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- Liu, Qing, et al.
(författare)
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Linomide and antibody-targeted superantigen therapy abolishes formation of liver metastases in mice.
- 2003
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Ingår i: European Surgical Research. - : S. Karger AG. - 0014-312X .- 1421-9921. ; 35:6, s. 457-463
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Tidskriftsartikel (refereegranskat)abstract
- Hematogenous spread of tumor cells and metastasis formation in the liver are insidious aspects of cancer progression and are not frequently amenable to curative treatment. We examined the effect of Linomide and antibody-targeted therapy against the formation of hepatic metastases in vivo. For this purpose, syngenic B16 melanoma cells transfected with GA733-2 (a human colon cancer cell surface antigen) were injected into a mesenteric vein of C57/Bl6 mice. To test bacterial superantigen (Sag) targeting for immunotherapy of liver metastases, we used genetically fused proteins consisting of SEA and a Fab moiety of a GA733-2 tumor-reactive antibody (C215Fab-SEA). Linomide dose-dependently reduced hepatic metastases, and at 300 mg/kg this reduction was more than 80%. Treatment with C215Fab-SEA decreased metastases formation by 49% and the combination of Linomide and C215Fab-SEA was found to completely abolish liver metastases (>99% reduction). Taken together, our novel data suggest that Linomide and antibody-targeted superantigen therapy individually markedly reduce and together abolish liver metastases. Considering that current therapy of hepatic metastases is mainly limited to surgical resection in a subgroup of patients, these findings indicate that Linomide alone or in combination with antibody-targeted superantigen may provide a novel approach against liver metastases.
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2. |
- Torkvist, L, et al.
(författare)
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Heparin protects against skin flap necrosis: relationship to neutrophil recruitment and anti-coagulant activity
- 2004
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Ingår i: Inflammation Research. - : Springer Science and Business Media LLC. - 1420-908X .- 1023-3830. ; 53:1, s. 1-3
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Tidskriftsartikel (refereegranskat)abstract
- Objective and design: Heparin has been shown to improve survival of surgical skin flaps. However, it is not known whether the protective effect of heparin is related to it's anticoagulative or anti-inflammatory effects. Methods: Surgical flaps were raised in the dorsal skin of Sprague-Dawley rats. Neutrophil recruitment was determined by measuring the tissue content of myeloperoxidase (MPO) and clotting time was estimated by assessment of activated partial thromboplastin time (APTT) in plasma. Results: Administration of heparin (150 U/kg) significantly increased skin flap survival from 44 % in vehicle-treated controls to 91 %. This heparin treatment increased APTT by 4.5 fold. However, administration of 150 U/kg of heparin had no effect on skin flap neutrophil recruitment. In contrast, we found that the polysaccharide fucoidan reduced MPO and also improved skin flap survival. Conclusions: In conclusion, we demonstrate that protective effect of clinically relevant doses of heparin correlates with its' ability to prolong clotting time and not to inhibition of neutrophil accumulation in the healing of skin flaps.
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