No abstract

BACKGROUNDIn prostate cancer (PCa), abnormal expression of several microRNAs (miRNAs) has been previously reported. Increasing evidence shows that aberrant epigenetic regulation of miRNAs is a contributing factor to their altered expression in cancer. In this study, we investigate whether expression of miR‐200c and miR‐141 in PCa is related to the DNA methylation status of their promoter.METHODSPCR analysis of miR‐200c and miR‐141, and CpG methylation analysis of their common promoter, was performed in PCa cell‐lines and in archived prostate biopsy specimens. The biological significance of miR‐200c and miR‐141 expression in prostate cancer cells was assessed by a series of in vitro bioassays and the effect on proposed targets DNMT3A and TET1/TET3 was investigated. The effect on promoter methylation status in cells treated with demethylating agents was also examined.RESULTSmiR‐200c and miR‐141 are both highly elevated in LNCaP, 22RV1, and DU145 cells, but significantly reduced in PC3 cells. This correlates inversely with the methylation status of the miR‐200c/miR‐141 promoter, which is unmethylated in LNCaP, 22RV1, and DU145 cells, but hypermethylated in PC3. In PC3 cells, miR‐200c and miR‐141 expression is subsequently elevated by treatment with the demethylating drug decitabine (5‐aza‐2′deoxycytidine) and by knockdown of DNA methyltransferase 1 (DNMT1), suggesting their expression is regulated by methylation. Expression of miR‐200c and miR‐141 in prostate biopsy tissue was inversely correlated with methylation in promoter CpG sites closest to the miR‐200c/miR‐141 loci. In vitro, over‐expression of miR‐200c in PC3 cells inhibited growth and clonogenic potential, as well as inducing apoptosis. Expression of the genes DNMT3A and TET1/TET3 were down‐regulated by miR‐200c and miR‐141 respectively. Finally, treatment with the soy isoflavone genistein caused demethylation of the promoter CpG sites closest to the miR‐200c/miR‐141 loci resulting in increased miR‐200c expression.CONCLUSIONSOur findings provide evidence that miR‐200c and miR‐141 are under epigenetic regulation in PCa cells. We propose that profiling their expression and methylation status may have potential as a novel biomarker or focus of therapeutic intervention in the diagnosis and prognosis of PCa. Prostate 76:1146–1159, 2016. © 2016 The Authors. The Prostate published by Wiley Periodicals, Inc.

These findings provide evidence that miR-24 has a tumor suppressor role in prostate cancer and also targets p27 and p16 in prostate cancer cells. We propose that it may be a useful progression biomarker or focus of therapeutic intervention for this disease.

Evaluation of the dual-stain biomarker showed a high level of agreement across all evaluators suggesting that CINtec PLUS cytology will perform well in the hands of cytotechnologists and pathologist reviewers and could be introduced into cellular pathology laboratories that employ ThinPrep LBC with a minimum effort.

Cervical cancer is the fourth most common cancer affecting women worldwide but mortality can be decreased by early detection of pre-malignant lesions. The Pap smear test is the most commonly used method in cervical cancer screening programmes. Although specificity is high for this test, it is widely acknowledged that sensitivity can be poor mainly due to the subjective nature of the test. There is a need for new objective tests for the early detection of pre-malignant cervical lesions. Over the past two decades, Raman spectroscopy has emerged as a promising new technology for cancer screening and diagnosis. The aim of this study was to evaluate the potential of Raman spectroscopy for cervical cancer screening using both Cervical Intraepithelial Neoplasia (CIN) and Squamous Intraepithelial Lesion (SIL) classification terminology. ThinPrep® Pap samples were recruited from a cervical screening population. Raman spectra were recorded from single cell nuclei and subjected to multivariate statistical analysis. Normal and abnormal ThinPrep® samples were discriminated based on the biochemical fingerprint of the cells using Principal Component Analysis (PCA). Principal Component Analysis - Linear Discriminant Analysis (PCA-LDA) was employed to build classification models based on either CIN or SIL terminology. This study has shown that Raman spectroscopy can be successfully applied to the study of routine cervical cytology samples from a cervical screening programme and that the use of CIN terminology resulted in improved sensitivity for high grade cases.

No abstract

HPV16 and HPV18 genotyping triage in young women with borderline cytology or mild dyskaryosis: effect of age on genotype-specific risk of high-grade CIN Objective: Human papillomavirus (HPV) triage of borderline cytology or mild dyskaryosis is limited by the higher prevalence of HPV in women with these findings relative to those with high-grade cervical intraepithelial neoplasia (≥CIN2). This is particularly relevant in young women in whom HPV prevalence is discernible. In a previous analysis of HPV triage and colposcopy outcomes in Northern Ireland, we revealed a substantial amount of prevalent high-grade disease in women below 30 years of age. We explored the role of genotyping for HPV16/HPV18 in this population by assessing the risk of high-grade lesions associated with these genotypes and the effect of age on type-specific risk. Methods: Of the 866 women eligible for HPV triage, those who tested positive for HPV were referred to colposcopy. The relative risk of ≥CIN2 for HPV16, HPV18 and non-HPV16/18 high-risk genotype positivity was determined for cobas â HPV Test-positive results.Results: The relative risk of high-grade CIN was significantly greater in women infected with HPV16 and/or HPV18 compared with non-HPV16/18 infections, regardless of age (2.23 and 0.45, respectively). In women under 30 years of age, HPV16-associated risk of ≥CIN2 was significantly greater than that of HPV18 and the non-HPV16/18 genotypes (1.74 versus 1.03 and 0.58, respectively). In women aged ≥30 years, HPV18 infection presented the greatest risk of ≥CIN2 (3.03). The relative risk of ≥CIN2 associated with non-HPV16/18 genotypes was lower (range, 0.32-0.58) for both age groups. Conclusion: This analysis demonstrates the value of genotyping for HPV16/HPV18 and age stratification to improve the specificity of HPV triage and to tailor management relative to the risk of high-grade CIN and cancer.Keywords: human papillomavirus, genotyping, young women, triage, cervical abnormalitiesThe causal relationship between persistent infection of the cervix with high-risk (oncogenic) human papillomavirus (hrHPV) and cervical cancer has been firmly established. 1 Furthermore, many studies have provided substantial evidence that HPV16 and HPV18 confer the greatest risk for invasive disease, as these high-risk types are found in over 70% of cervical cancers worldwide. 2,3 The recognition that cervical cancer is caused by persistent infection with one of 14 oncogenic HPV types triggered the development of new HPV-related technologies for cervical cancer prevention, notably prophylactic HPV vaccination against HPV types 16 and 18, and HPV testing. Many studies have demonstrated that testing for hrHPV DNA is more sensitive than cytology for the identification of women with pre-cancerous highgrade cervical intraepithelial neoplasia lesions (CIN2 or CIN3); however, it is less specific as most infections

The cause of category III A prostatitis, chronic prostatitis/chronic male pelvic pain syndrome category A (CP/CPPS A), is uncertain. Treatments for it are based on consensus opinion rather than on scientific data. Our aim was to examine the effect of zafirlukast, a leucotriene antagonist, on the symptoms of CP/CPPS A in our genitourinary (GU) medicine unit. CP/CPPS A was diagnosed by comparative white cell counts of split urine (Stamey) analysis or by finding an excess of polymorphs in expressed prostatic fluid. Symptom change was assessed by the National Institutes of Health Chronic Prostatitis Symptom Index (CPSI). Patients were given zafirlukast or placebo for four weeks in a random double-blind fashion. All patients also received doxycycline. In all, 31 patients were asked to participate and 17 entered the study. No difference in outcome could be shown between the active (10) and placebo (seven) patients. Zafirlukast cannot be demonstrated to be useful in the symptomatic treatment of CP/CPPS A. The problems of recruitment into this study (in spite of a large number of patients with prostatic type pain being seen in our unit) suggest that multicentre treatment trials using non-invasive diagnostic techniques such as the CPSI (rather than single GU medicine units diagnosing CP/CPPS A by uncomfortable direct prostatic testing) are likely to be the most effective and objective methods of undertaking treatment trials in the CP/ CPPS A field in the future.