Epigenetic reprogramming of primary pancreatic cancer cells counteracts their in vivo tumourigenicity.

Pancreatic ductal adenocarcinoma (PDAC) arises through accumulation of multiple genetic alterations. However, cancer cells also acquire and depend on cancer-specific epigenetic changes. To conclusively demonstrate the crucial relevance of the epigenetic programme for the tumourigenicity of the cancer cells, we used cellular reprogramming technology to reverse these epigenetic changes. We reprogrammed human PDAC cultures using three different techniques - (1) lentivirally via induction of Yamanaka Factors (OSKM), (2) the pluripotency-associated gene OCT4 and the microRNA mir-302, or (3) using episomal vectors as a safer alternative without genomic integration. We found that induction with episomal vectors was the most efficient method to reprogram primary human PDAC cultures as well as primary human fibroblasts that served as positive controls. Successful reprogramming was evidenced by immunostaining, alkaline phosphatase staining, and real-time PCR. Intriguingly, reprogramming of primary human PDAC cultures drastically reduced their in vivo tumourigenicity, which appeared to be driven by the cells' enhanced differentiation and loss of stemness upon transplantation. Our study demonstrates that reprogrammed primary PDAC cultures are functionally distinct from parental PDAC cells resulting in drastically reduced tumourigenicity in vitro and in vivo. Thus, epigenetic alterations account at least in part for the tumourigenicity and aggressiveness of pancreatic cancer, supporting the notion that epigenetic modulators could be a suitable approach to improve the dismal outcome of patients with pancreatic cancer.

[Prevalence of urodynamic anomalies in women with recurrent urinary tract infection]. / Prevalencia de alteraciones urodinámicas en las infecciones urinarias recidivantes de la mujer.

OBJECTIVES: To check the urodynamic data in patients with recurrent urinary tract infection in order to demonstrate a cause justifying them. METHODS: We performed a transverse comparative study in a series of 114 women, with a mean age of 51.9 yr. (typical deviation: 23.5 yr.), divided into groups of 57 women each: group I with recurrent urinary tract infection (UTI) and group II without recurrent urinary tract infection (no UTI). Patients underwent history, physical examination, and video-urodynamic study. All data were collected in an Access database and subsequently imported to the SPSS statistical analysis software. Fisher's exact test, Pearson's chi-square, and Student's t-test were applied. ROC curve was calculated. A logistic regression multivalue model was elaborated. RESULTS: significant differences were only found in the values of maximum voiding flow (lower in the UTI group), post void residual volume (greater in the UTI group), and pressure of the involuntary detrusor contraction (lower in the UTI group). Nevertheless, post void residual was the only independent variable, becoming the other two dependent variables. The ideal cut point between post void residual and urinary tract infection was 48.5 ml. The determination coefficient for the model was 0.13. No significant relationships were found between urinary tract infection and, among others, presence and degree of cystocele, detrusor hyperactivity, and stress urinary incontinence. CONCLUSIONS: Postvoid residual would explain 13% of the recurrent urinary tract infection in women. The remainder would be secondary to other factors not included in the model.