Publications by authors named "Brendler C"

Neonicotinoids (NEOs) are widely used insecticides that are ubiquitous in agricultural use. Since NEOs are found in natural waters as well as in tap water and human urine in regions where NEOs are widely used, NEOs pose a potential hazard to non-target organisms such as animals and humans. Some of the commonly detected NEOs are imidacloprid (IMD), thiamethoxam (TMX), and its metabolite clothianidin (CLO).

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Background: Although active surveillance (AS) is an increasingly adopted treatment paradigm for management of very low risk prostate cancer, many men and their partners face a variety of AS-related psychosocial stressors. Stressors may include anxiety and fear of progression, which may negatively affect short- and long-term psychosocial adjustment and influence early withdrawal from AS in order to seek definitive therapies such as surgery or radiation. Here we describe the protocol for an NCI-funded trial, which seeks to examine the efficacy of mindfulness training compared with a time/attention-matched health promotion control condition in a geographically generalizable sample of men on AS and their spouses.

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Background: Genome-wide association studies have identified thousands of disease-associated single nucleotide polymorphisms (SNPs). A subset of these SNPs may be additively combined to generate genetic risk scores (GRSs) that confer risk for a specific disease. Although the clinical validity of GRSs to predict risk of specific diseases has been well established, there is still a great need to determine their clinical utility by applying GRSs in primary care for cancer risk assessment and targeted intervention.

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Background: To assess the feasibility of a novel DNA-based probe panel to detect copy number alterations (CNAs) in prostate tumor DNA and its performance for predicting clinical progression.

Methods: A probe panel was developed and optimized to measure CNAs in trace amounts of tumor DNA (2 ng) isolated from formalin-fixed paraffin-embedded tissues. Ten genes previously associated with aggressive disease were targeted.

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Background: Mutations in DNA repair genes are associated with aggressive prostate cancer (PCa).

Objective: To assess whether germline mutations are associated with grade reclassification (GR) in patients undergoing active surveillance (AS).

Design, Setting, And Participants: Two independent cohorts of PCa patients undergoing AS; 882 and 329 patients from Johns Hopkins and North Shore, respectively.

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Progress in prostate cancer racial disparity research has been hampered by a lack of appropriate research tools and better understanding of the tumor biology. Recent gene expression studies suggest that the tumor microenvironment (TME) may contribute to racially disparate clinical outcomes in prostate cancer. Analysis of the prostate TME has shown increased reactive stroma associated with chronic inflammatory infiltrates in African-American (AA) compared with European-American (EA) patients with prostate cancer.

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Purpose: Family history assigns equivalent risk to all relatives based upon the degree of relationship. Recent genetic studies have identified single nucleotide polymorphisms (SNPs) that can be used to calculate a genetic risk score (GRS) to determine prostate cancer (PCa) risk. We sought to determine whether GRS can stratify PCa risk among individuals in families considered to be at higher risk due their family history of PCa.

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Prostate tumors make metabolic adaptations to ensure adequate energy and amplify cell cycle regulators, such as centrosomes, to sustain their proliferative capacity. It is not known whether cancer-associated fibroblasts (CAFs) undergo metabolic re-programming. We postulated that CAFs augment lipid storage and amplify centrosomal or non-centrosomal microtubule-organizing centers (MTOCs) through a pigment epithelium-derived factor (PEDF)-dependent lipid-MTOC signaling axis.

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Background: Germline mutations in CHEK2 have been associated with prostate cancer (PCa) risk. Our objective is to examine whether germline pathogenic CHEK2 mutations can differentiate risk of lethal from indolent PCa.

Methods: A case-case study of 703 lethal PCa patients and 1455 patients with low-risk localized PCa of European, African, and Chinese origin was performed.

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Background: Prostate-specific antigen (PSA) and PSA-velocity (PSAV) have been used to identify men at risk of prostate cancer (PrCa). The IMPACT study is evaluating PSA screening in men with a known genetic predisposition to PrCa due to BRCA1/2 mutations. This analysis evaluates the utility of PSA and PSAV for identifying PrCa and high-grade disease in this cohort.

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Background: Although the clinical validity of risk-associated single nucleotide polymorphisms (SNPs) for assessment of disease susceptibility has been consistently established, risk reclassification from increasing numbers of implicated risk-associated SNPs raises concern that it is premature for clinical use. Our objective is to assess the degree and impact of risk reclassification with the increasing number of SNPs.

Methods: A total of 3239 patients from the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial were included.

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Background: The performance of prostate health index (phi) in predicting prostate biopsy outcomes has been well established for patients with prostate-specific antigen (PSA) values between 2 and 10 ng/mL. However, the performance of phi remains unknown in patients with PSA >10 ng/mL, the vast majority in Chinese biopsy patients. We aimed to assess the ability of phi to predict prostate cancer (PCa) and high-grade disease (Gleason Score ≥7) on biopsy in a Chinese population.

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Background: Germline mutations in BRCA1/2 and ATM have been associated with prostate cancer (PCa) risk.

Objective: To directly assess whether germline mutations in these three genes distinguish lethal from indolent PCa and whether they confer any effect on age at death.

Design, Setting, And Participants: A retrospective case-case study of 313 patients who died of PCa and 486 patients with low-risk localized PCa of European, African, and Chinese descent.

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Purpose: Using patient reported outcomes measures we identified the most informative set of factors associated with quality of life in a large sample of men treated for localized prostate cancer.

Materials And Methods: We examined relationships with quality of life using FACIT (Functional Assessment of Chronic Illness Therapy). We also hypothesized variables in a sample of men diagnosed with localized prostate cancer who represented different time points since treatment, including less than 12 months in 70, 1 to 3 years in 344, greater than 3 to 5 years in 291 and greater than 5 years in 97.

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Background: While family history (FH) has been widely used to provide risk information, it captures only a small proportion of subjects with higher genetic susceptibility. Our objective is to assess whether a genetic risk score (GRS) calculated from prostate cancer (PCa) risk-associated single nucleotide polymorphisms (SNPs) can supplement FH for more effective risk stratification for PCa screening decision-making.

Methods: A GRS was calculated based on 29 PCa risk-associated SNPs for 4,528 men of European descent in the placebo arm of the Prostate Cancer Prevention Trial (PCPT).

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Unprecedented progress has been made in genomic personalized medicine in the last several years, allowing for more individualized healthcare assessments and recommendations than ever before. However, most of this progress in prostate cancer (PCa) care has focused on developing and selecting therapies for late-stage disease. To address this issue of limited focus, we propose a model for incorporating genomic-based personalized medicine into all levels of PCa care, from prevention and screening to diagnosis, and ultimately to the treatment of both early-stage and late-stage cancers.

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Objective: In a pilot randomized controlled trial, examine the feasibility and preliminary efficacy of an 8-week, mindfulness training program (Mindfulness Based Stress Reduction) in a sample of men on active surveillance on important psychological outcomes including prostate cancer anxiety, uncertainty intolerance and posttraumatic growth.

Methods: Men were randomized to either mindfulness (n = 24) or an attention control arm (n = 19) and completed self-reported measures of prostate cancer anxiety, uncertainty intolerance, global quality of life, mindfulness and posttraumatic growth at baseline, 8 weeks, 6 months and 12 months.

Results: Participants in the mindfulness arm demonstrated significant decreases in prostate cancer anxiety and uncertainty intolerance, and significant increases in mindfulness, global mental health and posttraumatic growth.

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Genetic risk score (GRS) based on disease risk-associated single nucleotide polymorphisms (SNPs) is an informative tool that can be used to provide inherited information for specific diseases in addition to family history. However, it is still unknown whether only SNPs that are implicated in a specific racial group should be used when calculating GRSs. The objective of this study is to compare the performance of race-specific GRS and nonrace-specific GRS for predicting prostate cancer (PCa) among 1338 patients underwent prostate biopsy in Shanghai, China.

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Several different approaches are available to clinicians for determining prostate cancer (PCa) risk. The clinical validity of various PCa risk assessment methods utilizing single nucleotide polymorphisms (SNPs) has been established; however, these SNP-based methods have not been compared. The objective of this study was to compare the three most commonly used SNP-based methods for PCa risk assessment.

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Aim: The aim of this study was to examine the relationship between sexual dysfunction, repeat biopsies and other demographic and clinical factors in men on active surveillance (AS).

Methods: Patient-reported outcomes (PROs) measures were administered at enrollment and every 6 months to assess quality of life (QOL), psychosocial and urological health outcomes. Using mixed-effects models, we examined the impact of repeat biopsies, total number of cores taken, anxiety, age, and comorbidity on sexual function over the first 24 months of enrolling in AS.

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The development of novel therapies for breast cancer bone metastasis is a major unmet medical need. Toward that end, we have constructed an oncolytic adenovirus, Ad.dcn, and a nonreplicating adenovirus, Ad(E1-).

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Background: The incidence and mortality of prostate cancer (PCa) were historically low in China but have increased considerably in recent years. This study aimed to describe the detailed trend of PCa incidence and mortality in Shanghai, China.

Material And Methods: Incidence and mortality data of PCa in urban Shanghai during 1973 and 2009 were collected by the Shanghai Municipal Center for Disease Control and Prevention.

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Purpose: To determine whether nano-architectural interrogation of prostate field carcinogenesis can be used to predict prognosis in patients with early stage (Gleason 6) prostate cancer (PCa), which is mostly indolent but frequently unnecessarily treated.

Materials And Methods: We previously developed partial wave spectroscopic microscopy (PWS) that enables quantification of the nanoscale intracellular architecture (20-200 nm length scale) with remarkable accuracy. We adapted this technique to assess prostate needle core biopsies in a case control study from men with Gleason 6 disease who either progressed (n = 20) or remained indolent (n = 18) over a ~3 year follow up.

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