vitamin-k-semiquinone-radical and Brain-Neoplasms

Malignant gliomas are the most common primary brain tumors. Due to both their invasive nature and resistance to multimodal treatments, these tumors have a very high percentage of recurrence leading in most cases to a rapid fatal outcome. Recent data demonstrated that neural stem/progenitor cells possess an inherent ability to migrate towards glioma cells, track them in the brain and reduce their growth. However, mechanisms involved in these processes have not been explored in-depth. In the present report, we investigated interactions between glioma cells and neural stem/progenitor cells derived from the subventricular zone, the major brain stem cell niche. Our data show that neural stem/progenitor cells are attracted by cultured glioma-derived factors. Using multiple approaches, we demonstrate for the first time that the vitamin K-dependent factor protein S produced by glioma cells is involved in tumor tropism through a mechanism involving the tyrosine kinase receptor Tyro3 that, in turn, is expressed by neural stem/progenitor cells. Neural stem/progenitor cells decrease the growth of both glioma cell cultures and clonogenic population. Cultured neural stem/progenitor cells also engulf, by phagocytosis, apoptotic glioma cell-derived fragments and this mechanism depends on the exposure of phosphatidylserine eat-me signal and is stimulated by protein S. The disclosure of a role of protein S/Tyro3 axis in neural stem/progenitor cell tumor-tropism and the demonstration of a phagocytic activity of neural stem/progenitor cells towards dead glioma cells that is regulated by protein S open up new perspectives for both stem cell biology and brain physiopathology.

Topics: Animals; Apoptosis; Brain; Brain Neoplasms; Cell Line, Tumor; Cell Movement; Cell Proliferation; Glioma; Neural Stem Cells; Phagocytes; Protein S; Rats; Vitamin K

The antitumor effects of vitamin K2 were studied using three glioma cell lines: C6 (rat glioma cell), RBR17T and T98G (human glioma cell). The antitumor effects were estimated by count assay. The results was that vitamin K2 induced growth inhibition in a dose-dependent manner. The RBR 17T cells exposed to vitamin K2 for 72 hours resulted in oligonucleosomal DNA fragmentation and formed a ladder on agarose gel electrophoresis. Furthermore, the RBR17T cells exposed to vitamin K2 for 24 hours were significantly accumulated in the G0G1 phase of the cell cycle. Those results suggested that vitamin K2 can inhibit the proliferation of cells through the induction of cell cycle arrest and apoptosis for tumor cells. The combined treatment of vitamin K2 with ACNU or 5-FU or INF-beta or 1,25-dihydroxyvitamin D3 enhanced growth inhibition significantly. In conclusion, vitamin K2 can be a useful drug for the treatment of glioma.

Topics: Animals; Antineoplastic Agents; Apoptosis; Brain Neoplasms; Cell Cycle; Cell Division; Glioma; Rats; Tumor Cells, Cultured; Vitamin D; Vitamin K

Factor VII deficiency is characterized by epistaxis, bruising, hemarthrosis, menorrhagia, gastrointestinal bleeding, hematuria, and intracranial hemorrhage during infancy. Causes of acquired factor VII deficiency include liver disease, Vitamin K deficiency, and warfarin administration. Congenital factor VII deficiency is an autosomal recessive disorder, with the homozygotes having a severe deficiency and the heterozygotes a moderate deficiency of factor VII. Orthopedic, gynecological, cardiothoracic, and abdominal surgical procedures have been successfully performed in patients with factor VII deficiency both with and without factor VII replacement. We present two patients with moderate and moderately severe factor VII deficiency who successfully underwent intracranial procedures using plasma during the perioperative period for factor VII replacement. One patient successfully underwent stereotactic placement of mesial temporal lobe depth electrodes and subdural strip electrodes followed by anterior temporal lobectomy for medically refractory seizures. The second patient successfully underwent craniotomy for an olfactory groove meningioma. No bleeding complications were encountered with any of the three intracranial procedures performed. These cases represent the first reported cases of successful intracranial procedures in patients with factor VII deficiency, other than shunting procedures performed for intraventricular hemorrhage during infancy.

Topics: Adult; Aged; Blood Transfusion; Brain; Brain Neoplasms; Craniotomy; Electrodes, Implanted; Factor VII Deficiency; Female; Humans; Male; Meningioma; Neurosurgery; Psychosurgery; Seizures; Stereotaxic Techniques; Temporal Lobe; Vitamin K

Topics: Brain Neoplasms; Bromodeoxyuridine; Dactinomycin; DNA; Fluorouracil; Glycogen; Humans; Neoplasms; Oxygen; Radiation-Sensitizing Agents; RNA; Vitamin K