mycophenolic-acid and Urinary-Bladder-Neoplasms

To compared the effects of three immunosuppressive agents, i.e. sirolimus (SRL), cyclosporine A (CsA) and mycophenolate mofetil (MMF), with different mechanisms of action on the in vitro growth of various tumor cell lines of human transitional cell carcinoma of bladder cell lines EJ and T24 and in vivo growth of cell line of EJ in nude mice model.. The effects of SRL, CsA and MMF on the proliferation of transitional cell carcinoma of bladder cell lines were examined with the method of methyl thiazolyl tetrazolium (MTT). The effects of these immunosuppressants on tumor growth and metastasis were explored in a nude mice model with human transitional cell carcinoma of bladder cell line EJ. Forty-two nude mice were divided into 7 groups to receive normal saline (control), SRL, CsA, MMF, SRL + CsA, SRL + MMF and CsA + MMF respectively (n = 6 each).. The in vitro cell proliferation was inhibited by SRL and MMF versus the control groups. But no obvious inhibition of proliferation was observed at < 1000 ng/ml in the CsA-treated group. In the in vivo nude mice mode, the tumor volume of SRL, CsA group were lower than that in control group ((441 ± 231), (463 ± 110) vs (1032 ± 382) mm(3), both P < 0.05). In the in vivo nude mice mode of EJ treated by SRL, CsA, SRL + CsA, SRL + MMF and CsA + MMF, tumor volume at Day 23 was the lowest in the SRL + CsA group ((191 ± 92) vs (1032 ± 382) mm(3), P < 0.05). There was an inhibition of 75.26% in SRL + CsA group versus the control groups.. SRL and MMF demonstrate dose-dependent antiproliferative effects in human transitional cell carcinoma of bladder cell both in vitro and in vivo. CsA can inhibit the growth of human transitional cell carcinoma of bladder cell lines EJ cells in vivo.

Topics: Animals; Carcinoma, Transitional Cell; Cell Line, Tumor; Cell Proliferation; Cyclosporine; Humans; Mice; Mice, Nude; Mycophenolic Acid; Sirolimus; Urinary Bladder Neoplasms

Malignant tumor is the most common complication occurred in transplant recipients. It is widely recognized that immunosuppressive treatments increase the risk of cancer in transplant recipients. The efficacy and safety of rapamycin (RPM) in combination with low-dose calcineurin inhibitor (CNI) in treating 15 renal allograft recipients which developed urothelial carcinoma were observed.. Immunosuppressive regimen in all recipients was altered with rapamycin to replace mycophenolate mofetil (MMF) or azathioprine (Aza). The initial loading dosage was 2 mg/d, and the next dosage was 1 mg/d. The dosage of rapamycin was carefully adjusted according to the blood drug level and concentration of the drug was maintained at 4 - 6 microg/L. In all the 15 patients, the calcineurin inhibitor was reduced down to one third of the original dosage after the rapamycin blood concentration became stable. Surgical treatment and intravesical instillation chemotherapy were carried out in all patients. Recurrence of the tumor was monitored throughout the study. Post-transplant renal function and side effects were also closely monitored.. Among the 15 patients, 9 had no tumor recurrence in 2 years, 2 had tumor recurrences twice, and 4 had once. There was no acute rejection observed during RPM treatment. Post-transplant renal function in 11 patients was improved, with a decreased creatinine level. Hyperlipoidemia and thrombocytopenia were the most frequent adverse events which responded well to corresponding treatments.. Among the renal allograft recipients with urothelial carcinoma, combination of rapamycin and low dose calcineurin inhibitor treatment is effective and safe.

Topics: Adult; Azathioprine; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Sirolimus; Urinary Bladder Neoplasms; Urothelium

Topics: Administration, Oral; Animals; Drug Evaluation; Molecular Conformation; Mycophenolic Acid; Neoplasms, Experimental; Time Factors; Urinary Bladder Neoplasms