Micronutrients attenuate progression of prostate cancer by elevating the endogenous inhibitor of angiogenesis, Platelet Factor-4

<p>Abstract</p> <p>Background</p> <p>Longstanding evidence implicates an inadequate diet as a key factor in the onset and progression of prostate cancer. The purpose herein was to discover, validate and characterize functional biomarkers of dietary supplementation capable of suppressing the course of prostate cancer <it>in vivo</it>.</p> <p>Methods</p> <p>The <it>Lady </it>transgenic mouse model that spontaneously develops prostate cancer received a diet supplemented with a micronutrient cocktail of vitamin E, selenium and lycopene ad libitum. A proteomic analysis was conducted to screen for serum biomarkers of this dietary supplementation. Candidate peptides were validated and identified by sequencing and analyzed for their presence within the prostates of all mice by immunohistochemistry.</p> <p>Results</p> <p>Dietary supplementation with the combined micronutrients significantly induced the expression of the megakaryocyte-specific inhibitor of angiogenesis, platelet factor-4 (P = 0.0025). This observation was made predominantly in mice lacking tumors and any manifestations associated with progressive disease beyond 37 weeks of life, at which time no survivors remained in the control group (P < 0.0001). While prostates of mice receiving standard chow were enlarged and burdened with poorly differentiated carcinoma, those of mice on the supplemented diet appeared normal. Immunohistochemical analysis revealed marked amplifications of both platelet binding and platelet factor-4 within the blood vessels of prostates from mice receiving micronutrients only.</p> <p>Conclusion</p> <p>We present unprecedented data whereby these combined micronutrients effectively promotes tumor dormancy in early prostate cancer, following initiation mutations that may drive the angiogenesis-dependent response of the tumor, by inducing platelet factor-4 expression and concentrating it at the tumor endothelium through enhanced platelet binding.</p

A Multidisciplinary Investigation of a Polycythemia Vera Cancer Cluster of Unknown Origin

Cancer cluster investigations rarely receive significant public health resource allocations due to numerous inherent challenges and the limited success of past efforts. In 2008, a cluster of polycythemia vera, a rare blood cancer with unknown etiology, was identified in northeast Pennsylvania. A multidisciplinary group of federal and state agencies, academic institutions, and local healthcare providers subsequently developed a multifaceted research portfolio designed to better understand the cause of the cluster. This research agenda represents a unique and important opportunity to demonstrate that cancer cluster investigations can produce desirable public health and scientific outcomes when necessary resources are available

Cildb: a knowledgebase for centrosomes and cilia

Ciliopathies, pleiotropic diseases provoked by defects in the structure or function of cilia or flagella, reflect the multiple roles of cilia during development, in stem cells, in somatic organs and germ cells. High throughput studies have revealed several hundred proteins that are involved in the composition, function or biogenesis of cilia. The corresponding genes are potential candidates for orphan ciliopathies. To study ciliary genes, model organisms are used in which particular questions on motility, sensory or developmental functions can be approached by genetics. In the course of high throughput studies of cilia in Paramecium tetraurelia, we were confronted with the problem of comparing our results with those obtained in other model organisms. We therefore developed a novel knowledgebase, Cildb, that integrates ciliary data from heterogeneous sources. Cildb links orthology relationships among 18 species to high throughput ciliary studies, and to OMIM data on human hereditary diseases. The web interface of Cildb comprises three tools, BioMart for complex queries, BLAST for sequence homology searches and GBrowse for browsing the human genome in relation to OMIM information for human diseases. Cildb can be used for interspecies comparisons, building candidate ciliary proteomes in any species, or identifying candidate ciliopathy genes

Feasibility and Safety of Silicone Rubber Contrast-Enhanced Microcomputed Tomography in Evaluating the Angioarchitecture of Prostatectomy Specimens1

This ethics committee-approved pilot study was carried out with informed consent. A protocol was developed to assess the feasibility of in vitro Microfil injection of prostate cancer specimens followed by analysis with micro-computed tomography (microCT) to characterize the functional vascularity of prostatic tissue and evaluate its safety with respect to the preservation of a specimen for pathologic examination. The visible prostatic arteries of two surgically resected prostates frompatients with known prostate cancer (PCa) were injected with MicrofilMV-122 contrast medium immediately after removal. The specimens were scanned using microCT and were qualitatively examined using three-dimensional analysis software (MicroView; GE Healthcare Biosciences). The Microfil perfusion in the two samples was sufficient to view the functional vascularity arising from a major prostatic artery, up to a resolution of 17.626 µm without any indication of adverse effects due to Microfil injection. Malignant prostatic regions showed a greater vascular density on histology but decreased vascular perfusion compared with benign prostatic regions. The use of microCT on Microfil-injected prostates seems to be a feasible and specimen-preserving method for visualizing the three-dimensional vessel patterns present in resected human prostates

The Influence of Demonstration Sites and Field Days on Adoption of Conservation Practices

For more than 100 years, demonstrations have been used by university extension programs and other conservation professionals to increase knowledge, awareness, and adoption of agricultural practices and technologies. However, there has been no systematic, empirical examination of the effect demonstrations have on adoption of agricultural innovations nor conservation practices. We examined the relationship between producer attendance at demonstration sites and field days of four conservation practices and the subsequent adoption of these practices using a mail survey (n = 513) and in-person interviews (n = 24) with agricultural producers in three regions of Indiana. Results show that there is a significant, moderate relationship between attendance and adoption of cover crops, nutrient management, and filter strips and a significant, weak relationship for two-stage ditches. Interviews with agricultural producers suggest that cover crop demonstration sites and field days allow for learning about practices from persons outside their regular social and professional network and provide tailored advice that allow producers to understand what to consider when making a decision to adopt a conservation practice. Results indicate that demonstration sites and field days do influence adoption of conservation practices; however, data do not control for the probability that those who attend are more likely to adopt regardless of attendance