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Sökning: WFRF:(Wester Kenneth)

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  • Carlsson, Jörgen, et al. (författare)
  • EGFR-expression in primary urinary bladder cancer and corresponding metastases and the relation to HER2-expression. On the possibility to target these receptors with radionuclides
  • 2015
  • Ingår i: Radiology and Oncology. - 1318-2099 .- 1581-3207. ; 49:1, s. 50-58
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. There is limited effect of tyrosine kinase inhibitors or "naked" antibodies binding EGFR or HER2 for therapy of metastasized urinary bladder canter and these methods are therefore not routinely used. Targeting radionuclides to the extracellular domain of the receptors is potentially a better possibility. Methods. EGFR- and HER2-expression was analyzed for primary tumors and corresponding metastases from 72 patients using immunohistochemistry and the internationally recommended HercepTest. Intracellular mutations were not analyzed since only the receptors were considered as targets and intracellular abnormalities should have minor effect on radiation dose. Results. EGFR was positive in 71% of the primary tumors and 69% of corresponding metastases. Local and distant metastases were EGFR-positive in 75% and 66% of the cases, respectively. The expression frequency of HER2 in related lesions was slightly higher (data from previous study). The EGFR-positive tumors expressed EGFR in metastases in 86% of the cases. The co-expression of EGFR and HER2 was 57% for tumors and 53% for metastases. Only 3% and 10% of the lesions were negative for both receptors in tumors and metastases, respectively. Thus, targeting these receptors with radionuclides might be applied for most patients. Conclusions. At least one of the EGFR- or HER2-receptors was present in most cases and co-expressed in more than half the cases. It is therefore interesting to deliver radionuclides for whole-body receptor-analysis, dosimetry and therapy. This can hopefully compensate for resistance to other therapies and more patients can hopefully be treated with curative instead of palliative intention.
  • Fagelskiold, Amanda Jabin, et al. (författare)
  • Insulin-secreting INS-1E cells express functional TRPV1 channels
  • 2012
  • Ingår i: Islets. - 1938-2014 .- 1938-2022. ; 4:1, s. 56-63
  • Tidskriftsartikel (refereegranskat)abstract
    • We have studied whether functional TRPV1 channels exist in the INS-1E cells, a cell type used as a model for beta-cells, and in primary beta-cells from rat and human. The effects of the TRPV1 agonists capsaicin and AM404 on the intracellular free Ca2+ concentration ([Ca2+]i) in the INS-1E cells were studied by fura-2based microfluorometry. Capsaicin increased [Ca2+] i in a concentration-dependent manner, and the [Ca2+] i increase was dependent on extracellular Ca2+. AM404 also increased [Ca2+] i in the INS-1E cells. Capsazepine, a specific antagonist of TRPV1, completely blocked the capsaicin- and AM404-induced [Ca2+] i increases. Capsaicin did not increase [Ca2+] i in the primary beta-cells from rat and human. Whole cell patch clamp configuration was used to record currents across the plasma membrane in the INS-1E cells. Capsaicin elicited inward currents that were inhibited by capsazepine. Western blot analysis detected TRPV1 proteins in the INS-1E cells and the human islets. Immunohistochemistry was used to study the expression of TRPV1, but no TRPV1 protein immunoreactivity was detected in the human islet cells and the human insulinoma cells. We conclude that the INS-1E cells, but not the primary beta-cells, express functional TRPV1 channels.
  • Häggarth, Lars, et al. (författare)
  • Diagnostic biomarkers of prostate cancer
  • 2011
  • Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa Healthcare. - 0036-5599 .- 1651-2065. ; 45:1, s. 60-67
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Diagnostic tissue biomarkers for prostate cancer (PC) include basal cell markers and α-methylacyl-coenzyme A-racemase (AMACR), often used in combination. Their sensitivity and specificity are not perfect and there is a need for additional diagnostic biomarkers for PC in cases that are difficult to diagnose on routine stained sections.MATERIAL AND METHODS: This study investigated the diagnostic accuracy of three novel tissue biomarkers for PC found through a search in the Human Protein Atlas database ( www.proteinatlas.com ): somatic cytochrome c (CYCS), intestinal cell kinase (ICK) and inhibitor of nuclear factor-κB kinase subunit beta (IKBKB), and compared the results with AMACR. A tissue microarray was constructed from 40 consecutive radical prostatectomy (RP) specimens including benign prostatic tissue, atrophy, high-grade prostatic intraepithelial neoplasia (HGPIN) and PC. Immunoreactivity was scored based on staining intensity and extent. Real-time polymerase chain reaction (PCR) was performed on malignant and benign frozen tissue samples from 32 RP specimens.RESULTS: All four biomarkers showed a stronger expression in PC and HGPIN than in benign tissue (p < 0.001). The highest diagnostic accuracy for PC was achieved with ICK and AMACR at 97%. The area under the curve for CYCS, ICK, IKBKB and AMACR was 0.859, 0.997, 0.865 and 0.983, respectively. The presence of mRNA transcripts of the genes was confirmed by real-time PCR in benign and malignant prostatic tissue.CONCLUSIONS: AMACR is an accurate diagnostic tissue marker for PC. However, in some PCs AMACR is false negative and a panel of CYCS, ICK and IKBKB may serve as ancillary diagnostic tool.
  • Jaraj, Sara Jonmarker, et al. (författare)
  • GAD1 is a biomarker for benign and malignant prostatic tissue
  • 2011
  • Ingår i: Scandinavian Journal of Urology and Nephrology. - 0036-5599 .- 1651-2065. ; 45:1, s. 39-45
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. Tissue-specific markers are useful for identification of tumour type in advanced cancers of unknown origin. This study investigated the expression of glutamate decarboxylase 1 (GAD1) in prostate and control tissue compared with the established prostate-specific markers prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA). Material and methods. A tissue microarray was constructed of 36 prostate adenocarcinomas, eight benign prostate samples and benign and malignant control tissues from urinary bladder, lung and rectum. Immunohistochemistry for GAD 1, PSA and PSMA was performed. The products of staining intensity and extent were analysed. The GAD1 antibody was validated by Western blot. Real-time polymerase chain reaction (RT-PCR) was performed on malignant and benign samples from each tissue type. Results. GAD 1 and PSA immunostains were significantly stronger in malignant and benign prostatic tissue than in controls. PSMA was stronger in prostate cancer than in urothelial and rectal cancer but had a lower specificity than GAD1 and PSA. GAD I expression decreased with increasing Gleason score. RT-PCR confirmed the presence of mRNA for GAD I, PSA and PSMA in prostate samples. Conclusion. GAD1 is expressed in benign and malignant prostatic tissue and may serve as a highly prostate-specific tissue biomarker.
  • Kettil, Gustav, 1990, et al. (författare)
  • Numerical investigation of upstream cylinder flow and characterization of forming fabrics
  • 2019
  • Ingår i: Nordic Pulp and Paper Research Journal. - 0283-2631. ; 34:3
  • Tidskriftsartikel (refereegranskat)abstract
    • In this work, the fundamentals of upstream flow over cylinders and forming fabrics are investigated, and measures for characterization of fabrics are proposed. Two-dimensional flow over one cylinder, two cylinders, and one and two rows of cylinders, are analysed numerically. By studying different configurations and various Reynolds numbers, the upstream flow features are characterized. It is concluded that cylinders have a short range of upstream flow impact, shortest for rows of cylinders with small spacings. For R e - [ 10, 80 ]Re\in [10,80], the Reynolds number dependency is weak. It is shown that a downstream row positioned in tandem has negligible impact on the upstream flow, while a displaced second row influences the upstream flow if the spacing in the first row is larger than one diameter. The pressure drop required to drive the flow over the cylinders depends non-linearly on the porosity of the configuration. Flow measures of the upstream flow are proposed, which in addition to the volume flow per area are used to characterize fabric flow properties. The conclusions from the cylinder study also hold for industrial fabrics, and it can be explained how properties of the fabric influence the final paper. The wave-length of flow periodicity is studied in relation to drainage marking. This study demonstrates that simulations can greatly improve pure experimental-based fabric characterization. © 2019 Walter de Gruyter GmbH, Berlin/Boston.
  • Kettil, Gustav, et al. (författare)
  • Numerical upscaling of discrete network models
  • 2020
  • Ingår i: BIT (Copenhagen). - 0006-3835. ; 60:1, s. 67-92
  • Tidskriftsartikel (refereegranskat)abstract
    • In this paper a numerical multiscale method for discrete networks is presented. The method gives an accurate coarse scale representation of the full network by solving sub-network problems. The method is used to solve problems with highly varying connectivity or random network structure, showing optimal order convergence rates with respect to the mesh size of the coarse representation. Moreover, a network model for paper-based materials is presented. The numerical multiscale method is applied to solve problems governed by the presented network model.
  • Lindén, Mårten, et al. (författare)
  • Proteomic analysis of urinary biomarker candidates for nonmuscle invasive bladder cancer
  • 2012
  • Ingår i: Proteomics. - 1615-9853 .- 1615-9861. ; 12:1, s. 135-144
  • Tidskriftsartikel (refereegranskat)abstract
    • Nonmuscle invasive tumors of the bladder often recur and thereby bladder cancer patients need regular re-examinations which are invasive, unpleasant, and expensive. A noninvasive and less expensive method, e.g. a urine dipstick test, for monitoring recurrence would thus be advantageous. In this study, the complementary techniques mass spectrometry (MS) and Western blotting (WB)/dot blot (DB) were used to screen the urine samples from bladder cancer patients. High resolving MS was used to analyze and quantify the urinary proteome and 29 proteins had a significantly higher abundance (p<0.05) in bladder cancer samples compared with control urine samples. The increased abundance found in urine from bladder cancer patients compared with controls was confirmed with Western blot for four selected proteins; fibrinogen β chain precursor, apolipoprotein E, α-1-antitrypsin, and leucine-rich α-2-glycoprotein 1. Dot blot analysis of an independent urine sample set pointed out fibrinogen β chain and α-1-antitrypsin as most interesting biomarkers having sensitivity and specificity values in the range of 66-85%. Exploring the Human Protein Atlas (HPA) also revealed that bladder cancer tumors are the likely source of these proteins. They have the potential of being useful in diagnosis, monitoring of recurrence and thus may improve the treatment of bladder tumors, especially nonmuscle invasive tumors.
  • Loskog, Angelica, et al. (författare)
  • Human urinary bladder carcinomas express adenovirus attachment and internalization receptors
  • 2002
  • Ingår i: Gene Therapy. - 0969-7128 .- 1476-5462. ; 9:9, s. 547-553
  • Tidskriftsartikel (refereegranskat)abstract
    • The use of adenoviral vectors as potent gene delivery systems requires expression of the Coxsackievirus/adenovirus receptor (CVADR) on the target cell surface. This receptor is important for virus attachment to the cell surface. For effective internalization of the vector into the target cell the integrins alpha(v)beta(3) and/or alpha(v)beta(5) are needed. Since there have been reports of loss of CVADR in bladder cancer cell lines, we wanted to investigate the expression of this receptor in bladder carcinoma biopsies. Surgical biopsies, as well as five human bladder cancer cell lines, were analyzed for expression of CVADR, the integrins alpha(v)beta(3) and alpha(v)beta(5) and MHC class I. Further, we studied the ability to transduce these cell lines using adenoviral vectors. Immunohistochemistry revealed that all biopsies (27/27) were positive for CVADR. Some variation in expression was evident, and superficially growing tumors stained more strongly than invasive ones. Most human tumors expressed the integrin alpha(v)beta(5) (14/24), whereas integrin alpha(v)beta(3) was less frequently seen (3/20). The established cell lines were efficiently transduced with adenoviral vectors, and transduction could be reduced with anti-CVADR antibodies. The abundance of appropriate viral receptors on tumor biopsy cells is a further argument for using adenoviral vectors in gene therapy of bladder cancer.
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