374 research outputs found
Sequence dependent antitumour efficacy of the vascular disrupting agent ZD6126 in combination with paclitaxel
The clinical success of small-molecule vascular disrupting agents (VDAs) depends on their combination with conventional therapies. Scheduling and sequencing remain key issues in the design of VDAâchemotherapy combination treatments. This study examined the antitumour activity of ZD6126, a microtubule destabilising VDA, in combination with paclitaxel (PTX), a microtubule-stabilising cytotoxic drug, and the influence of schedule and sequence on the efficacy of the combination. Nude mice bearing MDA-MB-435 xenografts received weekly cycles of ZD6126 (200âmgâkgâ1 i.p.) administered at different times before or after PTX (10, 20, and 40âmgâkgâ1 i.v.). ZD6126 given 2 or 24âh after PTX showed no significant benefit, a result that was attributed to a protective effect of PTX against ZD6126-induced vascular damage and tumour necrosis, a hallmark of VDA activity. Paclitaxel counteracting activity was reduced by distancing drug administrations, and ZD6126 given 72âh after PTX potentiated the VDA's antitumour activity. Schedules with ZD6126 given before PTX improved therapeutic activity, which was paralleled by a VDA-induced increase in cell proliferation in the viable tumour tissue. Paclitaxel given 72âh after ZD6126 yielded the best response (50% tumours regressing). A single treatment with ZD6126 followed by weekly administration of PTX was sufficient to achieve a similar response (57% remissions). These findings show that schedule, sequence and timing are crucial in determining the antitumour efficacy of PTX in combination with ZD6126. Induction of tumour necrosis and increased proliferation in the remaining viable tumour tissue could be exploited as readouts to optimise schedules and maximise therapeutic efficacy
Vascular disrupting agent for neovascular age related macular degeneration: a pilot study of the safety and efficacy of intravenous combretastatin A-4 phosphate
BACKGROUND:
This study was designed to assess the safety, tolerability, and efficacy of intravenous infusion of CA4P in patients with neovascular age-related macular degeneration (AMD). METHODS:
Prospective, interventional, dose-escalation clinical trial. Eight patients with neovascular AMD refractory to at least 2 sessions of photodynamic therapy received CA4P at a dose of 27 or 36 mg/m2 as weekly intravenous infusion for 4 consecutive weeks. Safety was monitored by vital signs, ocular and physical examinations, electrocardiogram, routine laboratory tests, and collection of adverse events. Efficacy was assessed using retinal fluorescein angiography, optical coherence tomography, and best corrected visual acuity (BCVA). RESULTS:
The most common adverse events were elevated blood pressure (46.7%), QTc prolongation (23.3%), elevated temperature (13.3%), and headache (10%), followed by nausea and eye injection (6.7%). There were no adverse events that were considered severe in intensity and none resulted in discontinuation of treatment. There was reduction of the excess foveal thickness by 24.15% at end of treatment period and by 43.75% at end of the two-month follow-up (pâ=â0.674 and 0.161, respectively). BCVA remained stable throughout the treatment and follow-up periods. CONCLUSIONS:
The safety profile of intravenous CA4P was consistent with that reported in oncology trials of CA4P and with the class effects of vascular disruptive agents; however, the frequency of adverse events was different. There are evidences to suggest potential efficacy of CA4P in neovascular AMD. However, the level of systemic safety and efficacy indicates that systemic CA4P may not be suitable as an alternative monotherapy to current standard-of-care therapy
Designing photonic bandgap fibers for particle acceleration
Abstract Photonic bandgap (PBG) fibers with hollow cor
Evaluation of Hungarian Wines for Resveratrol by Overpressured Layer Chromatography
A method, including solid phase extraction sample preparation, overpressured layer chromatographic separation and subsequent densitometric evaluation, was developed for measurement of total resveratrol (cis- and trans-isomers) content of wine. The amount of resveratrol was determined in wine samples from different winemaking regions of Hungary. The total resveratrol was high in Hungarian red wines (3.6â11 mg/L), and much lower in white ones (0.04â1.5 mg/L)
Enhancement of the anti-tumour effect of cyclophosphamide by the bioreductive drugs AQ4N and tirapazamine
The ability of the bioreductive drugs AQ4N and tirapazamine to enhance the anti-tumour effect of cyclophosphamide was assessed in three murine tumour models. In male BDF mice implanted with the T50/80 mammary carcinoma, AQ4N (50â150 mg kgâ1) in combination with cyclophosphamide (100 mg kgâ1) produced an effect equivalent to a single 200 mg kgâ1dose of cyclophosphamide. Tirapazamine (25 mg kgâ1) in combination with cyclophosphamide (100 mg kgâ1) produced an effect equivalent to a single 150 mg kgâ1dose of cyclophosphamide. In C3H mice implanted with the SCCVII or RIF-1 tumours, enhancement of tumour cell killing was found with both drugs in combination with cyclophosphamide (50â200 mg kgâ1); AQ4N (50â200 mg kgâ1) produced a more effective combination than tirapazamine (12.5â50 mg kgâ1). Unlike tirapazamine, which showed a significant increase in toxicity to bone marrow cells, the combination of AQ4N (100 mg kgâ1) 6 h prior to cyclophosphamide (100 mg kgâ1) resulted in no additional toxicity towards bone marrow cells compared to that caused by cyclophosphamide alone. In conclusion, AQ4N gave a superior anti-tumour effect compared to tirapazamine when administered with a single dose of cyclophosphamide (100 mg kgâ1). © 2000 Cancer Research Campaig
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Beam Coupling to Optical Scale Accelerating Structures
Current research efforts into structure based laser acceleration of electrons utilize beams from standard RF linacs. These beams must be coupled into very small structures with transverse dimensions comparable to the laser wavelength. To obtain decent transmission, a permanent magnet quadrupole (PMQ) triplet with a focusing gradient of 560 T/m is used to focus into the structure. Also of interest is the induced wakefield from the structure, useful for diagnosing potential accelerator structures or as novel radiation sources
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