Clin Cancer Res
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Hypoxia-inducible factor-1 alpha (HIF-1 alpha) plays an important role in tumoral adaptation to hypoxic conditions by serving as a transcription factor for several crucial proteins, including vascular endothelial growth factor and carbonic anhydrase IX (CAIX). Here, we evaluated the significance of HIF-1 alpha in renal cell carcinoma (RCC). ⋯ HIF-1 alpha is an important independent prognostic factor for patients with metastatic clear cell RCC. Because HIF-1 alpha and CAIX are independently and differentially regulated in metastatic clear cell RCC, both tumor markers can be complementary in predicting prognosis.
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To determine the maximum tolerated dose of irinotecan when administrated with temozolomide every 28 days, in patients with recurrent malignant glioma who were also receiving CYP450 enzyme-inducing antiepileptic drugs (EIAED), and to characterize the pharmacokinetics of irinotecan and its metabolites. The study was also intended to assess whether temozolomide affects the conversion of irinotecan to SN-38. ⋯ The recommended phase II dose of irinotecan in combination with temozolomide for patients receiving EIAEDs is 500 mg/m(2), administrated every 15 days on a 28-day schedule. This study also confirmed that concomitant administration of EIAEDs increases irinotecan clearance and influences SN-38 disposition. No pharmacokinetic interaction was observed between temozolomide and irinotecan.
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Glioblastoma multiforme is the most frequent primary brain tumor in adults and represents one of the most lethal malignancies with a median survival of 12-16 months. We have previously shown that an oncolytic measles virus derivative expressing soluble human carcinoembryonic antigen (MV-CEA) has significant antitumor activity against glioblastoma multiforme cell lines and xenografts. Radiation therapy (RT) represents one of the mainstays of glioma treatment. Here we tested the hypothesis that the combination of RT with MV-CEA would have synergistic activity against gliomas. ⋯ There is synergy between MV-CEA and RT in vitro and in vivo. The synergistic effect of the combination seems to be due to increase in viral burst size and increase in apoptotic cell death. This latter effect is mostly mediated via the extrinsic caspase-8 pathway, activated via increased signaling through the Fas death receptor pathway. These results could have translational implications in glioma therapy.
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We investigated the clinical significance of E2F1 gene expression in relation to its target genes, thymidylate synthase (TS) and Survivin, in case of non-small-cell lung cancer (NSCLC). ⋯ The present study revealed that E2F1 gene expression correlates with TS and Survivin gene expressions and tumor proliferation. During the progression of NSCLC, E2F1 overexpression could produce more aggressive tumors with a high proliferation rate and chemoresistance.