is essential for xenograft tumor development in mice injected with the human prostate cancer cell-line, LNCaP, and modulates cell migration and invasion.

Background And Objective: A growing body of literature suggests modulated expression of members of the opiorphin family of genes (, and ) is associated with cancer. Recently, overexpression of was shown to be associated with prostate cancer, with evidence of a role in overcoming the hypoxic barrier that develops as tumors grow. The primary goal of the present studies was to support and expand evidence for a role of in the development and progression of prostate cancer.

Role of opiorphin genes in prostate cancer growth and progression.

We describe the first studies investigating a role for opiorphin genes (, and ) in prostate cancer (PrCa). Databases and PrCa tissue arrays were screened for opiorphin expression. Xenografted tumor growth of human PrCa cells overexpressing was compared with controls in nude mice.

Identification and characterization of RSIY-11, a novel seminal peptide derived from semenogelin-1, which acts as a neutral endopeptidase inhibitor modulating sperm motility.

Purpose: Based on prior reports demonstrating that neutral endopeptidase (NEP) inhibitors increase sperm motility, the goal of our studies was to identify endogenous seminal peptides that inhibit NEP and investigate their potential effect on sperm motility.

Methods: Peptidomic analysis was performed on human seminal fluid, identifying 22 novel peptides. One peptide, named RSIY-11, derived from semenogelin-1, was predicted through sequence analysis to be a substrate and/or potential inhibitor of NEP.

Development and Application of a Novel Model System to Study "Active" and "Passive" Tumor Targeting.

Macromolecular reagents can be targeted to tumors through active and passive mechanisms. "Active" targeting involves moieties, such as receptor ligands, to direct tumor cell binding, whereas "passive" targeting relies on long reagent circulating half-life, abnormal tumor vasculature, and poor lymphatic drainage for tumor entrapment. Here, we sought to study the impact of reagent circulating half-life on "active" and "passive" tumor uptake.

Systemic Administration and Targeted Radiosensitization via Chemically Synthetic Aptamer-siRNA Chimeras in Human Tumor Xenografts.

Radiation therapy is a highly effective tool for treating all stages of prostate cancer, from curative approaches in localized disease to palliative care and enhanced survival for patients with distant bone metastases. The therapeutic index of these approaches may be enhanced with targeted radiation-sensitizing agents. Aptamers are promising nucleic acid delivery agents for short interfering RNAs (siRNA) and short hairpin RNAs (shRNA).

Real-time, near-infrared fluorescence imaging with an optimized dye/light source/camera combination for surgical guidance of prostate cancer.

Purpose: The prostate-specific membrane antigen (PSMA) is a surface glycoprotein overexpressed on malignant prostate cells, as well as in the neovasculature of many tumors. Recent efforts to target PSMA for imaging prostate cancer rely on suitably functionalized low-molecular-weight agents. YC-27 is a low-molecular-weight, urea-based agent that enables near-infrared (NIR) imaging of PSMA in vivo.

Evaluation of prostate-specific membrane antigen as an imaging reporter.

Unlabelled: Genetic reporters provide a noninvasive method to monitor and evaluate a population of cells. The ideal properties of a gene reporter-probe system include biocompatibility, lack of immunogenicity, low background expression or signal, and high sensitivity of detection. The prostate-specific membrane antigen (PSMA) is an attractive candidate for a genetic reporter as it is a human transmembrane protein with a selective expression pattern, and there are several PSMA imaging agents available for clinical and preclinical applications.

Development and screening of a series of antibody-conjugated and silica-coated iron oxide nanoparticles for targeting the prostate-specific membrane antigen.

The prostate-specific membrane antigen (PSMA) is an established target for the delivery of cancer therapeutic and imaging agents due to its high expression on the surface of prostate cancer cells and within the neovasculature of other solid tumors. Here, we describe the synthesis and screening of antibody-conjugated silica-coated iron oxide nanoparticles for PSMA-specific cell targeting. The humanized anti-PSMA antibody, HuJ591, was conjugated to a series of nanoparticles with varying densities of polyethylene glycol and primary amine groups.

Monitoring nanoparticle-mediated cellular hyperthermia with a high-sensitivity biosensor.

Aim: To develop and apply a heat-responsive and secreted reporter assay for comparing cellular response to nanoparticle (NP)- and macroscopic-mediated sublethal hyperthermia.

Materials & Methods: Reporter cells were heated by water bath (macroscopic heating) or iron oxide NPs activated by alternating magnetic fields (nanoscopic heating). Cellular responses to these thermal stresses were measured in the conditioned media by secreted luciferase assay.

Selective cancer targeting via aberrant behavior of cancer cell-associated glucocorticoid receptor.

Glucocorticoid receptors (GRs) are ubiquitous, nuclear hormone receptors residing in cell types of both cancer and noncancerous origin. It is not known whether cancer cell-associated GR alone can be selectively manipulated for delivery of exogenous genes to its nucleus for eliciting anticancer effect. We find that GR ligand, dexamethasone (Dex) in association with cationic lipoplex (termed as targeted lipoplex) could selectively manipulate GR in cancer cells alone for the delivery of transgenes in the nucleus, a phenomenon that remained unobserved in normal cells.

Haloperidol-associated stealth liposomes: a potent carrier for delivering genes to human breast cancer cells.

Sigma receptors are membrane-bound proteins that are overexpressed in certain human malignancies including breast cancer. These receptors show very high affinity for various sigma ligands including neuroleptics like haloperidol. We hypothesized that in associating haloperidol-linked lipid into the cationic lipid-DNA complex, we can specifically target and deliver genes to breast cancer cells that overexpress sigma receptors.