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  • 1.
    Abrahamsson, Annelie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Rzepecka, Anna
    Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Romu, Thobias
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Borga, Magnus
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Dahlqvist Leinhard, Olof
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Lundberg, Peter
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Kihlberg, Johan
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Dabrosin, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Dense breast tissue in postmenopausal women is associated with a pro-inflammatory microenvironment in vivo2016In: Oncoimmunology, ISSN 2162-4011, E-ISSN 2162-402X, Vol. 5, no 10, article id e1229723Article in journal (Refereed)
    Abstract [en]

    Inflammation is one of the hallmarks of carcinogenesis. High mammographic density has been associated with increased risk of breast cancer but the mechanisms behind are poorly understood. We evaluated whether breasts with different mammographic densities exhibited differences in the inflammatory microenvironment.Postmenopausal women attending the mammography-screening program were assessed having extreme dense, n = 20, or entirely fatty breasts (nondense), n = 19, on their regular mammograms. Thereafter, the women were invited for magnetic resonance imaging (MRI), microdialysis for the collection of extracellular molecules in situ and a core tissue biopsy for research purposes. On the MRI, lean tissue fraction (LTF) was calculated for a continuous measurement of breast density. LTF confirmed the selection from the mammograms and gave a continuous measurement of breast density. Microdialysis revealed significantly increased extracellular in vivo levels of IL-6, IL-8, vascular endothelial growth factor, and CCL5 in dense breast tissue as compared with nondense breasts. Moreover, the ratio IL-1Ra/IL-1 was decreased in dense breasts. No differences were found in levels of IL-1, IL-1Ra, CCL2, leptin, adiponectin, or leptin:adiponectin ratio between the two breast tissue types. Significant positive correlations between LTF and the pro-inflammatory cytokines as well as between the cytokines were detected. Stainings of the core biopsies exhibited increased levels of immune cells in dense breast tissue.Our data show that dense breast tissue in postmenopausal women is associated with a pro-inflammatory microenvironment and, if confirmed in a larger cohort, suggests novel targets for prevention therapies for women with dense breast tissue.

  • 2.
    Cao, Renhai
    et al.
    Karolinska Institute, Sweden.
    Ji, Hong
    Karolinska Institute, Sweden.
    Yang, Yunlong
    Karolinska Institute, Sweden.
    Cao, Yihai
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Institute, Sweden; University of Leicester, England; Glenfield Hospital, England.
    Editorial Material: Collaborative effects between the TNF alpha-TNFR1-macrophage axis and the VEGF-C-VEGFR3 signaling in lymphangiogenesis and metastasis in ONCOIMMUNOLOGY, vol 4, issue 3, pp2015In: Oncoimmunology, ISSN 2162-4011, E-ISSN 2162-402X, Vol. 4, no 3, p. e989777-Article in journal (Other academic)
    Abstract [en]

    Although inflammation and metastasis are two well-known hallmarks of malignant disease, the relationship between inflammation and lymphatic metastasis is an unexplored research area. We recently elucidated a sophisticated mechanism by which TNF alpha-induced tumor inflammation conscripts macrophage-mediated VEGF-C-VEGFR3 signaling in lymphangiogenesis and metastasis.

  • 3.
    Kreutzman, Anna
    et al.
    Helsinki Univ Hosp, Finland; Univ Helsinki, Finland.
    Yadav, Bhagwan
    Helsinki Univ Hosp, Finland; Univ Helsinki, Finland.
    Brummendorf, Tim H.
    Univ Klinikum RWTH Aachen, Germany.
    Gjertsen, Bjorn Tore
    Univ Bergen, Norway; Univ Bergen, Norway.
    Hee, Moon Lee
    Helsinki Univ Hosp, Finland; Univ Helsinki, Finland.
    Janssen, Jeroen
    Vrije Univ Amsterdam Med Ctr, Netherlands.
    Kasanen, Tiina
    Univ Helsinki, Finland; Helsinki Univ Hosp, Finland.
    Koskenvesa, Perttu
    Univ Helsinki, Finland; Helsinki Univ Hosp, Finland.
    Lotfi, Kourosh
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Markevarn, Berit
    Umea Univ Hosp, Sweden.
    Olsson-Stromberg, Ulla
    Uppsala Univ, Sweden; Uppsala Univ Hosp, Sweden.
    Stentoft, Jesper
    Aarhus Univ Hosp, Denmark.
    Stenke, Leif
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Soderlund, Stina
    Uppsala Univ Hosp, Sweden.
    Udby, Lene
    Zealand Univ Hosp, Denmark.
    Richter, Johan
    Skane Univ Hosp, Sweden.
    Hjorth-Hansen, Henrik
    St Olavs Hosp, Norway; Norwegian Univ Sci and Technol NTNU, Norway.
    Mustjoki, Satu
    Helsinki Univ Hosp, Finland; Univ Helsinki, Finland.
    Immunological monitoring of newly diagnosed CML patients treated with bosutinib or imatinib first-line2019In: Oncoimmunology, ISSN 2162-4011, E-ISSN 2162-402X, Vol. 8, no 9, article id e1638210Article in journal (Refereed)
    Abstract [en]

    Changes in the immune system induced by tyrosine kinase inhibitors (TKI) have been shown to positively correlate with therapy responses in chronic myeloid leukemia (CML). However, only a few longitudinal studies exist and no randomized comparisons between two TKIs have been reported. Therefore, we prospectively analyzed the immune system of newly diagnosed CML patients treated with imatinib (n = 20) or bosutinib (n = 13), that participated in the randomized BFORE trial (NCT02130557). Comprehensive immunophenotyping, plasma protein profiling, and functional assays to determine activation levels of T and NK cells were performed at diagnosis, 3, and 12 months after therapy start. All results were correlated with clinical parameters such as Sokal risk and BCR-ABL load measured according to IS%. At diagnosis, low Sokal risk CML patients had a higher frequency of cytotoxic cells (CD8 + T and NK cells), increased cytotoxic potential of NK cells and lower frequency of naive and central memory CD4 + T cells. Further, soluble plasma protein profile divided patients into two distinct clusters with different disease burden at diagnosis. During treatment, BCR-ABL IS% correlated with immunological parameters such as plasma proteins, together with different memory subsets of CD4+ and CD8 + T cells. Interestingly, the proportion and cytotoxic potential of NK cells together with several soluble proteins increased during imatinib treatment. In contrast, no major immunological changes were observed during bosutinib treatment. In conclusion, imatinib and bosutinib were shown to have differential effects on the immune system in this randomized clinical trial. Increased number and function of NK cells were especially observed during imatinib therapy.

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