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1.
Philos Trans A Math Phys Eng Sci ; 377(2139): 20180018, 2019 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-30966932

RESUMO

Volcanism is the surface expression of magma intrusion, crystallization, assimilation and hybridization processes operating throughout the crust over a range of time periods. Many magmas, including those erupted at subduction zones, have complex textures that reflect these processes. Here, we use textural and geochemical characteristics of calcic amphiboles to help identify multiple ingredients of subduction zone magmatism at Mt Lamington volcano, Papua New Guinea. Our approach uses existing trace element partitioning schemes to calculate the compositions of amphibole equilibrium melts (AEMs). The AEM compositions show that Mt Lamington andesites and plutonic enclaves are dominated by fractionation of amphibole + plagioclase + biotite, with assimilation of plagioclase and zircon. Magnesiohastingsite crystals in the andesite and diktytaxitic mafic enclaves reflect multiple episodes of recharge by more primitive, geochemically variable melts. The andesite also contains clots with rounded grains and melt on grain boundaries. These features indicate slow crystallization, and the retention of melt films could significantly enhance the potential for remobilization of crystals by infiltrating melts or during magma mixing. Variations in crystallization conditions could thus significantly affect the mush microstructure. We suggest that this could result in a significant bias of the volcanic record towards the preferential incorporation of more slowly cooled plutonic material from the lower crust or from more thermally mature plumbing systems. This article is part of the Theo Murphy meeting issue 'Magma reservoir architecture and dynamics'.

2.
Br J Cancer ; 104(4): 593-8, 2011 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-21285987

RESUMO

BACKGROUND: On the basis of preclinical studies of NC-6004, a cisplatin-incorporated micellar formulation, we hypothesised that NC-6004 could show lower toxicity than cisplatin and show greater anti-tumour activity in phase I study. METHODS: A total of 17 patients were recruited in a range of advanced solid tumour types. NC-6004 was administered intravenously (i.v.) every 3 weeks. The dose escalation started at 10 mg m(-2) and was increased up to 120 mg m(-2) according to the accelerated titration method and modified Fibonacci method. RESULTS: One dose-limiting toxicity (DLT) occurred in a patient who was given 90 mg m(-2) of NC-6004, otherwise any significant cisplatin-related toxicity was not observed or generally mild toxicity was observed. Despite the implementation of post-hydration and pre-medication regimen, renal impairment and hypersensitivity reactions still developed at 120 mg m(-2), which led to the conclusion that the maximum tolerated dose was 120 mg m(-2), and the recommended dose was 90 mg m(-2), although DLT was not defined as per protocol. Stable disease was observed in seven patients. The maximum concentration and area under the concentration-time curve of ultrafilterable platinum at 120 mg m(-2) NC-6004 were 34-fold smaller and 8.5-fold larger, respectively, than those for cisplatin. CONCLUSION: The delayed and sustained release of cisplatin after i.v. administration contributes to the low toxicity of NC-6004.


Assuntos
Cisplatino/administração & dosagem , Neoplasias/tratamento farmacológico , Compostos Organoplatínicos/farmacologia , Ácido Poliglutâmico/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Cisplatino/farmacocinética , Progressão da Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Injeções Intravenosas , Masculino , Dose Máxima Tolerável , Micelas , Pessoa de Meia-Idade , Modelos Biológicos , Neoplasias/metabolismo , Neoplasias/patologia , Ácido Poliglutâmico/farmacologia , Polímeros/administração & dosagem , Polímeros/farmacocinética
3.
Br J Cancer ; 101(8): 1290-7, 2009 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-19755992

RESUMO

BACKGROUND: Hypoxia is as an indicator of poor treatment outcome. Consistently, hypoxic HCT116 colorectal cancer cells are resistant to oxaliplatin, although the mechanistic basis is unclear. This study sought to investigate the relative contribution of HIF-1 (hypoxia-inducible factor-1)-mediated gene expression and drug penetrance to oxaliplatin resistance using three-dimensional spheroids. METHODS: Hypoxia-inducible factor-1alpha function was suppressed by the stable expression of a dominant-negative form in HCT116 cells (DN). Cells were drug exposed as monolayer or multicellular spheroid cultures. Cells residing at differing oxygenation status were isolated from Hoechst 33342-treated spheroids using flow cytometry. Sub-populations were subjected to clonogenic survival assays and to Inductively-Coupled Plasma Mass Spectroscopy to determine oxaliplatin uptake. RESULTS: In spheroids, a sensitivity gradient (hypoxic

Assuntos
Antineoplásicos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Fator 1 Induzível por Hipóxia/fisiologia , Compostos Organoplatínicos/farmacologia , Hipóxia Celular , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Resistencia a Medicamentos Antineoplásicos , Células HCT116 , Humanos , Compostos Organoplatínicos/farmacocinética , Oxaliplatina , Esferoides Celulares
4.
J Phys Condens Matter ; 21(36): 364207, 2009 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-21832313

RESUMO

The geochemical signature of diamond-forming fluids can be used to unravel diamond-forming processes and is of potential use in the detection of so-called 'conflict' diamonds. While fluid-rich fibrous diamonds can be analyzed by a variety of techniques, very few data have been published for fluid-poor, gem-quality diamonds because of their very low impurity levels. Here we present a new ICPMS-based (ICPMS: inductively coupled plasma mass spectrometry) method for the analysis of trace element concentrations within fluid-poor, gem-quality diamonds. The method employs a closed-system laser ablation cell. Diamonds are ablated and the products trapped for later pre-concentration into solutions that are analyzed by sector-field ICPMS. We show that our limits of quantification for a wide range of elements are at the sub-pg to low pg level. The method is applied to a suite of 10 diamonds from the Cullinan Mine (previously known as Premier), South Africa, along with other diamonds from Siberia (Mir and Udachnaya) and Venezuela. The concentrations of a wide range of elements for all the samples (expressed by weight in the solid) are very low, with rare earth elements along with Y, Nb, Cs ranging from 0.01 to 2 ppb. Large ion lithophile elements (LILE) such as Rb and Ba vary from 1 to 30 ppb. Ti ranges from ppb levels up to 2 ppm. From the combined, currently small data set we observe two kinds of diamond-forming fluids within gem diamonds. One group has enrichments in LILE over Nb, whereas a second group has normalized LILE abundances more similar to those of Nb. These two groups bear some similarity to different groups of fluid-rich diamonds, providing some supporting evidence of a link between the parental fluids for both fluid-inclusion-rich and gem diamonds.

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