Project description:Genome-wide DNA methylation profiling of prostate specimens from a clinical trial of genistein supplementation prior to prostatectomy.
Project description:Prior studies support the notion that the experimental chemopreventive agent, genistein, inhibits prostate cancer (PCa) cell movement in humans and that this in turn inhibits metastatic spread, thereby preventing PCa-specific death. As many effects have been ascribed to genistein, it has been considered a non-specific agent. However, its effects are concentration-dependent, and the vast majority of studies use concentrations greater than 3 logs above those associated with dietary consumption. Genistein is found in soy, and individuals consuming soy-based diets have blood concentrations of free genistein in the low nanomalar range. Using dosing guided by phase I pharmacokinetic studies in US men, prospective treatment of men on a phase II trial with genistein for one month prior to radical prostatectomy for localized PCa. Here we conducted an unbiased screening for effects of genistein in prostate as well as evaluate changes between normal and cancer cells.
Project description:Patients with high-risk localized prostate cancer (tumor-node-metastasis ≥ T2b or prostate-specific antigen ≥ 15 ng/mL or Gleason glade ≥ 4+3) were enrolled into a phase II clinical trial of neoadjuvant chemotherapy with docetaxel and mitoxantrone followed by prostatectomy. Pretreatment prostate tissue was acquired by needle biopsy and posttreatment tissue was acquired by prostatectomy. Prostate epithelium was captured by microdissection, and transcript levels were quantitated by cDNA microarray hybridization. To evaluate gene expression alterations after chemotherapy, neoplastic epithelium from pretreated biopsy and posttreated prostatectomy specimens were laser captured separately (∼3,000 cells per sample). cDNA synthesized from amplified total RNA of pre-treated biopsy samples and post-treatment surgical samples were hybridized head-to-head, alternating Cy3 and Cy5 to custom-made microarrays composed of 6,200 clones derived from the Prostate Expression Database.
Project description:Patients with high-risk localized prostate cancer (tumor-node-metastasis ≥ T2b or prostate-specific antigen ≥ 15 ng/mL or Gleason glade ≥ 4+3) were enrolled into a phase II clinical trial of neoadjuvant chemotherapy with docetaxel and mitoxantrone followed by prostatectomy. Pretreatment prostate tissue was acquired by needle biopsy and posttreatment tissue was acquired by prostatectomy. Prostate epithelium was captured by microdissection, and transcript levels were quantitated by cDNA microarray hybridization.
Project description:Clinical resection specimens of prostate tissue (radical prostatectomy and TUR-P) over the course of hormone deprivation therapy were flow sorted according to their DNA content (Ploidy) and subjected to aCGH analysis to identify possiple chromosomal abberations which could confer castration resistance.
Project description:We have investigated the effects of genistein on several prostate cancer cell lines, including the ARCaP-E/ARCaP-M model of the epithelial-to-mesenchymal transition (EMT), to analyze effects on their epigenetic state. In addition, we investigated the effects of combined treatment of genistein with the histone deacetylase inhibitor vorinostat on survival in prostate cancer cells. Using whole-genome expression profiling and whole-genome methylation profiling, we have determined the genome-wide differences in genetic and epigenetic responses to genistein in prostate cancer cells before and after undergoing the EMT. Also, cells were treated with genistein, vorinostat, and a combination treatment, where cell death and cell proliferation was determined.
Project description:We have investigated the effects of genistein on several prostate cancer cell lines, including the ARCaP-E/ARCaP-M model of the epithelial-to-mesenchymal transition (EMT), to analyze effects on their epigenetic state. In addition, we investigated the effects of combined treatment of genistein with the histone deacetylase inhibitor vorinostat on survival in prostate cancer cells. Using whole-genome expression profiling and whole-genome methylation profiling, we have determined the genome-wide differences in genetic and epigenetic responses to genistein in prostate cancer cells before and after undergoing the EMT. Also, cells were treated with genistein, vorinostat, and a combination treatment, where cell death and cell proliferation was determined.
Project description:Proteome characterization of gland confined prostate tumors and non-malignant prostate tissue. Whole cell protein extracts were purified from FFPE radical prostatectomy specimens for a total of 28 tumor samples and 8 adjacent non-malignant prostate tissues. Associated ProteomeXchange identifiers: PXD003430, PXD003515, PXD004132, PXD003615, PXD003636, PXD004159.
Project description:Proteome characterization of gland confined prostate tumors and non-malignant prostate tissue. Whole cell protein extracts were purified from FFPE radical prostatectomy specimens for a total of 28 tumor samples and 8 adjacent non-malignant prostate tissues. Associated ProteomeXchange identifiers: PXD003430, PXD003452, PXD003515, PXD004132, PXD003636, PXD004159.
