RESUMO
Pharmacological ascorbate has been proposed as a potential anti-cancer agent when combined with radiation and chemotherapy. The anti-cancer effects of ascorbate are hypothesized to involve the autoxidation of ascorbate leading to increased steady-state levels of H2O2; however, the mechanism(s) for cancer cell-selective toxicity remain unknown. The current study shows that alterations in cancer cell mitochondrial oxidative metabolism resulting in increased levels of O2â - and H2O2 are capable of disrupting intracellular iron metabolism, thereby selectively sensitizing non-small-cell lung cancer (NSCLC) and glioblastoma (GBM) cells to ascorbate through pro-oxidant chemistry involving redox-active labile iron and H2O2. In addition, preclinical studies and clinical trials demonstrate the feasibility, selective toxicity, tolerability, and potential efficacy of pharmacological ascorbate in GBM and NSCLC therapy.
Assuntos
Ácido Ascórbico/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Ferro/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ácido Ascórbico/administração & dosagem , Ácido Ascórbico/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Linhagem Celular Tumoral , Quimiorradioterapia/métodos , Feminino , Glioblastoma/metabolismo , Humanos , Peróxido de Hidrogênio/farmacologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/radioterapia , Masculino , Camundongos Nus , Oxigênio/metabolismo , Radiossensibilizantes/farmacologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Paroxysmal cold hemoglobinuria is caused by a biphasic IgG autoantibody that triggers complement-mediated intravascular hemolysis. Paroxysmal cold hemoglobinuria has not previously been reported to occur in association with pregnancy. CASE PRESENTATION: We report a case of an 18 year old female who presented in early pregnancy with acute hemolytic anemia and a positive Donath-Landsteiner antibody test. She was diagnosed with paroxysmal cold hemoglobinuria and treated supportively. Her hemolysis resolved within 6 weeks. Because maternal IgG autoantibodies can cross the placenta, the patient was monitored closely throughout her pregnancy for recurrence. The outcome of the pregnancy was successful, with no evidence of neonatal anemia or hemolysis. CONCLUSION: This patient had a classic presentation of paroxysmal cold hemoglobinuria with rapid onset of hemolytic anemia that resolved spontaneously. To our knowledge, this is the first report of paroxysmal cold hemoglobinuria presenting during pregnancy.
RESUMO
Adult medulloblastoma is a rare intracranial tumor. Our patient is a 61 year old woman treated with cranial irradiation 15 years previously for a low grade astrocytoma in the left posterior temporal lobe that was recently diagnosed with medulloblastoma in the right cerebellum. This is the first reported case of radiation induced adult medulloblastoma.