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  • 1
    ISSN: 1434-0879
    Keywords: Key words Superficial bladder cancer ; Bioluminescence ; Retinoids ; Cancer therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Retinoids have been shown to have activity in both preclinical and clinical bladder cancer studies but their exact role in its treatment and prevention remains obscure. In this study cytostatic activity of a novel 9-cis-retinoic acid (9-cis-RA) was compared with two other retinoids: tretinoin and isotretinoin, in three different bladder cancer cell lines: RT4 (well differentiated), 5637 (moderately differentiated) and T24 (poorly differentiated). The three retinoids were incubated at concentrations of 0.3, 3 and 30 μg/ml with bladder cancer cells in microtitre plates for 3 and 6 days. The cytostatic effect was estimated by using luminometric measuring of ATP activity of viable cells in suspension. Compared with the older retinoids, tretinoin and isotretinoin, the highest concentration of 9-cis-RA had a cytostatic efficacy in all three bladder cancer cell lines tested. A clear dose–response relationship was observed in isotretinoin-treated cultures after 6 days and in all 9-cis-RA-treated cultures. Tretinoin was either ineffective or had a stimulating effect on poorly differentiated tumour cells. To conclude, isotretinoin and 9-cis-RA had a cytostatic effect on human bladder cancer cells in vitro. However, the possibility of stimulating cancer growth at small doses, at least with tretinoin, and toxicity at high doses must be considered when planning clinical trials.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1434-0879
    Keywords: Bladder cancer ; BCG ; Interferon-α ; Cytostatic activity in vitro
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The cytostatic activity of five Bacillus Calmette-Guérin (BCG) strains (Pasteur, Evans, Tice, RIVM and Connaught) on human transitional cell cancer T24 cells was examined. A striking effect was noted even in 2-day cultures, and the effect was more pronounced when the cells were incubated for 5 days with different BCG strains alone. The concentrations needed were about the same as those used in clinical practice (109 colonyforming units of Pasteur strain in 100 ml buffered saline solution). Combination with mitomycin C or interferon-α-2b potentiated the cytostatic effect. A slight difference in cytostatic activity between different BCG strains was found.
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  • 3
    ISSN: 1434-0879
    Keywords: Key words Superficial bladder cancer ; p21WAF1/CIP1 ; Prognosis ; Cyclin D1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Immunoreactivity of p21WAF1/CIP1 and cyclin D1 proteins was assessed in a cohort of 207 patients with superficial (pTa-pT1) bladder cancer followed up for a mean of 4.9 years. The results of the immunostainings were compared with T category, WHO grade, tumor cell proliferation rate (MIB-1 score), the expressions of p53 and bcl-2 as well as survival. Sixty-eight percent and 75% of the tumors were p21WAF1/CIP1 positive (≥5% of cells positive) and cyclin D1 positive (≥10% of cells positive), respectively. The p21WAF1/CIP1 expression was related to cyclin D1 immunolabelling (P 〈 0.001) but not to the other variables studied. The expression of cyclin D1 was inversely associated with T category (P=0.001), WHO grade (P=0.006), MIB-1 score (P=0.014), p53 expression (P=0.001), and bcl-2 (P=0.011) immunoreactivity. In univariate analysis, T category (P=0.0001), WHO grade (P 〈 0.0001), MIB-1 score (P 〈 0.0001), bcl-2 (P=0.0092), p53 (P=0.0016) and p21WAF1/CIP1 (P=0.009) expressions were significant prognostic factors with regard to tumor progression, whereas cyclin D1 was without any prognostic significance (P=0.1). Out of 123 p21 positive tumors 21 progressed, whereas only 2 out of 58 p21 negative tumors progressed. In multivariate analysis, the MIB-1 score was the only independent predictor of cancer-specific survival (P=0.03), whereas tumor grade (P=0.002) and cyclin D1 expression (P=0.04) were independent predictors of tumor recurrence. Only the WHO grade (P=0.04) retained its prognostic value indicating the risk of progression. We suggest that in superficial bladder cancer p21WAF1/CIP1 and cyclin D1 immunohistochemistry provide no additional prognostic information compared with already established prognostic factors for predicting the risk of progressive disease.
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  • 4
    ISSN: 1434-0879
    Keywords: Superficial bladder cancer ; MIB-1 ; S-phase fraction ; M/V index
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cell proliferation of transitional cell bladder cancer (TCC) was determined by MIB-1 immunolabeling, volume-corrected mitotic index (M/V index) and S-phase fraction measurement in 207 patients with superficial (Ta-T1) bladder cancer. The results were compared to T category, WHO grade and DNA-ploidy. The MIB-1 score was related to T category (P〈0.001), WHO grade (P〈0.001), DNA ploidy (P〈0.0001), M/V index (P〈0.0001) and fraction of cells in S phase (P〈0.0001). The mean MIB-1 score was 6.37% for G1, 14.59% for G2 and 28.59% for G3 carcinomas (P〈0.001). The MIB-1 score for Ta tumors was 9.24% and for T1 tumors 25.34% (P〈0.001). The M/V index was 3.9 for G1, 11.5 for G2 and 25.9 for G3 tumors (P〈0.0001). The M/V index for Ta tumors was 6.4 and 25.3 for T1 tumors (P〈0.0001). WHO grade 1 tumors had 7.7%, grade 2 tumors 13.8% and grade 3 tumors 21.8% of cells in S phase (P〈0.001). Of grade 1 tumors, 97% were diploid and 3% aneuploid, and 78% of grade 2 tumors were diploid and 22% aneuploid. Of grade 3 tumors, 30% were diploid and 70% aneuploid (P〈0.001). Of Ta tumors, 92% were diploid and 8% aneuploid, respectively, whereas 40% of T1 tumors were diploid and 60% aneuploid (P〈0.0001). The results show that quantitative cell proliferation indices are associated with T category and WHO grade in superficial bladder cancer. The prognostic value of the S-phase fraction and mitotic index has been demonstrated in several previous analyses of prognostic factors while the value of MIB-1 score on bladder cancer prognosis remains to be established in further follow-up studies.
    Type of Medium: Electronic Resource
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