S‐phase fraction of human prostate adenocarcinoma studied with in vivo bromodeoxyuridine labeling

Abstract

Forty-six patients with adenocarcinoma of the prostate were given an intravenous infusion of the thymidine analogue, bromodeoxyuridine (BrdU), 200 mg/m2, at the time of needle biopsy or transurethral resection to label tumor cells in the DNA synthesis phase. The tumor specimens were stained by an indirect immunoperoxidase method with anti-BrdU monoclonal antibody. The BrdU labeling index, S-phase fraction, was determined by counting the number of BrdU-labeled cells in the tissue sections. S-phase fraction correlates with the results of histologic tumor grade, Gleason score, and growth patterns. The higher S-phase fraction may indicate biologic malignancy. Moreover, the degree of heterogeneity concerning S-phase fraction distribution within prostate cancer tissue could be evaluated and the findings compared with the morphologic appearance. The authors results suggest that the measurement of BrdU labeling index in prostate cancer may prove to be a new objective and quantitative assay for biologic potential of individual tumors.

Cell proliferation, DNA repair, and p53 function are not required for programmed death of prostatic glandular cells induced by androgen ablation.

“…While androgenindependent prostatic cancer cells do not activate programmed cell death following androgen ablation, death may be induced in these cancer cells by a variety of chemotherapeutic agents if these cells are proliferating (20). Unfortunately, the rate ofcell proliferation ofhuman prostatic cancer cells in vivo is remarkably low (i.e., >1-2% per day) (21,22 (23). Since double-stranded fragmentation of genomic DNA is induced duriprg programmed cell death (6,16,18) (8), and an aliquot was processed for radioautography as described (7 Table 2).…”

Comparison of BrdUrd and [3H]TdR incorporation to estimate cell proliferation, cell loss, and potential doubling time in tumor xenografts

“…This method is faster and simpler than PLM and has the added advantage of being applicable to studies of tumor cell proliferation in the patient. The latter feature is important, as the results of several clinical studies indicate that the cell kinetic properties of a tumor may be of prognostic value for response to therapy (5,7,8,12,13,16,19,22,26).…”

Highlights of Natural Products in Prostate Cancer Drug Discovery

“…A relevant issue on PC drug discovery is the ability to target both androgen-sensitive and androgen-insensitive cells in order to avoid recurrence phenomena, which could be accomplished by multi-target drugs. In addition, androgen-insensitive PC cells have a very low rate of proliferation (Nemoto et al, 1990). Less than 10% of such cells proliferate during a given day thus leaving an extremely small therapeutic index for anti-proliferation drugs.…”