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Publications (10 of 33) Show all publications
Avenel, C., Tolf, A., Dragomir, A. & Carlbom, I. (2019). Glandular Segmentation of Prostate Cancer: An Illustration of How the Choice of Histopathological Stain Is One Key to Success for Computational Pathology. Frontiers in Bioengineering and Biotechnology, 7, Article ID 125.
Open this publication in new window or tab >>Glandular Segmentation of Prostate Cancer: An Illustration of How the Choice of Histopathological Stain Is One Key to Success for Computational Pathology
2019 (English)In: Frontiers in Bioengineering and Biotechnology, E-ISSN 2296-4185, Vol. 7, article id 125Article in journal (Refereed) Published
Abstract [en]

Digital pathology offers the potential for computer-aided diagnosis, significantly reducing the pathologists' workload and paving the way for accurate prognostication with reduced inter-and intra-observer variations. But successful computer-based analysis requires careful tissue preparation and image acquisition to keep color and intensity variations to a minimum. While the human eye may recognize prostate glands with significant color and intensity variations, a computer algorithm may fail under such conditions. Since malignancy grading of prostate tissue according to Gleason or to the International Society of Urological Pathology (ISUP) grading system is based on architectural growth patterns of prostatic carcinoma, automatic methods must rely on accurate identification of the prostate glands. But due to poor color differentiation between stroma and epithelium from the common stain hematoxylin-eosin, no method is yet able to segment all types of glands, making automatic prognostication hard to attain. We address the effect of tissue preparation on glandular segmentation with an alternative stain, Picrosirius red-hematoxylin, which clearly delineates the stromal boundaries, and couple this stain with a color decomposition that removes intensity variation. In this paper we propose a segmentation algorithm that uses image analysis techniques based on mathematical morphology and that can successfully determine the glandular boundaries. Accurate determination of the stromal and glandular morphology enables the identification of the architectural pattern that determine the malignancy grade and classify each gland into its appropriate Gleason grade or ISUP Grade Group. Segmentation of prostate tissue with the new stain and decomposition method has been successfully tested on more than 11000 objects including well-formed glands (Gleason grade 3), cribriform and fine caliber glands (grade 4), and single cells (grade 5) glands.

Place, publisher, year, edition, pages
FRONTIERS MEDIA SA, 2019
Keywords
digital pathology, computational pathology, prostate cancer, prostate gland segmentation, histopathological stain, Picrosirius red, hematoxylin
National Category
Medical Image Processing
Identifiers
urn:nbn:se:uu:diva-391013 (URN)10.3389/fbioe.2019.00125 (DOI)000475372000001 ()31334225 (PubMedID)
Funder
Swedish Research Council, 2009-5418Swedish Research Council, 2012-3667Vinnova, 2017-00444Vinnova, 2018-02137
Available from: 2019-08-21 Created: 2019-08-21 Last updated: 2019-08-21Bibliographically approved
Niinivirta, M., Enblad, G., Lindskog, C., Pontén, F., Dragomir, A. & Ullenhag, G. (2019). Tumoral pyruvate kinase L/R as a predictive marker for the treatment of renal cancer patients with sunitinib and sorafenib. Journal of Cancer, 10(14), 3224-3231
Open this publication in new window or tab >>Tumoral pyruvate kinase L/R as a predictive marker for the treatment of renal cancer patients with sunitinib and sorafenib
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2019 (English)In: Journal of Cancer, ISSN 1837-9664, Vol. 10, no 14, p. 3224-3231Article in journal (Other academic) Published
Abstract [en]

Background and aims: Treatment with tyrosine kinase inhibitors (TKI) like sunitinib and sorafenib has improved the prognosis of patients with metastatic renal cell cancer (mRCC). No predictive marker is available to select patients who will gain from these treatments. Tumoral pyruvate kinase L/R (PKLR) is a membrane protein with highly specific expression in the renal tubule. We have previously shown that the tumoral expression of cubilin (CUBN) is associated with progression free survival (PFS) in mRCC patients treated with sunitinib and sorafenib. The aim of the present study was to investigate if PKLR can predict response in these patients, alone and/or in combination with CUBN.

Methods: A tissue microarray (TMA) was constructed of tumor samples from 139 mRCC patients. One hundred and thirty-six of these patients had been treated with sunitinib or sorafenib in the first or second-line setting. Thirty patients suffered from early severe toxicity leading to the termination of treatment. The remaining patients (n=106) were selected for the current study.

Results: Fifty-five (52%) of the tumors expressed membranous PKLR. Patients with PKLR tumor expression experienced a significantly longer PFS compared to patients with no expression (eight versus five months, p = 0.019). Overall survival (OS) was also significantly better for patients with PKLR expression. In addition, the combined expression of PKLR and CUBN resulted in a higher predictive value than either marker alone.

Conclusions: In this real world study we show that tumoral PKLR membrane expression is a positive predictive biomarker for sunitinib and sorafenib treatment in patients suffering from mRCC. Our results also indicate that the combined expression with cubilin more accurately than PKLR alone can select patients with no benefit from treatment.

National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:uu:diva-360611 (URN)10.7150/jca.30130 (DOI)000470088200017 ()
Funder
Knut and Alice Wallenberg Foundation
Available from: 2018-09-16 Created: 2018-09-16 Last updated: 2019-06-26Bibliographically approved
Larsson, A., Karnevi, E., Nodin, B., Sorbye, H., Dragomir, A., Pfeiffer, P., . . . Ponten, F. (2018). Expression of podocalyxin-like protein and epidermal growth factor receptor in metastatic colorectal cancer: Prognostic impact and relationship with response to cetuximab.. In: : . Paper presented at ASCO 2018.
Open this publication in new window or tab >>Expression of podocalyxin-like protein and epidermal growth factor receptor in metastatic colorectal cancer: Prognostic impact and relationship with response to cetuximab.
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2018 (English)Conference paper, Poster (with or without abstract) (Refereed)
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-365898 (URN)
Conference
ASCO 2018
Available from: 2018-11-14 Created: 2018-11-14 Last updated: 2018-11-14
Lindahl, K., Astrom, E., Dragomir, A., Symoens, S., Coucke, P., Larsson, S., . . . Kindmark, A. (2018). Homozygosity for CREB3L1 premature stop codon in first case of recessive osteogenesis imperfecta associated with OASIS-deficiency to survive infancy. Bone, 114, 268-277
Open this publication in new window or tab >>Homozygosity for CREB3L1 premature stop codon in first case of recessive osteogenesis imperfecta associated with OASIS-deficiency to survive infancy
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2018 (English)In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 114, p. 268-277Article in journal (Refereed) Published
Abstract [en]

Background: Mutations of the endoplasmic reticulum (ER) stress transducer OASIS (encoded by CREB3L1), cause severe recessive osteogenesis imperfecta (OI) not compatible with surviving the neonatal period, as has been shown in two unrelated families through a whole gene deletion vs. a qualitative alteration of OASIS Heterozygous carriers in the described families have exhibited a mild phenotype. OASIS is a transcription factor highly expressed in osteoblasts, and OASIS(-/-) mice exhibit severe osteopenia and spontaneous fractures. Here, we expand the clinical spectrum by a detailed phenotypic characterization of the first case of OASIS-associated OI surviving the neonatal period, with heterozygous family members being unaffected.

Methods: All OI-associated genes were sequenced. Primary human osteoblast-like cell (hOB) and fibroblast (FB) cultures were obtained for qPCR, and steady-state collagen biochemistry. FB, hOB and skin biopsies were ultrastructurally analyzed. Bone was analyzed by |mu CT, histomorphometry, quantitative backscattered electron imaging (qBEI), and Raman microspectroscopy.

Results: The proband, a boy with severe OI, had blue sclera and tooth agenesis A homozygous CREB3L1 stop codon mutation was detected by sequencing, while several family members were heterozygotes Markedly low levels of CREB3L1 mRNA were confirmed by qPCR in hOBs (16%) and FB (21%), however, collagen I levels were only reduced in hOBs (5-10%) Electron microscopy of hOBs showed pronounced alterations, with numerous myelin figures and diminished RER vs. normal ultrastructure of FB. Bone histomorphometry and qBEI were similar to collagen I OI, with low trabecular thickness and mineral apposition rate, and increased bone matrix mineralization. Raman microspectroscopy revealed low level of glycosaminoglycans. Clinical response to lifelong bisphosphonate treatment was as expected in severe OI with steadily increasing bone mineral density, but despite this the boy suffered repeated childhood fractures.

Conclusions: Deficiency of OASIS can cause severe OI compatible with surviving the neonatal period A marked decrease of collagen type I transcription was noted in bone tissue, but not in skin, and ultrastructure of hOBs was pathological. Results also suggested OASIS involvement in glycosaminoglycan secretion in bone.

Keywords
Osteogenesis imperfecta, Recessive, Collagen type 1, Glycosaminoglycan, OASIS, CREB3L1
National Category
Orthopaedics Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-362634 (URN)10.1016/j.bone.2018.06.019 (DOI)000441369000029 ()29936144 (PubMedID)
Available from: 2018-10-09 Created: 2018-10-09 Last updated: 2019-04-02Bibliographically approved
Hotz, A., Fagerberg, C., Vahlquist, A., Bygum, A., Törmä, H., Rauschendorf, M.-A., . . . Fischer, J. (2018). Identification of mutations in SDR9C7 in six families with autosomal recessive congenital ichthyosis [Letter to the editor]. British Journal of Dermatology, 178(3), E207-E209
Open this publication in new window or tab >>Identification of mutations in SDR9C7 in six families with autosomal recessive congenital ichthyosis
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2018 (English)In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 178, no 3, p. E207-E209Article in journal, Letter (Other academic) Published
National Category
Dermatology and Venereal Diseases Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-357658 (URN)10.1111/bjd.15994 (DOI)000428701000008 ()28906551 (PubMedID)
Available from: 2018-08-24 Created: 2018-08-24 Last updated: 2019-04-02Bibliographically approved
Mezheyeuski, A., Strell, C., Hrynchyk, I., Guren, T. K., Dragomir, A., Doroshenko, T., . . . Portyanko, A. (2018). Treatment-related survival associations of claudin-2 expression in fibroblasts of colorectal cancer. Virchows Archiv, 472(3), 395-405
Open this publication in new window or tab >>Treatment-related survival associations of claudin-2 expression in fibroblasts of colorectal cancer
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2018 (English)In: Virchows Archiv, ISSN 0945-6317, E-ISSN 1432-2307, Vol. 472, no 3, p. 395-405Article in journal (Refereed) Published
Abstract [en]

Claudin-2 is a trans-membrane protein-component of tight junctions in epithelial cells. Elevated claudin-2 expression has been reported in colorectal cancer (CRC). The aim of this study was to investigate the expression patterns of claudin-2 in human CRC samples and analyze its association with clinical characteristics and treatment outcome. TMAs of primary tumors from two cohorts of metastatic CRC (mCRC) were used. Claudin-2 IHC staining was evaluated in a semi-quantitative manner in different regions and cell types. Claudin-2 expression was also analyzed by immunofluorescence in primary cultures of human CRC cancer-associated fibroblasts (CAFs). Initial analyses identified previously unrecognized expression patterns of claudin-2 in CAFs of human CRC. Claudin-2 expression in CAFs of the invasive margin was associated with shorter progression-free survival. Subgroup analyses demonstrated that the survival associations occurred among cases that received 5-FU+oxaliplatin combination treatment, but not in patients receiving 5-FU +/- irinotecan. The finding was validated by analyses of the independent cohort. In summary, previously unreported stromal expression of claudin-2 in CAFs of human CRC was detected together with significant association between high claudin-2 expression in CAFs and shorter survival in 5-FU+oxaliplatin-treated mCRC patients.

Place, publisher, year, edition, pages
SPRINGER, 2018
Keywords
Colorectal cancer, Cell adhesion, Claudin-2, Cancer-associated fibroblasts
National Category
Cancer and Oncology Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-352989 (URN)10.1007/s00428-017-2263-3 (DOI)000429350100009 ()29134439 (PubMedID)
Funder
The Cancer Research Funds of RadiumhemmetSwedish Research CouncilSwedish Cancer SocietySwedish Institute
Available from: 2018-07-17 Created: 2018-07-17 Last updated: 2019-04-02Bibliographically approved
Feresiadou, A., Casar Borota, O., Dragomir, A., Oldfors, C. H., Stålberg, E. & Oldfors, A. (2018). Tubular aggregates in congenital myasthenic syndrome. Neuromuscular Disorders, 28(2), 174-175
Open this publication in new window or tab >>Tubular aggregates in congenital myasthenic syndrome
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2018 (English)In: Neuromuscular Disorders, ISSN 0960-8966, E-ISSN 1873-2364, Vol. 28, no 2, p. 174-175Article in journal, Editorial material (Other academic) Published
Place, publisher, year, edition, pages
PERGAMON-ELSEVIER SCIENCE LTD, 2018
National Category
Neurology Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-356900 (URN)10.1016/j.nmd.2017.11.009 (DOI)000428487300011 ()29311015 (PubMedID)
Funder
Swedish Research Council, 2012-201
Available from: 2018-08-09 Created: 2018-08-09 Last updated: 2019-04-02Bibliographically approved
Suveer, A., Sladoje, N., Lindblad, J., Dragomir, A. & Sintorn, I.-M. (2017). Cilia ultrastructural visibility enhancement by multiple instance registration and super-resolution reconstruction. In: Swedish Symposium on Image Analysis: . Swedish Society for Automated Image Analysis
Open this publication in new window or tab >>Cilia ultrastructural visibility enhancement by multiple instance registration and super-resolution reconstruction
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2017 (English)In: Swedish Symposium on Image Analysis, Swedish Society for Automated Image Analysis , 2017Conference paper, Published paper (Other academic)
Place, publisher, year, edition, pages
Swedish Society for Automated Image Analysis, 2017
National Category
Medical Image Processing
Research subject
Computerized Image Processing
Identifiers
urn:nbn:se:uu:diva-335371 (URN)
Available from: 2017-12-04 Created: 2017-12-04 Last updated: 2018-08-24
Gupta, A., Suveer, A., Lindblad, J., Dragomir, A., Sintorn, I.-M. & Sladoje, N. (2017). Convolutional neural networks for false positive reduction of automatically detected cilia in low magnification TEM images. In: Image Analysis: Part I. Paper presented at SCIA 2017, June 12–14, Tromsø, Norway (pp. 407-418). Springer
Open this publication in new window or tab >>Convolutional neural networks for false positive reduction of automatically detected cilia in low magnification TEM images
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2017 (English)In: Image Analysis: Part I, Springer, 2017, p. 407-418Conference paper, Published paper (Refereed)
Abstract [en]

Automated detection of cilia in low magnification transmission electron microscopy images is a central task in the quest to relieve the pathologists in the manual, time consuming and subjective diagnostic procedure. However, automation of the process, specifically in low magnification, is challenging due to the similar characteristics of non-cilia candidates. In this paper, a convolutional neural network classifier is proposed to further reduce the false positives detected by a previously presented template matching method. Adding the proposed convolutional neural network increases the area under Precision-Recall curve from 0.42 to 0.71, and significantly reduces the number of false positive objects.

Place, publisher, year, edition, pages
Springer, 2017
Series
Lecture Notes in Computer Science, ISSN 0302-9743 ; 10269
National Category
Computer Vision and Robotics (Autonomous Systems)
Research subject
Computerized Image Processing
Identifiers
urn:nbn:se:uu:diva-334218 (URN)10.1007/978-3-319-59126-1_34 (DOI)000454359300034 ()978-3-319-59125-4 (ISBN)
Conference
SCIA 2017, June 12–14, Tromsø, Norway
Funder
VINNOVA, 2016-02329
Available from: 2017-05-19 Created: 2017-11-21 Last updated: 2019-04-17Bibliographically approved
Suveer, A., Sladoje, N., Lindblad, J., Dragomir, A. & Sintorn, I.-M. (2017). Enhancement of cilia sub-structures by multiple instance registration and super-resolution reconstruction. In: Image Analysis: Part II. Paper presented at SCIA 2017, June 12–14, Tromsø, Norway (pp. 362-374). Springer
Open this publication in new window or tab >>Enhancement of cilia sub-structures by multiple instance registration and super-resolution reconstruction
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2017 (English)In: Image Analysis: Part II, Springer, 2017, p. 362-374Conference paper, Published paper (Refereed)
Abstract [en]

Ultrastructural analysis of cilia cross-sectional images using transmission electron microscopy (TEM) assists the pathologists to diagnose Primary Ciliary Dyskinesia, a genetic disease. The current diagnostic procedure is manual and difficult because of poor signal-to-noise ratio in TEM images. In this paper, we propose an automated multi-step registration approach to register many cilia cross-sectional instances. The novelty of the work is in the utilization of customized weight masks at each registration step to achieve good alignment of the specific cilium regions. Registration is followed by super-resolution reconstruction to enhance the substructural information. Landmarks matching based evaluation of registration results in pixel alignment error of 2.35±1.82" role="presentation">2.35±1.82 pixels, and the subjective analysis of super-resolution reconstructed cilium shows a clear improvement in the visibility of the substructures such as dynein arms, radial spokes, and central pair.

Place, publisher, year, edition, pages
Springer, 2017
Series
Lecture Notes in Computer Science, ISSN 0302-9743 ; 10270
National Category
Medical Image Processing
Research subject
Computerized Image Processing
Identifiers
urn:nbn:se:uu:diva-334225 (URN)10.1007/978-3-319-59129-2_31 (DOI)000454360300031 ()978-3-319-59128-5 (ISBN)
Conference
SCIA 2017, June 12–14, Tromsø, Norway
Available from: 2017-05-19 Created: 2017-11-21 Last updated: 2019-04-17Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-2777-8114

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