levetiracetam and Ovarian-Neoplasms

Anti-N-methyl-D-aspartate receptor encephalitis is an autoimmune syndrome that presents with personality changes, autonomic dysfunction, and neurologic deterioration. Most patients with this syndrome progress from psychosis to seizure to catatonia, often associated with abnormal movements, autonomic instability, and hypoventilation. First-line treatment constitutes resection of the associated neoplasm, corticosteroids, intravenous immunoglobulin, and plasma exchange. Second-line treatment includes rituximab and cyclophosphamide. A case of confirmed anti-N-methyl-D-aspartate receptor encephalitis is presented that illustrates the diagnostic and treatment challenges associated with this syndrome and underscores the nursing implications of medical management during immunosuppression. This case study recommends surface cooling and a pharmaceutical regimen for management of autonomic storming, which is a hallmark of this disorder.

Topics: Adult; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Anticonvulsants; Cyclophosphamide; Fatal Outcome; Female; Headache; Humans; Immunologic Factors; Immunosuppressive Agents; Levetiracetam; Ovarian Neoplasms; Piracetam; Rituximab; Seizures

Histone deacetylases (HDACs) are often overexpressed in cancer cells, leading to altered expression and activity of numerous proteins involved in carcinogenesis. Recent evidence suggests that expression of class I HDACs is increased in ovarian carcinomas and plays a significant role in carcinogenesis and resistance to chemotherapeutic agents. Two compounds, valproic acid (VPA) and levetiracetam (LEV), exhibit HDAC inhibitor (HDACI) activity in various cell types, but data concerning their activity in ovarian cancer are lacking. Here we compared the effects of VPA and LEV as HDACIs, using a human ovarian cancer cell line, OVCAR-3. Cells were cultured with VPA or LEV at concentrations between 1 and 10 mM for 1-24h. HDAC activity was determined by fluorometric assay and confirmed by western blotting. Expression of HDAC genes was determined by real-time PCR and HDAC proteins expression was evaluated by western blotting. Additionally, we used high-performance liquid chromatography to determine whether OVCAR-3 cells can metabolize LEV to its major metabolite, 2-pyrrolidinone-n-butyric acid (PBA), which might exert HDACI activity. LEV, however, had no apparent effect on HDAC activity, or gene and protein expression. The OVCAR-3 cell line was able to metabolize LEV to PBA, but the effect was small. Our observations suggest that VPA should be considered as a possible adjunctive drug in ovarian cancer treatment.

Topics: Antineoplastic Agents; Cell Line, Tumor; Female; Histone Deacetylase 2; Histone Deacetylase Inhibitors; Histone Deacetylases; Humans; Levetiracetam; Ovarian Neoplasms; Piracetam; Valproic Acid

We report here two cases of autoimmune encephalitis associated with antibodies against the N-methyl-D-aspartate receptor. The primary cause was an ovarian teratoma in one case. The outcomes were good. The first case was a late diagnosis, despite a typical clinical presentation. The clinical presentation of this disease remains unknown, especially in the intensive care unit. The treatment was recently codified and transformed the prognosis of this encephalitis. The second case was early treated in the course of the disease, due to the experience related to the previous case. In case of unexplained acute or subacute encephalitis or psychiatric-like disorders without prior medical history, the determination of the level of expression of antibodies against the N-methyl-D-aspartate receptors and other antineuroreceptors antibodies can help to identify this diagnosis. The initial picture of the disease, its variability and the unawareness of the recent reports on this encephalitis may lead to a wrong diagnosis and inappropriate management.

Topics: Adrenal Cortex Hormones; Adult; Anticonvulsants; Autoimmune Diseases of the Nervous System; Critical Care; Early Diagnosis; Electroencephalography; Female; Glasgow Coma Scale; Humans; Immunization, Passive; Levetiracetam; Limbic Encephalitis; Magnetic Resonance Imaging; Marijuana Smoking; Mental Disorders; Nervous System Diseases; Ovarian Neoplasms; Piracetam; Receptors, N-Methyl-D-Aspartate; Teratoma; Tomography, X-Ray Computed

Concentration- and time-dependent effects of two antiepileptic drugs (AEDs), levetiracetam (LEV) and valproic acid (VPA), on proliferation, cytotoxicity and expression of cell cycle regulatory genes were investigated in a human ovarian cancer cell line, OVCAR-3. Cells were cultured with VPA or LEV, at concentrations between 100 μM and 10 mM. Cell proliferation was determined by alamarBlue and BrdU incorporation assays; cytotoxic effects by tetrazolium hydroxide (XTT), acid phosphatase (AP) and lactate dehydrogenase (LDH) assays. Expression of cell cycle regulatory genes was determined by real-time PCR. Exposure to VPA caused a concentration- and time-dependent decrease in cell proliferation (alamarBlue and BrdU incorporation assays), cytotoxic effects above 2.5 mM (XTT and AP assays) and modulated expression of genes primarily responsible for cell cycle arrest in G(1) phase. Cell proliferation was unaffected by exposure to LEV for 24 h and 120 h (alamarBlue assay), but increased when exposed to LEV for 72 h and 168 h, at concentrations from 250 μM to 1 mM. The BrdU incorporation assay showed no effect of LEV on cell proliferation. LEV was cytotoxic at higher concentrations (AP assay), but modulation in expression of cell cycle regulatory genes was not observed. Changes in LDH release were not observed with either AED. In summary, VPA apparently decreased cell proliferation by down-regulating genes responsible for transition from G(1) to S phase and up-regulating genes responsible for G(1) phase arrest, which suggest its potential as an anticancer drug. LEV does not exhibit such action.

Topics: Anticonvulsants; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; Cell Survival; Female; G1 Phase; Gene Expression Regulation, Neoplastic; Genes, cdc; Humans; Levetiracetam; Ovarian Neoplasms; Piracetam; S Phase; Valproic Acid

We have previously shown that due to its cytotoxic and cytostatic activities, valproic acid (VPA), but not levetiracetam (LEV), may have potential as a drug for treating human ovarian cancer. In the present study, we compare apoptotic mechanisms including gene and protein expression in the human ovarian cancer cell line, OVCAR-3, following exposure to VPA and LEV.. Cells were cultured with VPA or LEV at concentrations between 0.1 mM and 10 mM. Apoptosis was assessed by DNA fragmentation assay and expression of apoptosis-regulatory genes determined by real-time PCR and confirmed by western blotting. Time-dependent effects of VPA and LEV on activity of caspases (-3, -8 and -9) activity were evaluated by fluorescent assay and western blotting.. Exposure to VPA at concentrations above 5 mM resulted in an increase in DNA fragmentation, modulated expression of genes and proteins associated with apoptosis and activated caspases cascade. Exposure to LEV, however, did not affect DNA fragmentation and modulation of the mechanisms of apoptosis was not observed in LEV-treated cells at all doses used.. Exposure to high concentrations of VPA significantly stimulated apoptosis, by modulating the expression of genes and proteins responsible for cell death and also by activation of caspases cascade. Such effects were not observed with LEV. These data suggest that VPA should be seriously evaluated as an anti-cancer drug for ovarian cancer.

Topics: Antineoplastic Agents; Apoptosis; Blotting, Far-Western; Caspase 3; Caspase 8; Caspase 9; Cell Line, Tumor; DNA Fragmentation; Dose-Response Relationship, Drug; Female; Gene Expression Regulation, Neoplastic; Humans; Levetiracetam; Ovarian Neoplasms; Piracetam; Time Factors; Valproic Acid