N-(4-Hydroxyphenyl)retinamide (4HPR) is currently used in cancer prevention and therapy trials. It is thought that its e ects result from induction of apoptosis. 4HPR-induced apoptosis in human cervical carcinoma C33A cells involves enhanced generation of reactive oxygen species (ROS). In this study we explored the mechanism by which 4HPR increases ROS and induces apoptosis in these cells. 4HPR induced cytochrome c release from mitochondria to cytoplasm, activated caspase-3, and caused a membrane permeability transition (MPT). All these 4HPR's e ects, as well as the induction of apoptosis, were inhibited by antioxidants, which decrease ROS. Thenoyltri¯uoroacetone, a mitochondrial respiratory chain (MRC) complex II inhibitor, and carbonylcyanide m-chlorophenyl hydrazone, which uncouples electron transfer and ATP synthesis and inhibits ROS generation by MRC, inhibited 4HPR-induced ROS generation very e ectively. Rotenone, an MRC complex I inhibitor was less e ective and azide, an MRC complex IV inhibitor, exhibited a marginal e ect. In contrast, antimycin A, an MRC complex III inhibitor, enhanced 4HPR-induced ROS generation. These ®ndings suggest that 4HPR enhances ROS generation by a ecting a target between complex II and complex III, presumably coenzyme Q. This e ect is followed by release of cytochrome c, increased caspase-3 activity, induction of MPT and eventual DNA fragmentation and cell death.
BACKGROUND:
The current study aimed to evaluate the efficacy of superselective high‐dose cisplatin infusion with concomitant radiotherapy (RADPLAT) for previously untreated patients with advanced cancer of the nasal cavity and paranasal sinuses.
METHODS:
Between October 1999 and December 2006, 47 patients were given superselective intra‐arterial infusions of cisplatin (100‐120 mg/m2 per week) with simultaneous intravenous infusions of thiosulfate to neutralize cisplatin toxicity and conventional external‐beam radiotherapy (65‐70 grays).
RESULTS:
There were 7 patients (14.9%) diagnosed with T3, 22 (46.8%) with T4a, and 18 (38.3%) with T4b disease. During the median follow‐up period of 4.6 years, the 5‐year local progression‐free survival rate was 78.4% for all patients (n = 47), 69.0% for patients with T4b disease (n = 18), and 83.2% for patients with
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