Morito Sugimoto

Preclinical biodistribution and safety study of reduced expression in immortalized cells/Dickkopf-3-encoding adenoviral vector for prostate cancer gene therapy

The biodistribution and safety of adenoviral vectors encoding the human REIC/Dkk-3 tumor suppressor gene (Ad-REIC) were examined in this preclinical study for in situ prostate cancer gene therapy. First, the in vitro apoptotic effects of Ad-REIC in normal and cancer cells derived from the prostate and liver were examined. Significant apoptotic effects were observed at 100 MOI (multiplicity of infection) in prostate cancer cells (LNCaP, PC3) and hepatoma cells (HEP3B and HEPG2); however, no effects were seen in normal cells. To analyze the safety of intraprostatic Ad-REIC administration, the biodistribution and histology after Ad-REIC injection were evaluated in various organs of normal male C57BL6 mice. In a supporting study, vector dissemination following intravenous injection of Ad-REIC into tail veins was determined. To evaluate whether Ad-REIC was present in the collected tissue specimens, human REIC gene detection was performed using DNA-PCR. Intraprostatic treatment administered at lower doses showed vector biodistribution into the colon, urinary bladder and prostate. At higher doses, vector dissemination was observed in tissues more distant from the prostate, including the lung, thymus, heart, liver and adrenal gland. After intravenous injection of Ad-REIC, dissemination was observed in the liver and spleen. These results indicate that the biodistribution of Ad-REIC is determined by the dose and route of administration. Although acute inflammatory effects were observed in the prostate after intraprostatic administration at higher doses, no abnormal histological findings were noted in the other tissues, including those of intravenously treated mice. Regarding the safety of Ad-REIC administration, no deaths and no signs of toxicity or unusual behavior were observed in the mice in any treatment group. Based on these preclinical experiments, adenovirus-mediated in situ REIC/Dkk-3 gene therapy is considered to be safe for use as a treatment for human prostate cancer.

MP11-19 TARGETED ANTIBIOTIC PROPHYLAXIS BY β-LACTAMS BASED ON RECTAL SWAB CULTURE IS NOT SUFFICIENT TO PREVENT INFECTIVE COMPLICATIONS AFTER TRANSRECTAL PROSTATE BIOPSY

Group B: 188 patients who were given amikacin 15 mg / kg intramuscularly 60-120 min before the procedure. All patients underwent urinalysis and urine culture before and after the procedure. We identified post biopsy complications: bacteriuria, urinary tract infection, orchitis, pyelonephritis, sepsis, all of them were evaluated, all patients with a severe condition were hospitalized. The variables were correlated using Fishers Exact Test. RESULTS: In Group A, 4.3% of patients presented a febrile UTI and 0.97% presented sepsis. In Group B, 5.3% presented febrile UTI and .53% presented sepsis. Comparing both groups, we found no relationship between the dose and the risk for complications (p1⁄40.52). In the group analysis considering DM, a significant relationship for complication risks was not found, Group A (p1⁄40.62) and Group B (p1⁄40.58). The same in the analysis of overweight and obesity no significant relationship with complications was found, Group A (p1⁄40.85) and Group B (p1⁄40.65). CONCLUSIONS: Given its efficacy and simplicity, a single dose of 500mg of levofloxacin represents an excellent prophylaxis method in transrectal prostate biopsies guided by ultrasound. However, a single dose of amikacin shows similar results as levofloxacin, thus it can significantly reduce the cost of antibacterial therapy and have a similar safety profile.