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A series of cationic porphyrins has been identified as G-quadruplex interactive agents (QIAs) that stabilize telomeric G-quadruplex DNA and thereby inhibit human telomerase; 50% inhibition of telomerase activity was achieved in HeLa cell-free extract at porphyrin concentrations in the range < or = 50 microM. Cytotoxicity of the porphyrins in vitro was(More)
BACKGROUND We carried out a large randomized trial of a brief form of cognitive therapy, manual-assisted cognitive behaviour therapy (MACT) versus treatment as usual (TAU) for deliberate self-harm. METHOD Patients presenting with recurrent deliberate self-harm in five centres were randomized to either MACT or (TAU) and followed up over 1 year. MACT(More)
Oncogene amplification has been observed in a broad spectrum of human tumors and has been associated with a poor prognosis for patients with several different types of malignancies. Importantly, at biopsy, the amplified genes localize to acentric extrachromosomal elements such as double-minute chromosomes (DMs) in the vast majority of cases. We show here(More)
BACKGROUND The treatment of deliberate self-harm (parasuicide) remains limited in efficacy. Despite a range of psychosocial, educational and pharmacological interventions only one approach, dialectical behaviour therapy, a form of cognitive-behaviour therapy (CBT), has been shown to reduce repeat episodes, but this is lengthy and intensive and difficult to(More)
Oncogene amplification in tumor cells results in the overexpression of proteins that confer a growth advantage in vitro and in vivo. Amplified oncogenes can reside intrachromosomally, within homogeneously staining regions (HSRs), or extrachromosomally, within double minute chromosomes (DMs). Since previous studies have shown that low concentrations of(More)
PURPOSE This study was performed to evaluate the activity of the multitargeted antifolate (MTA or LY231514) against a broad range of human tumors taken directly from patients. MATERIALS AND METHODS Human tumor colony-forming units were treated with MTA at concentrations of 0.1, 1.0, and 10 microg/ml in 1-h exposure studies. The responses of a limited(More)
FB642(methyl-2-benzimidazolecarbamate, carbendazim) is a systemic fungicide belonging to the benzimidazole family with antitumor activity against a broad spectrum of tumors both in vitro and in vivo such as pancreas, prostate, colon, and breast. Although the preclinical antitumor activity of FB642 has been well explored, its mechanism of action has not been(More)
PURPOSE To assess the feasibility of administering PN401, an oral uridine prodrug, as a rescue agent for the toxic effects of fluorouracil (5-FU), and to determine the maximum-tolerated dose of 5-FU when given with PN401, with an 8-hour treatment interval between these agents. PATIENTS AND METHODS Patients with advanced solid malignancies were treated(More)
OBJECTIVES The research examined: (i) whether high risk parasuicide patients showed a deficit in positive future thinking but no increase in negative future thinking; and (ii) whether such a deficit could be remedied by a brief, manual-assisted psychological intervention (manual assisted cognitive-behaviour therapy; MACT). DESIGN A cross-sectional, mixed(More)
Tumor types expressing a neuroendocrine phenotype secrete neuropeptides with paracrine or autocrine growth factor activity. The efficacy of these paracrine or autocrine loops depends on the expression of specific receptors on tumor cells. Once specific receptors are identified, specific neuropeptide antagonists disrupting paracrine and autocrine loops could(More)