ubiquinone and Liver-Neoplasms

Interest in ubiquinone (UQ) has increased during recent years, mainly because of its antioxidant function and its use as a dietary supplement. However, our knowledge of the biosynthesis, catabolism, and regulation of this lipid in mammalian tissues is quite limited. UQ exhibits a high rate of turnover in all tissues indicating that cells possess efficient metabolic pathways for handling this compound and controlling its tissue levels. Besides reviewing the generally accepted metabolic pathway, alternative synthetic mechanisms are described. The lack of data concerning catabolism and regulation of this compound is emphasized. Reasons for the rather limited uptake of dietary UQ are discussed and alternative mechanisms for its beneficial effects on organ function are suggested. Since appropriate tissue uptake of dietary UQ probably only occurs in deficient states, the definition of partial UQ deficiency and its consequences is urgently needed. The possibility of raising tissue UQ levels by drug treatment or natural metabolites is raised as a choice of preference for the future.

Topics: Aging; Animals; Antioxidants; Diet; Dolichols; Half-Life; Humans; Lipid Metabolism; Liver; Liver Neoplasms; Mevalonic Acid; Oxidative Stress; Ubiquinone

It has been reported that higher levels of oxidative stress and inflammation play a key role in the progression of hepatocellular carcinoma (HCC) after surgery. Coenzyme Q10 is an endogenous lipid-soluble antioxidant. To date, no intervention study has investigated coenzyme Q10 supplementation in HCC patients after surgery. The purpose of this study was to investigate oxidative stress, antioxidant enzymes activity, and inflammation levels in HCC patients after surgery following administration of coenzyme Q10 (300 mg/day).. This study was designed as a single-blinded, randomized, parallel, placebo-controlled study. Patients who were diagnosed with primary HCC (n = 41) and were randomly assign to a placebo (n = 20) or coenzyme Q10 (300 mg/day, n = 21) group after surgery. The intervention lasted for 12 weeks. Plasma coenzyme Q10, vitamin E, oxidative stress antioxidant enzymes activity and inflammatory markers levels were measured.. The oxidative stress (p = 0.04) and inflammatory markers (hs-CRP and IL-6, p < 0.01) levels were significantly decreased, and the antioxidant enzymes activity was significantly increased (p < 0.01) after 12 weeks of coenzyme Q10 supplementation. In addition, the coenzyme Q10 level was significantly negatively correlated with the oxidative stress (p = 0.01), and positively correlated with antioxidant enzymes activity (SOD, p = 0.01; CAT, p < 0.05; GPx, p = 0.04) and vitamin E level (p = 0.01) after supplementation.. In conclusion, we demonstrated that a dose of 300 mg/d of coenzyme Q10 supplementation significantly increased the antioxidant capacity and reduced the oxidative stress and inflammation levels in HCC patients after surgery.. Clinical Trials.gov Identifier: NCT01964001.

Topics: Aged; Antioxidants; Biomarkers; Body Mass Index; Body Weight; C-Reactive Protein; Carcinoma, Hepatocellular; Catalase; Dietary Supplements; Female; Humans; Inflammation; Interleukin-6; Linear Models; Liver Neoplasms; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Single-Blind Method; Superoxide Dismutase; Ubiquinone; Vitamin E

Between 82.8% and 92.5% of participants in any BMI group were responders by AS, and between 91.3% and 100% were responders by BBPS in the right colon. Efficacy was consistent across BMI groups, with no clear trends. Greater than 83% of participants in any BMI group found the preparation 'easy' or 'acceptable' to ingest, and the majority (>58%) rated SPMC oral solution as 'better' than a prior bowel preparation. In all BMI groups, safety data were similar to the overall cohort. Commonly reported, drug-related, treatment-emergent AEs were, by ascending BMI group, nausea (1.1%, 5.3%, 1.0%, 5.7%, and 0%) and headache (1.1%, 4.1%, 1.0%, 5.7%, and 0%).. Ready-to-drink SPMC oral solution had consistent, good quality colon cleansing, and favorable tolerability among participants of all BMI groups.. NCT03017235.. The pretreatment serum AST/ALT ratio predicts poor disease outcome and response rate in patients with advanced PDAC treated with gemcitabine/nab-paclitaxel and might represent a novel and inexpensive marker for individual risk assessment in the treatment of pancreatic cancer.. Of the 98 patients included in the study, 58 had CR (59%), 28 had PR (29%), and 12 patients had NR (12%). The percent splenic tissue embolized was significantly greater in the CR group compared to the PR group (P = 0.001). The percent volume of splenic tissue embolized was linearly correlated with the magnitude of platelet increase without a minimum threshold. At least one line of chemotherapy was successfully restarted in 97% of patients, and 41% of patients did not experience recurrence of thrombocytopenia for the duration of their survival. The major complication rate was 8%, with readmission following initial hospitalization for persistent "post-embolization syndrome" symptoms the most common.. In cancer patients with hypersplenism-related thrombocytopenia, PSAE is a safe intervention that effects a durable elevation in platelet counts across a range of malignancies and following the re-initiation of chemotherapy.. Postoperative CRP elevation was a better predictor of prognosis in patients with gastric cancer than the occurrence of intra-abdominal infectious complications.. In clinical practice, mixed-species malaria infections are often not detected by light microscopy (LM) or rapid diagnostic test, as a low number of parasites of one species may occur. Here, we report the case of an 8-year-old girl migrating with her family from Afghanistan with a two-species mixed infection with

Topics: 3-Hydroxybutyric Acid; Acetazolamide; Acrylates; Administration, Intravenous; Adolescent; Adult; Aerosols; Afghanistan; Aflatoxin M1; Agaricales; Aged; Aged, 80 and over; Agricultural Irrigation; Air Pollutants; alpha-L-Fucosidase; Amino Acid Sequence; Androgen Antagonists; Animals; Antibodies, Bacterial; Antigens, Bacterial; Antineoplastic Agents; Antioxidants; Apoptosis; Artifacts; Autophagy; B7-H1 Antigen; Bacterial Proteins; Bacterial Typing Techniques; Bariatric Surgery; Base Composition; Bayes Theorem; Bile; Bioelectric Energy Sources; Biosensing Techniques; Body Mass Index; Brain; Brazil; Breast Neoplasms; Bufo arenarum; Burkholderia; C-Reactive Protein; Cadmium; Carbon Compounds, Inorganic; Carbon-13 Magnetic Resonance Spectroscopy; Carbonic Anhydrase Inhibitors; Carbonic Anhydrases; Carcinoma, Transitional Cell; Case-Control Studies; CD4-Positive T-Lymphocytes; Cell Count; Cell Hypoxia; Cell Line, Tumor; Cell Proliferation; Characiformes; Child; China; Cities; Cobalt; Colonic Neoplasms; Copper Sulfate; Cross-Sectional Studies; Cyclin-Dependent Kinase Inhibitor p16; Cytokines; Deoxycytidine; Diagnosis, Differential; Digestive System; Dihydroxyphenylalanine; Disease Models, Animal; DNA (Cytosine-5-)-Methyltransferase 1; DNA Barcoding, Taxonomic; DNA, Bacterial; Dose-Response Relationship, Drug; Down-Regulation; Edetic Acid; Electrochemical Techniques; Electrodes; Embolization, Therapeutic; Embryo, Nonmammalian; Environmental Monitoring; Enzyme-Linked Immunosorbent Assay; Epithelial-Mesenchymal Transition; Fatty Acids; Feces; Female; Follow-Up Studies; Food Contamination; Forkhead Box Protein M1; Fresh Water; Fungicides, Industrial; Gallium Isotopes; Gallium Radioisotopes; Gastrectomy; Gastric Bypass; Gastric Outlet Obstruction; Gastroplasty; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genes, Bacterial; Genetic Markers; Genome, Bacterial; Genome, Mitochondrial; Glioma; Glycogen Synthase Kinase 3 beta; Goats; Gonads; Guatemala; Halomonadaceae; HEK293 Cells; Helicobacter Infections; Helicobacter pylori; Hepacivirus; Histone-Lysine N-Methyltransferase; Hormones; Humans; Hydroxybutyrate Dehydrogenase; Hypersplenism; Hypoxia-Inducible Factor 1, alpha Subunit; Immunohistochemistry; Iran; Japan; Lactuca; Laparoscopy; Larva; Ligands; Liver Neoplasms; Lymphocyte Activation; Macrophages; Malaria; Male; Mercury; Metabolic Syndrome; Metals, Heavy; Mice; Middle Aged; Milk, Human; Mitochondria; Models, Molecular; Molecular Structure; Mothers; Multilocus Sequence Typing; Muscles; Mutation; Nanocomposites; Nanotubes, Carbon; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasms; Neoplastic Cells, Circulating; Neoplastic Stem Cells; Neuroimaging; Nitriles; Nitrogen Isotopes; Non-alcoholic Fatty Liver Disease; Nuclear Magnetic Resonance, Biomolecular; Obesity; Obesity, Morbid; Oligopeptides; Oxidation-Reduction; Pancreatic Neoplasms; Particle Size; Particulate Matter; Pepsinogen A; Pesticides; Pharmacogenetics; Phosphatidylinositol 3-Kinases; Phospholipids; Phylogeny; Plasmodium ovale; Plasmodium vivax; Platelet Count; Polyhydroxyalkanoates; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Postoperative Complications; Pregnancy; Prevalence; Prognosis; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Domains; Proto-Oncogene Proteins c-akt; Proton Magnetic Resonance Spectroscopy; Pseudogenes; PTEN Phosphohydrolase; Pyrazoles; Pyrimidines; Radiographic Image Interpretation, Computer-Assisted; Radiopharmaceuticals; Rats, Long-Evans; Rats, Sprague-Dawley; RAW 264.7 Cells; Reactive Oxygen Species; Real-Time Polymerase Chain Reaction; Receptor, Notch3; Receptors, G-Protein-Coupled; Receptors, Urokinase Plasminogen Activator; Recombinant Proteins; Repressor Proteins; Resveratrol; Retrospective Studies; Risk Assessment; Risk Factors; RNA, Messenger; RNA, Ribosomal, 16S; Salinity; Salvage Therapy; Seasons; Sequence Analysis, DNA; Seroepidemiologic Studies; Signal Transduction; Skin; Snails; Soluble Guanylyl Cyclase; Solutions; Spain; Species Specificity; Spheroids, Cellular; Splenic Artery; Stomach Neoplasms; Streptococcus pneumoniae; Structure-Activity Relationship; Sulfonamides; Sunlight; Surface Properties; Surgical Instruments; Surgical Wound Infection; Survival Rate; Tetrahydrouridine; Thinness; Thrombocytopenia; Tissue Distribution; Titanium; Tomography, X-Ray Computed; TOR Serine-Threonine Kinases; Tumor Microenvironment; Tumor Necrosis Factor-alpha; Turkey; Ubiquinone; Urologic Neoplasms; Viral Envelope Proteins; Wastewater; Water Pollutants, Chemical; Weather; Wnt Signaling Pathway; Xenograft Model Antitumor Assays; Young Adult

Topics: Acyltransferases; Adaptor Proteins, Signal Transducing; Antineoplastic Agents, Phytogenic; Antrodia; Autophagy; beta Catenin; Carcinoma, Hepatocellular; Hep G2 Cells; Humans; Liver Neoplasms; Signal Transduction; TOR Serine-Threonine Kinases; Transcription Factors; Ubiquinone; Wnt Proteins; YAP-Signaling Proteins

(1) Background: Hepatocellular carcinoma (HCC) is the second leading cause of cancer deaths worldwide, and surgical resection is the main treatment for HCC. To date, no published study has examined the status of coenzyme Q10 in patients with HCC after surgery. Thus, the purpose of this study was to investigate the correlations between the level of coenzyme Q10, oxidative stress, and inflammation in patients with HCC after surgery; (2) Methods: 71 primary HCC patients were recruited. Levels of coenzyme Q10, vitamin E, oxidative stress (malondialdehyde), antioxidant enzymes activity (superoxidase dismutase, catalase, and glutathione peroxidase), and inflammatory markers (high sensitivity C-reactive protein; tumor necrosis factor-α; and interleukin-6) were measured; (3) Results: Patients with HCC had a significantly lower levels of coenzyme Q10 (

Topics: Adult; Aged; Aged, 80 and over; Aspartate Aminotransferases; Blood Glucose; C-Reactive Protein; Carcinoma, Hepatocellular; Creatinine; Glutathione Peroxidase; Humans; Inflammation; Interleukin-6; Linear Models; Liver Neoplasms; Malondialdehyde; Middle Aged; Oxidative Stress; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Tumor Necrosis Factor-alpha; Ubiquinone; Vitamin E; Young Adult

Mitochondria are a major source of reactive oxygen species (ROS) and are also the target of cellular ROS. ROS damage to mitochondria leads to dysfunction that further enhances the production of mitochondrial ROS. This feed-forward vicious cycle between mitochondria and ROS induces cell death. Within a few minutes of radiation exposure, NADPH oxidase is activated to elevate the ROS level. Activated NADPH oxidase might induce the feed-forward cycle of mitochondria and this is a possible mechanism for cancer cell death induced by heavy ion irradiation. We found that after 4 Gy of (12) C(6+) ion radiation of HepG2 cells, the NADPH oxidase membrane subunit gp91(phox) was not involved in enzyme activation through increased expression; however, the subunit p47(phox) was involved in activation by being translocated to the membrane. (12) C(6+) ion radiation clearly decreased the ΔΨm of HepG2 cells, increasing mitochondrial DNA damage and inducing cell death. Pretreatment with apocynin (APO, an NADPH oxidase inhibitor) effectively prevented the ΔΨm decrease, mitochondrial DNA damage, and cell death induced by radiation. However, these protective effects were not observed with APO treatment after irradiation exposure. These data demonstrated that NADPH oxidase activation was an initiator in mitochondrial damage. Once mitochondria entered the feed-forward cycle, cell fate was no longer controlled by NADPH oxidase. Only antioxidants that targeted mitochondria such as MitoQ could break the cycle and release cells from death.

Topics: Adaptor Proteins, Signal Transducing; Antioxidants; Apoptosis; Carcinoma, Hepatocellular; Enzyme Activation; Heavy Ion Radiotherapy; Hep G2 Cells; Humans; Liver Neoplasms; Membrane Glycoproteins; Mitochondria, Liver; NADPH Oxidase 2; NADPH Oxidases; Organophosphorus Compounds; Oxidation-Reduction; Reactive Oxygen Species; Ubiquinone

Ubiquinone (Q) is a product in the cholesterol synthesis pathway and is an essential component of the respiratory chain in the mitochondrial membrane. In addition, extra-mitochondrial Q has anti-oxidative properties and this fraction is increased during carcinogenesis. The aim of the present study was to investigate if extra-mitochondrial level of Q is affected by statin treatment in a rat model for liver cancer, and if this change correlates with inhibited carcinogenesis. To do this we isolated sub-cellular fractions of rat livers from a previous experiment where we have shown anti-carcinogenic effects of statins. The levels of Q(8), Q(9) and Q(10) were analysed with liquid chromatography-mass spectrometry. The Q(9)-levels, constituting the major part of Q in rats, were not significantly affected in any of the sub-cellular compartments. The levels of Q(10), constituting a minor part of Q in rats but the major part of Q in humans, were significantly decreased by about 60% in the statin treated rats. The decrease was present in all sub-cellular compartments, but was most pronounced in the cytosol. There was a significant correlation between extra-mitochondrial Q(10) levels and inhibited carcinogenesis. No such correlation was observed with extra-mitochondrial Q(9). The reduced Q(10)-levels might be explained by the reduced availability of isoprene units during statin treatment, shifting the synthesis towards isoforms with shorter side-chains. In line with this hypothesis there were increased levels of Q(8)-levels during statin treatment. The results support our previous suggestion that at least part of the anti-carcinogenic effect of statins in our rat model is mediated by effects on synthesis of Q. We also demonstrate a shift in the Q-synthesis pathway towards isoforms with shorter side-chains during statin treatment. The ratio between the different Q-isoforms might be used as a more sensitive marker of statin-induced inhibition of Q than measuring total Q levels.

Topics: Animals; Anticarcinogenic Agents; Disease Models, Animal; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Isoenzymes; Liver Neoplasms; Male; Mitochondria, Liver; Rats; Rats, Inbred F344; Ubiquinone

5'AMP-activated protein kinase (AMPK) and the mammalian target of rapamycin (mTOR) are two serine/threonine protein kinases responsible for cellular energy homeostasis and translational control, respectively. Evidence suggests that these two kniases are potential targets for cancer chemotherapy against hepatocellular carcinoma (HCC). Antroquinonol that is isolated from Antrodia camphorate, a well-known Traditional Chinese Medicine for treatment of liver diseases, displayed effective anticancer activity against both HBV DNA-positive and -negative HCC cell lines. The rank order of potency against HCCs is HepG2>HepG2.2.15>Mahlavu>PLC/PRF/5>SK-Hep1>Hep3B. Antroquinonol completely abolished cell-cycle progression released from double-thymidine-block synchronization and caused a subsequent apoptosis. The data were supported by down-regulation and reduced nuclear translocation of G1-regulator proteins, including cyclin D1, cyclin E, Cdk4 and Cdk2. Further analysis showed that the mRNA expressions of the G1-regulator proteins were not modified by antroquinonol, indicating an inhibition of translational but not transcriptional levels. Antroquinonol induced the assembly of tuberous sclerosis complex (TSC)-1/TSC2, leading to the blockade of cellular protein synthesis through inhibition of protein phosphorylation including mTOR (Ser(2448)), p70(S6K) (Thr(421)/Ser(424) and Thr(389)) and 4E-BP1 (Thr(37)/Thr(46) and Thr(70)). Furthermore, the AMPK activity was elevated by antroquinonol. Compound C, a selective AMPK inhibitor, significantly reversed antroquinonol-mediated effects suggesting the crucial role of AMPK. Besides, the loss of mitochondrial membrane potential and depletion of mitochondrial content indicated the mitochondrial stress caused by antroquinonol. In summary, the data suggest that antroquinonol displays anticancer activity against HCCs through AMPK activation and inhibition of mTOR translational pathway, leading to G1 arrest of the cell-cycle and subsequent cell apoptosis.

Topics: Adenylate Kinase; Base Sequence; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Proliferation; DNA Primers; Flow Cytometry; Humans; Liver Neoplasms; Phosphorylation; Protein Kinases; Reverse Transcriptase Polymerase Chain Reaction; TOR Serine-Threonine Kinases; Ubiquinone

Coenzyme Q (CoQ) is an essential component of the mitochondrial electron transport chain and serves as an electron donor and acceptor in mitochondrial energy-linked respiration. CoQ1 was shown to prevent ROS formation and cell death in complex 1 inhibited cells. Low concentrations of capsaicin like CoQ1 inhibited ROS formation but CoQ1 was more effective at restoring the mitochondrial membrane potential collapse caused by complex 1 inhibitors such as rotenone. At low concentrations, capsaicin acts as a CoQ mimic by protecting against rotenone induced ROS formation and mitochondrial membrane potential collapse. Lipid peroxidation in isolated rat hepatocytes induced by cumene hydroperoxide and chloroacetaldehyde was also prevented. At higher concentrations, capsaicin and CoQ1 became cytotoxic. Hep G2 cells were more susceptible than hepatocytes. The cytotoxic mechanism for both capsaicin and CoQ1 was shown to involve a collapse of the mitochondrial membrane potential, however, only capsaicin caused ROS formation. The capsaicin side chain was required for capsaicin induced cytotoxicity. The anticancer properties of CoQ1 and capsaicin should prove useful for inducing tumor cell apoptosis.

Topics: Animals; Antineoplastic Agents; Capsaicin; Carcinoma, Hepatocellular; Cell Death; Cell Division; Cytoprotection; Hepatocytes; Humans; Lipid Peroxidation; Liver Neoplasms; Male; Membrane Potentials; Mitochondria, Liver; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Rotenone; Structure-Activity Relationship; Tumor Cells, Cultured; Ubiquinone

To assess the degree of oxidative stress, we measured plasma ubiquinone-10 percentage (%CoQ-10) in total amounts of ubiquinone-10 in patients with chronic active hepatitis, liver cirrhosis, and hepatocellular carcinoma, and in age-matched control subjects, %CoQ-10 values were 12.9 +/- 10.3 (n = 28), 10.6 +/- 6.8 (n = 28), 18.9 +/- 11.1 (n = 20), and 6.4 +/- 3.3 (n = 16), respectively, showing a significant increase in oxidative stress in patient groups as compared to control subjects. There were no differences in total amounts of ubiquinone-10 and ubiquinol-10 among the four groups. We next measured %CoQ-10 in plasmas obtained from nine patients treated with percutaneous transluminal coronary angioplasty (PTCA). Plasmas were collected when hospitalized, and at the time (0, 4, 8, 12, 16, and 20 hr, and 1, 2, 3, 4, and 7 days) after the PTCA. %CoQ-10 values before and right after PTCA were 9.9 +/- 2.8 and 11.4 +/- 2.0, respectively, reached a maximum (20-45) at 1 or 2 days later, and decreased to 7.9 +/- 2.7 at 7 days after PTCA, indicating an increase in oxidative stress in patients during coronary reperfusion.

Topics: Adult; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Ascorbic Acid; beta Carotene; Bilirubin; Biomarkers; Carcinoma, Hepatocellular; Carotenoids; Female; Hepatitis; Humans; Liver Cirrhosis; Liver Neoplasms; Lycopene; Male; Middle Aged; Oxidative Stress; Reference Values; Ubiquinone; Uric Acid; Vitamin E

We have applied our method for the simultaneous detection of plasma ubiquinol-10 (reduced form) and ubiquinone-10 (oxidized form) (S. Yamashita and Y. Yamamoto, Anal. Biochem. 250, 66-73, 1997) to plasmas of normal subjects (n = 16) and patients with chronic active hepatitis (n = 28), liver cirrhosis (n = 16), and hepatocellular carcinoma (n = 20) to evaluate the pressure of oxidative stress in these patients. The average ubiquinone-10 percentages (+/- S.D.) in total ubiquinone-10 and ubiquinol-10 in the four groups were 6.4 +/- 3.3, 12.9 +/- 10.3, 10.6 +/- 6.8, and 18.9 +/- 11.1, respectively, indicating a significant increase in ubiquinone-10 percentage in patient groups in comparison to normal subjects. These results and a significant decrease in the plasma ascorbate level in patient groups indicate that oxidative stress is evident after the onset of hepatitis and the subsequent cirrhosis and liver cancer.

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; beta Carotene; Biomarkers; Carcinoma, Hepatocellular; Carotenoids; Cholesterol; Cholesterol Esters; Female; Hepatitis, Chronic; Humans; Liver Cirrhosis; Liver Diseases; Liver Neoplasms; Lycopene; Male; Middle Aged; Oxidative Stress; Ubiquinone; Vitamin E

Oxidative stress is defined as a disturbance in the prooxidant-antioxidant balance in favor of the former and has been suggested to be a relevant factor in aging as well as in different pathological conditions, such as heart attack, diabetes, and cancer. Ubiquinol is very sensitive against oxygen radicals and gives ubiquinone as an oxidation product. Therefore, the ratio of ubiquinol to ubiquinone should be a good marker of oxidative stress because of its definition. A method for the simultaneous detection of ubiquinol-10 and ubiquinone-10 in human plasma is described. Heparinized human plasma was mixed with 5 volumes of methanol and 10 volumes of hexane. After vigorous shaking and centrifugation, the hexane phase (5 microliters) was injected immediately and directly on to reverse-phase HPLC equipped with an on-line reduction column and an electrochemical detector in order to avoid the oxidation of ubiquinol to ubiquinone. It was found that the ratio of ubiquinol-10 to ubiquinone-10 was about 95/5 in human plasma from healthy donors. A significant increase in the oxidized form (ubiquinone-10) content was observed in plasmas of patients with hepatitis, cirrhosis, and hepatoma when compared with normal subjects, suggesting increased oxidative stress in these patients.

Topics: Biomarkers; Carcinoma, Hepatocellular; Chromatography, High Pressure Liquid; Coenzymes; Electrochemistry; Hepatitis; Hexanes; Humans; Liver Cirrhosis; Liver Diseases; Liver Neoplasms; Oxidation-Reduction; Oxidative Stress; Reactive Oxygen Species; Solvents; Ubiquinone; Vitamin E

Over 35 years, data and knowledge have internationally evolved from biochemical, biomedical and clinical research on vitamin Q10 (coenzyme Q10; CoQ10) and cancer, which led in 1993 to overt complete regression of the tumors in two cases of breast cancer. Continuing this research, three additional breast cancer patients also underwent a conventional protocol of therapy which included a daily oral dosage of 390 mg of vitamin Q10 (Bio-Quinone of Pharma Nord) during the complete trials over 3-5 years. The numerous metastases in the liver of a 44-year-old patient "disappeared," and no signs of metastases were found elsewhere. A 49-year-old patient, on a dosage of 390 mg of vitamin Q10, revealed no signs of tumor in the pleural cavity after six months, and her condition was excellent. A 75-year-old patient with carcinoma in one breast, after lumpectomy and 390 mg of CoQ10, showed no cancer in the tumor bed or metastases. Control blood levels of CoQ10 of 0.83-0.97 and of 0.62 micrograms/ml increased to 3.34-3.64 and to 3.77 micrograms/ml, respectively, on therapy with CoQ10 for patients A-MRH and EEL.

Topics: Adult; Aged; Antineoplastic Agents; Breast Neoplasms; Coenzymes; Female; Follow-Up Studies; Humans; Liver Neoplasms; Mastectomy, Segmental; Middle Aged; Time Factors; Ubiquinone

Surgical samples of human hepatic tissue were analysed morphologically and biochemically and highly differentiated hepatomas were compared with two control groups: morphologically normal liver tissue surrounding the tumour, and tissue from normal livers. In tumour homogenates cholesterol levels were more than twice, ubiquinone levels about half and the concentration of free dolichol about 10% of the control value. The levels of dolichyl phosphate were basically similar, whereas the phospholipid level was slightly lower in the tumours. In microsomes isolated from hepatomas, the level of cholesterol was about 30% higher than the control value. HMG-CoA reductase activity in microsomes isolated from hepatomas was elevated almost 100% in comparison to control. In hepatomas, no major alterations in the compositions of dolichol or dolichyl phosphate could be observed. The relative amounts of alpha-saturated and alpha-unsaturated polyprenols were also basically unaltered in hepatomas. Liver samples were incubated with 3H-mevalonic acid and radioactivity was monitored in polyprenols. With control tissue, incorporation was considerably higher in alpha-unsaturated polyprenols than in their alpha-saturated counterparts. In the tumours the rates of incorporation into both polyprenol fractions were much lower, although still higher in the alpha-unsaturated fraction. Labelling of polyisoprenols containing 19 isoprene residues was higher than that of 20 residues. The pattern of labelling in the polyisoprenyl-P fraction was similar. In hepatomas the incorporation into cholesterol and ubiquinone-10 was about 100% higher and 50% lower respectively compared with control tissue. The results in this study of hepatomas indicate that the levels of various lipids may be influenced not only by the regulatory enzyme HMG-CoA reductase, but also by other enzymes catalysing reactions subsequent to this regulatory point. It is also suggested that levels of cholesterol, ubiquinone and dolichol may be regulated independently subsequent to the branch point at farnesylpyrophosphate.

Topics: Carcinoma, Hepatocellular; Cholesterol; Dolichol Phosphates; Dolichols; Humans; Liver Neoplasms; Terpenes; Ubiquinone

The levels of cholesterol, ubiquinone and dolichol and the polyprenol composition of dolichol in human hepatocellular carcinomas (hepatomas) with different degrees of differentiation were analyzed and compared with healthy liver tissue. Dolichols were also analyzed in liver metastases. The total level of cholesterol was increased, while the levels of dolichol and ubiquinone were decreased in all hepatomas, but no correlation between these levels and the degree of differentiation of the hepatomas could be observed. The level of dolichol decreased more in the hepatomas than in the liver metastases. The dolichol fraction from hepatomas with a low degree of differentiation contained higher relative amounts of short polyisoprenols (D17) and slightly lower relative amounts of D21 compared with healthy liver tissue, metastatic liver tumors or hepatomas with a high degree of differentiation. The significance of the lipid values found in the different groups is discussed.

Topics: Adult; Carcinoma, Hepatocellular; Cell Membrane; Cholesterol; Dolichols; Humans; Liver Neoplasms; Middle Aged; Terpenes; Ubiquinone

The lipid composition of human hepatocellular carcinomas was examined. The level of dolichol in the tumours was decreased compared to control tissue, whereas the concentration of dolichyl phosphate did not exhibit any major change. A decrease in the amount of dolichyl ester was also observed. The pattern of individual polyisoprenoids in the free dolichol pool was changed in several carcinomas with a relative increase in the shorter dolichols. The isoprenol composition in the dolichyl ester and phosphate fractions of tumours were basically similar to those of controls. alpha-Unsaturated polyisoprenols are present in control livers at a level of 3% of the total free polyisoprenoid fraction, while this value was increased in the tumours. Similar to dolichol, the amount of ubiquinone was also decreased. The content of cholesterol was increased, while the fatty acid pattern of the dolichyl esters showed minor alterations. These modifications in lipid content indicate different mechanisms for the regulation of dolichol and dolichyl phosphate concentrations. The high levels of sterols in contrast to the low polyisoprenol content suggests interference with the regulation of the mevalonate pathway, which is the common biosynthetic route for cholesterol, ubiquinone and dolichol.

Topics: Adult; Aged; Carcinoma, Hepatocellular; Cholesterol; Dolichol Phosphates; Dolichols; Fatty Acids; Humans; Liver Neoplasms; Middle Aged; Ubiquinone

The lipid compositions of homogenates and microsomal fractions derived from surgical samples of highly differentiated human hepatoma, morphologically normal regions outside the tumours and from normal livers were analysed. A few enzyme activities were also assayed. Hepatoma microsomes demonstrated considerably lowered levels of cytochromes P-450 and b5. Hepatoma homogenates exhibited increased levels of cholesterol, normal amounts of dolichyl-P and slightly lowered levels of total phospholipid. The levels of dolichol, dolichol ester and ubiquinone in hepatoma homogenates were prominently decreased. In tumour microsomes the levels of cholesterol and dolichyl phosphate were increased considerably while the levels of phospholipid and dolichol were lowered. The phospholipid composition of tumour homogenates was roughly similar to that of control tissue. In tumour microsomes the relative amounts of phosphatidylserine and phosphatidylinositol were about 30% decreased, whereas the major phospholipids showed minor increases in amount. The rate and pattern of incorporation of [3H]glycerol into individual phospholipids in liver slices from control and hepatoma tissue did not differ to any larger extent. The fatty acid composition of tumour homogenates exhibited minor differences in comparison to the control with the greatest changes in the sphingomyelin fraction. In hepatoma microsomes the fatty acid compositions of the major phospholipids were altered moderately, with evident decreases in the relative amounts of the long-chain polyunsaturated fatty acids. In hepatoma homogenates the fatty acid composition of dolichol esters differed only slightly from the control pattern. These results indicate that the major disturbance in the lipid metabolism of highly differentiated hepatomas is localized to the mevalonate pathway, thus affecting mainly the levels of cholesterol, dolichol and ubiquinone.

Topics: Carcinoma, Hepatocellular; Cholesterol; Cytochrome b Group; Cytochrome P-450 Enzyme System; Cytochromes b5; Dolichols; Fatty Acids; Humans; Lipids; Liver; Liver Neoplasms; Microsomes, Liver; Middle Aged; Phospholipids; Ubiquinone

Topics: Carcinoma, Hepatocellular; Cholesterol; Diterpenes; Dolichols; Humans; Hydroxymethylglutaryl CoA Reductases; Liver; Liver Neoplasms; Microsomes; Microsomes, Liver; Ubiquinone

Topics: Biopsy; Diagnostic Errors; Dihydrolipoamide Dehydrogenase; Esterases; Histocytochemistry; Humans; Laparotomy; Liver; Liver Diseases; Liver Neoplasms; Methods; NADH, NADPH Oxidoreductases; Oxidoreductases; Postoperative Complications; Ubiquinone

Topics: Abdominal Muscles; Aged; Animals; Ascites; Carcinoma; Carcinoma, Hepatocellular; Chromatography, Paper; Female; Humans; Intestinal Neoplasms; Intestine, Large; Liver; Liver Neoplasms; Male; Middle Aged; Mitochondria; Mitochondria, Liver; Neoplasm Metastasis; Neoplasms; Neoplasms, Experimental; Oxidoreductases; Stomach Neoplasms; Ubiquinone

Topics: Animals; Ascites; Carcinoma, Hepatocellular; Coenzymes; Electron Transport Complex II; Liver Neoplasms; Liver Neoplasms, Experimental; Mechlorethamine; Naphthoquinones; Neoplasms, Experimental; Oxidoreductases; Rats; Succinate Dehydrogenase; Succinates; Succinic Acid; Tetrazolium Salts; Ubiquinone; Vitamin K; Vitamin K 3

Topics: Biochemical Phenomena; Carcinoma, Hepatocellular; Coenzymes; Liver; Liver Neoplasms; Ubiquinone