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  • 1
    ISSN: 1437-7799
    Keywords: Key words Peritoneal dialysis ; Fibrotic process ; Collagen gel contraction ; Cytokines ; IL-6 ; TGF-β1 ; RT-PCR ; Wound healing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. In a fibrotic process the interaction between resident cells and extracellular matrices is important in the control of cell function. Our preliminary experiments indicated that concentrated peritoneal dialysis effluent caused contraction of collagen matrices by peritoneal fibroblasts. In this study we attempted to mimic the inflammatory milieu present during peritoneal inflammation and assessed its effect on fibroblast activation. Methods. Rat peritoneal fibroblasts (RPFB) were isolated by a time-elapsed differential subculture from mixtures of primary cultures of peritoneal resident cells, and then cultured in collagen matrices. Various inflammatory mediators, known to be present in the peritoneal cavity during inflammation, (i.e., interleukin-6 [IL-6], IL-1β, and tumor necrosing factor (TNF)α were added to three-dimensional-RPFB cultures (1 × 105/ml) prior to their incubation for either 48 h or 10 days. The contractility of collagen matrices over this time period was monitored, as was the expression of transforming growth factor (TGF)-β1 mRNA. Experimental conditions were: (i) control gels, (ii) gels with IL-6, (iii) gels with IL-1β, (iv) gels with TNFα, (v) gels with each cytokine plus glucose (90 mM). Results. With 48 h stimulation, a greater than tenfold increase in TGF-β1 mRNA expression (measured as the ratio to TGF-β1/glyceraldehyde 3-phosphate dehydrogenase [GAPDH] mRNA) was observed compared with the control, and this was accompanied by gel contraction. With 10-day stimulation, both IL-1β and TNFα suppressed the expression of TGF-β1 mRNA as well as suppressing gel contraction. There was a 30% to 40% gel contraction accompanied by elongation of RPFB morphology in the IL-6 and control groups. The addition of glucose promoted the extension of RPFB and gel contraction by up to 60% in both the IL-1β- and TNFα-supplemented groups. Conclusion. These in vitro findings suggest that a balance of inflammatory cytokines influences rat peritoneal fibroblast (RPFB) gene expression, causing changes in the interaction between extracellular matrices and peritoneal fibroblasts.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1437-7772
    Keywords: Key words Esophageal carcinoma ; Chemotherapy ; p53 ; p21 ; bcl-2 ; bax
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. Chemotherapy is an important component of the multimodal approach to the treatment of advanced esophageal squamous cell carcinoma. Methods. We investigated the associations between p53, p21 (Waf1), bcl-2, and bax expression and response to chemotherapy (cisplatin + 5-fluorouracil + leucovorin) in 43 patients with advanced esophageal squamous cell carcinoma. The expression of p53, p21 (Waf1), bcl-2, and bax proteins was analyzed immunohistologically in pretreatment biopsy and post-treatment resected specimens. Results. The 23 patients who had objective evidence of either a complete response (CR) or a partial response (PR) to chemotherapy survived for significantly longer than the 20 patients who had no response (NR). The expression of p53, p21 (Waf1), bcl-2, and bax was detected in 26 (61%), 12 (28%), 6 (14%), and 19 (44%) of the pretreatment biopsy specimens, respectively. The response to chemotherapy was not independently associated with the expression of any of these proteins. However, in the 26 patients with p53-expressing tumors, the response rate was 80% in patients whose tumor also expressed p21, whereas it was 19% in those whose tumor did not coexpress p21. No change in p53 expression was observed before and after chemotherapy, except in 1 patient; however, p21 expression appeared to be induced by chemotherapy in 5 patients. Patient survival was also not independently associated with the expression of any of these proteins. However, patients with p53-negative or p21-positive tumors had a better response to chemotherapy and survived for longer than those with p53-positive and p21-negative tumors. Conclusion. p53 and p21 expression in biopsy specimens obtained before chemotherapy could be useful predictors of response and survival in patients with advanced esophageal squamous cell carcinoma.
    Type of Medium: Electronic Resource
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