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Prostate Carcinoma Cell Line (prostate + carcinoma_cell_line)
Selected AbstractsInduction of apoptosis in the LNCaP human prostate carcinoma cell line and prostate adenocarcinomas of SV40T antigen transgenic rats by the Bowman,Birk inhibitorPATHOLOGY INTERNATIONAL, Issue 11 2009MingXi Tang The soybean-derived serine protease inhibitor, Bowman,Birk inhibitor (BBI), has been reported as a potent chemoprevention agent against several types of tumors. The present study was undertaken to evaluate the effects of BBI on androgen-sensitive/dependent prostate cancers using a human prostate cancer cell (LNCaP) and the transgenic rats developing adenocarcinoma of the prostate (TRAP) model. Treatment of LNCaP prostate cancer cells with 500 µg/mL BBI resulted in inhibition of viability measured on WST-1 assays, with induction of connexin 43 (C×43) and cleaved caspase-3 protein expression. Feeding of 3% roughly prepared BBI (BBIC) to TRAP from the age 3 weeks to 13 weeks resulted in significant reduction of the relative epithelial areas within the acinus and multiplicity of the adenocarcinomas in the lateral prostate lobes. C×43- and terminal deoxynucleotidyl transferase mediated dUTP-biotin end labeling of fragmented DNA (TUNEL)-positive apoptotic cancer cells were more frequently observed in the lateral prostates treated with BBIC than in the controls. These in vivo and in vitro results suggest that BBI possesses chemopreventive activity associated with induction of C×43 expression and apoptosis. [source] Allogeneic retrovirally transduced, IL-2- and IFN-,-secreting cancer cell vaccine in patients with hormone refractory prostate cancer,a phase I clinical trialTHE JOURNAL OF GENE MEDICINE, Issue 7 2007T. H. Brill Background The purpose of this vaccine study was to determine the safety and feasibility of vaccination with an allogeneic prostate carcinoma cell line, LNCaP, expressing recombinant interleukin-2 (IL-2) and interferon-, (IFN-,) and to evaluate the efficacy of inducing tumor-specific immune responses in HLA-A2-matched patients with hormone refractory prostate cancer (HRPC). Methods In a dose-escalating phase I study, HLA-A2-matched HRPC patients received four vaccinations of irradiated allogeneic LNCaP cells retrovirally transduced to secrete IL-2 and IFN-, at study day 1, 15, 29 and 92 and subsequently every 91 days unless tumor progression was evident. Results Three patients receiving the first dose level (7.5 million cells) showed no evidence of dose-limiting toxicity or vaccine-related adverse events including autoimmunity. One of three patients receiving the second dose level (15 million cells) developed a transient self-limiting grade 3 local injection site reaction (ulceration) after the eighth vaccination. Vaccine-induced immune responses against a broad array of prostate tumor associated antigens were detected in all six patients. Two of the three patients receiving the higher dose showed a decline in serum prostate-specific antigen (PSA) values of more than 50%, with one patient remaining on protocol for 3 years. Conclusions Immunisation with the allogeneic LNCaP/IL-2/IFN-, vaccine is safe and feasible without any dose-limiting toxicity or autoimmunity. A 50% PSA decline was achieved in two of the six patients. This encouraging data provides the scientific rationale for further investigation of the vaccine in a phase II trial. Copyright © 2007 John Wiley & Sons, Ltd. [source] Discovery and Potency Optimization of 2-Amino-5-arylmethyl-1,3-thiazole Derivatives as Potential Therapeutic Agents for Prostate CancerARCHIV DER PHARMAZIE, Issue 7 2009Mikhail Krasavin Abstract A new chemical series was identified via high-throughput screening as having antiproliferative activity on DU-145 human prostate carcinoma cell line (hit compound potency , 2.9 ,M). Medicinal chemistry optimization of two peripheral diversity vectors of the hit molecule, independently, led to SAR generalizations and identification of the ,best' moieties. The latter were merged in a single compound that exhibited an over 100-fold better potency than the hit compound. For the most potent compounds it was confirmed that the observed antiproliferative potency was not associated with the compounds' non-specific cytotoxicity. [source] In vivo imaging of retinoic acid receptor ,2 transcriptional activation by the histone deacetylase inhibitor MS-275 in retinoid-resistant prostate cancer cellsTHE PROSTATE, Issue 1 2005David Z. Qian Abstract BACKGROUND In retinoid resistant epithelial tumors, the lack of retinoic acid receptor ,2 (RAR,2) expression due to epigenetic silencing impairs the activation of retinoid target genes including RAR,2, and has been associated with the development of cancer. In this study we developed a strategy to monitor the re-activation of RAR,2 by chromatin remodeling agents combined with retinoids in real time, and to correlate the RAR,2 re-activation with anti-tumor activity. METHODS We selected the RAR,2-negative retinoid resistant human prostate carcinoma cell line PC3 and stably transfected it with a luciferase expression vector under the control of a functional segment of RAR,2 promoter (pGL2-RAR,2-PC3). Then, we used the bioluminescence technology to monitor the reporter gene expression in real time both in vitro and in vivo following combination treatment with the histone deacetylase inhibitor MS-275 and 13- cis retinoic acid (CRA). Based on the effective dose for the RAR,2 re-activation, we tested the anti-tumor activity of this drug combination. RESULTS Following combination treatment with MS-275 and CRA, we observed endogenous RAR,2 re-expression, acetylation at the RAR,2 promoter level, and synergistic activation of the luciferase reporter gene by real time imaging both in vitro and in vivo. Combination treatment with MS-275 and CRA restored retinoid sensitivity in human prostate carcinoma cell lines, and had a greater inhibitory effect on tumor cell growth than single agents in vitro and in vivo. CONCLUSIONS This study provides evidence that HDAC inhibitors restore retinoid sensitivity in prostate cancer cells, and in vivo real time imaging of RAR,2 activation may represent a useful tool to study the pharmacodynamics of combination therapy with HDAC inhibitors and retinoids. © 2005 Wiley-Liss, Inc. [source] |