| 1. |
- Ericsson, Peter, et al.
(författare)
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ECL Cell Histamine Mobilization Studied byGastric Submucosal Microdialysis in Awake Rats:Methodological Considerations.
- 2003
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Ingår i: Pharmacology and Toxicology. - : Wiley. - 1600-0773 .- 0901-9928. ; 93:2, s. 57-65
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Tidskriftsartikel (refereegranskat)abstract
- The ECL cells are endocrine/paracrine cells in the acid-producing part of the stomach. They secrete histamine in response to circulating gastrin. Gastric submucosal microdialysis has been used to study ECL-cell histamine mobilization in awake rats. In the present study we assess the usefulness and limitations of the technique. Microdialysis probes were implanted in the gastric submucosa. Histological analysis of the stomach wall around the probe revealed a moderate, local inflammatory reaction 1-2 days after implantation; the inflammation persisted for at least 10 days. Experiments were conducted 3 days after the implantation. The "true" submucosal histamine concentration was determined by perfusing at different rates (the zero flow method) or with different concentrations of histamine at a constant rate (the no-net-flux method): in fasted rats it was calculated to be 87±5 (means±S.E.M.) nmol/l and 76±9 nmol/l, respectively. The corresponding histamine concentrations in fed rats were 93±5 and 102±8 nmol/l, respectively. With a perfusion rate of 74 mul/hr the recovery of submucosal histamine was 49%, at 34 mul/hr the recovery increased to 83%. At a perfusion rate below 20 mul/hr the microdialysate histamine concentration was close to the actual concentration in the submucosa. The ECL-cell histamine mobilization was independent of the concentrations of Ca2+ in the perfusion medium (0-3.4 mmol/l Ca2+). In one experiment, histamine mobilization in response to gastrin (10 nmol/kg/hr subcutaneously) was monitored in rats pretreated with prednisolone (60 mg/kg) or indomethacin (15 mg/kg). The two antiinflammatory agents failed to affect the concentration of histamine in the microdialysate either before or during the gastrin challenge, which was in accord with the observation that the inflammatory reaction was modest and that inflammatory cells were relatively few around the probe and in the wall of the probe. In another experiment, rats were given aminoguanidine (10 mg/kg) or metoprine (10 mg/kg) 4 hr before the start of gastrin infusion (5 nmol/kg/hr intravenously). Metoprine (inhibitor of histamine N-methyl transferase) did not affect the microdialysate histamine concentration, while aminoguanidine (inhibitor of diamine oxidase) raised both basal and gastrin-stimulated histamine concentrations. We conclude that microdialysis can be used to monitor changes in the concentration of histamine in the submucosa of the stomach, and that the inflammatory reaction to the probe is moderate and does not affect the submucosal histamine mobilization.
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| 2. |
- Kuhling, H, et al.
(författare)
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Expression of cyclins E, A, and B, and prognosis in lymph node-negative breast cancer
- 2003
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Ingår i: Journal of Pathology. - : Wiley. - 0022-3417. ; 199:4, s. 424-431
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Tidskriftsartikel (refereegranskat)abstract
- Unexpected outcomes in breast cancer demand a refinement of prognostic criteria. This study therefore investigated the prognostic relevance of cyclin expression in a cohort of 332 T1-T2 NO infiltrating ductal carcinomas with long-term follow-up (median 99 months). By univariate analysis, tumour size, histopathological grade, hormone receptor content, cyclin E, cyclin B, and the Ki-S5 (Ki-67) index significantly predicted disease-specific and metastasis-free survival. Cyclin A did not achieve statistical significance. In a multivariate analysis, both cyclin E [relative risk (RR) 2.01, p = 0.021] and cyclin B (RR 1.85, p = 0.033) were selected as independent prognosticators of metastasis-free survival when the Ki-67 index was omitted, but (only cyclin E expression was associated with disease-specific survival (RR 2.56, p = 0.006). When Ki-67 was included as a covariate, cyclin E lost its significance with respect to disease-specific survival but remained significant for metastasis-free survival. In an analogous analysis including Ki-67, the number of concurrently overexpressed cyclins did not attain statistical significance regarding disease-specific survival but was selected as the leading predictor of metastatic disease. It is concluded that combined overexpression of cyclins may imply genetic instability enhancing metastatic potential, but that survival ultimately depends on the proliferative activity of tumour cells. Copyright (C) 2003 John Wiley Sons, Ltd.
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| 3. |
- Rudolph, P, et al.
(författare)
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Differential prognostic impact of the cyclins E and B in premenopausal and postmenopausal women with lymph node-negative breast cancer
- 2003
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 105:5, s. 674-680
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Tidskriftsartikel (refereegranskat)abstract
- Searching for new prognostic factors, we investigated the influence of cyclin expression on breast cancer prognosis. A total of 273 archival tumor specimens from patients with pT1/pT2 NO breast cancers treated by surgery and local irradiation were immunostained for cyclins E, A and B. Outcome was evaluated as metastasis-free (MFS) and diseasespecific survival (DSS) over a median observation period of 99 months. In postmenopausal women, DSS was significantly predicted by cyclin E, and in premenopausal patients by cyclin B. No statistical significance was found for cyclin A. When the prognostic impact of cyclins was compared to that of standard prognostic indicators in a multivariate analysis, both cyclin E and cyclin B were selected as independent predictors of survival in postmenopausal and premenopausal patients, respectively. After inclusion of Ki-67 in the model, cyclin E lost its significance, whereas cyclin B remained the only independent prognostic factor with a hazard ratio of 4.5 (p = 0.026) for tumor-related death. Assessment of cyclin expression may, therefore, refine current prognostic models if considered in relation to menopausal status. The prognostic relevance of cyclins is likely attributable to an influence on proliferation, cell survival and genetic instability. Awareness of the molecular mechanisms leading to deregulated cyclin expression may guide decisions for risk-adapted therapy regimens.
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