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Advanced prostate cancer cells preferentially metastasize to bone by acquiring a bone phenotype that allows metastatic cells to thrive in the skeletal environment. Identification of factors that promote the expression of ectopic bone genes—process known as osteomimicry—leading to tumor progression is crucial to prevent and treat metastatic prostate cancer and prolong life expectancy for patients. Here, we identify the extracelular matrix protein mindin in the secretome of prostate adenocarcinoma cells and show that mindin overexpression in human and mouse TRAMP-C1-induced prostate tumors correlates with upregulated levels of bone-related genes in the tumorigenic prostate tissues. Moreover, mindin silencing decreased osteomimicry in adenocarcinoma cells and in the prostate tumor mice model, as well as reduced tumor cell proliferation, migration and adhesion to bone cells. Inhibition of the extracellular signal-regulated kinase 1/2 (ERK 1/2) phosphorylation decreased the proliferative, migratory and pro-adhesion actions of mindin on prostate tumor cells. In addition, conditioned media obtained by crosstalk stimulation of either osteocytes or osteoblasts with the secretome of TRAMP-C1 cells promoted osteomimicry in prostate tumor cells; an effect inhibited by mindin silencing of TRAMP-C1 cells. In vivo, tibiae of primary tumor-bearing mice overexpressed the pro-angiogenic and pro-metastattic factor vascular endothelial growth factor receptor 2 (VEGFR2) in a mindin-dependent manner. Our findings indicate that mindin is a novel regulator of osteomimicry in prostate tumors and potentially mediates tumor-bone cell crosstalk, suggesting its promising role as a target to inhibit bone metastases.

SummaryBackground Prebiotics have been shown to reduce abdominal symptoms in patients with functional gut disorders, despite that they are fermented by colonic bacteria and may induce gas-related symptoms. Aim To investigate changes in the metabolic activity of gut microbiota induced by a recognised prebiotic. Methods Healthy subjects (n = 20) were given a prebiotic (2.8 g/day HOST-G904, HOST Therabiomics, Jersey, Channel Islands) for 3 weeks. During 3-day periods immediately before, at the beginning and at the end of the administration subjects were put on a standard diet (low fibre diet supplemented with one portion of high fibre foods) and the following outcomes were measured: (i) number of daytime gas evacuations for 2 days by means of an event marker; (ii) volume of gas evacuated via a rectal tube during 4 h after a test meal; and (iii) microbiota composition by faecal Illumina MiSeq sequencing. Results At the beginning of administration, HOST-G904 significantly increased the number of daily anal gas evacuations (18 ± 2 vs. 12 ± 1 pre-administration; P < 0.001) and the volume of gas evacuated after the test meal (236 ± 23 mL vs. 160 ± 17 mL pre-administration; P = 0.006). However, after 3 weeks of administration, these effects diminished (11 ± 2 daily evacuations, 169 ± 23 mL gas evacuation). At day 21, relative abundance of butyrate producers (Lachnospiraceae) correlated inversely with the volume of gas evacuated (r = −0.52; P = 0.02). Conclusion The availability of substrates induces an adaptation of the colonic microbiota activity in bacterial metabolism, which produces less gas and associated issues. Clinical trials.gov NCT02618239.

The interactions between steroid and nonsteroid hormones in the prostate are of special interest during the growth phase of the gland. The purpose of this work is to study the influence of prolactin (PL), with or without androgenic blockade, on epithelial cells from peripubertal rat ventral prostate. Twenty male peripubertal Sprague-Dawley rats were grouped as controls, or treated with cyproterone acetate (CA), CA plus PL (CA-PL), or PL. The total number (N total) of epithelial cells, and their labeling indices to proliferative cell nuclear antigen (LI PCNA), apoptosis (LI apoptosis) and androgen receptors (LI AR) were measured. CA and PL treatment significantly decrease the N total, but the LI PCNA was unchanged. We have observed a greater LI apoptosis in pharmacologically castrated animals without PL than in the rats with androgenic blockade with PL. The LI AR does not change with CA treatment in the ventral region, but the PL significantly increases it. Androgenic blockade and PL decrease the number of epithelial cells from the ventral prostate. These changes are not attributable to the decrease of cell proliferation, rather to the increase of epithelial apoptosis. The increase of cells expressing AR after treatment with PL might be attributed to the decrease of testosterone secretion caused by the hyperprolactinemia. PL does not modulate the size of the ventral prostate in prepubertal rats.

This work deals with the quantification of serotonin-immunoreactive prostate neuroendocrine cells (NECs) in rats exposed to prolactin in normal, cyproterone acetate-exposed, and bromocriptine-exposed animals to establish the possible influence of prolactin with or without androgenic blockade on this cell population. Thirty male peripubertal Sprague-Dawley rats were grouped as controls (CT) and those treated with cyproterone acetate (CA), cyproterone acetate plus prolactin, cyproterone acetate plus bromocriptine, prolactin (PL), and bromocriptine (BC). The volume of ductal epithelium (Vep) and total number (NSER) of the NECs serotonin-immunoreactive were measured. NECs were detected in the periurethral ducts. Compared to CT, Vep was increased in PL and BC and NSER was decreased in CA and increased in the prolactin or bromocriptine groups. The androgenic blockade decreases NSER in rat prostate; PL induces in normal and cyproterone acetate-treated rats the increase of NSER; and BC exerts a local effect over the prostate similar to that described for PL.

BACKGROUND This work was undertaken to study the prostate neuroendocrine cells (PNEC) during the post-natal development of rats. METHODS Forty male Wistar rats (pre-pubertals, pubertals, young, and aged adults) were used for immunohistochemistry of chromogranin A (cgA), serotonin (SER), and protein gene product 9.5 (PGP9.5). They were also evaluated for numerical cell density (NV SER) and PNEC number per prostate (N SER). Five additional young adult rats were used for a RT-PCR study (mRNA cgA detection). RESULTS Weak immunoreactivity to cgA was observed in pubertal rats. No PNEC immunostained to PGP 9.5 was observed. Cells expressing SER were detected in all the groups exclusively located in periurethral ducts. The NV SER increased significantly in pubertal animals. In aged animals, it decreased to levels observed in pre-pubertal rats. The N SER increased significantly from pre-pubertal to young adults, decreasing in aged adults. There was weak production of cgA mRNA, with more expression in the dorsal prostate. CONCLUSIONS PNEC differ in rats when compared to humans: they are weakly immunopositive to cgA, do not express PGP 9.5, only show immunoreactivity to SER, and do not appear in acini. The changes in the amount of rat PNEC during the post-natal development suggest an androgenic influx. PNEC might regulate the contractility of periurethral ducts. Prostate 57: 176–185, 2003. © 2003 Wiley-Liss, Inc.

Intensively cultivated lands of the Andalusian east coast (South of Spain) were sampled in 3 areas, with 3 plots and a non-cultivated control plot per area, and at two depths, 0–25 cm and 25–50 cm. In each plot and depth, 3 samples were taken, made up of 5 subsamples. The analysis of elements such as arsenium (As), cadmium (Cd), copper (Cu), mercury (Hg), and lead (Pb) were made by two different digestion methods: 2 hours with acqua regia in an oil bath at 140°C, or 10 minutes with nitric acid in closed recipients inside a microwave oven. Results show differences for most of the elements between areas and between methods, and sometimes between depths. Average values per plot were always below the critical levels accepted for agricultural use. A detailed exam of values for each plot suggests reliability on the determination of As and Cu, in each case. There were few occasional anomalies in the determination of Cd, Hg, and Pb. This could be related either to irregular distributions of the elements in the so...

This work was undertaken to study the prostate neuroendocrine cells (PNEC) during the post-natal development of rats.Forty male Wistar rats (pre-pubertals, pubertals, young, and aged adults) were used for immunohistochemistry of chromogranin A (cgA), serotonin (SER), and protein gene product 9.5 (PGP9.5). They were also evaluated for numerical cell density (NV SER) and PNEC number per prostate (N SER). Five additional young adult rats were used for a RT-PCR study (mRNA cgA detection).Weak immunoreactivity to cgA was observed in pubertal rats. No PNEC immunostained to PGP 9.5 was observed. Cells expressing SER were detected in all the groups exclusively located in periurethral ducts. The NV SER increased significantly in pubertal animals. In aged animals, it decreased to levels observed in pre-pubertal rats. The N SER increased significantly from pre-pubertal to young adults, decreasing in aged adults. There was weak production of cgA mRNA, with more expression in the dorsal prostate.PNEC differ in rats when compared to humans: they are weakly immunopositive to cgA, do not express PGP 9.5, only show immunoreactivity to SER, and do not appear in acini. The changes in the amount of rat PNEC during the post-natal development suggest an androgenic influx. PNEC might regulate the contractility of periurethral ducts.

The choline-binding domain (ChoBD) of the carboxy-terminal region of the Streptococcus pneumoniae amidase LYTA (C-LYTA) presents a strong affinity for tertiary amines. We report a method for single-step purification of proteins expressed in the methylotrophic yeast Pichia pastoris based on the fusion of C-LYTA to the protein of interest. We show that C-LYTA can be efficiently expressed and secreted in this host. Tagged proteins fused to this binding domain can be purified on inexpensive DEAE matrices. It therefore provides a useful system for the purification of recombinant proteins with high specificity suitable for industrial purposes.

The effect of isoproturon [N,N-dimethyl N′4-(1-methyl-ethyl) phenyl urea] on the germination, growth of root and ultrastructure of the photosynthetic apparatus was investigated in two wheat cultivars (Triticum sativum L. cvs Castan and Esquilache) and a weed (Lolium rigidum Gaud.). No inhibition of germination was apparent in any of the three plants studied. The inhibition of root growth was considerably significant, especially in cv. Esquilache. After 48 h treatment with isoproturon (340 μM), the chloroplasts of the two wheat cultivars were found to be similar, showing a higher number of grana with fewer thylakoids per granum (lower stacking degree), broader grana stacks than in the control and an absence of starch. However, after 60 h of treatment, swelling of the thylakoids occurred in the Esquilache cultivar. The rye grass was the most affected by the herbicide; at low concentration (3.4 μM) the number and size of the grana decreased considerably and the stroma thylakoids were destroyed. At higher concentration (17 μM), there was a strong accumulation in certain areas of the stroma of a substance with a lipid-like appearance, probably derived from the disintegrating thylakoids. At the same concentrations some chloroplast envelopes were completely desintegrated. The Hill reaction of the three plants exhibited a similar sensitivity towards the herbicide.