Conference report and review: current status of biomarkers potentially associated with prostate cancer outcomes.

Purpose: The use of prostate specific antigen screening to diagnose and monitor prostate cancer is associated with well-known shortcomings. A 2-day Prostate Cancer Biomarker Conference was convened to identify promising areas of research and focus efforts on the most critical needs.

Materials And Methods: The conference provided a forum for the presentation and discussion of ongoing prostate cancer biomarker research.

A phase I and pharmacokinetic study of silybin-phytosome in prostate cancer patients.

Silibinin is a polyphenolic flavonoid isolated from milk thistle with anti-neoplastic activity in several in vitro and in vivo models of cancer, including prostate cancer. Silybin-phytosome is a commercially available formulation containing silibinin. This trial was designed to assess the toxicity of high-dose silybin-phytosome and recommend a phase II dose.

Binding and cytotoxicity of conjugated and recombinant fusion proteins targeted to the gonadotropin-releasing hormone receptor.

Pokeweed antiviral protein (PAP) is a plant-derived, highly potent ribosome inactivating protein that causes inhibition of protein translation and rapid cell death. We and others have delivered this protein to various cell types, including cancer cells, using hormones to specifically target cells bearing the hormone receptor. Here, we compare binding and cytotoxicity of GnRH-PAP hormonotoxins prepared either by protein conjugation (GnRH-PAP conjugate) or through recombinant DNA technology (GnRH-PAP fusion).

Epidermal growth factor receptor mediates silibinin-induced cytotoxicity in a rat glioma cell line.

Silibinin, derived from milk thistle extract, has been shown to inhibit growth factor receptor-mediated mitogenic and cell survival signaling, and to alter cell cycle regulators. Alteration in pathways regulating cell growth likely account for silibinin's inhibition of tumor growth. Since the epidermal growth factor receptor (EGFR) is a key regulator in cell signaling pathways, in the present study we directly tested the hypothesis that the EGFR plays a key role in mediating silibinin cytotoxicity to cancer cells.

GnRH-PAP hormonotoxin targets cytotoxicity to prostate cancer cell lines.

Pokeweed antiviral protein (PAP) is a plant-derived, highly potent ribosome inactivating protein that causes inhibition of protein translation and rapid cell death. We have previously described potent cytotoxic activity of a GnRH (gonadotropin-releasing hormone) receptor-targeted conjugate protein (GnRH-PAP) and demonstrated that cytotoxicity depended on the number of GnRH receptors and the duration of exposure. Here, we demonstrate that the GnRH-PAP conjugate was cytotoxic to three different prostate cancer cell lines, supporting the feasibility of using such hormonotoxins as novel therapeutics for hormone-responsive cancers such as prostate cancer.