Journal article
Bropirimine as neoadjuvant therapy decreases residual disease and expression of markers PCNA and TGF-beta(1) in a rat orthotopic prostate adenocarcinoma
Methods and findings in experimental and clinical pharmacology, Vol.19(4), pp.261-267
05/01/1997
PMID: 9228652
Abstract
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 II; 4) those treated,vith 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 nor significant (p = 0.07) by multiple regression analysis. However; prostatectomy alone, by Student's t 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.
Details
- Title: Subtitle
- Bropirimine as neoadjuvant therapy decreases residual disease and expression of markers PCNA and TGF-beta(1) in a rat orthotopic prostate adenocarcinoma
- Creators
- G LievanoD DiDomenicoJ BrownP BridgesM RubensteinM ShawP Guinan
- Resource Type
- Journal article
- Publication Details
- Methods and findings in experimental and clinical pharmacology, Vol.19(4), pp.261-267
- Publisher
- J R PROUS SA
- PMID
- 9228652
- ISSN
- 0379-0355
- Number of pages
- 7
- Language
- English
- Date published
- 05/01/1997
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Urology
- Record Identifier
- 9984319971302771
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