- Email: [email protected]
332 DEVELOPMENT OF A NOVEL HUMAN PROSTATE CANCER EXPLANT MODEL
Vol. 187, No. 4S, Supplement, Sunday, May 20, 2012
THE JOURNAL OF UROLOGY姞
e135
Further, the explants are responsive with respect to de novo proliferation in a dose responsive manner, as demonstrated by BrdU incorporation, Ki67 IHC and nuclear uptake of AR in response to DHT treatment. The explants can be used to study the transcriptional effects of DHT on AR regulated genes by both QPCR analyses and by western blot analyses. Finally, the explants can be used to evaluate sensitivity and on-target action of the prostate cancer specimens to various drugs, such as MDV3100, as evidenced by ki67 staining and expression of androgen responsive genes. The explants can also be used to validate the utility of novel agents such as peptidomimetics which are taken up by the explants and show targeted disruption of the protein complexes in response to the agents. CONCLUSIONS: These data strongly support the use of a novel human explant system for rapid evaluation of the effect of various drugs on the prostate specimens. This explant system does not have any of the artifactual growth on plastic petridishes and replicates the prostatic microenvironment well. This explant system may represent a rapid cost-effective approach for evaluation of drug effect for an individual patient. Source of Funding: Thompson research fund.
Prostate Cancer: Epidemiology and Natural History II Moderated Poster Sunday, May 20, 2012
Source of Funding: This study was developed with internal funding from the Research Programs Committees (RPC) and Urology Department of the Cleveland Clinic. Intuitive Surgical provided the da Vinci® Fluorescence Imaging Vision System for the experiment.
332 DEVELOPMENT OF A NOVEL HUMAN PROSTATE CANCER EXPLANT MODEL Preethi Ravindranathan, Ganesh Raj*, Dallas, TX INTRODUCTION AND OBJECTIVES: Current systems for evaluation of prostate cancer tumors with implantation of prostatic tumors into the subrenal capsule of nude mice are often cumbersome and plagued by poor tumor take rates. Genetic profiling of prostate cancers are still in their infancy and require much more validation before their utility in the clinic. With the possibility of over 100 new drugs on the horizon for prostate cancer, there is an unmet need for a system to rapidly evaluate the drug sensitivity of primary or metastatic prostate tumors in order to tailor the therapies. METHODS: A novel method of culturing prostate cancer explants derived from patients undergoing a radical prostatectomy for prostate cancer was developed. Basically, the tumor from high-volume prostate cancers was identified from the bivalved prostate within 30 minutes of surgical extirpation, was minced and then placed on a sponge matrix in culture and incubated in the presence of RPMI media for 0-6 days. The specimens were then processed for either molecular or immunohistochemical evaluation. RESULTS: The explants maintain normal histology over time as evidenced by a detailed assessment of tumor morphology before and following culture for various time points. There are no significant changes in cell morphology, nuclear size and shape, degree of hyperplasia, tissue integrity, or degree of tissue hypoxia (IHC for HIF1␣) and stromal architecture compared to control.
10:30 AM-12:30 PM
333 RADICAL RETROOUBIC PROSTATECTOMY VS ROBOT ASSISTED LAPAROSCOPIC RADICAL PROSTATECTOMY: A QUALITY OF LIFE COMPARISON John Gannon*, Christopher Dechet, Robert Stephenson, Arthur Hartz, Tao He, Salt Lake City, UT INTRODUCTION AND OBJECTIVES: To evaluate and compare the quality of life outcomes of patients undergoing radical retropubic prostatectomy (RRP) and Robotically Assisted Laparoscopic Radical Prostatectomy (RALRP). METHODS: Eight hundred and thirty-six, non-randomized patients undergoing RRP or RALRP at one institution involving 2 surgeons were prospectively evaluated using the long form Expanded Prostate Cancer Index Composite (EPIC). Patients were evaluated preoperatively and post-operatively at 3, 6, 9, 12, 18, and 24 months. RESULTS: Excluding patients with Stage ⬎T3, Gleason score ⬎7 and patients undergoing a non-nerve sparing procedure, 418 patients underwent RALRP and 421 patients underwent RRP by 2 surgeons. Significant differences existed between tumor grade, stage, Gleason score (p⬍0.05) and age; reflecting an institutional bias to select higher grade and higher volume tumors for RRP. No significant difference was noted in post-operative complications by clavian scores. Robotic surgery had no significant impact on EPIC urinary function scores. Age had a significant impact on post-operative urinary function. Of the 243 patients who had a nerve sparing procedure and adequate pre-operative sexual function, no significant difference was noted between robotic and open prostatectomy. Age and degree of nerve sparing had a significant impact on post-operative sexual function (p⬍0.05). CONCLUSIONS: Our non-randomized prospective comparison of quality of life outcomes between patients undergoing RRP vs RALRP revealed no significant differences in post-operative urinary and sexual function scores.
THE JOURNAL OF UROLOGY姞
e135
Further, the explants are responsive with respect to de novo proliferation in a dose responsive manner, as demonstrated by BrdU incorporation, Ki67 IHC and nuclear uptake of AR in response to DHT treatment. The explants can be used to study the transcriptional effects of DHT on AR regulated genes by both QPCR analyses and by western blot analyses. Finally, the explants can be used to evaluate sensitivity and on-target action of the prostate cancer specimens to various drugs, such as MDV3100, as evidenced by ki67 staining and expression of androgen responsive genes. The explants can also be used to validate the utility of novel agents such as peptidomimetics which are taken up by the explants and show targeted disruption of the protein complexes in response to the agents. CONCLUSIONS: These data strongly support the use of a novel human explant system for rapid evaluation of the effect of various drugs on the prostate specimens. This explant system does not have any of the artifactual growth on plastic petridishes and replicates the prostatic microenvironment well. This explant system may represent a rapid cost-effective approach for evaluation of drug effect for an individual patient. Source of Funding: Thompson research fund.
Prostate Cancer: Epidemiology and Natural History II Moderated Poster Sunday, May 20, 2012
Source of Funding: This study was developed with internal funding from the Research Programs Committees (RPC) and Urology Department of the Cleveland Clinic. Intuitive Surgical provided the da Vinci® Fluorescence Imaging Vision System for the experiment.
332 DEVELOPMENT OF A NOVEL HUMAN PROSTATE CANCER EXPLANT MODEL Preethi Ravindranathan, Ganesh Raj*, Dallas, TX INTRODUCTION AND OBJECTIVES: Current systems for evaluation of prostate cancer tumors with implantation of prostatic tumors into the subrenal capsule of nude mice are often cumbersome and plagued by poor tumor take rates. Genetic profiling of prostate cancers are still in their infancy and require much more validation before their utility in the clinic. With the possibility of over 100 new drugs on the horizon for prostate cancer, there is an unmet need for a system to rapidly evaluate the drug sensitivity of primary or metastatic prostate tumors in order to tailor the therapies. METHODS: A novel method of culturing prostate cancer explants derived from patients undergoing a radical prostatectomy for prostate cancer was developed. Basically, the tumor from high-volume prostate cancers was identified from the bivalved prostate within 30 minutes of surgical extirpation, was minced and then placed on a sponge matrix in culture and incubated in the presence of RPMI media for 0-6 days. The specimens were then processed for either molecular or immunohistochemical evaluation. RESULTS: The explants maintain normal histology over time as evidenced by a detailed assessment of tumor morphology before and following culture for various time points. There are no significant changes in cell morphology, nuclear size and shape, degree of hyperplasia, tissue integrity, or degree of tissue hypoxia (IHC for HIF1␣) and stromal architecture compared to control.
10:30 AM-12:30 PM
333 RADICAL RETROOUBIC PROSTATECTOMY VS ROBOT ASSISTED LAPAROSCOPIC RADICAL PROSTATECTOMY: A QUALITY OF LIFE COMPARISON John Gannon*, Christopher Dechet, Robert Stephenson, Arthur Hartz, Tao He, Salt Lake City, UT INTRODUCTION AND OBJECTIVES: To evaluate and compare the quality of life outcomes of patients undergoing radical retropubic prostatectomy (RRP) and Robotically Assisted Laparoscopic Radical Prostatectomy (RALRP). METHODS: Eight hundred and thirty-six, non-randomized patients undergoing RRP or RALRP at one institution involving 2 surgeons were prospectively evaluated using the long form Expanded Prostate Cancer Index Composite (EPIC). Patients were evaluated preoperatively and post-operatively at 3, 6, 9, 12, 18, and 24 months. RESULTS: Excluding patients with Stage ⬎T3, Gleason score ⬎7 and patients undergoing a non-nerve sparing procedure, 418 patients underwent RALRP and 421 patients underwent RRP by 2 surgeons. Significant differences existed between tumor grade, stage, Gleason score (p⬍0.05) and age; reflecting an institutional bias to select higher grade and higher volume tumors for RRP. No significant difference was noted in post-operative complications by clavian scores. Robotic surgery had no significant impact on EPIC urinary function scores. Age had a significant impact on post-operative urinary function. Of the 243 patients who had a nerve sparing procedure and adequate pre-operative sexual function, no significant difference was noted between robotic and open prostatectomy. Age and degree of nerve sparing had a significant impact on post-operative sexual function (p⬍0.05). CONCLUSIONS: Our non-randomized prospective comparison of quality of life outcomes between patients undergoing RRP vs RALRP revealed no significant differences in post-operative urinary and sexual function scores.