ubiquinone and Neoplasms

Coenzyme Q

Topics: Biological Availability; Dietary Supplements; Humans; Migraine Disorders; Neoplasms; Neurodegenerative Diseases; Neuromuscular Diseases; Quality of Life; Ubiquinone

Dihydroorotate dehydrogenase (DHODH) is an enzyme of the de novo pyrimidine synthesis pathway that provides nucleotides for RNA/DNA synthesis essential for proliferation. In mammalian cells, DHODH is localized in mitochondria, linked to the respiratory chain via the coenzyme Q pool. Here we discuss the role of DHODH in the oxidative phosphorylation system and in the initiation and progression of cancer. We summarize recent findings on DHODH biology, the progress made in the development of new, specific inhibitors of DHODH intended for cancer therapy, and the mechanistic insights into the consequences of DHODH inhibition.

Topics: Cell Proliferation; Dihydroorotate Dehydrogenase; Electron Transport; Enzyme Inhibitors; Humans; Mitochondria; Neoplasms; Oxidative Phosphorylation; Oxidoreductases Acting on CH-CH Group Donors; Ubiquinone

Lipid peroxidation has been associated with a wide array of (patho)physiological conditions. Remarkably, in the last few years, a novel cell death modality termed ferroptosis was recognized as a process initiated by iron-dependent oxidation of lipids. The sensitivity to ferroptosis is determined by the activity of antioxidant systems working on the repair of oxidized phospholipids and also metabolic pathways controlling the availability of substrates susceptible to lipid peroxidation. Non-enzymatic antioxidants such as vitamin E, which has long been acknowledged as an efficient inhibitor of lipid peroxidation, play an important and often neglected role in subverting ferroptosis. Recent works dissecting the mechanisms that determine ferroptosis sensitivity have provided further insights into the contribution of alternative metabolic pathways able to suppress lipid peroxidation. Specifically, the role of ubiquinone and tetrahydrobiopterin (BH4) has been brought forth, with the identification of specific enzymatic systems responsible for their regeneration, as critical factors suppressing ferroptosis. Therefore, in the present manuscript, we address these emerging concepts and propose that the characterization of these antioxidant repair mechanisms will not only open a new understanding of disease conditions where ferroptosis plays a role but also offer opportunities to identify and sensitize cells to ferroptosis in the context of cancer treatment.

Topics: Animals; Antioxidants; Biopterins; Cell Death; Ferroptosis; Gene Expression Regulation; Humans; Iron; Lipid Peroxidation; Lipids; Neoplasms; Oxidation-Reduction; Oxygen; Reactive Oxygen Species; Ubiquinone; Vitamin E

Coenzyme Q-10 (CoQ10) is a widely used alternative medication or dietary supplement and one of its roles is as an antioxidant. It naturally functions as a coenzyme and component of oxidative phosphorylation in mitochondria. Decreased levels have been demonstrated in diseased myocardium and in Parkinson disease. Farnesyl pyrophosphate is a critical intermediate for CoQ10 synthesis and blockage of this step may be important in statin myopathy. Deficiency of CoQ10 also has been associated with encephalomyopathy, severe infantile multisystemic disease, cerebellar ataxia, nephrotic syndrome, and isolated myopathy. Although supplementation with CoQ10 has been reported to be beneficial in treating hypertension, congestive heart failure, statin myopathy, and problems associated with chemotherapy for cancer treatement, this use of CoQ10 as a supplement has not been confirmed in randomized controlled clinical trials. Nevertheless, it appears to be a safe supplementary medication where usage in selected clinical situations may not be inappropriate. This review is an attempt to actualize the available information on CoQ10 and define its potential benefit and appropriate usage.

Topics: Animals; Cardiovascular Diseases; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Muscular Diseases; Neoplasms; Ubiquinone

The study of rare genetic diseases usually inspires the research of cancer biology. Fanconi anemia (FA), is a rare cancer susceptibility syndrome with an incidence of only 1 per 350,000 births. FA is an autosomal recessive disease with three main features: chromosome instability, hypersensitivity to DNA cross-linking agents such as mitomycin C (MMC), cisplatin and so on, and susceptible to a number of cancer types, mainly leukemia and squamous cell carcinomas of the head and neck or gynecologic system. DNA crosslinking agents may led to DNA cross-linking lesion, and Fanconi anemia pathway plays a key role in repairing its cross-linking. However, FA pathway is closely linked with carcinogenesis and tumor drug resistance. This paper mainly focuses on the FA pathway and its progress in cancer research.

Topics: Cross-Linking Reagents; DNA; DNA Repair; Fanconi Anemia; Fanconi Anemia Complementation Group Proteins; Humans; Neoplasms; Signal Transduction; Ubiquinone

Milk fat is characterized by extensive pro-health activity. Its unique components, such as: short chain saturated fatty acids, conjugated linoleic acid (CLA), vaccenic acid, ether lipids (alkiloglicerols and alkiloglicerophospholipids), 13-methyltetradecanic acid and bioactive components of antioxidative activity, are important in prophylaxis, and even in therapy of cancer diseases. Advantageous influence to maintain pro- and antioxidative balance of organism is revealed by the components of milk fat: conjugated linoleic acid, vitamins A and E, and coenzyme Q10. Moreover, vitamin D3, phospholipids, ether lipids, cholesterol and 13-methyltetradecanic acid also reveal antioxidative activity.

Topics: Animals; Antioxidants; Cholecalciferol; Dietary Fats; Humans; Linoleic Acid; Milk; Neoplasms; Phospholipids; Ubiquinone; Vitamin A; Vitamin E

Succinate:quinone reductase (SQR) of Complex II occupies a unique central point in the mitochondrial respiratory system as a major source of electrons driving reactive oxygen species (ROS) production. It is an ideal pharmaceutical target for modulating ROS levels in normal cells to prevent oxidative stress-induced damage or alternatively,increase ROS in cancer cells, inducing cell death.The value of drugs like diazoxide to prevent ROS production,protecting normal cells, whereas vitamin E analogues promote ROS in cancer cells to kill them is highlighted. As pharmaceuticals these agents may prevent degenerative disease and their modes of action are presently being fully explored. The evidence that SDH/Complex II is tightly coupled to the NADH/NAD+ ratio in all cells,impacted by the available supplies of Krebs cycle intermediates as essential NAD-linked substrates, and the NAD+-dependent regulation of SDH/Complex II are reviewed, as are links to the NAD+-dependent dehydrogenases, Complex I and the E3 dihiydrolipoamide dehydrogenase to produce ROS. This review collates and discusses diverse sources of information relating to ROS production in different biological systems, focussing on evidence for SQR as the main source of ROS production in mitochondria, particularly its relevance to protection from oxidative stress and to the mitochondrial-targeted anti cancer drugs (mitocans) as novel cancer therapies [corrected].

Topics: alpha-Tocopherol; Cell Death; Coenzyme A; Dihydrolipoamide Dehydrogenase; Fatty Acids, Nonesterified; Humans; Mitochondria; NAD(P)H Dehydrogenase (Quinone); Neoplasms; Organophosphorus Compounds; Protective Agents; Reactive Oxygen Species; Succinic Acid; Ubiquinone

The promising theoretical possibilities of antioxidant prevention and protection against vascular diseases and neoplasms could not have been realized as yet. The author searches into the causes of this failure by analyzing data of recent literature. Previous preventive trials as well as newly discovered pharmacological and molecular biological effects of antioxidants are reviewed. Results of meta-analyses on prevention trials of vascular disease by vitamin-E and those of gastrointestinal cancers are also included. The lately recognized properties of antioxidants are surveyed with special regard to their capability of modulating apoptosis, inducing gene expressions and their transformation into pro-oxidants. The harmful consequence of high doses of a single antioxidant is emphasized. The retinoids, vitamins D and K possess both pro-apoptotic and antiproliferative activity, while N-acetylcysteine exerts mainly anti-apoptotic effects. Since the effects of the eight vitamin E homologues are different in many respects, alpha-tocopherol can not be regarded as vitamin E of full value. Antioxidant supply from natural sources does not seem to be sufficient for an adequate preventive effect. The author recommends such a combination in which physiological amounts of vitamins C, D, K and B-complex, N-acetylcysteine, vitamin E of natural origin might be complemented by allopurinol, co-enzyme Q-10 and alpha-lipoic acid. A diet rich in flavonoids and carotenoids is essential. Application of appropriate laboratory methods is of great value in the individualization, monitoring and control of antioxidant treatment.

Topics: Acetylcysteine; Allopurinol; Antioxidants; Apoptosis; Ascorbic Acid; Cardiovascular Diseases; Clinical Trials as Topic; Coenzymes; Flavonoids; Humans; Meta-Analysis as Topic; Neoplasms; Selenium; Ubiquinone; Vitamin A; Vitamin D; Vitamin E; Vitamin K; Vitamins

Preclinical and clinical studies suggest that anthracycline-induced cardiotoxicity can be prevented by administering coenzyme Q10 during cancer chemotherapy that includes drugs such as doxorubicin and daunorubicin. Studies further suggest that coenzyme Q10 does not interfere with the antineoplastic action of anthracyclines and might even enhance their anticancer effects. Preventing cardiotoxicity might allow for escalation of the anthracycline dose, which would further enhance the anticancer effects. Based on clinical investigation, although limited, a cumulative dose of doxorubicin of up to 900 mg/m2, and possibly higher, can be administered safely during chemotherapy as long as coenzyme Q10 is administered concurrently. The etiology of the dose-limiting cardiomyopathy that is induced by anthracyclines can be explained by irreversible damage to heart cell mitochondria, which differ from mitochondria of other cells in that they possess a unique enzyme on the inner mitochondrial membrane. This enzyme reduces anthracyclines to their semiquinones, resulting in severe oxidative stress, disruption of mitochondrial energetics, and irreversible damage to mitochondrial DNA. Damage to mitochondrial DNA blocks the regenerative capability of the organelle and ultimately leads to apoptosis or necrosis of myocytes. Coenzyme Q10, an essential component of the electron transport system and a potent intracellular antioxidant, appears to prevent damage to the mitochondria of the heart, thus preventing the development of anthracycline-induced cardiomyopathy.

Topics: Animals; Anthracyclines; Antibiotics, Antineoplastic; Antioxidants; Cardiomyopathies; Coenzymes; Cytoprotection; Dose-Response Relationship, Drug; Drug Therapy, Combination; Heart; Heart Failure; Humans; Mitochondria, Heart; Neoplasms; Ubiquinone

Coenzyme Q10 (ubiquinone) is a naturally occurring compound widely distributed in animal organisms and in humans. The primary compounds involved in the biosynthesis of ubiquinone are 4-hydroxybenzoate and the polyprenyl chain. An essential role of coenzyme Q10 is as an electron carrier in the mitochondrial respiratory chain. Moreover, coenzyme Q10 is one of the most important lipophilic antioxidants, preventing the generation of free radicals as well as oxidative modifications of proteins, lipids, and DNA, it and can also regenerate the other powerful lipophilic antioxidant, alpha-tocopherol. Antioxidant action is a property of the reduced form of coenzyme Q10, ubiquinol (CoQ10H2), and the ubisemiquinone radical (CoQ10H*). Paradoxically, independently of the known antioxidant properties of coenzyme Q10, the ubisemiquinone radical anion (CoQ10-) possesses prooxidative properties. Decreased levels of coenzyme Q10 in humans are observed in many pathologies (e.g. cardiac disorders, neurodegenerative diseases, AIDS, cancer) associated with intensive generation of free radicals and their action on cells and tissues. In these cases, treatment involves pharmaceutical supplementation or increased consumption of coenzyme Q10 with meals as well as treatment with suitable chemical compounds (i.e. folic acid or B-group vitamins) which significantly increase ubiquinone biosynthesis in the organism. Estimation of coenzyme Q10 deficiency and efficiency of its supplementation requires a determination of ubiquinone levels in the organism. Therefore, highly selective and sensitive methods must be applied, such as HPLC with UV or coulometric detection.

Topics: Animals; Antioxidants; Coenzymes; Cytoprotection; Free Radicals; Humans; Mitochondria; Neoplasms; Neurodegenerative Diseases; Ubiquinone

Coenzyme Q (ubiquinone, 2-methyl-5,6-dimethoxy-1,4-benzoquinone), soluble natural fat quinine, is crucial to optimal biological function. The coenzyme Q molecule has amphipathic (biphasic) properties due to the hydrophilic benzoquinone ring and the lipophilic poly isoprenoid side-chain. The nomenclature of coenzyme Q-n is based on the amount of isoprenoid units attached to 6-position on the benzoquinone ring. It was demonstrated that coenzyme Q, in addition to its role in electron transport and proton transfer in mitochondrial and bacterial respiration, acts in its reduced form (ubiquinol) as an antioxidant. Coenzyme Q-10 functions as a lipid antioxidant regulating membrane fluidity, recycling radical forms of vitamin C and E, and protecting membrane phospholipids against peroxidation. The antioxidant property, high degree of hydrophobicity and universal occurrence in biological system, suggest an important role for ubiquinone and ubiquinol in cellular defense against oxidative damage. Coenzyme Q-10 is a ubiquitous and endogenous lipid-soluble antioxidant found in all organisms. Neurodegenerative disorders, cancer, cardiovascular diseases and diabetes mellitus and especially aging and Alzheimer's disease exhibit altered levels of ubiquinone or ubiquinol, indicating their likely crucial role in the pathogenesis and cellular mechanisms of these ailments. This review is geared to discuss the biological effect of coenzyme Q with an emphasis on its impact in initiation, progression, treatment and prevention of neurodegenerative, cardiovascular and carcinogenic diseases.

Topics: Aging; Animals; Antioxidants; Cardiovascular Diseases; Diabetes Mellitus; Humans; Lipid Peroxidation; Neoplasms; Neurodegenerative Diseases; Oxidative Stress; Ubiquinone

The aim of this systematic review was to summarize and evaluate the evidence available for oral supplementation with coenzyme Q10 (CoQ10) to improve the tolerability of cancer treatments.. Searches for all published and unpublished controlled trials were carried out on seven databases. Manufacturers of CoQ10 were identified and contacted. Controlled clinical trials of monopreparations of CoQ10 administered orally to cancer patients were included. No language restrictions were imposed. Data were extracted independently by two authors according to predefined criteria.. Six studies were included in the review, including three randomized clinical trials and three nonrandomized clinical trials. Patients in five of six studies received anthracyclines. The results suggested that CoQ10 provides some protection against cardiotoxicity or liver toxicity during cancer treatment. However, because of inadequate reporting and analysis, as well as questionable validity of outcome measures, the results are not conclusive.. Suggestions that CoQ10 might reduce the toxicity of cancer treatments have not been tested by rigorous trials. Further investigations are necessary to determine whether CoQ10 can improve the tolerability of cancer treatments.

Topics: Antineoplastic Agents; Antioxidants; Coenzymes; Controlled Clinical Trials as Topic; Cytoprotection; Humans; Neoplasms; Ubiquinone

ECTO-NOX (because of their cell surface location) proteins comprise a family of NAD(P)H oxidases of plants and animals that exhibit both oxidative and protein disulfide isomerase-like activities. The two biochemical activities, hydroquinone [NAD(P)H] oxidation and protein disulfide--thiol interchange alternate, a property unprecedented in the biochemical literature. A tumor-associated ECTO-NOX (tNOX) is cancer-specific and drug-responsive. The constitutive ECTO-NOX (CNOX) is ubiquitous and refractory to drugs. The physiological substrate for the oxidative activity appears to be hydroquinones of the plasma membrane such as reduced coenzyme Q10. ECTO-NOX proteins are growth-related and drive cell enlargement. Also indicated are roles in aging and in neurodegenerative diseases. The regular pattern of oscillations appears to be related to alpha-helix-beta-structure transitions and serves biochemical core oscillator of the cellular biological clock. Period length is independent of temperature (temperature compensated) and synchrony is achieved through entrainment.

Topics: Aging; Amino Acid Motifs; Amino Acid Sequence; Animals; Biological Clocks; Cell Division; Cell Membrane; Coenzymes; Humans; Models, Biological; Molecular Sequence Data; Multienzyme Complexes; NADH, NADPH Oxidoreductases; Neoplasms; Neurodegenerative Diseases; Oxygen; Prions; Sequence Homology, Amino Acid; Temperature; Time Factors; Ubiquinone

Topics: Antioxidants; Ascorbic Acid; Coenzymes; Humans; Neoplasms; Ubiquinone; Vitamin E

Randomized controlled trials are generally regarded as the gold standard of study designs to determine causality. The inclusion of a placebo group in these trials, when appropriate, is critical to access the efficacy of a drug or supplement. The placebo response itself has received some attention in the medical literature over the past fifty years. The recent increasing utilization of dietary supplements and herbal medications by patients makes it imperative to reevaluate the placebo response in conventional and alternative medicine. This article will review some of the negative and positive results from randomized trials utilizing dietary supplements (androstenedione, beta-carotene, CoQ10, garlic, soy, vitamin C and E...) for a number of non-urologic and urologic conditions, including cancer.

Topics: Androstenedione; Antioxidants; beta Carotene; Coenzymes; Complementary Therapies; Dehydroepiandrosterone; Garlic; Heart Failure; Hot Flashes; Humans; Libido; Neoplasms; Placebo Effect; Randomized Controlled Trials as Topic; Ubiquinone; Vitamin E

Coenzyme Q10 or ubiquinone has been shown to have both anti-cancer and immune system enhancing properties when tested in animals. Preliminary results reported here suggest that it might inhibit tumour-associated cytokines. Clinical studies conducted with combination therapies of CoQ10 and other antioxidants are ongoing, but the results are difficult evaluate owing to the lack of proper control groups and of initial randomisation. Also on the basis of some anti-cancer effects of antioxidants reported in literature, further animal studies and a proper clinical trial of coenzyme Q10 in cancer patients are needed.

Topics: Animals; Anticarcinogenic Agents; Antineoplastic Agents; Antioxidants; Clinical Trials as Topic; Coenzymes; Cytokines; Humans; Neoplasms; Ubiquinone

The literature concerning the importance of coenzyme Q10 in health and disease has been reviewed. Usual dietary intake together with normal in vivo synthesis seems to fulfil the demands for Q10 in healthy individuals. The importance of Q10 supplementation for general health has not been investigated in controlled experiments. The literature allows no firm conclusions about the significance of Q10 in physical activity. In different cardiovascular diseases, including cardiomyopathy, relatively low levels of Q10 in myocardial tissue have been reported. Positive clinical and haemodynamic effects of oral Q10 supplementation have been observed in double-blind trials, especially in chronic heart failure. These effects should be further examined. No important adverse effects have been reported from experiments using daily supplements of up to 200 mg Q10 for 6-12 months and 100 mg daily for up to 6 y.

Topics: Cardiovascular Diseases; Dietary Supplements; Disease; Health; Humans; Neoplasms; Ubiquinone

New data on blood levels of vitamin Q10 in 116 cancer patients reveal an incidence of 23.1% of patients (N=17) with breast cancer whose blood levels were below 0.5 microg/ml. The incidence of breast cancer cases with levels below 0.6 microg/ml was 38.5%. The incidence is higher (p<0.05) than that for a group of ordinary people. Patients (N=15) with myeloma showed a mean blood level of 0.67 +/- 0.17 microg/ml. The incidence of a vitamin Q10 blood level below 0.7 microg/ml for these 15 cases of myeloma was 53.3%, which is higher (p<0.05) than the 24.5% found for a group of ordinary people.

Topics: Animals; Breast Neoplasms; Coenzymes; Female; Humans; Male; Multiple Myeloma; Neoplasms; Neoplasms, Experimental; Reference Values; Ubiquinone

Topics: Anticarcinogenic Agents; Antioxidants; Coronary Disease; Diet; Flavonoids; Humans; Neoplasms; Ubiquinone; Vitamins

Over ca. 25 years, assays in animal models established the hematopoietic activities of coenzyme Q's in rhesus monkeys, rabbits, poultry, and children having kwashiorkor. Surprisingly, a virus was found to cause a deficiency of CoQ9. Patients with AIDS showed a-"striking"-clinical response to therapy with CoQ10. The macrophage potentiating activity of CoQ10 was recorded by the carbon clearance method. CoQ10 significantly increased the levels of IgG in patients. Eight new case histories of cancer patients plus two reported cases support the statement that therapy of cancer patients with CoQ10, which has no significant side effect, has allowed survival on an exploratory basis for periods of 5-15 years. These results now justify systematic protocols.

Topics: Aged; Animals; Bone Marrow; Coenzymes; Female; Humans; Male; Middle Aged; Neoplasms; Survival Analysis; Ubiquinone

The role of Se in biology appears from the evidence now at hand to be as a catalyst par excellence. As unique prosthetic group of a variety of enzymes, presumably as Se(2-), Se functions with tocopherol to protect cell and organelle membranes from oxidative damage, to facilitate the union between oxygen and hydrogen at the end of the metabolic chain, and to transfer ions across cell membranes, in protein synthesis in erythrocytes and in liver organelles, in immunoglobulin synthesis, and in ubiquinone syntheses. As perhaps the most versatile and rapid nucleophile, Se is thought to amplify and orient SH in equilibrium -S-S-interactions involving glutathione and proteins. Its toxicity appears to be due to overaccumulation of selenite ions, which act as oxidants to inhibit SH interactions. Such toxicity is readily avoided or reversed in many ways. Although not yet recognized as essential for man, Se is clearly essential for many animal species and some microorganisms. As the active selenide, Se emerged as the target for many heavy metal toxicities; contrariwise, as a specific antidote against heavy metal toxicities. Despite all this, its unusual toxicity and the many preconceived notions about Se continue to confuse attitudes toward the safe uses of selenicals. From a suspected cause of cancer, Se metamorphosed, via evidence over many years, into something of possible anticancer value. Interrelations between Se, Vitamin E, the ubiquinones, and various chronic diseases appear as beckoning research areas. The reported veterinary values of Se-tocopherol combinations in animals, together with clinical evidence, plus human and animal evidence for safety, offer promise for intensive medical investigation. The historical confusion and misunderstandings regarding Se must be corrected, however, before advantage can be taken of its potential for human welfare. The many misjudgments about Se, ever since 1900 and more obviously since the 1930s, have involved other trace elements. Unrealistic regulations stemming from these misunderstandings prevail worldwide. Evidence suggests that, once the nutrition biochemistry and toxicology of Se is sufficiently understood and appreciated, major breakthroughs in agriculture, medicine, and public health can result. Much has been accomplished along these lines in New Zealand in animal agriculture, in the US and other countries in veterinary medicine, and in Mexico in human medicine.

Topics: Animals; Arthritis; Cattle; Chemical Phenomena; Chemistry; Cricetinae; Dermatitis; Haplorhini; Homeostasis; Humans; Immunity; Mice; Neoplasms; Nutritional Physiological Phenomena; Rabbits; Rats; Selenium; Sulfides; Suspensions; Trace Elements; Ubiquinone; Vitamin E

Topics: Aging; Animals; Animals, Domestic; Arsenic; Carcinogens; Drug Tolerance; Humans; Insecticides; Neoplasms; Nutrition Disorders; Selenium; Sulfur; Ubiquinone; Vitamin E

Topics: Animals; Cattle; Electron Transport; Hormones; Mitochondria, Liver; NAD; Neoplasms; Photosynthesis; Rats; Succinate Dehydrogenase; Ubiquinone; Vitamin A Deficiency; Vitamin E Deficiency

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

Lovastatin, an inhibitor of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (the major regulatory enzyme of the mevalonate pathway of cholesterol synthesis), displays antitumor activity in experimental models. We therefore conducted a Phase I trial to characterize the tolerability of lovastatin administered at progressively higher doses to cancer patients. From January 1992 to July 1994, 88 patients with solid tumors (median age, 57 +/- 14 years) were treated p.o. with 7-day courses of lovastatin given monthly at doses ranging from 2 to 45 mg/kg/day. The inhibitory effects of lovastatin were monitored through serum concentrations of cholesterol and ubiquinone, two end products of the mevalonate pathway. Concentrations of lovastatin and its active metabolites were also determined, by bioassay, in the serum of selected patients. Cyclical treatment with lovastatin markedly inhibited the mevalonate pathway, evidenced by reductions in both cholesterol and ubiquinone concentrations, by up to 43 and 49% of pretreatment values, respectively. The effect was transient, however, and its magnitude appeared to be dose independent. Drug concentrations reached up to 3.9 micrometer and were in the range associated with antiproliferative activity in vitro. Myopathy was the dose-limiting toxicity. Other toxicities included nausea, diarrhea, and fatigue. Treatment with ubiquinone was associated with reversal of lovastatin-induced myopathy, and its prophylactic administration prevented the development of this toxicity in a cohort of 56 patients. One minor response was documented in a patient with recurrent high-grade glioma. Lovastatin given p.o. at a dose of 25 mg/kg daily for 7 consecutive days is well tolerated. The occurrence of myopathy, the dose-limiting toxicity, can be prevented by ubiquinone supplementation. To improve on the transient inhibitory activity of this dosing regimen on the mevalonate pathway, alternative schedules based on uninterrupted administration of lovastatin should also be studied.

Topics: Adult; Aged; Antineoplastic Agents; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lovastatin; Male; Middle Aged; Neoplasms; Ubiquinone

Tissue resident memory CD8

Topics: Animals; CD8-Positive T-Lymphocytes; Cell Respiration; Cholesterol; Humans; Immunologic Memory; Intestine, Small; Lymphocytes, Tumor-Infiltrating; Metabolomics; Mevalonic Acid; Mice; Mitochondria; Neoplasms; Ubiquinone; Virus Diseases; Viruses

SMIP004-7 is a small molecule inhibitor of mitochondrial respiration with selective in vivo anti-cancer activity through an as-yet unknown molecular target. We demonstrate here that SMIP004-7 targets drug-resistant cancer cells with stem-like features by inhibiting mitochondrial respiration complex I (NADH:ubiquinone oxidoreductase, complex I [CI]). Instead of affecting the quinone-binding site targeted by most CI inhibitors, SMIP004-7 and its cytochrome P450-dependent activated metabolite(s) have an uncompetitive mechanism of inhibition involving a distinct N-terminal region of catalytic subunit NDUFS2 that leads to rapid disassembly of CI. SMIP004-7 and an improved chemical analog selectively engage NDUFS2 in vivo to inhibit the growth of triple-negative breast cancer transplants, a response mediated at least in part by boosting CD4

Topics: Electron Transport Complex I; Mitochondria; Neoplasms; Ubiquinone

Topics: Animals; Emulsions; G(M1) Ganglioside; Immunotherapy; Mice; N-Acetylneuraminic Acid; Neoplasms; Selectins; Ubiquinone

Ferroptosis, a new form of programmed cell death, not only promotes the pathological process of various human diseases, but also regulates cancer progression. Current perspectives on the underlying mechanisms remain largely unknown. Herein, we report a member of the NEET protein family, CISD3, exerts a regulatory role in cancer progression and ferroptosis both in vivo and in vitro. Pan-cancer analysis from TCGA reveals that expression of CISD3 is generally elevated in various human cancers which are consequently associated with a higher hazard ratio and poorer overall survival. Moreover, knockdown of CISD3 significantly accelerates lipid peroxidation and accentuates free iron accumulation triggered by Xc

Topics: Animals; Cell Line, Tumor; Cell Survival; Cystine; Disease Progression; Ferroptosis; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Glutamine; Homeostasis; Humans; Iron; Iron-Sulfur Proteins; Lipid Peroxides; Mice, Nude; Mitochondria; Mitochondrial Dynamics; Mitochondrial Proteins; Mitophagy; Neoplasms; Organophosphorus Compounds; Piperazines; Ubiquinone; Xenograft Model Antitumor Assays

Heat shock protein 90 (Hsp90) family proteins are molecular chaperones that modulate the functions of various substrate proteins (clients) implicated in pro-tumorigenic pathways. In this study, the mitochondria-targeted antioxidant mitoquinone (MitoQ) was identified as a potent inhibitor of mitochondrial Hsp90, known as a tumor necrosis factor receptor-associated protein 1 (TRAP1). Structural analyses revealed an asymmetric bipartite interaction between MitoQ and the previously unrecognized drug binding sites located in the middle domain of TRAP1, believed to be a client binding region. MitoQ effectively competed with TRAP1 clients, and MitoQ treatment facilitated the identification of 103 TRAP1-interacting mitochondrial proteins in cancer cells. MitoQ and its redox-crippled SB-U014/SB-U015 exhibited more potent anticancer activity

Topics: Animals; Antineoplastic Agents; Binding Sites; HeLa Cells; HSP90 Heat-Shock Proteins; Humans; Mice, Nude; Neoplasms; Organophosphorus Compounds; Ubiquinone; Xenograft Model Antitumor Assays

Extracellular glutamine represents an important energy source for many cancer cells and its metabolism is intimately involved in maintaining redox homeostasis. The heightened metabolic activity within tumor tissues can result in glutamine deficiency, necessitating metabolic reprogramming responses. Here, dual mechanisms involving the stress-responsive transcription factor DDIT3 (DNA damage induced transcript 3) that establishes an interrelationship between glycolysis and mitochondrial respiration are revealed. DDIT3 is induced during glutamine deprivation to promote glycolysis and adenosine triphosphate production via suppression of the negative glycolytic regulator TIGAR. In concert, a proportion of the DDIT3 pool translocates to the mitochondria and suppresses oxidative phosphorylation through LONP1-mediated down-regulation of COQ9 and COX4. This in turn dampens the sustained levels of reactive oxygen species that follow glutamine withdrawal. Together these mechanisms constitute an adaptive survival mechanism permitting tumor cells to survive metabolic stress induced by glutamine starvation.

Topics: Animals; Apoptosis Regulatory Proteins; Electron Transport Complex IV; Energy Metabolism; Gene Expression Regulation, Neoplastic; Glutamine; Glycolysis; HCT116 Cells; Humans; Mice; Mice, Knockout; Neoplasms; Oxidative Phosphorylation; Phosphoric Monoester Hydrolases; Transcription Factor CHOP; Ubiquinone

Oncogene activation and loss of tumor suppressor function changes the metabolic activity of cancer cells to drive unrestricted proliferation. Moreover, cancer cells adapt their metabolism to sustain growth and survival when access to oxygen and nutrients is restricted, such as in poorly vascularized tumor areas. We show here that p53-deficient colon cancer cells exposed to tumor-like metabolic stress in spheroid culture activated the mevalonate pathway to promote the synthesis of ubiquinone. This was essential to maintain mitochondrial electron transport for respiration and pyrimidine synthesis in metabolically compromised environments. Induction of mevalonate pathway enzyme expression in the absence of p53 was mediated by accumulation and stabilization of mature SREBP2. Mevalonate pathway inhibition by statins blocked pyrimidine nucleotide biosynthesis and induced oxidative stress and apoptosis in p53-deficient cancer cells in spheroid culture. Moreover, ubiquinone produced by the mevalonate pathway was essential for the growth of p53-deficient tumor organoids. In contrast, inhibition of intestinal hyperproliferation by statins in an Apc/KrasG12D-mutant mouse model was independent of

Topics: Animals; Apoptosis; Cell Line, Tumor; Cell Survival; Citric Acid Cycle; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Intestinal Mucosa; Mevalonic Acid; Mice; Mice, Transgenic; Neoplasms; Pyrimidines; Signal Transduction; Sterol Regulatory Element Binding Protein 2; Stress, Physiological; Tumor Microenvironment; Tumor Suppressor Protein p53; Ubiquinone; Xenograft Model Antitumor Assays

The mitochondrial electron transport chain (ETC) is necessary for tumour growth

Topics: Animals; Cell Line, Tumor; Cell Proliferation; Ciona intestinalis; Citric Acid Cycle; Cytosol; Dihydroorotate Dehydrogenase; Electron Transport; Electron Transport Complex I; Electron Transport Complex II; Electron Transport Complex III; Humans; Levilactobacillus brevis; Male; Mice; Mitochondria; Mitochondrial Proteins; Multienzyme Complexes; NAD; NADH, NADPH Oxidoreductases; Neoplasms; Oxidative Phosphorylation; Oxidoreductases; Oxidoreductases Acting on CH-CH Group Donors; Plant Proteins; Ubiquinone

Cancer cells without mitochondrial DNA (mtDNA) do not form tumors unless they reconstitute oxidative phosphorylation (OXPHOS) by mitochondria acquired from host stroma. To understand why functional respiration is crucial for tumorigenesis, we used time-resolved analysis of tumor formation by mtDNA-depleted cells and genetic manipulations of OXPHOS. We show that pyrimidine biosynthesis dependent on respiration-linked dihydroorotate dehydrogenase (DHODH) is required to overcome cell-cycle arrest, while mitochondrial ATP generation is dispensable for tumorigenesis. Latent DHODH in mtDNA-deficient cells is fully activated with restoration of complex III/IV activity and coenzyme Q redox-cycling after mitochondrial transfer, or by introduction of an alternative oxidase. Further, deletion of DHODH interferes with tumor formation in cells with fully functional OXPHOS, while disruption of mitochondrial ATP synthase has little effect. Our results show that DHODH-driven pyrimidine biosynthesis is an essential pathway linking respiration to tumorigenesis, pointing to inhibitors of DHODH as potential anti-cancer agents.

Topics: Animals; Cell Line, Tumor; Cell Respiration; Dihydroorotate Dehydrogenase; DNA, Mitochondrial; Humans; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mitochondria; Neoplasms; Oxidative Phosphorylation; Oxidoreductases Acting on CH-CH Group Donors; Pyrimidines; Ubiquinone

Coenzyme Q (CoQ) is an isoprenoid quinine that functions as an electron carrier in the mitochondrial respiratory chain in eukaryotes. CoQ having shorter isoprenoid chains, especially CoQ1 and CoQ2, selectively inhibited the in vitro activity of eukaryotic DNA polymerase (pol) gamma, which is a mitochondrial pol. These compounds did not influence the activities of nuclear DNA replicative pols such as alpha, delta and epsilon, and nuclear DNA repair-related pols such as beta, eta, iota, kappa and lambda. CoQ also inhibited DNA topoisomerase II (topo II) activity, although the enzymatic characteristics, including modes of action, amino acid sequences and three-dimensional structures, were markedly different from those of pol gamma. These compounds did not inhibit the activities of procaryotic pols such as Escherichia coli pol I, and other DNA metabolic enzymes such as human immunodeficiency virus reverse transcriptase, T7 RNA polymerase and bovine deoxyribonuclease I. CoQ1, which has the shortest isoprenoid chains, had the strongest inhibitory effect on pol gamma and topo II activities among CoQ1-CoQ10, with 50% inhibitory concentration (IC50) values of 12.2 and 15.5 microM, respectively. CoQ1 could prevent the growth of human promyelocytic leukemia cells, HL-60, and the 50% lethal dose (LD50) value was 14.0 microM. The cells were halted at S phase and G1 phase in the cell cycle, and suppressed mitochondrial proliferation. From these results, the relationship between the inhibition of pol gamma/topo II and cancer cell growth by CoQ is discussed.

Topics: Apoptosis; Cell Cycle; Cell Proliferation; DNA Polymerase gamma; DNA-Directed DNA Polymerase; HL-60 Cells; Humans; Inhibitory Concentration 50; Lethal Dose 50; Neoplasms; Nucleic Acid Synthesis Inhibitors; Topoisomerase II Inhibitors; Ubiquinone

Topics: Animals; Antineoplastic Agents; Antioxidants; Cisplatin; Coenzymes; Doxorubicin; Drug Interactions; Glutathione; Humans; Neoplasms; Oxidative Stress; Reactive Oxygen Species; Treatment Outcome; Ubiquinone

The objective of this study was to test the hypothesis that doxorubicin treatment for cancer in childhood and adolescence causes a dose-related decrease in the concentration of plasma coenzyme Q(10). The concentration of plasma coenzyme Q(10) was measured before and after administration of doxorubicin in six patients, and before and after chemotherapy in six patients undergoing treatments that did not include doxorubicin. There was a significant increase in the concentration of plasma coenzyme Q(10) in post-treatment samples compared to pre-treatment samples in patients treated with doxorubicin (P=0.008; n=32), whereas there were no significant changes in plasma coenzyme Q(10) concentrations in patients treated with chemotherapy that did not include doxorubicin. (P=0.770; n=30). We hypothesise that the increase in plasma coenzyme Q(10) that was observed in patients undergoing doxorubicin treatment is due to release of coenzyme Q(10) from apoptotic or necrotic cardiac tissue. We conclude that the cardiotoxicity due to doxorubicin therapy does not involve acute myocardial depletion of coenzyme Q(10).

Topics: Adolescent; Adult; Antineoplastic Agents; Antioxidants; Child; Child, Preschool; Cholesterol; Coenzymes; Cytoprotection; Doxorubicin; Female; Heart Diseases; Humans; Male; Neoplasms; Ubiquinone

In the human, coenzyme Q10 (vitamin Q10) is biosynthesized from tyrosine through a cascade of eight aromatic precursors. These precursors indispensably require eight vitamins, which are tetrahydrobiopterin, vitamins B6, C, B2, B12, folic acid, niacin, and pantothenic acid as their coenzymes. Three of these eight vitamins (the coenzyme B6, and the coenzymes niacin and folic acid) are indispensable in the biosynthesis of the four bases (thymidine, guanine, adenine, and cytosine) of DNA. One or more of the three vitamins required for DNA are known to cause abnormal pairing of the four bases, which can then result in mutations and the diversity of cancer. The coenzyme B6, required for the conversion of tyrosine to p-hydroxybenzoic acid, is the first coenzyme required in the cascade of precursors. A deficiency of the coenzyme B6 can cause dysfunctions, prior to the formation of vitamin Q10, to DNA. Former data on blood levels of Q10 and new data herein on blood levels of B6, measured as EDTA, in cancer patients established deficiencies of Q10 and B6 in cancer. This complete biochemistry relating to biosyntheses of Q10 and the DNA bases is a rationale for the therapy of cancer with Q10 and other entities in this biochemistry.

Topics: Breast Neoplasms; Coenzymes; DNA; Female; Humans; Incidence; Neoplasms; Purines; Pyrimidines; Reference Values; Sweden; Ubiquinone; Vitamins

The aim of the study was to quantify the use of alternative therapy, and especially the use of coenzyme Q10 in cancer patients. The study was conducted as a cross-sectional questionnaire study. During a two week period all in- and out-patients in the Department of Oncology and Haematology, Odense University Hospital, were asked about their use of alternative treatment. A total of 769 questionnaires were answered, a response rate of 97%. Of these patients 343 (45%) used alternative medicine, and 137 (18%) used coenzyme Q10. The use of alternative medicine and coenzyme Q10 was more frequent in women than in men, and in patients with recurrent disease than in patients with primary disease. A search of the literature revealed no documentation for the use of coenzyme Q10 either as an antineoplastic agent or as an adjunct to antineoplastic therapy. It might be possible that coenzyme Q10 can protect the myocardium from doxorubicin induced damage.

Topics: Adult; Age Factors; Female; Humans; Male; Middle Aged; Neoplasms; Sex Factors; Surveys and Questionnaires; Ubiquinone

Topics: Coenzymes; Free Radicals; Humans; Neoplasms; Ubiquinone

Serum levels of coenzyme Q10 (CoQ10) as well as lipids were determined in patients during total parenteral nutrition (TPN). The mean CoQ10 levels (M +/- SD) were 0.77 +/- 0.30 microgram/ml for 108 normal subjects and 0.59 +/- 0.35 microgram/ml for 95 patients before TPN. The mean CoQ10 level of the patients decreased significantly to 0.35 +/- 0.23 microgram/ml one week after the start of TPN, and then remained almost unchanged during TPN for up to 6 weeks. When the patients receiving TPN (TPN patients) were grouped according to their clinical diagnoses, the mean CoQ10 level of patients with cancer was significantly lower than that of the other patients without cancer in 4 week therapy, but there was no difference in the levels between the patients with and without diseases of the gastrointestinal tract. Serum levels of total cholesterol (T-Chol) and esterified cholesterol in TPN patients also declined below their respective normal ranges, but not to the same extent in comparison to CoQ10. The levels of triglycerides (TG), phospholipids (PL), non-esterified fatty acids, low density lipoproteins, very low density lipoproteins, chylomicrons, and cholesterol in the high density lipoprotein fraction in serum of TPN patients were within their normal ranges. The levels of CoQ10 in TPN patients were correlative to those of T-Chol, TG, and PL, and decreased rapidly prior to the latter levels.

Topics: Adolescent; Adult; Aged; Cholesterol; Coenzymes; Female; Health Status; Humans; Lipids; Male; Middle Aged; Neoplasms; Parenteral Nutrition, Total; Ubiquinone

Cardiotoxicity induced by adriamycin and protective effect by coenzyme Q10 were studied in 80 closely-followed patients receiving chemotherapy with adriamycin. Serial electrocardiograms were recorded immediately before and after the administration of adriamycin each times. The electrocardiographic parameters (heart rate, P-Q duration, QRS-duration, QRS voltage and QTc-duration) were analyzed. In patients treated with adriamycin alone, QTc-duration was prolonged significantly. On the other hand, in patients treated with adriamycin plus coenzyme Q10, QTc-duration was not significantly prolonged. This Suggests that coenzyme Q10 may reduce negative inotropic action induced by adriamycin. Further, the QRS voltage was also significantly decreased in patients treated with adriamycin alone, but was not decreased in patients treated with adriamycin plus coenzyme Q10. These findings suggest that some electrocardiographic changes due to adriamycin may be prevented by coenzyme Q10.

Topics: Coenzymes; Doxorubicin; Electrocardiography; Female; Gastrointestinal Neoplasms; Heart; Heart Rate; Humans; Leukemia; Lung Neoplasms; Lymphoma; Male; Middle Aged; Neoplasms; Time Factors; Ubiquinone

Three classes of immunostimulating drugs are described, each representing a different approach to the problem of pharmacological immunostimulation. The rationale for the use of microbes or microbial agents as immunostimulators rests on the fact that some micro-organisms, especially those that replicate intracellularly, carry a special potential to activate macrophages. Clinically, the use of these agents in patients with tumors and infections has been disappointing; however, there have been positive exceptions like the responsiveness of melanomas and bladder carcinomas to the injection of BCG. Many of the inconclusive results may be due to insecurities in the dosage of microbial preparations and to a general lack in standardization. Some structures with high efficacy and low toxicity which have recently evolved from this field deserve further investigation. A number of structurally unrelated synthetic compounds was found to influence immune parameters. Levamisole can today be classified as an immunostimulating drug with limited utility in recurring infections and in chronic polyarthritis. Several immunostimulating drugs which have attracted interest contain a purine as the effective component. This is not surprising in view of the fact that many genetically determined immunodeficiencies can be traced to defects of enzymes which play a crucial role in purine biosynthesis. Finally, the potential role of lymphokines as stimulators of the immunosystem is briefly described. Some of these glycoproteins have recently become available for clinical trials. Others will be made available through genetic engineering. The therapeutic utility of these compounds is not yet clear; they will, however, be of great value as probes for the study of immune functions and for the development of immunopharmacology.

Topics: Adjuvants, Immunologic; Animals; Bacterial Infections; Bacterial Vaccines; Humans; Immunity, Cellular; Immunization; Immunologic Deficiency Syndromes; Mice; Neoplasms; Polysaccharides, Bacterial; Ubiquinone

Topics: Aged; Breast Neoplasms; Cytochrome c Group; Dermatitis; Electron Transport; Female; Humans; Neoplasms; Radiation Injuries; Skin Ulcer; Ubiquinone; Uterine Cervical Neoplasms; Wound Healing

Topics: Adult; Aged; Coenzymes; Female; Humans; Immunoglobulin G; Male; Middle Aged; Neoplasms; Ubiquinone

An unique combination treatment for cancer patients has been attempted in our department. The treatment consists of 500 rad irradiation of cobalt 60 on the first day and drip infusion of mixture of 50mg adriamycin, 500mg cyclophosphamide and 500mg 5-fluorouracil on the next day. This combination therapy was repeated every 3 weeks. The myocardial intoxication may be a great problem in this therapy. Investigation was performed in 40 cancer patients in order to clarify of Coenzyme Q10 (CoQ10) could show any protecting effect upon the possible myocardial intoxication. All patients were divided into 2 groups; one with CoQ10 of 20 patients, who received CoQ10 of 90mg/day orally and the other without CoQ10 of 20 patients. In the group without CoQ10, cardiothoracic ratio (CTR) and pulse rate increased significantly in all patients and on ECG low voltage of QRS complex was seen in 2 cases, changes of ST-segment, T-wave and appearance of arrhythmia were more than frequent in the group without CoQ10 than that with CoQ10. It is concluded that CoQ10 is effective for protecting the myocardium in this cancer therapy.

Topics: Adult; Aged; Breast Neoplasms; Coenzymes; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Electrocardiography; Female; Fluorouracil; Heart; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Thyroid Neoplasms; Ubiquinone

Topics: Adjuvants, Immunologic; Animals; Anti-Bacterial Agents; Bacterial Infections; Humans; Immunity; Mice; Neoplasms; T-Lymphocytes; Ubiquinone

Topics: Adult; Aged; Aspartate Aminotransferases; Cardiac Output; Erythrocytes; Heart Rate; Humans; Middle Aged; Neoplasms; Succinate Dehydrogenase; Ubiquinone; Vitamin B 6 Deficiency

Topics: Alopecia; Animals; Doxorubicin; Drug Therapy, Combination; Neoplasms; Rabbits; Ubiquinone

Topics: Animals; Cattle; Doxorubicin; Heart; Humans; Hydroxybenzoates; Mitochondria; Mitochondria, Liver; Neoplasms; Rats; Ubiquinone

Topics: Animals; Antibody Formation; Antineoplastic Agents; Chick Embryo; Cricetinae; Haplorhini; Humans; Lipid Metabolism; Metabolism, Inborn Errors; Mice; Neoplasms; Peroxides; Phenylalanine; Rabbits; Rats; Sarcoma 180; Succinate Dehydrogenase; Turkeys; Tyrosine; Ubiquinone

Topics: Humans; Immunity; Immunotherapy; Mononuclear Phagocyte System; Neoplasms; Ubiquinone

Topics: Adult; Aged; Brain Neoplasms; Bronchial Neoplasms; Death, Sudden; DNA; Esophageal Neoplasms; Female; Heart Ventricles; Humans; Male; Middle Aged; Myocardium; Neoplasms; RNA; Stomach Neoplasms; Ubiquinone

Topics: Accidents; Adolescent; Adult; Aged; Aging; Animals; Child; Child, Preschool; Coronary Disease; Female; Heart Diseases; Humans; Infant; Infant, Newborn; Liver; Male; Middle Aged; Neoplasms; Rats; Refrigeration; Ubiquinone; Vitamin A

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: Autoradiography; Female; Humans; Leg; Melanoma; Middle Aged; Neoplasms; Radiation Protection; Radioisotopes; Radiotherapy Dosage; Tritium; Ubiquinone; Vitamin K

Topics: Animals; Anura; Clostridium; Fungi; Haplorhini; Insecta; Liver; Mice; Mycoplasma; Myocardium; Neoplasms; Neoplasms, Experimental; Nerve Tissue; Research; Sharks; Ubiquinone

Topics: Humans; Neoplasms; Quinones; Ubiquinone