A non-invasive 25-Gene PLNM-Score urine test for detection of prostate cancer pelvic lymph node metastasis.

Background: Prostate cancer patients with pelvic lymph node metastasis (PLNM) have poor prognosis. Based on EAU guidelines, patients with >5% risk of PLNM by nomograms often receive pelvic lymph node dissection (PLND) during prostatectomy. However, nomograms have limited accuracy, so large numbers of false positive patients receive unnecessary surgery with potentially serious side effects.

Experimental in vivo model to evaluate the impact of Cernitin™ on pain response on induced chronic bladder inflammation.

Objective: Inflammation of the urinary bladder may cause burdensome pain also called bladder pain syndrome (BPS). A limitation in understanding BPS pathophysiology is the lack of appropriate preclinical model. Previously published clinical and preclinical studies revealed positive impact of Cernitin™ on pain relief in chronic prostatitis.

Non-invasive Urine Test for Molecular Classification of Clinical Significance in Newly Diagnosed Prostate Cancer Patients.

To avoid over-treatment of low-risk prostate cancer patients, it is important to identify clinically significant and insignificant cancer for treatment decision-making. However, no accurate test is currently available. To address this unmet medical need, we developed a novel gene classifier to distinguish clinically significant and insignificant cancer, which were classified based on the National Comprehensive Cancer Network risk stratification guidelines.

Development and validation of a 25-Gene Panel urine test for prostate cancer diagnosis and potential treatment follow-up.

Background: Heterogeneity of prostate cancer (PCa) contributes to inaccurate cancer screening and diagnosis, unnecessary biopsies, and overtreatment. We intended to develop non-invasive urine tests for accurate PCa diagnosis to avoid unnecessary biopsies.

Methods: Using a machine learning program, we identified a 25-Gene Panel classifier for distinguishing PCa and benign prostate.

The functional interlink between AR and MMP9/VEGF signaling axis is mediated through PIP5K1α/pAKT in prostate cancer.

Currently, no effective targeted therapeutics exists for treatment of metastatic prostate cancer (PCa). Given that matrix metalloproteinases 9 (MMP9) and its associated vascular endothelial growth factor (VEGF) are critical for tumor vascularization and invasion under castration-resistant condition, it is therefore of great importance to define the functional association and interplay between androgen receptor (AR) and MMP9 and their associated key survival and invasion pathways in PCa cells. Here, we found that there was a significant correlation between MMP9 and AR protein expression in primary and metastatic PCa tissues, and a trend that high level of MMP9 expression was associated with poor prognosis.

The effects of Cernitin® on inflammatory parameters and benign prostatic hyperplasia: An in vitro study.

The pollen extract Cernitin® is widely used for treatment of benign prostatic hyperplasia (BPH) and non-bacterial chronin prostatitis. However, little is known about the underlying molecular mechanisms to explain the clinical effects of Cernitin®. In this study, we sought to investigate the cellular mechanisms by which Cernitin® induces its effects on human prostatic cell lines BPH-1 and WPMY-1 and primary human peripheral blood mononuclear cells (hPBMCs) in vitro.

Cell-based evidence regarding the role of FSH in prostate cancer.

Introduction: Conversion of androgen-responsive prostate cancer (CaP) to castration-resistant CaP is associated with an acceleration of the disease that often requires treatment modalities other than androgen deprivation therapy only. Recently, follicle-stimulating hormone (FSH) has been shown to play a role in CaP growth, and clinical data showed that high serum concentration of FSH in chemically castrated CaP patients was associated with a shorter time of progression to castration-resistant CaP. In this study, we sought to investigate if FSH could have direct effects on CaP cells, possibly through the androgen receptor and androgen receptor regulated genes, such as prostate-specific antigen (PSA).

Correction: Interaction between c-jun and Androgen Receptor Determines the Outcome of Taxane Therapy in Castration Resistant Prostate Cancer.

[This corrects the article DOI: 10.1371/journal.pone.

Targeted suppression of AR-V7 using PIP5K1α inhibitor overcomes enzalutamide resistance in prostate cancer cells.

One mechanism of resistance of prostate cancer (PCa) to enzalutamide (MDV3100) treatment is the increased expression of AR variants lacking the ligand binding-domain, the best characterized of which is AR-V7. We have previously reported that Phosphatidylinositol-4-phosphate 5-kinase alpha (PIP5Kα), is a lipid kinase that links to CDK1 and AR pathways. The discovery of PIP5Kα inhibitor highlight the potential of PIP5K1α as a drug target in PCa.

Different expression levels of glycans on leukemic cells-a novel screening method with molecularly imprinted polymers (MIP) targeting sialic acid.

Sialic acid (SA) is normally expressed on the cell membranes and is located at the terminal position of the sugar chains. SA plays an important role for regulation of the innate immunity, function as markers of the cells and can be recognized by a variety of receptors. Interestingly, the level of SA expression is increased on metastatic cancer cells.

Sialic Acid-Imprinted Fluorescent Core-Shell Particles for Selective Labeling of Cell Surface Glycans.

The expression of cell surface glycans terminating with sialic acid (SA) residues has been found to correlate with various disease states there among cancer. We here report a novel strategy for specific fluorescence labeling of such motifs. This is based on sialic acid-imprinted core-shell nanoparticles equipped with nitrobenzoxadiazole (NBD) fluorescent reporter groups allowing environmentally sensitive fluorescence detection at convenient excitation and emission wavelengths.

Influence of Melatonin on the Proliferative and Apoptotic Responses of the Prostate under Normal and Hyperglycemic Conditions.

The antitumor properties of melatonin (MLT) are known for prostate cancer cells. This study investigated whether MLT affects prostate maturation and interferes with tissue injuries induced by diabetes. MLT was administered to Wistar rats from 5 weeks of age in the drinking water (10 μg/kg b.

Interaction between c-jun and androgen receptor determines the outcome of taxane therapy in castration resistant prostate cancer.

Taxane based chemotherapy is the standard of care treatment in castration resistant prostate cancer (CRPC). There is convincing evidence that taxane therapy affects androgen receptor (AR) but the exact mechanisms have to be further elucidated. Our studies identified c-jun as a crucial key player which interacts with AR and thus determines the outcome of the taxane therapy given.

Enzalutamide as a second generation antiandrogen for treatment of advanced prostate cancer.

Prostate cancer (PCa) is the most common malignancy, and the third leading cancer-related cause of death among men of the Western world. Upon PCa progression into metastatic disease, androgen deprivation therapy is applied as the first-line treatment, and has been shown to be effective in most patients, leading to a decrease in serum prostate-specific antigen and relief of disease-related symptoms. However, advanced PCa almost inevitably progresses to a castration-resistant state, and is currently regarded as incurable.

Cyclin A1 modulates the expression of vascular endothelial growth factor and promotes hormone-dependent growth and angiogenesis of breast cancer.

Alterations in cellular pathways related to both endocrine and vascular endothelial growth factors (VEGF) may contribute to breast cancer progression. Inhibition of the elevated levels of these pathways is associated with clinical benefits. However, molecular mechanisms by which endocrine-related pathways and VEGF signalling cooperatively promote breast cancer progression remain poorly understood.

Expression and localization of serotonin receptors in human breast cancer.

The aim of this study was to examine the expression of serotonin receptors in patients with breast cancer and to explore their utility as diagnostic and prognostic markers. Immunohistochemical analysis was performed to examine the expression of serotonin (5-HT) receptor subtypes 1A, 1B, 2B and 4 in a tissue microarray containing tumor specimens from 102 patients. Statistical analysis was performed to correlate the expression of these proteins with regard to clinical parameters.

Expression of serotonin receptors 5-HT1A, 5-HT1B, 5-HT2B and 5-HT4 in ovary and in ovarian tumours.

Background: Recently we have shown that serotonin receptors may be involved in prostate cancer development. In ovarian carcinogenesis, oestrogen may play a role. As oestrogen seems to mediate at least some of its biological effects through serotonin, we decided to evaluate if serotonin receptors are expressed in ovary and in ovarian tumours and if the expression is correlated to ovarian tumour development.

Androgen Receptor Enhances p27 Degradation in Prostate Cancer Cells through Rapid and Selective TORC2 Activation.

Androgen receptor (AR) plays a central role in prostate cancer (PCa) growth, with androgen deprivation or AR down-regulation causing cell-cycle arrest and accumulation of the p27 cyclin-dependent kinase inhibitor. The molecular basis for this AR regulation of cell-cycle progression remains unclear. Here we demonstrate that androgen can rapidly reduce p27 protein in PCa cells by increasing its proteasome-mediated degradation.

Regional distribution of neuroendocrine cells in the urogenital duct system of the male rat.

Background: Neuroendocrine (NE) cells are frequently present in the human prostate and urethra, whereas they are lacking in the other urogenital organs. This study was undertaken as there are only few detailed studies available on the distribution, form and function of NE cells and the structure of excretory ducts of the accessory sex organs in the male rat.

Methods: Systematic gross anatomical dissections were combined with immunohistochemical and electron microscopic studies of the excretory ducts of the urogenital glands in male rats, with particular focus on the distribution and ultrastructure of the NE cells.

Properties and effects of a novel liquid crystal nanoparticle formulation of docetaxel in a prostate cancer mouse model.

Treatment with docetaxel is the standard of care as first line chemotherapy in castration resistant prostate cancer. Due to serious side effects from the commercially available Taxotere formulation, we aimed to develop a safe and effective nanoparticle formulation of docetaxel. Liquid crystal nanoparticles (LCNPs), based on phosphatidyl choline, glycerol dioleate and polysorbate 80 dispersed in excess aqueous solution, were produced by simple procedures as carriers of docetaxel.

Serotonin activates MAP kinase and PI3K/Akt signaling pathways in prostate cancer cell lines.

Purpose: This study was conducted to examine the effects of 5-HT on extracellular signal-regulated kinase 1/2 (Erk1/2) and Akt pathways in prostate cancer (PC) cells.

Methods: PC cell lines PC-3, Du145, and LNCaP stimulated with 5-HT in the presence of MEK or PI3K inhibitors and 5-HT receptor subtype 1A antagonist were analyzed by Western blotting and immunofluorescence. The proliferation assay BrdU and Boyden chamber were used to determine proliferation and migration, respectively.

The effect of a novel botanical agent TBS-101 on invasive prostate cancer in animal models.

Background: Traditional Botanical Supplement-101 (TBS-101) is a newly developed proprietary botanical agent containing seven standardized botanical extracts, including: Panax ginseng, cranberry, green tea, grape skin, grape seed, Ganoderma lucidum and chamomile. Each of the components has been consumed either in the regular diet or as natural supplement. When used as a single agent, each of these seven botanicals has been implicated in chemoprevention and therapy in various types of cancer.

Malignant lesions in the ventral prostate of alloxan-induced diabetic rats.

The aim of this study was to evaluate the changes caused by chronic diabetes in the rat ventral prostate and to establish a correlation between diabetes and the development of prostatic lesions. Male rats received alloxan (42 mg/kg b.w.

Multiple cellular mechanisms related to cyclin A1 in prostate cancer invasion and metastasis.

Background: Cyclin A1 is a cell cycle regulator that has been implicated in the progression of prostate cancer. Its role in invasion and metastasis of this disease has not been characterized.

Methods: Immunohistochemistry and cDNA microarray analyses were used to assess protein and mRNA expression of cyclin A1 and proteins with roles in metastasis, including vascular endothelial growth factor (VEGF), metalloproteinase 2 (MMP2), and MMP9, in human prostate cancer.