Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Selenium (Se) in a large-scale human supplementation trial has been shown to significantly reduce the incidence of prostate cancer in elderly men. Because Se is known to interact with cadmium (Cd), it has been suggested that its cancer protective action could be attributable in part to its interaction with Cd, a toxic and suspected carcinogenic element, which is found in many foods, in drinking water, and in the environment. Cadmium is considered a significant prostate cancer risk factor as it stimulates the growth of prostate epithelial cells and promotes their malignant transformation. Accordingly, prostate cancer risk is determined not only by Se status, but also the degree of Cd exposure. Determinations of Se and Cd in 129 prostates of deceased men aged 15-99 yr revealed Cd to accumulate in the prostate. Whereas the atomic Se/Cd ratios of the prostates of young men were invariably >1, indicating a stoichiometric excess of Se over Cd, they were found to decline with age, approaching the 1:1 ratio in elderly nonsmokers, a fact suggestive of the formation of a 1:1 Cd-Se complex. The associated physiological inactivation of Se could account for the increase of the prostate cancer risk with advancing age. The Se/Cd ratios dropped more steeply and consistently with age in smokers than in nonsmokers. In the prostates of some smokers, Se/Cd ratios even reached values <1, indicating a stoichiometric excess of Cd over Se. The excessive accumulation of Cd in the prostates of smokers along with sub-optimal Se intakes could explain why smokers develop more aggressive and lethal forms of prostate cancer than nonsmokers.
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PMID:Selenium/cadmium ratios in human prostates: indicators of prostate cancer risk of smokers and nonsmokers, and relevance to the cancer protective effects of selenium. 1577 34

The use of low-energy photon emitters for brachytherapy applications, as in the treatment of prostate or ocular tumours, has increased significantly over the last few years. Several new seed models utilizing 103Pd and 125I have recently been introduced. Following the TG43U1 recommendations of the AAPM (American Association of Physicists in Medicine) (Rivard et al 2004 Med. Phys. 31 633), dose distributions around these low-energy photon emitters are characterized by the dose rate constant, the radial dose function and the anisotropy function in water. These functions and constants can be measured for each new seed in a solid phantom (i.e. solid water such as WT1) using high spatial resolution detectors such as very small thermoluminescent detectors. These experimental results in solid water must then be converted into liquid water by using Monte Carlo simulations. This paper presents the dosimetric parameters of a new palladium seed, OptiSeed (produced by International Brachytherapy (IBt), Seneffe, Belgium), made with a biocompatible polymeric shell and with a design that differs from the hollow titanium encapsulated seed, InterSource103, produced by the same company. A polymer encapsulation was chosen by the company IBt in order to reduce the quantity of radioactive material needed for a given dose rate, and to improve the symmetry of the radiation field around the seed. The necessary experimental data were obtained by measurements with LiF thermoluminescent dosimeters (1 mm3) in a solid water phantom (WT1) and then converted to values in liquid water using Monte Carlo calculations (MCNP-4C). Comparison of the results with a previous study by Reniers et al (2002 Appl. Radiat. Isot. 57 805) shows very good agreement for the dose rate constant and for the radial dose function. In addition, the results also indicate an improvement in isotropy compared to a conventional titanium encapsulated seed. The relative dose (anisotropy value relative to 90 degrees ) from the seed at a distance of 3 cm is close to 70% at 0 degrees whereas that for the titanium encapsulated InterSource103seed is close to 40%. This paper also presents some new Monte Carlo calculations relating to shadowing produced by the seeds in an array implanted for a prostate cancer treatment. Recently, Mobit and Badragan (2004 Phys. Med. Biol. 49 3171) reported shadowing resulting in a 10% decrease in dose from titanium encapsulated 125I seed. We used Monte Carlo simulations (MCNP-4C) to evaluate shadowing for the InterSource103 titanium encapsulated seed and the OptiSeed polymer encapsulated seed. For a specific geometry specified, dose decreases of 13% and 7% were found for the InterSource103 titanium encapsulated and the OptiSeed polymer encapsulated seed, respectively.
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PMID:Dosimetric study of a new polymer encapsulated palladium-103 seed. 1579 39

Dietary patterns reflect combinations of dietary exposures, and here we examine these in relation to prostate cancer risk. In a case-control study, 80 incident primary prostate cancer cases and 334 urology clinic controls were enrolled from 1997 through 1999 in Kingston, Ontario, Canada. Food-frequency questionnaires were completed prior to diagnosis and assessed intake in the 1-year period 2-3 years prior to enrollment. Among controls, dietary intake was used in principal components analyses to identify patterns that were then evaluated with all subjects in relation to prostate cancer risk using unconditional logistic regression, controlling for age. Four dietary patterns were identified: Healthy Living, Traditional Western, Processed and Beverages. Increased prostate cancer risk is apparent in relation to the Processed pattern, composed of processed meats, red meats, organ meats, refined grains, white bread, onions and tomatoes, vegetable oil and juice, soft drinks and bottled water. The OR for the highest tertile compared to baseline is 2.75 (95% CI 1.40-5.39), with a dose-response pattern (trend test p < 0.0035). Our results suggest that a dietary pattern including refined grain products, processed meats and red and organ meats contributes to increased prostate cancer risk. Since dietary information was collected before subjects knew their diagnosis, recall bias was avoided.
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PMID:Dietary patterns and risk of prostate cancer in Ontario, Canada. 1582 70

Magnetic resonance spectroscopic imaging (MRSI) has proven to be a powerful tool for the metabolic characterization of prostate cancer in patients before and following therapy. The metabolites that are of particular interest are citrate and choline because an increased choline-to-citrate ratio can be used as a marker for cancer. High-field systems offer the advantage of improved spectral resolution as well as increased magnetization. Initial attempts at extending MRSI methods to 3 T have been confounded by the J-modulation of the citrate resonances. A new pulse sequence is presented that controls the J-modulation of citrate at 3 T such that citrate is upright, with high amplitude, at a practical echo time. The design of short (14 ms) spectral-spatial refocusing pulses and trains of nonselective refocusing pulses are described. Phantom studies and simulations showed that upright citrate with negligible sidebands is observed at an echo time of 85 ms. Studies in a human subject verified that this behavior is reproduced in vivo and demonstrated that the water and lipid suppression of the new pulse sequence are sufficient for application in prostate cancer patients.
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PMID:Sequence design for magnetic resonance spectroscopic imaging of prostate cancer at 3 T. 1584 47

Estrogens and androgens are proposed to play a role in the pathogenesis of prostate cancer. The effective metabolites, estradiol and 5alpha-dihydrotestosterone are produced from testosterone by aromatase and 5alpha-reductase, respectively. Metabolites of vitamin D have shown to inhibit the growth of prostate cancer cells. The aim of the present study was to verify whether 25-hydroxyvitamin D(3) (25OHD(3)), 1alpha,25-dihydroxyvitamin D(3) [1alpha,25-(OH)(2)D(3)], dexamethasone, and progesterone regulate the expression of aromatase and 5alpha-reductase in human prostate cancer cells. LNCaP and PC3 cells were treated with 25OHD(3), 1alpha,25-(OH)(2)D(3), dexamethasone, or progesterone. Aromatase and 5alpha-reductase mRNA was quantified by real-time RT-PCR and aromatase enzyme activity was measured by the [(3)H] water assay. Aromatase enzyme activity in LNCaP and PC3 cells was increased by both 10nM dexamethasone, 1-100 nM 1alpha,25-(OH)(2)D(3) and 100 nM-10 microM progesterone. The induction was enhanced when hormones were used synergistically. Real-time RT-PCR analysis showed no regulation of the expression of aromatase mRNA by any steroids tested in either LNCaP or PC3 cells. The expression of 5alpha-reductase type I mRNA was not regulated by 1alpha,25-(OH)(2)D(3) and no expression of 5alpha-reductase type II was detected in LNCaP.
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PMID:Regulation of aromatase and 5alpha-reductase by 25-hydroxyvitamin D(3), 1alpha,25-dihydroxyvitamin D(3), dexamethasone and progesterone in prostate cancer cells. 1586 60

Andrographolide was extracted and purified from Andrographis panicula using hexane and water partitioning followed by ethyl acetate extraction and chromatography. It showed selective cytotoxicity to prostate cancer PC-3 cells in vitro. The morphological and biochemical changes induced by the extract in carcinoma PC-3 cell death were studied. In andrographolide-treated cells, evidence of apoptosis such as cell shrinkage and surface microvilli loss after 4-hour treatment and chromatin condensation and fragmentation in H&E-stained cells between 4 to 8 hours after treatment were observed. Under electron microscopy, membrane blebbing and apoptotic bodies formation were seen after 8-hour treatment. Using immunocytochemistry staining and cellular caspase-3 activity assay, andrographolide-treated cells showed considerable caspase-3 activation and caspase-8 in PC-3 cells at 4 and 2 hours after treatment, respectively. This suggests andrographolide-induced cell death was achieved through the apoptotic pathway, via the activation of an extrinsic caspase cascade.
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PMID:Morphological and biochemical changes of andrographolide-induced cell death in human prostatic adenocarcinoma PC-3 cells. 1587 75

A practical liquid chromatography-tandem mass spectrometric (LC-MS-MS) method for the determination of prostatic 5alpha-dihydrotestosterone (DHT) and testosterone (T) has been developed. The prostatic androgens were extracted with MeOH-H2O (3:7, v/v), purified with an Oasis HLB cartridge, derivatized with the permanently charged reagent 2-hydrazino-1-methylpyridine (HMP), and subjected to LC-MS-MS analysis using electrospray ionization (ESI) operated in the positive ion mode. The derivatization with HMP was very effective at increasing the detectability using the positive-ESI-MS. The method allowed the reproducible and accurate quantification of ng g(-1) tissue levels of prostatic androgens in 10 mg of tissue. That is, the intra- and inter-assay coefficients of variation were below 8.1 and 9.3%, respectively, and the analytical recoveries of the androgens were quantitative. The limits of quantitation for DHT and T were both 1.0 ng g(-1) tissue. The developed method was used to determine DHT and T in the prostates of patients with benign prostatic hyperplasia and prostate cancer, and satisfactory results were obtained.
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PMID:Determination of prostatic androgens in 10 mg of tissue using liquid chromatography-tandem mass spectrometry with charged derivatization. 1590 88

We have developed a novel water-dispersible oleic acid (OA)-Pluronic-coated iron oxide magnetic nanoparticle formulation that can be loaded easily with high doses of water-insoluble anticancer agents. Drug partitions into the OA shell surrounding iron oxide nanoparticles, and the Pluronic that anchors at the OA-water interface confers aqueous dispersity to the formulation. Neither the formulation components nor the drug loading affected the magnetic properties of the core iron oxide nanoparticles. Sustained release of the incorporated drug is observed over 2 weeks under in vitro conditions. The nanoparticles further demonstrated sustained intracellular drug retention relative to drug in solution and a dose-dependent antiproliferative effect in breast and prostate cancer cell lines. This nanoparticle formulation can be used as a universal drug carrier system for systemic administration of water-insoluble drugs while simultaneously allowing magnetic targeting and/or imaging.
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PMID:Iron oxide nanoparticles for sustained delivery of anticancer agents. 1593 80

High spectral and spatial resolution (HiSS) MRI of rodent tumors has previously been performed using conventional spectroscopic imaging to obtain images with improved contrast and anatomic detail. The work described here evaluates the use of much faster echo-planar spectroscopic imaging (EPSI) to acquire HiSS data from rodent tumor models of prostate cancer. A high-resolution EPSI pulse sequence was implemented on a 4.7 T Bruker scanner. Three-dimensional EPSI data were Fourier-transformed along the k-space and temporal (free-induction decay) axes to produce detailed water and fat spectra associated with each small image voxel. The data were used to generate images of spectral parameters, e.g. peak-height images for each small voxel. Two variants of EPSI were performed; gradient-echo or spin-echo excitation with EPSI readout. These imaging methods were tested in commonly used rodent prostate cancers, including seven mice implanted with non-metastatic AT2.1 (n=3) and metastatic AT3.1 (n=4) prostate tumors on the hind leg, and 10 mice implanted with LNCaP prostate cancers in situ. The peak-height images derived from EPSI datasets provide more detailed tumor anatomy, improved signal-to-noise and contrast-to-noise ratios compared with the gradient-echo or spin-echo images at all echo times. The results suggest that HiSS MRI data from small animal models of prostate cancer can be acquired using EPSI, and that this approach improves imaging of heterogeneous tissue and vascular environments inside the tumors compared with conventional MR techniques.
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PMID:Comparison of high-resolution echo-planar spectroscopic imaging with conventional MR imaging of prostate tumors in mice. 1597 57

The mechanism by which the androgen receptor (AR) distinguishes between agonist and antagonist ligands is poorly understood. AR antagonists are currently used to treat prostate cancer. However, mutations commonly develop in patients that convert these compounds to agonists. Recently, our laboratory discovered selective androgen receptor modulators, which structurally resemble the nonsteroidal AR antagonists bicalutamide and hydroxyflutamide but act as agonists for the androgen receptor in a tissue-selective manner. To investigate why subtle structural changes to both the ligand and the receptor (i.e. mutations) result in drastic changes in activity, we studied structure-activity relationships for nonsteroidal AR ligands through crystallography and site-directed mutagenesis, comparing bound conformations of R-bicalutamide, hydroxyflutamide, and two previously reported nonsteroidal androgens, S-1 and R-3. These studies provide the first crystallographic evidence of the mechanism by which nonsteroidal ligands interact with the wild type AR. We have shown that changes induced to the positions of Trp-741, Thr-877, and Met-895 allow for ligand accommodation within the AR binding pocket and that a water-mediated hydrogen bond to the backbone oxygen of Leu-873 and the ketone of hydroxyflutamide is present when bound to the T877A AR variant. Additionally, we demonstrated that R-bicalutamide stimulates transcriptional activation in AR harboring the M895T point mutation. As a whole, these studies provide critical new insight for receptor-based drug design of nonsteroidal AR agonists and antagonists.
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PMID:Structural basis for accommodation of nonsteroidal ligands in the androgen receptor. 1612 72


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