Functional validation of metabolic genes that distinguish Gleason 3 from Gleason 4 prostate cancer foci.

Background: Gleason grade is among the most powerful clinicopathological classification systems used to assess risk of lethal potential in prostate cancer, yet its biologic basis is poorly understood. Notably, pure low-grade cancers, comprised predominantly of Gleason pattern 3 (G3) are typically indolent, with lethal potential emerging with the progression of higher-grade Gleason patterns 4 (G4) or 5. One of the hallmarks of more aggressive cancer phenotypes is the stereotyped set of metabolic characteristics that transformed cells acquire to facilitate unregulated growth.

Combining Desmopressin and Docetaxel for the Treatment of Castration-Resistant Prostate Cancer in an Orthotopic Model.

Background/aim: Desmopressin is a synthetic analogue of the antidiuretic hormone vasopressin. It has recently been demonstrated to inhibit tumor progression and metastasis in breast cancer models. Docetaxel is a chemotherapy agent for castrate-resistant prostate cancer (CRPC).

Cannabinoid WIN 55,212-2 induces cell cycle arrest and apoptosis, and inhibits proliferation, migration, invasion, and tumor growth in prostate cancer in a cannabinoid-receptor 2 dependent manner.

Background: Cannabinoids have demonstrated anticarcinogenic properties in a variety of malignancies, including in prostate cancer. In the present study, we explored the anti-cancer effects of the synthetic cannabinoid WIN 55,212-2 (WIN) in prostate cancer.

Methods: Established prostate cancer cells (PC3, DU145, LNCaP) were treated with varying concentrations of WIN.

Total energy expenditure and vigorous-intensity physical activity are associated with reduced odds of reclassification among men on active surveillance.

Background: Research examining the association between physical activity (PA) and prostate cancer (PCa) has accumulated; however, few studies have examined this association in the context of active surveillance. The current study examines this among men initially diagnosed with favorable-risk PCa and managed by active surveillance at Sunnybrook Health Sciences Centre in Canada and the Royal Marsden Hospital in the United Kingdom.

Methods: Participants completed a questionnaire on daily participation in non-leisure, transport, and recreational PA.

Evaluating Metformin as a Potential Chemosensitizing Agent when Combined with Docetaxel Chemotherapy in Castration-resistant Prostate Cancer Cells.

Background/aim: Docetaxel, the first-line chemotherapy for metastatic castration-resistant prostate cancer (mCRPC), provides certain survival benefits, but is associated with significant toxicity. A novel therapeutic approach for mCRPC is combining docetaxel with a chemosensitizing agent. We hypothesized that metformin, a potential chemosensitizer, would improve docetaxel efficacy in CRPC cells.

The Effect of Metformin Use during Docetaxel Chemotherapy on Prostate Cancer Specific and Overall Survival of Diabetic Patients with Castration Resistant Prostate Cancer.

Purpose: Docetaxel is the first line chemotherapy currently used to treat patients with symptomatic metastatic castration resistant prostate cancer. Although it provides survival benefits, it is associated with significant side effects. Novel therapeutic options are needed for patients with metastatic castration resistant prostate cancer and an approach is combining docetaxel with chemosensitizing agents.

Urinary DNA Methylation Biomarkers for Noninvasive Prediction of Aggressive Disease in Patients with Prostate Cancer on Active Surveillance.

Purpose: Patients with prostate cancer on active surveillance are monitored by repeat prostate specific antigen measurements, digital rectal examinations and prostate biopsies. A subset of patients on active surveillance will later reclassify with disease progression, prompting definitive treatment. To minimize the risk of under treating such patients on active surveillance minimally invasive tests are urgently needed incorporating biomarkers to identify patients who will reclassify.

Designing a broad-spectrum integrative approach for cancer prevention and treatment.

Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.

A combination of desmopressin and docetaxel inhibit cell proliferation and invasion mediated by urokinase-type plasminogen activator (uPA) in human prostate cancer cells.

Background: This study was designed to assess the effectiveness of a combination treatment using both desmopressin and docetaxel in prostate cancer treatment. Desmopressin is a well-known synthetic analogue of the antidiuretic hormone vasopressin. It has recently been demonstrated to inhibit tumor progression and metastasis in in vivo models.

Capsaicin reduces the metastatic burden in the transgenic adenocarcinoma of the mouse prostate model.

Background: Capsaicin, the active compound in chili peppers, has demonstrated anti- carcinogenic properties in vitro in a number of malignancies, including the prostate. In the present study, we investigate the chemopreventive potential of capsaicin on prostate cancer using the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. The TRAMP is a murine model that resembles the progression of human disease.

The effects of serum from prostate cancer patients with elevated body mass index on prostate cancer cells in vitro.

We examined whether serum from obese, compared to non-obese, PCa (prostate cancer) patients creates a growth-enhancing tumor micro-environment in vitro. Serum from 80 subjects was divided into four groups: normal weight men with and without PCa and overweight/obese men with and without PCa. Cell proliferation, migration, and invasion were measured in LNCaP, and PC3 cells treated with patient serum were obtained from the above groups.

Cancer prevention and therapy through the modulation of the tumor microenvironment.

Cancer arises in the context of an in vivo tumor microenvironment. This microenvironment is both a cause and consequence of tumorigenesis. Tumor and host cells co-evolve dynamically through indirect and direct cellular interactions, eliciting multiscale effects on many biological programs, including cellular proliferation, growth, and metabolism, as well as angiogenesis and hypoxia and innate and adaptive immunity.

Capsaicin: a novel radio-sensitizing agent for prostate cancer.

Introduction: Radio-sensitizing agents sensitize tumor cells to the lethal effects of radiotherapy (RT) allowing for use of lower doses of radiation to achieve equivalent cancer control, while minimizing adverse effects to normal tissues. Given their limited toxicity and ability to easily integrate into the diet, compounds occurring naturally in the diet make ideal potential radio-sensitizing agents. In this study, we have examined whether capsaicin, the active compound in chilli peppers, can modulate the response to RT in preclinical models of prostate cancer (PCa).

Exercise does not counteract the effects of a "westernized" diet on prostate cancer xenografts.

Background: The relationships between diet, exercise, and prostate cancer (PCa) remain unclear. We have previously reported that a "Western" diet promotes PCa tumor growth in vivo. Presently, we report the effects of sustained aerobic exercise on PCa progression in animals fed a high-fat diet versus a standard diet.

Diet, obesity, and cancer progression: are adipocytes the link?

Obesity has been linked to more aggressive characteristics of several cancers, including breast and prostate cancer. Adipose tissue appears to contribute to paracrine interactions in the tumor microenvironment. In particular, cancer-associated adipocytes interact reciprocally with cancer cells and influence cancer progression.

Population based study of long-term rates of surgery for urinary incontinence after radical prostatectomy for prostate cancer.

Purpose: Urinary incontinence can be a significant complication of radical prostatectomy. It can be treated with post-prostatectomy surgical procedures. The long-term rate of patients who undergo these surgeries, including artificial urinary sphincter or urethral sling insertion, is not well described.

New variants at 10q26 and 15q21 are associated with aggressive prostate cancer in a genome-wide association study from a prostate biopsy screening cohort.

Purpose: To identify and examine polymorphisms of genes associated with aggressive and clinical significant forms of prostate cancer among a screening cohort.

Experimental Design: We conducted a genome-wide association study among patients with aggressive forms of prostate cancer and biopsy-proven normal controls ascertained from a prostate cancer screening program. We then examined significant associations of specific polymorphisms among a prostate cancer screened cohort to examine their predictive ability in detecting prostate cancer.

Induction of specific human cytotoxic T cells using dendritic cells transduced with an adenovector encoding rat epidermal growth factor receptor 2.

This study demonstrates the ability to generate antigen-specific cytotoxic T cells (CTLs) against HER2 using a xenoantigenic immune stimulation strategy. Dendritic cells (DCs) were transduced with an adenovirus vector incorporating full-length cDNA for rat (xenoantigen) epidermal growth factor receptor 2 (Adv-HER2). Stimulation of autologous T cells with Adv-HER2 infected DCs led to enhanced HER2-specific reactivity as assessed by quantitative real-time polymerase chain reaction (qRT-PCR) for T cell IFN-γ mRNA.

Prospective multi-institutional study evaluating the performance of prostate cancer risk calculators.

Purpose: Prostate cancer risk calculators incorporate many factors to evaluate an individual's risk for prostate cancer. We validated two common North American-based, prostate cancer risk calculators.

Patients And Methods: We conducted a prospective, multi-institutional study of 2,130 patients who underwent a prostate biopsy for prostate cancer detection from five centers.

A whole-genome SNP association study of NCI60 cell line panel indicates a role of Ca2+ signaling in selenium resistance.

Epidemiological studies have suggested an association between selenium intake and protection from a variety of cancer. Considering this clinical importance of selenium, we aimed to identify the genes associated with resistance to selenium treatment. We have applied a previous methodology developed by our group, which is based on the genetic and pharmacological data publicly available for the NCI60 cancer cell line panel.

Diet and prostate cancer: mechanisms of action and implications for chemoprevention.

As one of the most prevalent cancers, prostate cancer has enormous public health significance and prevention strategies would attenuate its economic, emotional, physical and social impact. Until recently, however, we have had only modest information about risk factors for this disease, apart from the well-established characteristics of age, family history and place of birth. The large worldwide variation in the incidence of prostate cancer and the increased risk in migrants who move from low-risk to high-risk countries provide strong support for modifiable environmental factors, particularly diet, in its etiology.

Antiproliferative mechanisms of the flavonoids 2,2'-dihydroxychalcone and fisetin in human prostate cancer cells.

We have previously demonstrated the antiproliferative effect of two flavonoids-2,2'-dihydroxychalcone (DHC), a novel synthetic flavonoid, and fisetin, a naturally occurring flavonol-in prostate cancer cells. In this study, we further examine the mechanisms of these compounds on survival and proliferation pathways. DHC and fisetin (1-50 microM) caused a dose-dependent reduction in viability, a concomitant increase in apoptosis in PC3 cells at 72 h, and a decrease in clonogenic survival at 24 h treatment.

Protective effect of metformin in CD1 mice placed on a high carbohydrate-high fat diet.

A high carbohydrate-high fat (HC-HF) diet-associated with hyperinsulinemia has been previously reported to induce accelerated growth of prostate cancer in a xenograft model. High energy supply and insulin/insulin growth factor-1 axis are two of the mechanisms proposed. We hypothesize that metformin may have a protective effect against prostate cancer progression by affecting metabolisms associated with high energy intake.