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  • 1
    Electronic Resource
    Electronic Resource
    Heart valve dysfunction resulting from cellular rejection in a novel heterotopic transplantation rat model (2000)
    Springer
    Transplant international 13 (2000), S. S528 
    Details
    ISSN: 1432-2277
    Keywords: Key words Implantation model ; Aortic valves ; Valve dysfunction ; Rejection ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Structural failure of heart valve allografts may be related to technical factors or immunological reactions. To circumvent nonimmunological factors a new rat implantation model was developed to study whether alloreactivity results in histopathological changes and valve dysfunction. Syngeneic (WAG-WAG, DA-DA) and allogeneic (WAG-BN, WAG-DA) transplantation was carried out using this new technique, and the function of explanted valves was assessed 21 days later by retrograde comptence testing. Additionally, grafts were examined using standard histological and immunohistochemical techniques. There was no leakage during retrograde injection in nine of tem syngeneic and two of ten allogeneic grafts. Microscopically, syngeneic valves appeared normal without fibrosis or intimal thickening, although CD8+ lymphocytes and macrophages were found in necrotic myocardial rim and adventitia. In contrast, allogeneic valves were deformed and noncellular, with extensive infiltration of CD4+, CD8+ and CD68+ cells in adventitia and media. Absence of fibrosis and intimal thickening in syngeneic transplanted valves indicated circumvention of nonimmunological factors. Allogeneic valve transplantation induces cellular infiltration in the graft with subsequent graft failure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001470050395
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  • 2
    Electronic Resource
    Electronic Resource
    Laparoscopic surgery in the rat (1996)
    Springer
    Surgical endoscopy and other interventional techniques 10 (1996), S. 490-494 
    Details
    ISSN: 1432-2218
    Keywords: Laparoscopy ; Rat ; Tumor take ; Weight loss ; Pneumoperitoneum ; Bowel resection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: The ability of laparoscopic techniques to treat malignant disease is controversial. We developed a rat model to assess metabolic and oncological effects of laparoscopic surgery. Methods: Experiment I. The postoperative body weight in 10 rats having laparoscopic bowel resection (group I), 10 rats having open bowel resection (group II) and 5 rats having anesthesia only (group III) was determined. Experiment II. Tumor take was scored in 11 rats having laparoscopic bowel resection (group IV), 11 rats having open bowel resection (group V), 6 rats having CO2 pneumoperitoneum without bowel resection (group VI) and 6 rats having anesthesia only (group VII). All rats had CC531 cancer cells injected intraperitoneally postoperatively. Results: Experiment I. Body weight loss in group I compared to group II (p〈0.036). Rats of group III lost no weight postoperatively. Experiment II. Tumor take was less in the subcutis (p=0.005), parietal peritoenum (p〈0.001) and bowel anastomosis (p=0.021) in group IV compared to group V. Tumor take was significantly greater at all sites except for subcutis in group VI compared to VII (all p〈0.022). Conclusions: Laparoscopic surgery is associated with less postoperative weight loss and less tumor take compared to open surgery. CO2 insufflation appears to increase tumor take.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00188392
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  • 3
    Electronic Resource
    Electronic Resource
    The chemosensitizer cyclosporin A enhances the toxic side-effects of doxorubicin in the rat (1994)
    Springer
    Journal of cancer research and clinical oncology 120 (1994), S. 533-538 
    Details
    ISSN: 1432-1335
    Keywords: Chemosensitizer ; Cyclosporin A ; Doxorubiein ; Multidrug resistance ; Toxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract the feasibility of using chemosensitizers in the circumvention of P-glycoprotein-mediated multidrug resistance has been shown in many studies. We recently reported on the chemosensitizing effect of cyclosporin A (CsA) on doxorubicin in a rat solid tumour model. Using the same experimental design we investigated the side-effects of the combination treatment. During the 35-day experiment doxorubicin treatment caused dose-dependent weight loss, which was enhanced by combination treatment with CsA. The main doxorubicin-related side-effects were myelosuppression (transient leucopenia and thrombopenia) and nephrotoxicity. Damage to the kidney was severe, leading to a nephrotic syndrome and resulting in ascites, pleural effusion, hypercholesterolaemia and hypertriglyceridaemia. These toxicities were enhanced by the addition of the chemosensitizer CsA. Mild doxorubicin-related cardiomyopathy and minimal hepatotoxicity were seen on histological examination. There were no signs of enhanced toxicity of the combination treatment in tissues with known high expression levels of P-glycoprotein, like the liver, adrenal gland and large intestine. CsA had a low toxicity profile, as it only caused a transient rise in bilirubin. In conclusion, the chemosensitizer CsA enhanced the side-effects of the anticancer drug doxorubiein without altering the toxicity pattern. There was no evidence of a therapeutic gain by adding CsA to doxorubicin, compared to single-agent treatment with doxorubicin in 25%–33% higher doses, because of the enhanced toxicity of the combination treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01221030
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  • 4
    Electronic Resource
    Electronic Resource
    In vitro and in vivo chemosensitizing effect of cyclosporin A on an intrinsic multidrug-resistant rat colon tumour (1993)
    Springer
    Journal of cancer research and clinical oncology 119 (1993), S. 609-614 
    Details
    ISSN: 1432-1335
    Keywords: Cyclosporin A ; Multidrug resistance ; P glycoprotein ; Chemosensitizing ; In vivo
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Colon tumours are intrinsically resistant to chemotherapy and most of them express the multidrug transporter P glycoprotein (Pgp). Whether this Pgp expression determines their resistance to anticancer agents in patients is not known. We report here on the reversibility of intrinsic multidrug resistance in a syngeneic, solid tumour model. CC531 is a rat colon carcinoma that expresses Pgp, as was shown with the monoclonal antibody C-219. In vitro the sensitivity to doxorubicin, daunorubicin and colchicine was enhanced by the addition of the chemosensitizers verapamil and cyclosporin A (CsA), while the sensitivity to cisplatin was not enhanced. In a daunorubicin accumulation assay verapamil and CsA enhanced the daunorbicin content of CC531 cells. In vivo CsA was injected intramuscularly for 3 consecutive days at a dose of 20 mg kg−1 day−1. This resulted in whole-blood CsA levels above 2 μmol/l, while intratumoral CsA levels amounted to 3.6 μmol/kg. In a subrenal capsule assay the maximal tolerable dose of doxorubicin (4 mg/kg) significantly reduced tumour growth. Doxorubicin at 3 mg/kg was not effective, but in combination with CsA this dose was as effective as 4 mg/kg doxorubicin. These experiments show that adequate doses of the chemosensitizing drug CsA can be obtained in vivo, resulting in increased antitumoral activity of doxorubicin in vivo. The in vitro and in vivo data together suggest that the chemosensitization by CsA is mediated by Pgp. This finding may have implications for the application of CsA and CsA-like chemosensitizers in the clinical setting.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01372724
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  • 5
    Electronic Resource
    Electronic Resource
    Combined effect of 5-fluorouracil and interferon on experimental liver metastases of rat colon carcinoma (1985)
    Springer
    Journal of cancer research and clinical oncology 109 (1985), S. 156-158 
    Details
    ISSN: 1432-1335
    Keywords: Experimental liver metastases ; Colon tumor ; 5-Fu ; Interferon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The combined effect of 5-Fluorouracil (5-Fu) and partially purified rat interferon (RIFN) was assessed on experimental liver metastases of a transplantable colon tumor in rats. Treatment was given for 8 weeks and started 1 week after inoculation into the portal vein of 5×105 tumor cells. Administration of 105 units RIFN/kg/day for 7 days, in alternate weeks, had no effect on the number or size of liver metastases as judged by laparotomy on days 30 and 50, whereas treatment with 5-Fu at a dose of 15 mg/kg once a week had a moderate but significant inhibitory influence. The combined administration of RIFN and 5-Fu led to earlier development of liver metastases than in the control group. There was no difference in survival time between the control group and the RIFN-treated group; all animals died within 20 weeks after tumor cell injection. However, three of eight animals in the 5-Fu group and, surprisingly, four of ten animals in the RIFN+ 5-Fu group survived for more than 20 weeks and were found to be free of tumor when inspected after 175 days. The data indicate that 5-Fu, given either alone or combined with RIFN, is effective in about 40% of cases, and further suggest that RIFN has tumor-enhancing properties in those animals in which treatment with 5-Fu has no antitumor effect.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00391891
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  • 6
    Electronic Resource
    Electronic Resource
    Cyclosporin A enhances locoregional metastasis of the CC531 rat colon tumour (1997)
    Springer
    Journal of cancer research and clinical oncology 123 (1997), S. 21-24 
    Details
    ISSN: 1432-1335
    Keywords: Cyclosporin A ; Growth promotion ; Metastasis ; Multidrug resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The immunosuppressive drug cyclosporin A has been evaluated recently in phase II trials in cancer therapy as a reverter of P-glycoprotein-mediated multidrug resistance. As an immunosuppressive agent, cyclosporin A potentially can enhance tumour growth. We investigated this potency of cyclosporin A in the weakly immunogenic CC531 colon adenocarcinoma model, using the same dose that had previously been shown to intensify the antitumour activity of doxorubicin in vivo. In vitro cyclosporin A caused no growth acceleration and only in high doses was growth inhibition of CC531 cells observed. In vivo no evidence of growth enhancement was found in short-term assays but, after 4 weeks, rats treated with cyclosporin A had a significantly higher tumour load, mainly consisting of locoregional metastases. These experiments in the CC531 tumour model show that cyclosporin A, used as a reverter of multidrug resistance, may produce short-term improvement of antitumour activity but may also induce enhancement of tumour metastasis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01212610
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