bropirimine and Prostatic-Neoplasms

Urological cancers have a variety of biological characteristics. Thus, anti-cancer agents in this field are often developed focusing on the biological characteristics. For example, LH-RH agonist and anti-androgens have been developed for androgen-sensitive prostate cancer, interferons and IL-2 for renal cell cancer, and BCG for superficial bladder cancer. In this manuscript, new agents which are thought to be promising in the urological field, bropirimine for bladder cancer and liarozole for prostate cancer, are briefly introduced.

Topics: Androgen Antagonists; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Carcinoma, Renal Cell; Cytosine; Humans; Imidazoles; Kidney Neoplasms; Male; Prostatic Neoplasms

Paclitaxel, bropirimine and linomide therapy was evaluated in a murine prostate cancer model. All drugs were effective in impeding tumor growth but the mechanisms of action varied. Paclitaxel inhibited bcl-2 expression suggesting an apoptotic mechanism. Bropirimine, while inhibiting bcl-2 expression also significantly depressed tumor necrosis factor-alpha (TNF-alpha) expression. In the bropirimine treated group there was also a correlation between angiogenesis and cyclin D expression. Finally, linomide significantly decreased angiogenesis. Since the mechanism of action of these drugs differ, combining them at lower doses might maintain therapeutic efficacy while reducing toxicity.

Topics: Animals; Antineoplastic Agents; Cell Division; Cytosine; Hydroxyquinolines; Immunohistochemistry; Male; Mice; Models, Biological; Paclitaxel; Prostatic Neoplasms; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Inbred F344

Bropirimine is an oral immunostimulant found to have efficacy in human transitional cell carcinoma in situ following the initial discovery of its antitumor activity against the murine bladder cancer MBT-2. To determine if bropirimine might have activity in prostate cancer, it was tested against two rodent prostate cancer cell lines in vivo.. Tumors resulted from subcutaneous injection of PAIII and Dunning MAT-LyLu rodent prostate cancer cells. Bropirimine was given at 250 mg/kg orally on different schedules, and tumor volume and survival were recorded.. In the PAIII model, bropirimine prevented growth when given the day of tumor injection, and 95% of advanced tumors regressed completely when start of therapy was delayed. Bropirimine also caused growth inhibition and prolongation of survival in the MAT-LyLu model.. Bropirimine immunotherapy is very effective in vivo against the PAIII cell line, and it has significant growth inhibition against the Dunning MAT-LyLu cell line.

Topics: Adjuvants, Immunologic; Administration, Oral; Animals; Antineoplastic Agents; Cell Division; Cytosine; Disease Models, Animal; Immunotherapy; Interferon Inducers; Male; Prostatic Neoplasms; Random Allocation; Rats; Rats, Wistar; Treatment Outcome; Tumor Cells, Cultured

The role of bropirimine in prostate cancer remains unexplored. To address the efficacy of this immune modulator as neoadjuvant therapy we utilized the orthotopic placement of the Dunning AT-3 tumor. 2.4-2.6 x 10(6) Dunning AT-3 cells were injected into the ventral prostates of 50 Copenhagen X Fischer rats. Animals were then divided into 5 groups consisting of: 1) untreated controls; 2) those treated with ventral prostatectomy alone (performed 10-12 days following tumor cell inoculation); 3) those treated with ventral prostatectomy plus bropirimine (10 mg/kg) on postimplantation days 1, 3, 5, 10 and 11; 4) those treated with ventral prostatectomy plus bropirimine (100 mg/kg), at the same schedule; and 5) those treated with ventral prostatectomy plus bropirimine (500 mg/kg), at the same schedule. Animals were sacrificed 10 days after prostatectomy, autopsied, and residual disease was weighed. Prostate weights upon removal following neoadjuvant treatment and residual disease remaining after 20-22 days were expressed in grams (g). Following prostatectomy, mean prostate weights were: Group 2, 0.67 +/- 0.11; Group 3, 0.53 +/- 0.11; Group 4, 0.54 +/- 0.12; Group 5, 0.44 +/- 0.09. The effect of bropirimine was significant (p = 0.0001) by multiple regression analysis. In addition, mean residual tumor weights (expressed in grams) after 20-22 days were: Group 1, 12.7 +/- 1.9; Group 2, 6.7 +/- 4.8; Group 3, 5.2 +/- 5.9; Group 4, 3.8 +/- 3.5; and Group 5, 2.8 +/- 3.5. The effect of bropirimine was not significant (p = 0.07) by multiple regression analysis. However, prostatectomy alone, by Student's test, significantly (p = 0.04) reduced residual mean tumor weights by 47% and the additional effect of bropirimine upon residual disease was significant (p = 0.038) if a Chi-square analysis is applied. Finally, a multivariate analysis of the overall effect of bropirimine in rats treated with prostatectomy was significant (p = 0.002). The effect of bropirimine on expression of proliferating cell nuclear antigen (PCNA) and transforming growth factor beta 1 (TGF-beta 1) was also evaluated immunohistochemically and expression of both tumor markers was significantly reduced (p < 0.05). We conclude that bropirimine may have a role as a neoadjuvant therapy when combined with prostatectomy.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Biomarkers, Tumor; Cytosine; Down-Regulation; Gene Expression Regulation, Neoplastic; Injections, Intraperitoneal; Male; Neoplasm, Residual; Proliferating Cell Nuclear Antigen; Prostatic Neoplasms; Rats; Rats, Inbred F344; Transforming Growth Factor beta; Tumor Cells, Cultured

To evaluate bropirimine for in vivo activity in rodent prostate cancer.. Subcutaneously injected PAIII and Dunning MAT-LyLu rodent prostate cancer cells caused solid tumors and death in controls. Bropirimine was given on varying schedules at 250 mg./kg. by gavage, and tumor volume and survival were recorded.. Bropirimine prevented growth when given on the day of tumor injection and caused 95% of advanced tumors to regress completely in the PAIII model. Bropirimine caused significant growth inhibition and prolongation of survival in the MAT-LyLu model.. Bropirimine has statistically significant in vivo activity against both of these rodent prostate cancer cell lines.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Cytosine; Male; Neoplasm Transplantation; Prostatic Neoplasms; Rats; Rats, Inbred Strains; Time Factors; Tumor Cells, Cultured