Comparison of the cytotoxic activities of chemotherapeutic drugs using a human bladder cancer cell line

Hepburn, Peter J.; Oliver, R. T. D.; Riley, Patrick A.; Hill, Bridget T.; Masters, J. R. W.

doi:10.1007/bf00571753

Cited by 13 publications

(3 citation statements)

References 28 publications

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“…The drug acts on neoplastic cells at phase G 0 , being able to interact not only with DNA but also with mRNA. In vitro studies on TCC of bladder cell lines, mitoxantrone was shown to be one of the most vigorous cytotoxic agents tested [36]. Intravesical mitoxantrone appears to hold promise as an effective chemoprophylactic compound.…”

Section: Mitoxantronementioning

confidence: 98%

Intravesical Therapy of Superficial Bladder Cancer

Moutzouris

2000

CPD

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Transurethral resection (TUR) of the superficial transitional cell carcinoma (TCC) of the bladder is known to be insufficient in controlling the disease because of the unacceptable rates of recurrence, progression and ultimate cystectomy. Adjuvant intravesical chemo-and/or immunotherapy is administered in an effort to enhance the efficacy of surgery alone. The initial tumor stage and grade, the multifocality of this cancer and the history of previous recurrences remain the determinant factors in survival. It is important to decide exactly which patients are at risk, and, therefore, do need treatment. Knowledge of the natural history of the disease will facilitate this decision making, although the natural history of TCC is largely unpredictable owing to tumor heterogeneity. Several cytotoxic and immune modifying agents have been used intravesically in different treatment schedules. However, despite their effectiveness, no consensus exists about the optimal antineoplastic regimen. The selection of the latter is a subject of continuous investigation. Intravesical treatment with cytotoxic drugs has been demonstrated to achieve an acceptable reduction in short- and intermediate-term recurrence rates, but has no proven ability in preventing disease progression to muscle-invasive cancer or prolonging survival. On the other hand, bacillus Calmette-Guerin (BCG) currently appears to be the most effective agent for intravesical use, especially in patients with high grade and stage neoplasms but the optimum strain, dosage and duration schedule have not been determined. Clinical trials have shown that BCG provides long-term protection from tumor recurrence, while there is evidence that it may favorably alter the progression rate of the disease with prolongation of survival. Toxicity of intravesical chemo- and immunotherapy still remains a major problem and attempts at reducing the dosage, and, thus, toxicity without affecting efficacy are underway. This review endeavors to present updated information on intravesical chemotherapy in treating superficial bladder cancer, the expanding role of intravesical immunotherapy, the recent work comparing various immunotherapeutic regimens with chemotherapeutic intravesical therapies, and the progress made towards achieving optimal treatment regimens.

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Section: Mitoxantronementioning

confidence: 98%

Intravesical Therapy of Superficial Bladder Cancer

Moutzouris

2000

CPD

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“…Experience is limited with cytostatic mitoxantrone and the immunomodulator IFN·-2b. Mitoxantrone is known to exhibit a steep cytotoxic activity when compared with other chemotherapeutic drugs in vitro [9]. Also, bladder cancer cells are found to express more recombinant IFN·-2b receptors than do normal cells [10].…”

Section: Discussionmentioning

confidence: 93%

Adjuvant Intravesical Mitoxantrone versus Recombinant Interferon-α after Transurethral Resection of Superficial Bladder Cancer: A Randomized Prospective Study

et al. 2004

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Objective: To determine the efficacy and safety of two different doses of intravesical mitoxantrone and of recombinant interferon-α (IFNα-2b), instilled after transurethral resection (TUR) of superficial transitional cell carcinoma (TCC) of the bladder. Material and Methods: 208 patients (mean age 62.05 years) with primary or recurrent superficial (TaG1, T1G1, T1G2) bladder cancer were randomly allocated into four groups, after TUR of all visible tumors. Group A (45 patients) received no further therapy; group B (56 patients) received 10 mg of mitoxantrone (6 weekly and 20 fortnightly instillations), group C (54 patients) 20 mg of mitoxantrone (3 fortnightly and 10 monthly instillations) and group D (53 patients) received 100 MU of IFNα-2b (8 weekly, 8 fortnightly and 6 monthly instillations). Results: During the follow-up (mean 21.09 months), 29 (64.44%) patients in group A had recurrence, compared with 19 (33.92%) in group B, 17 (31.48%) in group C and 15 (28.3%) patients in group D (p < 0.005). Furthermore, the differences in simple recurrence rates were statistically more significant (p < 0.05), when group A was compared with the three other groups in the terms of T1G2, recurrent and multiple neoplasms. Twenty-nine patients (10, 7, 8, and 4 in groups A–D) experienced tumor progression, and the differences between the four groups were not statistically significant (p > 0.05). The mean recurrence time was 9.03 months in group A, 13.74 in group B, 14.24 in group C and 17.4 months in group D (p < 0.001), and the recurrence rate per 100 patient-months was 4.39, 1.57, 1.48 and 1.06, respectively (p < 0.05). Toxicity (grade 1–3) was recorded in 23.21% in group B, in 31.48% in group C and in 9.43% in group D (p < 0.01). Conclusion: The two doses of mitoxantrone resulted in similar efficacy for the prevention of superficial bladder cancer recurrences, with the dose of 10 mg of mitoxantrone being related to fewer side effects. In comparison with mitoxantrone, the adjuvant intravesical immunotherapy with 100 MU of IFNα-2b showed a better combination of efficacy and safety.

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“…The continuous cell lines T24 and RT112 were both derived from transitional cell carcinomas of the human bladder and were grown as monolayers using conditions described elsewhere (Hepburn et al, 1985). The T24 cells were almost twice as sensitive (IC, 7.6pg/ml) as RT112 cells (ICw 14.4pg/ml) after a 1 h exposure to a cytotoxic range of concentrations of cisplatin.…”

Section: U Kmentioning

confidence: 99%

Characterization of cisplatin-induced DNA damage in human bladder tumour cell lines

Bedford

Masters

Hill

1986

Biochemical Society Transactions

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sera and aliquots assayed for EH activity. None of the clones expressed more activity than the mouse control cells. When extracts were treated with the anti-human antiserum, however, no greater reduction in EH activity occurred than occurred with the mouse cell pellets. It can be concluded, therefore, that none of the hybrids was expressing human EH activity. There are several possible explanations for this. Firstly, the gene coding for human EH could be located on chromosome 6. It has proved impossible to test for this to date since all clones examined segregated this chromosome. It could also be possible that either chromosome 3 or 22 was segregated from these clones. Finally, it may be that the human EH gene was present in some of these clones but was not expressed. This has been reported for tyrosine aminotransferase expression in hybrid cells but is not the case for aryl hydrocarbon hydroxylase or glutathione S-epoxide transferases (Benedict er a/., 1972; Silberstein & Shows, 1982). Further work is in progress to test these possibilities.

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Comparison of the cytotoxic activities of chemotherapeutic drugs using a human bladder cancer cell line

Cited by 13 publications

References 28 publications

Intravesical Therapy of Superficial Bladder Cancer

Intravesical Therapy of Superficial Bladder Cancer

Adjuvant Intravesical Mitoxantrone versus Recombinant Interferon-α after Transurethral Resection of Superficial Bladder Cancer: A Randomized Prospective Study

Characterization of cisplatin-induced DNA damage in human bladder tumour cell lines

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