sirolimus and nitazoxanide

To understand the effect of Nitazoxanide (NTZ), Rapamycin, Thalidomide, alone and in combination with BCG on bladder cancer (BC) histopathology and programmed death-ligand 1 (PD-L1) and anti-cytotoxic T lymphocyte antigen 4 (CTLA4) expression.. Female Fisher-344 rats underwent intravesical N-methyl-N-nitrosourea (MNU) followed by weekly intravesical treatment with saline (controls, n = 10), BCG (n = 10), NTZ (n = 8), BCG plus NTZ (n = 8), Rapamycin (n = 10) BCG plus Rapamycin (n = 10), Thalidomide (n = 10), and BCG plus Thalidomide (n = 10), and euthanized after 8 weeks and their bladders were investigated for BC and PD-L1 and CTLA4 expression.. Rapamicyn alone and in combination with BCG had the lowest number of bladder neoplasias in the histopathology exam (1/10). Neoplastic lesions were found in 4/10 BCG recipients, 5/10 Thalidomide recipients, 4/10 Thalidomide plus BCG recipients, 5/8 NTZ and 3/8 NTZ plus BCG recipients. Adding NTZ to BCG increased the expression of PD-L1 and adding Rapamycin or Thalidomide decreased PD-L1 and CTLA4 expression compared to BCG alone. Rapamycin alone significantly increased CTLA4 and slightly increased PD-L1 expression but its combination with BCG significantly decreased both markers. Thalidomide had a similar effect; however, it was only slightly different from the control and BCG alone groups.. Intravesical BCG combination treatment seems to effectively prevent BC development in an immunecompetent clinically relevant animal model, introducing Thalidomide, Nitazoxanide, and specially Rapamycin as candidates in the intravesical immunotherapy advancement. Our study contributes in understanding the mechanism of cancer immunotherapy.

Topics: Adjuvants, Immunologic; Administration, Intravesical; Animals; B7-H1 Antigen; BCG Vaccine; CTLA-4 Antigen; Female; Rats; Sirolimus; Thalidomide; Urinary Bladder Neoplasms

Diarrhoea in transplantation may be secondary to infectious agents and immunosuppressive drugs. The use of combined immunosuppressive drugs increases the incidence of infectious diarrhoea. We retrospectively collected all diarrhoea episodes during a 3-year period in 199 pediatric renal transplant recipients, including 47 patients receiving a kidney transplant during this period. We diagnosed 64 diarrhoea episodes (32% of the patients, 10.7% per year). Fourteen diarrhoea episodes could be attributed to the immunosuppressive treatment, and 12 remained without diagnosis. Nineteen patients (<10%) receiving mycophenolic acid (MPA) developed diarrhoea, 14 of whom had episodes attributable to the immunosuppressive treatment. Reducing the MPA dose or switching to another immunosuppressant did not induce graft rejection, if at all, for at least 6 months. Thirty-eight diarrhoea episodes were caused by infectious agents: viruses in 16 patients, bacterial agents in ten patients, Candida albicans in four cases and parasitic agents in eight cases (Giardia lambdia in one patient and Cryptosporidium in seven patients). In our cohort, Cryptosporidium was responsible for 18% of the infectious diarrhoea and 11% of all causes of diarrhoea, and it affected 3.5% of the newly transplanted patients during the 3-year study period. The clinical presentation of the disease was profuse and persistent diarrhoea with acute renal failure in all patients. We propose that oocysts be screened for in the stool during the early stages of tests for determining the origin of infectious diarrhoea. Disease treatment requires early specific treatment (nitazoxanide) for extended periods of time in conjunction with supportive rehydration.

Topics: Adolescent; Antiparasitic Agents; Biopsy; Child; Cohort Studies; Cryptosporidiosis; Diarrhea; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Kidney; Kidney Transplantation; Male; Mycophenolic Acid; Nitro Compounds; Prednisone; Sirolimus; Tacrolimus; Thiazoles; Time Factors; Transplantation, Homologous; Treatment Outcome