Scott D. Perrapato

Standardizing Analysis of Circulating MicroRNA: Clinical and Biological Relevance

Circulating microRNAs (c‐miRNAs) provide a new dimension as clinical biomarkers for disease diagnosis, progression, and response to treatment. However, the discovery of individual miRNAs from biofluids that reliably reflect disease states is in its infancy. The highly variable nature of published studies exemplifies a need to standardize the analysis of miRNA in circulation. Here, we show that differential sample handling of serum leads to inconsistent and incomparable results. We present a standardized method of RNA isolation from serum that eliminates multiple freeze/thaw cycles, provides at least three normalization mechanisms, and can be utilized in studies that compare both archived and prospectively collected samples. It is anticipated that serum processed as described here can be profiled, either globally or on a gene by gene basis, for c‐miRNAs and other non‐coding RNA in the circulation to reveal novel, clinically relevant epigenetic signatures for a wide range of diseases. J. Cell. Biochem. 115: 805–811, 2014.

Decipher test impacts decision making among patients considering adjuvant and salvage treatment after radical prostatectomy: Interim results from the Multicenter Prospective PRO-IMPACT study

Patients with prostate cancer and their providers face uncertainty as they consider adjuvant radiotherapy (ART) or salvage radiotherapy (SRT) after undergoing radical prostatectomy. The authors prospectively evaluated the impact of the Decipher test, which predicts metastasis risk after radical prostatectomy, on decision making for ART and SRT.

Cognitive and Affective Representations of Active Surveillance as a Treatment Option for Low-Risk Prostate Cancer

Benefits of early diagnosis and treatment remain debatable for men with low-risk prostate cancer. Active surveillance (AS) is an alternative to treatment. The goal of AS is to identify patients whose cancer is progressing rapidly while avoiding treatment in the majority of patients. The purpose of this study was to explore cognitive and affective representations of AS within a clinical environment that promotes AS a viable option for men with low-risk prostate cancer. Participants included patients for whom AS and active treatment were equally viable options, as well as practitioners who were involved in consultations for prostate cancer. Data were generated from semistructured interviews and audits of consultation notes and were analyzed using thematic analysis. Nineteen patients and 16 practitioners completed a semistructured interview. Patients generally viewed AS as a temporary strategy that was largely equated with inaction. There was variation in the degree to which inaction was viewed as warranted or favorable. Patient perceptions of AS were generally malleable and able to be influenced by information from trusted sources. Encouraging slow deliberation and multiple consultations may facilitate greater understanding and acceptance of AS as a viable treatment option for low-risk prostate cancer.

Qualitative insights into how men with low-risk prostate cancer choosing active surveillance negotiate stress and uncertainty.

BackgroundActive surveillance is a management strategy for men diagnosed with early-stage, low-risk prostate cancer in which their cancer is monitored and treatment is delayed. This study investigated the primary coping mechanisms for men following the active surveillance treatment plan, with a specific focus on how these men interact with their social network as they negotiate the stress and uncertainty of their diagnosis and treatment approach.MethodsThematic analysis of semi-structured interviews at two academic institutions located in the northeastern US. Participants include 15 men diagnosed with low-risk prostate cancer following active surveillance.ResultsThe decision to follow active surveillance reflects the desire to avoid potentially life-altering side effects associated with active treatment options. Men on active surveillance cope with their prostate cancer diagnosis by both maintaining a sense of control over their daily lives, as well as relying on the support provided them by their social networks and the medical community. Social networks support men on active surveillance by encouraging lifestyle changes and serving as a resource to discuss and ease cancer-related stress.ConclusionsSupport systems for men with low-risk prostate cancer do not always interface directly with the medical community. Spousal and social support play important roles in helping men understand and accept their prostate cancer diagnosis and chosen care plan. It may be beneficial to highlight the role of social support in interventions targeting the psychosocial health of men on active surveillance.

Revisiting Prostate Cancer Screening Practices Among Vermont Primary Care Physicians

The objective of this study was to assess the prostate cancer screening practices of Vermont primary care physicians and compare them with a prior study in 2001. An electronic survey was created and emailed to all currently practicing primary care physicians in Vermont. Data was stratified by practice length, practice location, university affiliation, and internal medicine versus family practice. Surveys were received from 123 (27.2%) primary care physicians. 27.7% of physicians in practiceu2009<10xa0years recommended prostate specific antigen (PSA) testing, compared with 55.9% of those practicing ≥10xa0years (pu2009=u20090.006). Of those who modified their recommendations in the past 5xa0years, 96.1% reported that the United States Preventive Services Task Force (USPSTF) 2012 statement influenced them. Respondents who continued to use PSA testing were less likely to stop screening after age 80 compared with those surveyed in 2001 (51% in 2014 vs. 74% in 2001; pu2009<0.001). Primary care physicians in practice for 10 or more years were more likely to recommend PSA-based screening than those in practice for less time. The USPSTF statement discouraging PSA-based screening for prostate cancer has had significant penetrance among Vermont primary care physicians.

Nanoparticle‐based targeted cancer strategies for non‐invasive prostate cancer intervention

Prostate cancer is screened by testing circulating levels of the prostate‐specific antigen (PSA) biomarker, monitoring changes over time, or a digital rectal exam. Abnormal results often lead to prostate biopsy. Prostate cancer positive patients are stratified into very low‐risk, low‐risk, intermediate‐risk, and high‐risk, based on clinical classification parameters, to assess therapy options. However, there remains a gap in our knowledge and a compelling need for improved risk stratification to inform clinical decisions and reduce both over‐diagnosis and over‐treatment. Further, current strategies for clinical intervention do not distinguish clinically aggressive prostate cancer from indolent disease. This mini‐review takes advantage of a large number of functionally characterized microRNAs (miRNA), epigenetic regulators of prostate cancer, that define prostate cancer cell activity, tumor stage, and circulate as biomarkers to monitor disease progression. Nanoparticles provide an effective platform for targeted delivery of miRNA inhibitors or mimics specifically to prostate tumor cells to inhibit cancer progression. Several prostate–specific transmembrane proteins expressed at elevated levels in prostate tumors are under investigation for targeting therapeutic agents to prostate cancer cells. Given that prostate cancer progresses slowly, circulating miRNAs can be monitored to identify tumor progression in indolent disease, allowing identification of miRNAs for nanoparticle intervention before the crucial point of transition to aggressive disease. Here, we describe clinically significant and non‐invasive intervention nanoparticle strategies being used in clinical trials for drug and nucleic acid delivery. The advantages of mesoporous silica‐based nanoparticles and a number of candidate miRNAs for inhibition of prostate cancer are discussed.

PD71-01 DECIPHER TEST IMPACTS DECISION-MAKING AMONG PATIENTS CONSIDERING ADJUVANT AND SALVAGE TREATMENT FOLLOWING RADICAL PROSTATECTOMY: INTERIM RESULTS FROM THE MULTICENTER PROSPECTIVE PRO-IMPACT STUDY

Menopause women are known to be sensitive to cold stress, but the mechanism is not clearly known. The aim of this study is to show that menopause causes impairment of micro blood flow in the bladder mucosa and dermis under the skin and up-regulates TRPM8 channels which induces cold stress related frequency in rats. METHODS: A total of 18 Spontaneously Hypertensive rats at postnatal week 10 were used in the experiments. The rats were randomly divided into 2 groups, including 9 with sham operation and 9 with bilateral ovariectomy. At 4 weeks after surgery, cystometography (CMG) was performed. CMG was first performed in room temperature (RT) for 20 minuets. Rats were then put into low temperature (LT) for 40 minutes. After LT, rats were put into RT for 20 minutes. After CMG, the whole bladder and dermis under the lumbar skin was harvested and real-time RT-PCR was performed. Immunohistochemistry was also performed and impairment of micro blood flow was evaluated by hypoxia-inducible factor-1 (HIF-1) staining. RESULTS: Results of the CMG are shown in Fig 1. Basal pressure and micturition pressure did not show a difference between control rats and ovariectomy rats, but change rate with cold stress in voiding interval and micturition volume showed a significant exacerbate. Results of real-time RT-PCR are shown in Fig 2. Up-regulation of TRPM8 in the dermis and TRPV1 in the bladder mucosa was seen in ovariectomy rats. Immunohistochemistry showed increase of HIF-1 in the bladder mucosa and dermis. CONCLUSIONS: Ovariectomy causes impairment of micro blood flow in the bladder mucosa and dermis which induces cold stress frequency by up-regulating TRPM8 channels.