RESUMEN
Prostate cancer (PCa) is a significant cause of male morbidity in the United States. Despite recent advances in diagnosis and therapeutic interventions, significant fraction of cases still progress to an advanced stage. Various genetic/epigenetic elements that facilitate this progression are not yet completely known and the mechanism that favors advanced disease is an area of investigation. A characteristic feature associated with progressive disease is deletion of chromosome 8p (chr8p) region, that harbors tumor-suppressor NKX3.1. Previous studies from our group has shown that there are cluster of microRNAs (miRNAs) located within this region whose loss favors advanced, metastatic disease. miR-4287 is a novel miRNA located within this region that has not been studied before. In the present study, we analyzed the role of miR-4287 in PCa using clinical tissues and cell lines. We observed that miR-4287 is significantly downregulated in patient-derived tumor tissues. Receiver operating curve (ROC) analysis showed that miR-4287 distinguishes prostate cancer from normal with a specificity of 88.24% and with an Area under the curve (AUC) of 0.66. Further, we found that miR-4287 levels correlate inversely with patients' serum prostate-specific antigen levels. Ectopic over-expression of miR-4287 in PCa cell lines showed that miR-4287 plays a tumor suppressor role. miR-4287 led to an increase in G2/M phase of cell cycle in PCa cell lines. Further, ectopic miR-4287 inhibited PCa epithelial-to-mesenchymal transition (EMT) by directly repressing SLUG and stem cell marker CD44. Since miR-4287 specifically targets metastasis pathway mediators, miR-4287 has potential diagnostic and therapeutic significance in preventing advanced, metastatic disease.
RESUMEN
Laboratory management should be an integral part of training in pathology residency and fellowships. Herein, we have outlined some basic laboratory management topics a graduating cytopathology fellow should be familiar with. An overview of regulatory agencies that have oversight over laboratory testing, cytopathology laboratory accreditation, pre-analytic, analytic and post-analytic quality assurance, billing/coding, basic statistics, verification/validation of testing, physician credentialing, board certification/maintenance of certification, and malpractice in cytopathology are addressed. This review is by no means all inclusive, but rather a guide to the basic management related topics to be covered during cytopathology subspecialty training.
RESUMEN
To study the multifaceted biology of prostate cancer, pre-clinical in vivo models offer a range of options to uncover critical biological information about this disease. The human orthotopic prostate cancer xenograft mouse model provides a useful alternative approach for understanding the specific interactions between genetically and molecularly altered tumor cells, their organ microenvironment, and for evaluation of efficacy of therapeutic regimens. This is a well characterized model designed to study the molecular events of primary tumor development and it recapitulates the early events in the metastatic cascade prior to embolism and entry of tumor cells into the circulation. Thus it allows elucidation of molecular mechanisms underlying the initial phase of metastatic disease. In addition, this model can annotate drug targets of clinical relevance and is a valuable tool to study prostate cancer progression. In this manuscript we describe a detailed procedure to establish a human orthotopic prostate cancer xenograft mouse model.