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Sökning: WFRF:(Willén Roger) > (2005-2009) > (2008) > Willén Roger

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1.
  • Fredin, Maria Fritsch, 1970, et al. (författare)
  • The application and relevance of ex vivo culture systems for assessment of IBD treatment in murine models of colitis
  • 2008
  • Ingår i: Pharmacological Research. - : Elsevier BV. - 1043-6618 .- 1096-1186. ; 58:3-4, s. 222-231
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to investigate the relevance of mouse ex vivo cultures as a first screening model for new therapeutic agents of Inflammatory Bowel Disease (IBD). Two murine models (dextran sodium sulphate (DSS)-induced colitis and Gαi2-deficient mice) and two anti-inflammatory agents (methyl-prednisolone and the proteasome inhibitor MG132) were evaluated. The in vivo effects of methyl-prednisolone were assessed in both models. Ex vivo colonic tissue from both mouse models were cultured in the presence or absence of the drugs and TaqMan Low-Density arrays were used to assess the regulation of inflammatory genes before and after drug treatment. Colitis induced a similar inflammatory gene profile in both mouse models in in vivo studies and in ex vivo cultures. The differences encountered reflected the different phases of colitis in the models, e.g. innate cytokine/chemokine profile in the DSS model and T cell related markers in Gαi2-deficient mice. After steroid treatment, a similar pattern of genes was suppressed in the two mouse models. We confirmed the suppression of inflammatory gene expression for IL-1β, IL-6 and iNOS in ex vivo and in vivo colons from both mouse models by quantitative RT-PCR. Importantly, the inflammatory responses in the murine ex vivo culture system reflected the in vivo response in the inflamed colonic tissue as assessed by changes in inflammatory gene expression, suggesting that the murine culture system can be used for validation of future IBD therapies.
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2.
  • Lindahl, Bengt, et al. (författare)
  • Adjuvant tamoxifen in breast cancer patients affects the endometrium by time, an effect remaining years after end of treatment and results in an increased frequency of endometrial carcinoma
  • 2008
  • Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 28:2B, s. 1259-1262
  • Tidskriftsartikel (refereegranskat)abstract
    • Tamoxifen is the most used adjuvant drug in breast cancer treatment. Its main action is as an anti-oestrogen, but in the endometrium of some patients it acts as an oestrogen. Some investigators have even reported an increased risk of developing endometrial carcinoma. The question of how to follow-up these patients and how to identify patients at risk of developing endometrial premalignant changes was investigated by the noninvasive ultrasound method. The follow-up of 292 patients from before the start of adjuvant treatment with tamoxifen and 94 without tamoxifen treatment was conducted at regular intervals. The changes in endometrial thickness as measured by ultrasound and histopathological changes are reported. A thicker endometrium was found in patients with receptor positive breast cancer even before the treatment with tamoxifen started. Cumulative increasing thickness was found during treatment and this thicker endometrium remained until almost 3 years after the end of treatment. If the endometrium was <3 mm after 3 months of treatment the probability that it would be thin after 5 years was high. An increased risk of developing endometrial carcinoma was found, however due to this regular follow-up the cancer was identified at an early stage.
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3.
  • Nilsson, Ingrid, et al. (författare)
  • Helicobacter ganmani infection associated with a spontaneous outbreak of inflammatory bowel-like disease in an IL-10-deficient mouse colony
  • 2008
  • Ingår i: Scandinavian Journal of Laboratory Animal Science. - 0901-3393. ; 35:1, s. 13-24
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: A breeding colony of IL-10 deficient B6.129P2-Il10(tmICgn/J) mice, kept under conventional conditions, developed an inflammatory bowel-like disease (IBD) with rectal prolapse and blood tinged diarrhoea. No clinical signs of disease were observed at the time of arrival to our animal house. These animals were originally planned to serve as a negative control group in an experimental infection study with Helicobacter species to investigate colonization of the murine gut. Results: A spiral-shaped, Gram-negative bacterium was isolated from the breeding mice colony. In a first group of six animals, tissue specimens from the liver, small and large intestines, faeces and blood, were analysed by culture, PCR-denaturing gradient gel electrophoresis (PCR-DGGE), species-specific PCR assays and DNA-sequencing, histology and serology. Helicobacter ganmani, but no other Helicobacter species, was isolated from the liver, small bowel, caecum, colon and faeces. We found inflammation in caeca, colon and livers, most pronounced in the caecal areas of culture positive mice with a severe typhlitis with cystic dilatation of glandular structures and irregular crypt architecture. Some animals showed a pronounced colitis with mucosal and sub-mucosal inflammatory infiltrates. Other animals displayed large lymphoid infiltrates in the livers and hepatitis. Tissue samples and sera from 18 additional animals from the same breeding colony were analysed by the same methods, except for culture. H. ganmani was identified by PCR in most tissue samples of the 18 additional animals as well. Sero-conversion to H. ganmani correlated well with histopathological changes. Conclusions: Our findings emphasize the importance of using Helicobacter-free animals to develop murine models of chronic hepatitis and colitis.
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