vitamin-b-12 and Neuroblastoma

Topics: Adolescent; Adult; Age Factors; Child; Child, Preschool; Deglutition Disorders; Female; Ganglioneuroma; Horner Syndrome; Humans; Hypertension; Infant; Infant, Newborn; Lung Diseases; Lung Neoplasms; Male; Mediastinal Neoplasms; Mediastinum; Meningocele; Middle Aged; Neoplasm Regression, Spontaneous; Neoplasms, Nerve Tissue; Neurilemmoma; Neuroblastoma; Neurofibroma; Neurofibromatosis 1; Neurologic Manifestations; Osteoarthropathy, Secondary Hypertrophic; Pain; Paraganglioma, Extra-Adrenal; Pheochromocytoma; Sex Factors; Vitamin B 12

Oxidative stress is closely linked to Alzheimer's disease (AD), and is detected peripherally as well as in AD-vulnerable brain regions. Oxidative stress results from an imbalance between the generation and degradation of reactive oxidative species (ROS), leading to the oxidation of proteins, nucleic acids, and lipids. Extensive lipid changes have been found in post mortem AD brain tissue; these changes include the levels of total phospholipids, sphingomyelin, and ceramide, as well as plasmalogens, which are highly susceptible to oxidation because of their vinyl ether bond at the sn-1 position of the glycerol-backbone. Several lines of evidence indicate that a deficiency in the neurotropic vitamin B12 is linked with AD. In the present study, treatment of the neuroblastoma cell line SH-SY5Y with vitamin B12 resulted in elevated levels of phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, and plasmalogens. Vitamin B12 also protected plasmalogens from hydrogen peroxide (H

Topics: Alzheimer Disease; Humans; Hydrogen Peroxide; Neuroblastoma; Oxidative Stress; Plasmalogens; Reactive Oxygen Species; Sphingomyelins; Vitamin B 12

Homocysteine is an excitatory amino acid implicated in multiple diseases including amyotrophic lateral sclerosis (ALS). Information on the toxicity of homocysteine in motor neurons is limited and few studies have examined how this toxicity can be modulated. In NSC-34D cells (a hybrid cell line derived from motor neuron-neuroblastoma), homocysteine induces apoptotic cell death in the millimolar range with a TC₅₀ (toxic concentration at which 50% of maximal cell death is achieved) of 2.2 mM, confirmed by activation of caspase 3/7. Induction of apoptosis was independent of short-term reactive oxygen species (ROS) generation. Methyl Vitamin B12 (MeCbl) and methyl tetrahydrofolate (MTHF), used clinically to treat elevated homocysteine levels, were tested for their ability to reverse homocysteine-mediated motor neuron cell death. MeCbl in the micromolar range was able to provide neuroprotection (2 h pretreatment prior to homocysteine) and neurorescue (simultaneous exposure with homocysteine) against millimolar homocysteine with an IC₅₀ (concentration at which 50% of maximal cell death is inhibited) of 0.6 μM and 0.4 μM, respectively. In contrast, MTHF (up to 10 μM) had no effect on homocysteine-mediated cell death. MeCbl inhibited caspase 3/7 activation by homocysteine in a time- and dose-dependent manner, whereas MTHF had no effect. We conclude that MeCbl is effective against homocysteine-induced cell death in motor neurons in a ROS-independent manner, via a reduction in caspase activation and apoptosis. MeCbl decreases Hcy induced motor neuron death in vitro in a hybrid cell line derived from motor neuron-neuroblastoma and may play a role in the treatment of late stage ALS where HCy levels are increased in animal models of ALS.

Topics: Animals; Apoptosis; Caspase 3; Caspase 7; Cell Line, Tumor; Dose-Response Relationship, Drug; Homocysteine; Inhibitory Concentration 50; Mice; Motor Neurons; Neuroblastoma; Neuroprotective Agents; Reactive Oxygen Species; Tetrahydrofolates; Time Factors; Vitamin B 12; Vitamin B Complex

Increased homocysteine has in some cases been linked with an increased incidence of Alzheimer's disease and motor neuron disease. Folate or B12 deficiency increases homocysteine, but controversy exists as to whether their levels also correlate with either disorder. Since their presence within various dietary constituents may confound interpretation, we tested the impact of deprivation of either or both in the closed environment of neuronal cell cultures. Deprivation of either increased cytosolic calcium, reactive oxygen species, intracellular homocysteine, and apoptosis, but deprivation of both fostered substantially larger increases, supporting the notion that both are required for optimal neuroprotection.

Topics: Calcium; Cell Line, Tumor; Folic Acid; Folic Acid Deficiency; Homocysteine; Humans; Nerve Degeneration; Neuroblastoma; Neurons; Reactive Oxygen Species; Vitamin B 12; Vitamin B 12 Deficiency

Transformed cells have been documented to be methionine-dependent, suggesting that inhibition of methionine synthesis might be useful for cancer therapy. Methylenetetrahydrofolate reductase synthesises 5-methyltetrahydrofolate, the methyl donor utilised in methionine synthesis from homocysteine by vitamin B(12)-dependent methionine synthase. We hypothesised that methylenetetrahydrofolate reductase inhibition would affect cell viability through decreased methionine synthesis. Using medium lacking methionine, but containing homocysteine and vitamin B(12) (M-H+), we found that nontransformed human fibroblasts could maintain growth. In contrast, four transformed cell lines (one colon carcinoma, two neuroblastoma and one breast carcinoma) increased proliferation only slightly in the M-H+ medium. To downregulate methylenetetrahydrofolate reductase expression, two phosphorothioate antisense oligonucleotides, EX5 and 677T, were used to target methylenetetrahydrofolate reductase in the colon carcinoma line SW620; 400 nM of each antisense oligonucleotide decreased cell survival by approximately 80% (P<0.01) and 70% (P<0.0001), respectively, compared to cell survival after the respective control mismatched oligonucleotide. Western blotting and enzyme assays confirmed that methylenetetrahydrofolate reductase expression was decreased. Two neuroblastoma and two breast carcinoma lines also demonstrated decreased survival following EX5 treatment whereas nontransformed human fibroblasts were not affected. This study suggests that methylenetetrahydrofolate reductase may be required for tumour cell survival and that methylenetetrahydrofolate reductase inhibition should be considered for anti-tumour therapy.

Topics: Antineoplastic Agents; Breast Neoplasms; Carcinoma; Cell Line; Colonic Neoplasms; Enzyme Inhibitors; Exons; Female; Fibroblasts; Genetic Therapy; Homocysteine; Humans; Methionine; Methylenetetrahydrofolate Reductase (NADPH2); Neoplasm Proteins; Neuroblastoma; Oligodeoxyribonucleotides, Antisense; Oxidoreductases Acting on CH-NH Group Donors; RNA, Messenger; RNA, Neoplasm; Thionucleotides; Tumor Cells, Cultured; Vitamin B 12

Serum vitamin B12, serum and red cell folate and serum vitamin B12 binding proteins were determined in 18 patients with neuroblastoma, with ages ranging from 8 months to 14 years. A mean value of serum vitamin B12 level was slightly but not significantly lower than that of the normal subjects but all of them had serum vitamin B12 levels over 150 pg/ml. There was no relationship between serum vitamin B12 levels and hemoglobin, hematocrit or white cells. Transcobalamin I (TCI) was significantly increased resulting in slightly elevated UBBC and normal TBBC levels in these patients. This could be a compensatory mechanism for the low serum vitamin B12 by increasing the unsaturated vitamin B12 binding capacity of TCI. All these findings indicated that the status of vitamin B12 in patients with neuroblastoma was within the normal limits. Treatment of neuroblastoma by giving a high dose of vitamin B12 would therefore not give any direct therapeutic effect. Both serum and red cell folate concentrations were significantly lower in the group of patients. As only 2 out of 18 patients had low serum folate and none of them had red cell folate lower than the lower limit of normal subjects; therefore these patients were only in the state of negative folate balance.

Topics: Adolescent; Child; Child, Preschool; Female; Folic Acid; Humans; Infant; Male; Neuroblastoma; Transcobalamins; Vitamin B 12

Between 1949 and 1978, 119 children with the diagnosis of neuroblastoma or ganglioneuroblastoma were treated at the Washington University Medical Center. Of these, 50 (41%) were alive and disease-free 3 or more years after diagnosis. Important prognostic variables included stage of tumor (Evans staging), histology, age at diagnosis, and site of primary tumor. A stepwise logistic regression analysis of these data has shown that, in order of significance, stage, histology and age at diagnosis are independent prognostic variables. Sex of the patient and nodal status at diagnosis (where known) were not significant prognostic variables. No effects of individual treatment modalities could be detected. This study confirms the overwhelming influence of factors unrelated to treatment in determining the prognosis of neuroblastoma.

Topics: Adolescent; Antineoplastic Agents; Child; Child, Preschool; Combined Modality Therapy; Female; Follow-Up Studies; Ganglia, Sympathetic; Ganglioneuroma; Humans; Infant; Infant, Newborn; Lymphatic Metastasis; Male; Nervous System Neoplasms; Neuroblastoma; Prognosis; Vitamin B 12

Topics: Adult; Female; Humans; Lung Abscess; Neuroblastoma; Sympathetic Nervous System; Vitamin B 12

Topics: Age Factors; Child, Preschool; Female; Follow-Up Studies; Ganglioneuroma; Humans; Infant; Infant, Newborn; Lymphatic Metastasis; Male; Neoplasm Regression, Spontaneous; Neuroblastoma; Pelvic Neoplasms; Prognosis; Vitamin B 12

Topics: Adrenal Glands; Autopsy; Biological Assay; Cobalt Isotopes; Diaphragm; Digestive System; Humans; Infant; Kidney; Liver; Lung; Male; Mediastinal Neoplasms; Myocardium; Neuroblastoma; Pancreas; Spleen; Testis; Urinary Bladder; Vitamin B 12

Topics: Adult; Female; Humans; Kidney Neoplasms; Neoplasm Regression, Spontaneous; Neuroblastoma; Pregnancy; Pregnancy Complications; Vitamin B 12

Topics: Age Factors; Child; Child, Preschool; Humans; Infant; Neoplasm Metastasis; Neoplasm Regression, Spontaneous; Neuroblastoma; Retrospective Studies; Vitamin B 12

Topics: Age Factors; Bone Marrow; Bone Marrow Cells; Child, Preschool; Cobalt Isotopes; Cyclophosphamide; Female; Ganglia, Autonomic; Ganglioneuroma; Hemoglobins; Humans; Infant; Male; Neoplasm Metastasis; Neoplasms, Nerve Tissue; Neuroblastoma; Prognosis; Radiography; Scoliosis; Vincristine; Vitamin B 12

Topics: Burns; Humans; Hydrocephalus; Infant; Male; Mechlorethamine; Meningitis; Methotrexate; Neuroblastoma; Polymyxins; Pseudomonas Infections; Vitamin B 12

Topics: Abdominal Neoplasms; Adolescent; Adult; Aged; Breast Neoplasms; Carcinoma; Child; Cobalt Isotopes; Female; Gastric Juice; Gastrointestinal Neoplasms; Genital Neoplasms, Female; Hodgkin Disease; Humans; Intestinal Mucosa; Iodine Isotopes; Leiomyosarcoma; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Male; Mesothelioma; Methods; Middle Aged; Neuroblastoma; Pancreatic Neoplasms; Povidone; Radiation Effects; Radioisotope Teletherapy; Splenic Neoplasms; Time Factors; Triolein; Vitamin B 12

Topics: Bone Neoplasms; Female; Humans; Infant; Male; Neoplasm Metastasis; Neuroblastoma; Vitamin B 12

Topics: Adrenal Gland Neoplasms; Humans; Infant, Newborn; Infant, Newborn, Diseases; Liver Neoplasms; Male; Mandelic Acids; Neoplasm Metastasis; Neuroblastoma; Prognosis; Skin Neoplasms; Vitamin B 12

Topics: Aged; Female; Hemangiosarcoma; Humans; Infant; Liver Neoplasms; Male; Neoplasm Metastasis; Neuroblastoma; Skin Neoplasms; Vitamin B 12

Topics: Age Factors; Child, Preschool; Cyclophosphamide; Dactinomycin; Humans; Infant; Mechlorethamine; Neoplasm Metastasis; Neuroblastoma; Nitrogen Mustard Compounds; Prognosis; Vincristine; Vitamin B 12

Topics: Adrenal Gland Neoplasms; Antineoplastic Agents; Bone Neoplasms; Child, Preschool; Female; Fetus; Humans; Infant; Infant, Newborn; Infant, Premature; Neoplasm Metastasis; Neuroblastoma; Pregnancy; Radiography, Abdominal; Teratoma; Vitamin B 12

Topics: Adolescent; Adult; Child; Child, Preschool; Cyclophosphamide; Female; Humans; Infant; Male; Neuroblastoma; Retrospective Studies; Vitamin B 12

Topics: Adolescent; Child; Child, Preschool; Female; Humans; Male; Neuroblastoma; Sympathetic Nervous System; Vitamin B 12

Topics: Abdominal Neoplasms; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Neuroblastoma; Nitrogen Mustard Compounds; Vitamin B 12

Topics: Adolescent; Antineoplastic Agents; Child; Child, Preschool; Female; Humans; Male; Neuroblastoma; Vitamin B 12

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

Topics: Child; Corrinoids; Drug Therapy; Hematinics; Humans; Infant; Infant, Newborn; Neoplasm Regression, Spontaneous; Neuroblastoma; 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: 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; Corrinoids; Humans; Neuroblastoma; Vitamin B 12; Vitamin B Complex

Topics: Anti-Bacterial Agents; Antibiotics, Antitubercular; Corrinoids; Dermatologic Agents; Humans; Ireland; Neuroblastoma; Vitamin B 12

Topics: Corrinoids; Hematinics; Neuroblastoma; Vitamin B 12; Vitamin B Complex

Topics: Abdominal Neoplasms; Corrinoids; Humans; Neuroblastoma; Vitamin B 12; Vitamin B Complex

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: Bone Neoplasms; Corrinoids; Cyclophosphamide; Humans; Infant; Lymphatic Metastasis; Neuroblastoma; Prognosis; Radiography; Vitamin B 12

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