was obtained for the proportion of T(reg) in TMA versus WS using manual evaluation and a correlation coefficient of 0.77 with DIA. T(reg) counts using manual evaluation correlated in turn with DIA, with a coefficient of 0.79 for the 117 TMA sections and 0.65 for the 39 WS.

Conclusion:  Because a high correlation was observed between TMA and WS, TMA can be utilized when evaluating cells in the tumour microenvironment. DIA appears to provide a reliable measurement method, provided that manual control of the tumour slides is conducted.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-170983 (URN)10.1111/j.1365-2559.2012.04185.x (DOI)000305604900004 ()22394012 (PubMedID)
Note

De två första författarna delar förstaförfattarskapet.

Available from: 2012-03-14 Created: 2012-03-14 Last updated: 2017-12-07Bibliographically approved
Simonsson, M. (2011). Quantification of Radiation Induced DNA Damage Response in Normal Skin Exposed in Clinical Settings. (Doctoral dissertation). Uppsala: Acta Universitatis Upsaliensis
Open this publication in new window or tab >>Quantification of Radiation Induced DNA Damage Response in Normal Skin Exposed in Clinical Settings
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The structure, function and accessibility of epidermal skin provide aunique opportunity to study the DNA damage response (DDR) of a normaltissue. The in vivo response can be examined in detail, at a molecularlevel, and further associated to the structural changes, observed at atissue level. We collected an extensive skin biopsy material frompatients undergoing fractionated radiotherapy for 5 to 7 weeks. Several end-points inthe DDR pathways were examined before, during and after the treatment.

Quantification of DNA double strand break (DSB) signalling focirevealed a hypersensitivity to doses below 0.3Gy. Furthermore, aconsiderable amount of foci persisted between fractions. The low dosehypersensitivity was observed throughout the treatment and was alsoobserved for several key parameters further downstream in the DDR-pathway, such as p21-associated checkpoint activation, apoptosisinduction and reduction in basal keratinocyte density (BKD).Furthermore, for dose fractions above 1.0 Gy, a distinct acceleration inDDR was observed half way into treatment. This was manifested as anaccelerated loss of basal keratinocytes, mirrored by a simultaneousincrease in DSBs and p21 expression.

Quantifications of mitotic events revealed a pronounced suppression ofmitosis throughout the treatment which was clearly low dosehypersensitive. Thus, no evidence of accelerated repopulation could beobserved for fraction doses ranging from 0.05 to 2Gy.

Our results suggest that the keratinocyte response primarily isdetermined by checkpoints, which leads to pre-mitotic cell elimination by permanent growth arrest and apoptosis.

A comparison between the epidermal and dermal sub-compartments revealsa consistent up-regulation of the DDR response during treatment. Adifference was however observed in the recovery phase after treatment,where miR-34a and p21 remain up-regulated in dermis more persistentlythan in epidermis. Our observations suggest that the recovery phaseafter treatment can provide important clues to understand clinicalobservations such as the early and late effects observed in normaltissues during fractionated radiotherapy.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2011. p. 51
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 631
Keywords
DNA damage response, low-dose hypersensitivity, dose response, normal tissue, epidermis, dermis, keratinocyte, fractionated radiotherapy, DNA double strand break, DSB, foci, gamma-H2AX, 53BP1, p21, checkpoint, apoptosis, mitosis, micro-RNA, miR-34a
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:uu:diva-134600 (URN)978-91-554-7969-5 (ISBN)
Public defence
2011-01-14, Hörsal Betty Pettersson, Blåsenhus, von Kraemers Allé 1, Uppsala, 09:00 (English)
Opponent
Supervisors
Available from: 2010-12-23 Created: 2010-11-29 Last updated: 2011-01-13Bibliographically approved
Simonsson, M., Qvarnström, F., Nyman, J., Johansson, K.-A., Garmo, H. & Turesson, I. (2008). Low-dose hypersensitive gammaH2AX response and infrequent apoptosis in epidermis from radiotherapy patients. Radiotherapy and Oncology, 88(3), 388-397
Open this publication in new window or tab >>Low-dose hypersensitive gammaH2AX response and infrequent apoptosis in epidermis from radiotherapy patients
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2008 (English)In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 88, no 3, p. 388-397Article in journal (Refereed) Published
Abstract [en]

BACKGROUND AND PURPOSE: A low-dose hypersensitivity to radiation can be observed in vitro for many human cell types in terms of increased cell kill per dose unit for doses below 0.5Gy. Quantification of the double-strand break marker gammaH2AX in samples taken in clinical radiotherapy practice has the potential to provide important information about how induction and repair of severe DNA damage and apoptosis are linked to low-dose hypersensitivity. MATERIAL AND METHODS: The effects of exposure to low doses (0.05-1.1Gy) were investigated in skin biopsies taken from prostate cancer patients undergoing the first week of radiotherapy. gammaH2AX foci and apoptotic cells were visualised by immunohistochemistry and quantified by image analysis. RESULTS: The gammaH2AX foci pattern in biopsies taken 30min after a single fraction revealed a low-dose hypersensitivity below 0.3Gy (p=0.0009). The result was consistent for repeated fractions (p=0.00001). No decrease in foci numbers could be detected when comparing biopsies taken 30min and 2h after single fractions of 0.4 and 1.2Gy. The result was consistent for repeated fractions. Only 43 of 168,000 cells in total were identified as apoptotic, yet a dose dependency could be detected after 1week of radiotherapy (p=0.003). CONCLUSIONS: We describe a method based on gammaH2AX to study DNA damage response and apoptosis in a clinical setting. A gammaH2AX hypersensitive response to low doses can be observed in epidermal skin, already 30min following delivered fraction. A very low frequency of apoptosis in normal epithelium suggests that this effect is not an important part of the in vivo response to low doses.

Keywords
γH2AX, Hypersensitivity, Apoptosis, Epidermis, Normal tissue, Parp-1; DNA damage, DNA repair, Double strand breaks, DSB, Digital image analysis, Foci
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-17482 (URN)10.1016/j.radonc.2008.04.017 (DOI)000260203800012 ()18524402 (PubMedID)
Available from: 2008-06-24 Created: 2008-06-24 Last updated: 2017-12-08Bibliographically approved
Qvarnström, O. F., Simonsson, M., Johansson, K.-A., Nyman, J. & Turesson, I. (2004). DNA double strand break quantification in skin biopsies.. Radiother Oncol, 72(3), 311-7
Open this publication in new window or tab >>DNA double strand break quantification in skin biopsies.
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2004 (English)In: Radiother Oncol, ISSN 0167-8140, Vol. 72, no 3, p. 311-7Article in journal (Other scientific) Published
Keywords
Biopsy, DNA Damage, Humans, Immunohistochemistry, Male, Prostatic Neoplasms/radiotherapy, Reproducibility of Results, Research Support; Non-U.S. Gov't, Skin/pathology/*radiation effects
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-70012 (URN)15450730 (PubMedID)
Available from: 2005-04-14 Created: 2005-04-14 Last updated: 2011-01-12
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