Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) are synthetic surfactants used in Japan. An epidemiological study of workers exposed to PFOA revealed a significant increase in prostate cancer mortality. A cross-sectional study of PFOA-exposed workers showed that PFOA perturbs sex hormone homeostasis. We analyzed their concentrations in surface water samples collected from all over Japan by LC/MS with a solid phase extraction method. The lowest limits of detection (LOD) (ng/L) were 0.06 for PFOA and 0.04 for PFOS. The lowest limits of quantification (LOQ) (ng/L) were 0.1 for both analytes. The levels [geometric mean (GM); geometric standard deviation (GS)] (ng/L) of PFOA and PFOS in the surface waters were GM (GS): 0.97 (3.06) and 1.19 (2.44) for Hokkaido-Tohoku (n=16); 2.84(3.56) and 3.69 (3.93) for Kanto (n=14); 2.50 (2.23) and 1.07 (2.36) for Chubu (n=17); 21.5 (2.28) and 5.73 (3.61) for Kinki (n=8); 1.51 (2.28) and 1.00 (3.42) for Chugoku (n=9); 1.93 (2.40) and 0.89 (3.09) for Kyushu-Shikoku (n=15). The GM of PFOA in Kinki was significantly higher than in other areas (ANOVA p<0.01). Systematic searches of Yodo and Kanzaki Rivers revealed two highly contaminated sites, a public-water-disposal site for PFOA and an airport for PFOS. The former was estimated to release 18 kg of PFOA/d. PFOA in drinking water in Osaka city [40 (1.07) ng/L] was significantly higher than in other areas. The present study confirms that recognizable amounts of PFOA are released in the Osaka area and that people are exposed to PFOA through drinking water ingestion.
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PMID:Perfluorooctanoate and perfluorooctane sulfonate concentrations in surface water in Japan. 1496 Aug 30

Arsenite is ubiquitous in the environment, particularly in the form of contaminated water. Although this metal is a known human carcinogen, its exact mechanism of action remains unclear. P70S6K1 phosphorylates the ribosomal 40S protein leading to increased protein translation, and is an important regulator of cell growth and proliferation. Hypoxia inducible factor-1 (HIF-1) is a basic helix-loop-helix transcription factor composed of two subunits, HIF-1alpha and HIF-1beta. HIF-1 activates the transcription of a number of genes that mediate angiogenesis and tumor formation. In this study we demonstrated that arsenite treatment increased levels of p70S6K1 phosphorylation and p70S6K1 activity in a PI3K and mTOR sensitive manner. We have also shown that arsenite specifically induces HIF-1alpha, but not HIF-1beta, protein levels in prostate cancer cells in a mTOR-dependent manner.
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PMID:Arsenite induces p70S6K1 activation and HIF-1alpha expression in prostate cancer cells. 1497 42

A peptide-doxorubicin conjugate (I) is a drug candidate that has been evaluated for the treatment of prostate cancer. During the high-performance liquid chromatographic (HPLC)-fluorescence analysis of clinical samples for compound I and its two known metabolites [doxorubicin (II) and leucine-doxorubicin (III)], additional metabolites are observed in postdose human plasma extracts. Using neutral loss, precursor, and product ion tandem mass spectrometric (MS-MS) experiments, two of these metabolites are identified as doxorubicinol (IV) and leucine-doxorubicinol (V), the active 13-hydroxy metabolites of doxorubicin and leucine-doxorubicin, respectively. A third metabolite, 7-deoxydoxorubicinol aglycone (VI), is detected using single-ion monitoring at m/z 399 in the negative ionization mode. The product ion mass spectrum of this metabolite contains a major fragment at m/z 351, resulting from the loss of water and formaldehyde from the pseudomolecular ion. An HPLC-MS-MS method for simultaneous analysis of II, III, IV, V, and VI is developed utilizing gradient HPLC with a combination of positive/negative ionization MS in the multiple reaction monitoring mode and monitoring the appropriate MS-MS transitions. Using this methodology, rat, dog, and human plasma metabolite profiles are compared and found to be qualitatively similar. Simultaneous fluorescence and MS detection experiments confirm that the peaks observed in the HPLC-fluorescence chromatograms of plasma extracts correspond to each of the five metabolites (II-VI).
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PMID:The identification of three human metabolites of a peptide-doxorubicin conjugate using HPLC-MS-MS in positive and negative ionization modes. 1529 32

Clusterin (CLU) protein is widely distributed in animal tissues and is involved in many different processes, including apoptosis and neoplastic transformation. Green tea catechins (GTC) are known to exert chemopreventive effects in many cancer models, including transgenic adenocarcinoma mouse prostate (TRAMP) mice that spontaneously develop prostate cancer (CaP). We report here that growth of SV40-immortalized human prostate epithelial cells (PNT1A) as well as tumorigenic, poorly differentiated prostate cancer cells (PC-3) was potently inhibited by EGCG, the major green tea catechin, while normal human prostate epithelial cells were not significantly affected. IC(50) doses of EGCG for 24 h caused caspase cascade activation and CLU protein accumulation in both cells lines but not in normal cells, in which CLU remained undetectable. While 100% of TRAMP mice developed CaP, only 20% of those receiving 0.3% GTC in drinking water developed the neoplasm. In TRAMP mice, the CLU gene was dramatically down-regulated during onset and progression of CaP. In GTC-treated TRAMP mice in which tumor progression was chemoprevented, CLU mRNA and protein progressively accumulated in the prostate gland. CLU dropped again to undetectable levels in animals in which GTC chemoprevention failed and CaP developed. Up-regulation of histone H3 and down-regulation of growth arrest-specific gene 1 (Gas1) mRNAs in CaP-developing TRAMP mice demonstrated a high proliferation rate in tumors, while the opposite occurred in the glands of GTC chemoprevented animals. Failure of GTC chemoprevention caused induction of both histone H3 and Gas1 and down-regulation of CLU. Immunohistochemistry experiments confirmed CLU down-regulation during CaP onset and progression, and CLU sustained expression in chemoprevented TRAMP mice. A possible role for CLU as a novel tumor-suppressor gene in the prostate is thus suggested.
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PMID:The chemopreventive action of catechins in the TRAMP mouse model of prostate carcinogenesis is accompanied by clusterin over-expression. 1535 31

Lycopene is one of the major carotenoids and is found almost exclusively in tomatoes and tomato products. Since tomato consumption is associated with decreased risk of prostate cancer, characterizing the effects of lycopene on cell growth or survival, cell cycle progression, and apoptosis in LCNaP human prostate cancer cells might elucidate the mechanisms of actions of lycopene. To discover the possible anti-cancer mechanism of lycopene, water-soluble lycopene was used, and cell cycle arrest and apoptosis were measured. Placebo formulation at each lycopene dose at 0.1, 1, and 5 microM was used as a control. After 6, 24, and 48 hours of incubation, cells were harvested and measured for cell viability. Lycopene at 1 microM inhibited cell growth by 31%, compared with its placebo formulation after a 48-hour incubation. Lycopene at 5 microM increased the number of cells in the G(2)/M phase of the cell cycle from 13% to 28% and decreased S-phase cells from 45% to 29%, while no shifts in cell cycle were detected in placebo-treated groups. Apoptosis was observed at the 5 microM lycopene formulation at the late stages during the 24- and 48-hour treatments. Lycopene, therefore, deserves further study as a potential chemopreventive/chemotherapeutic agent.
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PMID:Cell cycle arrest and induction of apoptosis by lycopene in LNCaP human prostate cancer cells. 1538 20

Whole-body imaging of therapeutic response in human bone marrow was achieved without introduced contrast agents using diffusion-weighted echo-planar magnetic resonance imaging of physiologic water. Bone marrow disease was identified relative to the strong overlying signals from water and lipids in other anatomy through selective excitation of the water resonance and generation of image contrast that was dependent upon differential nuclear relaxation times and self-diffusion coefficients. Three-dimensional displays were generated to aid image interpretation. The geometric distortion inherent in echo-planar imaging techniques was minimized through the acquisition of multiple axial slices at up to 12 anatomic stations over the entire body. Examples presented include the evaluation of therapeutic response in bone marrow during cytotoxic therapy for leukemia and metastatic prostate cancer and during cytokine administration for marrow mobilization prior to stem cell harvest.
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PMID:Imaging therapeutic response in human bone marrow using rapid whole-body MRI. 1556 75

Signaling through NF-kappaB has been implicated in the malignant phenotype as well as the chemoresistance of various cancers. Here we show that the natural compounds acetyl-beta-boswellic acid and acetyl-11-keto-beta-boswellic acid (AKbetaBA) inhibit proliferation and elicit cell death in chemoresistant androgen-independent PC-3 prostate cancer cells in vitro and in vivo. Induction of apoptosis was demonstrated in cultured PC-3 cells by several parameters including mitochondrial cytochrome c release and DNA fragmentation. At the molecular level these compounds inhibit constitutively activated NF-kappaB signaling by intercepting the IkappaB kinase (IKK) activity; signaling through the interferon-stimulated response element remained unaffected, suggesting specificity for IKK inhibition. The impaired phosphorylation of p65 and the reduced nuclear translocation of NF-kappaB proteins were associated with down-regulation of the constitutively overexpressed and NF-kappaB-dependent antiapoptotic proteins Bcl-2 and Bcl-x(L). In addition, expression of cyclin D1, a crucial cell cycle regulator, was reduced as well. Down-regulation of IKK by antisense oligodeoxynucleotides confirmed the essential role of IKK inhibition for the proliferation of the PC-3 cells. Both compounds tested were active in vivo, yet AKbetaBA proved to be far superior. Indeed, topical application of water-soluble AKbetaBA-gamma-cyclodextrin on PC-3 tumors xenografted onto chick chorioallantoic membranes induced concentration-dependent inhibition of proliferation as well as apoptosis. Similarly, in nude mice carrying PC-3 tumors, systemic application of AKbetaBA-gamma-cyclodextrin inhibited tumor growth and triggered apoptosis in the absence of detectable systemic toxicity. Thus, AKbetaBA and related compounds acting on IKK might provide a novel approach for the treatment of chemoresistant human tumors such as androgen-independent human prostate cancers.
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PMID:Inhibition of IkappaB kinase activity by acetyl-boswellic acids promotes apoptosis in androgen-independent PC-3 prostate cancer cells in vitro and in vivo. 1557 74

This study deals with the study of the optimization of the volume of organic phase (X1), the volume of aqueous phase (X2), and the drug:phosphotidylcholine (PC): cholesterol (Chol) molar ratio (X3) using 3(3) factorial 26-term logit model to maximize the Flutamide absorption at the target site in the treatment of prostatic cancer by maximizing the entrapment of Flutamide (FLT) in the preparation of FLT liposomes. FLT liposomes are expected to be an excellent carrier for FLT to the prostatic cancer site based on the use of liposomes with other drugs. A 3(3) factorial 26-term logit model for coded factors X1, X2, and X3 is used to develop a second-order response surface regression equation for predicting percent entrapment efficiency (%EE) for FLT. In turn, the regression equation is used to develop contour plots that show the %EE is maximized at the level of 1:15:2 of the drug: PC: Chol molar ratio with the volume of organic phase (chloroform: methanol) (1:2) at 5 mL and the volume of distilled water at 1.5 mL.
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PMID:Optimization of formulation parameters for the preparation of flutamide liposomes by 3(3) factorial 26-term logit model. 1558 Oct 73

A risk assessment of the triazine herbicide atrazine has been conducted by first analyzing the toxicity database and subsequently estimating exposure. Margins of safety (MOS) were then calculated. Toxicity was assessed in animal studies and exposure was estimated from occupational and dietary sources. In acute toxicity studies, atrazine caused developmental toxicity in the rabbit [no observed effect level (NOEL) 5 mg kg(-1) day(-1)] and cardiotoxicity in a dog chronic study (NOEL 0.5 mg kg(-1) day(-1)); cancer (mammary glands) resulted from lifetime exposure. The mammary tumors, which occurred specifically in female Sprague-Dawley rats, were malignant, increased in a dose-dependent manner and were also observed with other, related triazines. Evidence for a genotoxic basis for these tumors was either equivocal or negative. Triazines have been shown to be clastogenic in Chinese hamster ovary cells, in vitro, but without showing a convincing dose/response relationship. Atrazine can be converted into genotoxic N-nitrosoatrazine in the environment or the digestive system, suggesting that N-nitrosamines derived from triazines could be oncogenic. However, it was concluded that N-nitrosotriazines are unlikely to play a significant role in triazine-induced rat mammary gland tumors. An endocrine basis for the mammary tumors, involving premature aging of the female SD rat reproductive system, has been proposed. A suppression of the luteinizing hormone surge during the estrus cycle by atrazine leads to the maintenance of elevated blood levels of 17beta-estradiol (E2) and prolactin. The mechanism for tumor development may include one or more of the following: the induction of aromatase (CYP19) and/or other P450 oxygenases, an antagonist action at the estrogen feedback receptor in the hypothalamus, an agonist action at the mammary gland estrogen receptor or an effect on adrenergic neurons in the hypothalamic-pituitary pathway. None of these has been excluded as a target because there has been a lack of a rigorous attempt to address the mechanism of action for mammary tumors at the molecular level. The potential occupational exposure to atrazine was assessed during mixing, loading and application. Absorbed daily dosage values were 1.8-6.1 microg kg(-1) day(-1). The MOS values (animal NOEL/human exposure) for short-term (acute) exposure were 820-2800. Longer-term occupational exposure and risk were also calculated. Detectable crop residues are generally absent at harvest. Theoretical calculations of acute dietary exposure used tolerance levels, along with secondary residues, and water, for which there is a maximum contamination level; atrazine plus the three main chlorotriazine metabolites were combined. MOS values were above 2000 for all population subgroups. Dietary exposure to atrazine is therefore extremely unlikely to result in human health hazard. Recent publications have reported a possible feminization of frogs, measured in laboratory and field studies. This is assumed to be due to the induction of aromatase, but no measurements of enzyme activity have been reported. In field studies, the water bodies with the greatest numbers of deformed frogs sometimes had the lowest concentrations of atrazine. Other studies have also cast doubt on the feminization theory, except perhaps at very high levels of atrazine. Epidemiology studies have investigated the possibility that atrazine may result in adverse effects in humans. Although some studies have claimed that atrazine exposure results in an elevated risk of prostate cancer, the published literature is inconclusive with respect to cancer incidence.
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PMID:A risk assessment of atrazine use in California: human health and ecological aspects. 1565 6

The potential anti-angiogenic activities of water-soluble condensed tannins isolated from black beans were evaluated using HEL 299 normal human fibroblast lung cells, Caco-2 colon, MCF-7 and Hs578T breast, and DU 145 human prostatic cancer cells. Condensed tannins at 0.24-24 microM did not affect the growth of normal cells, but dose-dependently induced cancer cell death by apoptosis as shown by a concentration-dependent decrease in ATP and cell gross morphology. After 24h exposure to Caco-2, MCF-7, Hs578T, and DU 145 cancer cells, water-soluble black bean condensed tannins at 24 microM suppressed fetal bovine serum stimulated cell migration, the secretion of matrix metalloproteinase-2 (MMP-2 or gelatinase A), matrix metalloproteinase-9 (MMP-9 or gelatinase B), and vascular endothelial growth factor VEGF(165) receptor expression by the cancer cells in the conditioned media. The potential health enhancing properties of condensed tannins from black beans as inhibitors of angiogenesis is discussed.
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PMID:Inhibition of Caco-2 colon, MCF-7 and Hs578T breast, and DU 145 prostatic cancer cell proliferation by water-soluble black bean condensed tannins. 1567 Aug 92


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