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At least 451 records · Page 25Linked to original sources
PubMed2002

Progesterone: a novel adjunct to intravesical chemotherapy.

OBJECTIVE: To investigate the effect of progesterone on multidrug-resistant urothelial cell lines, as the failure of intravesical chemotherapeutic drugs is often caused by multidrug resistance (MDR), mediated by the drug efflux pump P-glycoprotein (PGP), the function of which can be down-regulated by various compounds including steroid hormones. MATERIALS AND METHODS: Two urothelial cell lines (RT112S and MGH-U1S) and their MDR sublines (RT112R, to cisplatin; and MGH-U1R, a cell line expressing PGP) were used to assess the cytotoxic effects of progesterone, epirubicin and their combination. Cytotoxicity was assessed using a tetrazolium-based assay and in situ confocal microscopy. RESULTS: Cell lines sensitive to epirubicin (MGH-U1S, RT112S and RT112R) required a much lower dose of epirubicin to kill half the cells than did the MDR cell line. Progesterone was intrinsically cytotoxic to all cell lines with little difference among them. Combined therapy had no cumulative effect on epirubicin-sensitive cell lines, but reversed MDR in the MGHU1R cell line, both assessed by confocal microscopy and by the tetrazolium assay. CONCLUSIONS: Progesterone can reverse MDR in urothelial cells in vitro. This, combined with its effects on cell differentiation and apoptosis, together with its safety and tolerability compared to other MDR agents, suggests it may be a valuable adjunct to intravesical chemotherapy.

Administration, Intravesical↗
PubMed1988

The induction of bladder tumors in F344 rats by intravesicular administration of some nitrosamines.

Three nitrosamines, metabolically related and formed in vivo from the bladder carcinogen nitrosomethyl-n-octylamine, were administered to groups of 12 female F344 rats by intraurethral instillation twice a week for 30 weeks. All three compounds induced tumors in the urinary bladder. Nitrosomethyl-2-oxopropylamine at 10 mg/ml was the most potent, causing death of half of the animals with tumors at 43 weeks, following a total dose of 1.0 mmol; most of the rats also had tumors of the nasal mucosa, and there were some tumors of the kidney and kidney pelvis. Nitrosomethyl-2-hydroxypropylamine at 10 mg/ml (total dose 1.0 mmol) was much less effective, the median week of death being 83 weeks. In addition to bladder tumors, this group had tumors of the nasal mucosa, esophagus, and kidney. Nitrosomethyl-3-carboxypropylamine at 75 mg/ml and a total dose of 6.2 mmol per rat induced a high incidence of bladder tumors and tumors of the kidney pelvis, but not tumors of the nasal mucosa; the median week of death for this group was 55 weeks. It is concluded that nitrosomethyl-n-alkylamines that induce bladder tumors by oral administration to rats are metabolized to nitrosomethyl-3-carboxypropylamine, which is excreted in the urine and further metabolized to nitrosomethyl-2-oxopropylamine, the proximate bladder carcinogen.

Administration, Intravesical↗
PubMed1994

Extirpation and fulguration of multiple superficial bladder tumour recurrences under intravesical lignocaine anaesthesia.

OBJECTIVE: To register the results, complications and patient acceptance of bladder tumour operations under local anaesthesia. PATIENTS AND METHODS: Intravesical lignocaine was the anaesthesia used in 30 patients with multiple bladder tumour recurrences. The largest tumour was extirpated with large flexible biopsy forceps and the others were fulgurated. RESULTS: All visible tumours were extirpated or fulgurated except in one patient, where the operation had to be terminated due to unsatisfactory anaesthesia. All left the hospital within 2 h of surgery. Complications were minor and patient acceptance was very high. CONCLUSION: These operations have previously been performed under spinal anaesthesia in this department and the present modification reduced costs by approximately 70%. Patients who had only minor discomfort associated with routine cystoscopy under urethral anaesthesia were well suited for extirpation and fulguration of multiple small tumours under intravesical lignocaine.

Administration, Intravesical↗
PubMed1995

Bacillus Calmette-Guérin in superficial bladder cancer: consensus and controversies.

In this overview, Bacillus Calmette-Guérin (BCG) immunotherapy in superficial bladder cancer items are discussed on which consensus has been reached and on which controversies exist. The evaluation of the optimal route of administration has shown that intravesical instillation of BCG alone is accepted as the best route of administration. In searching for the appropriate BCG strain, the analysis of the results of 6 substrains has made clear that no particular strain has shown superiority over others. In finding the optimal treatment schedule there is strong evidence that maintenance therapy is superior to induction therapy alone. No consensus has been reached about the optimal dose for BCG therapy nor about how the toxicity of BCG treatment can be reduced. Although some reports have stated that BCG immunotherapy is superior to chemotherapy for the treatment of patients with superficial bladder cancer, more data are needed to prove this statement. In conclusion, although BCG has been proven to be very effective in the treatment of patients with superficial bladder cancer, it is certainly not a panacea for all patients with superficial bladder cancer.

Administration, Intravesical↗
PubMed1991

[Chemosensitivity test on superficial urinary bladder cancer using the dye exclusion assay--model of intravesical chemotherapy].

A chemosensitivity test was carried out on superficial bladder cancers using the trypan blue dye exclusion assay for the purpose of screening chemosensitive drugs for intravesical chemotherapy. Transplantable murine bladder tumor cells (MBT-2) were incubated, in vitro, in the presence of adriamycin (4, 40, 400, 1000 micrograms/ml) as well as verapamil (3, 30, 100, 500 micrograms/ml) at 5% CO2, 37 degrees C for two hours. After cellular viabilities were calculated, MBT-2 cells were inoculated into the hind limbs of mice. The cellular viability was correlated well with the ratio of tumor appearance, tumor growth inhibition and prolongation of survival, and was dose dependent in the adriamycin treated groups. On the other hand, a reduction of cellular viability, tumor growth inhibition and prolongation of survival were seen in the high dose verapamil (100, 500 micrograms/ml) treated groups. Human superficial bladder cancer cells were incubated in the presence of adriamycin, 4'-0-tetrahydropyranyladriamycin, mitomycin C and pepleomycin (1000 micrograms/ml) and/or verapamil (500 micrograms/ml). The reduction rates of cellular viability markedly varied with the kind of anticancer drugs. A reduction of cellular viability of human tumor cells as well as MBT-2 cells was seen in the verapamil treated groups. This rapid and handy assay seems to be useful for the purpose of screening chemosensitive drugs for intravesical chemotherapy.

Administration, Intravesical↗
PubMed2000

Intravesical mitoxantrone in superficial bladder cancer.

Twenty-five patients with Ta-T1 transitional cell carcinoma of the bladder were treated by transurethral resection (TUR) followed by intravesical chemoprophylaxis with mitoxantrone (10 mg diluted in 50 ml normal saline) administered weekly for 6 weeks. After a mean follow-up of 12 months, 76% of patients in the whole group, 69% in the newly diagnosed patients and 89% in the group of previously relapsed patients remained relapse free. These rates compare favorably with the other prophylactic agents available. Therapy was well tolerated in most patients, with only two patients reporting grade 3 local toxicity. We conclude that mitoxantrone is an effective and safe agent for intravesical chemotherapy.

Administration, Intravesical↗
PubMed1996

Intravesical chemotherapy for superficial bladder tumors category Ta/T1: who should be treated and how?

Superficial bladder cancer is the presenting feature in 75% to 80% of patients with newly diagnosed bladder carcinoma. Treatment goals are (1) to eradicate existing disease, (2) to provide prophylaxis against recurrence, and (3) to prohibit muscular invasion and metastases to lymph nodes. First-line treatment for stages Ta and T1 disease is transurethral resection (TUR). Recurrence rates with surgery alone, however, range from 40% to 80%. Study results show a statistically significant benefit in treatment results over those observed with TUR alone when adjuvant intravesical instillation of cytotoxic agents or immunomodulators is added. Patient characteristics are important factors in determining which patients might benefit from adjuvant treatment. Based on several trials reported by the European Organization for the Research and Treatment of Cancer Genitourinary Group, the following conclusions can be drawn: (1) patients with < 1 recurrence/year or with a primary solitary bladder tumor category Ta G2-3 or T1 G1-3 may benefit from a single, early instillation of a cytotoxic agent, (2) solitary Ta G1 lesions may be treated with TUR alone, (3) adjuvant therapy with cytotoxic agents should be instituted as soon as possible after TUR (this is not feasible with immunotherapy), (4) for patients treated within 6 hours after or on the day of TUR, a 6-month course of therapy is sufficient, whereas a 12-month course provides better results for patients in whom such early intravesical instillation is not feasible.

Administration, Intravesical↗
PubMed2006

Contemporary intravesical treatment options for urothelial carcinoma of the bladder.

To provide a comprehensive review of intravesical treatment options for non-muscle-invasive bladder cancer, we performed a search of the PubMed database for articles between 1980 and 2006 that reported on intravesical agents for treating this disease. Data were compiled and analyzed, emphasizing findings from large multicenter trials, studies providing reproducible results, data that could be confirmed by cross-referencing the literature, and phase I or II studies for pertinent novel agents. A critical analysis of evidence shows that: 1) treatment with Bacillus Calmette-Guérin (BCG), including a maintenance schedule (with or without interferon-alpha), is the most effective therapy for limiting recurrence, is the only therapy that reduces the incidence of progression, and overall is superior to chemotherapy; 2) mitomycin C, gemcitabine, anthracyclines, and thiotepa provide similar benefits for preventing recurrence in patients with minimal effect on progression; and 3) using chemotherapeutic agents immediately after transurethral resection (when use of BCG is contraindicated because of the risk for systemic absorption) reduces the recurrence rate by up to 50% and seems to be the ideal method of chemotherapy. Although various clinical factors dictate which agent is most appropriate for an individual patient, the current literature supports a single perioperative dose of intravesical mitomycin C followed, in appropriate cases, by induction and maintenance therapy with intravesical BCG.

Adjuvants, Immunologic↗