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At least 613 records · Page 34Linked to original sources
PubMed1989

[Comparative study on prophylactic intravesical instillation of bacillus Calmette-Guerin (BCG) and adriamycin for superficial bladder cancers].

In this study we evaluated 77 patients with superficial bladder cancer who were treated with either intravesical bacillus Calmette-Guerin (BCG) (44 patients) or doxorubicin hydrochloride (Adriamycin, ADR) (33 patients) for prophylaxis of tumor recurrence after transurethral resection. The estimated actuarial probability of non-recurrence rate at three years for the BCG group was 73.0%, and the actuarial non-recurrence rate for the ADR group was 27.3%; a statistically significant difference (p = 0.0013). A comparison between the two groups was also made according to the patient's background, including whether the tumor was initial or recurrent, solitary or multiple, and the tumor grade. In all areas of the study, except for grade-1 tumors, the BCG group was significantly superior to the ADR group. The efficacy of BCG therapy as a result of different BCG treatment protocol was evaluated for six weekly instillations 1) without further maintenance instillation, 2) followed by 12 months of maintenance, and 3) followed by more than 18 months of maintenance. Long-term maintenance BCG instillation group (more than 18 months) showed the most favorable results, however, the differences were not statistically significant. These results indicate that intravesical BCG instillation was significantly superior to ADR in the prevention of bladder cancer recurrence and that six weekly intravesical BCG instillations may provide adequate prophylactic effects against recurrence of superficial bladder cancers.

Actuarial Analysis↗
PubMed1992

[Clinical results of prophylactic intravesical chemotherapy on superficial bladder cancer using the dye exclusion assay].

A chemosensitivity test was carried out on superficial bladder cancer using the dye exclusion assay for the purpose of screening chemosensitive drugs for prophylactic intravesical chemotherapy. Bladder cancer cells of each patients were incubated, in vitro, in the presence of adriamycin, (2"R)-4'-0-tetrahydropyranyladriamycin, mitomycin C, pepleomycin and 4'-epi-adriamycin (500 micrograms/ml) at 5%, CO2, 37 degrees C for 2 hours. The cytotoxic effect of the drugs was evaluated by the ratio of stained cells by trypan-blue. The most effective drug was instilled postoperatively into the bladder 3 times for the first week, and every 2 weeks during the following 14 weeks. In 18 patients followed more than 4 months the prophylactic effect was evaluated. Fifteen of the 18 patients completed the protocol, but the remaining 3 patients failed to complete to the instillation because of severe irritability of the bladder. Tumor recurrence was demonstrated in two patients. Non-recurrence rates of tumors at 12 and 24 months were 93.8% and 82.0%, respectively. These results suggested that this rapid and handy assay was useful for the purpose of screening chemosensitive drugs for the intravesical chemotherapy.

Administration, Intravesical↗
PubMed2000

Role of neurokinin receptors in the behavioral effect of intravesical antigen infusion in guinea pig bladder.

PURPOSE: To characterize a guinea pig behavior model of bladder pain due to intravesical antigen infusion and to determine the role of neurokinin receptor subtypes in mediating this behavior. MATERIALS AND METHODS: The influence of subtype-selective neurokinin receptor antagonists on increased abdominal licking behavior in response to intravesical antigen infusion in guinea pigs immunized with ovalbumin (OA) was determined. RESULTS: Intravesical OA infusion for 30 minutes induced a significantly greater frequency (about 3-fold) of abdominal licking behavior than during either the 30 minutes pre-challenge or post challenge saline infusions. Treatment with IP capsaicin 7 to 10 days before OA challenge abolished the intravesical antigen-induced behavior. IP injection of the NK1 receptor antagonist CP 99994 (10 mg./kg. or 30 mg./kg.), 30 minutes pretreatment, inhibited the increase in the average number of abdominal licks during antigen infusion. The 30 mg./kg., but not the 10 mg./kg. dose increased the percent of animals showing antinociceptive activity (defined as 4 or less abdominal licks during the antigen infusion). The NK2 receptor antagonist SR 48968 reduced the antigen-induced abdominal licking behavior at IP doses of 3 and 10 mg./kg. but was ineffective at 1 mg./kg. The NK3 receptor antagonist SB 235375 (30 mg./kg., IP) did not reduce this behavior. CONCLUSIONS: These results suggest a role for activation of NK1 and NK2, but not NK3 receptors, by tachykinins released from capsaicin-sensitive nerves, in the increased abdominal licking behavior response of guinea pigs to intravesical antigen infusion.

Administration, Intravesical↗
PubMed1992

Long-term immunobiological effects of intravesical bacillus Calmette-Guérin against bladder carcinoma recurrences.

Intravesical bacillus Calmette-Guérin is a highly effective therapy against superficial bladder cancer recurrences and urothelial carcinoma in situ, the antitumoral effects of which seem to be linked to immunological effector mechanisms. To characterize further these mechanisms which contribute to the long-term effectiveness of BCG therapy, the local mononuclear cell subsets as well as the local cytokine production were assessed in the bladder wall of patients receiving intravesical BCG immunotherapy with special regard to long-term persisting changes, using immuno-enzymatical staining methods. All patients exhibited a significant increase after BCG in the local mononuclear cell population, with a predominance of the helper T-cell subset. Immunocompetent cells expressed activation markers for a prolonged period. Furthermore, a significant increase in the local cytokine production after the initial course of BCG was demonstrable, which persisted even after 12 to 21 months. These changes suggest that the BCG-induced activation of the local immune system persists over a long period after an initial course of intravesical therapy.

Administration, Intravesical↗
PubMed1996

Update on the Dutch Cooperative Trial: mitomycin versus bacillus Calmette-Guérin-Tice versus bacillus Calmette-Guérin RIVM in the treatment of patients with pTA-pT1 papillary carcinoma and carcinoma in situ of the urinary bladder. Dutch South East Cooperative Urological Group.

Prophylactic intravesical treatment with chemotherapeutic agents or one of the different strains of the immunomodulator bacillus Calmette-Guérin (BCG) reduces tumor recurrence and may prevent progression after transurethral resection (TUR) of superficial bladder cancer. Clinical and pathological prognostic factors are used to categorize different groups at risk for disease recurrence and progression. Solitary low-grade (G1, 2A), low-stage (pTa) tumors have less than a 5% risk of progression, while pT1 G3 tumors with concomitant carcinoma in situ (CIS) have a considerably higher risk of progression and metastases. Thus, prospective clinical trials should consider the different risks associated with different prognostic groups and stratify patients accordingly. The Dutch Cooperative Trial evaluated mitomycin versus BCG-Tice versus BCG-RIVM in 469 patients with pTA/pT1 carcinoma and CIS of the urinary bladder after TUR. Of 437 evaluable patients, 50 had CIS, 254 had pTA tumors, and 133 had pT1 tumors. No statistical differences were observed in toxicity between the two strains of BCG, but local and systemic side effects were more frequent in the BCG groups versus the mitomycin group. No differences in response rate were observed between the 3 treatment groups in patients with CIS. A statistically significant difference in favor of mitomycin was seen, however, in patients with papillary tumors. Mitomycin and BCG-RIVM were equally effective, and mitomycin proved significantly more effective than BCG-Tice. No significant difference in efficacy was observed between the two strains of BCG. Disease recurrence during the study in patients with papillary tumors was seen in 43% of mitomycin-treated patients, 64% of the BCG-Tice group, and 46% of patients treated with BCG-Rivm. However, a subgroup analysis for time to first recurrence for pTa versus pT1 and for grade 1 and 2 versus grade 3 papillary tumors showed no statistically significant between-group difference. Further studies comparing identical regimens, doses, and patient groups are needed to define more clearly which patient groups and tumors are more likely to respond to intravesical therapy.

Adjuvants, Immunologic↗
PubMed1998

BCG-induced interleukin-6 upregulation and BCG internalization in well and poorly differentiated human bladder cancer cell lines.

Intravesical bacillus Calmette-Guerin (BCG) is a successful therapy for superficial bladder cancer. However, the working mechanism of BCG after intravesical instillation is not completely understood. A functional role of urothelial (tumor) cells in the initiation of the BCG-induced immune reaction should be considered. Here, the possibility of a causal relationship between BCG-induced interleukin-6 (IL-6) synthesis and BCG internalization by urothelial tumor cells was examined in a series of human transitional bladder cancer (TCC) cell lines with different degrees of differentiation. The results showed that the well differentiated TCC cell lines, RT4, SBC-2, and SBC-7, did not possess the capacity to internalize BCG, which was associated with an inability to upregulate IL-6 synthesis when stimulated with BCG. Moreover, these cell lines expressed a low level of constitutive IL-6 synthesis. In contrast, the poorly differentiated TCC cells, T-24, TCC-SUP and J-82, were able to internalize BCG. In T24 and J82, but not in TCC-SUP cells, BCG internalization appeared to result in an upregulation of IL-6 synthesis. Constitutive IL-6 synthesis of the high grade cell lines was found to be cell line-dependent: both TCC-SUP and J82 cells exhibited a high level of constitutive IL-6 synthesis, whereas T24 cells exhibited a low level. The possible relationship between BCG internalization and IL-6 upregulation was studied in detail with the T24 cell line, which exhibited a low constitutive and high BCG-inducible IL-6 synthesis, using anti-BCG antibodies (alphaBCG) and Cytochalasin B as internalization inhibitors. Upregulation of IL-6 synthesis was significantly inhibited by alphaBCG or Cytochalasin B, indicating that internalization is a prerequisite for BCG-induced upregulation of IL-6 synthesis. In conclusion, upregulation of IL-6 production due to BCG internalization by poorly differentiated bladder carcinoma cells may be part of the mode of action of intravesical BCG therapy.

Administration, Intravesical↗