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The mammalian hypothalamus strongly influences ingestive behaviour through several different signalling molecules and receptor systems. Here we show that CART (cocaine- and amphetamine-regulated transcript), a brain-located peptide, is a satiety factor and is closely associated with the actions of two important regulators of food intake, leptin and(More)
The human HDAC (histone deacetylase) family, a well-validated anticancer target, plays a key role in the control of gene expression through regulation of transcription. While HDACs can be subdivided into three main classes, the class I, class II and class III HDACs (sirtuins), it is presently unclear whether inhibiting multiple HDACs using pan-HDAC(More)
Cremophor EL (polyoxyethylene castor oil) and Tween 80, used as solvents for cyclosporin A and VP-16, respectively, were found to reverse the multidrug resistant (MDR) phenotype. In daunorubicin (DNR) resistant Ehrlich ascites tumor cells (EHR2/DNR+), both solvents at percentages of 0.01% (v/v) enhanced DNR accumulation to sensitive levels. Cremophor EL and(More)
Clinical data describing the phenotypes and treatment of patients represents an underused data source that has much greater research potential than is currently realized. Mining of electronic health records (EHRs) has the potential for establishing new patient-stratification principles and for revealing unknown disease correlations. Integrating EHR data(More)
Accidental extravasation of anthracyclines is a feared complication. Present treatment consists of local cooling and extensive surgical debridement, which often results in severe morbidity. All clinically important anthracyclines are topoisomerase II poisons that are antagonized by topoisomerase II catalytic inhibitors such as dexrazoxane. Therefore, we(More)
Maleimide, N-ethyl-maleimide (NEM), and N-methyl-maleimide (NMM) were identified as potent catalytic inhibitors of purified human topoisomerase IIalpha, whereas the ring-saturated analog succinimide was completely inactive. Catalytic inhibition was not abrogated by topoisomerase II mutations that totally abolish the effect of bisdioxopiperazine compounds on(More)
Expression of DNA topoisomerase IIalpha (topo IIalpha) is cell cycle-regulated at both the transcriptional and the post-transcriptional levels. In order to identify cis-acting elements responsible for transcriptional regulation during the cell cycle, we investigated NIH/3T3 cells stably transfected with luciferase reporter plasmids containing various(More)
The complex catalytic cycle of topoisomerase II is the target of important antitumor agents. Topoisomerase II poisons, such as etoposide and daunorubicin, inhibit the resealing of DNA breaks created by the enzyme. This enzyme-coupled cell kill is susceptible to pharmacological regulation by drugs interfering with other steps in the enzyme's catalytic cycle(More)
BACKGROUND The purpose of this study was to assess the efficacy and tolerability of i.v. dexrazoxane [Savene (EU), Totect (US)] as acute antidote in biopsy-verified anthracycline extravasation. PATIENTS AND METHODS Two prospective, open-label, single-arm, multicentre studies in patients with anthracycline extravasation were carried out. Patients with(More)