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Sökning: WFRF:(Bagge U)

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1.
  • Einarsdottir, Berglind Osk, 1979, et al. (författare)
  • A patient-derived xenograft pre-clinical trial reveals treatment responses and a resistance mechanism to karonudib in metastatic melanoma
  • 2018
  • Ingår i: Cell Death & Disease. - 2041-4889. ; 9:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Karonudib (TH1579) is a novel compound that exerts anti-tumor activities and has recently entered phase I clinical testing. The aim of this study was to conduct a pre-clinical trial in patient-derived xenografts to identify the possible biomarkers of response or resistance that could guide inclusion of patients suffering from metastatic melanoma in phase II clinical trials. Patient-derived xenografts from 31 melanoma patients with metastatic disease were treated with karonudib or a vehicle for 18 days. Treatment responses were followed by measuring tumor sizes, and the models were categorized in the response groups. Tumors were harvested and processed for RNA sequencing and protein analysis. To investigate the effect of karonudib on T-cell-mediated anti-tumor activities, tumor-infiltrating T cells were injected in mice carrying autologous tumors and the mice treated with karonudib. We show that karonudib has heterogeneous anti-tumor effect on metastatic melanoma. Thus, based on the treatment responses, we could divide the 31 patient-derived xenografts in three treatment groups: progression group (32%), suppression group (42%), and regression group (26%). Furthermore, we show that karonudib has anti-tumor effect, irrespective of major melanoma driver mutations. Also, we identify high expression of ABCB1, which codes for p-gp pumps as a resistance biomarker. Finally, we show that karonudib treatment does not hamper T-cell-mediated anti-tumor responses. These findings can be used to guide future use of karonudib in clinical use with a potential approach as precision medicine.
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2.
  • Nannmark, Ulf, 1958, et al. (författare)
  • Inhibition of leukocyte phagocytosis by serotonin and its possible role in tumor cell destruction.
  • 1992
  • Ingår i: Cancer letters. - : Elsevier. - 0304-3835 .- 1872-7980. ; 62:1, s. 83-6
  • Tidskriftsartikel (refereegranskat)abstract
    • Intraportal tumour cell (TC) injection activates platelets which release serotonin (5-HT). Thrombocytopenia or 5-HT blockade decrease the hepatic lodgement of the injected TCs. A hypothetical explanation of this is 5-HT inhibition of TC killing by phagocytes (e.g. leukocytes and Kupffer cells). In this study, leukocyte phagocytosis was analysed by a chemiluminescence technique at different 5-HT concentrations. Significant inhibition of phagocytosis occurred at 5-HT concentrations of 10(-4) M to 10(-8) M, with maximum inhibition at 10(-4) M. Comparable concentrations of 5-HT may be found locally in the liver during TC infusion, supporting the hypothesis that 5-HT has an inhibitory effect on phagocyte-mediated TC killing.
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4.
  • Bjursten, Lars Magnus, et al. (författare)
  • Joint inflammation in rabbits induced by preformed immune complexes
  • 1981
  • Ingår i: International Archives of Allergy and Applied Immunology. - : Karger. - 0020-5915. ; 64:1, s. 67-71
  • Tidskriftsartikel (refereegranskat)abstract
    • The rabbit knee joint was used to evaluate the inflammatory properties of immune complexes with different contents of antigen. Immune complexes made in vitro with antiserum from hyperimmunized rabbits and bovine serum albumin as antigen were injected into the joints. The reactivity of the individual animal was established by injection of normal rabbit serum into the contralateral joint. The number of leukocytes washed out from the joints at fixed intervals was used as a measure of the inflammatory properties of the immune complexes. With immune complexes formed at antigen excess the highest numbers of leukocytes, with a predominance of granulocytes, were found after 6 h of exposure. However, these complexes gave only weak complement activation in vitro, measured with a hemolysis assay. Complexes formed at optimal precipitation proportions gave high complement activation in vitro but only a small number of leukocytes in the joints at 6 h exposure. This finding may be explained by a rapid phagocytosis of the latter complexes while complexes formed at antigen excess are not readily phagocytized. This hypothesis is supported by the observation that higher leukocyte counts were found after shorter exposure times to complexes formed at optimal precipitation proportions than after exposure to complexes with antigen excess.
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5.
  • Bjursten, Lars Magnus, et al. (författare)
  • The kinetics of leucocyte migration into rabbit knee joints elicited by preformed immune complexes with different in vitro characteristics
  • 1983
  • Ingår i: Immunology. - : Wiley-Blackwell. - 0019-2805. ; 49:2, s. 205-213
  • Tidskriftsartikel (refereegranskat)abstract
    • Immune complexes were formed in vitro with antibodies obtained from rabbits immunized with bovine serum albumin in Freund's complete (FCA) or incomplete (FIA) adjuvant. The antibodies were mixed with different amounts of antigen. Immune complexes formed at maximum precipitation proportions were efficient in complement activation, whereas immune complexes formed at antigen excess had weak complement-activating properties. When injected into rabbit knee joints, the immune complexes formed at maximum precipitation proportions with FCA or FIA antibodies caused a moderate leucocyte migration into the joints with maximum cell counts 6-8 hr after injection. Injection into the joints of immune complexes formed with FCA antibodies at antigen excess induced a pronounced leucocyte migration with maximum numbers 18 hr after injection. Immunofluorescent studies indicated that these immune complexes became associated with the leucocyte membrane, whereas immune complexes formed at maximum precipitation proportions were found in the leucocyte granulae, indicating that only the complement-activating immune complexes were efficiently eliminated.
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6.
  • Blomqvist, G, et al. (författare)
  • Differences in lodgement of tumour cells in muscle and liver
  • 1988
  • Ingår i: Clinical and Experimental Metastasis. - : Springer. - 1573-7276. ; 6:4, s. 285-289
  • Tidskriftsartikel (refereegranskat)abstract
    • Differences in the lodgement of circulating tumour cells in various organs are considered an important factor in metastatic organ selection. The present vital microscopic studies show that the pattern of intravascular arrest of tumour cells in muscle after intra-arterial injection is similar to that observed earlier, in the liver, after intraportal injection. However, parallel isotope studies on the lodgement process (at 5 min and 3 h after injection) showed that the tumour cells trapped in the muscle microvasculature were destroyed at a higher rate than in the liver. Tumour cells kept in test tubes, and thus not being subjected to the shearing forces of the circulation, had a higher survival rate than cells trapped in the muscle. The results indicate that stronger retardation forces acting on the tumour cells in muscle (arterial dissemination) than in the liver (venous dissemination) may be one mechanism behind the increased tumour cell destruction in muscle.
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8.
  • Thomsen, P, et al. (författare)
  • Acute synovitis induced by preformed immune complexes
  • 1986
  • Ingår i: Scandinavian Journal of Rheumatology. - : Taylor & Francis. - 1502-7732. ; 15:2, s. 134-142
  • Tidskriftsartikel (refereegranskat)abstract
    • The morphology of acute immune complex (IC) elicited synovitis in rabbit knee joints was studied, as well as IC-induced leukocyte activation in vivo and in vitro. Acute synovitis was induced by intra-articular injection of in vitro preformed, complement activating bovine serum albumin (BSA)-anti-BSA IC. Within 30 min, migration of polymorphonuclear granulocytes (PMNGs) was observed. Scanning electron microscopy showed that adhering, apparently activated leukocytes were attached to the synovial lining, often forming clusters. Phagocytosis of IC was evident, as immunoglobulins were detected within the leukocyte cytoplasm by the direct immunofluorescence technique. At the peak accumulation of PMNGs, focal erosions of the synovial lining were observed. Later, monocytes and macrophages appeared and degenerated PMNGs were found, sometimes within the cytoplasm of large macrophages. Chemiluminescence experiments showed a maximum in vitro activation of leukocytes by complement activating IC formed near optimal precipitation proportions and in slight antigen excess, whereas IC in large antigen excess gave a smaller and later response.
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9.
  • Thomsen, P, et al. (författare)
  • Inhibitory effect of honey bee venom on immune complex mediated leukocyte migration into rabbit knee-joints
  • 1984
  • Ingår i: Agents and Actions. - : Birkhäuser Verlag. - 0065-4299. ; 14:5-6, s. 662-666
  • Tidskriftsartikel (refereegranskat)abstract
    • The anti-inflammatory effect of purified honey bee venom (HBV) was studied using a recently described animal model in which preformed immune complexes were injected into rabbit knee-joints. As little as a single injection of 1.2 micrograms HBV/kg body weight subcutaneously significantly reduced the immune complex induced joint inflammation as measured by reduction in leukocyte counts in the joint fluid. This decrease was obvious 3 and 6 but not 9 hours after induction of the inflammation. There was no significant effect on leukocyte random migration, chemotactic responsiveness or phagocytosis, indicating that HBV did not interfere with normal phagocyte motility and ingestion. The modifying effects by HBV on the inflammatory response to immune complexes in vivo is most likely due to interference with other components of the inflammatory response.
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10.
  • Thomsen, P, et al. (författare)
  • Proliferative synovitis in rabbit knee joints induced by antigen and preformed immune complexes
  • 1985
  • Ingår i: Scandinavian Journal of Rheumatology. - : Taylor & Francis. - 1502-7732. ; 14:3, s. 239-251
  • Tidskriftsartikel (refereegranskat)abstract
    • Knee joints of non-immunized rabbits were repeatedly injected with bovine serum albumin (BSA) and preformed BSA-anti-BSA immune complexes which had differing precipitation profiles and abilities to activate complement. Ten days after the last of six injections the antibody and lymphoproliferative responses to BSA were analysed and correlated to the degree of arthritis. Joint swelling, increased numbers of joint fluid leukocytes and morphological changes typical of proliferative synovitis were found only in those rabbits injected with a large dose of antigen or with immune complexes prepared in antigen excess of poor precipitation and complement-activating properties in vitro. The degree of arthritis correlated with the development of humoral and lymphoproliferative immune responses to BSA.
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