Pigment epithelium-derived factor, a human testis epididymis secretory product, promotes human prostate stromal cell growth in culture.

PURPOSE: We identified and characterized unrecognized testicular secretory proteins that impact human prostate growth. MATERIALS AND METHODS: Human spermatocele fluid served as a source of testicular epididymal secretions and prostatectomy specimen benign prostatic hyperplasia stromal cells as the in vitro prostate growth promoting effects indicator. RMPI plus medium supplemented with 10% fetal bovine serum MALDI-TOF, MS FBS and ITS+ (Collaborative Research-Becton Dickinson, Bedford, Massachusetts) served as positive and negative controls, respectively. Whole and fractionated spermatocele fluid or specific proteins without and with select polyclonal or monoclonal antibodies were added to routine 6-day cultures. The observation of significantly increased 6-day cell counts compared with appropriate controls (p <0.05) was judged to reflect cell growth. Amino acid microsequencing and MALDI-TOF MS sequence analysis were done on persistent protein bands from active spermatocele fluid fractions. RESULTS: Whole and fractionated human spermatocele fluid increased stromal cell culture numbers significantly. Sequence analysis of 47 and 17 kDa 1-dimensional gel bands in the final active fraction identified a major peptide with sequence homology to human pigment epithelium-derived factor (PEDF). The presence of PEDF was confirmed by Western blot analysis. Addition of recombinant PEDF to incomplete medium significantly increased stromal cell culture number. PEDF antibodies neutralized or markedly decreased the stromal stimulating effect of spermatocele fluid and PEDF. CONCLUSIONS: The observations presented provide evidence for human testis/epididymis secretion of PEDF and for a PEDF in vitro growth promoting effect on benign prostatic hyperplasia stroma. The concept that testicular epididymal secretory proteins may influence normal and abnormal prostate growth warrants continued consideration.

Biochemical disease-free survival following adjuvant and salvage irradiation after radical prostatectomy.

PURPOSE: To present the biochemical cure rates (biochemically no evidence of disease) after external irradiation (RT) in patients with high-risk prostate cancer after radical prostatectomy. METHODS AND MATERIALS: Seventy-six patients who underwent radical prostatectomy and subsequent RT were included in this analysis. No patient received hormonal therapy. Adjuvant RT was administered in 35 patients (46%), and 41 patients (54%) underwent salvage RT. After prostatectomy, the Gleason score was <7 in 87%, and 24% had seminal vesicle invasion. The median RT dose in the adjuvant RT and salvage RT groups was 60 Gy and 65 Gy, respectively. The biochemical cure rate was defined as a serum prostate-specific antigen of < or =0.2 ng/mL. RESULTS: The overall 5-year Kaplan-Meier biochemical control rate from the end of RT was 70%. The 5-year biochemical cure rate for adjuvant RT was significantly superior to that after salvage RT (86% vs. 57%). The significant predictors of biochemical failure were seminal vesicle invasion in the adjuvant RT group and the presence of Gleason grade 4 or 5 in the salvage RT group. The clinical local control rate in the prostate bed was 100%. CONCLUSION: This report demonstrates the efficacy of RT in achieving high biochemical cure rates after radical prostatectomy. Additional clinical studies are required to determine the optimal treatment of patients at high risk of biochemical failure after postprostatectomy RT.

Detection of Carcinoma of the Prostate Utilizing Biochemical Observations.

This review presents the current status of attempts to identify individuals with a high risk of carcinoma of the prostate by using biochemical, immunochemical, and immunologic studies of body fluids. Blood, urine, and prostatic fluid have been subjected to a variety of analyses in attempts to find alterations that are sufficiently specific and sensitive enough to be useful in the early recognition of patients with a high probability of localized or disseminated carcinoma of the prostate. A variety of immunologic and immunochemical techniques to identify and quantify acid phosphatase of prostatic origin in the serum are currently being explored for this purpose; as yet, none has achieved the specificity-sensitivity relationship necessary for widespread clinical application. Biochemical studies of prostatic fluid have disclosed a reversal of the lactic dehydrogenase (LDH) isoenzyme pattern with a predominance of LDH-V and increased levels of transferrin, complement C3 and possibly complement C4 in association with carcinoma of the prostate. The value of these non-specific changes is increased by the probable direct relationship between prostatic epithelial cell metabolism and changes in prostatic fluid composition. These approaches to identify individuals with a high risk of carcinoma of the prostate hold promise; they should be continued and expanded.