Iron-specific Signal Separation from within Heavy Metal Stained Biological Samples Using X-Ray Microtomography with Polychromatic Source and Energy-Integrating Detectors.

Biological samples are frequently stained with heavy metals in preparation for examining the macro, micro and ultra-structure using X-ray microtomography and electron microscopy. A single X-ray microtomography scan reveals detailed 3D structure based on staining density, yet it lacks both material composition and functional information. Using a commercially available polychromatic X-ray source, energy integrating detectors and a two-scan configuration labelled by their energy- "High" and "Low", we demonstrate how a specific element, here shown with iron, can be detected from a mixture with other heavy metals.

Nfib Regulates Transcriptional Networks That Control the Development of Prostatic Hyperplasia.

A functional complex consisting of androgen receptor (AR) and forkhead box A1 (FOXA1) proteins supports prostatic development, differentiation, and disease. In addition, the interaction of FOXA1 with cofactors such as nuclear factor I (NFI) family members modulates AR target gene expression. However, the global role of specific NFI family members has yet to be described in the prostate.

FOXA1 deletion in luminal epithelium causes prostatic hyperplasia and alteration of differentiated phenotype.

The forkhead box (Fox) superfamily of transcription factors has essential roles in organogenesis and tissue differentiation. Foxa1 and Foxa2 are expressed during prostate budding and ductal morphogenesis, whereas Foxa1 expression is retained in adult prostate epithelium. Previous characterization of prostatic tissue rescued from embryonic Foxa1 knockout mice revealed Foxa1 to be essential for ductal morphogenesis and epithelial maturation.

Mash1 expression is induced in neuroendocrine prostate cancer upon the loss of Foxa2.

Neuroendocrine (NE) prostate tumors and neuroendocrine differentiation (NED) in prostatic adenocarcinomas have been associated with poor prognosis. In this study, we used the TRAMP mouse model that develops NE prostate tumors to identify key factors that can lead to NED. We have previously reported that NE tumors express the forkhead transcription factor, Foxa2, Mash1 (mouse achaete scute homolog-1), as well as Synaptophysin.

Neuroendocrine differentiation in the 12T-10 transgenic prostate mouse model mimics endocrine differentiation of pancreatic beta cells.

Background: Neuroendocrine (NE) prostate cancer develops as an aggressive disease that does not respond to androgen ablation therapy. It has been demonstrated that the paracrine action of NE cells facilitates the progression of androgen dependent adenocarcinoma to an androgen independent state, suggesting a significant role for NE cells during failure of androgen ablation therapy.

Methods: To investigate the pathways that are involved in NE differentiation of prostate cancer, we have looked at the expression of genes known to be involved in endocrine differentiation of beta-cells in the pancreas.

The loss of TGF-beta signaling promotes prostate cancer metastasis.

In breast and colon cancers, transforming growth factor (TGF)-beta signaling initially has an antineoplastic effect, inhibiting tumor growth, but eventually exerts a proneoplastic effect, increasing motility and cancer spread. In prostate cancer, studies using human samples have correlated the loss of the TGF-beta type II receptor (T beta R II) with higher tumor grade. To determine the effect of an inhibited TGF-beta pathway on prostate cancer, we bred transgenic mice expressing the tumorigenic SV40 large T antigen in the prostate with transgenic mice expressing a dominant negative T beta R II mutant (DN II R) in the prostate.