Membrane translocation and activation of GnRH receptor sensitize prostate cancer cells to radiation.

Background: GnRH analogs are widely used as neoadjuvant agents for radiotherapy in prostate cancer (PCa) patients, with well-documented effects in reducing tumor bulk and increasing progression-free survival. GnRH analogs act locally in the prostate by triggering apoptosis of PCa cells via activation of the GnRH receptor (GnRHR). During PCa progression, the distribution of GnRHR within the cell is altered, with reduced expression in the cell membrane and remaining sequestered in the endoplasmic reticulum.

Functional characteristics of cancer stem cells and their role in drug resistance of prostate cancer.

Cancer stem cells (CSCs) have the ability to self-renew and differentiate to give rise to heterogeneous phenotype of the tumor cells. It is believed that these cells are involved in metastasis, recurrence and therapy resistance in various cancers. CSCs have been identified in prostate cancer (PCa), one of the most diagnosed malignancies in men over the world, for which chemotherapy resistance is a major problem in the treatment of castration-resistant advanced stages.

Molecular signature of cancer stem cells isolated from prostate carcinoma and expression of stem markers in different Gleason grades and metastasis.

Prostate cancer (PCa) is the most frequently diagnosed malignancy in men worldwide. Chemotherapy response is very poor and resistance to hormone-based treatments is frequent in advances stages. Recently, tumor-initiating cells or cancer stem cells (CSCs) have been identified in several cancers, including PCa.

Pharmacoperone IN3 enhances the apoptotic effect of leuprolide in prostate cancer cells by increasing the gonadotropin-releasing hormone receptor in the cell membrane.

Gonadotropin-releasing hormone (GnRH) agonists are widely used for the treatment of advanced prostate cancer (PCa). Agonists activate the GnRH receptor (GnRH-R), triggering apoptosis in PCa cells. In gonadotropes, the amount of GnRH-R in the plasma membrane is regulated by protein folding and endoplasmic reticulum retention, mechanisms that can be overcome by the pharmacoperone IN3.

Chemotherapy sensitivity recovery of prostate cancer cells by functional inhibition and knock down of multidrug resistance proteins.

Background: In several cancer types, expression of multidrug resistance (MDR) proteins has been associated with lack of chemotherapy response. In advanced prostate cancer (PCa) the use of chemotherapy is mainly palliative due to its high resistance. Previously, we described that MDR phenotype in PCa could be related with high basal and drug-induced expression of MDR proteins P-Glycoprotein (P-Gp), MRP1, and LRP.

Expression of multidrug resistance proteins in prostate cancer is related with cell sensitivity to chemotherapeutic drugs.

Background: Multidrug resistance (MDR) proteins have been associated with the lack of chemotherapy response. Expression of these proteins has been described in the prostate, but there is no information about their role in the chemotherapy response of prostate cancer (PC). We studied the gene and protein expression of MDR proteins in primary cell cultures from PC tumors and PC cell lines, their relationship with chemotherapy and their effects on cell survival.

The expression of syndecan-1 and -2 is associated with Gleason score and epithelial-mesenchymal transition markers, E-cadherin and beta-catenin, in prostate cancer.

The epithelial-mesenchymal transition (EMT) is considered a key step in tumor progression, where the invasive cancer cells change from epithelial to mesenchymal phenotype. During this process, a decrease or loss in adhesion molecules expression and an increase in migration molecules expression are observed. The aim of this work was to determine the expression and cellular distribution of syndecan-1 and -2 (migration molecules) and E-cadherin and beta-catenin (adhesion molecules) in different stages of prostate cancer progression.

Gonadotropin releasing hormone analogs induce apoptosis by extrinsic pathway involving p53 phosphorylation in primary cell cultures of human prostatic adenocarcinomas.

Background: Gonadotropin-releasing-hormone (GnRH) analogs are widely used to block hypothalamic-pituitary-gonadal axis and inhibit blood androgen levels in patients with prostate cancer (PCa). In addition, GnRH analogs induce proliferation arrest and apoptosis through GnRH receptors expressed on the membrane of PCa cells. Possible molecular mechanisms involved in GnRH-mediated apoptosis on prostate cancer cells were studied.

Characterizing Prostiva RF treatments of the prostate for BPH with gadolinium-enhanced MRI.

Transurethral needle ablation (TUNA) is an accepted and effective therapy for the treatment of lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). Prostiva (Medtronic, Shoreview, MN) is the newest-generation device, which includes a new needle design and radio frequency (RF) generator. This device creates temperatures of 120 degrees C and necrotic lesions in less than 2.

Evaluation of MENT on primary cell cultures from benign prostatic hyperplasia and prostate carcinoma.

7-alpha-Methyl-19-Nortestosterone (MENT) is a synthetic androgen more potent than testosterone (T) and cannot be reduced at 5-alpha position. No important effects of MENT on prostate growth have been reported. However, little is known about the effect of MENT on benign prostatic hyperplasia (BPH) or prostate carcinoma (CaP).

Characterizing TUNA ablative treatments of the prostate for benign hyperplasia with gadolinium-enhanced magnetic resonance imaging.

Background And Purpose: Transurethral Needle Ablation of the prostate TUNA has been accepted as an office-based treatment for benign prostatic hyperplasia (BPH) for many years. Clinical outcomes have been reported, but the amount and location of the necrosis produced have yet to be characterized. The necrosis caused by TUNA was evaluated by gadolinium-enhanced magnetic resonance imaging (MRI) of the pelvis.

Intraprostatic injection of alcohol gel for the treatment of benign prostatic hyperplasia: preliminary clinical results.

Benign prostatic hyperplasia (BPH) is one of the most common diseases ailing older men. Office-based procedures offer the advantage of being more effective than medications, while limiting the adverse effects, cost, and recovery of surgery. This study presents preliminary data on a new procedure that utilizes intraprostatic alcohol gel injection to ablate prostatic tissue.

Interstitial temperature mapping during Prolieve transurethral microwave treatment: imaging reveals thermotherapy temperatures resulting in tissue necrosis and patent prostatic urethra.

Objectives: Temperature mapping of the prostate during transurethral microwave thermotherapy and imaging of the resultant zones of tissue necrosis have been previously performed using several commercial systems. This study was performed using the Prolieve Thermodilatation System, which simultaneously compresses the prostate with a 46F balloon circulating heated fluid and delivering microwave energy into the prostate.

Methods: Interstitial temperature mapping during Prolieve treatment was performed on 10 patients with benign prostatic hyperplasia using 24 temperature sensors arrayed throughout the prostate.

Effect of leuprolide and cetrorelix on cell growth, apoptosis, and GnRH receptor expression in primary cell cultures from human prostate carcinoma.

Contradictory data have been reported regarding the effect of GnRH agonists and antagonists on cell growth and survival, using prostate cancer-derived cell lines expressing either endogenous or exogenous GnRH receptors. We addressed the issue studying the effect of leuprolide (agonist) and cetrorelix (antagonist) on cell growth, apoptosis and GnRH receptor expression using a primary cell coculture system. Also, binding characteristics of prostate GnRH receptor in this culture system are described.

Joint effect among p53, CYP1A1, GSTM1 polymorphism combinations and smoking on prostate cancer risk: an exploratory genotype-environment interaction study.

Aim: To assess the role of several genetic factors in combination with an environmental factor as modulators of prostate cancer risk. We focus on allele variants of low-penetrance genes associated with cell control, the detoxification processes and smoking.

Methods: In a case-control study we compared people carrying p53cd72 Pro allele, CYP1A1 M1 allele and GSTM1 null genotypes with their prostate cancer risk.

In vivo temperature mapping of prostate during treatment with TherMatrx TMx-2000 device: heat field and MRI determinations of necrotic lesions.

Background And Purpose: The effectiveness of any thermotherapy device is determined by the temperatures created and how long they are applied. Understanding the heating characteristics of a thermotherapy device is vital to its correct implementation. Interstitial temperature mapping was used to determine the heat field created within the prostate by the TherMatrx TMx-2000 transurethral microwave thermotherapy (TUMT) device.

Ablation of stage T1/T2 prostate cancer with permanent interstitial temperature self-regulating rods.

Purpose: To determine if stage T(1)/T(2) prostate cancer can be treated safely and effectively with interstitial thermal ablation.

Patients And Methods: Twenty patients with biopsy-confirmed prostate cancer were enrolled in the protocol. The average age was 71.

Effect of GnRH analogs on the expression of TrkA and p75 neurotrophin receptors in primary cell cultures from human prostate adenocarcinoma.

Background: GnRH analogs have antiproliferative and/or apoptotic effects on prostate cancer cells. Also, neurotrophin receptors TrkA and p75 have been reported in normal prostate suggesting a role in the gland growth control. In prostate cancer, TrkA receptors seem to be overexpressed and p75 receptors show a decreased expression.

Relationship among metabolizing genes, smoking and alcohol used as modifier factors on prostate cancer risk: exploring some gene-gene and gene-environment interactions.

Background: Prostate cancer (PCa) is one of the most common male cancers, but the burden of this disease shows remarkable worldwide variation. The role of susceptibility low penetrance genes and environmental factors in the etiology of (PCa) is unclear, but may involve, in some cases, multiple alleles at multiple loci and environmental factors.

Study Objectives: To assess whether CYP1A1, GSTM1, GSTT1 susceptibility genotypes, smoking status and alcohol consumption factors contribute to PCa risk, gene-gene and gene-environment interactions were analyzed.

Glutathione peroxidase activity in cell cultures from different regions of human epididymis.

Aim: To study the secretory activity and androgen regulation of glutathione peroxidase (GPx) in epithelial cell cultures from human epididymis.

Methods: Tissue was obtained from patients undergoing therapeutic orchidectomy for prostatic cancer. Epithelial cell cultures were obtained from the caput, corpus and cauda epididymides.

Secretion of prostatic specific antigen, proliferative activity and androgen response in epithelial-stromal co-cultures from human prostate carcinoma.

We investigate the proliferative activity, prostatic specific antigen (PSA) secretion, morphology and androgen response of human prostate tumour epithelial cells co-cultured with stromal cells in a bicameral system. Stromal and epithelial cells were isolated from prostate adenocarcinoma by enzyme digestion and cultured in defined media. Immunocytochemistry for prostate carcinoma tumour antigen (PCTA-1) was performed for culture purity evaluation.

Cooled transurethral microwave thermotherapy for intractable chronic prostatitis--results of a pilot study after 1 year.

Objectives: To evaluate the side effects, tolerability, and efficacy of transurethral microwave thermotherapy with urethral cooling (cooled TUMT) for chronic prostatitis/chronic pelvic pain syndrome in a prospective feasibility trial. Cooled TUMT, using the Targis system from Urologix, is an established treatment option for benign prostatic hyperplasia (BPH) with minimal side effects.

Methods: Patients with intractable chronic prostatitis/chronic pelvic pain syndrome and symptoms for more than 3 of the 6 months before treatment (National Institutes of Health-Chronic Prostatitis Symptom Index [NIH-CPSI] pain score of at least 8) were randomized to cooled TUMT at an intraprostatic temperature of either approximately 55 degrees C or approximately 70 degrees C.

[Gene-gene and gene-environment interactions as modifier factors of prostatic cancer risk: "a case-only" design study].

Background: The role of susceptibility low penetrance genes and environmental factors in the etiology of prostate cancer (PCa) is unclear, but may involve in some cases multiple alleles at multiple loci.

Aim: To evaluate the association of gene-gene and gene-environment interactions with PCa.

Patients And Methods: One hundred three subjects with biopsy proven PCa were studied, using a case-only design.

Evaluation of microwave thermotherapy with histopathology, magnetic resonance imaging and temperature mapping.

Purpose: Interstitial temperature mapping was used to determine the heat field within the prostate by the Coretherm (ProstaLund, Lund, Sweden) transurethral microwave thermotherapy device. Gadolinium enhanced magnetic resonance imaging (MRI) and histopathology were used to determine the extent and pattern of coagulation necrosis following treatment. The cell kill assessment feature of the device was compared with MRI and histopathology.

Gadolinium-enhanced MRI in the evaluation of minimally invasive treatments of the prostate: correlation with histopathologic findings.

Objectives: To explore the use of magnetic resonance imaging (MRI) with gadolinium enhancement as a noninvasive method to image the extent of ablation after minimally invasive treatment. Minimally invasive methods for ablating prostatic tissue have emerged as a viable option in the treatment of prostate disease. As these devices enter the mainstream of patient care, imaging methods that verify the exact location, extent, and pattern of the ablation are needed.