Clin Cancer Res
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The aim of the study was to investigate the pathophysiology of oxaliplatin-induced neurotoxicity using clinical nerve excitability techniques that provide information about axonal ion channel function. ⋯ The present study provides evidence that oxaliplatin-induced neurotoxicity is mediated through an effect on axonal Na(+) channels. Clinical nerve excitability techniques may prove beneficial in monitoring for early signs of neurotoxicity and in the assessment of future prophylactic therapies.
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In this study, we investigated the mechanisms by which temozolomide enhances radiation response in glioblastoma cells. ⋯ The present study shows that temozolomide enhances radiation response most effectively in MGMT-negative glioblastomas by increasing the degree of radiation-induced double-strand DNA damage. In MGMT-positive glioblastomas, depletion of MGMT by the addition of O(6)-benzylguanine significantly enhances the antitumor effect of concurrent radiation + temozolomide. These are among the first data showing mechanisms of synergy between radiation and temozolomide and the effect of MGMT.
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Somatic mutations in the epidermal growth factor receptor (EGFR) have been identified in patients with advanced non-small cell lung cancer who achieve dramatic clinical and radiographic response to the EGFR tyrosine kinase inhibitors (TKI) gefitinib and erlotinib. These mutations in EGFR are found more frequently in patients with adenocarcinomas, nonsmokers, patients of Asian ethnicity, and in females: the same populations that are the most likely to have a clinical response when treated with EGFR TKIs. ⋯ These findings suggest that for patients with advanced non-small cell lung cancer bearing EGFR mutations, treatment with an EGFR TKI should be incorporated as at least part of their initial therapy. These approaches are being studied in ongoing clinical trials and will spur the development of additional technology for EGFR mutation detection.
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Elevated proportions of regulatory T cells (T(reg)) are present in patients with a variety of cancers, including malignant glioma, yet recapitulative murine models are wanting. We therefore examined T(regs) in mice bearing malignant glioma and evaluated anti-CD25 as an immunotherapeutic adjunct. ⋯ Systemic anti-CD25 administration does not entirely eliminate T(regs) but does prevent T(reg) function. This leads to safe enhancement of tumor immunity in a murine glioma model that recapitulates the tumor-induced changes to the CD4 and T(reg) compartments seen in patients with malignant glioma.
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Bevacizumab is a recombinant, humanized monoclonal antibody against vascular endothelial growth factor. Erlotinib HCl is a reversible, highly selective epidermal growth factor receptor tyrosine kinase inhibitor. Additionally, both agents have shown benefit in patients with previously treated non-small cell lung cancer (NSCLC). ⋯ The median overall survival for the 34 patients treated at the phase II dose was 12.6 months, with progression-free survival of 6.2 months. Encouraging antitumor activity and safety of erlotinib plus bevacizumab support further development of this combination for patients with advanced NSCLC. A randomized phase II trial has been completed, and a phase III trial is ongoing.