| 1. |
- 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. |
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| 3. |
- Swahn, Fredrik, et al.
(författare)
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Endoscopic retrograde cholangiopancreatography with rendezvous cannulation reduces pancreatic injury
- 2013
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Ingår i: World Journal of Gastroenterology. - : Baishideng Publishing Group Inc.. - 1007-9327 .- 2219-2840. ; 19:36, s. 6026-6034
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To examine whether rendezvous endoscopic retrograde cholangiopancreatography (ERCP) is associated with less pancreatic damage, measured as leakage of proenzymes, than conventional ERCP. METHODS: Patients (n = 122) with symptomatic gallstone disease, intact papilla and no ongoing inflammation, were prospectively enrolled in this case-control designed study. Eighty-one patients were subjected to laparoscopic cholecystectomy and if intraoperative cholangiography suggested common bile duct stones (CBDS), rendezvous ERCP was performed intraoperatively (n = 40). Patients with a negative cholangiogram constituted the control group (n = 41). Another 41 patients with CBDS, not subjected to surgery, underwent conventional ERCP. Pancreatic proenzymes, procarboxypeptidase B and trypsinogen-2 levels in plasma, were analysed at 0, 4, 8 and 24 h. The proenzymes were determined in-house with a double-antibody enzyme linked immunosorbent assay. Pancreatic amylase was measured by an enzymatic colourimetric modular analyser with the manufacturer's reagents. All samples were blinded at analysis. RESULTS: Post ERCP pancreatitis (PEP) occurred in 3/41 (7%) of the patients cannulated with conventional ERCP and none in the rendezvous group. Increased serum levels indicating pancreatic leakage were significantly higher in the conventional ERCP group compared with the rendezvous ERCP group regarding pancreatic amylase levels in the 4- and 8-h samples (P = 0.0015; P = 0.03), procarboxypeptidase B in the 4- and 8-h samples (P < 0.0001; P < 0.0001) and trypsinogen-2 in the 24-hour samples (P = 0.03). No differences in these markers were observed in patients treated with rendezvous cannulation technique compared with patients that underwent cholecystectomy alone (control group). Post procedural concentrations of pancreatic amylase and procarboxypeptidase B were significantly correlated with pancreatic duct cannulation and opacification. CONCLUSION: Rendezvous ERCP reduces pancreatic enzyme leakage compared with conventional ERCP cannulation technique. Thus, laparo-endoscopic technique can be recommended with the ambition to minimise the risk for post ERCP pancreatitis. (C) 2013 Baishideng. All rights reserved.
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| 4. |
- Thorlacius, Henrik
(författare)
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Mediator synergism in mast celldependent inflammation : role of histamine for leukocyte recruitment
- 1996
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of the present thesis was to study functional interactions between histamine and chemotactic mediators, and the role of histamine for leukocyte recruitment in mast cell-dependent inflammation. Leukocyte rolling, adhesion and emigration. and vascular permeability were studied in vivo by the use of intravital microscopy of the rat mesentery and hamster cheek pouch, and of a complementary histological approach in the undisturbed rat mesentery. Topical challenge with the mast cell secretagogue compound 48/80 increased leukocyte rolling fraction and decreased rolling velocity in post capillary venules of the exposed rat mesentery prepared for intravital microscopy. These effects were inhibited by pretreatment with a monoclonal antibody directed against P-selectin, but not by the combined treatment with H1- and H2-receptor antagonists (mepyramine and cimetidine). Topical application of histamine did not increase leukocyte rolling fraction or reduce rolling velocity once spontaneous leukocyte rolling had developed. In the undisturbed rat mesentery lacking spontaneous leukocyte rolling, it was found by the use of a histological approach that the accumulation of polymorphonuclear leukocytes (PMNL) induced by compound 48/80 was markedly inhibited by combined H1- and H2-receptor blockade. These findings indicate that mast cell activation induces P-selectin-dependent leukocyte rolling via the release of histamine in conjunction with other mediator(s). Moreover, compound 48/80 stimulation caused an increase in leukocyte adhesion which was also inhibited by the monoclonal antibody against P-selectin, illustrating a critical relationship between leukocyte rolling and adhesion. In the undisturbed rat mesentery, the H1-receptor antagonist (diphenhydramine) inhibited histamine-induced leukocyte rolling substantially, whereas two H2-receptor antagonists (cimetidine and ranitidine) were inactive in this respect. However, when cimetidine was added to the diphenhydramine treatment, the histamine response was further reduced. Moreover, in contrast to an H3-receptor agonist, stimulation with either an H1-receptor agonist or two different H2-receptor agonists was sufficient to provoke significant leukocyte rolling. These findings show that histamine-induced leukocyte rolling involves both H1- and H2-receptors, although the contribution of the H1-receptor appears to the be most important. The duration of the histamine-induced PMNL rolling was approximately 2 h. Furthermore, inhibition of NO synthesis did not affect the PMNL response to histamine stimulation. Pretreatment with the glucocorticoid dexamethasone almost abolished the histamine-induced leukocyte rolling in the rat mesentery, possibly via inhibition of the expression and/or function of PMNL P-selection ligand(s). Topical administration of histamine caused a four fold potentiation of chemoattractant-induced leukocyte adhesion in the exposed rat mesentery. On the other hand, the histamine challenge (which did not increase the fraction of rolling leukocytes) enhanced rolling leukocyte flux in a strictly blood flow-dependent way, caused a clear-cut increase in venular permeability and prolonged the adhesion of leukocytes provoked by chemoattractants. These effects (in addition to induction of P-selectin-dependent rolling) of histamine may contribute to the potentiating effect of histamine on chemoattractant-induced leukocyte adhesion. Furthermore, it was found that threshold doses of histamine could markedly potentiate chemoattractant-induced leukocyte adhesion in the hamster cheek pouch. Moreover, in immunized hamsters, treatment with aH1-receptor antagonist (mepyramine) in a concentration high enough to completely reverse the histamine-induced venular plasma leakage greatly reduced allergic leukocyte accumulation. In conclusion, these findings show that histamine plays an important role for leukocyte recruitment by interacting with chemotactic factors through a combination of distinct actions in the microcirculation, and that complete inhibition of histamine-induced microvascular actions may be necessary to reduce leukocyte accumulation in mast cell-dependent inflammation.
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| 5. |
- 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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