The side-effect profile of toremifene resembles that of tamoxifen. The efficacy of toremifene seems to be no less than that of tamoxifen. The trend for fewer breast cancer recurrences in the ER-positive subgroup is encouraging, but a longer follow-up is needed to confirm this.
Differentiated thyroid carcinomas (DTC) (papillary, follicular and follicular type of papillary) have a favourable prognosis, but a proportion of patients develop recurrences and eventually die of the disease. Various prognostic factors have been identified and been used to create the current staging classifications (AGES, AMES, MACIS, EORTC, UICC-TNM). We examined 499 DTC patients retrospectively to validate known prognostic factors that enable them to be recognised as having either a low or a high risk of death related to a recurrence of DTC, by reference to the current staging classifications. Sixty-nine of them (14%) had local or distant recurrences, the mean time to recurrence being 7.7 years. The 10-year disease-free survival rate was 80%, and the ten-year overall survival rate for the entire group was 91%, with a mean survival time of 8.7 years. Male gender, a follicular type of tumour, larger tumour size, extrathyroidal invasion outside the capsule and nodal metastases were all related to a higher incidence of tumour recurrence, and the follicular type of histology, age > 45 years, larger tumour size and local invasion entailed poorer survival. The AMES and to some extent the EORTC classification were not reproducible in this material, mainly because some prognostic variants were no longer encountered or were insufficient in number to allow reliable conclusions to be drawn. The MACIS staging classification leaves the definition of the intermediate and high risk groups too wide and is therefore not very reliable. Pooling of stages I and II improved the relevance of the TNM classification. All the current staging classifications are able to discern a low risk DTC group well. We achieved a highly accurate definition of risk in the present material using only two parameters, age (cut-off value 50 years) and extracapsular invasion of the thyroid gland.
NOTE.-Phosphomannomutase and protein were measured as described elsewhere (Van Schaftingen and Jaeken 1995; Jaeken et al. 1997a). Phosphomannose isomerase was assayed at 30ЊC in a reaction mixture (1 ml) containing 50 mM Hepes, pH 7.1, 5 mM MgCl 2 , 25 mM KCl, 1 mM dithiothreitol, 0.6 mM NAD ϩ , 0.5 mM mannose 6phosphate, 2.5 U/ml glucose 6-phosphate dehydrogenase from Leuconostoc mesenteroides, and 10 mg/ml phosphoglucose isomerase with 10 ml of an extract containing 5-20 mg protein/ml. Control and PMM deficient measures are mean values ע SD. Where two data are given, the values were obtained on two different subcultures.
Summary We determined nuclear DNA content from 308 archival paraffin-embedded malignant breast tumours and evaluated the survival of the patients by univariate and multivariate statistical analyses. The overall 8-year survival rate of stage I-III breast cancer patients was 74.3% in DNA-diploid and 51.2% in DNA-aneuploid tumours (P<0.0001). DNA ploidy had prognostic significance in both node-negative and node-positive breast cancer Dowle et al., 1987;Kallioniemi et al., 1987a) and the content of oestrogen and progesterone receptors (Bichel et al., 1982;Moran et al., 1984;Coulson et al., 1984;Horsfall et al., 1986;Kallioniemi et al., 1987a). Whether DNA ploidy is an independent prognostic indicator or merely related to other prognostic factors is unclear (McGuire & Dressler, 1985;Cornelisse et al., 1987;Dowle et al., 1987).In the present study we evaluated the clinicopathological correlations and prognostic value of DNA DNA flow cytometry Paraffin-embedded tumours were processed for DNA flow cytometry by a previously described modification (Kallioniemi et al., 1987a) of the method of Hedley and coworkers . Briefly, 50 jgm sections from the paraffin-embedded tumours were dewaxed with xylene, rehydrated and digested overnight with trypsin. One to 6 sections from different parts of the primary tumour were processed for DNA flow cytometry. The nuclear suspension was stained with ethidium bromide, digested with RNAase and analysed with an EPICS C flow cytometer using 488 nm excitation. DNA index of aneuploid peaks and the coefficient of variation (CV) of all DNA peaks were Correspondence: O.-P. Kallioniemi.
Early clinical experience with a robotic-assisted angioplasty system demonstrated feasibility, safety, and procedural effectiveness comparable to manual operation. In addition, the total operator exposure to radiation was significantly low. A larger study is warranted to verify the safety and effectiveness of robotic-assisted percutaneous coronary intervention.
The antitumor effects of a new antiestrogen, Fc-1157a have been studied in vitro and in vivo. In vitro the effect of Fc-1157a was comparable to that of tamoxifen. The effect was dose-dependent, and at concentrations higher than 10(-6) mol/1 Fc-1157a induced real cell death of the MCF-7 cells. In DMBA-induced mammary cancer in rats Fc-1157a decreased the number of new tumors and inhibited the growth of existing tumors, these effects being statistically highly significant. The ratio of growing tumors to stable and regressing tumors was significantly decreased. Although these effects were slightly stronger with Fc-1157a than with tamoxifen, the difference between these two compounds was not statistically significant. Murine uterine sarcoma, an estrogen receptor-negative tumor, was resistant to tamoxifen, but was statistically significantly inhibited by high doses (100 and 200 mg/kg-1 day-1 for 5 days) of Fc-1157a. The antitumor effects of Fc-1157a are due mainly to the antiestrogenic activity. At high concentrations in vitro and at high doses in vivo Fc-1157a exerts antitumor effects some of which are different from those of tamoxifen and are directed even against estrogen receptor-negative tumors. The exact mechanism of the observed cytolytic effect at high doses is unknown.
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