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)

Fractal methods were used to analyze quantitative differences in secretory membrane activities of two rat prostate cancer cell lines (Mat-LyLu and AT-2) of strong and weak metastatic potential, respectively. Each cell's endocytic activity was determined by horseradish peroxidase uptake. Digital images of the patterns of vesicular staining were evaluated by multifractal analyses: generalized fractal dimension (Dq) and its Legendre transform f(alpha), as well as partitioned iterated function system -- semifractal (PIFS-SF) analysis. These approaches revealed consistently that, under control conditions, all multifractal parameters and PIFS-SF codes determined had values greater for Mat-LyLu compared with AT-2 cells. This would agree generally with the endocytic/vesicular activity of the strongly metastatic Mat-LyLu cells being more developed than the corresponding weakly metastatic AT-2 cells. All the parameters studied were sensitive to tetrodotoxin (TTX) pre-treatment of the cells, which blocked voltage-gated Na+ channels (VGSCs). Some of the parameters had a "simple" dependence on VGSC activity, whereby pre-treatment with TTX reduced the values for the MAT-LyLu cells and eliminated the differences between the two cell lines. For other parameters, however, there was a "complex" dependence on VGSC activity. The possible physical/physiological meaning of the mathematical parameters studied and the nature of involvement of VGSC activity in control of endocytosis/secretion are discussed.
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PMID:Patterning of endocytic vesicles and its control by voltage-gated Na+ channel activity in rat prostate cancer cells: fractal analyses. 1502 23

Alpha-methylacyl-coenzyme A racemase (AMACR; P504S) is a mitochondrial and peroxisomal enzyme involved in the metabolism of branched-chain fatty acid and bile acid intermediates. Recently, AMACR has been demonstrated to be overexpressed in localized and metastatic prostate cancer and in high-grade prostatic intraepithelial neoplasia but not in normal prostatic glands, suggesting that it may be an important tumor marker. This study examines AMACR expression in a variety of human cancers to assess its viability as a tumor marker in the clinical setting. Two hundred sixty-three cancers from different sites were examined in three multitumor tissue micro arrays, which included two or three tissue cores (1.0 mm in diameter) from each neoplastic and normal tissue specimen. Cancers studied included breast (94 cases), prostate (38), lung (28), endometrium (27), colon (29), ovary (26), and melanoma (21). Normal tissues in the microarray were prostate (15), lung (6), endometrium (5), colon (4), ovary (2), and skin (3). Sections were immunostained, after prior pressure cooker antigen retrieval, using rabbit monoclonal AMACR antibody (1:40) (Zeta Corp, Sierra Madre, CA) and horseradish peroxidase-labeled polymer conjugated secondary antibody (Envision, Dako, Carpinteria, CA). A section of prostate cancer and prostatic intraepithelial neoplasia was used as positive control. Protein expression was scored as negative, weak (faint cytoplasmic or granular apical staining), moderate (diffuse granular cytoplasmic stain), and strong (diffuse intense cytoplasmic stain). Only moderate and strong staining was considered as positive staining, based on prior work. AMACR protein overexpression was found in several cancers, including prostate (34/38 [89.5%]), colon (13/29 [44.8%]), lung (4/28 [14.3%]), melanoma (2/21 [9.5%]), endometrium (2/27 [7.4%]), and breast (3/94 [3.2%]). None of the ovarian cancers (26 cases) demonstrated AMACR overexpression. AMACR expression was not present in any of the normal tissues nor in benign prostatic tissue associated with prostate carcinomas. This study suggests that AMACR is potentially an important tumor marker, particularly for prostate and colon cancer. It may be a useful adjunct to an immunohistochemical panel employed in the differential diagnosis of colon versus ovarian and breast carcinoma; the latter two infrequently express AMACR.
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PMID:Utility of alpha-methylacyl coenzyme A racemase (p504s antibody) as a diagnostic immunohistochemical marker for cancer. 1608 51

The tumor suppressor gene Smad4 (DPC4) has been localized to chromosome 18q21.1 and is a member of the Smad family that mediates the transforming growth factor beta signaling pathway suppressing epithelial cell growth. However, variable expression of this protein has been reported, with a loss in some cancers and increased expression in others. Given both the variability and lack of consensus reported regarding Smad4 expression in prostate cancer, we assessed Smad4 immunoreactivity in prostatic adenocarcinomas (PACs). Formalin-fixed, paraffin-embedded tissue sections from 133 PACs were immunostained by a manual method using indirect biotin streptavidin horseradish peroxidase and diaminobenzidine detection using a monoclonal mouse antihuman Smad4 antibody (sc-7966; Santa Cruz Biotechnology Inc, Santa Cruz, Calif). Nuclear immunoreactivity and cytoplasmic immunoreactivity were each semiquantitatively scored based on intensity and percentage of positive cells. Deoxyribonucelic acid ploidy was determined on Feulgen-stained tissue sections by static image analysis. Results were correlated with morphological and prognostic variables. Variable nuclear and cytoplasmic Smad4 positivity was noted in the adjacent benign glands in all cases. Of 133 PACs, 64 (48%) featured increased nuclear and 68 (51%) featured increased cytoplasmic protein expression. Nuclear Smad4 overexpression correlated with tumor grade (P = .02), stage (P = .04), and DNA ploidy (P = .04). Cytoplasmic overexpression correlated with tumor grade (P = .04) and DNA ploidy (P = .04) while showing a trend for correlation with tumor stage (P = .08). Neither nuclear nor cytoplasmic Smad4 overexpression correlated with postsurgical biochemical disease recurrence. Smad4 protein expression persists in PACs compared with benign glands, with both nuclear and cytoplasmic overexpression correlating with prognostic variables indicative of aggressive tumor behavior. Given the significant reported variability of Smad4 in several different cancers, further studies in prostate and other tumors are warranted to elucidate its role in tumorigenesis.
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PMID:Smad4 protein expression correlates with grade, stage, and DNA ploidy in prostatic adenocarcinomas. 1626 Feb 74

We have previously shown that the anticancer agent doxorubicin undergoes oxidation and inactivation when exposed to myeloperoxidase-containing human leukemia HL-60 cells, or to isolated myeloperoxidase, in the presence of hydrogen peroxide and nitrite. In the current study we report that commercial fetal bovine serum (FBS) alone oxidizes doxorubicin in the presence of hydrogen peroxide and that nitrite accelerates this oxidation. The efficacy of inactivation was dependent on the concentration of serum present; no reaction was observed when hydrogen peroxide or serum was omitted. Peroxidase activity assays, based on oxidation of 3,3',5,5'-tetramethylbenzidine, confirmed the presence of a peroxidase in the sera from several suppliers. The peroxidative activity was contained in the >10000 MW fraction. We also found that hemoglobin, a heme protein likely to be present in commercial FBS, is capable of oxidizing doxorubicin in the presence of hydrogen peroxide and that nitrite further stimulates the reaction. In contrast to intact doxorubicin, the serum + hydrogen peroxide + nitrite treated drug appeared to be nontoxic for PC3 human prostate cancer cells. Together, this study shows that (pseudo)peroxidases present in sera catalyze oxidation of doxorubicin by hydrogen peroxide and that this diminishes the tumoricidal activity of the anthracycline, at least in in vitro settings. Finally, this study also points out that addition of H2O2 to media containing FBS will stimulate peroxidase-type of reactions, which may affect cytotoxic properties of studied compounds.
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PMID:Inactivation of anthracyclines by serum heme proteins. 1749 96

Prostate cancer represents a major clinical public health challenge. Both epidemiological and clinical intervention studies support the protective role of selenium against development of prostate cancer. However, the mechanisms responsible for the inhibitory activity by this micronutrient remain elusive. Furthermore, literature reports consistently have shown that the dose and form of selenium are important factors in cancer chemoprevention. Thus, in the present investigation using androgen responsive (AR) lymph node carcinoma of the prostate (LNCaP) and its androgen-independent clone (AI) LNCaP C4-2 human prostate cancer cells, we compared the effects of selenomethionine (SM) and 1,4-phenylenebis(methylene)selenocyanate (p-XSC) on cell growth, DNA synthesis, and on proteomic profiles. p-XSC (5-20 microM) significantly inhibited cell growth in both cell types in a dose-dependent manner; SM was also effective but at much higher doses (50-100 microM). We hypothesize that the inhibition of cell growth is due, in part, to selenium interaction with redox-sensitive proteins. Using 2D gel electrophoresis, both organoselenium compounds altered the expression, to a varied extent, of several unrecognized selenium-responsive proteins. Employing matrix-assisted laser-desorption ionization (MALDI) and time-of-flight (TOF; MALDI-TOF) followed by tandem mass spectrometric analysis, we identified the following proteins: cofilin-2, heterogeneous nuclear ribonucleoprotein, single-stranded mitochondrial DNA binding protein, chaperonin 10, nucleoside diphosphate kinase 6, and chain A Horf 6 human peroxidase enzyme. This is the first report showing that SM and p-XSC are capable of altering these proteins; their roles in prostate cancer prevention warrant further investigations.
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PMID:Effects of naturally occurring and synthetic organoselenium compounds on protein profiling in androgen responsive and androgen independent human prostate cancer cells. 1844 60

Nitric oxide ((.)NO) induces apoptosis at high concentrations by S-nitrosating proteins such as glyceraldehyde-3-phosphate dehydrogenase. This literature analysis revealed that failure to sustain high (.)NO concentrations is common to all cancers. In cervical, gastric, colorectal, breast, and lung cancer, the cause of this failure is the inadequate expression of inducible nitric oxide synthase (iNOS), resulting from the inhibition of iNOS expression by TGF-beta1 at the mRNA level. In bladder, renal, and prostate cancer, the reason for the insufficient (.)NO levels is the depletion of arginine, resulting from arginase overexpression. Arginase competes with iNOS for arginine, catalyzing its hydrolysis to ornithine and urea. In gliomas and ovarian sarcomas, low (.)NO levels are caused by inhibition of iNOS by N-chlorotaurine, produced by infiltrating neutrophils. Stimulated neutrophils express myeloperoxidase, catalyzing H2O2 oxidation of Cl- to HOCl, which N-chlorinates taurine at its concentration of 19 mM in neutrophils. In squamous cell carcinomas of the skin, ovarian cancers, lymphomas, Hodgkin's disease, and breast cancers, low (.)NO concentrations arise from the inhibition of iNOS by N-bromotaurine, produced by eosinophil-peroxidase-expressing infiltrating eosinophils. Eosinophil peroxidase catalyzes the H2O2 oxidation of Br- to HOBr, which N-brominates taurine to N-bromotaurine at its concentration of 15 mM in eosinophils. In microvascularized tumors, the (.)NO concentration is further depleted; (.)NO is rapidly consumed by red blood cells (RBCs) through S-nitrosation of RBC glutathione and hemoglobin, and by oxidation to nitrate by RBC oxyhemoglobin. Angiogenesis-inhibiting antibodies are currently used to treat cancers; their mode of action is not, as previously thought, reduction of the tumor O2 or nutrient supply. They actually decrease the loss of (.)NO to RBCs.
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PMID:Apoptosis-inducing high (.)NO concentrations are not sustained either in nascent or in developed cancers. 1875 45

The epithelial-mesenchymal transition (EMT) is considered a key step in tumor progression, where the invasive cancer cells change from epithelial to mesenchymal phenotype. During this process, a decrease or loss in adhesion molecules expression and an increase in migration molecules expression are observed. The aim of this work was to determine the expression and cellular distribution of syndecan-1 and -2 (migration molecules) and E-cadherin and beta-catenin (adhesion molecules) in different stages of prostate cancer progression. A quantitative immunohistochemical study of these molecules was carried out in tissue samples from benign prostatic hyperplasia and prostate carcinoma, with low and high Gleason score, obtained from biopsies archives of the Clinic Hospital of the University of Chile and Dipreca Hospital. Polyclonal specific antibodies and amplification system of estreptavidin-biotin peroxidase and diaminobenzidine were used. Syndecan-1 was uniformly expressed in basolateral membranes of normal epithelium, changing to a granular cytoplasmatic expression pattern in carcinomas. Syndecan-2 was observed mainly in a cytoplasmatic granular pattern, with high immunostaining intensity in areas of low Gleason score. E-cadherin was detected in basolateral membrane of normal epithelia showing decreased expression in high Gleason score samples. beta-Catenin was found in cell membranes of normal epithelia changing its distribution toward the nucleus and cytoplasm in carcinoma samples. We concluded that changes in expression and cell distribution of E-cadherin and beta-catenin correlated with the progression degree of prostate adenocarcinoma, suggesting a role of these molecules as markers of progression and prognosis. Furthermore, changes in the pattern expression of syndecan-1 and -2 indicate that both molecules may be involved in the EMT and tumor progression of prostate cancer.
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PMID:The expression of syndecan-1 and -2 is associated with Gleason score and epithelial-mesenchymal transition markers, E-cadherin and beta-catenin, in prostate cancer. 1945 Sep 93

Biotransformation of dihydroresveratrol by crude Momordica charantia peroxidase provided six new acyclic bis[bibenzyls] 1-6. Their structures were established on the basis of NMR and MS analyses as C-C, C-O-C, and C-CH(2)-C dimers of dihydroresveratrol. Compounds 1-6 were tested for antiproliferative activity against human prostate cancer PC3 cell line in vitro, and 2 and 6 were found to be more potent than the parent compound.
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PMID:Biocatalytic production of acyclic bis[bibenzyls] from dihydroresveratrol by crude Momordica charantia peroxidase. 1969 37

Protein arrays that measure multiple protein cancer biomarkers in clinical samples hold great promise for reliable early cancer detection. Herein, we report a prototype 4-unit electrochemical immunoarray based on single-wall carbon nanotube forests for the simultaneous detection of multiple protein biomarkers for prostate cancer. Immunoarray procedures were designed to measure prostate specific antigen (PSA), prostate specific membrane antigen (PSMA), platelet factor-4 (PF-4), and interleukin-6 (IL-6) simultaneously in a single serum sample. All of these proteins are elevated in serum of patients with prostate cancer, but they have widely different relative levels of serum concentration. Horseradish peroxidase (HRP) was used as label on detection (secondary) antibodies in a sandwich immunoassay scheme. Biotinylated secondary antibodies (Ab(2)) that bind specifically to streptavidin-HRP conjugates provided 14-16 labels per antibody and gave the necessary higher sensitivity required for PF-4 and IL-6 detection at physiological levels. Conventional singly labeled Ab(2)-HRP conjugates were sufficient for PSA and PSMA detection. Immunoarrays were used to measure four biomarkers in clinical human serum samples of prostate cancer patients and controls with excellent correlation to referee enzyme-linked immunosorbent (ELISA) assays.
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PMID:Single-wall carbon nanotube forest arrays for immunoelectrochemical measurement of four protein biomarkers for prostate cancer. 1977 54

Indole-3-acetic acid (IAA) has recently shown anticancer activity in combination with horseradish peroxidase. The current study demonstrated that IAA irradiated with ultraviolet B (IAA(UVB)) is able to generate free radicals and induce cell death in a time-dependent fashion in PC-3 prostate cancer cells, while PC-3 cells treated with IAA alone exhibited no toxic responses. It was also found through Western blot analysis that the cytotoxic effect of IAA(UVB) resulted from apoptosis. Treatment with IAA(UVB) for 24 hours showed a significant increase in phosphorylated p38 mitogen-activated protein kinase and c-Jun N-terminal kinase, the stress signaling proteins. Furthermore, pro-caspases (-3, -8, and -9) were clearly down-regulated and poly(ADP-ribose) polymerase cleavages were demonstrated in the group treated with IAA(UVB). Flow cytometric analysis also demonstrated the induction of apoptosis by IAA(UVB) in PC-3 cells. In conclusion, this study demonstrated that IAA induced cell death in combination with UVB irradiation by increasing apoptosis in PC-3 cells.
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PMID:UVB-activated indole-3-acetic acid induces apoptosis of PC-3 prostate cancer cells. 2111 13


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