vitamin-k-semiquinone-radical and Neuroblastoma

Gastroschisis is the most common abdominal wall defect. It is characterized by herniation of the intestine and other abdominal organs through a defect in the abdominal wall. Neuroblastoma is the most common malignant tumor observed during the neonatal period. It is a neuroendocrine tumor derived from neural crest cells that develops into the adrenal gland.. We report on the undescribed association between gastrochisis and congenital neuroblastoma, diagnosised during the prenatal period. The mother was a 20-year-old healthy pregnant woman in her second pregnancy. Obstetric ultrasound examination showed a fetus presenting an abdominal wall defect on the right side of the umbilical cord, compatible with gastroschisis, and a hyperechogenic and spherical solid lesion on the left adrenal gland. Fetal magnetic resonance imaging disclosed similar features associated to a heterogeneous aspect of the liver. The diagnosis of metastatic neuroblastoma was confirmed after birth through liver biopsy. At 2 days of life, the prothrombrin time was abnormal, and the patient needed vitamin K.. We cannot rule out the possibility that a clotting defect, commonly observed in disseminated malignancies such as a metastatic neuroblastoma may be associated with the etiology of the gastroschisis, as this defect may result from a thrombosis occurring around 3 to 4 weeks of gestation, a period when neuroblasts development occurs into the adrenal medulla. However, we cannot exclude the possibility that both events may have occurred simultaneously by chance.

Topics: Abdominal Wall; Adrenal Gland Neoplasms; Adrenalectomy; Antifibrinolytic Agents; Female; Fetus; Gastroschisis; Gestational Age; Humans; Infant, Newborn; Liver Neoplasms; Neuroblastoma; Pregnancy; Thrombosis; Ultrasonography, Prenatal; Vitamin K; Young Adult

In this paper we report on our studies of the effect of menadione on the uptake of MIBG in the neuroendocrine cell lines PC12 and SK-N-SH. Menadione inhibits the uptake of MIBG in both cell lines in a dose-dependent manner. Inhibition of MIBG uptake is most pronounced in the PC12 cell line. Comparison of the inhibitory action of menadione on the uptake and retention of MIBG with that of imipramine and reserpine suggests that menadione inhibits uptake 1 mediated uptake as well as granular storage.

Topics: 3-Iodobenzylguanidine; Adrenergic Uptake Inhibitors; Animals; Antineoplastic Agents; Cytoplasmic Granules; Hemostatics; Humans; Imipramine; Iodine Radioisotopes; Iodobenzenes; Neuroblastoma; PC12 Cells; Rats; Reserpine; Vitamin K

Oxidative stress has been implicated in the mechanism of aging and neurodegenerative disorders such as Alzheimer's disease (AD). Menadione causes oxidative stress by generating reactive oxygen species through its redox cycling and these free radicals are detoxified subsequently at the expense of intracellular thiol homeostasis. In non-neuronal cells, the cytoskeleton is a prime target of menadione-induced thiol oxidation. We used cultured human neuroblastoma MSN cells in this study to determine how tau proteins in neuronal cells are affected by menadione exposure. Menadione caused a dose-dependent thiol oxidation in these cells just like their non-neuronal counterparts. A prominent consequence of such oxidative insult in these neuronal cells was tau dephosphorylation. This dephosphorylation resulted in disappearance of phosphorylated 57-kDa tau with a concomitant emergence of 53-kDa tau whose full-length nature is indicated by its reactivity with antibodies Alz 50, Tau-1 and Tau-46. Immunochemical analyses using phosphorylation-dependent immunoprobes Tau-1 and PHF-1 with the aid of alkaline phosphatase demonstrated that 53-kDa tau was derived from dephosphorylation of 57-kDa tau. Despite its effect on thiol oxidation, menadione treatment did not lead to cytoskeletal changes reminiscent of the neurofibrillary tangles of AD. The data thus indicate that tau dephosphorylation constitutes a major feature of the menadione-induced oxidative injury in these neuronal cells.

Topics: Cell Survival; Cells, Cultured; Hemostatics; Humans; Immunohistochemistry; Neuroblastoma; Phosphorylation; tau Proteins; Vitamin K

To confirm or refute a possible association of parenteral vitamin K prophylaxis and childhood cancer.. Population based case-control study. Comparison of vitamin K exposure in children with leukaemia or other common tumours with two control groups.. State of Lower Saxony (north western part of Germany); case recruitment from the German childhood cancer registry.. 272 children with leukaemia, nephroblastoma, neuroblastoma, rhabdomyosarcoma, and tumours of the central nervous system diagnosed between 1 July 1988 and 30 June 1993; children were aged between 30 days and 15 years at diagnosis. 334 population based controls without diagnoses of cancer matched to the leukaemia cases for age and sex.. Parenteral vitamin K prophylaxis (intramuscular and subcutaneous) versus oral and no vitamin K prophylaxis.. An association between parenteral vitamin K exposure and childhood cancer (leukaemias and other tumours combined) could not be confirmed (odds ratio 1.04, 95% confidence interval 0.74 to 1.48). For leukaemias the observed odds ratio was only 0.98 (0.64 to 1.50) (comparison of leukaemia cases with local controls 1.24 (0.68 to 2.25); state controls 0.82 (0.50 to 1.36)). These odds ratios remained almost unchanged when several potential confounders were considered in the logistic regression model.. This population based study adds substantial evidence that there is no association between parenteral vitamin K and childhood cancer.

Topics: Adolescent; Case-Control Studies; Central Nervous System Neoplasms; Child; Child, Preschool; Female; Germany; Humans; Infant; Infant, Newborn; Injections, Intramuscular; Injections, Subcutaneous; Kidney Neoplasms; Leukemia; Male; Neoplasms; Neuroblastoma; Population Surveillance; Rhabdomyosarcoma; Risk Factors; Vitamin K; Vitamin K Deficiency; Wilms Tumor

The effects of intracellularly generated H2O2 on cell viability, morphology, and biochemical markers of injury have been investigated in a clonal cell line of neuronal origin (140-3, mouse neuroblastoma X rat glioma) as a cell culture model for the role of oxidative stress in the long-term loss of neurons in the brain. The H2O2 was generated from the redox cycling of menadione, or by the oxidation of serotonin catalyzed by monoamine oxidase, to simulate the effect of amine neurotransmitter turnover. Incubation with menadione at concentrations as low as 10 microM for several hours resulted in significant losses of cell viability and altered morphology. Similar effects were evident in the presence of serotonin only after incubation overnight with concentrations > 1 mM. The cytotoxicity of either agent was potentiated by preincubation with specific inhibitors of two enzymes important to cellular antioxidant defenses, 3-amino-1,2,4-triazole for catalase and 1,3-bis(chloromethyl)-1-nitrosourea for glutathione reductase. Activity of another antioxidant enzyme of particular importance to antioxidant defenses in brain, the selenoprotein glutathione peroxidase, was stimulated fourfold by growth of cultures in the presence of sodium selenite as a source of active-site Se for the enzyme. The only effect of the selenite on other functionally coupled antioxidant enzymes was a decrease in activity of superoxide dismutase at concentrations > 200 nM. The selenite substantially protected cells against oxidative stress induced by combinations of menadione, 3-amino-1,2,4-triazole, and 1,3-bis(chloromethyl)-1-nitrosourea, but was only marginally effective with serotonin as a source of oxidative stress. The monoamine oxidase inhibitor pargyline increased cell survival in the presence of serotonin, demonstrating the role of this enzyme in its cytotoxicity. DNA damage (single strand breaks), but not lipid peroxidation, correlated with the cytotoxic effects of menadione.

Topics: Animals; Brain; Carmustine; Catalase; Cell Fractionation; Cell Survival; Clone Cells; Cytosol; Glioma; Glutathione Peroxidase; Glutathione Reductase; Hybrid Cells; Hydrogen Peroxide; Kinetics; Mice; Mitochondria; Monoamine Oxidase; Neuroblastoma; Neurons; Pargyline; Rats; Serotonin; Superoxide Dismutase; Tumor Cells, Cultured; Vitamin K

During a Phase I study of intravenous vitamin E-free alcohol (all-rac-alpha-tocopherol or Ephynal) in patients with neuroblastoma, we noticed a bleeding diathesis in two patients receiving 2300 mg/m2 daily for four or more days in succession. Both blood prothrombin time and accelerated partial thromboplastin times were prolonged. These spontaneously returned to normal levels three days after interrupting vitamin E infusions. It was also noted that factors VII, IX and X were decreased, which corresponded with the prolonged PT and APTT. It was found that by infusing menadiol sodium diphosphate just prior to the vitamin E, these inhibiting effects on procoagulant factors could be abrogated and high dosages of vitamin E-free alcohol safely given.

Topics: Blood Coagulation Factors; Child; Child, Preschool; Drug Interactions; Factor IX; Factor VII; Factor X; Humans; Male; Neuroblastoma; Partial Thromboplastin Time; Prothrombin; Prothrombin Time; Vitamin E; Vitamin K

Topics: Animals; Cell Division; Cells, Cultured; Choline O-Acetyltransferase; Glioma; Melanoma; Mice; Neoplasms, Experimental; Neuroblastoma; Rats; Tyrosine 3-Monooxygenase; Vitamin K

Topics: Animals; Carcinogens; Dicumarol; Dinitrophenols; In Vitro Techniques; Mice; Mitochondria; Neoplasms, Experimental; Neuroblastoma; Quinidine; Vitamin K