The Fine Structure of the Epithelial Cells of the Mouse Prostate : I. Coagulating Gland Epithelium

The fine structure of the epithelial cells of the anterior lobe, or coagulating gland, of the mouse prostate has been investigated by electron microscopy. This organ is composed of small tubules, lined by tall, simple cuboidal epithelium surrounded by connective tissue and smooth muscle. The epithelial cells are limited by a distinct plasma membrane, which covers minute projections of the cytoplasm into the lumen. The cell membranes of adjacent cells are separated by a narrow layer of structureless material of low density. The cavities of the endoplasmic reticulum are greatly dilated, and the cytoplasmic matrix is reduced to narrow strands, in which the various organelles are visible. The content of the cavities of the endoplasmic reticulum appears as structureless material of lesser density than the cytoplasmic matrix. Material which may be interpreted as secretion products can be seen in the lumina of the tubules. The possible nature of the material inside the cisternal spaces and the secretory mechanisms in these cells is discussed.     

Visualizing the Prostate Gland by MR Imaging in Young and Old Mice

Purpose

Prostate imaging requires optimization in young and old mouse models. We tested which MR sequences and field strengths best depict the prostate gland in young and old mice; and, whether prostate MR signal, size, and architecture change with age.

Technique

Magnetic resonance imaging (MRI) of the prostate of young (2 months) and old (18 months) male nude mice (n = 6) was performed at 4.7 and 7 T and SCID mice (n = 6) at 7 T field strengths, using T1, fat suppressed T1, DWI, T2, fat suppressed T2, as well as T2-based- and proton density-based Dixon “water only” sequences. Images were ranked for best overall sequence for prostate visualization, prostate delineation, and quality of fat suppression. Prostate volume and signal characteristics were compared and histology was performed.

Results

T2-based-Dixon “water only” images ranked best overall for prostate visualization and delineation as well as fat suppression (n = 6, P<0.001) at both 4.7 T and 7 T in nude and 7T in SCID mice. Evaluated in nude mice, T2-based Dixon “water only” had greater prostate CNR and lower fat SNR at 7 T than 4.7 T (P<0.001). Prostate volume was less in older than younger mice (n = 6, P<0.02 nude mice; n = 6, P<0.002 SCID mice). Prostate T2 FSE as well as proton density-based and T2-based-Dixon “water only” signal intensity was higher in younger than older mice (P<0.001 nude mice; P<0.01 SCID mice) both at 4.7 and 7 T. This corresponded to an increase in glandular hyperplasia in older mice by histology (P<0.01, n = 6).

Conclusion

T2-based Dixon “water only” images best depict the mouse prostate in young and old nude mice at 4.7 and 7 T. The mouse prostate decreases in size with age. The decrease in T2 and T2-based Dixon “water only” signal with age corresponds with glandular hyperplasia. Findings suggest age should be an important determinant when choosing models of prostate biology and disease.     

Prostate Gland Lengths and Iceball Dimensions Predict Micturition Functional Outcome Following Salvage Prostate Cryotherapy in Men with Radiation Recurrent Prostate Cancer

Introduction

Tissue cryoablation is a potential curative option for solid malignancies, including radiation recurrent prostate cancer (RRPC). Case series of salvage cryotherapy (SCT) in RRPC have reported promising disease free survival (DFS) outcomes and acceptable toxicity profile. While many men receive SCT, no predictive factors for treatment induced side effects are known. The aim of this study is to validate the oncologic outcome of SCT in a large multi-centre patient cohort and to identify potential parameters associated with an increased risk of micturition symptoms.

Patients and Methods

In this retrospective analysis, we studied 283 consecutive patients with RRPC treated by SCT in three independent U.K. centres (between 2001 and 2011). Two freeze-thaw cycles of transperineal cryotherapy were performed under transrectal ultrasound guidance by a single surgeon in each of the 3 sites. We analysed clinico-pathological factors against tumour response. Functional outcomes were assessed by continence status and IPSS questionnaire. Predictive factors for SCT-induced micturition symptoms were analysed in a sub-group (n = 42) of consecutive cases.

Results

We found that nadir post-SCT PSA levels strongly associated with DFS. The DFS rates at 12- and 36-month were 84% and 67% for the ≤1 ng/ml group and 56% and 14% for the >1 ng/ml group, respectively (p<0.001). Correlative analysis revealed highly significant association between patients'' post-SCT micturition status with prostate gland and iceball lengths following SCT. Finally, in a reduction model, both gland length and maximal length of iceball were highly associated with patients'' IPSS outcome (p<0.001).

Conclusion

We report the largest European patient cohort treated with SCT for RRPC. Oncologic outcome guided by nadir PSA of <1 ng/ml is consistent with earlier single-centre series. For the first time, we identified physical parameters to predict micturition symptoms following SCT. Our data will directly assist on-going and future trial design in cryotherapy in prostate cancer.     

Co-Occurring Gland Angularity in Localized Subgraphs: Predicting Biochemical Recurrence in Intermediate-Risk Prostate Cancer Patients

Quantitative histomorphometry (QH) refers to the application of advanced computational image analysis to reproducibly describe disease appearance on digitized histopathology images. QH thus could serve as an important complementary tool for pathologists in interrogating and interpreting cancer morphology and malignancy. In the US, annually, over 60,000 prostate cancer patients undergo radical prostatectomy treatment. Around 10,000 of these men experience biochemical recurrence within 5 years of surgery, a marker for local or distant disease recurrence. The ability to predict the risk of biochemical recurrence soon after surgery could allow for adjuvant therapies to be prescribed as necessary to improve long term treatment outcomes. The underlying hypothesis with our approach, co-occurring gland angularity (CGA), is that in benign or less aggressive prostate cancer, gland orientations within local neighborhoods are similar to each other but are more chaotically arranged in aggressive disease. By modeling the extent of the disorder, we can differentiate surgically removed prostate tissue sections from (a) benign and malignant regions and (b) more and less aggressive prostate cancer. For a cohort of 40 intermediate-risk (mostly Gleason sum 7) surgically cured prostate cancer patients where half suffered biochemical recurrence, the CGA features were able to predict biochemical recurrence with 73% accuracy. Additionally, for 80 regions of interest chosen from the 40 studies, corresponding to both normal and cancerous cases, the CGA features yielded a 99% accuracy. CGAs were shown to be statistically signicantly () better at predicting BCR compared to state-of-the-art QH methods and postoperative prostate cancer nomograms.     

Formation and Transformation of the Human Prostate Gland in Prenatal and Neonatal Periods of Development

Russian Journal of Developmental Biology - The purpose of this study was to determine the morphometric parameters of epithelial cords, ducts, and acini of the human prostate gland and their lining...     

Retinal Vessel Segmentation: An Efficient Graph Cut Approach with Retinex and Local Phase

Our application concerns the automated detection of vessels in retinal images to improve understanding of the disease mechanism, diagnosis and treatment of retinal and a number of systemic diseases. We propose a new framework for segmenting retinal vasculatures with much improved accuracy and efficiency. The proposed framework consists of three technical components: Retinex-based image inhomogeneity correction, local phase-based vessel enhancement and graph cut-based active contour segmentation. These procedures are applied in the following order. Underpinned by the Retinex theory, the inhomogeneity correction step aims to address challenges presented by the image intensity inhomogeneities, and the relatively low contrast of thin vessels compared to the background. The local phase enhancement technique is employed to enhance vessels for its superiority in preserving the vessel edges. The graph cut-based active contour method is used for its efficiency and effectiveness in segmenting the vessels from the enhanced images using the local phase filter. We have demonstrated its performance by applying it to four public retinal image datasets (3 datasets of color fundus photography and 1 of fluorescein angiography). Statistical analysis demonstrates that each component of the framework can provide the level of performance expected. The proposed framework is compared with widely used unsupervised and supervised methods, showing that the overall framework outperforms its competitors. For example, the achieved sensitivity (0:744), specificity (0:978) and accuracy (0:953) for the DRIVE dataset are very close to those of the manual annotations obtained by the second observer.     

Sphingosine Kinase-1 Is Central to Androgen-Regulated Prostate Cancer Growth and Survival

Background

Sphingosine kinase-1 (SphK1) is an oncogenic lipid kinase notably involved in response to anticancer therapies in prostate cancer. Androgens regulate prostate cancer cell proliferation, and androgen deprivation therapy is the standard of care in the management of patients with advanced disease. Here, we explored the role of SphK1 in the regulation of androgen-dependent prostate cancer cell growth and survival.

Methodology/Principal Findings

Short-term androgen removal induced a rapid and transient SphK1 inhibition associated with a reduced cell growth in vitro and in vivo, an event that was not observed in the hormono-insensitive PC-3 cells. Supporting the critical role of SphK1 inhibition in the rapid effect of androgen depletion, its overexpression could impair the cell growth decrease. Similarly, the addition of dihydrotestosterone (DHT) to androgen-deprived LNCaP cells re-established cell proliferation, through an androgen receptor/PI3K/Akt dependent stimulation of SphK1, and inhibition of SphK1 could markedly impede the effects of DHT. Conversely, long-term removal of androgen support in LNCaP and C4-2B cells resulted in a progressive increase in SphK1 expression and activity throughout the progression to androgen-independence state, which was characterized by the acquisition of a neuroendocrine (NE)-like cell phenotype. Importantly, inhibition of the PI3K/Akt pathway—by negatively impacting SphK1 activity—could prevent NE differentiation in both cell models, an event that could be mimicked by SphK1 inhibitors. Fascinatingly, the reversability of the NE phenotype by exposure to normal medium was linked with a pronounced inhibition of SphK1 activity.

Conclusions/Significance

We report the first evidence that androgen deprivation induces a differential effect on SphK1 activity in hormone-sensitive prostate cancer cell models. These results also suggest that SphK1 activation upon chronic androgen deprivation may serve as a compensatory mechanism allowing prostate cancer cells to survive in androgen-depleted environment, giving support to its inhibition as a potential therapeutic strategy to delay/prevent the transition to androgen-independent prostate cancer.     

Hyperpolarized MRI of Human Prostate Cancer Reveals Increased Lactate with Tumor Grade Driven by Monocarboxylate Transporter 1

1. Download : Download high-res image (109KB)
2. Download : Download full-size image

     

Driven to autoimmunity: the nod mouse

In the lymphoid system, T cells respond to space or under-crowding by dividing to maintain their numbers. In this issue of Cell, evidence is provided that this homeostatic proliferation, coupled with excess production of a cytokine, IL-21, is a key factor in susceptibility to autoimmune diabetes.