0000000000413883
AUTHOR
Robert L. Vessella
Effects of phenylbutyrate on proliferation and apoptosis in human prostate cancer cells in vitro and in vivo.
Phenylbutyrate (PB) is a potent differentiating agent and currently under investigation for the treatment of prostate cancer (CaP) and other malignancies. We have studied the impact of PB in vitro and in vivo on differentiation, proliferation and apoptosis in the LNCaP and LuCaP 23.1 prostate cancer xenograft models. In vitro we found that i) PB increased PSA secretion/cell, ii) inhibited cell proliferation in a time- and dose-dependent manner resulting in a cell cycle arrest in G1-phase and iii) induced apoptosis at concentrations of 2.5 mM after 3 days of treatment. In PB treated animals tumor growth stabilized or regressed. Combination of castration and PB treatment had a synergistic ant…
Characterization of C4-2 Prostate Cancer Bone Metastases and Their Response to Castration
New well-characterized preclinical models of prostate cancer (CaP) bone metastases are needed to improve our understanding of the development of CaP-related bone disease in patients. Here we describe characterization of a model consisting of direct injection of C4–2 cells into tibias. Introduction: Prostate cancer (CaP) has a high proclivity to metastasize to bone. Development and characterization of preclinical models of CaP bone metastases are of high interest. The objective of this study was to characterize C4–2 bone metastases and their response to castration. Materials and Methods: Cell suspensions of C4-2, a subline of LNCaP, were injected directly into the tibias of intact male mice.…
Detection of circulating prostate cells by reverse transcriptase-polymerase chain reaction of human glandular kallikrein (hK2) and prostate-specific antigen (PSA) Messages
Abstract Objectives To investigate the clinical value of human glandular kallikrein (hK2) reverse transcriptase-polymerase chain reaction (RT-PCR) for detection of prostate cells in circulation and to compare the results with those obtained from prostate-specific antigen (PSA) RT-PCR. Methods We examined peripheral blood (PB) and bone marrow (BM) samples of 13 patients with advanced-stage prostate cancer and 63 patients with clinically localized disease for the presence of circulating prostate cells. An RT-PCR protocol with a two-step amplification cycle and hot-start conditions was used. Results The limit of detection of the PCR portion is similar for PSA and hK2 (5 to 10 copies of the pla…
C-Kit and Its Ligand Stem Cell Factor: Potential Contribution to Prostate Cancer Bone Metastasis
AbstractThe tyrosine kinase receptor c-kit and its ligand stem cell factor (SCF) have not been explored in prostate cancer (PC) bone metastasis. Herein, we found that three human PC cell lines and bone marrow stromal cells express a membrane-bound SCF isoform and release a soluble SCF. Bone marrow stromal cells revealed strong expression of c-kit, whereas PC cells showed very low levels of the receptor or did not express it all. Using an experimental model of PC bone metastasis, we found that intraosseous bone tumors formed by otherwise c-kit–negative PC3 cells strongly expressed c-kit, as demonstrated using immunohistochemical and Western blot analyses. Subcuta-neous PC3 tumors were, howev…
The percentage of free prostate-specific antigen does not predict extracapsular disease in patients with clinically localized prostate cancer before radical prostatectomy
Objective To determine whether the percentage of free/total prostate-specific antigen (f/tPSA) can predict the pathological features in patients with clinically localized prostate cancer before radical prostatectomy. Patients and methods Univariate and multivariate logistic regression was used to analyse data from 171 untreated patients who underwent radical prostatectomy. Variables included the total PSA (tPSA), fPSA, f/tPSA, biopsy Gleason score, clinical stage and patient age. Results In 115 patients with pathologically organ-confined tumours ( pT2N0) the mean (sd) tPSA value was 6.9 (5.6) ng/mL; in 56 patients with extracapsular disease ( pT3pN0/N+) it was 10.2 (7.6) ng/mL; the respecti…