Summary 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 O2•− 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.

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SUMMARY 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 O2.− 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.

Physicians and surgeons must be vigilant of the diagnosis of cervical necrotizing fasciitis as early clinical findings may be subtle and prompt identification to facilitate aggressive intervention is required to preclude catastrophic local and systemic morbidity and mortality.

ClinicalTrials.gov Identifier: NCT00010452.

In 4 experiments the authors used a variant of the picture-word interference paradigm to investigate whether there is a temporal overlap in the activation of words during sentence production and whether there is a flow of semantic and phonological information between them. Experiments 1 and 2 demonstrate that 2 semantically related nouns produce interference effects either when they are in the same or different phrases of a sentence. Experiments 3 and 4 demonstrate that 2 phonologically related nouns produce facilitation effects but only when they are within the same phrase of a sentence. The results argue against strictly serial models of multiple-word access and provide evidence of a flow of semantic and phonological information between words during sentence production.

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