uu.seUppsala University Publications
Change search
Refine search result
1 - 26 of 26
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1.
    Agnarsdóttir, Margrét
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Ponten, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Wagenius, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Mucci, Lorelei
    Channing Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, USA, Department of Epidemiology, Harvard School of Public Health, Boston, USA .
    Magnusson, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Eaker-Fält, Sonja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    MITF as a Prognostic Marker in Cutaneous Malignant MelanomaManuscript (preprint) (Other academic)
    Abstract [en]

    Background: Microphthalmia associated transcription factor (MITF) protein has a central role in the differentiation and survival of melanocytes. The aim of the study was to investigate whether MITF can be employed as a prognostic marker in patients operated on for cutaneous malignant melanoma.

    Methods: A cohort study design based on information collected from population-based registers. For included patients tissue microarrays and immunohistochemistry were employed to study the protein expression of MITF in the primary malignant melanoma tumors by estimating the fraction of positive tumor cells and the staining intensity.

    Results: The vast majority of tumors expressed MITF in >25% of the tumor cells with a strong staining intensity and looking at these factors individually these patients had a better prognosis. When cell fraction and intensity were combined a high-risk group dying of malignant melanoma was identified as those with 25% -75% of tumor cells staining with weak intensity and those with <25% of tumor cells staining with strong intensity. However, the majority of the deaths occurred in the lower risk groups.

    Conclusions: Although a high-risk group for death in malignant melanoma was identified we conclude that MITF is not useful as a prognostic marker because of the distribution of that particular expression in the population.

    Impact: Our results indicate a bi-phasic pattern of MITF expression and although not useful as a prognostic marker these results are in line with other experimental studies and are relevant to explore further.

     

  • 2.
    Agnarsdóttir, Margrét
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Rexhepaj, Elton
    UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Ireland.
    Magnusson, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Patil, Tushar
    Lab Surgpath, Mumbai, India.
    Johansson, Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Jirström, Karin
    Center for Molecular Pathology, Department of Laboratory Medicine, Skåne University Hospital, Lund University, Malmö, Sweden .
    Uhlen, Mathias
    Department of Proteomics, School of Biotechnology, AlbaNova University Center, KTH-Royal Institute of Technology, SE-10691 Stockholm, Sweden .
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Gallagher, William
    UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Ireland. .
    Ponten, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Protein Biomarkers in Malignant Melanoma: An Image Analysis-Based Study on Melanoma Markers of Potential Clinical RelevanceManuscript (preprint) (Other academic)
    Abstract [en]

    The thickness of a primary malignant melanoma tumor is the most important prognostic indicator for a patient with primary cutaneous malignant melanoma. To optimize the management and treatment of melanoma patients there is an unmet need to identify characteristics that can further stratify melanoma patients into high or low risk for progressive disease. Despite numerous studies no single marker has yet been shown to add significant prognostic information. An algorithmic approach, combining data from several markers provides an attractive model to identify patients of increased risk of dying from malignant melanoma. The primary aim of the present study was to analyze the correlation between clinical outcome and protein expression patterns of multiple proteins in malignant melanoma tumors using immunohistochemistry and tissue microarrays. Candidate proteins were identified based on a selective and differential expression pattern in melanoma tumors and tested in a cohort of 143 melanoma patients. Protein expression was analyzed using both manual scoring and automated image analysis-based algorithms. We found no single marker of prognosis that was independent of tumor thickness. When combining potential prognostic markers we could define a prognostic index, based on RBM3, MITF, SOX10 and Ki-67, that was independent of tumor thickness in multivariate analysis. Our findings suggest that a good prognosis signature can be identified in melanoma patients with tumors showing a low fraction of Ki-67 positive tumor cells and a high fraction of RBM3 positive tumor cells combined with low intensity levels of SOX10 and MITF.

     

  • 3.
    Alimohammadi, Mohammad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Dubois, Noemie
    Sköldberg, Filip
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Hallgren, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Tradivel, Isabelle
    Hedstrand, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Haavik, Jan
    Husebye, Eystein
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Rorsman, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Meloni, Antonella
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Vilattes, Bernard
    Kajosaari, Merja
    Egner, William
    Sargur, Ravishankar
    Amoura, Zahir
    Grimfeld, Alain
    Pontén, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    De Luca, Filippo
    Betterle, Corrado
    Perheentupa, Jaakko
    Kämpe, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Pulmonary Autoimmunity as a Feature of Autoimmune Polyendocrine Syndrome Type 1 and Identification of KCNRG as a Bronchial Autoantigen2009In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 106, no 11, p. 4396-4401Article in journal (Refereed)
    Abstract [en]

    Patients with autoimmune polyendocrine syndrome type 1 (APS-1) suffer from multiple organ-specific autoimmunity with autoantibodies against target tissue-specific autoantigens. Endocrine and nonendocrine organs such as skin, hair follicles, and liver are targeted by the immune system. Despite sporadic observations of pulmonary symptoms among APS-1 patients, an autoimmune mechanism for pulmonary involvement has not been elucidated. We report here on a subset of APS-1 patients with respiratory symptoms. Eight patients with pulmonary involvement were identified. Severe airway obstruction was found in 4 patients, leading to death in 2. Immunoscreening of a cDNA library using serum samples from a patient with APS-1 and obstructive respiratory symptoms identified a putative potassium channel regulator (KCNRG) as a pulmonary autoantigen. Reactivity to recombinant KCNRG was assessed in 110 APS-1 patients by using immunoprecipitation. Autoantibodies to KCNRG were present in 7 of the 8 patients with respiratory symptoms, but in only 1 of 102 APS-1 patients without respiratory symptoms. Expression of KCNRG messenger RNA and protein was found to be predominantly restricted to the epithelial cells of terminal bronchioles. Autoantibodies to KCNRG, a protein mainly expressed in bronchial epithelium, are strongly associated with pulmonary involvement in APS-1. These findings may facilitate the recognition, diagnosis, characterization, and understanding of the pulmonary manifestations of APS-1.

  • 4. Askling, J
    et al.
    Fored, C M
    Baecklund, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Brandt, L
    Backlin, Carin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Ekbom, A
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Bertilsson, L
    Cöster, L
    Geborek, P
    Jacobsson, L T
    Lindblad, S
    Lysholm, J
    Rantapää-Dahlqvist, S
    Saxne, T
    Klareskog, L
    Feltelius, N
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Haematopoietic malignancies in rheumatoid arthritis: lymphoma risk and characteristics after exposure to tumour necrosis factor antagonists2005In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 64, no 10, p. 1414-1420Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Patients with rheumatoid arthritis (RA) are at increased risk of malignant lymphomas, and maybe also of leukaemia and multiple myeloma. The effect of tumour necrosis factor (TNF) antagonists on lymphoma risk and characteristics is unclear.

    OBJECTIVE:

    To assess expected rates and relative risks of haematopoietic malignancies, especially those associated with TNF antagonists, in large population based cohorts of patients with RA.

    METHODS:

    A population based cohort study was performed of patients with RA (one prevalent cohort (n = 53,067), one incident cohort (n = 3703), and one TNF antagonist treated cohort 1999 through 2003 (n = 4160)), who were linked with the Swedish Cancer Register. Additionally, the lymphoma specimens for the 12 lymphomas occurring in patients with RA exposed to TNF antagonists in Sweden 1999 through 2004 were reviewed.

    RESULTS:

    Study of almost 500 observed haematopoietic malignancies showed that prevalent and incident patients with RA were at increased risk of lymphoma (SIR = 1.9 and 2.0, respectively) and leukaemia (SIR = 2.1 and 2.2, respectively) but not of myeloma. Patients with RA treated with TNF antagonists had a tripled lymphoma risk (SIR = 2.9) compared with the general population. After adjustment for sex, age, and disease duration, the lymphoma risk after exposure to TNF antagonists was no higher than in the other RA cohorts. Lymphomas associated with TNF antagonists had characteristics similar to those of other RA lymphomas.

    CONCLUSION:

    Overall, patients with RA are at equally increased risks for lymphomas and leukaemias. Patients with RA treated with TNF antagonists did not have higher lymphoma risks than other patients with RA. Prolonged observation is needed to determine the long term effects of TNF antagonists on lymphoma risk.

  • 5.
    Blokzijl, Andries
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular tools.
    Friedman, Mikaela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular tools.
    Pontén, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Landegren, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular tools.
    Profiling protein expression and interactions: proximity ligation as a tool for personalized medicine2010In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 268, no 3, p. 232-245Article, review/survey (Refereed)
    Abstract [en]

    Blokzijl A, Friedman M, Ponten F, Landegren U (From the Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden). Profiling protein expression and interactions: proximity ligation as a tool for personalized medicine. (Review) J Intern Med 2010; 268: 232-245. The ability to detect very low levels of expressed proteins has enormous potential for early diagnostics and intervention at curable stages of disease. An extended range of targets such as interacting or post-translationally modified proteins can further improve the potential for diagnostics and patient stratification, and for monitoring response to treatment. These are critical building blocks for personalized treatment strategies to manage disease. The past few decades have seen a remarkably improved understanding of the molecular basis of disease in general, and of tumour formation and progression in particular. This accumulated knowledge creates opportunities to develop drugs that specifically target molecules or molecular complexes critical for survival and expansion of tumour cells. However, tumours are highly variable between patients, necessitating the development of diagnostic tools to individualize treatment through parallel analysis of sets of biomarkers. The proximity ligation assay (PLA) can address many of the requirements for advanced molecular analysis. The method builds on the principle that recognition of target proteins by two, three or more antibodies can bring in proximity DNA strands attached to the antibodies. The DNA strands can then participate in ligation reactions, giving rise to molecules that are amplified for highly sensitive detection. PLA is particularly well suited for sensitive, specific and multiplexed analysis of protein expression, post-translational modifications and protein-protein interactions. The analysis of this extended range of biomarkers will prove critical for the development and implementation of personalized medicine.

  • 6. Brennan, Donal J.
    et al.
    O'Connor, Darran P.
    Rexhepaj, Elton
    Pontén, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Gallagher, William M.
    Antibody-based proteomics: fast-tracking molecular diagnostics in oncology2010In: Nature Reviews. Cancer, ISSN 1474-175X, E-ISSN 1474-1768, Vol. 10, no 9, p. 605-617Article, review/survey (Refereed)
    Abstract [en]

    The effective implementation of personalized cancer therapeutic regimens depends on the successful identification and translation of informative biomarkers to aid clinical decision making. Antibody-based proteomics occupies a pivotal space in the cancer biomarker discovery and validation pipeline, facilitating the high-throughput evaluation of candidate markers. Although the clinical utility of these emerging technologies remains to be established, the traditional use of antibodies as affinity reagents in clinical diagnostic and predictive assays suggests that the rapid translation of such approaches is an achievable goal. Furthermore, in combination with, or as alternatives to, genomic and transcriptomic methods for patient stratification, antibody-based proteomics approaches offer the promise of additional insight into cancer disease states. In this Review, we discuss the current status of antibody-based proteomics and its contribution to the development of new assays that are crucial for the realization of individualized cancer therapy.

  • 7. Grama, D
    et al.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Wilander, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Mårtensson, H
    Cedermark, B
    Ahrén, B
    Kristoffersson, A
    Rastad, J
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Åkerström, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Pancreatic tumors in multiple endocrine neoplasia type 1: clinical presentation and surgical treatment1992In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 16, no 4, p. 611-618Article in journal (Refereed)
    Abstract [en]

    Among 33 patients with endocrine pancreatic tumors due to multiple endocrine neoplasia type 1 (MEN-1), 19 (58%) patients had hypergastrinemia, 7 (21%) patients had hyperinsulinism, and 7 (21%) patients had clinically non-functioning lesions. At least one gross tumor was found in all patients undergoing pancreatic surgery, including those with negative localization studies prior to operation. The patients also had additional macroscopic tumors as well as numerous microadenomas, and the lesions frequently were positive for immunostaining with multiple hormones, mainly pancreatic polypeptide, insulin, glucagon, and somatostatin. Duodenal endocrine lesions were found in 4 of 5 investigated patients and stained with gastrin and somatostatin antibodies. Distal, mainly subtotal pancreatic resection, was performed in 18 patients, eventually combined with caput tumor enucleation or duodenotomy, while a few patients underwent only tumor enucleation or a Whipple procedure. The long-term outcome of operation was most favorable in patients with hyperinsulinism; only 1 patient had clinical recurrence. Patients with hypergastrinemia experienced only transitory lowering of serum gastrin values after pancreatic surgery and 47% of them had or developed metastases. Such tumor spread was seen in 57% of the patients with non-functioning lesions. Nine patients died from progressive tumor disease during follow-up. Consistent with previous studies, we found that surgery is indicated in MEN-1 patients with hyperinsulinism even if a lesion is not visualized by radiology. In addition, these indications should be extended to also include patients with only biochemical markers of disease, including elevations of gastrin, as these indicate the presence of gross tumors.

  • 8.
    Hassan, Saadia Bashir
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    de la Torre, Manuel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Karlsson, Mats O.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, Division of Pharmacokinetics and Drug Therapy.
    Larsson, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Jonsson, Elin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    A hollow fiber model for in vitro studies of cytotoxic compounds: Activity of the cyanoguanidine CHS 8282001In: Anti-Cancer Drugs, ISSN 0959-4973, E-ISSN 1473-5741, Vol. 12, no 1, p. 33-42Article in journal (Refereed)
    Abstract [en]

    The hollow fiber assay is currently used as an in vivo model for anticancer drug screening in nude mice, but it can also be used as an in vitro model. In the current study, an in vitro hollow fiber model was used to study the effect and mode of induced cell death of a new cyanoguanidine, CHS 828. Human leukemia, adenocarcinoma and lymphoma cell lines as well as primary cultures of human tumor cells from patients with chronic lymphocytic leukemia (CLL) and ovarian cancer (OC) and normal human lymphocytes were cultured in semipermeable hollow fibers. The fibers were incubated for 3 or 14 days prior to CHS 828 exposure for 72 h, followed by determination of living cell density by MTT staining. For cell morphology, using harvested cultures on cytospin slides had technical advantages compared to using paraffin sections of the formalin-fixed fibers. CHS 828 showed higher antitumor activity on CLL and normal human lymphocyte cultures compared to OC cultures, and cell lines cultured 3 days were more sensitive than those cultured 14 days. Morphological examination of CHS 828-treated cultures revealed a mixture of apoptosis and necrosis.

  • 9.
    Issac Niwas, Swamidoss
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Kårsnäs, Andreas
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Uhlmann, Virginie
    Imaging Platform, Broad Institute of Harvard and MIT, Cambridge, Massachusetts MA, USA and Biomedical Imaging Group, École Polytechnique Fédérale de Lausanne (EPFL), Switzerland.
    Ponnusamy, Palanisamy
    Dept. of Electronics and Communication Engineering (ECE), National Institute of Technology (NIT), Tiruchirappalli, India.
    Kampf, Caroline
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Simonsson, Martin
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Wählby, Carolina
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Science for Life Laboratory, SciLifeLab. Broad Institute of Harvard and Massachusetts Institute Technology (MIT), Cambridge, Massachusetts, MA, USA, .
    Strand, Robin
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Automated classification of immunostaining patterns in breast tissue from the Human Protein Atlas2013In: Journal of Pathology Informatics, ISSN 2229-5089, E-ISSN 2153-3539, Vol. 4, no 14Article in journal (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 (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.

  • 10.
    Khan, Tanweera Shaheena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Imam, Hassan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Juhlin, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Gröndal, Staffan
    Tibblin, Sten
    Wilander, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Streptozocin and o,p'DDD in the treatment of adrenocortical cancer patients: long-term survival in its adjuvant use2000In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 11, no 10, p. 1281-1287Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    To evaluate the efficacy of streptozocin and o.p'DDD (SO) in adrenocortical cancer (ACC) patients since other chemotherapeutic regimens have limited effects.

    PATIENTS AND METHODS:

    We performed a phase II study with SO therapy in 40 ACC patients (median age 44 years). Oral o,p'DDD administration (1-4 g/d, every day) was given together with intravenous streptozocin (1 g/d for five days, thereafter 2 g once every three weeks). 5HT3-receptor blocker was used as standard premedication for streptozocin.

    RESULTS:

    The SO therapy was found to have significant effects on disease-free interval (P = 0.02) as well as on survival (P = 0.01) in adjuvantly treated cases (n = 17) in comparison to the patients who did not get any therapy after complete resection (n = 11). Complete or partial response was obtained in 36.4% of patients with measurable disease (n = 22). The overall two-year and five-year survival rates were 70% and 32.5%, respectively. The presence of metastases at diagnosis was identified as a poor prognostic factor (P = 0.02).

    CONCLUSIONS:

    The present study necessitates further randomized clinical study of SO therapy in the treatment of ACC, mainly as adjuvant treatment immediately after curative intended surgery, and could be developed into a regular treatment regimen.

  • 11.
    Ladjevardi, Sam
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Weis, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Tolf, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Häggman, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    von Below, Catrin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Jorulf, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    A Comparison of Different Imaging Techniques for Localisation of Cancers in the Prostate2014In: Open Prostate Cancer Journal, ISSN 1876-8229, Vol. 7, p. 1-6Article in journal (Refereed)
    Abstract [en]

    The diagnostic accuracy of standard transrectal ultrasound-guided (TRUL) biopsy is limited due to the finite number of cores that can be obtained. It has been shown that the technique is not sufficiently reliable in defining the location and extent of prostatic cancer. The main aim of this study was to investigate the effectiveness of magnetic resonance imaging (MRI), and positron emission tomography (PET/CT) imaging techniques in pinpointing potential tumour lesions prior to prostate biopsy.

    Material and methods

    The study cohort consisted of 45 men with a raised prostate specific-antigen (PSA) level and/or suspected prostate cancer (PCa) at digital rectal examinations (DRE). Of the 45 patients, 23 had PCa detected with core needle biopsy (CNB). All had 11C acetate PET/CT imaging. Ten of those 23 patients underwent radical prostatectomy (RP), of those ten patients, eight patients had MR spectroscopic imaging (MRSI) with 3 T and six had diffusion weighted imaging (DWI) with apparent diffusion coefficient calculation (MRI DWI ADC). CNB, PET/CT, 2D MRSI and ADC map results were compared with postoperative specimen histopathology.

    Results

    The sensitivity of CNB, PET/CT, MRSI and DWI ADC were 0.53, 0.55, 0.79 and 0.95, whereas the specificity of was 0.88, 0.87, 0.46 and 0.73, respectively.

    Conclusion

    MRI improves the PCa detection by defining the areas of interest for targeted CNB of the prostate and can reduce the number of biopsies required

  • 12.
    Leja, Justyna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
    Essaghir, Ahmed
    Essand, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
    Wester, Kenneth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Tötterman, Thomas H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
    Lloyd, Ricardo
    Vasmatzis, George
    Demoulin, Jean-Baptiste
    Giandomenico, Valeria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
    Novel markers for enterochromaffin cells and gastrointestinal neuroendocrine carcinomas2009In: Modern Pathology, ISSN 0893-3952, E-ISSN 1530-0285, Vol. 22, no 2, p. 261-272Article in journal (Refereed)
    Abstract [en]

    The gene expression profile of metastasizing serotonin-producing neuroendocrine carcinomas, which arise from enterochromaffin cells in the jejunum and ileum, is still largely unknown. The aim of this study was to identify genes and proteins, which are preferentially expressed by neuroendocrine carcinoma and enterochromaffin cells and therefore potential novel biomarkers and/or therapeutic targets. Six carcinoma specimens and six normal ileal mucosas were profiled by Affymetrix microarrays. Advanced bioinformatics identified differentially and specifically expressed genes, which were validated by quantitative real-time-PCR on tumor cells extracted by laser capture microdissection and normal enterochromaffin cells extracted by immunolaser capture microdissection. We identified six novel marker genes for neuroendocrine carcinoma cells: paraneoplastic antigen Ma2 (PNMA2), testican-1 precursor (SPOCK1), serpin A10 (SERPINA10), glutamate receptor ionotropic AMPA 2 (GRIA2), G protein-coupled receptor 112 (GPR112) and olfactory receptor family 51 subfamily E member 1 (OR51E1). GRIA2 is specifically expressed by neuroendocrine carcinoma cells whereas the others are also expressed by normal enterochromaffin cells. GPR112 and OR51E1 encode proteins associated with the plasma membrane and may therefore become targets for antibody-based diagnosis and therapy. Hierarchical clustering shows high similarity between primary lesions and liver metastases. However, chemokine C-X-C motif ligand 14 (CXCL14) and NK2 transcription factor related locus 3 Drosophila (NKX2-3) are expressed to a lower level in liver metastases than in primary tumors and normal enterochromaffin cells, which implies a role in neuroendocrine carcinoma differentiation. In conclusion, this study provides a list of genes, which possess relatively specific expression to enterochromaffin and neuroendocrine carcinoma cells and genes with differential expression between primary tumors and metastases. We verified six novel marker genes that may be developed as biomarkers and/or therapeutic targets.

  • 13.
    Micke, Patrick
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Holmberg, L.
    Edlund, Karolina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Lambe, M.
    Univ Uppsala Hosp.
    Thomas, A.
    Göransson, H.
    Uppsala University.
    Eckman, S.
    Univ Uppsala Hosp.
    Bergqvist, M.
    Univ Uppsala Hosp.
    Lamberg, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Berglund, A. L.
    Univ Uppsala Hosp.
    Nyberg, F.
    Isaksson, A.
    Uppsala University.
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Gene Copy Number Aberrations are Associated with Survival in Histological Subgroups of Non Small Cell Lung Cancer2010In: Journal of Molecular Diagnostics, ISSN 1525-1578, E-ISSN 1943-7811, Vol. 12, no 6, p. 909-909Article in journal (Other academic)
  • 14.
    Molin, Daniel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Edström, Annika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Glimelius, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Nilsson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Mast cell infiltration correlates with poor prognosis in Hodgkin's lymphoma2002In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 119, no 1, p. 122-124Article in journal (Refereed)
    Abstract [en]

    Hodgkin's lymphoma (HL) is characterized by a few Hodgkin, Reed-Sternberg cells (HRS) surrounded by benign cells. We recently reported that mast cells were the predominant CD30L-positive cells in HL tumours, and that they activate HRS in vitro through CD30L-CD30 interaction. Here, we investigated the clinical importance of mast cell infiltration in the tumours of 123 patients. Tumour specimens were stained with a mast-cell-specific antibody that detects tryptase. Mast cells were detected in virtually every case and increasing numbers of mast cells correlated to nodular sclerosis histology (P = 0.008). Patients with higher mast cell infiltration had a worse relapse-free survival (P = 0.01).

  • 15. Murphy, C
    et al.
    Wang, S
    Macy, S
    Makovitzky, J
    Athanasou, N
    Westermark, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Weiss, D T
    Solomon, A
    Nature of os labrum-associated amyloid deposits:  2011In: Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis, ISSN 1744-2818, Vol. 18, no Suppl 1, p. 206-207Article in journal (Refereed)
  • 16.
    Pielberg, Gerli Rosengren
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Golovko, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Sundström, Elisabeth
    Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, SE-751 24 Uppsala, Sweden.
    Curik, Ino
    Animal Science Department, Faculty of Agriculture, University of Zagreb, HR-10000 Zagreb, Croatia.
    Lennartsson, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Ludwig Institute for Cancer Research.
    Seltenhammer, Monika H.
    Department of Clinical Surgery and Ophthalmology, University of Veterinary Medicine, A-1200 Vienna, Austria.
    Druml, Thomas
    Department of Sustainable Agricultural Systems, University of Natural Resources and Applied Life Sciences, Vienna, A-1180 Vienna, Austria.
    Binns, Matthew
    Royal Veterinary College, Royal College Street, London, NW1 0TU, UK.
    Fitzsimmons, Carolyn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Lindgren, Gabriella
    Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, SE-751 24 Uppsala, Sweden.
    Sandberg, Kaj
    Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, SE-751 24 Uppsala, Sweden.
    Baumung, Roswitha
    Department of Sustainable Agricultural Systems, University of Natural Resources and Applied Life Sciences, Vienna, A-1180 Vienna, Austria.
    Vetterlein, Monika
    Centre for Anatomy and Cell Biology, Department of Cell Biology and Ultrastructure Research, Medical University of Vienna, A-1080 Vienna, Austria.
    Strömberg, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Grabherr, Manfred
    Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA.
    Wade, Claire
    Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA; Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
    Lindblad-Toh, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Pontén, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Heldin, Carl-Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Ludwig Institute for Cancer Research.
    Sölkner, Johann
    Department of Sustainable Agricultural Systems, University of Natural Resources and Applied Life Sciences, Vienna, A-1180 Vienna, Austria.
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    A cis-acting regulatory mutation causes premature hair graying and susceptibility to melanoma in the horse2008In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 40, no 8, p. 1004-1009Article in journal (Refereed)
    Abstract [en]

    In horses, graying with age is an autosomal dominant trait associated with a high incidence of melanoma and vitiligo-like depigmentation. Here we show that the Gray phenotype is caused by a 4.6-kb duplication in intron 6 of STX17 (syntaxin-17) that constitutes a cis-acting regulatory mutation. Both STX17 and the neighboring NR4A3 gene are overexpressed in melanomas from Gray horses. Gray horses carrying a loss-of-function mutation in ASIP (agouti signaling protein) had a higher incidence of melanoma, implying that increased melanocortin-1 receptor signaling promotes melanoma development in Gray horses. The Gray horse provides a notable example of how humans have cherry-picked mutations with favorable phenotypic effects in domestic animals.

  • 17.
    Rolny, Charlotte
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Cancer and Vascular Biology.
    Mazzone, Massimiliano
    Tugues, Sònia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Cancer and Vascular Biology.
    Laoui, Damya
    Johansson, Irja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Coulon, Cathy
    Squadrito, Mario Leonardo
    Segura, Inmaculada
    Li, Xiujuan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Cancer and Vascular Biology.
    Knevels, Ellen
    Costa, Sandra
    Vinckier, Stefan
    Dresselaer, Tom
    Åkerud, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    De Mol, Maria
    Salomäki, Henriikka
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Phillipson, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Wyns, Sabine
    Larsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Buysschaert, Ian
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Himmelreich, Uwe
    Van Ginderachter, Jo A.
    De Palma, Michele
    Dewerchin, Mieke
    Claesson-Welsh, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Cancer and Vascular Biology.
    Carmeliet, Peter
    HRG Inhibits Tumor Growth and Metastasis by Inducing Macrophage Polarization and Vessel Normalization through Downregulation of PIGF2011In: Cancer Cell, ISSN 1535-6108, E-ISSN 1878-3686, Vol. 19, no 1, p. 31-44Article in journal (Refereed)
    Abstract [en]

    Polarization of tumor-associated macrophages (TAMs) to a proangiogenic/immune-suppressive (M2-like) phenotype and abnormal, hypoperfused vessels are hallmarks of malignancy, but their molecular basis and interrelationship remains enigmatic. We report that the host-produced histidine-rich glycoprotein (HRG) inhibits tumor growth and metastasis, while improving chemotherapy. By skewing TAM polarization away from the M2- to a tumor-inhibiting M1-like phenotype, HRG promotes antitumor immune responses and vessel normalization, effects known to decrease tumor growth and metastasis and to enhance chemotherapy. Skewing of TAM polarization by HAG relies substantially on downregulation of placental growth factor (PIGF). Besides unveiling an important role for TAM polarization in tumor vessel abnormalization, and its regulation by HRG/PIGF, these findings offer therapeutic opportunities for anticancer and antiangiogenic treatment.

  • 18. Schmidt, Marcus
    et al.
    Hellwig, Birte
    Hammad, Seddik
    Othman, Amnah
    Lohr, Miriam
    Chen, Zonglin
    Böhm, Daniel
    Gebhard, Susanne
    Petry, Ilka Brigitte
    Lebrecht, Antje
    Cadenas, Cristina
    Marchan, Rosemarie
    Stewart, Joanna
    Solbach, Christine
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Edlund, Karolina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Göransson Kultima, Hanna
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Rody, Achim
    Berglund, Anders
    Lambe, Mats
    Isaksson, Anders
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Karn, Thomas
    Müller, Volkmar
    Gerhold-Ay, Aslihan
    Cotarelo, Christina
    Sebastian, Martin
    Kronenwett, Ralf
    Bojar, Hans
    Lehr, Hans-Anton
    Sahin, Ugur
    Koelbl, Heinz
    Gehrmann, Mathias
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Rahnenführer, Jörg
    Hengstler, Jan G
    A comprehensive analysis of human gene expression profiles identifies stromal immunoglobulin kappa C as a compatible prognostic marker in human solid tumors2012In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 18, no 9, p. 2695-2703Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

    Although the central role of the immune system for tumor prognosis is generally accepted a single robust marker is not yet available.

    EXPERIMENTAL DESIGN:

    Based on ROC (receiver operating characteristic) analyses robust markers were identified from a 60 gene B-cell derived metagene and analyzed in gene expression profiles of 1810 breast cancer, 1056 non-small cell lung cancer, 513 colorectal and 426 ovarian cancer patients. Protein and RNA levels were examined in paraffin embedded tissue of 330 breast cancer patients. The cell types were identified using immunohistochemical co-staining and confocal fluorescence microscopy.

    RESULTS:

    We identified immunoglobulin kappa C (IGKC) which as a single marker is similarly predictive and prognostic as the entire B-cell metagene. IGKC was consistently associated with metastasis free survival across different molecular subtypes in node-negative breast cancer (n=965) and predicted response to anthracycline-based neoadjuvant chemotherapy (n=845) [P less than 0.001]. In addition, IGKC gene expression was prognostic in non-small cell lung cancer and colorectal cancer. No association was observed in ovarian cancer. IGKC protein expression was significantly associated with survival in paraffin embedded tissues of 330 breast cancer patients. Tumor infiltrating plasma cells were identified as the source of IGKC expression

    CONCLUSION:

    Our findings provide IGKC as a novel diagnostic marker for risk stratification in human cancer and support concepts to exploit the humoral immune response for anti-cancer therapy. It could be validated in several independent cohorts and performed similarly well in RNA from fresh frozen as well as from paraffin tissue and on protein level by immunostaining.

  • 19.
    Skogseid, Britt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Grama, D
    Rastad, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lindgren, PG
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lörelius, Lars-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Wilander, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Åkerström, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Operative tumor yield obviates preoperative pancreatic localization in multiple endocrine neoplasia type 11995In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 238, no 3, p. 281-288Article in journal (Refereed)
    Abstract [en]

    The efficiency of pancreatic tumour localization was prospectively evaluated in 12 consecutive patients with multiple endocrine neoplasia type 1 (MEN1), who were subjected to extirpation of 56 islet cell neoplasms of 0.2-4 cm in diameter (mean 0.8 cm) during pancreatic resection and enucleation. Computed tomography, angiography of the coeliac trunc and superior mesenteric artery, and percutaneous ultrasound correctly localized 7-12% of the tumours and 21-37% of the 19 lesions measuring at least one centimetre in diameter. Transhepatic portal vein sampling correctly located tumour sites in the proximal or distal portions of the pancreas in four out of six patients, but demonstrated unsatisfactory specificity. Intra-operative ultrasound and bidigital palpation of the pancreas had overall sensitivities of 86 and 45%, respectively, and eight lesions below 0.3 cm in diameter remained undetected with intraoperative ultrasound. It is concluded that diagnosis of endocrine pancreatic neoplasms is biochemical in MEN1 and that broad screening of tumour markers efficiently reveals pancreatic involvement decades before the development of a clinically overt disease. Intra-operative ultrasound is a requisite for pancreatic endocrine surgery in MEN1, and it obviates the need for conventional pancreatic imaging unless a pre-operative search for metastatic disease and anatomical aberrations is considered important.

  • 20.
    Stridsberg, Mats
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Lundqvist, Gudmar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Wilander, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research.
    Islet amyloid polypeptide (IAPP) in patients with neuroendocrine tumours1995In: Regulatory Peptides, ISSN 0167-0115, E-ISSN 1873-1686, Vol. 55, no 2, p. 119-131Article in journal (Refereed)
    Abstract [en]

    Although IAPP was first discovered and isolated from amyloid deposits in an endocrine pancreatic tumour (EPT), surprisingly few reports have investigated the potential use of IAPP as a marker for neuroendocrine tumour growth. In this study we present results from plasma measurements of IAPP in 102 patients with neuroendocrine tumours. Four of 35 patients (11%) with midgut carcinoid tumours, but none of the patients (4 and 5, respectively) with lung carcinoids or with rectal carcinoids displayed elevated plasma levels of IAPP. Five of 31 patients (16%) with sporadic EPT and 3 of 27 patients (11%) with EPT and multiple endocrine neoplasia type 1 syndrome disclosed elevated IAPP levels. Within the different syndromes, 1/11 individuals with insulinoma, 2/16 with gastrinoma, 0/2 with glucagonoma, 0/3 with VIPoma and 5/26 with non-functioning tumours showed elevated plasma levels of IAPP. In two patients, the plasma IAPP levels were extremely elevated. These patients also exhibited altered glucose homeostasis. In response to a standardised mixed meal test, IAPP increased in parallel to the insulin, pancreatic polypeptide, gastrin and glucose responses. In MEN1 patients with hypercalcaemia due to increased secretion of parathyroid hormone, the plasma levels of IAPP were significantly higher before than after surgical removal of the parathyroid adenomas. However in normocalcaemic patients, no correlation between the blood calcium and plasma IAPP levels was found. Immunocytochemical staining of tumour tissue showed that 9/13 (69%) of insulin producing tumours, 4/14 (29%) of non-functioning tumours and 1/9 (11%) of gastrin producing tumours were IAPP immunoreactive. Amyloid deposits were always IAPP immunoreactive. In conclusion, increased circulating levels of IAPP occurred in 12% of 102 patients with neuroendocrine tumours. In 2 patients with extremely elevated plasma levels of IAPP, effects on glucose homeostasis were recorded. Thus, IAPP may be useful as an additional marker for neuroendocrine tumour growth in selected cases.

  • 21.
    Thunberg, Ulf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Linderoth, Johan
    Roos, Göran
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Berglund, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    BCL2 expression in de novo Diffuse Large B-cell Lymphoma partly reflects normal differences in age distribution2009In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 146, no 6, p. 683-684Article in journal (Refereed)
  • 22.
    Thunberg, Ulf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Tobin, Gerard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Johnson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Söderberg, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular tools.
    Padyukov, Leonid
    Hultdin, Magnus
    Klareskog, Lars
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Roos, Göran
    Rosenquist, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Polymorphism in the P2X7 receptor gene and survival in chronic lymphocytic leukaemia2002In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 360, no 9349, p. 1935-1939Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    The P2X7 receptor is a ligand-gated cation channel that mediates ATP-induced apoptotic death in haemopoietic and chronic lymphocytic leukaemia (CLL) cells. We aimed to investigate the clinical effect of a single nucleotide polymorphism in the P2X7 receptor gene (1513A-->C) and correlate findings with the immunoglobulin heavy chain variable (V(H)) gene mutation status, a prognostic marker in CLL.

    METHODS:

    We investigated tumour DNA in 170 patients with CLL using PCR-RFLP analysis with HhaI restriction enzyme cleavage to screen for the polymorphism in the P2X7 receptor gene. The VH gene mutation status was assessed in 165 patients by PCR amplification and nucleotide sequencing. We correlated the findings of the P2X7 receptor genotype with the V(H) gene mutation data and overall survival and screened for the P2X7 receptor polymorphism in 200 healthy controls.

    FINDINGS:

    Of the 170 patients, 35 (21%) were heterozygous and one (1%) homozygous for the 1513C allele; whereas 134 (79%) had the 1513A/A genotype of the P2X7 receptor gene. Overall survival was significantly longer for patients with CLL heterozygous for the 1513C allele than those with the 1513A/A genotype. Median survival for heterozygous patients was 104 months (range 33-467) and 72 months (1-190) for homozygous patients (p=0.009). Of the 165 patients with CLL in whom we assessed the V(H) gene mutation status, the V(H) genes were mutated in 71 (43%) patients and unmutated in 94; 18 (25%) of the 71 patients with mutated genes had 1513C allele compared with 17 (18%) of 94 who had unmutated genes. In patients with mutated VH genes, those with CLL who were 1513C positive had 53 months' longer median survival than did those with the 1513A/A genotype (151 vs 98 months, p=0.011).

    INTERPRETATION:

    The P2X7 polymorphism could affect clinical outcome in CLL, especially in patients with mutated V(H) genes. Studies are necessary to elucidate the biological role of the P2X7 polymorphism in CLL in vivo.

  • 23.
    Tobin, Gerard
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Thunberg, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Johnson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Söderberg, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular tools.
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Sällström, Jan
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Roos, Göran
    Rosenquist, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Response to "Do B-cell chronic lymphocytic leukemia patients with Ig VH3-21 genes constitute a new subset of chronic lymphocytic leukemia?": IgVH3-21 gene usage in chronic lymphocytic leukemia2002In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 100, no 3, p. 1098-1099Article in journal (Other academic)
  • 24.
    Tsolakis, Apostolos V.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Grimelius, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Falkmer, Sture E.
    Waldum, Helge L.
    Saras, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Janson, Eva Tiensuu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Obestatin/ghrelin cells in normal mucosa and endocrine tumours of the stomach2009In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 160, no 6, p. 941-949Article in journal (Refereed)
    Abstract [en]

    Objective:

    Obestatin and ghrelin are derived from the same gene and co-expressed in the same endocrine cells. Vesicular monoamine transporter-2 (VMAT-2), a marker for enterochromaffin-like (ECL) cells, is considered to be expressed in ghrelin cells. The aim was to establish if the two peptides and the transporter are co-expressed, both in normal gastric mucosa and in gastric endocrine tumours.

    Design:

    An immunohistochemical study was performed on gastric biopsy material and on surgical specimens from 63 patients with gastric endocrine tumours and from individuals with normal gastric mucosa. Cells displaying obestatin immunoreactivity were examined regarding co-localization with ghrelin and VMAT-2. Both single- and double-immunostaining techniques were applied. Obestatin concentration in blood was measured in a subgroup of these patients. The results were correlated to various clinico-pathological parameters.

    Results:

    In the normal mucosa, obestatin/ghrelin-immunoreactive cells rarely co-expressed VMAT-2. In most tumour tissue specimens, only a fraction of neoplastic cells displayed immunoreactivity to obestatin, and these cells always co-expressed ghrelin. Neoplastic obestatin-/ ghrelin-IR cells invariably expressed VMAT-2, except for two ghrelinomas. The obestatin concentrations in blood were consistently low and did not correlate to clinico-pathological data.

    Conclusions:

    Obestatin and ghrelin immunoreactivity always occurred in the same endocrine cells in the gastric mucosa but these cells only occasionally co-expressed VMAT-2, opposite to the findings in tumours. These results indicate that endocrine cells expressing obestatin and ghrelin mainly differ from VMAT-2 expressing cells (ECL-cells) and can develop into pure ghrelinomas. Plasma concentrations of obestatin did not correlate to cellular expression.

  • 25.
    Westermark, Gunilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Westermark, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Importance of aggregated islet amyloid polypeptide for the progressive beta-cell failure in type 2 diabetes and in transplanted human islets2008In: Experimental diabetes research, ISSN 1687-5214, Vol. 2008, p. 528354-Article in journal (Refereed)
  • 26.
    Zainuddin, Norafiza
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Berglund, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Wanders, Alkwin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Ren, Zhi-Ping
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Lindell, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Pathology.
    Kanduri, Meena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Hematology and Immunology.
    Roos, Göran
    Department of Medical Biosciences, Pathology, Umeå University, Umeå.
    Rosenquist, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Hematology and Immunology.
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    TP53 mutations predict for poor survival in de novo diffuse large B-cell lymphoma of germinal center subtype2009In: Leukemia research: a Forum for Studies on Leukemia and Normal Hemopoiesis, ISSN 0145-2126, E-ISSN 1873-5835, Vol. 33, no 1, p. 60-66Article in journal (Refereed)
    Abstract [en]

    Presence of TP53 mutations has been associated with poor prognosis in diffuse large B-cell lymphoma (DLBCL), although this has remained controversial. The TP53 codon 72 polymorphism has shown negative impact on cancer survival, but this has not been analyzed in DLBCL. Furthermore, the MDM2 SNP309 has been associated with earlier age of onset in DLBCL. Here, we investigated the clinical impact of TP53 mutations, MDM2 SNP309 and TP53 codon 72 polymorphisms on survival in DLBCL of germinal center (GC) and non-GC subtypes. Thirteen of the 102 (12.7%) patients displayed TP53 mutations. Overall, TP53 mutations had a significant effect on lymphoma-specific survival (LSS, P=0.009) and progression-free survival (PFS, P=0.028). In particular, inferior survival was observed in TP53-mutated DLBCLs of GC subtype (LSS, P=0.002 and PFS, P=0.006). Neither MDM2 SNP309 nor the TP53 codon 72 polymorphism had an impact on age of onset or survival. Altogether, our data suggests that TP53 mutations are associated with poor outcome in GC-DLBCL patients.

1 - 26 of 26
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf