Vitamin D, Sunlight and Prostate Cancer Risk

Prostate cancer is the second common cancer in men worldwide. The prevention of prostate cancer remains a challenge to researchers and clinicians. Here, we review the relationship of vitamin D and sunlight to prostate cancer risk. Ultraviolet radiation of the sunlight is the main stimulator for vitamin D production in humans. Vitamin D's antiprostate cancer activities may be involved in the actions through the pathways mediated by vitamin D metabolites, vitamin D metabolizing enzymes, vitamin D receptor (VDR), and VDR-regulated genes. Although laboratory studies including the use of animal models have shown that vitamin D has antiprostate cancer properties, whether it can effectively prevent the development and/or progression of prostate cancer in humans remains to be inconclusive and an intensively studied subject. This review will provide up-to-date information regarding the recent outcomes of laboratory and epidemiology studies on the effects of vitamin D on prostate cancer prevention

Oxidative Stress and DNA Methylation in Prostate Cancer

The protective effects of fruits, vegetables, and other foods on prostate cancer may be due to their antioxidant properties. An imbalance in the oxidative stress/antioxidant status is observed in prostate cancer patients. Genome oxidative damage in prostate cancer patients is associated with higher lipid peroxidation and lower antioxidant levels. Oxygen radicals are associated with different steps of carcinogenesis, including structural DNA damage, epigenetic changes, and protein and lipid alterations. Epigenetics affects genetic regulation, cellular differentiation, embryology, aging, cancer, and other diseases. DNA methylation is perhaps the most extensively studied epigenetic modification, which plays an important role in the regulation of gene expression and chromatin architecture, in association with histone modification and other chromatin-associated proteins. This review will provide a broad overview of the interplay of oxidative stress and DNA methylation, DNA methylation changes in regulation of gene expression, lifestyle changes for prostate cancer prevention, DNA methylation as biomarkers for prostate cancer, methods for detection of methylation, and clinical application of DNA methylation inhibitors for epigenetic therapy

Antiangiogenic Effects and Therapeutic Targets of Azadirachta indica Leaf Extract in Endothelial Cells

Azadirachta indica (common name: neem) leaves have been found to possess immunomodulatory, anti-inflammatory and anti-carcinogenic properties. The present study evaluates anti-angiogenic potential of ethanol extract of neem leaves (EENL) in human umbilical vein endothelial cells (HUVECs). Treatment of HUVECs with EENL inhibited VEGF induced angiogenic response in vitro and in vivo. The in vitro proliferation, invasion and migration of HUVECs were suppressed with EENL. Nuclear fragmentation and abnormally small mitochondria with dilated cristae were observed in EENL treated HUVECs by transmission electron microscopy. Genome-wide mRNA expression profiling after treatment with EENL revealed differentially regulated genes. Expression changes of the genes were validated by quantitative real-time polymerase chain reaction. Additionally, increase in the expression of HMOX1, ATF3 and EGR1 proteins were determined by immunoblotting. Analysis of the compounds in the EENL by mass spectrometry suggests the presence of nimbolide, 2′,3′-dehydrosalannol, 6-desacetyl nimbinene and nimolinone. We further confirmed antiproliferative activity of nimbolide and 2′,3′-dehydrosalannol in HUVECs. Our results suggest that EENL by regulating the genes involved in cellular development and cell death functions could control cell proliferation, attenuate the stimulatory effects of VEGF and exert antiangiogenic effects. EENL treatment could have a potential therapeutic role during cancer progression

The Diverse Properties of the Most Ultraviolet Luminous Galaxies Discovered by the Galaxy Evolution Explorer

We report on the properties of a sample of ultraviolet luminous galaxies (UVLGs) selected by matching the Galaxy Evolution Explorer (GALEX) Surveys with the Sloan Digital Sky Survey Third Data Release. Out of 25362 galaxies between 0.02x10^10 L_solar at 1530 Angstroms (observed wavelength). The properties of this population are well correlated with ultraviolet surface brightness. We find that the galaxies with low UV surface brightness are primarily large spiral systems with a mixture of old and young stellar populations, while the high surface brightness galaxies consist primarily of compact starburst systems. In terms of the behavior of surface brightness with luminosity, size with luminosity, the mass-metallicity relation, and other parameters, the compact UVLGs clearly depart from the trends established by the full sample of galaxies. The subset of compact UVLGs with the highest surface brightness (``supercompact UVLGs'') have characteristics that are remarkably similar to Lyman Break Galaxies at higher redshift. They are much more luminous than typical local ultraviolet-bright starburst galaxies and blue compact dwarf galaxies. They have metallicities that are systematically lower than normal galaxies of the same stellar mass, indicating that they are less chemically evolved. In all these respects, they are the best local analogs for Lyman Break Galaxies.Comment: Fixed error in ObjID column of Table 1. 30 pages, 12 figures. Accepted for the GALEX special issue of ApJS. Abstract abridge

Recent star formation in nearby galaxies from GALEX imaging:M101 and M51

The GALEX (Galaxy Evolution Explorer) Nearby Galaxies Survey is providing deep far-UV and near-UV imaging for a representative sample of galaxies in the local universe. We present early results for M51 and M101, from GALEX UV imaging and SDSS optical data in five bands. The multi-band photometry of compact stellar complexes in M101 is compared to population synthesis models, to derive ages, reddening, reddening-corrected luminosities and current/initial masses. The GALEX UV photometry provides a complete census of young compact complexes on a approximately 160pc scale. A galactocentric gradient of the far-UV - near-UV color indicates younger stellar populations towards the outer parts of the galaxy disks, the effect being more pronounced in M101 than in M51.Comment: This paper will be published as part of the Galaxy Evolution Explorer (GALEX) Astrophysical Journal Letters Special Issue. Full paper available from http://dolomiti.pha.jhu.edu . Links to full set of papers will be available at http://www.galex.caltech.edu/PUBLICATIONS/ after November 22, 200

Interleukin-1 polymorphisms associated with increased risk of gastric cancer

Helicobacter pylori infection is associated with a variety of clinical outcomes including gastric cancer and duodenal ulcer disease. The reasons for this variation are not clear, but the gastric physiological response is influenced by the severity and anatomical distribution of gastritis induced by H. pylori. Thus, individuals with gastritis predominantly localized to the antrum retain normal (or even high) acid secretion, whereas individuals with extensive corpus gastritis develop hypochlorhydria and gastric atrophy, which are presumptive precursors of gastric cancer. Here we report that interleukin-1 gene cluster polymorphisms suspected of enhancing production of interleukin-1-beta are associated with an increased risk of both hypochlorhydria induced by H. pylori and gastric cancer. Two of these polymorphism are in near-complete linkage disequilibrium and one is a TATA-box polymorphism that markedly affects DNA-protein interactions in vitro. The association with disease may be explained by the biological properties of interleukin-1-beta, which is an important pro-inflammatory cytokine and a powerful inhibitor of gastric acid secretion. Host genetic factors that affect interleukin-1-beta may determine why some individuals infected with H. pylori develop gastric cancer while others do no

Panoramic GALEX FUV and NUV imaging of M31 and M33

We present Galaxy Evolution Explorer (GALEX) far-UV and near-UV mosaic observations covering the entirety of M31 and M33. For both targets, we measure the decline of surface brightness (in FUV and NUV) and changes in FUV--NUV color as a function of galactocentric radius. These UV radial profiles are compared to the distribution of ionized gas traced by H-alpha emission. We find that the extent of the UV emission, in both targets, is greater than the extent of the observed HII regions and diffuse ionized gas. We determine the ultraviolet diffuse fraction in M33 using our FUV observations and compare it to the H-alpha diffuse fraction obtained from wide-field narrow-band imaging. The FUV diffuse fraction appears to be remarkably constant near 0.65 over a large range in galactocentric radius, with departures to higher values in circumnuclear regions and, most notably, at the limit of the H-alpha disk. We suggest that the increase in FUV diffuse fraction at large galactocentric radii could indicate that a substantial portion of the diffuse emission beyond this point is not generated in situ but rather scattered from dust, after originating in the vicinity of the disk's outermost HII regions. Radial variation of the H-alpha diffuse fraction was also measured. We found the H-alpha diffuse fraction generally near 0.4 but rising toward the galaxy center, up to 0.6. We made no attempt to correct our diffuse fraction measurements for position-dependent extinction, so the quoted values are best interpreted as upper limits given the plausibly higher extinction for stellar clusters relative to their surroundings.Comment: This paper will be published as part of the Galaxy Evolution Explorer (GALEX) Astrophysical Journal Letters Special Issue. Links to the full set of papers will be available at http://www.galex.caltech.edu/PUBLICATIONS/ after November 22, 2004. Individual high-resolution figures can be found at http://dolomiti.pha.jhu.edu/publgoto.htm

GALEX Observations of the Ultraviolet Halos of NGC 253 and M82

We present Galaxy Evolution Explorer (GALEX) images of the prototypical edge-on starburst galaxies M82 and NGC253. Our initial analysis is restricted to the complex of ultraviolet (UV) filaments in the starburst-driven outflows in the galaxy halos. The UV luminosities in the halo are too high to be provided by shock-heated or photoionized gas except perhaps in the brightest filaments in M82, suggesting that most of the UV light is the stellar continuum of the starburst scattered into our line of sight by dust in the outflow. This interpretation agrees with previous results from optical imaging polarimetry in M82. The morphology of the UV filaments in both galaxies shows a high degree of spatial correlation with H-alpha and X-ray emission. This indicates that these outflows contain cold gas and dust, some of which may be vented into the intergalactic medium (IGM). UV light is seen in the ``H-alpha cap'' 11 kpc North of M82. If this cap is a result of the wind fluid running into a pre-existing gas cloud, the gas cloud contains dust and is not primordial in nature but was probably stripped from M82 or M81. If starburst winds efficiently expel dust into the IGM, this could have significant consequences for the observation of cosmologically distant objects.Comment: This paper will be published as part of the Galaxy Evolution Explorer (GALEX) Astrophysical Journal Letters Special Issue. Links to the full set of papers will be available at http://www.galex.caltech.edu/PUBLICATIONS/ after November 22, 200

Retigeric Acid B Exhibits Antitumor Activity through Suppression of Nuclear Factor-κB Signaling in Prostate Cancer Cells in Vitro and in Vivo

Previously, we reported that retigeric acid B (RB), a natural pentacyclic triterpenic acid isolated from lichen, inhibited cell growth and induced apoptosis in androgen-independent prostate cancer (PCa) cells. However, the mechanism of action of RB remains unclear. In this study, we found that using PC3 and DU145 cells as models, RB inhibited phosphorylation levels of IκBα and p65 subunit of NF-κB in a time- and dosage-dependent manner. Detailed study revealed that RB blocked the nuclear translocation of p65 and its DNA binding activity, which correlated with suppression of NF-κB-regulated proteins including Bcl-2, Bcl-xL, cyclin D1 and survivin. NF-κB reporter assay suggested that RB was able to inhibit both constitutive activated-NF-κB and LPS (lipopolysaccharide)-induced activation of NF-κB. Overexpression of RelA/p65 rescued RB-induced cell death, while knockdown of RelA/p65 significantly promoted RB-mediated inhibitory effect on cell proliferation, suggesting the crucial involvement of NF-κB pathway in this event. We further analyzed antitumor activity of RB in in vivo study. In C57BL/6 mice carrying RM-1 homografts, RB inhibited tumor growth and triggered apoptosis mainly through suppressing NF-κB activity in tumor tissues. Additionally, DNA microarray data revealed global changes in the gene expression associated with cell proliferation, apoptosis, invasion and metastasis in response to RB treatment. Therefore, our findings suggested that RB exerted its anti-tumor effect by targeting the NF-κB pathway in PCa cells, and this could be a general mechanism for the anti-tumor effect of RB in other types of cancers as well