vitamin-k-semiquinone-radical and Prostatic-Neoplasms

Use of vitamin K antagonists (VKAs) has been suggested to reduce the risk of prostate cancer. We conducted a nested case-control study using Danish demographic and health data registries and summarized existing evidence in a meta-analysis. The case-control study included all Danish men aged 40-85 years with incident histologically verified prostate adenocarcinoma between 2005 and 2015 (cases). For each case, we selected 10 age-matched controls. We used conditional logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CI) for prostate cancer associated with long-term VKA use adjusted for concomitant drug use, medical history and socioeconomic status. Among 38,832 prostate cancer cases, 1,089 (2.8%) had used VKAs for 3 or more years compared to 10,803 (2.8%) controls yielding a crude OR of 1.01 (95% CI, 0.95-1.08). Multivariable adjustment for covariates had limited influence on the association (OR, 1.03; 95% CI, 0.97-1.10). We observed no dose-response relationship (e.g. OR for 5-10 years of use, 1.06 95% CI, 0.97-1.16). We included 8 studies in the meta-analysis reporting effect estimates from 0.51 (95% CI, 0.23-1.13) to 1.10 (95% CI, 0.94-1.40). Using random effect methods, a pooled effect estimate of 0.86 (95% CI, 0.70-1.05) was obtained; however, there was considerable across-study heterogeneity (I

Topics: Adult; Aged; Aged, 80 and over; Case-Control Studies; Denmark; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Logistic Models; Male; Middle Aged; Odds Ratio; Phenprocoumon; Prostatic Neoplasms; Registries; Vitamin K; Warfarin

Vitamin K antagonists (VKAs) may have potential antitumor effects in prostate cancer. However, the findings of observational studies are inconsistent. The purpose of the present study was to estimate the quantitative association between VKAs use and prostate cancer risk by combining the results of all eligible observational studies.. PubMed and Web of Science database were searched from inception until May, 2018. A DerSimonian random-effects model was used to combine the studies. Study heterogeneity was measured using the chi-squared and I statistics.. Six eligible studies were eventually included in our meta-analysis. There was an inverse but not statistically significant association between ever use of VKAs and the risk of prostate cancer (relative risk [RR] 0.84, 95% confidence interval [CI] 0.70-1.01, P = .063) with large heterogeneity across studies (P < .001 for heterogeneity, I = 94.6%). When analysis restricted to long term of VKAs user (>3 years), the pooled risk estimate was 0.83 (0.77-0.90) without obvious heterogeneity (P = .597, I = 0.0%).. This meta-analysis indicates that VKAs use may be associated with a decreased risk of prostate cancer, especially in long-term users.

Topics: Humans; Male; Observational Studies as Topic; Prostatic Neoplasms; Risk; Vitamin K

Although vitamin deficiency is encountered infrequently in developed countries, inadequate intake of several vitamins is associated with chronic disease.. To review the clinically important vitamins with regard to their biological effects, food sources, deficiency syndromes, potential for toxicity, and relationship to chronic disease.. We searched MEDLINE for English-language articles about vitamins in relation to chronic diseases and their references published from 1966 through January 11, 2002.. We reviewed articles jointly for the most clinically important information, emphasizing randomized trials where available.. Our review of 9 vitamins showed that elderly people, vegans, alcohol-dependent individuals, and patients with malabsorption are at higher risk of inadequate intake or absorption of several vitamins. Excessive doses of vitamin A during early pregnancy and fat-soluble vitamins taken anytime may result in adverse outcomes. Inadequate folate status is associated with neural tube defect and some cancers. Folate and vitamins B(6) and B(12) are required for homocysteine metabolism and are associated with coronary heart disease risk. Vitamin E and lycopene may decrease the risk of prostate cancer. Vitamin D is associated with decreased occurrence of fractures when taken with calcium.. Some groups of patients are at higher risk for vitamin deficiency and suboptimal vitamin status. Many physicians may be unaware of common food sources of vitamins or unsure which vitamins they should recommend for their patients. Vitamin excess is possible with supplementation, particularly for fat-soluble vitamins. Inadequate intake of several vitamins has been linked to chronic diseases, including coronary heart disease, cancer, and osteoporosis

Topics: Ascorbic Acid; Avitaminosis; Blood Coagulation; Breast Neoplasms; Carotenoids; Chronic Disease; Colorectal Neoplasms; Coronary Disease; Dietary Supplements; Female; Folic Acid; Fractures, Bone; Humans; Lung Neoplasms; Male; Neoplasms; Neural Tube Defects; Prostatic Neoplasms; Risk Factors; Vitamin A; Vitamin B 12; Vitamin B 6; Vitamin D; Vitamin E; Vitamin K; Vitamins

Topics: Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; Humans; Male; Prostatic Neoplasms; Vitamin K

Systems genetics is key for integrating a large number of variants associated with diseases. Vitamin K (VK) is one of the scarcely studied disease conditions. In this work, we ascertained the differentially expressed genes (DEGs) and variants associated with individual subpopulations of VK disease phenotypes,

Topics: Biomarkers; Humans; Male; Prostatic Neoplasms; RNA, Long Noncoding; Vitamin K; Vitamin K Deficiency

Disseminated intravascular coagulation (DIC) is a pathological systemic condition resulting from aberrant activation of the coagulation system. It is characterised by the release and activation of procoagulants into the blood, with an associated consumption coagulopathy. Its association with solid and haematological malignancies is well described in literature. This case describes an elderly man, known to have prostate cancer, who following transurethral resection of the prostate developed DIC with haematuria, spontaneous ecchymoses and mucosal bleeding. Subsequent investigations revealed a prostate-specific antigen (PSA) >1000 µg/L, and staging CT showed multiple sclerotic metastatic lesions affecting the thoracic and lumbar vertebra, as well as infiltration into his left femur. Coagulation normalised with blood products and vitamin K within 1 week, and the patient responded to antiandrogen therapy with a reduction in pain and PSA on discharge.

Topics: Aged, 80 and over; Androgen Antagonists; Antifibrinolytic Agents; Biomarkers, Tumor; Diagnosis, Differential; Disseminated Intravascular Coagulation; Hematuria; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Spinal Neoplasms; Treatment Outcome; Vitamin K

Laboratory studies often involve analyses of highly skewed data for which means are not an adequate measure of central tendency because they are sensitive to outliers. Attempts to transform skewed data to symmetry are not always successful, and medians are better measures of central tendency for such skewed distributions. When medians are compared across groups, confounding can be an issue, so there is a need for adjusted medians.. We illustrate the use of quantile regression to obtain adjusted medians. The method is illustrated by use of skewed nutrient data obtained from black and white men attending a prostate cancer screening. For 3 nutrients, saturated fats, caffeine, and vitamin K, we obtained medians adjusted by age, body mass index, and calories for men in each race group.. Quantile regression, linear regression, and log-normal regression produced substantially different adjusted estimates of central tendency for saturated fats, caffeine, and vitamin K.. Our method was useful for analysis of skewed and other nonnormally distributed continuous outcome data and for calculation of adjusted medians.

Topics: Bias; Caffeine; Clinical Laboratory Techniques; Fatty Acids; Humans; Male; Mass Screening; Prostatic Neoplasms; Regression Analysis; Vitamin K

Human prostate cancer cells (DU145) implanted into nude mice are deficient in DNase activity. After administration of a vitamin C/vitamin K(3) combination, both alkaline DNase (DNase I) and acid DNase (DNase II) activities were detected in cryosections with a histochemical lead nitrate technique. Alkaline DNase activity appeared 1 hr after vitamin administration, decreased slightly until 2 hr, and disappeared by 8 hr after treatment. Acid DNase activity appeared 2 hr after vitamin administration, reached its highest levels between 4 and 8 hr, and maintained its activity 24 hr after treatment. Methyl green staining indicated that DNase expression was accompanied by a decrease in DNA content of the tumor cells. Microscopic examination of 1-microm sections of the tumors indicated that DNase reactivation and the subsequent degradation of DNA induced multiple forms of tumor cell death, including apoptosis and necrosis. The primary form of vitamin-induced tumor cell death was autoschizis, which is characterized by membrane damage and the progressive loss of cytoplasm through a series of self-excisions. These self-excisions typically continue until the perikaryon consists of an apparently intact nucleus surrounded by a thin rim of cytoplasm that contains damaged organelles.

Topics: Animals; Ascorbic Acid; Cell Death; Coloring Agents; Deoxyribonucleases; Drug Synergism; Enzyme Reactivators; Histocytochemistry; Humans; Lead; Male; Methyl Green; Mice; Mice, Nude; Microscopy, Electron; Nitrates; Prostatic Neoplasms; Vitamin K; Xenograft Model Antitumor Assays

Multicellular prostate tumor spheroids develop intrinsic P-glycoprotein (Pgp)-mediated multidrug resistance with the appearance of quiescent cell areas. We have investigated the effect of intracellular reactive oxygen species (ROS) on Pgp expression in large, quiescent and drug-resistant multicellular spheroids (diameter 250 +/- 50microm). Using the ROS-sensitive fluorescence dye 2;7;-dichlorodihydrofluorescein diacetate (H(2)DCFDA), we demonstrated that these tumor spheroids are characterized by reduced intracellular ROS compared with drug-sensitive small spheroids (diameter 60 +/- 20microm) consisting predominantly of proliferating cells. The prooxidants hydrogen peroxide, menadione and glyceraldehyde raised ROS in large tumor spheroids and significantly down-regulated Pgp within 24 hr. Comparable effects were achieved with the known Pgp-reversing agents sodium orthovanadate, quinidine and cyclosporin A but not with verapamil. Consequently, the retention and toxicity of the anthracycline doxorubicin was increased in tumor spheroids treated with prooxidants. Co-administration of prooxidants and the free radical scavenger ebselen did not alter Pgp levels, indicating that down-regulation of Pgp is mediated via ROS. Down-regulation of Pgp by H(2)O(2) was abolished when either forskolin, 8-Br-cAMP or IBMX, which raise intracellular cAMP levels, was co-administered, indicating that Pgp expression is regulated by protein kinase A (PKA). Furthermore, Pgp was down-regulated by the PKA inhibitors Rp-cAMPs and H89. Since prooxidants stimulated the growth of multicellular spheroids and down-regulated the cyclin-dependent kinase inhibitor p27(kip1), we conclude that ROS-mediated Pgp down-regulation may be paralleled by recruitment of drug-resistant quiescent cells in the depth of the tumor tissue for cell-cycle activity.

Topics: Antineoplastic Agents; ATP Binding Cassette Transporter, Subfamily B, Member 1; Cell Cycle; Cell Cycle Proteins; Cyclic AMP-Dependent Protein Kinases; Cyclin-Dependent Kinase Inhibitor p27; Doxorubicin; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Gene Expression Regulation, Neoplastic; Glyceraldehyde; Humans; Hydrogen Peroxide; Male; Microtubule-Associated Proteins; Oxidants; Oxidation-Reduction; Phenotype; Prostatic Neoplasms; Reactive Oxygen Species; Spheroids, Cellular; Tumor Cells, Cultured; Tumor Suppressor Proteins; Vitamin K

The cellular function of the intrinsic prion protein (PrPc) remains largely unknown. In the present study PrPc expression was investigated in multicellular prostate tumor spheroids and was correlated to the intracellular redox state as evaluated using the fluorescent dye 2'7'-dichlorodihydrofluorescein diacetate (H2DCFDA). In small tumor spheroids (diameter 100 +/- 20 microm) reactive oxygen species (ROS) levels were increased as compared with large (diameter 250 +/- 50 microm) spheroids. ROS generation was mediated by the mitochondrial respiratory chain and a NADPH oxidaselike enzyme, because carbonylcyanide-m-chlorophenylhydrazone (CCCP), rotenone, and diphenylene iodonium chloride (DPI) significantly reduced ROS levels. The elevated ROS were correlated to an increased expression of PrPc, Cu/Zn superoxide dismutase (SOD-1), and catalase in small as compared with large spheroids. In large tumor spheroids, PrPc was predominantly expressed in the peripheral cell layers and colocalized with SOD-1 and catalase. Raising intracellular ROS in large tumor spheroids by hydrogen peroxide, menadione, buthionine sulfoximine (BSO), and incubation in glutamine-reduced medium increased PrPc expression. In small spheroids PrPc was downregulated after incubation with the radical scavengers dehydroascorbate (DHA) and vitamin E. Our data indicate that PrPc expression in tumor spheroids is related to the intracellular redox state and may participate in antioxidative defense.

Topics: Antioxidants; Buthionine Sulfoximine; Catalase; Enzyme Inhibitors; Fluorescent Dyes; Free Radical Scavengers; Gene Expression Regulation; Glutamate-Cysteine Ligase; Glutathione; Humans; Hydrogen Peroxide; Male; Oxidation-Reduction; Prions; Prostatic Neoplasms; Reactive Oxygen Species; Superoxide Dismutase; Tumor Cells, Cultured; Vitamin K

Transmission and scanning electron microscopy and flow cytometry were employed to characterize the cytotoxic effects of vitamin C (VC), vitamin K3 (VK3), or VC-VK3 combinations on a human prostate carcinoma cell line (DU145) following a 1-h vitamin treatment and a 24-h incubation in culture medium. Cells exposed to VC exhibited membranous blebs, aberrant microvillar morphology, mitochondria with swollen cristae and intramitochondrial deposits, as well as nucleoli with segregated components. VK3-treated cells displayed a damaged cytoskeleton and membranes, a cytoplasm which contained large lumen, condensed polysomes, and severely damaged mitochondria with residual bodies, and nuclei which exhibited chromatic condensation, pyknosis, and karyolysis. VC-VK3-treated cells exhibited characteristics consistent with necrosis, i.e. swollen mitochondria and swollen, achromatic nuclei with marginated chromatin and intact envelopes, while other cells displayed characteristics consistent with apoptosis, i.e. expulsion of organelle-containing blebs, margination of nuclear chromatin, and segregation of nucleolar components. Vitamin treatment also decreased DNA synthesis, induced a S/G2 block in the cell cycle, and resulted in the accumulation of fragmented DNA. These results suggested that increased oxidative stress, subsequent membrane damage, and DNA fragmentation were responsible for enhanced cytotoxicity of the vitamin combination.

Topics: Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; DNA; Drug Synergism; Flow Cytometry; Hemostatics; Humans; Male; Microscopy, Electron; Microscopy, Electron, Scanning; Prostatic Neoplasms; Thymidine; Tritium; Tumor Cells, Cultured; Vitamin K

Vitamins C, K3 (VC, VK3) and a VC/VK3 combination with a VC:VK3 ratio of 100:1 were assayed for their antitumour activity against two human prostatic carcinoma cell lines. Co-administration of the vitamins enhanced the antitumour activity 5- to 20-fold even with a 1 h exposure time. While exogenous catalase destroyed the antitumour activity, hydrogen peroxide-induced lipid peroxidation was negligible. Analysis of cellular ATP and thiol levels as well as DNA and protein synthesis revealed: a transient increase in ATP production, a decrease in DNA synthesis, an increase in protein synthesis and a decrease in thiol levels. These results suggested that the increased cytotoxicity of the vitamin combination was due to redox cycling and increased oxidative stress.

Topics: Adenosine Triphosphate; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; Carcinoma; Catalase; DNA, Neoplasm; Humans; Hydrogen Peroxide; Lipid Peroxidation; Male; Neoplasm Proteins; Prostatic Neoplasms; Sulfhydryl Compounds; Tumor Cells, Cultured; Vitamin K

A MTT/formazan assay was used to evaluate the antitumor activity of vitamin C (Vit C), vitamin K3 (Vit K3), or vitamin C:vitamin K3 combinations against a human prostatic carcinoma cell line (DU145). Both Vit C and Vit K3 alone exhibited antitumor activity, but only at elevated doses. When Vit C and Vit K3 were combined at a C:K3 ratio of 100:1 and administered to the carcinoma cells, the 50% cytotoxic concentrations (CD50) of the vitamins decreased 10- to 60-fold. Subsequently, the DU145 cells were examined with transmission and scanning electron microscopy (TEM and SEM) following a 1 hour treatment with Vit C, Vit K3, or Vit C/K3 combined at their 50% cytotoxic dose. Our morphological data suggest that vitamin treatment with individual vitamins affects the cytoskeleton, the mitochondria, and other membranous components of the cell. Treatment with the vitamin combination appears to potentiate the effects of the individual vitamin treatment. Specifically, there are abundant necrotic cells. The surviving cells display morphological defects characteristic of cell injury.

Topics: Antineoplastic Agents; Ascorbic Acid; Carcinoma; Cell Membrane; Coloring Agents; Cytoskeleton; Drug Synergism; Drug Therapy, Combination; Humans; Male; Microscopy, Electron; Microscopy, Electron, Scanning; Mitochondria; Prostatic Neoplasms; Tetrazolium Salts; Thiazoles; Tumor Cells, Cultured; Vitamin K

Menadione-catalyzed H2O2 production by viable cells is proportional to viable cell number. The correlations between the viable cell number and the concentration of H2O2 produced are determined with the rapid chemiluminescent assay (S. Yamashoji, T. Ikeda, and K. Yamashoji, 1989, Anal. Biochem. 181, 149-152). This chemiluminescent assay of viable cells requires only 10 min and is much faster than NR (neutral red) inclusion and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) reduction assays, which require 3-5 h. When viable cells are incubated with antitumor drugs, detergents, mycotoxins, and glycoalkaloids for 24-48 h, a decrease in menadione-catalyzed H2O2 production in a dose- or incubation time-dependent manner is observed. In general, the 50% inhibition concentration determined by the chemiluminescent assay is lower than that determined by NR inclusion and MTT reduction assays, and the order of relative cytotoxic effects of agents is the same among these assays. Furthermore, clear cytotoxic effects are observed by the chemiluminescent assay after 1 h exposure of trypsinized cells to toxic compounds. Therefore, the chemiluminescent assay is expected to be more useful for the rapid detection of cytotoxic compounds than NR inclusion and MTT reduction assays.

Topics: 3T3 Cells; Adenocarcinoma; Animals; Antineoplastic Agents; Cell Count; Cell Line; Cell Survival; Coloring Agents; Humans; Hydrogen Peroxide; Indicators and Reagents; Luminescent Measurements; Male; Mice; Prostatic Neoplasms; Tetrazolium Salts; Thiazoles; Tomatine; Tumor Cells, Cultured; Vitamin K

The production of H2O2 by intact cells is promoted in the presence of menadione and is proportional to the density of viable cells. The concentration of H2O2 produced is determined by the measurement of chemiluminescence which is generated in the mixture of H2O2, pyrene, and bis(2,4,6-trichlorophenyl)oxalate. This method is applied to the measurement of viable yeast, mammalian, and plant cells. For example, viable yeast cell density above 10(4) cells/ml is determined for 2 min, and mammalian cell density and the activity of plant tissues are determined for 10 and 5 min, respectively.

Topics: Animals; Cell Division; Chemical Phenomena; Chemistry; Colorimetry; Humans; Hydrogen Peroxide; Luminescent Measurements; Male; Plant Cells; Prostatic Neoplasms; Saccharomyces cerevisiae; Tumor Cells, Cultured; Vitamin K

Serum contents of prostatic acid phosphatase, neopterin, osteocalcin, tissue polypeptide antigen and CA-50 were measured before onset of treatment in 83 patients suffering from prostatic carcinoma. In an attempt to identify patients with poor prognosis the data were related to patient survival after 2 years. It was found that the standard cut off values, obtained from the upper limits of normal, healthy subjects, were sensitive but had low specificity. A better relation to prognosis was usually found at a higher discrimination limit. The degree of elevation appears more important than the elevation of the markers as such in indicating a poor prognosis. By systematic adjustment of the discrimination levels, higher specificity can be obtained with little loss of sensitivity.

Topics: Acid Phosphatase; Antigens, Neoplasm; Antigens, Surface; Antigens, Tumor-Associated, Carbohydrate; Biomarkers, Tumor; Biopterins; Calcium-Binding Proteins; Humans; Male; Neopterin; Osteocalcin; Peptides; Prostatic Neoplasms; Reference Values; Tissue Polypeptide Antigen; Vitamin K

Fifty-four subjects were studied: 36 advanced prostatic adenocarcinoma patients in stage D and 18 normal age-matched male controls. Serum alkaline phosphatase, serum acid phosphatase, plasma osteocalcin, 24-h urinary hydroxyproline excretion, and 24-h whole-body retention of [99mTc]-methylene diphosphonate were measured in all subjects before and 3, 6, and 9 weeks after the start of treatment. Skeletal metastases were identified by radiography and/or [99mTc]-methylene diphosphonate bone scan. The results confirm that acid phosphatase is a significant marker in prostatic cancer; serum alkaline phosphatase may be useful in the evaluation and monitoring of bone metastases but it is not always specific; urinary excretion of hydroxyproline is an index of osteoclastic activity; serum osteocalcin may be considered more specific in the evaluation and monitoring of osteoblastic bone metastases in prostatic cancer.

Topics: 1-Carboxyglutamic Acid; Acid Phosphatase; Aged; Aged, 80 and over; Alkaline Phosphatase; Biomarkers, Tumor; Bone and Bones; Bone Neoplasms; Calcium-Binding Proteins; Humans; Hydroxyproline; Male; Middle Aged; Neoplasms, Hormone-Dependent; Osteocalcin; Prostatic Neoplasms; Radionuclide Imaging; Vitamin K

Topics: Acid Phosphatase; Aged; Antigens, Neoplasm; Antigens, Tumor-Associated, Carbohydrate; Biopterins; Calcium-Binding Proteins; Clinical Enzyme Tests; Clinical Laboratory Techniques; Enzyme-Linked Immunosorbent Assay; Humans; Male; Methods; Middle Aged; Neopterin; Osteocalcin; Peptides; Prostate; Prostatic Neoplasms; Pteridines; Radioimmunoassay; Tissue Polypeptide Antigen; Vitamin K

Topics: Animals; Humans; Male; Mice; Mice, Nude; Neoplasms, Experimental; Prostatic Hyperplasia; Prostatic Neoplasms; Tritium; Vitamin K

Topics: Acid Phosphatase; Animals; Disease Models, Animal; Dogs; Humans; Male; Mice; Mice, Nude; Prostatic Neoplasms; Rats; Rats, Inbred Strains; Substrate Specificity; Vitamin K

Topics: Acid Phosphatase; Adipose Tissue; Animals; Haplorhini; Hydrolysis; Injections, Intravenous; Intestines; Liver; Male; Muscles; Organophosphorus Compounds; Prostate; Prostatic Neoplasms; Radiation-Sensitizing Agents; Spleen; Testis; Tritium; Urinary Bladder; Vitamin K

Topics: Adenocarcinoma; Aged; Atrial Fibrillation; Blood Transfusion; Cephalothin; Digoxin; Disseminated Intravascular Coagulation; Gangrene; Gastrointestinal Hemorrhage; Gentamicins; Heparin; Humans; Hydronephrosis; Hypothermia; Lymphatic Metastasis; Male; Prostatic Neoplasms; Pyelonephritis; Stomach Neoplasms; Vitamin K