vitamin-b-12 and Neoplasms

Cobalamin or vitamin B12 (B12) is a cofactor for methionine synthase and methylmalonyl-CoA mutase, two enzymes implicated in key pathways for cell proliferation: methylation, purine synthesis, succinylation and ATP production. Ensuring these functions in cancer cells therefore requires important cobalamin needs and its uptake through the transcobalamin II receptor (TCII-R). Thus, both the TCII-R and the cobalamin-dependent metabolic pathways constitute promising therapeutic targets to inhibit cancer development. However, the link between cobalamin and solid cancers is not limited to cellular metabolism, as it also involves the circulating transcobalamins I and II (TCI or haptocorrin and TCII) carrier proteins, encoded by

Topics: Humans; Neoplasms; Transcobalamins; Vitamin B 12

Patients with cancer have been reported to show elevated plasma concentrations of vitamin B12, thus causing uncertainties regarding safety of vitamin B12. We conducted a systematic literature search and a scoping review of human studies published in PubMed between January 2005 and March 2022, to investigate the association between vitamin B12 (concentrations of B12 biomarkers, intake, and genetic determinants) and cancer. Except for liver cancer, the association between plasma vitamin B12 concentrations and cancer was not consistent across the studies. Vitamin B12 intake from food, or food and supplements, showed even less consistent associations with cancer. There was no evidence for temporality, coherence, or a biologically meaningful dose-response relationship between plasma vitamin B12 concentrations and cancer. Genetically determined high plasma vitamin B12 was likely to be associated with cancer. Available randomized controlled trials have used a high dose of multivitamin supplements and cancer was the unplanned outcome, thus the causality of B12 in cancer cannot be judged based on these trials. Additionally, low plasma vitamin B12 concentrations were common in patients with cancer. Therefore, there is not sufficient evidence to assume that high plasma vitamin B12, high B12 intake, or treatment with pharmacological doses of vitamin B12, is causally related to cancer. Low vitamin B12 status in patients with cancer needs to be diagnosed and treated in order to prevent the hematological and neurological sequela of the deficiency.

Topics: Dietary Supplements; Folic Acid; Humans; Neoplasms; Nutritional Status; Vitamin B 12; Vitamin B 12 Deficiency; Vitamins

Chemotherapy and radiotherapy are the most frequent treatment for patients suffering from malignant progression of cancer. Even though new treatments are now being implemented, administration of these chemotherapeutic agents remains as the first line option in many tumor types. However, the secondary effects of these compounds represent one of the main reasons cancer patients lose life quality during disease progression. Recent data suggests that Ocoxin, a plant extract and natural compound based nutritional complement rich in antioxidants and anti-inflammatory mediators exerts a positive effect in patients receiving chemotherapy and radiotherapy. This mixture attenuates the chemotherapy and radiotherapy-related side effects such as radiation-induced skin burns and mucositis, chemotherapy-related diarrhea, hepatic toxicity and blood-infection. Moreover, it has been proven to be effective as anticancer agent in different tumor models both

Topics: Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; Chemoradiotherapy; Clinical Trials as Topic; Drug Resistance, Neoplasm; Drug Synergism; Drug-Related Side Effects and Adverse Reactions; Folic Acid; Humans; Neoplasms; Pantothenic Acid; Plant Extracts; Radiation Injuries; Radiation Tolerance; Treatment Outcome; Vitamin B 12; Vitamin B 6; Zinc Sulfate

Methionine dependence of tumor cell lines, the inability to grow in tissue culture media lacking methionine but supplemented with homocysteine, has been known for decades, but an understanding of the mechanism underlying this phenomenon remains incomplete. Methionine dependence of certain glioma and melanoma cell lines has been linked to alterations in the metabolism of cobalamin (vitamin B

Topics: DNA Methylation; Genomics; Humans; Methionine; Neoplasms; Oxidoreductases; Sequence Analysis, RNA; Vitamin B 12

The number of individuals partaking in veganism has increased sharply in the last decade. Therefore, it is critical to look at the implications of vegan diets for public health. Although there are multiple health benefits of a vegan diet, studies have also linked the diet with deficiencies in various micronutrients. This study focuses on vitamin B

Topics: Diet, Vegan; DNA Methylation; Humans; Neoplasms; Vitamin B 12; Vitamin B 12 Deficiency

Methionine-dependency is a common feature of cancer cells, which cannot proliferate without constant inputs of exogenous methionine even in the presence of its precursor, homocysteine. The endogenous synthesis of methionine is catalyzed by methionine synthase, which transfers the methyl group of 5-methyltetrahydrofolate (5-methylTHF) to homocysteine in the presence of vitamin B12 (cobalamin, cbl). Diverse mechanisms can produce it, including somatic mutations, aberrant DNA methylation (epimutations) and altered expression of genes. Around twenty somatic mutations have been reported as a cause of methionine dependency. Some of them are contributors but not sufficient on their own to cause methionine dependency. Epigenetic invalidation of MMACHC gene expression triggers methionine dependency of the MeWo-LC1 melanoma cancer cell line. This epimutation is generated by aberrant antisense transcription of the adjacent gene PRDX1. Methionine dependency involves the abnormal expression of 1-CM genes in cancer stem cells. It is related to an increased demand for methionine and SAM, which is not compensated by the increased production of formate by glycine decarboxylase pathway in lung cancer tumor spheres. Tumor spheres of glioblastoma U251 are methionine-dependent through disruption of folate metabolism. The rescue of the growth of glioblastoma stem cells by folate shows the considerable importance to evaluate the influence of supplements and dietary intake of folate on the risk of tumor development, in particular in countries subjected to mandatory food fortification in folic acid. Dietary methionine restriction or the use of methioninase represent promising anticancer therapeutic strategies that deserve to be explored in combination with chemotherapy.

Topics: Cell Line, Tumor; Epigenesis, Genetic; Folic Acid; Homocysteine; Humans; Methionine; Neoplasms; Neoplastic Stem Cells; Vitamin B 12

Environmental pollutants, such as pesticides, herbicides, additives to food and water, and electromagnetic fields threaten public health by promotion of cancer, heart disease and chronic diseases of aging. Many of these pollutants cause adverse health outcomes by effects on mitochondrial function to produce oxidative stress through loss of the active site complex for oxidative phosphorylation, thioretinaco ozonide oxygen nicotinamide adenine dinucleotide phosphate, from opening of the mitochondrial permeability transition pore. Glyphosate, fluoride, and electromagnetic fields are examples of carcinogenic pollutants that promote loss and decomposition of the active site for oxidative phosphorylation, producing mitochondrial dysfunction and oxidative stress. Ionizing radiation has long been known to be carcinogenic, and non-ionizing electromagnetic fields from microwaves, radar, cell phones and cathode ray screens are carcinogenic and produce deleterious effects on capillaries, nerve cells, blood brain barrier, embryonic and germ cells, lenses and cardiac function. Adverse health effects of electromagnetic fields include cataracts, infertility, congenital malformations, cancer, lymphocytosis, leukemia, hearing loss, blindness, retinal hemorrhages, cardiac arrhythmias, dermatitis, hair loss, depression, memory loss, premature aging, heart attacks, and weaponized mind control. The hyperhomocysteinemia, suppressed immunity, and altered oxidative metabolism observed in atherosclerosis and dementia are attributed to deficiency of adenosyl methionine which results from increased polyamine biosynthesis by pathogenic microbes that are demonstrated in atherosclerotic plaques and cerebral plaques. Thus, environmental pollutants potentially promote diseases of aging, atherosclerosis, cancer, and premature aging by production of mitochondrial dysfunction.

Topics: Aging; Animals; Atherosclerosis; Carcinogenesis; Electromagnetic Fields; Environmental Pollution; Fluorides; Glycine; Glyphosate; Homocysteine; Humans; Hyperhomocysteinemia; Mitochondria; Neoplasms; Oxidative Phosphorylation; Oxidative Stress; Vitamin B 12

Ocoxin Oral Solution (OOS) is a nutritional supplement whose formulation includes several plant extracts and natural products with demonstrated antitumoral properties. This review summarizes the antitumoral action of the different constituents of OOS. The action of this formulation on different preclinical models as well as clinical trials is reviewed, paying special attention to the mechanism of action and quality of life improvement properties of this nutritional supplement. Molecularly, its mode of action includes a double edge role on tumor biology, that involves a slowdown in cell proliferation accompanied by cell death induction. Given the safety and good tolerability of OOS, and its potentiation of the antitumoral effect of other standard of care drugs, OOS may be used in the oncology clinic in combination with conventional therapies.

Topics: Amino Acids; Animals; Antineoplastic Agents; Apoptosis; Ascorbic Acid; Cell Line, Tumor; Cell Proliferation; Cinnamomum zeylanicum; Dietary Supplements; Disease Models, Animal; Drug Evaluation, Preclinical; Folic Acid; Glucosamine; Glycyrrhiza; Humans; Neoplasms; Pantothenic Acid; Plant Extracts; Sucrose; Tea; Vitamin B 12; Vitamin B 6; Zinc Sulfate

The recently delineated structure- and reactivity-based concept of antivitamins B

Topics: Animals; Antimetabolites; Humans; Neoplasms; Vitamin B 12; Vitamins

A century ago a fat-soluble vitamin from leafy vegetables, later named vitamin E, was discovered to enhance fertility in animals. Vitamin E consists of 8 isomers of tocopherols and tocotrienols, each containing chromanol groups that confer antioxidant properties and differ only in the 15-carbon saturated phytyl poly-isoprenoid side chain of tocopherols and the 15-carbon unsaturated farnesyl poly-isoprenoid side chain of tocotrienols. Although tocotrienol was first isolated from rubber plants in 1964, its importance in multiple disease processes was not recognized until two decades later, when the cholesterol-lowering and anti-cancer effects were first reported. Tocotrienol (T3) protects against radiation injury and mitochondrial dysfunction by preventing opening of the mitochondrial permeability transition pore, thereby inhibiting loss of the active site for oxidative phosphorylation, thioretinaco ozonide oxygen ATP, from mitochondria by complex formation with the active site, TR

Topics: Aging; Animals; Arteriosclerosis; Cholesterol; Diterpenes; Homocysteine; Humans; Mitochondria; NAD; Neoplasms; Neurodegenerative Diseases; Oxidation-Reduction; Oxidative Phosphorylation; Permeability; Squalene; Tocotrienols; Vitamin B 12

High serum levels of vitamin B12 or cobalamin, also called hypervitaminemia B12, is a frequently underestimated biological abnormality. According to the literature, some of the entities related to this finding are solid neoplasia (primary or metastatic) and acute or chronic hematological diseases. Other causes include liver disorders, monoclonal gammapathy of undetermined significance, renal failure and, less frequently, excess of vitamin B12 intake, inflammatory or autoimmune diseases, and transient hematological disorders (neutrophilia and secondary eosinophilia). This article reports on causes of hypervitaminosis B12, our experience and a review of the literature.. Los altos niveles de vitamina B12 o cobalamina, también denominado hipervitaminosis B12 es una anormalidad analítica frecuentemente subestimada. De acuerdo con la literatura algunas de las entidades relacionadas con este hallazgo son las neoplasias sólidas (primarias o metastásicas) y las enfermedades hematológicas agudas o crónicas. Otras causas incluyen la afección hepática, la gammapatía monoclonal de significación indeterminada, la insuficiencia renal y, con menor frecuencia, un exceso de consumo de vitamina B12, enfermedades inflamatorias o autoinmunes y los trastornos hematológicos transitorios (neutrofilia y eosinofilia secundaria). Este artículo informa sobre causas de hipervitaminosis B12, nuestra experiencia y hace una revisión de la literatura.

Topics: Acute Kidney Injury; Hematologic Diseases; Humans; Liver Diseases; Neoplasms; Nutrition Disorders; Vitamin B 12

Topics: Adult; Aged; Alleles; Alzheimer Disease; Carbon; Child; Congenital Abnormalities; Female; Genotype; Homocysteine; Humans; Male; Methylmalonic Acid; Neoplasms; Polymorphism, Single Nucleotide; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency; White People

The purpose of this mini review is to evaluate the literature on B vitamins and chemotherapy-induced peripheral neuropathy.. One hundred and five journal articles were evaluated and nine manuscripts were included. There was one in vitro, one was an animal and seven were human studies. The in vitro study was a safety study on vitamin B

Topics: Animals; Humans; Neoplasms; Niacinamide; Organoplatinum Compounds; Oxaliplatin; Peripheral Nervous System Diseases; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Many nutrients are known for a wide range of activities in prevention and alleviation of various diseases. Recently, their potential role in regulating human health through effects on epigenetics has become evident, although specific mechanisms are still unclear. Thus, nutriepigenetics/nutriepigenomics has emerged as a new and promising field in current epigenetics research in the past few years. In particular, polyphenols, as part of the central dynamic interaction between the genome and the environment with specificity at physiological concentrations, are well known to affect mechanisms underlying human health. This review summarizes the effects of dietary compounds on epigenetic mechanisms in the regulation of gene expression including expression of enzymes and other molecules responsible for drug absorption, distribution, metabolism and excretion in cancer, metabolic syndrome, neurodegenerative disorders and hormonal dysfunction.

Topics: Antineoplastic Agents; Coffee; Curcumin; Diet; Epigenesis, Genetic; Folic Acid; Food; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; Humans; Metabolic Syndrome; Neoplasms; Neurodegenerative Diseases; Phytoestrogens; Polyphenols; S-Adenosylmethionine; Selenium; Trace Elements; Vitamin B 12; Vitamin B Complex; Vitamins

The Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is associated with various diseases (vascular, cancers, neurology, diabetes, psoriasis, etc) with the epidemiology of the polymorphism of the C677T that varies dependent on the geography and ethnicity. The 5,10-Methylenetetrahydrofolate reductase (MTHFR) locus is mapped on chromosome 1 at the end of the short arm (1p36.6). This enzyme is important for the folate metabolism which is an integral process for cell metabolism in the DNA, RNA and protein methylation. The mutation of the MTHFR gene which causes the C677T polymorphism is located at exon 4 which results in the conversion of valine to alanine at codon 222, a common polymorphism that reduces the activity of this enzyme. The homozygous mutated subjects have higher homocysteine levels while the heterozygous mutated subjects have mildly raised homocysteine levels compared with the normal, non-mutated controls. Hyperhomocysteinemia is an emerging risk factor for various cardiovascular diseases and with the increasing significance of this polymorphism in view of the morbidity and mortality impact on the patients, further prevention strategies and nutritional recommendations with the supplementation of vitamin B12 and folic acid which reduces plasma homocysteine level would be necessary as part of future health education. This literature review therefore focuses on the recent evidence-based reports on the associations of the MTHFR C677T polymorphism and the various diseases globally.

Topics: Diabetes Mellitus; Folic Acid; Genetic Predisposition to Disease; Homocysteine; Humans; Infertility; Mental Disorders; Methylenetetrahydrofolate Reductase (NADPH2); Neoplasms; Nervous System Diseases; Polymorphism, Genetic; Psoriasis; Vascular Diseases; Vitamin B 12

Antivitamins represent a broad class of compounds that counteract the essential effects of vitamins. The symptoms triggered by such antinutritional factors resemble those of vitamin deficiencies, but can be successfully reversed by treating patients with the intact vitamin. Despite being undesirable for healthy organisms, the toxicities of these compounds present considerable interest for biological and medicinal purposes. Indeed, antivitamins played fundamental roles in the development of pioneering antibiotic and antiproliferative drugs, such as prontosil and aminopterin. Their development and optimisation were made possible by the study, throughout the 20th century, of the vitamins' and antivitamins' functions in metabolic processes. However, even with this thorough knowledge, commercialised antivitamin-based drugs are still nowadays limited to antagonists of vitamins B9 and K. The antivitamin field thus still needs to be explored more intensely, in view of the outstanding therapeutic success exhibited by several antivitamin-based medicines. Here we summarise historical achievements and discuss critically recent developments, opportunities and potential limitations of the antivitamin approach, with a special focus on antivitamins K, B9 and B12 .

Topics: 4-Hydroxycoumarins; Animals; Anti-Bacterial Agents; Anticoagulants; Antineoplastic Agents; Bacteria; Bacterial Infections; Drug Discovery; Folic Acid; Folic Acid Antagonists; Humans; Indenes; Models, Molecular; Neoplasms; Vitamin B 12; Vitamin K; Vitamins

Hypercobalaminemia (high serum vitamin B12 levels) is a frequent and underestimated anomaly. Clinically, it can be paradoxically accompanied by signs of deficiency, reflecting a functional deficiency linked to qualitative abnormalities, which are related to defects in tissue uptake and action of vitamin B12. The aetiological profile of high serum cobalamin predominantly encompasses severe disease entities for which early diagnosis is critical for prognosis. These entities are essentially comprised of solid neoplasms, haematological malignancies and liver and kidney diseases. This review reflects the potential importance of the vitamin B12 assay as an early diagnostic marker of these diseases. A codified approach is needed to determine the potential indications of a search for high serum cobalamin and the practical clinical strategy to adopt upon discovery of elevated cobalamin levels. While low serum cobalamin levels do not necessarily imply deficiency, an abnormally high serum cobalamin level forms a warning sign requiring exclusion of a number of serious underlying pathologies. Functional cobalamin deficiency can thus occur at any serum level.

Topics: Biomarkers; Biomarkers, Tumor; Hematologic Diseases; Humans; Liver Diseases; Neoplasms; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

Hypervitaminemia B12 or high serum level of cobalamin B12 is a frequent and clinical underestimated abnormality. Clinically, it can be sometimes paradoxically accompanied by signs of deficiency reflecting a functional deficit in relation to qualitative abnormalities related to defects in tissue uptake and action of vitamin B12. Etiological profile of hypervitaminemias B12 has mostly serious disease entities and for which early diagnosis is crucial to the plan rather than prognostic. These entities are represented mainly by solid malignancies, hematological malignancies and liver diseases. This reflects the potential significance that may have the dosage of vitamin B12 as an early marker of diagnosis of these diseases. Codified approach is needed to determine the potential indications of the search for a hypervitaminemia B12 and practice what to do to pass before the discovery of a high serum level of cobalamin.

Topics: Hematologic Diseases; Humans; Liver Diseases; Metabolic Diseases; Models, Biological; Neoplasms; Professional Practice; Prognosis; Up-Regulation; Vitamin B 12

Proton pump (H(+)/K(+)-adenosine triphosphatase) inhibitors (PPIs) are widely used to treat patients with acid-related disorders because they are generally perceived to be safe and effective. However, as with any pharmacologic agent, they have the potential for side effects. Many studies have examined the side effects of long-term or short-term PPI exposure. We review the mechanism of action of PPIs, focusing on recently released products that might have greater risks of adverse effects than older products because of increased potency and/or duration of action. We summarize the data available on the putative adverse effects of PPI therapy and propose guidelines for clinicians who prescribe these agents to limit the potential for adverse outcomes in users of these effective therapeutic agents.

Topics: Animals; Bone and Bones; Calcium; Clopidogrel; Drug Interactions; Humans; Iron; Magnesium; Neoplasms; Proton Pump Inhibitors; Ticlopidine; Vitamin B 12

To review recent evidence that suggests vitamin B12 is associated with risk reduction for some chronic diseases and birth defects.. A MEDLINE search from 1999 to 2007 was performed using the key word vitamin B12. The most relevant articles (129) dealt with cardiovascular disease, cancer, mental health, and birth outcomes;most studies presented level II evidence.. Vitamin B12 might confer health benefits; however, such benefits are difficult to ascertain because of the complementary functions of vitamin B12 and folic acid. Vitamin B12 might lower high homocysteine levels below a threshold level achieved by folic acid alone. Furthermore, the interactions between the nutritional environment and genotype might have an important influence on vitamin B12, chronic disease risk, and risk of neural tube defects.. Vitamin B12 might help protect against chronic disease and neural tube defects, but more research, particularly in the area of nutritional genomics, is needed to determine how vitamin B12 might augment the benefits of folic acid. Some consideration should be given to the potential value of fortifying foods with vitamin B12 in addition to the current mandatory folic acid fortification of grains.

Topics: Cardiovascular Diseases; Congenital Abnormalities; Humans; Mental Disorders; Neoplasms; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B Complex

Topics: Antimetabolites, Antineoplastic; Drug Administration Schedule; Folic Acid; Glomerular Filtration Rate; Glutamates; Guanine; Humans; Kidney Failure, Chronic; Neoplasms; Pemetrexed; Vitamin B 12

Many studies have suggested that elevated homocysteine levels are an independent risk factor for cardiovascular disease, stroke and Alzheimer's disease. Lower levels of the three water-soluble vitamins--folate (folic acid), vitamin B6 and vitamin B12--are primary determinants of high blood homocysteine levels. In the fourth of an occasional series on vitamins, minerals and supplements, June Thompson looks at the role folate, in particular, may play in reducing homocysteine in the body and in protecting the body from some other diseases.

Topics: Alzheimer Disease; Cardiovascular Diseases; Chemoprevention; Dementia, Vascular; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Neoplasms; Primary Prevention; Risk Factors; Risk Reduction Behavior; Vitamin B 12; Vitamin B 6

Pemetrexed (ALIMTA, LY231514, MTA) is a novel antimetabolite that inhibits at least three enzymes involved in the folate pathway. These enzymes are thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase. Pemetrexed has demonstrated clinical activity in non-small cell lung cancer as well as in a broad array of other solid tumors, including mesothelioma, breast, colorectal, bladder, cervical, gastric and pancreatic cancer. In non-small cell lung cancer, single-agent activity has been documented in the first- and second-line settings in Phase II and Phase III trials. Promising activity has also been demonstrated when pemetrexed is combined with platinum compounds (cisplatin, carboplatin, and oxaliplatin), vinorelbine, and gemcitabine. Low level dietary supplement of folic acid and vitamin B12 has significantly decreased the mucosal and bone marrow toxicity of pemetrexed without compromising its antitumor effect.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Clinical Trials as Topic; Folic Acid; Glutamates; Guanine; Humans; Lung Neoplasms; Neoplasms; Pemetrexed; Platinum Compounds; Thymidylate Synthase; Vitamin B 12

Folate is a water-soluble B-vitamin and enzymatic cofactor that is necessary for the synthesis of purine and thymidine nucleotides and for the synthesis of methionine from homocysteine. Impairment of folate-mediated one-carbon metabolic pathways can result from B-vitamin deficiencies and/or single nucleotide polymorphisms, and increases risk for pathologies, including cancer and cardiovascular disease, and developmental anomalies including neural tube defects. Although several well validated metabolic and genomic biomarkers for folate deficiency exist, our understanding of the biochemical and genetic mechanisms whereby impaired folate metabolism increases risk for developmental anomalies and disease is limited, as are the mechanisms whereby elevated folate intake protects against these pathologies. Therefore, current initiatives to increase folate intakes in human populations to ameliorate developmental anomalies and prevent disease, while effective, lack predictive value with respect to unintended adverse outcomes.

Topics: Folic Acid; Food, Fortified; Humans; Neoplasms; Neural Tube Defects; Vitamin B 12

Inadequate folate status is associated with an increased risk for chronic diseases that may have a negative impact on the health of the aging population. Folate, a water-soluble vitamin, includes naturally occurring food folate and synthetic folic acid in supplements and fortified foods. Inadequate folate status may result in hyperhomocysteinemia, a significant risk factor for atherosclerotic vascular disease, changes in DNA that may result in pro-carcinogenic effects and increased risk for cognitive dysfunction. Folate status may be negatively influenced by inadequate intake, genetic polymorphisms and interactions with various drugs. In the US, folic acid is now added to enriched grain products and continues to be included in the majority of ready-to-eat breakfast cereals. Recent data indicate that the folate status in the US population has improved significantly, presumably due to the effects of fortification. Folic acid (not food folate) intake in excess of the Tolerable Upper Intake Level may mask the diagnosis of a vitamin B(12) deficiency, which is more prevalent in the elderly than younger individuals. When folic acid supplements are recommended, a multivitamin that includes vitamin B(12) should also be advised. To safely and effectively increase folate intake in the elderly, naturally occurring folate-rich food sources should be promoted. Folate-rich foods include orange juice, dark green leafy vegetables, asparagus, strawberries and legumes. These foods are also excellent sources of other health-promoting nutrients associated with chronic disease risk reduction.

Topics: Aged; Biological Availability; Cardiovascular Diseases; Cognition Disorders; Dietary Supplements; Female; Folic Acid; Folic Acid Deficiency; Food, Fortified; Humans; Male; Neoplasms; Nutrition Policy; Risk Factors; United States; Vegetables; Vitamin B 12; Vitamin B 12 Deficiency

Colorectal cancer and adenoma risk are inversely associated with higher total folate intake. Significant modifiers of cancer risk also include other methyl-related nutrients and alcohol. Adequate folate intake is particularly important for women at higher risk for breast cancer because of moderate alcohol consumption. The methylenetetrahydrofolate reductase (MTHFR) 677C-->T polymorphism is associated with a reduced risk of some forms of cancer. The protective effect of this folate-related polymorphism is dependent on adequate folate status. Cancer risk may be increased in individuals with the homozygous genotype for the MTHFR 677C-->T polymorphism who have low status of methyl-related nutrients including folate. Intake recommendations to potentially reduce cancer risk include substitution of low folate foods with folate-dense fruits and vegetables and in countries where there is no mandatory folic acid fortification, increased consumption of folic acid from available fortified foods or supplements. Adequate dietary intake of vitamin B-6 and methionine can be achieved by consumption of low fat, concentrated food sources of these nutrients. The recommended intake for vitamin B-12 for individuals >/==" BORDER="0">51 y should be provided predominately in crystalline form (e.g., fortified ready-to-eat cereal, supplements). If alcohol is consumed, consumption should be restricted to <15 g/d or <1 drink/d. The negative effects of low intakes of the methyl-related nutrients with high intakes of alcohol are additive, therefore changes in overall dietary patterns to ensure the consumption of a protective high methyl diet are recommended.

Topics: Adenoma; Alcohol Drinking; Colonic Neoplasms; Folic Acid; Humans; Methylation; Methylenetetrahydrofolate Reductase (NADPH2); Mutation, Missense; Neoplasms; Nutrition Policy; Polymorphism, Single Nucleotide; Risk Factors; Vitamin B 12

Diet is estimated to contribute to about one-third of preventable cancers -- about the same amount as smoking. Inadequate intake of essential vitamins and minerals might explain the epidemiological findings that people who eat only small amounts of fruits and vegetables have an increased risk of developing cancer. Recent experimental evidence indicates that vitamin and mineral deficiencies can lead to DNA damage. Optimizing vitamin and mineral intake by encouraging dietary change, multivitamin and mineral supplements, and fortifying foods might therefore prevent cancer and other chronic diseases.

Topics: Animals; Avitaminosis; DNA Damage; Folic Acid; Humans; Neoplasms; Nutritional Physiological Phenomena; Risk Factors; Trace Elements; Vitamin B 12; Vitamin B 6

Pemetrexed is a novel antifolate/antimetabolite that inhibits several folate-dependent enzymes, including thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide transformylase. As a class, antifolates have been associated with sporadic severe myelosuppression with gastrointestinal toxicity. Although infrequent, a combination of such toxicities carries a high risk of potentially life-threatening complications. Severe toxicity from pemetrexed-based therapy has become more predictable using the vitamin deficiency marker homocysteine and, to a lesser extent, methylmalonic acid. Evidence now suggests that reducing total plasma homocysteine levels by supplementation with folic acid and vitamin B(12) leads to a better safety profile for pemetrexed, while not adversely affecting its efficacy.

Topics: Antimetabolites, Antineoplastic; Clinical Trials as Topic; Folic Acid; Folic Acid Antagonists; Glutamates; Guanine; Homocysteine; Humans; Methylmalonic Acid; Neoplasms; Pemetrexed; Thymidylate Synthase; Vitamin B 12

Pemetrexed is a novel antifolate that inhibits several folate-dependent enzymes in addition to thymidylate synthase. Such a drug may have theoretical advantages over fluoropyrimidines and specifically acting antifolates. Phase I studies identified a preferred schedule of an intravenous dose once every 3 weeks. Phase II studies showed a broad spectrum of activity in solid tumors (ie, non-small cell lung, colorectal, and pancreatic cancers) usually considered refractory to most antimetabolites. Binary combinations with cisplatin, carboplatin, and gemcitabine have proven feasible and show encouraging activity in lung cancer and mesothelioma. Problems of sporadic life-threatening toxicity identified in early studies of this and other antifolates have been resolved by the discovery that they were caused by functional folate deficiency and may be avoided by a low-dose nutritional supplement of folic acid and vitamin B(12). Pemetrexed is a promising new drug that should make a contribution to solid tumor oncology.

Topics: Antimetabolites, Antineoplastic; Clinical Trials as Topic; Dietary Supplements; Drug Screening Assays, Antitumor; Folic Acid; Folic Acid Antagonists; Forecasting; Glutamates; Guanine; Humans; Neoplasms; Pemetrexed; Vitamin B 12

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: Abscess; Acute Disease; Antiviral Agents; Child; Ear Diseases; Electromyography; Facial Paralysis; Humans; Hypertension; Leukemia; Magnetic Resonance Imaging; Neoplasms; Neurophysiology; Radionuclide Imaging; Steroids; Virus Diseases; Vitamin B 12

In this review many examples are given of the complexities involved in using some biomarkers in relation to assessing the effects of dietary exposure, when there is frequently a need to determine changes following long-term low level exposure to dietary components. These range from understanding why the biomarker might be valuable and how best it can be measured, to the pitfalls which can occur in the interpretation of data. Analytical technique is considered in relation to folate and selenium, and flavonoid and carotenoid species are used to illustrate how the metabolism of a compound may alter the validity or adequacy of a marker. Vitamin A is discussed in relation to the difficulties which can arise when there are several biomarkers that may be available to assess exposure to one nutrient. Vitamin B12 is discussed in relation to the dietary choices made by individuals. Possible interactions and the role of measuring total antioxidant capacity is considered in some detail. In contrast to most nutrients, there is a marked lack of biomarkers of either exposure or effect for most non-nutrients. The role of biological effect monitoring is considered for dietary contaminants, fumonisins and polyhalogenated aromatic hydrocarbons. Aflatoxins are discussed to exemplify food contaminants for which the biomarker approach has been extensively studied. Finally some compounds which are deliberately added to foods and some which appear as processing contaminants are each considered briefly in relation to the requirement for a biomarker of exposure to be developed.

Topics: Aflatoxins; Antioxidants; Biomarkers; Brassica; Carotenoids; Developing Countries; Diet; Environmental Exposure; Flavonoids; Folic Acid; Food Additives; Food Analysis; Food Contamination; Free Radicals; Genetic Predisposition to Disease; Humans; Intestinal Absorption; Meat; Neoplasms; Nutritional Status; Polycyclic Aromatic Hydrocarbons; Predictive Value of Tests; Reproducibility of Results; Selenium; Selenium Compounds; Sensitivity and Specificity; Vitamin A; Vitamin B 12; Vitamin B Deficiency

Classically, deficiency of folic acid (folate) or vitamin B12 (cobalamin) was recognized by the presence of a macrocytic anemia resulting from megaloblastic changes in the bone marrow. A markedly changing paradigm has identified both new mechanisms for altered folate and cobalamin status and new sequelae and clinical interrelationships that include altered mechanisms of absorption, a changing pattern of neurologic deficits, an increased risk of vascular occlusive lesions, and an important relationship with the mechanisms of neoplastic transformation. Several of these newer characterizations relate to issues of neoplasia in the nonpregnant woman and to issues in pregnancy, such as the potential for developmental abnormalities of the fetal nervous system.

Topics: Anemia, Megaloblastic; Anemia, Pernicious; Female; Folic Acid; Folic Acid Deficiency; Humans; Hyperhomocysteinemia; Neoplasms; Neural Tube Defects; Pregnancy; Pregnancy Complications; Pregnancy Complications, Hematologic; Vascular Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Animals; Antibody Formation; Carcinogens; Choline; Choline Deficiency; Diet; DNA; Folic Acid; Folic Acid Deficiency; Humans; Immunity, Cellular; Lipotropic Agents; Liver; Liver Neoplasms; Methionine; Methylation; Neoplasms; Neoplasms, Experimental; Pharmaceutical Preparations; Risk; Tetrahydrofolates; Vitamin B 12; Vitamin B 12 Deficiency

This monograph on the clinical chemistry of vitamin B12 reviews the literature on daily requirements, methods for measurement, the effects of drugs on vitamin B12 metabolism absorption, pregnancy, clinical conditions associated with vitamin B12 deficiency, errors of metabolism, and reactions to vitamin therapy. Although only very small quantities of vitamin B12 are required to satisfy the daily requirement, a sufficient supply is stored in the liver to meet normal requirements for at least a 3-year period. A number of drugs are known to affect the absorption of vitamin B12, including neomycin, potassium chloride, p-aminosalicylic acid, and colchicine. Significantly reduced serum concentrations of vitamin B12 have been noted in users of oral contraceptives (OCs), although concentrations still remain within the limits of normal. It appears that the vitamin B12 level in OC users reestablishes itself at a different and somewhat lower level. Vitamin B12 binding protein appears to remain unchanged. A vitamin B12 deficiency is unusual in pregnant women who consume a normal, varied diet. On the other hand, lactating women whose diets are low in animal protein and dairy products may have problems providing enough vitamin B12 to meet their own and their infant's needs; supplementary oral vitamins should be considered.

Topics: Absorption; Adult; Alcoholism; Anemia, Pernicious; Ascorbic Acid; Autoantibodies; Biguanides; Biological Transport; Chemical Phenomena; Chemistry; Chlorpromazine; Contraceptives, Oral; Diet; Female; Gastrectomy; Gastritis; Humans; Intrinsic Factor; Malabsorption Syndromes; Male; Metabolism, Inborn Errors; Middle Aged; Neoplasms; Nervous System Diseases; Nitrous Oxide; Nutritional Requirements; Pancreatic Diseases; Parasitic Diseases; Pregnancy; Pregnancy Complications; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adolescent; Adult; Aged; Aging; Animals; Child; Child, Preschool; Cobamides; Cyanides; Female; Food Analysis; Humans; Infant; Infant, Newborn; Intestinal Absorption; Lactation; Methods; Middle Aged; Neoplasms; Nitrous Oxide; Papio; Pregnancy; Streptomyces griseus; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Age Factors; Animals; Blood Coagulation; Cerebrovascular Disorders; Chemical and Drug Induced Liver Injury; Contraceptives, Oral; Contraceptives, Oral, Hormonal; Coronary Disease; Folic Acid; Humans; Hypertension; Metabolism; Myocardial Infarction; Neoplasms; Progestins; Skin; Smoking; Teratogens; Thromboembolism; Time Factors; Vitamin B 12

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Animals; Cells, Cultured; Cobamides; Enzyme Activation; Flavoproteins; Leukemia L1210; Methionine; Methyltransferases; Mice; NADP; Neoplasms; S-Adenosylmethionine; Transcobalamins; Vitamin B 12

Topics: Anemia; Anemia, Hemolytic; Blood Circulation; Bone Marrow; Catalase; Erythrocytes; Ferritins; Hemoglobins; Hemolysis; Hemorrhage; Humans; Iron; Metals; Mononuclear Phagocyte System; Neoplasm Metastasis; Neoplasms; Polysaccharides, Bacterial; Regional Blood Flow; Vitamin B 12

Topics: Humans; Neoplasms; Vitamin B 12

Topics: Chlortetracycline; Humans; Microscopy; Microscopy, Fluorescence; Myocardial Infarction; Neoplasms; Tetracycline; Trichloroacetic Acid; Ultraviolet Rays; Vitamin B 12

Folic acid and vitamin B12 play key roles in one-carbon metabolism. Disruption of one-carbon metabolism may be involved in the risk of cancer. Our aim was to assess the long-term effect of supplementation with both folic acid and vitamin B12 on the incidence of overall cancer and on colorectal cancer in the B Vitamins for the Prevention of Osteoporotic Fractures (B-PROOF) trial.. Long-term follow-up of B-PROOF trial participants (. Allocation to B vitamins was associated with a higher risk of overall cancer [171 (13.6%) vs. 143 (11.3%); HR 1.25; 95% confidence interval (CI), 1.00-1.53,. Folic acid and vitamin B12 supplementation was associated with an increased risk of colorectal cancer.. Our findings suggest that folic acid and vitamin B12 supplementation may increase the risk of colorectal cancer. Further confirmation in larger studies and in meta-analyses combining both folic acid and vitamin B12 are needed to evaluate whether folic acid and vitamin B12 supplementation should be limited to patients with a known indication, such as a proven deficiency.

Topics: Aged; Aged, 80 and over; Colorectal Neoplasms; Dietary Supplements; Double-Blind Method; Female; Folic Acid; Follow-Up Studies; Humans; Incidence; Male; Neoplasms; Netherlands; Osteoporotic Fractures; Vitamin B 12

The objective of the proposed clinical interventional trial is to demonstrate the efficacy of a novel therapeutic strategy in subjects with cancer and hyperhomocysteinemia. Following discovery of abnormal homocysteine thiolactone metabolism in cultured malignant cells, thioretinamide, the amide synthesized from retinoic acid and homocysteine thiolactone, and thioretinaco, the complex formed from cobalamin and thioretinamide, were demonstrated to have antineoplastic, anticarcinogenic, and anti-atherogenic properties in animal models. Retinol, ascorbate, and homocysteine thiolactone are necessary for biosynthesis of thioretinamide and thioretinaco by cystathionine synthase and for formation of thioretinaco ozonide from thioretinamide, cobalamin, and ozone. Thioretinaco ozonide is required for prevention of abnormal oxidative metabolism, aerobic glycolysis, suppressed immunity, and hyperhomocysteinemia in cancer.The pancreatic enzyme therapy of cancer promotes catabolism of proteins, nucleic acids, and glycosaminoglycans with excess homocysteinylated amino groups resulting from abnormal accumulation of homocysteine thiolactone in malignant cells. Dietary deficiencies of pyridoxal, folate, cobalamin, and nitriloside contribute to hyperhomocysteinemia in cancer, and in protein energy malnutrition. A deficiency of dietary sulfur amino acids downregulates cystathionine synthase, causing hyperhomocysteinemia.The organic sulfur compound diallyl trisulfide increases hydrogen sulfide production from homocysteine in animal models, inhibits Stat3 signaling in cancer stem cells, and produces apoptosis of malignant cells. The furanonaphthoquinone compound napabucasin inhibits Stat3 signaling and causes mitochondrial dysfunction, decreased oxidative phosphorylation, and apoptosis of malignant cells. The protocol of the proposed clinical trial in subjects with myelodysplasia consists of thioretinamide and cobalamin as precursors of thioretinaco ozonide, combined with pancreatic enzyme extracts, diallyl trisulfide, napabucasin, nutritional modification to minimize processed foods, vitamin supplements, essential amino acids, and beneficial dietary fats and proteins.

Topics: Adult; Aged; Aging; Drugs, Investigational; Homocysteine; Humans; Licensure; Middle Aged; Neoplasms; Oxidative Phosphorylation; Vitamin B 12

To advance knowledge about the cancer-chemopreventive potential of individual nutrients, we investigated the effects of B vitamin and/or ω-3 fatty acid supplements on cancer outcomes among survivors of cardiovascular disease.. This was an ancillary study of the Supplementation With Folate, Vitamins B(6) and B(12) and/or Omega-3 Fatty Acids (SU.FOL.OM3) secondary prevention trial (2003-2009). In all, 2501 individuals aged 45 to 80 years were randomized in a 2 × 2 factorial design to one of the following 4 daily supplementation groups: (1) 5-methyltetrahydrofolate (0.56 mg), pyridoxine hydrochloride (vitamin B(6); 3 mg) and cyanocobalamin (vitamin B(12); 0.02 mg); (2) eicosapentaenoic and docosahexaenoic acid (600 mg) in a 2:1 ratio; (3) B vitamins and ω-3 fatty acids; or (4) placebo. Overall and sex-specific hazard ratios (HRs) and 95% CIs regarding the cancer outcomes were estimated with Cox proportional hazards models.. After 5 years of supplementation, incident cancer was validated in 7.0% of the sample (145 events in men and 29 in women), and death from cancer occurred in 2.3% of the sample. There was no association between cancer outcomes and supplementation with B vitamins (HR, 1.15 [95% CI, 0.85-1.55]) and/or ω-3 fatty acids (HR, 1.17 [95% CI, 0.87-1.58]). There was a statistically significant interaction of treatment by sex, with no effect of treatment on cancer risk among men and increased cancer risk among women for ω-3 fatty acid supplementation (HR, 3.02 [95% CI, 1.33-6.89]).. We found no beneficial effects of supplementation with relatively low doses of B vitamins and/or ω-3 fatty acids on cancer outcomes in individuals with prior cardiovascular disease. Trial Registration  isrctn.org Identifier: ISRCTN41926726.

Topics: Aged; Aged, 80 and over; Anticarcinogenic Agents; Biomarkers; Chemoprevention; Dietary Supplements; Fatty Acids, Omega-3; Female; Folic Acid; Humans; Incidence; Male; Middle Aged; Neoplasms; Odds Ratio; Proportional Hazards Models; Research Design; Risk Factors; Secondary Prevention; Sex Factors; Treatment Failure; United States; Vitamin B 12; Vitamin B 6

Folate, vitamin B(6), and vitamin B(12) are thought to play an important role in cancer prevention.. To evaluate the effect of combined folic acid, vitamin B(6), and vitamin B(12) treatment on cancer risk in women at high risk for cardiovascular disease.. In the Women's Antioxidant and Folic Acid Cardiovascular Study, 5442 US female health professionals aged 42 years or older, with preexisting cardiovascular disease or 3 or more coronary risk factors, were randomly assigned to receive either a daily combination of folic acid, vitamin B(6), and vitamin B(12) or a matching placebo. They were treated for 7.3 years from April 1998 through July 31, 2005.. Daily supplementation of a combination of 2.5 mg of folic acid, 50 mg of vitamin B(6), and 1 mg of vitamin B(12) (n = 2721) or placebo (n = 2721).. Confirmed newly diagnosed total invasive cancer or breast cancer.. A total of 379 women developed invasive cancer (187 in the active treatment group and 192 in the placebo group). Compared with placebo, women receiving the active treatment had similar risk of developing total invasive cancer (101.1/10,000 person-years for the active treatment group vs 104.3/10,000 person-years for placebo group; hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.79-1.18; P = .75), breast cancer (37.8/10,000 person-years vs 45.6/10,000 person-years, respectively; HR, 0.83; 95% CI, 0.60-1.14; P = .24), or any cancer death (24.6/10,000 person-years vs 30.1/10,000 person-years, respectively; HR, 0.82; 95% CI, 0.56-1.21; P = .32).. Combined folic acid, vitamin B(6), and vitamin B(12) treatment had no significant effect on overall risk of total invasive cancer or breast cancer among women during the folic acid fortification era.. clinicaltrials.gov Identifier: NCT00000541.

Topics: Adult; Aged; Antioxidants; Breast Neoplasms; Cardiovascular Diseases; Dietary Supplements; Double-Blind Method; Female; Folic Acid; Follow-Up Studies; Humans; Middle Aged; Neoplasms; Risk; Vitamin B 12; Vitamin B 6; Vitamin B Complex

This phase I study was conducted to determine the toxicities, pharmacokinetics, and recommended doses of pemetrexed in cancer patients with normal and impaired renal function.. Patients received a 10-minute infusion of 150 to 600 mg/m2 of pemetrexed every 3 weeks. Patients were stratified for independent dose escalation by measured glomerular filtration rate (GFR) into four cohorts ranging from > or = 80 to less than 20 mL/min. Pemetrexed plasma and urine pharmacokinetics were evaluated for the first cycle. Patients enrolled after December 1999 were supplemented with oral folic acid and intramuscular vitamin B12.. Forty-seven patients were treated with 167 cycles of pemetrexed. Hematologic dose-limiting toxicities occurred in vitamin-supplemented patients (two; 15%) and non-supplemented patients (six; 18%), and included febrile neutropenia (four patients) and grade 4 thrombocytopenia (two patients). Nonhematologic toxicities included fatigue, diarrhea, and nausea, and did not correlate with renal function. Accrual was discontinued in patients with GFR less than 30 mL/min after one patient with a GFR of 19 mL/min died as a result of treatment-related toxicities. Pemetrexed plasma clearance positively correlated with GFR (r2 = 0.736), resulting in increased drug exposures in patients with impaired renal function. With vitamin supplementation, pemetrexed 600 mg/m2 was tolerated by patients with a GFR > or = 80 mL/min, whereas patients with a GFR of 40 to 79 mL/min tolerated a dose of 500 mg/m2.. Pemetrexed was well tolerated at doses of 500 mg/m2 with vitamin supplementation in patients with GFR > or = 40 mL/min. Additional studies are needed to define appropriate dosing for renally impaired patients receiving higher dose pemetrexed with vitamin supplementation.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Diarrhea; Drug Administration Schedule; Fatigue; Female; Folic Acid; Glutamates; Guanine; Humans; Kidney Failure, Chronic; Male; Middle Aged; Nausea; Neoplasms; Neutropenia; Pemetrexed; Thrombocytopenia; Vitamin B 12

The purpose of this study was to determine the maximum tolerated dose (MTD) and recommended dose (RD) of pemetrexed with folate and vitamin B12 supplementation (FA/VB(12)) in Japanese patients with solid tumours and to investigate the safety, efficacy, and pharmacokinetics of pemetrexed. Eligible patients had incurable solid tumours by standard treatments, a performance status 0-2, and adequate organ function. Pemetrexed from 300 to 1,200 mg m(-2) was administered as a 10-min infusion on day 1 of a 21-day cycle with FA/VB(12). Totally, 31 patients were treated. Dose-limiting toxicities were alanine aminotransferase (ALT) elevation at 700 mg m(-2), and infection and skin rash at 1,200 mg m(-2). The MTD/RD were determined to be 1,200/1,000 mg m(-2), respectively. The most common grade 3/4 toxicities were neutropenia (grade (G) 3:29, G4:3%), leucopenia (G3:13, G4:3%), lympopenia (G3:13%) and ALT elevation (G3:13%). Pemetrexed pharmacokinetics in Japanese were not overtly different from those in western patients. Partial response was achieved for 5/23 evaluable patients (four with non-small cell lung cancer (NSCLC) and one with thymoma). The MTD/RD of pemetrexed were determined to be 1,200/1,000 mg m(-2), respectively, that is, a higher RD than without FA/VB(12) (500 mg m(-2)). Pemetrexed with FA/VB(12) showed a tolerable toxicity profile and potent antitumour activity against NSCLC in this study.

Topics: Adult; Aged; Alanine Transaminase; Antineoplastic Agents; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Folic Acid; Glutamates; Guanine; Humans; Infusions, Intravenous; Japan; Male; Maximum Tolerated Dose; Middle Aged; Neoplasms; Neutropenia; Pemetrexed; Safety; Treatment Outcome; Vitamin B 12

Capecitabine is a novel fluoropyrimidine carbamate which is selectively activated after oral administration to 5-fluorouracil (5-FU) by a sequential triple enzyme pathway in liver and tumor cells. The cytotoxic activity of the metabolized 5-FU depends on thymidylate synthase (TS) inhibition, leading to defective DNA synthesis. Capecitabine has shown promising activity in all tumor types sensitive to 5-FU and is therefore investigated in many clinical trials. Since we observed an increase of mean corpuscular volume (MCV) of red blood cells under therapy with capecitabine, the current investigation aimed to quantitate this effect and to elucidate the underlying mechanisms. A total of 154 patients suffering from advanced cancer received capecitabine (2500 mg/m2/day for 14 days every 21 days) either as monotherapy, or in combination with other antineoplastic agents or biological response modifiers. During 3 consecutive cycles of therapy a complete blood cell count including the red cell indices MCV, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration was performed before each application of capecitabine. In addition, vitamin B12, folic acid and homocysteine were determined to define their role in increasing MCV. Restaging was performed after 9 weeks. Within 9 weeks, a statistically significant increase of MCV (without other hematologic abnormalities or clinical symptoms) could be observed (p<0.0001). Vitamin B12, folic acid and homocysteine levels did not change significantly during the observation period. When comparing the different increases of MCV during 9 weeks (deltaMCV) with respect to tumor response, deltaMCV tended to higher values in patients with tumor remission or stable disease than in patients with tumor progression. We conclude that serum levels within the normal range rule out severe deficiencies of vitamin B12, folic acid or homocysteine as an account of macrocytemia. We therefore hypothesize that an increased MCV (without concomitant anemia) in patients receiving capecitabine might be due to the 5-FU-induced TS inhibition also in erythroid precursor cells. Whether this increase in MCV might serve as a surrogate marker for tumor response has to be evaluated in further investigations.

Topics: Antimetabolites, Antineoplastic; Capecitabine; Deoxycytidine; Erythrocyte Indices; Erythrocytes; Female; Fluorouracil; Folic Acid; Hematinics; Homocysteine; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Retrospective Studies; Thymidylate Synthase; Vitamin B 12

The relationship between vitamin B12 levels and survival was studied in a group of 161 terminally ill cancer patients who were recruited consecutively between 1988 and 1989. Their average age was 74.7 years. The length of survival decreased with the increase in serum vitamin B12 levels (P = 0.0015, Cox model). In multivariate analyses, C-reactive protein (CRP) was the most important prognostic factor in this population, and vitamin B12 provided information independent of CRP in predicting survival. These data indicate that an elevated serum vitamin B12 level is a predictive factor for mortality in patients with cancer, independent of CRP or other factors. Multiplying it by the CRP makes it possible to create a new, easy-to-use prognostic index, which can distinguish different levels of mortality risk at three months.

Topics: Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Neoplasms; Pain; Palliative Care; Prognosis; Prospective Studies; Vitamin B 12

Topics: Analgesics; Clinical Trials as Topic; Cobamides; Coenzymes; Drug Tolerance; Female; Humans; Male; Neoplasms; Nerve Degeneration; Pain; Peripheral Nervous System Diseases; Vitamin B 12

Topics: Clinical Trials as Topic; Cobamides; Female; Humans; Neoplasms; Vitamin B 12

Based on the data of foreign and domestic literature, the question of the possible carcinogenesis of vitamin B

Topics: Administration, Oral; Humans; Neoplasms; Thiamine; Vitamin B 12; Vitamin B 12 Deficiency; Vitamins

Impact of micronutrient deficiency on childhood malignancy is unexplored. We estimated the prevalence of baseline micronutrient deficiency in children with cancer and its impact on event-free survival (EFS) and overall survival (OS).. Total 535 children [326 (60.9%) haematological and 209 (39.1%) solid malignancies] were enrolled with median follow-up of 66 months. Vitamin B. Selenium deficiency was independently predictive of adverse outcomes in childhood cancer, particularly in haematological malignancies. Zinc deficiency adversely affected solid tumours. The adjunct use of micronutrient supplementation in paediatric malignancies should be explored.

Topics: Child; Copper; Folic Acid; Hematologic Neoplasms; Humans; Longitudinal Studies; Malnutrition; Micronutrients; Neoplasms; Prevalence; Prospective Studies; Selenium; Vitamin B 12; Vitamins; Zinc

Suppressor of mothers against decapentaplegic homolog (SMAD) 4 is a pluripotent signaling mediator that regulates myriad cellular functions, including cell growth, cell division, angiogenesis, apoptosis, cell invasion, and metastasis, through transforming growth factor β (TGF-β)-dependent and -independent pathways. SMAD4 is a critical modulator in signal transduction and functions primarily as a transcription factor or cofactor. Apart from being a DNA-binding factor, the additional SMAD4 mechanisms in tumor suppression remain elusive. We previously identified methyl malonyl aciduria cobalamin deficiency B type (MMAB) as a critical SMAD4 binding protein using a proto array analysis. This study confirmed the interaction between SMAD4 and MMAB using bimolecular fluorescence complementation (BiFC) assay, proximity ligation assay (PLA), and conventional immunoprecipitation. We found that transient SMAD4 overexpression down-regulates MMAB expression via a proteasome-dependent pathway. SMAD4-MMAB interaction was independent of TGF-β signaling. Finally, we determined the effect of MMAB downregulation on cancer cells. siRNA-mediated knockdown of MMAB affected cancer cell metabolism in HeLa cells by decreasing ATP production and glucose consumption as well as inducing apoptosis. These findings suggest that SMAD4 controls cancer cell metabolism by regulating MMAB.

Topics: Amino Acid Metabolism, Inborn Errors; Cell Line, Tumor; HeLa Cells; Humans; Neoplasms; Smad4 Protein; Transforming Growth Factor beta; Vitamin B 12

Previous experimental studies showed that limiting methionine in the diet of animals or in cell culture media suppresses mammary cancer cell proliferation or metastasis. However, no previous study has investigated the associations of changes in methionine intake with survival among breast cancer survivors. We aimed to examine the association between changes in dietary intake of methionine, folate/folic acid, and vitamin B12 from before to after diagnosis of breast cancer, and mortality among breast cancer survivors.. We included 1553 postmenopausal women from the Women's Health Initiative who were diagnosed with invasive breast cancer and completed a food frequency questionnaire both before and after breast cancer diagnosis. Multivariable Cox proportional hazards regression models were used to estimate adjusted hazard ratios (HRs) and 95% confidence (CIs) of all-cause and breast cancer mortality associated with changes in methionine intake and changes in folate/folic acid and vitamin B12 intake.. Relative to pre-diagnosis, 28% of women decreased methionine intake by ≥20%, 30% of women increased methionine intake by ≥20%, and 42% of women had a relatively stable methionine intake (±19.9%) following breast cancer diagnosis. During a mean 16.1 years of follow up, there were 772 deaths in total, including 195 deaths from breast cancer. Compared to women with relatively stable methionine intake, women with decreased methionine intake had lower risks of all-cause (HR 0.78, 95% CI 0.62-0.97) and breast cancer mortality (HR 0.58, 95% CI 0.37-0.91) in fully adjusted models. In contrast, increased methionine intake or changes in folate/folic acid or vitamin B12 intake were not associated with all-cause or breast cancer mortality.. Among breast cancer survivors, decreased methionine intake after breast cancer diagnosis was associated with lower risk of all-cause and breast cancer mortality.

Topics: Animals; Eating; Female; Folic Acid; Methionine; Neoplasms; Postmenopause; Prospective Studies; Racemethionine; Risk Factors; Vitamin B 12

The relationships between cancer caused by HPV and some vitamins, as well as leucocytes and their ratios, have been investigated in the literature. Our aim is to evaluate these relationships at the level of genital wart in terms of the investigated parameters and lesion numbers. Data were obtained from 98 and 94 patients for groups one and two, including warts patients and healthy people respectively. The Neutrophil/Monocyte ratio and lesion numbers in the warts patients were reported and analysed in terms of vitamin B12 and D, ferritin and leucocytes. A correlation was established between lesion numbers, age and midcorpuscular volume (p <0.05). There was no correlation between lesion numbers and recurrence. According to the comparative analysis, there were differences in terms of ferritin, neutrophil, monocyte, haemoglobin, midcorpuscular volume and neutrophil/monocyte ratio between groups. The cut-off values for neutrophil, monocyte and N/M ratios were 56.45, 4.91 and 7.825 respectively. While our study showed that wart development may be affected by blood ferritin levels and in this situation, midcorpuscular volume, neutrophil, monocyte and N/M ratios may change, a relation was found between lesion numbers and age and mean midcorpsucular volume values only. However, further studies are needed to clarify this issue.

Topics: Condylomata Acuminata; Ferritins; Humans; Monocytes; Neoplasms; Neutrophils; Vitamin B 12; Vitamin D; Vitamins

Topics: Biological Transport; Endocytosis; Humans; Neoplasms; Porphyrins; Receptors, LDL; Vitamin B 12

Elevated plasma vitamin B12 has been associated with solid cancers, based on a single B12 measurement. We evaluated the incidence of solid cancers following B12 measurement in patients with persistent elevated B12, compared to patients without elevated B12 and to patients with non-persistent elevated B12. The study population included patients with at least two plasma B12 measurements without already known elevated-B12-related causes. Patients with elevated plasma B12 (≥ 1000 ng/L) at first measurement (n = 344) were matched for age and sex with patients having 2 normal B12 measurements (< 1000 ng/L) (NN group, n = 344). The patients with elevated plasma B12 at first measurement were split into 2 groups, according to the presence (EE group, n = 144) or the absence (EN group, n = 200) of persistent elevated plasma B12 at second measurement. We compared the cancer-free survival during 60 months between the groups after adjustment for the other elevated-B12-related causes in a survival competing risk model. Compared to the NN group, a persistent elevated plasma B12 ≥ 1000 ng/mL was strongly associated with the occurrence of solid cancer (HR 5.90 [95% CI 2.79-12.45], p < 0.001), contrary to non-persistent plasma B12 elevation (p = 0.29). These results could help to select patients in whom the screening for solid cancers would be of interest.

Topics: Aged; Aged, 80 and over; Case-Control Studies; Female; Humans; Incidence; Male; Middle Aged; Neoplasms; Vitamin B 12

To determine the prevalence of anemia, and to evaluate the etiology and risk factors of anemia in patients with newly diagnosed cancer.. In this cross-sectional study, 310 patients with newly diagnosed cancer who were referred to a university hospital in Turkey over a 6-month period and 218 age-matched healthy individuals as controls were evaluated in terms of anemia: complete blood count (CBC), ferritin, transferrin saturation (TS%), serum iron (SI), cobalamin (B12), and folate levels. Carcinoma of the breast (21.3%), lung (12.9%), and gastrointestinal tract (GIT) (35.8%) accounted for the majority of the patients, and 44.7% of the patients had metastatic disease.. Anemia was observed in 49.7% of patients with cancer and in 11.9% of healthy controls (p < 0.001). SI and TS% were lower in patients with cancer than in the controls (p < 0.001); however, the median serum ferritin level, which is also an acute-phase reactant, was higher in the patient group than the healthy matched controls (42.2 ng/mL and 41 ng/mL, respectively, p < 0.001). Folate and B12 deficiencies were seen more frequently in the cancer group than in the controls [6.5% and 0.9% (p < 0.001); 39.3% and 18.9% (p < 0.05), respectively]. In the cancer group, anemia was seen more frequently in the metastatic subgroup than in the non-metastatic subgroup (59.7% and 55.3%, respectively, p < 0.05). The prevalence of anemia was similar in both groups of patients with and without primary GIT cancers, as well as in patients who did and did not undergo tumor surgery (p > 0.05).. This study showed that, at the time a patient is diagnosed as having cancer, the patient already has a significant risk for anemia, nearly five times that of healthy people. Having metastatic disease, and having nutritional deficiencies as iron, B12, and folate were evaluated as possible risk factors for anemia in patients with newly diagnosed cancer, whereas cancer with GIT localization and previous history of tumor surgery were not.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Case-Control Studies; Cross-Sectional Studies; Female; Ferritins; Folic Acid; Folic Acid Deficiency; Humans; Iron; Male; Middle Aged; Neoplasms; Prevalence; Risk Factors; Turkey; Vitamin B 12; Vitamin B 12 Deficiency; Young Adult

A series of tricarbonyl manganese complexes bearing 4-ethynyl-2,2'-bipyridine and 5-ethynyl-1,10-phenanthroline α-diimine ligands were synthetized, characterized and conjugated to vitamin B

Topics: A549 Cells; Carbon Monoxide; Coordination Complexes; Crystallography, X-Ray; HT29 Cells; Humans; Ligands; Light; Manganese; MCF-7 Cells; Neoplasms; Organometallic Compounds; Phenanthrolines; Photolysis; Solubility; Vitamin B 12

Despite broad appreciation of their clinical utility, it has been unclear how vitamin B12 and folic acid (FA) function at the molecular level to directly prevent their hallmark symptoms of deficiency like anemia or birth defects. To this point, B12 and FA have largely been studied as cofactors for enzymes in the one-carbon (1C) cycle in facilitating the de novo generation of nucleotides and methylation of DNA and protein. Here, we report that B12 and FA function as natural antagonists of aryl hydrocarbon receptor (AhR). Our studies indicate that B12 and FA bind AhR directly as competitive antagonists, blocking AhR nuclear localization, XRE binding, and target gene induction mediated by AhR agonists like 2,3,7,8-tetrachlorodibenzodioxin (TCDD) and 6-formylindolo[3,2-b]carbazole (FICZ). In mice, TCDD treatment replicated many of the hallmark symptoms of B12/FA deficiency and cotreatment with aryl hydrocarbon portions of B12/FA rescued mice from these toxic effects. Moreover, we found that B12/FA deficiency in mice induces AhR transcriptional activity and accumulation of erythroid progenitors and that it may do so in an AhR-dependent fashion. Consistent with these results, we observed that human cancer samples with deficient B12/FA uptake demonstrated higher transcription of AhR target genes and lower transcription of pathways implicated in birth defects. In contrast, there was no significant difference observed between samples with mutated and intact 1C cycle proteins. Thus, we propose a model in which B12 and FA blunt the effect of natural AhR agonists at baseline to prevent the symptoms that arise with AhR overactivation.

Topics: Animals; Basic Helix-Loop-Helix Transcription Factors; Carbazoles; Congenital Abnormalities; Female; Folic Acid; Folic Acid Deficiency; Gene Expression; Humans; Male; Malnutrition; Mice; Mice, Inbred C57BL; Neoplasms; Polychlorinated Dibenzodioxins; Receptors, Aryl Hydrocarbon; Vitamin B 12; Vitamin B 12 Deficiency

A Comprehensive Geriatric Assessment (CGA) has been proposed to assess prognosis and to adapt oncological care in older patients with cancer. However, few biological markers are incorporated in the CGA.. This comparative study on older patients with cancer was realized before final therapeutic decision and during a CGA that included biological markers. Our objective study was to know if the serum vitamin B12-C-reactive protein index (BCI) can help to estimate early death and unplanned hospitalization. Associations between BCI and unplanned hospitalization or mortality were analyzed using ordered multivariate logistic regression.. We included 621 older cancer adults in outpatient care with a median age of 81 years (range, 70-98 years) from September 2015 to May 2018. In this study, 5.6% of patients died within 3 months, 8.8% had unplanned hospitalization within 1 month, and 11.4% had unplanned hospitalization within 3 months. Hypercobalaminemia was present in 83 patients (13.4%), and 34 patients (5.5%) had BCI >40,000. According to the multivariate analysis, BCI was a prognostic factor of mortality within 3 months and unplanned hospitalizations at 1 and 3 months. Impaired activities of daily living (ADL) and palliative care were also risk factors for mortality within 3 months. Impaired instrumental ADL, low albumin level, and palliative care were risk factors for unplanned hospitalization at 1 month.. BCI could be routinely added to the CGA process, as part of a pretreatment workup, in order to assess more precisely the frailties and to adapt oncological care in older patients treated for cancer.. Aging comes with an increase of frailties and comorbidities. To identify frailties in older patients with cancer, this study used a Comprehensive Geriatric Assessment, which allowed for the adaptation of each treatment plan in accordance with the individual needs of the patients. However, biological characteristics were not included in this assessment. This study showed that hypercobalaminemia and vitamin B12 -C-reactive protein index may be potential markers for cancer with poor prognosis, particularly in the older population. These biological markers can be used in geriatric oncology and general medicine.

Topics: Activities of Daily Living; Aged; Aged, 80 and over; C-Reactive Protein; Geriatric Assessment; Hospitalization; Humans; Neoplasms; Vitamin B 12

This study investigates the predictors of serum cobalamin concentrations in community-dwelling older adults and the relationship between serum cobalamin and plasma homocysteine.. Serum cobalamin and plasma homocysteine were measured by SimulTRAC-SNB radio assay and HPLC, respectively. Linear multiple regression analyses were performed with cross-sectional data of 352 participants aged 60-90 years to examine (1) the predictors of serum cobalamin and (2) the association between cobalamin and homocysteine status. Age, sex, body composition, diet, supplement use, smoking, serum folate, serum pyridoxal 5´-phosphate, serum creatinine, and selected diseases were considered as potential predicting/confounding factors.. Median values of serum cobalamin, plasma homocysteine, and dietary cobalamin intake were 256 pmol/L, 9.7 µmol/L, and 5.7 µg/day, respectively. In multiple regression analysis, cobalamin intake, sex, body composition, serum creatinine and smoking did not predict serum cobalamin (all P > 0.05). In contrast, age (β = 0.111, P = 0.031), serum folate (β = 0.410, P < 0.001) and diagnosis of chronic inflammatory bowel disease (IBD) (β = 0.101, P = 0.037) were positively and cancer diagnosis (β = -0.142, P = 0.003) was negatively associated with serum cobalamin. The model explained 23% of the variability of serum cobalamin. After exclusion of subjects with IBD/cancer diagnosis and/or vitamin B/multi-vitamin supplementation, only serum folate remained as positive predictor of serum cobalamin (β = 0.407, P < 0.001). Serum cobalamin was positively associated with inverse-transformed plasma homocysteine before (β = 0.298, P < 0.001) and after (β = 0.199, P < 0.001) multiple adjustments.. Serum folate but not cobalamin intake or age proves to be a main predictor of cobalamin status. Nevertheless, independent of serum folate and other potential confounders, serum cobalamin is inversely associated with plasma homocysteine.

Topics: Age Factors; Aged; Body Composition; Cross-Sectional Studies; Diet; Female; Folic Acid; Homocysteine; Humans; Independent Living; Inflammatory Bowel Diseases; Male; Neoplasms; Sex Factors; Vitamin B 12

Elevated vitamin B12 levels (B12) are associated with increased short-term cancer risk. However, the implications for early cancer detection in primary care have not been assessed.. Individuals with plasma B12 measurements were sampled from The Health Improvement Network primary care database, UK. Persons with low B12 levels were excluded together with persons with cancer or B12 treatment before date of B12 measurement. Incident cancer was the outcome of interest and was identified through Read codes. Individuals were disaggregated according to plasma B12 levels (unit: pmol/L): 150-600 (reference range values), 601-800, 801-1,000, and >1,000.. Among the 757,185 persons who met the inclusion criteria, we identified 33,367 incident cancers during 2,874,059 years of follow-up. We found a higher 1-year cancer risk among the 25,783 (3.4%) persons with elevated B12 levels compared with those with normal B12 levels. After multivariable adjustment for lifestyle factors and social deprivation, persons with B12 >1,000 pmol/L had a 1-year incidence rate ratio of 4.72 (95% confidence interval: 3.99-5.58). The association showed a nonlinear dose-response pattern, and it remained robust in stratified analyses, including when reducing the risk of confounding by indication in subanalyses. The risks were particularly elevated for liver cancer, pancreas cancer, and myeloid malignancies among persons with elevated B12 levels.. Elevated plasma B12 levels were associated with a higher 1-year cancer risk than normal B12 levels among persons seen in UK primary care, suggesting that some cancers may affect B12 metabolism.. Elevated B12 may mark occult cancer.

Topics: Aged; Cohort Studies; Databases, Factual; Humans; Male; Middle Aged; Neoplasms; Primary Health Care; Prospective Studies; Risk Factors; United Kingdom; Vitamin B 12

This study aimed to evaluate the influence that serum levels of vitamin B12, folate, and homocysteine have on the development of short-term postoperative cognitive decline in the elderly surgical oncology patient.. This study was part of a prospective cohort study focused on postoperative cognitive outcomes for patients 65 years of age or older undergoing surgery for a solid malignancy. Postoperative cognitive decline was defined as the change in the combined results of the Ruff Figural Fluency Test and the Trail-Making Test Parts A and B. Patients with the highest change in scores 2 weeks postoperatively compared with baseline were considered to be patients with cognitive decline. Patients with the lowest change were considered to be patients without cognitive decline. To analyze the effect of vitamin levels on the changes in postoperative cognitive scores, uni- and multivariate logistic regression analysis were performed.. The study enrolled 61 patients with and 59 patients without postoperative cognitive decline. Hyperhomocysteinemia was present in 14.2% of the patients. Patients with postoperative cognitive decline more often had hyperhomocysteinemia (27.9 vs 10.2%). Hyperhomocysteinemia was associated with a higher chance for the development of postoperative cognitive decline (odds ratio. Preoperative hyperhomocysteinemia is associated with the development of postoperative cognitive decline. The presence of preoperative hyperhomocysteinemia could be an indicator for an increased risk of postoperative cognitive decline developing in the elderly.

Topics: Aged; Aged, 80 and over; Case-Control Studies; Cognitive Dysfunction; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Male; Neoplasms; Preoperative Period; Vitamin B 12

The active site of oxidative phosphorylation and adenosine triphosphate (ATP) biosynthesis is proposed to consist of thioretinaco, a complex of two molecules of thioretinamide with cobalamin, oxidized to the disulfonium derivative, thioretinaco ozonide, and complexed with oxygen, nicotinamide adenine dinucleotide, inorganic phosphate and ATP. Reduction of the active site complex by electrons from mitochondrial electron transport complexes releases ATP from binding to the active site, producing nicotinamide riboside and hydroperoxide and generating a membrane potential from proton transport to the active site. Opening of the mitochondrial permeability transition pore from decreased mitochondrial melatonin leads to loss of the active site complex from mitochondrial membranes, as observed in aging and dementia. Loss of the active site complex from mitochondria also results from opening of the permeability transition pore and from decomposition of the disulfonium active site by electrophilic carcinogens, oncogenic viruses and microbes which cause depletion of adenosyl methionine because of increased biosynthesis of polyamines, and by free radical oxygen species generated by ionizing radiation, and by catecholamines. Thus the loss of thioretinaco ozonide from mitochondria produces the impaired oxidative phosphorylation, oxidative stress, calcium influx, apoptosis, aerobic glycolysis, and mitochondrial dysfunction that are observed in chemical carcinogenesis, microbial carcinogenesis, traumatic brain injury, aging and dementia.

Topics: Adenosine Triphosphate; Carcinogenesis; Catalytic Domain; Heterocyclic Compounds; Homocysteine; Humans; Mitochondria; Mitochondrial Diseases; Neoplasms; Oxidation-Reduction; Oxidative Phosphorylation; Oxidative Stress; Oxygen; Reactive Oxygen Species; Vitamin B 12

AMP-activated kinase (AMPK) is a major regulator of energy metabolism and a promising target for development of new treatments for type 2 diabetes and cancer. 5-Aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR), an adenosine analog, is a standard positive control for AMPK activation in cell-based assays. Some broadly used cell culture media, such as minimal essential medium α (MEMα), contain high concentrations of adenosine and other nucleosides. We determined whether such media alter AICAR action in skeletal muscle and cancer cells. In nucleoside-free media, AICAR stimulated AMPK activation, increased glucose uptake, and suppressed cell proliferation. Conversely, these effects were blunted or completely blocked in MEMα that contains nucleosides. Addition of adenosine or 2'-deoxyadenosine to nucleoside-free media also suppressed AICAR action. MEMα with nucleosides blocked AICAR-stimulated AMPK activation even in the presence of methotrexate, which normally markedly enhances AICAR action by reducing its intracellular clearance. Other common media components, such as vitamin B-12, vitamin C, and α-lipoic acid, had a minor modulatory effect on AICAR action. Our findings show that nucleoside-containing media, commonly used in AMPK research, block action of the most widely used pharmacological AMPK activator AICAR. Results of cell-based assays in which AICAR is used for AMPK activation therefore critically depend on media formulation. Furthermore, our findings highlight a role for extracellular nucleosides and nucleoside transporters in regulation of AMPK activation.

Topics: Adenosine; Aminoimidazole Carboxamide; AMP-Activated Protein Kinase Kinases; Ascorbic Acid; Cell Line, Tumor; Culture Media; Diabetes Mellitus, Type 2; Energy Metabolism; Glucose; Humans; Muscle, Skeletal; Neoplasms; Nucleosides; Protein Kinases; Ribonucleotides; Thioctic Acid; Vitamin B 12

Topics: Acute Disease; Aged; Aged, 80 and over; Comorbidity; Cross-Sectional Studies; Female; France; Health Services for the Aged; Hematologic Diseases; Humans; Male; Middle Aged; Neoplasms; Vitamin B 12

Both venous thromboembolism (VTE) and high plasma vitamin B12 levels (cobalamin, Cbl) are markers of occult cancer and aggressive cancer with a poor prognosis. In this population-based cohort study, we assessed VTE risk among cancer patients with high plasma Cbl levels.. We used Danish health registries to identify a Cb1 cohort of 25,310 cancer patients with a plasma Cbl measurement prior to cancer diagnosis. The cohort was subdivided according to Cbl levels (pmol/L): 200-600 (population reference range), 601-800 and >800. All VTE events were considered provoked and categorised as either cancer-associated if no other provoking factors were present before VTE or provoked by other risk factors (surgery, trauma, or pregnancy). We calculated cumulative incidence proportions and adjusted hazard ratios computed from Cox regression analysis (reference: plasma Cbl of 200-600pmol/L) for the risk of VTE before and after the cancer diagnosis date (index date).. The risk of cancer-associated VTE 30days after index date increased with higher Cbl levels. The cumulative incidence (95% CI) by Cbl levels was: 200-600pmol/L: 0.24 (0.18-0.31); 601-800pmol/L: 0.63 (0.34-1.09); >800pmol/L: 0.86 (0.49-1.40). Adjusted hazard ratios (95% CI) were: 601-800 vs. 200-600: 2.55 (1.32-4.92); >800 vs. 200-600: 2.36 (1.19-4.71). We found similar results for VTE provoked by other risk factors and for VTE occurring before index date, but scarcity of events produced uncertain risk estimates.. We demonstrated an association between high plasma Cbl levels and risk of VTE in cancer patients. Any clinical implications warrant further study.

Topics: Aged; Cohort Studies; Female; Humans; Neoplasms; Risk Factors; Venous Thromboembolism; Vitamin B 12

Topics: Carcinogenesis; Case-Control Studies; Child, Preschool; Female; Folic Acid; Folic Acid Deficiency; Greece; Homocysteine; Humans; Male; Neoplasms; Vitamin B 12; Vitamin B 12 Deficiency

Elevated plasma vitamin B12 levels (cobalamin, Cbl) are associated with increased short-term cancer risk among patients referred for this laboratory measurement. We aimed to assess prognosis in cancer patients with elevated plasma Cbl.. We conducted a population-based cohort study using data from Danish medical registries during 1998-2014. The study included 25,017 patients with a cancer diagnosis and Cbl levels of 200-600 pmol/L (reference/normal range), 601-800 pmol/L and >800 pmol/L measured up to one year prior to diagnosis, and a comparison cohort of 61,988 cancer patients without a plasma Cbl measurement. Patients treated with Cbl were excluded. Survival probability was assessed using Kaplan-Meier curves. Mortality risk ratios (MRR) were computed using Cox proportional hazard regression, adjusted for age, sex, calendar year, cancer stage and comorbidity, scored using the Charlson comorbidity index.. Survival probabilities were lower among patients with elevated Cbl levels than among patients with normal levels and among members of the comparison cohort [(1-year survival,%) Cbl: 200-600 pmol/L: 69.3%; 601-800 pmol/L: 49.6%; >800 pmol/L: 35.8%; comparison cohort: 72.6%]. Thirty-day mortality was elevated for patients with Cbl levels of 601-800 pmol/L or >800 pmol/L, compared to patients with levels of 200-600 pmol/L [(MRR (95% confidence interval): 601-800 pmol/L vs. 200-600 pmol/L: 1.9 (1.6-2.2); >800 pmol/L vs. 200-600 pmol/L: 2.7 (2.4-3.1)]. This association remained robust for 31-90-day and 91-365-day mortality, showing similar dose-response patterns.. Cancer patients with elevated Cbl levels had higher mortality than those with normal Cbl levels. These findings may have clinical significance for assessing the prognosis of cancer patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Child; Child, Preschool; Cohort Studies; Denmark; Female; Humans; Infant; Infant, Newborn; Male; Middle Aged; Neoplasms; Prognosis; Risk Assessment; Survival Rate; Vitamin B 12; Young Adult

Folate is involved in carbohydrate metabolism, a process that can have clinical implications regarding diabetes management. The aim of this study was to assess the relationship between serum folate and fatality among adults with diabetes.. A retrospective cohort study was conducted with 532 adults with diabetes who participated in Phase II of NHANES III (National Health and Nutrition Examination Survey III; 1991-1994). This study served as baseline and was linked to the National Death Index database for a 15-y (1991-2006) follow-up study. Estimates of hazard ratios (HRs) for all-cause and cancer-related deaths, cardiovascular disease (CVD), and diabetes for individuals with different serum folate levels were obtained from Cox proportional hazards regression.. The mean age of adults with diabetes and detected serum folate at baseline was 63.2 y (SD 13.8 y). During follow-up, diabetes was listed as a contributor for 138 of 299 deaths. For all-cause deaths, the fatality rate of the upper quartile (74.30/1000 person-years [PY]) was almost twofold higher than the lower quartile (41.75/1000 PY) of serum folate levels. After adjusting for several covariates, including serum vitamin B12, cotinine, homocysteine and CVD history at baseline; the HRs for all-cause fatalities were 1.00 (reference), 1.62 (95% confidence interval [CI], 1.06-2.47) and 1.76 (95% CI, 1.09-2.83) among adults with diabetes in the lower, intermediate, and upper quartiles of serum folate levels, respectively.. Results indicate that high serum folate concentrations are associated with an increased fatality risk among adults with diabetes. Further studies are warranted to determine the mechanism(s) of this phenomenon.

Topics: Aged; Cardiovascular Diseases; Cotinine; Diabetes Mellitus; Female; Folic Acid; Follow-Up Studies; Homocysteine; Humans; Male; Middle Aged; Neoplasms; Nutrition Surveys; Proportional Hazards Models; Retrospective Studies; Risk Factors; Socioeconomic Factors; Vitamin B 12

Treatment of neuropathic pain and chemotherapy-induced peripheral neuropathy (CIPN) in patients with malignancy is often unsuccessful. Functional vitamin B12 deficiency, defined by elevated levels of the B12-dependent metabolites, methylmalonic acid (MMA), and/or homocysteine, despite normal B12 values, may cause neuropathy and is associated with disorders linked to increased oxidative stress. Since both cancer and neurotoxic antineoplastic agents increase oxidative stress, a role for functional B12 deficiency in CIPN was considered.. A retrospective record review of 241 cancer subjects evaluated by the adult palliative care service for B12 deficiency in a university-based cancer center between October 2008 and September 2012 with measurement of B12, MMA, and/or homocysteine levels was performed.. B12 values were elevated (>900 pg/ml) in 30 % and low (≤300 pg/ml) in 17 % of subjects tested. Elevated MMA (>250 nmol/l) and homocysteine (>12.1 μmol/l) levels occurred in 38 and 23 % of subjects respectively and at least one metabolite was increased in 54 % of evaluable subjects. Even when B12 values were ≥1500 pg/ml (n = 36), increased MMA and homocysteine values occurred in 31 and 23 % of subjects, respectively. B12 therapy decreased MMA values in all four subjects studied and improved neurologic findings in the three subjects tested.. Functional vitamin B12 deficiency is common in subjects with advanced malignancy. Further studies are needed to determine if this disorder is a risk factor for CIPN and if B12 therapy has a role in the management and/or prevention of neuropathy and neuropathic pain in this population.

Topics: Aged; Female; Humans; Male; Methylmalonic Acid; Middle Aged; Neoplasms; Neuralgia; Peripheral Nervous System Diseases; Retrospective Studies; Risk Factors; Vitamin B 12; Vitamin B 12 Deficiency

The aim of this study was to investigate differences in dietary intakes between 30251 participants in the European Prospective Investigation into Cancer and Nutrition-Oxford study, comprising 18 244 meat eaters, 4 531 fish eaters, 6 673 vegetarians, and 803 vegans aged 30 to 90 years who completed semiquantitative food frequency questionnaires. We hypothesized that these groups characterized by varying degrees of animal product exclusion have significantly different intakes of many nutrients, with possible implications for dietary adequacy and compliance with population dietary goals. Nutrient intakes were estimated including fortification in foods, but excluding dietary supplements. Dietary supplementation practices were also evaluated. Highly significant differences were found in estimated nutrient intakes between meat eaters and vegans, with fish eaters and vegetarians usually having intermediate values. Meat eaters had the highest energy intakes, followed by fish eaters and vegetarians, whereas vegans had the lowest intakes. Vegans had the highest intakes of polyunsaturated fatty acids, dietary fiber, vitamins C and E, folate, magnesium, iron, and copper. Meat eaters had the highest intake of saturated fatty acids, protein, vitamin B2, vitamin B12, vitamin D, zinc, and iodine. Fish eaters had the highest intakes of calcium and selenium. There were no statistically significant differences in sodium and potassium intakes between dietary groups. With the exception of sodium intake, compliance with population dietary goals was high across diet groups. The results suggested a high prevalence of inadequacy for dietary vitamin B12 and iodine in vegans. The diet groups under study showed striking differences in dietary intakes, with possible implications for compliance with dietary recommendations, as well as cardiometabolic diseases risk.

Topics: Adult; Aged; Animals; Diet; Diet Records; Diet, Vegan; Diet, Vegetarian; Dietary Fats; Dietary Fiber; Dietary Supplements; Energy Intake; Europe; Female; Fishes; Humans; Iodine; Male; Meat; Micronutrients; Middle Aged; Neoplasms; Nutritional Physiological Phenomena; Patient Compliance; Prospective Studies; Vitamin B 12

Children are at greater risk for malnutrition due to increased needs of nutrients to obtain appropriate growth, and they exhibit elevated substrate needs due to cancer and its treatment. This study aimed to report anthropometric and biochemical evaluation of nutritional status in children with cancer at initial presentation and during treatment. A prospective, controlled study was performed in the pediatric oncology department of a tertiary care center. Control group consisted of the siblings of patients. Weight, height, body mass index, triceps skinfold thickness, and serum levels of total protein, albumin, prealbumin, serum lipids, trace minerals, C-reactive protein (CRP), and vitamins were compared in patients and controls at initial presentation and at 6th month after the onset of treatment. According to weight for height, the frequency of malnutrition was 16% at initial presentation and 22% at 6th month. Triceps skinfold thickness was significantly thinner in patients than controls at both measurements. Patients had lower levels of prealbumin, albumin, iron, folate, zinc, and vitamin C and higher levels of ferritin, vitamin B12, and copper. Serum CRP levels were significantly higher in cancer patients at initial presentation and seemed to be correlated with copper levels. Compared with other patients, malnourished patients had significantly higher levels of vitamin B12 at 6th month. Results of the current study demonstrate that trace minerals, vitamins, and anthropometric measures may yield important clues for nutritional status and disease activity in pediatric oncology patients. However, validation and updating these potential markers warrant further trials on larger series.

Topics: Adolescent; Blood Proteins; Body Weight; Child; Child, Preschool; Female; Humans; Male; Neoplasms; Nutritional Status; Prospective Studies; Vitamin B 12

Topics: Aged; Autoimmune Diseases; Female; France; Hematologic Diseases; Humans; Liver Diseases; Male; Metabolic Diseases; Neoplasms; Prevalence; Prognosis; Renal Insufficiency; Statistics as Topic; Vitamin B 12

Targeting cancer cells with vitamin B12 (cobalamin) is hampered by unwanted physiologic tissue uptake mediated by transcobalamin. Adhering to good manufacturing practice, we have developed a new (99m)Tc-cobalamin derivative ((99m)Tc(CO)3-[(4-amido-butyl)-pyridin-2-yl-methyl-amino-acetato] cobalamin, (99m)Tc-PAMA-cobalamin). The derivative shows no binding to transcobalamin but is recognized by haptocorrin, a protein present in the circulation and notably expressed in many tumor cells. In this prospective study, we investigated cancer-specific uptake of (99m)Tc-PAMA-cobalamin in 10 patients with various metastatic tumors.. Ten patients with biopsy-proven metastatic cancer were included. Dynamic imaging was started immediately after injection of 300-500 MBq of (99m)Tc-PAMA-cobalamin, and whole-body scintigrams were obtained at 10, 30, 60, 120, and 240 min and after 24 h. The relative tumor activity using SPECT/CT over the tumor region after 4 h was measured in comparison to disease-free lung parenchyma. Patients 3-10 received between 20 and 1,000 μg of cobalamin intravenously before injection of (99m)Tc-PAMA-cobalamin. The study population comprised 4 patients with adenocarcinomas of the lung, 3 with squamous cell carcinomas of the hypopharyngeal region, 1 with prostate adenocarcinoma, 1 with breast, and 1 with colon adenocarcinoma.. The median age of the study group was 61 ± 11 y. Six of 10 patients showed positive tumor uptake on (99m)Tc-PAMA-cobalamin whole-body scintigraphy. The scan was positive in 1 patient with colon adenocarcinoma, in 3 of 4 lung adenocarcinomas, in 1 of 3 hypopharyngeal squamous cell carcinomas, and in 1 breast adenocarcinoma. Renal uptake was between 1% and 3% for the left kidney. Predosing with cobalamin increased the tumor uptake and improved blood-pool clearance. The best image quality was achieved with a predose of 20-100 ug of cold cobalamin. The mean patient dose was 2.7 ± 0.9 mSv/patient.. To our knowledge, we report for the first time on (99m)Tc-PAMA-cobalamin imaging in patients with metastatic cancer disease and show that tumor targeting is feasible.

Topics: Aged; Aged, 80 and over; Biopsy; Female; Humans; Male; Middle Aged; Multimodal Imaging; Neoplasm Metastasis; Neoplasms; Organotechnetium Compounds; Prospective Studies; Radionuclide Imaging; Radiopharmaceuticals; Sensitivity and Specificity; Technetium; Time Factors; Tissue Distribution; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; Vitamin B 12; Whole Body Imaging

A high frequency of hypogonadism has been reported in male patients with advanced cancer. The current study was performed to evaluate the association between low testosterone levels, symptom burden, and survival in male patients with cancer.. Of 131 consecutive male patients with cancer, 119 (91%) had an endocrine evaluation of total (TT), free (FT), and bioavailable testosterone (BT); high-sensitivity C-reactive protein (CRP); vitamin B12; thyroid-stimulating hormone; 25-hydroxy vitamin D; and cortisol levels when presenting with symptoms of fatigue and/or anorexia-cachexia. Symptoms were evaluated by the Edmonton Symptom Assessment Scale. The authors examined the correlation using the Spearman test and survival with the log-rank test and Cox regression analysis.. The median age of the patients was 64 years; the majority of patients were white (85 patients; 71%). The median TT level was 209 ng/dL (normal: ≥ 200 ng/dL), the median FT was 4.4 ng/dL (normal: ≥ 9 ng/dL), and the median BT was 22.0 ng/dL (normal: ≥ 61 ng/dL). Low TT, FT, and BT values were all associated with worse fatigue (P ≤ .04), poor Eastern Cooperative Oncology Group performance status (P ≤ .05), weight loss (P ≤ .01), and opioid use (P ≤ .005). Low TT and FT were associated with increased anxiety (P ≤ .04), a decreased feeling of well-being (P ≤ .04), and increased dyspnea (P ≤ .05), whereas low BT was only found to be associated with anorexia (P = .05). Decreased TT, FT, and BT values were all found to be significantly associated with elevated CRP and low albumin and hemoglobin. On multivariate analysis, decreased survival was associated with low TT (hazards ratio [HR], 1.66; P = .034), declining Eastern Cooperative Oncology Group performance status (HR, 1.55; P = .004), high CRP (HR, 3.28; P < .001), and decreased albumin (HR, 2.52; P < .001).. In male patients with cancer, low testosterone levels were associated with systemic inflammation, weight loss, increased symptom burden, and decreased survival. A high frequency of hypogonadism has been reported in male patients with advanced cancer. In the current study, an increased symptom burden, systemic inflammation, weight loss, opioid use, and poor survival were found to be associated with decreased testosterone levels in male patients with cancer. Cancer 2014;120:1586-1593. © 2014 American Cancer Society.

Topics: Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Androgens; Anorexia; Biomarkers; C-Reactive Protein; Cachexia; Cost of Illness; Hemoglobins; Humans; Hydrocortisone; Hypogonadism; Inflammation; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasms; Quality of Life; Retrospective Studies; Serum Albumin; Testosterone; Texas; Thyrotropin; Vitamin B 12; Vitamin D; Weight Loss

Topics: Anemia; Antineoplastic Agents; Folic Acid; Humans; Iron; Neoplasms; Vitamin B 12

When increased serum cobalamin concentrations are encountered clinically they are usually attributed to parenteral supplementation, dietary factors, or otherwise ignored. However, recently, hypercobalaminaemia has been associated with numerous diseases in humans, most notably neoplastic and hepatic disorders. The aim of this retrospective, observational, cross-sectional study was to determine the significance of increased cobalamin in cats.. In total, 237 records were retrieved and 174 cats, of various ages and sexes met the inclusion criteria. A total of 42 cats had increased serum cobalamin concentration, and had not received prior supplementation. Multiple logistic regression analysis revealed that increased serum cobalamin concentration was positively related to pedigree breed (pedigree breeds more likely to have increased cobalamin concentration, odds ratio [OR] 4.24, 95% CI 1.78-10.15, P = 0.001), to having liver disease (OR 9.91, 95% CI 3.54-27.68), and to having a solid neoplasm (OR 8.54, 95% CI 1.10-66.45).. The results of the current study suggest that increased serum cobalamin concentrations should not be ignored in cats with no history of supplementation, and investigation for underlying hepatic or neoplastic disease is warranted.

Topics: Aging; Animals; Cat Diseases; Cats; Cross-Sectional Studies; Female; Liver Diseases; Male; Neoplasms; Odds Ratio; Retrospective Studies; Risk Factors; Sensitivity and Specificity; Vitamin B 12

Vitamin B12 (Cbl) deficiency may cause hematologic and neurologic dysfunction. Replacement therapy is effective in correcting hematologic abnormalities and improving neurologic symptoms. Cbl is known to have antioxidant activity. This antioxidant activity may antagonize the effects of chemotherapeutics (i.e. genotoxic effects of paclitaxel) on tumor DNA. We claim that Cbl replacement should be done more cautiously in patients receiving cytotoxic chemotherapy.

Topics: Antineoplastic Agents; Antioxidants; DNA, Neoplasm; Drug Interactions; Free Radicals; Humans; Neoplasms; Nervous System Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Elevated cobalamin level (ECL) is an epiphenomenon for several cancer types. The clinical significance of ECL at routine testing is, however, unknown. The aim of this study was to examine cancer incidences among persons with ECL.. In a cohort study, Funen County residents (inhabitants 476,580), Denmark, without cancer or injected cobalamin prescriptions were followed from first cobalamin measurement during 1999-2009. Follow-up was stratified according to age, gender, and whether the cobalamin level was elevated (> 1,200 pmol/L). Data from national registers on age-specific incidence of cancer in the general population were used to calculate standardised morbidity ratio (SMR).. A total of 490 persons with ECL and 40,104 with non-ECL were followed. Median age was 61 [IQR 44-77] years. Average follow-up was 2.0 years for ECL subjects and 2.7 years for non-ECL subjects. Cancer was diagnosed within the first 6 months of follow-up in 6.7% (CI 4.7-9.3) of ECL subjects and 2.6% (CI 2.4-2.7) of non-ECL subjects. In ECL and non-ECL subjects, SMR for cancer diagnoses were 15.1 (CI 10.4-21.2) and 5.0 (CI 4.7-5.3) within the first 6 months and 3.7 (CI 1.4-8.1) and 1.8 (CI 1.6-2.0) in the following six-month interval. Review of medical records revealed a suspicion of cancer or performance of relevant diagnostic tests in 87% at the time of cobalamin measurement.. Persons with ECL have a high incidence of cancer partly explained by the reasons for measuring cobalamin. It remains to be determined whether accidentally found ECL would justify a search for cancers.

Topics: Adult; Aged; Cohort Studies; Denmark; Female; Humans; Incidence; Male; Middle Aged; Neoplasms; Vitamin B 12

A substantial proportion of patients referred for plasma vitamin B12 (cobalamin [Cbl]) measurement present with high Cbl levels, which have been reported in patients with different cancer types. However, the cancer risk among patients with newly diagnosed high Cbl levels has not been adequately examined.. We conducted this cohort study using population-based Danish medical registries. Patients referred for Cbl measurement with levels greater than the lower reference limit (≥200 pmol/L) were identified from the population of Northern Denmark during the period of 1998 to 2009 using a database of laboratory test results covering the entire population. Data on cancer incidence (follow-up 1998-2010), Cbl treatment, and prior diagnoses were obtained from medical registries. Patients receiving Cbl treatment were excluded. Cancer risks were calculated as standardized incidence ratios (SIRs) with 95% confidence intervals (CIs), stratified by plasma Cbl levels. All statistical tests were two-sided.. We identified 333 667 persons without prevalent cancer and not receiving Cbl treatment. Six percent had Cbl levels greater than the upper reference limit (≥601 pmol/L). Cancer risk increased with higher Cbl levels and was highest during the first year of follow-up (Cbl 601-800 pmol/L: SIR = 3.44, 95% CI = 3.14 to 3.76; Cbl >800 pmol/L: SIR = 6.27, 95% CI = 5.70 to 6.88; both P < .001). The risks were particularly elevated for hematological and smoking- and alcohol-related cancers for persons with high Cbl levels.. High Cbl levels were associated with the risk of subsequently diagnosed cancer, mostly within the first year of follow-up. This may have clinical implications for the interpretation of high Cbl levels.

Topics: Adult; Aged; Biomarkers, Tumor; Cohort Studies; Denmark; Female; Humans; Incidence; Male; Middle Aged; Neoplasms; Registries; Risk Assessment; Risk Factors; Time Factors; Vitamin B 12

To identify the diseases that are associated with a high plasma concentration of vitamin B12 and to measure the strength of this association.. Retrospective study including all admissions between 1st May, 2005 and 30th April, 2008 in the UMAG pole departments (emergency, internal medicine, acute geriatrics and medical intensive care) with a test for plasma vitamin B12. The association between each of medical information system codes (solid tumors, malignant hematologic process, and renal disease) and a high or low vitamin B12 concentration was measured by odds ratios (OR) from logistic models taking into account repeated admissions, with adjustment for age and the weighted Charlson index.. Among 3702 admissions, 12% had a B12 more than 820pg/ml, 10.4% a B12 less than 180pg/ml and 77.6% a normal B12 concentration. After adjustment for age and the weighted Charlson index, high concentration of vitamin B12 was associated with interstitial renal diseases (OR 2.7; 95% CI: [1.7-4.2]), and cirrhosis or hepatitis (OR 4.3; [2.9-6.4]). After additional adjustment for these parameters, it was still associated with tumors (OR 1.8; [1.2-2.6]), malignant hematologic diseases (OR 2.1; [1.3-3.5]), metastasis (OR 2.9; [1.5-5.9]), liver metastasis (OR 6.2; [2.7-14.5]), liver carcinoma (LC) (OR 3.3; [1.1-10.4]), liver tumors other than LC (OR 4.7; [1.2-17.9]) and lymphoma (OR 3.2; [1.6-6.4]) but not with myeloma (OR 1.9; [0.6-1.4]). Low concentration of B12 was associated with myeloma (OR 2.9; [1.3-6.6]).. Finding a high plasma concentration of vitamin B12 should lead to a systematic search for a hepatic disease or a tumor, and particularly for a hepatic localization of a tumor.

Topics: Aged; Aged, 80 and over; Female; Humans; Length of Stay; Liver Diseases; Male; Middle Aged; Neoplasms; Osmolar Concentration; Prognosis; Retrospective Studies; Risk Factors; Vitamin B 12

Measurement of serum cobalamin levels is routinely used to diagnose cobalamin deficiency. Surprisingly, approximately 15% of patients have high cobalamin levels and no consensus exists regarding the clinical implications.. Hospital-treated patients above 18 years of age referred for serum cobalamin measurement were included in groups of patients [percentage cobalamin supplemented] with low (<200 pmol/L, n = 200 [6%]), normal (200-600, n = 202 [6%]) high (601-1000, n = 217 [27%]) and very high (>1000, n = 199 [53%]) cobalamin levels. Total and cobalamin-saturated (holo) transcobalamin, total haptocorrin, soluble TC receptor, sCD320, and methylmalonic acid were analyzed. Data on diagnoses and medical prescriptions was obtained through medical files and the Aarhus University Prescription Database.. Among patients not cobalamin supplemented median total haptocorrin and holo transcobalamin levels were markedly higher in the groups with high/very high cobalamin levels compared to groups with low/normal cobalamin levels. Median total transcobalamin and sCD320 levels were similar across the groups. A number of diagnoses were significantly associated to very high Cbl levels (odds ratio (95% confidence interval)): alcoholism (5.74 (2.76-11.96)), liver disease (8.53 (3.59-20.23)), and cancer (5.48 (2.85-10.55)). Elevated haptocorrin levels were seen in patients with alcoholism, cancer, liver-, renal-, autoimmune-, and bronchopulmonary disease. No clinical associations to sCD320 and total and holo transcobalamin levels were found.. In non-supplemented patients, high cobalamin levels were associated to high haptocorrin levels, and several diagnoses, including alcoholism, liver disease and cancer. Our study emphasizes that clinicians should take high serum cobalamin levels into consideration in the diagnostic process.

Topics: Aged; Alcoholism; Antigens, CD; Female; Humans; Liver Diseases; Male; Methylmalonic Acid; Middle Aged; Neoplasms; Receptors, Cell Surface; Transcobalamins; Vitamin B 12

In general practice, vitamin B12 levels are measured when searching an origin for an anemic status (usually megaloblastic anemia), for various neurological disorders (usually polyneuropathy) or for neurocognitive disorders. Although the pathologies associated with vitamin B12 deficiency are well known, hypervitaminemic B12 status is often fortuitous and frequent finding. The aim of this article is to present the disease entities associated with hypervitaminemia B12, the clinical implications of this dysvitaminosis and a practical approach when this laboratory abnormality is found.

Topics: Algorithms; Autoimmune Diseases; Female; Hematologic Diseases; Humans; Liver Diseases; Neoplasms; Pregnancy; Premature Birth; Renal Insufficiency; Vitamin B 12

Many different cancer types have previously been found to show increased uptake of the vitamins folate, vitamin B12, and biotin; however, it is not known whether these tumor lines show increased uptake of one or more of the vitamins. The current study was designed to examine the relative uptake of the three vitamins in 10 different types of cell lines. Rhodamine-labeled hydroxypropyl-methacrylamide (HPMA) was targeted with vitamin B(12), folate, or biotin, and the uptake of the labeled polymer was compared both in in vitro cell cultures and in mice-bearing tumors from a variety of tumor cell lines. Fluorescent microscopy of cell cultures and histological examination of tumor sections showed greatly increased uptake of the fluorescently labeled polymer in many tumors when the polymer was targeted with folate, biotin, or vitamin B(12). Tumors with enhanced uptake of vitamin B(12)- or folate-targeted rhodamine-HPMA also showed increased uptake of biotin-Rho-HPMA. In contrast, tumors with increased uptake of folate-Rho-HPMA did not show increased uptake of vitamin B12 (VB(12))-HPMA and vice versa. These findings suggest that vitamin-targeted polymers may greatly increase the uptake of drug-polymer complexes in certain tumors, which may result in an increased efficacy of antitumor agents, and which may allow for easier imaging of both the primary and metastatic tumors.

Topics: Acrylamides; Animals; Biotin; Cell Line, Tumor; Drug Carriers; Drug Delivery Systems; Folic Acid; Humans; Mice; Microscopy, Fluorescence; Neoplasms; Neoplasms, Experimental; Tissue Distribution; Vitamin B 12; Vitamins

Given the limited options available to treat canine cancers, the use of companion animals for evaluating new drugs may identify better therapies for veterinary and human oncology. The anti-tumor effects of nitrosylcobalamin (NO-Cbl), an apoptosis-inducing, vitamin B12-based carrier of nitric oxide (NO), was evaluated in four dogs with spontaneous cancer.. (1) A 13 year-old female spayed Giant Schnauzer with inoperable thyroid carcinoma and hypercalcemia. (2) A 6 year-old male neutered Golden Retriever with a malignant peripheral nerve sheath tumor (MPNST). (3) A ten yr-old neutered male Bichon Frise with apocrine gland anal sac adenocarcinoma (AGACA). (4) A 7 year-old female spayed Labrador mix with spinal meningioma following partial surgical resection. Tumor regression was measured by physical exam and verified using ultrasound (case 1) and MRI (case 2-4). Serum chemistries and hematologic parameters were monitored throughout the studies.. (1) The Giant Schnauzer demonstrated a 77% reduction in tumor volume after ten weeks of daily NO-Cbl treatment. (2) The Golden Retriever demonstrated a 53% reduction in tumor volume after 15 months of daily NO-Cbl therapy. (3) The Bichon Frise demonstrated a 43% regression of the primary tumor and a 90% regression of an iliac lymph node measured by MRI after 15 months of treatment. After 61 months, the dog currently has stable disease, normal liver enzymes, CBC analysis, and no evidence of toxicity. (4) The Labrador demonstrated complete regression of the residual tumor after 6 months of treatment.. We have shown previously that NO-Cbl is endocytosed by malignant cells, resulting in intra-tumoral NO release. In this study, we have shown that daily long-term use of NO-Cbl induced responses in all dogs without any signs of toxicity. The use of NO-Cbl capitalizes on the tumor-specific properties of the vitamin B12 receptor and represents a promising anti-cancer therapy.

Topics: Animals; Antineoplastic Agents; Dog Diseases; Dogs; Dose-Response Relationship, Drug; Female; Magnetic Resonance Imaging; Male; Neoplasms; Nitroso Compounds; Tumor Burden; Ultrasonography; Vitamin B 12

Topics: Aged; Biomarkers; C-Reactive Protein; Female; Humans; Kaplan-Meier Estimate; Life Expectancy; Male; Neoplasms; Palliative Care; Predictive Value of Tests; Prognosis; Survival Analysis; Vitamin B 12

This prospective, observational study investigated the haematological response to darbepoetin alfa (DA) administered every three weeks for the treatment of anaemia. Response was also assessed according to baseline characteristics including iron, folate and vitamin B12 status.. Anaemic adult patients with malignant non-myeloid cancer, starting or having already undergone chemotherapy received DA on day of inclusionand were followed up for up to 24 weeks. Concentration of haemoglobin (Hb), as well as iron, vitamin B12 and folate status where available, were recorded at inclusion, after a treatment period of 9 weeks and up to a maximum of 24 weeks or cessation of DA treatment, whichever was sooner.. The main outcome measure assessed in this study was the percentage of patients reaching a Hb concentration of at least 11 g/dL at least once at any time during the study.. A total of 2912 patients were included. The mean Hb concentration increased from 10.0 g/dL at inclusion to 11.4 g/dL at 9 weeks and 11.8 g/dL at 24 weeks. In 74.6% of patients the target Hb level of 11.0 g/dL or above was reached. After initiation of DA treatment, 9.5% of patients required a blood transfusion by week 9, and 5.6% thereafter. Vitamin B12 and folate status were unknown for 80.3% of patients and the iron status for 73.2% of patients. Compared with patients who remained untreated for vitamin B12 or folate deficiency, a higher percentage of patients with vitamin status within normal limits achieved the target Hb concentration. However, achievement of target Hb level appeared not to be affected by iron status.. In this study, the mean Hb level increased in anaemic cancer patients treated with DA and the majority of patients achieved the target Hb level. In contrast to the recommendations of guidelines (EORTC) encouraging the measurement of iron and vitamin levels, the present study demonstrated that data were not routinely collected for these factors.

Topics: Aged; Anemia; Antineoplastic Agents; Cohort Studies; Darbepoetin alfa; Dietary Supplements; Erythropoietin; Female; Folic Acid; France; Hematinics; Humans; Iron; Male; Middle Aged; Neoplasm Metastasis; Neoplasms; Prospective Studies; Vitamin B 12

Topics: Colorectal Neoplasms; Folic Acid; Follow-Up Studies; Humans; Hyperhomocysteinemia; Myocardial Infarction; Neoplasms; North America; Risk; Vitamin B 12; Vitamin B Complex

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Colorectal Neoplasms; Confounding Factors, Epidemiologic; Dietary Supplements; Female; Folic Acid; Humans; Incidence; Lung Neoplasms; Male; Neoplasms; Primary Prevention; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Risk Assessment; Selenium; United States; Vitamin B 12; Vitamin B 6; Vitamin E

Methionine dependence, the inability of cells to grow when the amino acid methionine is replaced in culture medium by its metabolic precursor homocysteine, is characteristic of many cancer cell lines and some tumors in situ. Most cell lines proliferate normally under these conditions. The methionine dependent tumorigenic human melanoma cell line MeWo-LC1 was derived from the methionine independent non-tumorigenic line, MeWo. MeWo-LC1 has a cellular phenotype identical to that of cells from patients with the cblC inborn error of cobalamin metabolism, with decreased synthesis of cobalamin coenzymes and decreased activity of the cobalamin-dependent enzymes methionine synthase and methylmalonylCoA mutase. Inability of cblC cells to complement the defect in MeWo-LC1 suggested that it was caused by decreased activity of the MMACHC gene. However, no potentially disease causing mutations were detected in the coding sequence of MMACHC in MeWo-LC1. No MMACHC expression was detected in MeWo-LC1 by quantitative or non-quantitative PCR. There was virtually complete methylation of a CpG island at the 5'-end of the MMACHC gene in MeWo-LC1, consistent with inactivation of the gene by methylation. The CpG island was partially methylated (30-45%) in MeWo and only lightly methylated (2-11%) in control fibroblasts. Infection of MeWo-LC1 with wild type MMACHC resulted in correction of the defect in cobalamin metabolism and restoration of the ability of cells to grow in medium containing homocysteine. We conclude that epigenetic inactivation of the MMACHC gene is responsible for methionine dependence in MeWo-LC1.

Topics: Alleles; Carrier Proteins; Cell Line, Tumor; Cell Proliferation; CpG Islands; DNA Methylation; DNA, Complementary; Epigenesis, Genetic; Gene Expression Regulation, Neoplastic; Humans; Methionine; Molecular Chaperones; Neoplasm Proteins; Neoplasms; Oxidoreductases; Transfection; Vitamin B 12

Topics: beta Carotene; Calcium; Clinical Trials as Topic; Folic Acid; Food-Drug Interactions; Humans; Micronutrients; Neoplasms; Research Design; Selenium; Trace Elements; Treatment Failure; Vitamin B 12; Vitamin B 6; Vitamin D; Vitamin E; Vitamins

Recently, concern has been raised about the safety of folic acid, particularly in relation to cancer risk.. To evaluate effects of treatment with B vitamins on cancer outcomes and all-cause mortality in 2 randomized controlled trials.. Combined analysis and extended follow-up of participants from 2 randomized, double-blind, placebo-controlled clinical trials (Norwegian Vitamin Trial and Western Norway B Vitamin Intervention Trial). A total of 6837 patients with ischemic heart disease were treated with B vitamins or placebo between 1998 and 2005, and were followed up through December 31, 2007.. Oral treatment with folic acid (0.8 mg/d) plus vitamin B(12) (0.4 mg/d) and vitamin B(6) (40 mg/d) (n = 1708); folic acid (0.8 mg/d) plus vitamin B(12) (0.4 mg/d) (n = 1703); vitamin B(6) alone (40 mg/d) (n = 1705); or placebo (n = 1721).. Cancer incidence, cancer mortality, and all-cause mortality.. During study treatment, median serum folate concentration increased more than 6-fold among participants given folic acid. After a median 39 months of treatment and an additional 38 months of posttrial observational follow-up, 341 participants (10.0%) who received folic acid plus vitamin B(12) vs 288 participants (8.4%) who did not receive such treatment were diagnosed with cancer (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.03-1.41; P = .02). A total of 136 (4.0%) who received folic acid plus vitamin B(12) vs 100 (2.9%) who did not receive such treatment died from cancer (HR, 1.38; 95% CI, 1.07-1.79; P = .01). A total of 548 patients (16.1%) who received folic acid plus vitamin B(12) vs 473 (13.8%) who did not receive such treatment died from any cause (HR, 1.18; 95% CI, 1.04-1.33; P = .01). Results were mainly driven by increased lung cancer incidence in participants who received folic acid plus vitamin B(12). Vitamin B(6) treatment was not associated with any significant effects.. Treatment with folic acid plus vitamin B(12) was associated with increased cancer outcomes and all-cause mortality in patients with ischemic heart disease in Norway, where there is no folic acid fortification of foods.. clinicaltrials.gov Identifier: NCT00671346.

Topics: Aged; Dietary Supplements; Female; Folic Acid; Follow-Up Studies; Humans; Male; Middle Aged; Mortality; Myocardial Ischemia; Neoplasms; Norway; Proportional Hazards Models; Randomized Controlled Trials as Topic; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Topics: Dietary Supplements; Folic Acid; Humans; Neoplasms; Risk Assessment; Time Factors; Vitamin B 12; Vitamin B Complex

The survival of whites who have been treated for pernicious anaemia (PA) is unaffected, apart from incurring a greater risk of gastric cancers. The long term outcome of PA in Chinese is unknown.. A hospital based prospective longitudinal study of Chinese PA patients was conducted. Patients with known cancers were excluded.. From 1994 to 2007, 199 intrinsic factor antibody (IFA) positive and 168 IFA negative patients were recruited. Both cohorts had similar baseline characteristics, except the IFA positive patients had more severe haematological findings and more thyrogastric immune features; also more IFA negative patients had type 2 diabetes mellitus and gastrointestinal (GI) disease or GI surgery. Both cohorts had a good haematological response but an unsatisfactory neurological response to treatment. Hypothyroidism developed in patients of both cohorts during follow-up. 24 IFA positive patients and 7 IFA negative patients developed cancers (p = 0.007) during follow-up. 20% of all cancers were gastric carcinoma. Mean survival of both cohorts was similar. Mean survival of IFA positive patients with and without cancers was 64 and 129 months, respectively (p<0.001), and that of IFA negative patients 36 and 126 months, respectively (p<0.001). Death rates were 31% in the IFA positive cohort and 21% in the IFA negative cohort (p = 0.028). Cancer related death rates of IFA positive and IFA negative cohorts were 37% and 14%, respectively (p = 0.014).. The survival period of Chinese with PA who have received treatment is good, but there is an increased risk of gastric cancers. IFA positive patients have a higher risk of developing all types of cancers and cancer related deaths than IFA negative patients.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Pernicious; Asian People; Female; Hong Kong; Humans; Kaplan-Meier Estimate; Longitudinal Studies; Male; Middle Aged; Neoplasms; Vitamin B 12; Vitamin B Complex

Vitamin B12 plays a functional role in a variety of organs and body systems and the list of these organs and body systems is growing. According to our working hypothesis ("Master Key Effect") vitamin B12 has some unique functions, which are still not accepted; vitamin B12 functions to keep body systems in balance, even under the stress of severe pathology. What is the explanation for elevation of cobalamin level in oncological patients? As yet I have not been able to find another explanation for high level of vitamin B12 in oncology patients other than that it is a compensatory mechanism. Perhaps following this body's "warning sign", we should start treatment with high doses of vitamin B12 to try to help the stabilization of normal function of the organs and systems. Laboratory researches should be continued to substantiate introduction of cobalamin as preliminary treatment of particular diseases.

Topics: Animals; Cell Line, Tumor; Cell Proliferation; DNA Methylation; Humans; Models, Biological; Neoplasms; Prognosis; Vitamin B 12

Topics: Aged; Aged, 80 and over; Female; Humans; Inpatients; Male; Mortality; Neoplasms; Survival Analysis; Vitamin B 12; Vitamin B 12 Deficiency

Cancer incidence and genomic damage of peripheral lymphocytes are elevated in patients with end-stage renal failure. Among other uraemic toxins, homocysteine (Hcy) levels are increased in most of these patients. In healthy individuals, plasma Hcy correlates with the degree of genomic damage observed in peripheral blood lymphocytes (PBL). The accumulation of Hcy can be reduced by supplementation with folic acid and vitamin B12. The aim of this study was to analyse whether this supplementation can also lower the genomic damage in PBL of haemodialysis patients. This may ultimately help to reduce cancer incidence in renal patients.. In a prospective study with 27 patients, we analysed the genomic damage in dialysis patients before and at different time points after the initiation of folate/vitamin B12 supplementation. Genomic damage was measured by the frequency of micronuclei, a subset of chromosomal aberrations, in PBL.. Supplementation with folic acid and vitamin B12 (more markedly with both) reduced the micronucleus frequency in PBL of dialysis patients. This was not mediated by altered lymphocyte proliferation capacity or changes in DNA cytosine-methylation. Plasma-Hcy was lowered more efficiently by the combined folic acid/vitamin B12 supplementation, and lymphocyte DNA of this group exhibited a nonsignificant trend for a reduction of 1,N(6)-etheno-2'-deoxyadenosine, a marker for oxidative stress.. A reduction of the genomic damage in PBL can be achieved in dialysis patients by supplementation with folic acid and vitamin B12. This may be mediated by Hcy reduction.

Topics: Aged; Aged, 80 and over; Case-Control Studies; DNA Damage; Female; Folic Acid; Genome, Human; Homocysteine; Humans; Kidney Failure, Chronic; Lymphocytes; Male; Micronucleus Tests; Middle Aged; Neoplasms; Prospective Studies; Renal Dialysis; Vitamin B 12

Topics: Cognition Disorders; Dose-Response Relationship, Drug; Folic Acid; Food, Fortified; Homocysteine; Humans; Immune System; Neoplasms; Nutrition Policy; Vitamin B 12; Vitamin B Complex

Recently, homocysteine production was observed in tumour cell lines and homocysteine was proposed as a tumour marker. Furthermore, homocysteine production by activated immunocompetent cells was demonstrated.. In this study, homocysteine metabolism and immune activation status were investigated in 128 patients suffering from various types of cancer (haematological disorders, lung cancer, gastrointestinal tumours, gynaecological cancer and tumours of other localisation) and healthy age-matched controls.. A high percentage of patients (39.1%) showed moderate hyperhomocysteinaemia, while cysteine, folate and vitamin B(12) concentrations were within reference ranges. Most patients were found to have elevated concentrations of the immune activation and inflammation markers neopterin and C-reactive protein (CRP), as well as a higher erythrocyte sedimentation rate (ESR). Patients of different cancer groups differed significantly regarding vitamin B(12) and neopterin concentrations; higher B(12) levels were also associated with tumour progression. Univariate regression analysis showed that CRP, ESR and neopterin were suited best to predict death. In multivariate analysis, neopterin was best suited to predicting death, while homocysteine and B vitamins were not associated with patient outcome. Homocysteine concentrations were correlated with folate and cysteine levels. Higher neopterin concentrations coincided with lower folate concentrations, but higher vitamin B(12) concentrations.. Associations between neopterin and folate concentrations may indicate that cellular immune activation might partly contribute to the development of folate deficiency in cancer patients, thus possibly also impairing homocysteine remethylation.

Topics: Aged; Biomarkers; Case-Control Studies; Cysteine; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Immune System; Male; Neoplasms; Neopterin; Vitamin B 12

Homocysteine is associated with age, folate and vitamin B(12). Our study investigated the functional and clinical characteristics of the elderly (aged 60-85 years) of San Teodoro, a village in Central Sicily, and evaluated associations with vitamin B(12), folate and homocysteine.. Subjects (n=280) were examined after door-to-door recruitment using interview, physician examination and laboratory tests.. A total of 19.3% of the population had a low blood level of folate (<7 nmol/L) and 3.2% had low vitamin B(12) concentration (<100 pmol/L). The level of dependency, determined by the Barthel index, influenced homocysteine blood levels (p<0.0001), independent of age (p<0.0001), folate (p=0.0028) and vitamin B(12) (p=0.0165). Homocysteine was significantly associated with stroke (p=0.0027) and peripheral arterial vascular disease (p=0.0001), but not with myocardial infarction, angina pectoris, venous thrombosis or cancer. Vitamin B(12) was lower in myocardial infarction and higher in diabetes and venous thrombosis compared to the other diseases.. The prevalence of deficits in folate and vitamin B(12) was paradoxically high in the mountainous northeastern area of Sicily. Our study also underlines the association of homocysteine with dependency of the elderly and with stroke and peripheral arteriopathy.

Topics: Aged; Aged, 80 and over; Aging; Cardiovascular Diseases; Diabetes Mellitus; Folic Acid; Homocysteine; Humans; Middle Aged; Neoplasms; Peripheral Vascular Diseases; Sicily; Stroke; Vitamin B 12

The vitamin B(12)/C-reactive protein Index (BCI) has been proposed as a prognostic indicator in patients with advanced cancer. The purpose of this study was to confirm the utility of the BCI in palliative care patients.. Patients with advanced cancer provided a blood specimen for analysis. Demographic and disease-related variables were recorded. Patients were followed up for at least 90 days or until death.. Patients (n = 329) were divided into three groups according to their BCI score. Patients in group 3 (BCI >40,000; median survival 29 days) had a significantly (P < 0.01) worse survival than patients in group 2 (BCI 10,001-40,000; median survival 43 days) and patients in group 1 (BCI < or =10,000; median survival 71 days). However, patients in group 1 did not have a significantly better prognosis than those in group 2 (P = 0.091). The point estimates for 90-day mortality for each of the three risk groups were different from the figures previously reported during the development phase of the BCI (group 1, 58.9% versus 47.2%; group 2, 64.0 versus 72.5%; group 3, 78.9% versus 90.6%).. An elevated BCI (>40,000) predicts poor survival in patients with advanced cancer.

Topics: Adult; Aged; Aged, 80 and over; C-Reactive Protein; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasms; Palliative Care; Predictive Value of Tests; Prognosis; Vitamin B 12

Vitamin D and holotranscobalamin (HTCII) deficiencies have been seen to demonstrate an association with various types of cancers. The objective of this study is to determine the frequency of vitamin D and HTCII deficiency in cancer patients. Our study investigated vitamin D, total B12, and HTCII levels in 70 cancer patients. Vitamin D status was measured as serum 25-hydroxyvitamin D [25(OH)D, Nichols Advantage assay], and serum B12 was measured as both total B12 and as the metabolically active HTCII (Immulite B12 assay followed by glass adsorption). Insufficiency of serum 25(OH)D levels for this study is defined based on differing literature standards of insufficiency and was selected to be either <50 or <75 nmol/l. When 25(OH)D insufficiency is defined as serum level of <75 nmol/l, 43 of 60 (72%) of cancer patients were found to be insufficient. At the lower definition of insufficiency, <50 nmol/l, 24 of 60 patients (40%) were insufficient. Of 52 patients, only 3 (6%) were found to have insufficient serum levels of total B12 (normal = >300 pg/ml), whereas 17 of 52 (34%) were found to be HTCII insufficient (normal = >69 pg/ml). Of these 17 patients, 14 (84.4%) had normal total B12 levels. Low serum levels of 25(OH)D strongly correlated with low serum HTCII. All 12 HTCII-deficient patients were vitamin D insufficient at the <75-nmol/l standard. Six of 12 HTCII-deficient patients (50%) were vitamin D deficient at the <50-nmol/l cutoff. The standard measurement of total serum B12 alone is inadequate for identifying patients with insufficient levels of metabolically active B12. Deficiency of vitamin D (72%) and HTCII (34%) is prevalent among newly diagnosed patients with cancer and could play a role in cancer development and host response to tumor and therapy. Possible explanations for combined HTCII and 25(OH)D deficiencies include patient age, presence of atrophic gastritis, and lack of sun exposure.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Biomarkers; Female; Humans; Male; Middle Aged; Neoplasms; Sunlight; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin D; Vitamin D Deficiency; Vitamins

Targeted chemotherapy for cancer treatment offers a great potential advantage in tumour treatment due to greater specificity of delivery which leads to increased dose of the cytotoxin delivered to the tumour relative to the rest of the body. In order to achieve such selective targeted delivery one needs to identify generic markers that are over-expressed on the surface of tumour cells but are not over-expressed on normal tissue. Work of several authors has shown that some cells, such as those of rapidly dividing, aggressive tumours, over-express surface receptors involved in the uptake of vitamin B(12) [B. Rachmilewitz, M. Rachmilewitz, B. Moshkowitz, J. Gross, J. Lab. Clin. Med. 78 (1971) 275-279; B. Rachmilewitz, A. Sulkes, M. Rachmilewitz, A. Fuks, Israel J. Med. Sci. 17 (1981) 874-879] or folate [P. Garin-Chesa, I. Campbell, P.E. Saigo, J.L. Lewis Jr., L.J. Old, W.J. Rettig, Am. J. Pathol. 142 (1993) 557-567; O.C. Boerman, C.C. van Niekerk, K. Makkink, T.G.J.M. Hanselaar, P. Kenemans, L.G. Poels, Int. J. Gynecol. Pathol. 10 (1991) 15-25; G. Toffoli, C. Cernigoi, A. Russo, A. Gallo, M. Bagnoli, M. Boiocchi, Int. J. Cancer 74 (1997) 193-194; J.A. Reddy, D. Dean, M.D. Kennedy, P.S. Low, J. Pharm. Sci. 88 (1999) 1112-1118; J.A. Reddy, P.S. Low, Crit. Rev. Ther. Drug Carrier Syst. 15 (1998) 587-627; G.J. Russell-Jones, K. McTavish, J.F. McEwan, in: Proceedings of the 2nd International Symposium on Tumor Targeted Delivery Systems, 2002]. Furthermore the degree of over-expression has been found to correlate with the stage of tumour growth, with the highest levels found on stage IV carcinomas. Using fluorescently-labelled polymers to which are linked the targeting agents, vitamin B(12), folate or biotin, the relative uptake of these polymers into various types of tumour cell lines grown both in vitro and in vivo has been examined. These studies have shown that while some tumour types do NOT over-express receptors involved in vitamin uptake, most tumour types over-express receptors for folate, or vitamin B(12). In either case there is also a greatly increased expression of a yet to be identified biotin receptor. In cases of receptor over-expression, binding of the targeted fluorochrome leads to rapid internalization of these molecules within the cells to levels that are two to thirty times higher than with non-targeted polymers. Using a number of cancer models, these studies were extended further and it was found that the increased expression of receptors also

Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Folic Acid; Methacrylates; Mice; Neoplasm Transplantation; Neoplasms; Polymers; Rhodamines; Vitamin B 12

Topics: Antioxidants; Biomarkers; Cardiovascular Diseases; Carotenoids; Female; Folic Acid; Fruit; Homocysteine; Humans; Male; Middle Aged; Morbidity; Neoplasms; Portugal; Risk Factors; Surveys and Questionnaires; Vegetables; Vitamin B 12; Vitamin B 6; Vitamin E

Fluorescent derivatives of cobalamin have been prepared by linking fluorophores to cobalamin through a propylamide spacer. Fluorescein, naphthofluorescein, and Oregon Green derivatives have been prepared in good yield by reaction of the fluorophore NHS-ester with beta-(3-aminopropyl)cobalamin to form fluorescent cobalamin conjugates (CobalaFluors) that are potentially suitable for the in vitro and in vivo imaging of transcobalamin receptors on cancer cells.

Topics: Boron Compounds; Fluoresceins; Fluorescent Dyes; Humans; Indicators and Reagents; Molecular Conformation; Molecular Structure; Neoplasms; Receptors, Cell Surface; Spectrophotometry; Vitamin B 12

Interestingly, plasma total homocysteine (tHcy) concentration is consistently higher in men than in women. This observation deserves further investigations because elevated tHcy concentrations have been shown to be independently associated with coronary, peripheral, and cerebral vascular diseases. It was the aim of the present study to define major determinants of plasma tHcy in a healthy middle-aged German population under particular consideration of the gender factor. The study population was obtained from an ongoing recruitment procedure for a cohort study and comprised 336 men and women, aged 40 to 65 years. Exclusion criteria were elevated creatinine levels in blood, history of skin or atherosclerotic diseases, current use of vitamins or other supplements, and heavy smoking. Plasma tHcy, folate, vitamin B12, vitamin B6, creatinine, testosterone and estradiol, protein, and hematocrit were measured. Fat-free mass was assessed by skinfold thickness. The C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR), a key enzyme of folate and homocysteine metabolism, was determined by polymerase chain reaction (PCR) with restriction enzyme analysis. In this population, plasma tHcy ranged from 5 to 46 micromol/L. The frequency of the T allele of the MTHFR was 0.29, which is lower than in other populations. A total of 54.2% of this population was homozygote for the wild-type, 39.6% heterozygote, and 6.2% homozygote for the mutation. tHcy correlated negatively with folate and cobalamin concentration in blood and positively with creatinine. No correlation was seen with vitamin B6. From the gender-related variables, tHyc correlated significantly with fat-free mass and testosterone and inversely with estradiol. The difference between gender with regard to tHcy was mainly explained by differences in fat-free mass, but also by estradiol concentrations. The following contributions to the variation of tHcy were seen in a multivariate regression model: plasma cobalamin (11%), creatinine (11%), plasma folate (8%), fat-free mass (5%), estradiol (2%), MTHFR polymorphisms (2%), and plasma protein (1%). We concluded that tHcy in the general population has a variety of determinants ranging from nutrition, internal metabolic parameters to gender-related variables.

Topics: Adult; Age Factors; Aged; Analysis of Variance; Body Mass Index; Cohort Studies; Female; Folic Acid; Germany; Gonadal Steroid Hormones; Homocysteine; Humans; Linear Models; Male; Middle Aged; Neoplasms; Nutritional Physiological Phenomena; Sex Factors; Vitamin B 12

Topics: Humans; Neoplasms; Radionuclide Imaging; Vitamin B 12

Topics: Biological Availability; Biomarkers; Cardiovascular Diseases; Choline; Congenital Abnormalities; Female; Folic Acid; Folic Acid Deficiency; Food, Fortified; Homocysteine; Humans; Male; Neoplasms; Neural Tube Defects; Nutrition Policy; Nutritional Status; Vitamin B 12; Vitamin B 12 Deficiency

A prospective population study of women in Gothenburg, Sweden was started in 1968-69 and comprised 1462 women aged 38, 46, 50, 54, or 60 years at baseline. Follow-up studies were carried out in 1974-75, 1980-81, and 1992-93. The baseline study included an extensive medical and dental examination. Serum mercury concentration (beta-HG) was determined in deep-frozen samples from all participants in 1968-69 and in a random subsample of sera from participants in 1980-81, about 20 years after the baseline examination. S-Hg was statistically significantly correlated with number of amalgam fillings at both examinations. Of 30 defined symptoms and 4 different clusters of symptoms, no one was independently correlated with S-Hg measured in the samples from 1968-69, while there was a negative statistically significant correlation with over-exertion and poor appetite in 1980-81. Blood hemoglobin and serum B-12 concentrations in 1968-69 were statistically significantly and positively correlated with S-Hg, while erythrocyte sedimentation rate and the serum concentrations of potassium and triglycerides were significantly and negatively correlated with S-Hg, also after including potential confounders. Blood hematocrit examined in 1980-81 was negatively correlated with S-Hg. When including potential confounders, serum IgA was also statistically significantly correlated with S-Hg, but not in univariate analysis. No statistically significant correlation was observed between S-Hg, on the one hand, and the incidence of diabetes, myocardial infarction, stroke, or cancer on the other, while a statistically significant negative correlation was observed with overall mortality when age and education were included as background variables. There were some correlations between biological variables and S-Hg, probably of no negative clinical significance, and we conclude that there is no association between disease and S-Hg on a population basis in middle-aged and older women.

Topics: Adult; Age Factors; Aged; Blood Sedimentation; Cerebrovascular Disorders; Confounding Factors, Epidemiologic; Dental Amalgam; Dental Restoration, Permanent; Diabetes Mellitus; Educational Status; Epidemiology; Fatigue; Feeding and Eating Disorders; Female; Follow-Up Studies; Hematocrit; Hemoglobins; Humans; Immunoglobulin A; Longitudinal Studies; Mercury; Middle Aged; Myocardial Infarction; Neoplasms; Potassium; Prospective Studies; Survival Rate; Sweden; Triglycerides; Vitamin B 12

To identify the defect in cobalamin metabolism in the human melanoma cell line MeWoLC1, and to determine how frequent this defect is in other methionine-dependent tumour cell lines.. Biochemical and somatic cell genetics study.. Aspects of cobalamin metabolism were measured in a panel of 14 human tumour cell lines that were unable to proliferate normally in medium in which methionine had been replaced by its metabolic precursor homocysteine (methionine-dependent cell lines).. The human melanoma cell line MeWoLC1 was unique among these cell lines, in that it was characterized by decreased uptake of cobalamin, decreased synthesis of coenzyme derivatives, and decreased functional activity of the cobalamin-dependent enzymes methionine synthase and methylmalonylCoA mutase. This phenotype was identical to that observed in fibroblasts from patients with the cblC and cblD inborn errors of cobalamin metabolism. The defect in cobalamin metabolism in MeWoLC1 was complemented in somatic cell complementation analysis by cblA, cblB, cblD, cblE and cblG fibroblasts, but not by cblC fibroblasts, strongly suggesting that the defect in this cell line affects the cblC locus. Similar changes in cellular cobalamin metabolism were not seen in any other methionine-dependent cell line in the panel, suggesting that there may be multiple causes of methionine dependence, and that inactivation of the cblC locus may not be a common cause of this phenotype in transformed cells.. The defect underlying methionine dependence in MeWoLC1 appears to involve the locus that is affected in patients with the cblC inborn error of metabolism. This defect does not seem to be common among other methionine-dependent cell lines.

Topics: Carbon Radioisotopes; Culture Media; Humans; Leukemia; Melanoma; Methionine; Neoplasms; Propionates; Tetrahydrofolates; Tumor Cells, Cultured; Vitamin B 12

We have recently reported a new and rapid assay to measure plasma holotranscobalamin II (holo TC II) as a means of exploring vitamin B12 status. In order to further evaluate the significance of plasma holoTC II in determining tissue cobalamin, we have chosen the red blood cell-vitamin B12 (RBC-B12) assay as a measure of tissue vitamin B12 content and studied the relationship between RBC-B12 and plasma holoTC II levels. Plasma holoTC II and RBC-B12 concentrations were concomitantly assayed in 20 hematologically normal controls and cancer patients. In our groups of controls, the mean value of RBC-B12 was determined as 241 +/- 51 pg/ml of packed erythrocytes (PE) with a range varying from 180 to 355 pg/ml PE. Preliminary results obtained in 32 cancer patients revealed lower holoTC II and RBC-B12 levels than the control group and a required threshold value of 70 pg/ml of holoTC II in order to maintain a normal RBC-B12 greater than 180 pg/ml PE.

Topics: Erythrocytes; Humans; Neoplasms; Plasma; Transcobalamins; Vitamin B 12

We describe a new and rapid assay for the measurement of plasma B12 bound to transcobalamin II (holotranscobalamin II) using the property of adsorption of the polypeptides of apotranscobalamin II and holotranscobalamin II to the hydrophobic surface of microfine glass particles. Acid-washed microfine glass was used to separate vitamin B12 bound to the glycoproteins transcobalamin I and transcobalamin III (haptocorrin or R binder) from that bound to transcobalamin II. Sephadex gel filtration separation of 57Co-labelled vitamin B12 binders confirmed that > 90% of holotranscobalamin II can be removed from plasma holohaptocorrin by adsorption to microfine glass particles. Since only holotranscobalamin II is capable of delivering vitamin B12 to metabolizing cells, plasma holotranscobalamin II content reflects the availability of B12 to cells. Use of this test in cancer patients undergoing either chemotherapy or radiation therapy revealed evidence of early negative B12 balance that in some instances was induced by the treatment itself.

Topics: Adsorption; Chromatography; Glass; Hematologic Tests; Homocysteine; Humans; Hydroxyurea; Microspheres; Neoplasms; Osmolar Concentration; Polycythemia; Reproducibility of Results; Transcobalamins; Vitamin B 12

The roles of vitamin B12 and folate in carcinogenesis are largely extensions of and linked to their roles in normal metabolism, particularly 1-carbon unit metabolism. A possible key area may be hypomethylation to "switch on" genes and methylation to "switch them off." Some vitamin analogues may act as antivitamins in these reactions, as may some vitamin-binding proteins. Others may act as specific delivery proteins. Using appropriate radioactive substrates and suspensions of vitamin-dependent normal and malignant cells, it may be possible to work out their positive and negative control of DNA synthesis.

Topics: Carcinogens; DNA Replication; Folic Acid; Folic Acid Deficiency; Humans; Neoplasms; Vitamin B 12; Vitamin B 12 Deficiency

The influence of external abdominal irradiation and cytostatic therapy on the vitamin status was studied in patients with cancer of the uterus, bladder or prostate and in patients with malignant lymphoma. It was found that the vitamin status of these patients at the beginning of therapy in general was adequate, though vitamin A and vitamin D levels were reduced. During radiotherapy decreases of vitamin E, vitamin C, vitamin B12 and folic acid levels were observed. Chemotherapy caused a decrease of the folic acid levels after a few months. No clinical symptoms of vitamin deficiency were observed.

Topics: Ascorbic Acid; Calcifediol; Female; Humans; Lymphoma; Male; Neoplasms; Prostatic Neoplasms; Urinary Bladder Neoplasms; Uterine Neoplasms; Vitamin A; Vitamin B 12; Vitamin E; Vitamins

Topics: Adult; Aged; Diabetes Mellitus; Drug Administration Schedule; Female; Humans; Liver Cirrhosis; Male; Middle Aged; Neoplasms; Riboflavin; Thiamine; Vitamin B 12

Biochemical investigations show a decreased bioavailability of 5-methyl-tetrahydrofolic acid in vitamin B12 deficient human cell cultures and bone marrow cells. Tetrahydrofolic acid cannot be liberated from its storage form. This so-called methyl-folate-trap results in a functional folic acid deficiency which is the pathogenetic principle of the defect in the cell proliferation in patients with vitamin B12 deficiency. This knowledge of biochemical mechanisms leads to the identification of rare disorders in the metabolism of vitamin B12 and folic acid. After methotrexate treatment a rescue effect with its antidote Leucovorin can only be achieved, if the ratio antidote: methotrexate is at least 10:1. This ratio is important in cell cultures as well as in bone marrow cells in vivo. The results lead to a formula for the calculation of the optimal dosis to reach a secure rescue for individual patients after high-dose methotrexate treatment. This makes the high-dose methotrexate regimen a treatment modality for malignant tumors without any side effects.

Topics: DNA; Folic Acid; Folic Acid Deficiency; Humans; Leucovorin; Methotrexate; Neoplasms; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia; Drug Therapy, Combination; Humans; Neoplasms; Pyridoxine; Thiamine; Vitamin B 12; Vitamin B Complex; Vitamins

Serum vitamin levels of 40 patients undergoing parenteral nutrition over a 5-to 42-day period were studied while the subjects received daily water-soluble and once weekly fat soluble vitamin formulations intravenously. Initial serum deficiencies of vitamins A, C, and folate were noted in a large portion of the severely malnourished population. At the replacement levels used in this study a small number of patients developed subnormal levels of vitamins A and D. Improvement in levels for vitamin C and folate were noted for most patients. Vitamin B12 deficiencies were not noted in any patient. Currently available commercial vitamin preparations can be used with safety in the parenterally nourished population and recommended guidelines for weekly infusion of both water and fat soluble vitamins are presented.

Topics: Adolescent; Adult; Aged; Ascorbic Acid Deficiency; Child; Female; Folic Acid Deficiency; Humans; Male; Middle Aged; Neoplasms; Nutritional Requirements; Parenteral Nutrition; Parenteral Nutrition, Total; Vitamin A Deficiency; Vitamin B 12; Vitamin D; Vitamins

Topics: Alloys; Anemia; Animals; Beer; Cobalt; Enzyme Inhibitors; Food Contamination; Heart Diseases; Heme; Humans; Hyperlipidemias; Iron; Joint Prosthesis; Lipids; Neoplasms; Tissue Distribution; Vitamin B 12

One hundred and thirty-nine patients with non-hematologic malignancy were studied to define the incidence of vitamin B12-related abnormalities and correlate them with clinical findings. Based on vitamin B12-binding patterns, the following relatively distinct groups were defined: (A) 50% had normal results; (B) 6% had very high transcobalamin (TC) I and vitamin B12 levels as reported in isolated instances previously: most had hepatic metastases and early death, and all had definite metastatic disease; (C) 11% had high vitamin B12 levels with little or no unsaturated TC I elevation: most also had hepatic and other metastases and early death; (D) 23% had high vitamin B12-binding capacity with normal TC I and vitamin B12 levels: there were no distinguishing features for this group other than an increased proportion of black patients; and (E) 10% had low vitamin B12 levels, in many cases not associated with vitamin B12 deficiency or other known causes of low serum levels. Thus, high serum vitamin B12 level, with or without unsaturated TC I elevation, usually implies a poor prognosis in a patient with cancer. However, while most such patients have hepatic and other metastases, hepatic involvement was not universal nor did most patients with hepatic disease have high vitamin B12 levels. High serum TC I thus is not always due to increased granulocytic proliferation or to hepatic tumor, and alternative mechanisms for TC I accumulation should be sought.

Topics: Black People; Blood Proteins; Carrier Proteins; Female; Humans; Liver Neoplasms; Male; Neoplasm Metastasis; Neoplasm Proteins; Neoplasms; Prognosis; Transcobalamins; Vitamin B 12

A prospective study of the clinical significance of macrocytosis (mean corpuscular volume 100 fL or more) was carried out for 9 months in a teaching hospital in 1975. Of the 140 patients with macrocytosis at the time of admission (0l7% of all hospital admissions) 46 (33%) had low activity of serum or erythrocyte folate, or both, and 16 (11%) had low serum vitamin B12 concentrations. Among the 78 patients with normal B12 and folate values the most commonly associated significant clinical conditions were alcoholism or hepatic disease (36 patients), malignant disease or the effects of chemotherapy (25 patients) and chronic obstructive lung disease (10 patients).

Topics: Adolescent; Adult; Aged; Alcoholism; Anemia; Erythrocyte Volume; Erythrocytes; Female; Folic Acid; Hemoglobins; Humans; Liver Diseases; Lung Diseases, Obstructive; Male; Middle Aged; Neoplasms; Vitamin B 12

Elevation of transcobalamin I and serum vitamin B12 levels has usually been associated with increased granulocytic proliferation, such as occurs in chronic myelogenous leukemia. Two patients with metastatic cancer had extremely high serum vitamin B12 and transcobalamin I levels--greater than those seen in even the most intense granulocytic proliferation--that were not explainable by leukocytosis. The subjects' serum vitamin B12 levels were 18,750 and 21,221 pg per milliliter (normal, 471 plus or minus 174 pg per milliliter, mean plus or minus S.D.) and unsaturated vitamin B12 binding capacity 158,750 and 5,400 pg per milliliter (normal, 1153 plus or minus 313 pg per milliliter) respectively. The abnormally elevated serum binder was shown to be identical with transcobalamin balamin I in every respect. Levels of transcobalamin II and serum third binder were normal. The cause of the binder abnormality is unknown, but factors other than granulocyte proliferation may control or contribute to the production or accumulation of transcobalamin I.

Topics: Adenocarcinoma; Aged; Animals; Blood Proteins; Carcinoma; Carrier Proteins; Cell Division; Chromatography, DEAE-Cellulose; Chromatography, Gel; Cobalt Radioisotopes; Colonic Neoplasms; Female; Granulocytes; Humans; Immune Sera; Leukemia, Myeloid; Leukocyte Count; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Neoplasms; Protein Binding; Rabbits; Radioligand Assay; Saliva; Stomach Neoplasms; Vitamin B 12

Topics: Anemia; Blood Transfusion; Humans; Leukopenia; Neoplasms; Pyridoxine; Vitamin B 12

Topics: Adult; Aged; Analgesics; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Neoplasms; Pain, Intractable; Vitamin B 12

Topics: Adult; Aged; Alpha-Globulins; Beta-Globulins; Blood Proteins; Child, Preschool; Chronic Disease; Female; Fever of Unknown Origin; Hodgkin Disease; Humans; Infections; Leukocyte Count; Leukocytosis; Liver Neoplasms; Lymphoma; Male; Middle Aged; Neoplasm Metastasis; Neoplasms; Protein Binding; Splenectomy; Vitamin B 12

Topics: Anemia; Arthritis, Rheumatoid; Blood Proteins; Bone Marrow; Bone Marrow Cells; Chronic Disease; Erythropoietin; gamma-Globulins; Hematocrit; Humans; Infections; Iron; Neoplasms; Protein Biosynthesis; Serum Albumin; Transferrin; Vitamin B 12

Topics: Anemia; Anemia, Hypochromic; Anemia, Macrocytic; Anemia, Pernicious; Blood Proteins; Female; Hematologic Diseases; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocyte Count; Liver Cirrhosis; Lupus Erythematosus, Systemic; Lymphoma; Male; Multiple Myeloma; Neoplasms; Polycythemia; Primary Myelofibrosis; Protein Binding; Uremia; Vitamin B 12

Topics: Adult; Age Factors; Aged; Analgesics; Carbamazepine; Ethanol; Female; Follow-Up Studies; Humans; Hypertension; Male; Middle Aged; Minnesota; Multiple Sclerosis; Neoplasms; Phenytoin; Sex Factors; Trigeminal Neuralgia; Vitamin B 12

Topics: Adolescent; Adult; Aged; Anemia; Anemia, Hypochromic; Biliary Tract Diseases; Biometry; Cardiovascular Diseases; Erythrocyte Count; Erythrocytes; Erythrocytes, Abnormal; Female; Gastrointestinal Diseases; Hematologic Diseases; Hemophilia A; Humans; Leukemia; Liver Diseases; Lung Diseases; Male; Middle Aged; Neoplasms; Pancreatic Diseases; Splenectomy; Thalassemia; Thyroid Diseases; Urologic Diseases; Vitamin B 12

Topics: Adenine; Animals; Carbon Isotopes; Cell Line; Chromatography, Paper; Culture Media; Culture Techniques; Deoxyuridine; DNA, Neoplasm; Folic Acid; Formates; Hydroxocobalamin; Mice; Neoplasms; Stimulation, Chemical; Thymidine; Vitamin B 12

Topics: Adult; Aged; Animals; Cricetinae; DNA; Female; Humans; Male; Mice; Middle Aged; Mitosis; Neoplasms; Neoplasms, Experimental; Rats; Vitamin B 12

Topics: Anemia; Blood Proteins; Humans; Inflammation; Leukemia, Myeloid; Liver Diseases; Neoplasms; Protein Binding; Vitamin B 12

Topics: Age Factors; Aged; Anemia; Anemia, Hypochromic; Arthritis, Rheumatoid; Blood Chemical Analysis; Blood Proteins; Blood Sedimentation; Bronchitis; England; Feces; Female; Folic Acid; Folic Acid Deficiency; Health Surveys; Hematologic Diseases; Hemoglobins; Hospitalization; Humans; Iron; Middle Aged; Neoplasms; Sex Factors; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adult; Aged; Biopsy; Body Weight; Folic Acid; Hemoglobins; Humans; Intestinal Absorption; Intestinal Mucosa; Intestines; Jejunum; Middle Aged; Neoplasms; Serum Albumin; Vitamin B 12; Xylose

Topics: Anemia, Pernicious; Humans; Methotrexate; Neoplasms; Prednisone; Purpura, Thrombocytopenic; Thrombocytopenia; Thrombocytosis; Vitamin B 12

Topics: Blood Proteins; Cachexia; Chronic Disease; Humans; Kidney Diseases; Liver Diseases; Liver Extracts; Neoplasms; Vitamin B 12

Topics: Adolescent; Adult; Alpha-Globulins; Anemia; Blood Cell Count; Blood Sedimentation; Female; Humans; Infections; Kidney Failure, Chronic; Male; Neoplasms; Protein Binding; Vitamin B 12

Topics: Adult; Aged; Anemia, Hypochromic; Anemia, Macrocytic; Anemia, Pernicious; Bone Marrow Examination; Cestode Infections; Erythrocytes; Female; Hematocrit; Hemoglobinometry; Humans; Hyperthyroidism; Hypothyroidism; Iron; Kidney Failure, Chronic; Leukocyte Count; Male; Middle Aged; Neoplasms; Pregnancy; Transferases; Vitamin B 12

Topics: Adolescent; Adult; Aged; Anorexia Nervosa; Blood; Blood Proteins; Body Weight; Cobamides; Coenzymes; Evaluation Studies as Topic; Feeding and Eating Disorders; Female; Gastrointestinal Diseases; Hemoglobinometry; Humans; Liver Diseases; Male; Middle Aged; Neoplasms; Respiratory Tract Diseases; Vitamin B 12

Topics: Adult; Aged; Aminopyrine; Analgesics; Female; Humans; Male; Middle Aged; Neoplasms; Neuralgia; Neuritis; Pain; Pyridoxine; Quinolines; Rheumatic Diseases; Vitamin B 12

Topics: Anemia, Macrocytic; Blood Chemical Analysis; FIGLU Test; Folic Acid; Humans; Leukemia; Lymphatic Diseases; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Multiple Myeloma; Neoplasms; Urine; Vitamin B 12

Topics: Antineoplastic Agents; Dextrans; Humans; Hydrocortisone; Lidocaine; Neoplasms; Palliative Care; Thiamine; Vitamin B 12

Topics: Child; Data Collection; Humans; Infant; Neoplasm Metastasis; Neoplasms; Neuroblastoma; Prognosis; United States; Vitamin B 12

Topics: Adult; Aged; Asthenia; Coenzymes; Deficiency Diseases; Emaciation; Humans; Liver Diseases; Middle Aged; Neoplasms; Respiratory Tract Diseases; Vitamin B 12

Topics: Anemia; Blood Cell Count; Diagnosis; Fractures, Spontaneous; Hematology; Hematopoietic System; Hepatomegaly; Iron; Liver Diseases; Neoplasms; Neurology; Osteopetrosis; Pathology; Radiography; Splenomegaly; Vitamin B 12

Topics: Child; Cyclophosphamide; Dactinomycin; Humans; Infant; Mechlorethamine; Methotrexate; Neoplasm Metastasis; Neoplasms; Neuroblastoma; Retroperitoneal Neoplasms; Toxicology; Urography; Vitamin B 12

Topics: Abdominal Neoplasms; Catecholamines; Child; Cyclophosphamide; Head and Neck Neoplasms; Humans; Neoplasm Metastasis; Neoplasms; Neuroblastoma; Pelvic Neoplasms; Radiography; Thoracic Neoplasms; Urine; Vitamin B 12

Topics: Antineoplastic Agents; Cobalt Isotopes; Humans; Hydroxocobalamin; Neoplasm Metastasis; Neoplasms; Postoperative Complications; Surgical Procedures, Operative; Vitamin B 12

Topics: Adrenocorticotropic Hormone; Corrinoids; Desoxycorticosterone; Diet; Esophageal Neoplasms; Gastrointestinal Neoplasms; Hematinics; Humans; Nandrolone; Neoplasms; Palliative Care; Stomach Neoplasms; Thiamine; Vitamin B 12

Topics: Ascorbic Acid; Blood Transfusion; Brazil; Breast Neoplasms; Cyclophosphamide; Female; Humans; Neoplasms; Ovarian Neoplasms; Thyroid Hormones; Urethral Neoplasms; Uterine Cervical Neoplasms; Vaginal Neoplasms; Vitamin B 12; Vitamin B Complex

Topics: Anemia; Anemia, Hemolytic; Blood Protein Disorders; Brain Neoplasms; Chlormerodrin; Chromium Isotopes; Clinical Laboratory Techniques; Cobalt Isotopes; Diuretics; Erythrocytes; Heart Diseases; Hypoproteinemia; Iodine Isotopes; Kidney Diseases; Liver Diseases; Lung Diseases; Neoplasms; Obesity; Organomercury Compounds; Polycythemia; Protein Deficiency; Pulmonary Embolism; Radiation Protection; Radioisotopes; Radiometry; Radionuclide Imaging; Schilling Test; Spleen; Thinness; Thyroid Diseases; Vitamin B 12

Topics: Corrinoids; Humans; Laryngeal Neoplasms; Maxillary Neoplasms; Neoplasms; Pathology; Surgical Procedures, Operative; Vitamin B 12

Topics: Corrinoids; Cytodiagnosis; Early Diagnosis; Fluorescence; Gastric Lavage; Humans; Microscopy; Microscopy, Fluorescence; Neoplasms; Stomach Neoplasms; Urine; Vitamin B 12

Topics: Anemia; Anemia, Pernicious; Erythrocyte Count; Geriatrics; Humans; Leukemia; Leukemia, Lymphoid; Leukopenia; Neoplasms; Reticulocytes; Vitamin B 12

Topics: Anemia; Anemia, Macrocytic; Anticonvulsants; Celiac Disease; Female; FIGLU Test; Folic Acid; Folic Acid Antagonists; Folic Acid Deficiency; Formiminoglutamic Acid; Histidine; Humans; Intestinal Diseases; Intestine, Small; Intestines; Liver Diseases; Metabolic Diseases; Neoplasms; Postoperative Complications; Pregnancy; Sprue, Tropical; Vitamin B 12

Topics: Breast Neoplasms; Cyclophosphamide; Drug Therapy, Combination; Fluorouracil; Hepatomegaly; Humans; Liver Neoplasms; Methotrexate; Neoplasm Metastasis; Neoplasms; Prednisone; Testosterone; Thiotepa; Toxicology; Vitamin B 12

This series presents further evidence for an association between reticulosis of the intestine and steatorrhoea. Although some patients have a definite past history of gluten enteropathy, it seems likely that in certain patients the reticulosis itself is the primary cause of the steatorrhoea.

Topics: Ascorbic Acid; Blood Transfusion; Body Weight; Bone Marrow Examination; Celiac Disease; Diet; Diet Therapy; Fats; Feces; Folic Acid; Humans; Intestinal Neoplasms; Intestinal Perforation; Intestine, Small; Iron; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Nandrolone; Neomycin; Neoplasms; Pathology; Prednisone; Sarcoma; Steatorrhea; Surgical Procedures, Operative; Vitamin A; Vitamin B 12; Vitamin B Complex; Vitamins; Water-Electrolyte Balance

Topics: Adolescent; Antineoplastic Agents; Child; Drug Therapy; Humans; Infant; Neoplasm Metastasis; Neoplasms; Neuroblastoma; Sympathetic Nervous System; Vitamin B 12

Topics: Animals; Cobalt Isotopes; Fibrosarcoma; Hematinics; Neoplasms; Neuroblastoma; Vitamin B 12

Topics: Abdominal Neoplasms; Antineoplastic Agents; Carcinoma, Hepatocellular; Child; Cyclophosphamide; Female; Fibrosarcoma; Granulosa Cell Tumor; Humans; Infant; Leiomyoma; Liver Neoplasms; Neoplasms; Neuroblastoma; Ovarian Neoplasms; Surgical Procedures, Operative; Teratoma; Vitamin B 12; Wilms Tumor

Topics: Blood Volume Determination; Cobalt Isotopes; Cold Temperature; Corrinoids; Hematinics; Humans; Neoplasms; Phosphorus Isotopes; Radioisotopes; Radionuclide Imaging; Radiotherapy; Thyroid Function Tests; Triiodothyronine; Triolein; Vitamin B 12

Topics: Amino Acids; Animals; Avian Sarcoma Viruses; Chick Embryo; Chickens; Chorioallantoic Membrane; Enzymes; Extraembryonic Membranes; Fowlpox virus; Glycine; Hyperplasia; Hypertrophy; Liver; Neoplasms; Poxviridae; Proteins; Research; Rous sarcoma virus; Sarcoma, Avian; Vitamin B 12

Topics: Child; Humans; Infant; Neoplasms; Neuroblastoma; Surgical Procedures, Operative; Vitamin B 12

Topics: Animals; Benzimidazoles; Carcinoma 256, Walker; Neoplasm Metastasis; Neoplasms; Pharmacology; Rats; Research; Sarcoma; Sarcoma, Experimental; Vitamin B 12

Topics: Carcinogenesis; Carcinoma, Hepatocellular; Chick Embryo; Embryo, Mammalian; Embryo, Nonmammalian; Hepatectomy; Liver; Liver Extracts; Liver Neoplasms; Neoplasms; Rats; Research; Tissue Culture Techniques; Vitamin B 12; Yeasts

Topics: Alopecia; Cerebellar Neoplasms; Child; Ependymoma; Humans; Neoplasms; Neurosurgery; Radiation Injuries; Vitamin B 12; X-Rays

Topics: Animals; Mice; Neomycin; Neoplasms; Vitamin B 12

Topics: Humans; Infections; Neoplasms; Radiotherapy; Rolitetracycline; Vitamin B 12

Topics: Animals; Carcinogens; Carcinoma, Hepatocellular; Liver Neoplasms; Liver Neoplasms, Experimental; Neoplasms; p-Dimethylaminoazobenzene; Rats; Riboflavin; Vitamin B 12

Topics: Hematinics; Liver; Neoplasms; Vitamin B 12

Topics: Animals; Biochemical Phenomena; Cobalt; Corrinoids; Humans; Mice; Neoplasms; Research Design; Tissue Culture Techniques; Vitamin B 12

Topics: Corrinoids; Heart Diseases; Hematinics; Hematologic Diseases; Humans; Neoplasms; Vitamin B 12

Topics: Corrinoids; Female; Genitalia; Genitalia, Female; Hematinics; Humans; Neoplasms; Vitamin B 12; Vitamins

Topics: Bone Marrow; Bone Marrow Diseases; Humans; Leukemia; Leukemia, Myeloid; Myeloproliferative Disorders; Neoplasms; Vitamin B 12

Topics: Biological Assay; Corrinoids; Hematinics; Hematologic Diseases; Humans; Lactobacillus; Neoplasms; Vitamin B 12

Topics: Animals; Carcinoma, Hepatocellular; Encephalomyelitis; Liver Neoplasms; Neoplasms; Rats; Vitamin B 12

Topics: F Factor; Humans; Neoplasms; Tissue Extracts; Vitamin B 12

Topics: Humans; Neoplasms; Vitamin B 12; Vitamin B Complex

Topics: Humans; Neoplasms; Vitamin B 12

Topics: Anemia; Anemia, Pernicious; Bone Marrow; Corrinoids; Hematinics; In Vitro Techniques; Neoplasms; Vitamin B 12

Topics: Humans; Neoplasms; Vitamin B 12

Topics: Corrinoids; Hematinics; Humans; Neoplasms; Radiation Injuries; Vitamin B 12; X-Ray Therapy

Topics: Corrinoids; Folic Acid; Hematinics; Humans; Neoplasms; Vitamin B 12; Vitamin B Complex