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Suramin as adjuvant therapy with radical prostatectomy
1Division of Cellular Biology, Hektoen Institute for Medical Research, Chicago IL 60612, USA.
Abstract:
Suramin is a newer agent employed in the management of prostate cancer. One suggested method of action is growth factor inhibition. While suramin has been employed to treat advanced disease its adjuvant role remains unexplored. To address this question we have employed a new model: the orthotopic placement of the Dunning AT-3 tumor. The purpose of this research was to assess the efficacy of adjuvant therapy in controlling residual disease. The method consisted of the injection of 2.4 to 2.6 x 10(6) AT-3 cells (harvested from flank tumors) into the ventral prostates of 29 Copenhagen X Fischer rats. The animals were then divided into four groups: 1) untreated controls (6 rats); 2) ventral prostatectomy only (10 rats); 3) ventral prostatectomy plus suramin (300mg/Kg) on post-op day 3 (5 rats); and 4) ventral prostatectomy plus cytoxan (50 mg/Kg) on post-op day 3 (8 rats). Prostatectomies were performed 10-12 days following AT-3 cell inoculation. Animals were sacrificed 10 days following prostatectomy, autopsied, and residual diseased weighed. All operating procedures: tumor cell inoculations, ventral prostatectomies, and necropsies were performed microsurgically employing a Zeiss operating microscope. The results (in mean tumor weights) were: Group 1, 20 +/- 1.4 gms; Group 2, 6.7 +/- 11.5 gms; Group 3, 2.7 +/- 3.8 gms; and Group 4, 2.2 +/- 2.5 gms. The differences between control and all treatment groups were significant: Group 1 vs. Group 2, P < 0.02; and Group 1 vs. Groups 3 and 4, P < 0.001. We conclude that prostatectomy resulted in a diminished weight of residual disease. Of more importance was the fact that adjuvant therapy further reduced residual disease. The orthotopic placement of the Dunning tumor may serve as a model to evaluate the place of suramin following radical prostatectomy.
Insights
This study explored suramin as an adjuvant therapy for prostate cancer using a rat model. Adjuvant suramin significantly reduced residual tumor weight after prostatectomy, suggesting its potential in post-surgical treatment.
Area of Science:
- Urology
- Oncology
- Pharmacology
Background:
- Suramin is a newer agent for prostate cancer management, potentially acting via growth factor inhibition.
- The adjuvant role of suramin in prostate cancer treatment remains unexplored.
- An orthotopic Dunning AT-3 tumor model in rats was developed to study adjuvant therapy efficacy.
Purpose of the Study:
- To assess the efficacy of adjuvant suramin therapy in controlling residual prostate cancer disease after surgery.
- To evaluate the Dunning AT-3 tumor model for assessing adjuvant therapies post-prostatectomy.
Main Methods:
- Orthotopic implantation of Dunning AT-3 tumor cells into rat prostates.
- Surgical prostatectomy was performed 10-12 days post-inoculation.
- Post-operative treatment groups included controls, prostatectomy alone, prostatectomy plus suramin, and prostatectomy plus cytoxan.
Main Results:
- All treatment groups showed a significant reduction in residual disease compared to untreated controls.
- Adjuvant suramin (300mg/Kg) and cytoxan (50 mg/Kg) significantly reduced residual tumor weight post-prostatectomy.
- Mean residual tumor weights were: controls (20 gms), prostatectomy only (6.7 gms), prostatectomy + suramin (2.7 gms), and prostatectomy + cytoxan (2.2 gms).
Conclusions:
- Prostatectomy effectively reduced residual disease in the Dunning AT-3 rat model.
- Adjuvant therapy with suramin or cytoxan further diminished residual disease after prostatectomy.
- The orthotopic Dunning tumor model is suitable for evaluating adjuvant suramin therapy in prostate cancer management.