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  • 1.
    Azar, Jimmy
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Busch, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Carlbom, Ingrid
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Histological Stain Evaluation for Machine Learning Applications2012In: Proceedings of the International Conference on Medical Image Computing and Computer Assisted Intervention, 2012Conference paper (Refereed)
  • 2.
    Bill-Axelson, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Holmberg, Lars
    Regional Cancer Center Uppsala Örebro.
    Garmo, Hans
    Regional Cancer Center Uppsala Örebro.
    Rider, Jennifer R.
    Taari, Kimmo
    Busch, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Nordling, Stig
    Häggman, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Andersson, Swen-Olof
    Spangberg, Anders
    Andren, Ove
    Palmgren, Juni
    Steineck, Gunnar
    Adami, Hans-Olov
    Johansson, Jan-Erik
    Radical Prostatectomy or Watchful Waiting in Early Prostate Cancer2014In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 370, no 10, 932-942 p.Article in journal (Refereed)
    Abstract [en]

    BackgroundRadical prostatectomy reduces mortality among men with localized prostate cancer; however, important questions regarding long-term benefit remain. MethodsBetween 1989 and 1999, we randomly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy and followed them through the end of 2012. The primary end points in the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) were death from any cause, death from prostate cancer, and the risk of metastases. Secondary end points included the initiation of androgen-deprivation therapy. ResultsDuring 23.2 years of follow-up, 200 of 347 men in the surgery group and 247 of the 348 men in the watchful-waiting group died. Of the deaths, 63 in the surgery group and 99 in the watchful-waiting group were due to prostate cancer; the relative risk was 0.56 (95% confidence interval [CI], 0.41 to 0.77; P=0.001), and the absolute difference was 11.0 percentage points (95% CI, 4.5 to 17.5). The number needed to treat to prevent one death was 8. One man died after surgery in the radical-prostatectomy group. Androgen-deprivation therapy was used in fewer patients who underwent prostatectomy (a difference of 25.0 percentage points; 95% CI, 17.7 to 32.3). The benefit of surgery with respect to death from prostate cancer was largest in men younger than 65 years of age (relative risk, 0.45) and in those with intermediate-risk prostate cancer (relative risk, 0.38). However, radical prostatectomy was associated with a reduced risk of metastases among older men (relative risk, 0.68; P=0.04). ConclusionsExtended follow-up confirmed a substantial reduction in mortality after radical prostatectomy; the number needed to treat to prevent one death continued to decrease when the treatment was modified according to age at diagnosis and tumor risk. A large proportion of long-term survivors in the watchful-waiting group have not required any palliative treatment. (Funded by the Swedish Cancer Society and others.) The randomized Swedish trial of prostatectomy versus watchful waiting in disease detected mainly clinically (not by PSA screening) continues to show a benefit for early prostatectomy. The number of men younger than 65 needed to treat to prevent one death is now four. The Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4), a randomized trial of radical prostatectomy versus watchful waiting in men with localized prostate cancer diagnosed before the era of prostate-specific antigen (PSA) testing, showed a survival benefit of radical prostatectomy as compared with observation at 15 years of follow-up.(1) By contrast, the Prostate Cancer Intervention versus Observation Trial (PIVOT), initiated in the early era of PSA testing, showed that radical prostatectomy did not significantly reduce prostate cancer-specific or overall mortality after 12 years.(2) PSA screening profoundly changes the clinical domain of study. Among other considerations, the substantial additional lead time ...

  • 3.
    Bill-Axelson, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Norlén, Bo Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Busch, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Norberg, Mona
    No increased prostate cancer incidence after negative transrectal ultrasound guided multiple biopsies in men with increased prostate specific antigen and/or abnormal digital rectal examination.2003In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 170, no 4 Pt 1, 1180-3 p.Article in journal (Refereed)
    Abstract [en]

    PURPOSE: We investigated the incidence of prostate cancer after negative transrectal ultrasound (TRUS) guided multiple biopsies. Our secondary aim was to calculate the sensitivity of the extended protocol used.

    MATERIALS AND METHODS: A cohort of 547 men with elevated prostate specific antigen and/or abnormal digital rectal examination but with results negative for prostate cancer on a mean of 9 TRUS guided biopsies was followed through record linkage to the national cancer Registry. The observed number of prostate cancers was compared with the expected number during the same calendar period in an age matched male population to determine the standardized incidence ratio. The sensitivity of TRUS with multiple biopsies after 5 years of followup was calculated. Relative survival was estimated if there was an excess death rate due to undiagnosed prostate cancer.

    RESULTS: We found 11 men diagnosed with prostate cancer. The expected number in the age standardized male population was 15, resulting in a standardized incidence ratio of 0.8 (95% CI 0.4 to 1.2). Five-year sensitivity of the extended protocol of TRUS guided biopsies was 95.2% (95% CI 93.5 to 96.4) and relative survival was more than 100%, indicating a selection of men deemed candidates for curative treatment.

    CONCLUSIONS: Men with clinical suspicion of prostate cancer who are examined by an extended protocol of TRUS guided biopsies negative for cancer do not have an increased incidence of prostate cancer within 6 years compared with an age matched male population. Five-year sensitivity of this protocol was high.

  • 4. Busund, L-T
    et al.
    Richardsen, E
    Busund, R
    Ukkonen, T
    Bjorsen, T
    Busch, C
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Stalsberg, H
    Significant expression of IGFBP2 in breast cancer compared with benign lesions.2005In: J Clin Pathol, ISSN 0021-9746, Vol. 58, no 4, 361-6 p.Article in journal (Refereed)
  • 5.
    Egevad, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Frimmel, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Centre for Image Analysis. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis.
    Mattson, Stefan
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Information Science, Statistics.
    Bengtsson, Ewert
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Centre for Image Analysis. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis.
    Busch, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Biopsy protocol stability in a three-dimensional model of prostate cancer: Changes in cancer yield after adjustment of biopsy positions1999In: Urology, ISSN 0090-4295, E-ISSN 1527-9995, Vol. 54, 862-868 p.Article in journal (Refereed)
  • 6.
    Egevad, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Frimmel, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Centre for Image Analysis. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis.
    Norberg, Mona
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Mattson, Stefan
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Information Science, Statistics.
    Carlbom, Ingrid
    Bengtsson, Ewert
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Centre for Image Analysis. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis.
    Busch, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Three-dimensional computer reconstruction of prostate cancer from radical prostatectomy specimens: Evaluation of the model by core biopsy simulation1999In: Urology, ISSN 0090-4295, E-ISSN 1527-9995, Vol. 53, 192-198 p.Article in journal (Refereed)
  • 7.
    Frimmel, Hans
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Centre for Image Analysis. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis.
    Egevad, Lars
    Bengtsson, Ewert
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Centre for Image Analysis. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis.
    Busch, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Modeling prostate cancer distributions1999In: Urology, ISSN 0090-4295, E-ISSN 1527-9995, Vol. 54, 1028-1034 p.Article in journal (Refereed)
  • 8.
    Frimmel, Hans
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Centre for Image Analysis. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis.
    Egevad, Lars
    Busch, Christer
    Bengtsson, Ewert
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Centre for Image Analysis. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis.
    Automatic registration and error detection of multiple slices using landmarks2001In: Analytical Cellular Pathology, ISSN 0921-8912, E-ISSN 1878-3651, Vol. 23, 159-165 p.Article in journal (Refereed)
  • 9. Glaessgen, Axel
    et al.
    Busch, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Norberg, Mona
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Häggman, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Nilsson, Bo
    Egevad, Lars
    Prediction of percent Gleason grade 4/5 by multiple core biopsies2006In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 40, no 6, 465-471 p.Article in journal (Refereed)
    Abstract [en]

    Objective. To evaluate whether percent Gleason grade 4/5 (i.e. the proportion of a tumor occupied by high-grade cancer) can be predicted by multiple needle biopsies. Material and methods. In 115 men, 8-14 (mean 10) biopsies were taken, including eight from standardized positions (apex, mid-medial, mid-lateral and base). Biopsies were reviewed and cancer lengths measured. All men underwent radical prostatectomy. The prostatectomy specimens were totally embedded and tumor volume measured planimetrically. Gleason scores and percent Gleason grade 4/5 were assessed for both biopsy and prostatectomy specimens. Results. Percent Gleason grade 4/5 in prostatectomy specimens was predicted correctly in 34% of cases and within 10%, 20% and 30% in 55%, 64% and 73% of cases, respectively. Biopsies had a sensitivity, specificity and accuracy for Gleason grade 4/5 of 62%, 87% and 69%, respectively. Positive and negative predictive values were 93% and 45%, respectively. The weighted kappa value for agreement was slightly higher for Gleason score (0.685) than for percent Gleason grade 4/5 (0.573). The univariate correlation for percent Gleason grade 4/5 in biopsies and the main tumor was r = 0.62, r(2) = 0.39 (p < 0.001). In univariate logistic regression, percent Gleason grade 4/5 on biopsies predicted the presence of any Gleason grade 4/5 cancer in the main tumor (p = 0.009). Conclusions. Gleason grade 4/5 in prostatectomy specimens correlates with findings in preoperative biopsies. Whether this measure will be used in routine practice remains to be seen.

  • 10.
    Grundmark, Birgitta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Loda, Massimo
    Busch, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    The Metabolic Syndrome and the Risk of Prostate Cancer under Competing Risks of Death from Other Causes2010In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 19, no 8, 2088-2096 p.Article in journal (Refereed)
    Abstract [en]

    Background:

    Associations between metabolic syndrome (MetS) components and prostate cancer development have not been studied comprehensively; results have been divergent. Using the National Cholesterol Education Program Adult Treatment panel III (NCEP) and International Diabetes Federation (IDF) definitions of the MetS, we investigated such associations taking competing risks of death into consideration.

    Methods:

    In the prospective Uppsala Longitudinal Study of Adult Men of 2,322 Caucasian men with 34 years of follow-up baseline, MetS measurements at age 50 years were used. Cumulative incidence of prostate cancer and death with/without the MetS were calculated. Competing risk of dying was taken into account by calculating the conditional probability of prostate cancer with/without the MetS.

    Results:

    Two hundred and thirty-seven prostate cancers were identified. Prostate cancer probability by age 80 years with baseline MetS compared with without MetS was nonsignificantly higher [5.2 percent units (confidence interval (CI), -0.8% to 11.3%; NCEP); 2.7 percent units (CI, -2.7% to 8.0%; IDF)]; cumulative incidence proportions of death was significantly higher [19.3 percent units (CI, 13.4-25.3%; NCEP); 15.3 percent units (CI, 9.5-21.1%; IDF)]; and conditional probability of prostate cancer considering death from other causes was significantly higher [7.3 percent-units (CI, 0.2-14.5%); odds ratio of 1.64 (CI, 1.03-2.23; NCEP)] and nonsignificantly higher [5.0 percent-units (CI, -1.6% to 11.6%); odds ratio of 1.43 (CI, 0.89-1.90; IDF].

    Conclusions:

    The MetS by the NCEP definition is associated with prostate cancer, taking the competing risk of early death from other causes into account. Impact: The results further highlight the public health effect of the increasing prevalence of MetS and the importance of considering competing risks when studying risk factors for cancer.

  • 11. Häggarth, Lars
    et al.
    Auer, Gert
    Busch, Christer
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Norberg, Mona
    Häggman, Michael
    Department of Surgical Sciences.
    Egevad, Lars
    The significance of tumor heterogeneity for prediction of DNA ploidy of prostate cancer.2005In: Scand J Urol Nephrol, ISSN 0036-5599, Vol. 39, no 5, 387-92 p.Article in journal (Refereed)
  • 12. Häggarth, Lars
    et al.
    Busch, Christer
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Norberg, Mona
    Häggman, Michael
    Department of Surgical Sciences.
    Norlén, Bo-Johan
    Department of Surgical Sciences.
    Egevad, Lars
    Prediction of the volume of large prostate cancers by multiple core biopsies.2005In: Scand J Urol Nephrol, ISSN 0036-5599, Vol. 39, no 5, 380-6 p.Article in journal (Refereed)
  • 13. Isfoss, Bjorn L.
    et al.
    Busch, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Hermelin, Helena
    Vermedal, Anette T.
    Kile, Marianne
    Braathen, Geir J.
    Majak, Bernard
    Berner, Aasmund
    Stem cell marker-positive stellate cells and mast cells are reduced in benign-appearing bladder tissue in patients with urothelial carcinoma2014In: Virchows Archiv, ISSN 0945-6317, E-ISSN 1432-2307, Vol. 464, no 4, 473-488 p.Article in journal (Refereed)
    Abstract [en]

    Survival after invasive bladder cancer has improved less than that of other common non-skin cancers. In many types of malignancy, treatment failure has been attributed to therapy-resistant stem-like cancer cells. Our aim was therefore to determine identities of stem cell marker-positive cells in bladder cancer tissue and to investigate possible associations between these cells and different forms of bladder neoplasia. We investigated tissue from 52 patients with bladder neoplasia and 18 patients with benign bladder conditions, from a cohort that had been previously described with regard to diagnosis and outcome. The samples were analysed immunohistologically for the stem cell markers aldehyde dehydrogenase 1 A1 (ALDH1) and CD44, and markers of cell differentiation. The majority of stem cell marker-positive cells were located in connective tissue, and a smaller fraction in epithelial tissue. Stem cell marker-positive cells exhibiting possible stem cell characteristics included cells in deeper locations of benign and malignant epithelium, and sub-endothelial cells in patients with or without neoplasia. Stem cell marker-positive cells with non-stem cell character included stellate cells, mast cells, endothelial cells, foamy histiocytes, and neurons. Significantly, ALDH1+ stellate cells and ALDH1+ mast cells were reduced in number in stroma of benign-appearing mucosa of bladder cancer patients. The stem cell markers ALDH1 and CD44 label several types of differentiated cells in bladder tissue. ALDH1+ stellate cells and mast cells appear to be reduced in stroma of normal-appearing mucosa of bladder cancer patients, and may be part of a "field effect" in cancer-near areas.

  • 14. Kirkali, Ziya
    et al.
    Chan, Theresa
    Manoharan, Murugesan
    Algaba, Ferran
    Busch, Christer
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Cheng, Liang
    Kiemeney, Lambertus
    Kriegmair, Martin
    Montironi, R
    Murphy, William M
    Sesterhenn, Isabell A
    Tachibana, Masaaki
    Weider, Jeff
    Bladder cancer: epidemiology, staging and grading, and diagnosis.2005In: Urology, ISSN 1527-9995, Vol. 66, no 6 Suppl 1, 4-34 p.Article in journal (Refereed)
  • 15. Loughlin, Maria
    et al.
    Carlbom, Ingrid
    Busch, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Douglas, Thomas
    Egevad, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Frimmel, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Centre for Image Analysis. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis.
    Norberg, Mona
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Sesterhenn, Isabell
    Frogge, James M.
    Three-dimensional modeling of biopsy protocols for localized prostate cancer1998In: Computerized Medical Imaging and Graphics, ISSN 0895-6111, E-ISSN 1879-0771, Vol. 22, 229-238 p.Article in journal (Refereed)
  • 16.
    Micke, Patrick
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Ludwiginstitutet för Cancerforskning.
    Bjørnsen, Tone
    Scheidl, Stefan
    Strömberg, Sara
    Department of Genetics and Pathology.
    Demoulin, Jean-Baptiste
    Ludwiginstitutet för Cancerforskning.
    Pontén, Fredrik
    Department of Genetics and Pathology.
    Lindahl, Per
    Busch, Christer
    Department of Genetics and Pathology.
    A fluid cover medium provides superior morphology and preserves RNA integrity in tissue sections for laser microdissection and pressure catapulting2004In: J Pathol, Vol. 202, no (1), 130-8 p.Article in journal (Refereed)
    Abstract [en]

    Abstract

    Laser microdissection and pressure catapulting has become a powerful tool to obtain homogeneous cell populations from tissue samples in nearly all fields of biomedical research. The isolated cells can be subsequently used for the analysis of proteins, DNA or RNA. However, the method requires physical access to the tissue surface and the sections therefore need to be air-dried and uncovered. The consequence is poor morphology, which severely reduces the potential of the technique, especially in non-homogeneous tissues or tissues with infiltrating immune cells. To overcome this limitation, a fluid cover medium was developed and the effects on frozen and paraffin wax-embedded tissue morphology were evaluated. The cover medium improved the morphology such that it was almost comparable to sections overlaid with glass coverslips. Moreover, the laser microdissection procedure was facilitated, since the medium allowed larger areas of tissues to be laser pressure-catapulted. Neither the isolation of proteins nor the extraction of genomic DNA was adversely affected by the use of the fluid cover medium. No significant differences in RNA quantity and integrity were detected by TaqMan real-time PCR for GAPDH, and microchip electrophoresis, between covered and uncovered tissue sections. In conclusion, this method provides considerably improved morphology for laser microdissection and pressure catapulting techniques without affecting RNA-dependent downstream applications. This not only facilitates established procedures, but will also extend the application to tissues that require superior morphological resolution.

  • 17. Mu, Y.
    et al.
    Zang, G.
    Engström, Ulla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research.
    Busch, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Landstrom, M.
    TGF beta-induced phosphorylation of Par6 promotes migration and invasion in prostate cancer cells2015In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 112, no 7, 1223-1231 p.Article in journal (Refereed)
    Abstract [en]

    Background: The Par complex - comprising partition-defective 6 (Par6), Par3, and atypical protein kinase C (aPKC) - is crucial for cell polarisation, the loss of which contributes to cancer progression. Transforming growth factor beta (TGF beta)-induced phosphorylation of Par6 on the conserved serine 345 is implicated in epithelial-to-mesenchymal transition (EMT) in breast cancer. Here we investigated the importance of phosphorylated Par6 in prostate cancer. Methods: We generated a p-Par6(345)-specific antibody and verified its specificity in vitro. Endogenous p-Par6(345) was analysed by immunoblotting in normal human prostate RWPE1 and prostate cancer (PC-3U) cells. Subcellular localisation of p-Par6(345) in migrating TGF beta-treated PC-3U cells was analysed by confocal imaging. Invasion assays of TGF beta-treated PC-3U cells were performed. p-Par6 expression was immunohistochemically analysed in prostate cancer tissues. Results: TGF beta induced Par6 phosphorylation on Ser345 and its recruitment to the leading edge of the membrane ruffle in migrating PC-3U cells, where it colocalised with aPKC zeta. The p-Par6-aPKC zeta complex is important for cell migration and invasion, as interference with this complex prevented prostate cancer cell invasion. High levels of activated Par6 correlated with aggressive prostate cancer. Conclusions: Increased p-Par6Ser(345) levels in aggressive prostate cancer tissues and cells suggest that it could be a useful novel biomarker for predicting prostate cancer progression.

  • 18.
    O'Hurley, Gillian
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Busch, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Fagerberg, Linn
    Hallstrom, Bjorn M.
    Stadler, Charlotte
    Tolf, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lundberg, Emma
    Schwenk, Jochen M.
    Jirstrom, Karin
    Bjartell, Anders
    Gallagher, William M.
    Uhlen, Mathias
    Pontén, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Analysis of the Human Prostate-Specific Proteome Defined by Transcriptomics and Antibody-Based Profiling Identifies TMEM79 and ACOXL as Two Putative, Diagnostic Markers in Prostate Cancer2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 8, e0133449Article in journal (Refereed)
    Abstract [en]

    To better understand prostate function and disease, it is important to define and explore the molecular constituents that signify the prostate gland. The aim of this study was to define the prostate specific transcriptome and proteome, in comparison to 26 other human tissues. Deep sequencing of mRNA (RNA-seq) and immunohistochemistry-based protein profiling were combined to identify prostate specific gene expression patterns and to explore tissue biomarkers for potential clinical use in prostate cancer diagnostics. We identified 203 genes with elevated expression in the prostate, 22 of which showed more than five-fold higher expression levels compared to all other tissue types. In addition to previously well-known proteins we identified two poorly characterized proteins, TMEM79 and ACOXL, with potential to differentiate between benign and cancerous prostatic glands in tissue biopsies. In conclusion, we have applied a genome-wide analysis to identify the prostate specific proteome using transcriptomics and antibody-based protein profiling to identify genes with elevated expression in the prostate. Our data provides a starting point for further functional studies to explore the molecular repertoire of normal and diseased prostate including potential prostate cancer markers such as TMEM79 and ACOXL.

  • 19. Oosterlinck, Willem
    et al.
    Kirkali, Ziya
    Sylvester, Richard
    da Silva, Fernando Calais
    Busch, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Algaba, Ferran
    Collette, Sandra
    Bono, Aldo
    Sequential Intravesical Chemoimmunotherapy with Mitomycin C and Bacillus Calmette-Guerin and with Bacillus Calmette-Guerin Alone in Patients with Carcinoma in Situ of the Urinary Bladder: Results of an EORTC Genito-Urinary Group Randomized Phase 2 Trial (30993)2011In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 59, no 3, 438-446 p.Article in journal (Refereed)
    Abstract [en]

    Background: Bacillus Calmette-Guerin (BCG) is the intravesical treatment of choice for carcinoma in situ (CIS). Objective: Our aim was to assess if sequential mitomycin C (MMC) plus BCG after transurethral resection (TUR) is worthy of further study in non-muscle-invasive bladder cancer patients with CIS. Design, setting, and participants: In a noncomparative phase 2 study, 96 patients with primary/secondary/concurrent CIS of the urinary bladder were randomized to sequential MMC plus BCG or to BCG alone after TUR. Intervention: Patients received six weekly instillations of MMC followed by six weekly instillations of BCG or six weekly instillations of BCG, 3 wk rest, and three further weekly instillations of BCG. Complete responders received three weekly maintenance instillations at 6, 12, 18, 24, 30, and 36 mo in accordance with the initial randomization. Measurements: End points were complete response (CR) rate at the first control cystoscopy 16-18 wk after start of treatment, disease-free interval, overall survival, and side effects. Results and limitations: Ninety-six patients were randomized, 48 to each treatment group. Ten patients were ineligible, and three did not start treatment. In all random-ized patients, CR rates on MMC plus BCG and BCG alone were 70.8% and 66.7%, respectively. In 83 eligible patients who started treatment, CR rates were 75.6% and 73.8%, respectively. Based on a median follow-up of 4.7 yr, 25 patients (52.1%) on MMC plus BCG and 22 patients (45.8%) on BCG alone were disease free. Twelve patients stopped treatment due to toxicity: three during induction (two MMC plus BCG, one BCG) and nine during maintenance (three MMC plus BCG, six BCG). Conclusions: In the treatment of patients with CIS, sequential chemoimmunotherapy with MMC plus BCG had acceptable toxicity. CR and disease-free rates were similar to those on BCG alone and to previous publications on sequential chemoimmunotherapy.

  • 20. Oosterlinck, Willem
    et al.
    Solsona, Eduardo
    Akaza, Hideyuki
    Busch, Christer
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Goebell, Peter J
    Malmstrom, Per-Uno
    Department of Oncology, Radiology and Clinical Immunology. Department of Surgical Sciences.
    Ozen, Haluk
    Sved, Paul
    Low-grade Ta (noninvasive) urothelial carcinoma of the bladder.2005In: Urology, ISSN 1527-9995, Vol. 66, no 6 Suppl 1, 75-89 p.Article in journal (Refereed)
  • 21.
    Ranefall, Petter
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Centre for Image Analysis. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis.
    Wester, Kenneth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Andersson, Ann-Catrin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Busch, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Bengtsson, Ewert
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Centre for Image Analysis.
    Automatic quantification of immunohistochemically stained cell nuclei based on standard reference cells1998In: Analytical Cellular Pathology, ISSN 0921-8912, E-ISSN 1878-3651, Vol. 17, no 2, 111-23 p.Article in journal (Refereed)
    Abstract [en]

    A fully automatic method for quantification of images of immunohistochemically stained cell nuclei by computing area proportions, is presented. Agarose embedded cultured fibroblasts were fixed, paraffin embedded and sectioned at 4 microm. They were then stained together with 4 microm sections of the test specimen obtained from bladder cancer material. A colour based classifier is automatically computed from the control cells. The method was tested on formalin fixed paraffin embedded tissue section material, stained with monoclonal antibodies against the Ki67 antigen and cyclin A protein. Ki67 staining results in a detailed nuclear texture with pronounced nucleoli and cyclin A staining is obtained in a more homogeneously distributed pattern. However, different staining patterns did not seem to influence labelling index quantification, and the sensitivity to variations in light conditions and choice of areas within the control population was low. Thus, the technique represents a robust and reproducible quantification method. In tests measuring proportions of stained area an average standard deviation of about 1.5% for the same field was achieved when classified with classifiers created from different control samples.

  • 22.
    Wester, Kenneth
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Andersson, Ann-Catrin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Ranefall, Petter
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Centre for Image Analysis. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis.
    Bengtsson, Evert
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Centre for Image Analysis.
    Malmström, Per-Uno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Busch, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Cultured human fibroblasts in agarose gel as a multi-functional control for immunohistochemistry: Standardization Of Ki67 (MIB1) assessment in routinely processed urinary bladder carcinoma tissue2000In: Journal of Pathology, ISSN 0022-3417, E-ISSN 1096-9896, Vol. 190, no 4, 503-11 p.Article in journal (Refereed)
    Abstract [en]

    Immunohistochemistry (IHC) in clinical practice is hampered by lack of standardization and by subjectivity in interpretation and quantitation. This study aimed to develop a control system for IHC in routinely fixed and histoprocessed tissues. Such a system should be easy to handle in clinical practice and should reflect variations in fixation time, section thickness, section storage conditions, and staining protocols. In addition, in image analysis quantitation of immunostained tissues, when using classifiers computed on IHC-control images, the control system should be very stable. Cultured human fibroblasts were suspended in agarose, transferred into a length of tubing and stored at 4 degrees C. Three pieces of the cellgel control were separately fixed, histoprocessed, and paraffin-embedded as external controls. One piece was prepared together with each of 18 bladder carcinoma biopsies as internal controls. Slides with sections from the biopsy and all types of cellgel controls were stored at different temperatures and then stained using three different IHC protocols. The fibroblasts were homogeneously distributed in the agarose gel. Variation in section thickness did not influence immunostaining as evaluated by the MIB1 labelling index (MIB1 LI). The external controls decreased notably in MIB1 LI with increased fixation time. This was not seen in the 18 internal controls that were each fixed with a fresh biopsy. However, section storage and immunostaining conditions influenced the MIB1 expression equally in all control types and to a similar degree to the biopsies. Furthermore, colour-based image analysis quantitation of MIB1 LI in biopsies proved stable and independent of the control type used to compute the classifier.

1 - 22 of 22
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