Explore the vast range of titles available.

Purpose Prostate cancer (PCa) is the second most common cause of cancer-related death among men in the United States. Due to the lipid-driven metabolic phenotype of PCa, imaging with 2-deoxy-2-[ 18 F]fluoro- d -glucose ([ 18 F]FDG) is suboptimal, since tumors tend to have low avidity for glucose. Procedures We have used the fat oxidation inhibitor etomoxir (2-[6-(4-chlorophenoxy)-hexyl]oxirane-2-carboxylate) that targets carnitine-palmitoyl-transferase-1 (CPT-1) to increase glucose uptake in PCa cell lines. Small hairpin RNA specific for CPT1A was used to confirm the glycolytic switch induced by etomoxir in vitro . Systemic etomoxir treatment was used to enhance [ 18 F]FDG-positron emission tomography ([ 18 F]FDG-PET) imaging in PCa xenograft mouse models in 24 h. Results PCa cells significantly oxidize more of circulating fatty acids than benign cells via CPT-1 enzyme, and blocking this lipid oxidation resulted in activation of the Warburg effect and enhanced [ 18 F]FDG signal in PCa mouse models. Conclusions Inhibition of lipid oxidation plays a major role in elevating glucose metabolism of PCa cells, with potential for imaging enhancement that could also be extended to other cancers.

Prostate-derived Ets factor (PDEF) is expressed in tissues of high epithelial content including prostate, although its precise function has not been fully established. Conventional therapies produce a high rate of cure for patients with localized prostate cancer, but there is, at present, no effective treatment for intervention in metastatic prostate cancer. These facts underline the need to develop new approaches for early diagnosis of aggressive prostate cancer patients, and mechanism based anti-metastasis therapies that will improve the outlook for hormone-refractory prostate cancer. In this study we evaluated role of prostate-derived Ets factor (PDEF) in prostate cancer. We observed decreased PDEF expression in prostate cancer cell lines correlated with increased aggressive phenotype, and complete loss of PDEF protein in metastatic prostate cancer cell lines. Loss of PDEF expression was confirmed in high Gleason Grade prostate cancer samples by immuno-histochemical methods. Reintroduction of PDEF profoundly affected cell behavior leading to less invasive phenotypes in three dimensional cultures. In addition, PDEF expressing cells had altered cell morphology, decreased FAK phosphorylation and decreased colony formation, cell migration, and cellular invasiveness. In contrast PDEF knockdown resulted in increased migration and invasion as well as clonogenic activity. Our results also demonstrated that PDEF downregulated MMP9 promoter activity, suppressed MMP9 mRNA expression, and resulted in loss of MMP9 activity in prostate cancer cells. These results suggested that loss of PDEF might be associated with increased MMP9 expression and activity in aggressive prostate cancer. To confirm results we investigated MMP9 expression in clinical samples of prostate cancer. Results of these studies show increased MMP9 expression correlated with advanced Gleason grade. Taken together our results demonstrate decreased PDEF expression and increased MMP9 expression during the transition to aggressive prostate cancer. These studies demonstrate for the first time negative regulation of MMP9 expression by PDEF, and that PDEF expression was lost in aggressive prostate cancer and was inversely associated with MMP9 expression in clinical samples of prostate cancer. Based on these exciting results, we propose that loss of PDEF along with increased MMP9 expression should serve as novel markers for early detection of aggressive prostate cancer.

This is the case of a man, aged 56 years, who presented with urinary intermittency, frequency, urgency, and dysuria 5 months after undergoing focal laser ablation (FLA) of Gleason 3+4=7 prostate cancer (PC). Cystoscopy revealed a foreign body obstruction of the bladder and the patient experienced immediate relief after its removal. Final pathology confirmed the diagnosis of the foreign body as a piece of necrotic prostatic tissue originating from the median lobe. To our knowledge, this is the first case of intermittent urethral obstruction by a sloughed median prostatic lobe following FLA. FLA is an emerging therapy for low- or intermediate-grade PCs, and this case highlights the need for continued evaluation of long-term outcomes of this procedure.

Background: Plant derivatives have been studied as therapies for prostate cancer based on their purported anti-inflammatory and antioxidant properties and low toxicities. The acai berry is an example of a plant rich in phytochemicals, which may slow the growth of prostate cancer. Methods: This was a phase II, Simon 2-stage clinical trial in patients with biochemically recurrent prostate cancer with a primary endpoint of prostate-specific antigen (PSA) response. Patients were asymptomatic, with a rising PSA of at least 0.2 ng/mL, and were treated with twice daily intake of Acai Juice Product until PSA progression, with a primary endpoint of PSA response. Results: Twenty-one patients were enrolled in the first stage of the trial. One of those patients had a PSA response within the study time period. The PSA doubling time was lengthened in 71% of patients (95% confidence interval = 48% to 89%) on the trial, and in a small number of responders, this was sustained over an extended time. Conclusions: This study did not meet its primary endpoint of 50% PSA response. Nevertheless, the overall tolerability and effects on PSA stabilization warrant further exploration in a biochemically recurrent population.

There is growing evidence that MRI-ultrasound (MR-US)-targeted biopsy (TB) has high detection rates of clinically significant prostate cancer (PCa) compared to standard transrectal ultrasound (TRUS)-guided biopsy. A radiologist plays a significant role in MR-US fusion biopsy planning. Here, we discuss six simple steps that can help set up a successful MR-US fusion biopsy program in collaboration with the urologist.

Herein, we assessed the stage-specific efficacy of inositol hexaphosphate (IP6, phytic acid), a bioactive food component, on prostate cancer (PCa) growth and progression in a transgenic mouse model of prostate cancer (TRAMP). Starting at 4, 12, 20, and 30 weeks of age, male TRAMP mice were fed either regular drinking water or 2% IP6 in water for ~8–15 weeks. Pathological assessments at study endpoint indicated that tumor grade is arrested at earlier stages by IP6 treatment; IP6 also prevented progression to more advanced forms of the disease (~55–70% decrease in moderately and poorly differentiated adenocarcinoma incidence was observed in advanced stage TRAMP cohorts). Next, we determined whether the protective effects of IP6 are mediated via its effect on the expansion of the cancer stem cells (CSCs) pool; results indicated that the anti-PCa effects of IP6 are associated with its potential to eradicate the PCa CSC pool in TRAMP prostate tumors. Furthermore, in vitro assays corroborated the above findings as IP6 decreased the % of floating PC-3 prostaspheres (self-renewal of CSCs) by ~90%. Together, these findings suggest the multifaceted chemopreventive-translational potential of IP6 intervention in suppressing the growth and progression of PCa and controlling this malignancy at an early stage.

The article by Polascik and coau- thors provides a timely synopsis of modem technologic advances in prostate cryoablation and a review of the rationale for and experience with targeted prostate treatments. Prostate cryoablation has a storied past, which can be briefly summarized as high excitement followed by near-com- plete abandonment. Fortunately, a few practitioners improved the technique and incorporated new technologies allowing for its resurrection. The au- thors mention a few improvements in a third-generation device, but numerous others have made prostate cryoablation much more safe and user-friendly, most notably the improvement in transrectal ultrasound imaging. The hope is that with larger cohorts and/or prospective studies this procedure will be on par with the mainstays of treatment for clinically localized prostate cancer. First, with the phenomena of multifocality and indolence, are all tumors clinically significant and therefore requiring treatment? The importance of determining biologic potential cannot be overemphasized, but this creates practical problems in outcomes research. Barring a major unanticipated advance, prostate-specific antigen (PSA) measurement and repeat prostate biopsy will almost certainly be the means by which oncologic efficacy will be assessed, provided these technologies are to be approved by an organization such as the US Food and Drug Administration. PSA will be a poor indicator, as significant portions of the prostate gland remain intact in targeted treatments. How can oncologic efficacy be assessed if a patient's initial multifocality or laterality is poorly understood? This would seemingly require that only hemiablation or targeted treatment be performed on patients with known unilateral disease, and most current staging modalities are insufficient for assessing this approach.