Potential Benefits of Black Chokeberry (Aronia melanocarpa) Fruits and Their Constituents in Improving Human Health.

Aronia berry (black chokeberry) is a shrub native to North America, of which the fresh fruits are used in the food industry to produce different types of dietary products. The fruits of Aronia melanocarpa (Aronia berries) have been found to show multiple bioactivities potentially beneficial to human health, including antidiabetic, anti-infective, antineoplastic, antiobesity, and antioxidant activities, as well as heart-, liver-, and neuroprotective effects. Thus far, phenolic compounds, such as anthocyanins, cyanidins, phenolic acids, proanthocyanidins, triterpenoids, and their analogues have been identified as the major active components of Aronia berries. These natural products possess potent antioxidant activity, which contributes to the majority of the other bioactivities observed for Aronia berries. The chemical components and the potential pharmaceutical or health-promoting effects of Aronia berries have been summarized previously. The present review article focuses on the molecular targets of extracts of Aronia berries and the examples of promising lead compounds isolated from these berries, including cyanidin-3-O-galactoside, chlorogenic acid, quercetin, and ursolic acid. In addition, presented herein are clinical trial investigations for Aronia berries and their major components, including cancer clinical trials for chlorogenic acid and COVID-19 trial studies for quercetin. Additionally, the possible development of Aronia berries and their secondary metabolites as potential therapeutic agents is discussed. It is hoped that this contribution will help stimulate future investigations on Aronia berries for the continual improvement of human health.

Molecular assays for the detection of prostate tumor derived nucleic acids in peripheral blood.

BACKGROUND: Prostate cancer is the second leading cause of cancer mortality in American men. Although serum PSA testing is widely used for early detection, more specific prognostic tests are needed to guide treatment decisions. Recently, the enumeration of circulating prostate epithelial cells has been shown to correlate with disease recurrence and metastasis following definitive treatment. The purpose of our study was to investigate an immunomagnetic fractionation procedure to enrich circulating prostate tumor cells (CTCs) from peripheral blood specimens, and to apply amplified molecular assays for the detection of prostate-specific markers (PSA, PCA3 and TMPRSS2:ERG gene fusion mRNAs). RESULTS: As few as five prostate cancer cells were detected per 5 mL of whole blood in model system experiments using anti-EpCAM magnetic particles alone or in combination with anti-PSMA magnetic particles. In our experiments, anti-EpCAM magnetic particles alone exhibited equivalent or better analytical performance with patient samples compared to a combination of anti-EpCAM + anti-PSMA magnetic particles. Up to 39% of men with advanced prostate cancer tested positive with one or more of the molecular assays tested, whereas control samples from men with benign prostate hyperplasia gave consistently negative results as expected. Interestingly, for the vast majority of men who tested positive for PSA mRNA following CTC enrichment, their matched plasma samples also tested positive, although CTC enrichment gave higher overall mRNA copy numbers. CONCLUSION: CTCs were successfully enriched and detected in men with advanced prostate cancer using an immunomagnetic enrichment procedure coupled with amplified molecular assays for PSA, PCA3, and TMPRSS2:ERG gene fusion mRNAs. Our results indicate that men who test positive following CTC enrichment also exhibit higher detectable levels of non-cellular, circulating prostate-specific mRNAs.

Clinical validation of the next-generation sequencing-based Extended RAS Panel assay using metastatic colorectal cancer patient samples from the phase 3 PRIME study.

PURPOSE: To validate a next-generation sequencing (NGS)-based companion diagnostic using the MiSeqDx® sequencing instrument to simultaneously detect 56 RAS mutations in DNA extracted from formalin-fixed paraffin-embedded metastatic colorectal cancer (mCRC) tumor samples from the PRIME study. The test's ability to identify patients with mCRC likely to benefit from panitumumab treatment was assessed. METHODS: Samples from PRIME, which compared first-line panitumumab + FOLFOX4 with FOLFOX4, were processed according to predefined criteria using a multiplex assay that included input DNA qualification, library preparation, sequencing, and the bioinformatics reporting pipeline. NGS mutational analysis of KRAS and NRAS exons 2, 3, and 4 was performed and compared with Sanger sequencing. RESULTS: In 441 samples, positive percent agreement of the Extended RAS Panel with Sanger sequencing was 98.7% and negative percent agreement was 97.6%. For clinical validation (n = 528), progression-free survival (PFS) and overall survival (OS) were compared between patients with RAS mutations (RAS Positive) and those without (RAS Negative). Panitumumab + FOLFOX4 improved PFS in RAS Negative patients (P = 0.02). Quantitative interaction testing indicated the treatment effect (measured by the hazard ratio of panitumumab + FOLFOX4 versus FOLFOX4) differed for RAS Negative versus RAS Positive for PFS (P = 0.0038) and OS (P = 0.0323). CONCLUSIONS: NGS allows for broad, rapid, highly specific analyses of genomic regions. These results support use of the Extended RAS Panel as a companion diagnostic for selecting patients for panitumumab, and utilization is consistent with recent clinical guidelines regarding mCRC RAS testing. Overall, approximately 13% more patients were detected with the Extended RAS Panel versus KRAS exon 2 alone. CLINICAL TRIAL REGISTRY IDENTIFIER: NCT00364013 (ClinicalTrials.gov).

ERG rearrangement metastasis patterns in locally advanced prostate cancer.

OBJECTIVES: To interrogate multifocal prostate cancer (PCa) to determine its predilection for metastasis, using ERG rearrangement as marker of clonality. A hallmark of PCa is that distinct tumor foci may arise independently, which has important biological and clinical implications. Recent studies characterizing ERG-rearranged PCa possessing intrafocal homogeneity but interfocal heterogeneity support this hypothesis. METHODS: We studied 26 patients who underwent prostatectomy and lymphadenectomy with at least 2 distinct PCa foci and 1 lymph node (LN) metastasis. Each focus was assessed for size, Gleason score, ERG rearrangement, and TMPRSS2-ERG transcript. RESULTS: Fifteen of 26 cases exhibited interfocal homogeneity with regard to ERG rearrangement (ie, presence vs absence of ERG rearrangement). ERG rearrangement was present in all foci for 6 and absent in all foci for 9 cases. Two cases revealed interfocal heterogeneity with regard to rearrangement mechanism (ie, rearrangement through insertion or deletion). Eight of 26 cases revealed interfocal heterogeneity with regard to rearrangement status. In all cases with at least 1 ERG rearranged focus, we found the corresponding LN metastasis harboring an ERG rearrangement. Interestingly, in a subset of cases the rearrangement status in the LN did not correspond to size or Gleason score. All but 2 ERG rearranged foci had detectable TMPRSS2-ERG transcript levels. CONCLUSIONS: When multifocal PCa demonstrates both ERG-positive and ERG-negative foci, the positive foci have a greater predilection for metastasis. Larger studies are needed to confirm the potential additional risk an ERG rearranged focus confers on the likelihood of disease progression.

Carpal tunnel syndrome and cubital tunnel syndrome: work-related musculoskeletal disorders in four symptomatic radiologists.

OBJECTIVE: This report describes work-related upper extremity musculoskeletal disorders in four radiologists and identifies risk factors and preventive measures for these syndromes. SUBJECTS AND METHODS: Four radiologists with complaints of upper extremity pain, numbness, and weakness or a combination of symptoms were examined by an occupational therapist. The work activities and duties of all 12 staff radiologists in our filmless department were subsequently evaluated. Time working as staff, workday hours, and academic activities were recorded. Nonoccupational activities were also noted. An industrial hygienist evaluated the department work areas and staff offices. RESULTS: One radiologist had bilateral carpal tunnel syndrome, and all four radiologists had cubital tunnel syndrome (two [50%] unilateral, two [50%] bilateral). The four spent 3.4 +/- 0.3 years (mean +/- standard error of the mean) as staff radiologists in our filmless department, performing computer keyboard and mouse or trackball image manipulation and work list navigation, typing preliminary reports and telephone notifications, and editing electronically and approving dictated final reports. All four are academically active and had significantly greater workday hours (p < 0.05) and performed more research (p < 0.003) than the asymptomatic radiologists. Three (75%) of four radiologists routinely performed sonography. The industrial hygienist identified hazardous working conditions, especially related to ergonomics, in the reviewing areas and staff offices. CONCLUSION: Current technology renders staff radiologists at risk for work-related, upper extremity musculoskeletal disorders, including carpal and cubital tunnel syndromes. Proper equipment, ergonomics, and professional consultation should be used in all radiology departments.