4,501 research outputs found
PHASE I STUDY OF PKC412 (N-BENZOYL-STAUROSPORINE), A NOVEL ORAL PROTEIN KINASE C INHIBITOR, COMBINED WITH GEMCITABINE AND CISPLATIN IN PATIENTS WITH NON-SMALL-CELL LUNG CANCER.
Phase II trial of raltitrexed ('Tomudex') in advanced small-cell lung cancer.
Raltitrexed, a thymidylate synthase inhibitor, was given to 21 patients with advanced small-cell lung cancer, at a dose of 3 mg m(-2) as a 15-min intravenous infusion at 21-day intervals. All of the patients had extensive disease and 17 had received prior therapy. Patients with disease refractory to primary chemotherapy were excluded. Forty-one treatment cycles were given (median two, range one to four). The drug was well tolerated. No objective tumour response was documented. The patients had chemoresistant disease, as shown by a response in only one of ten patients who went on to receive alternative cytotoxic regimens. We conclude that raltitrexed given in this schedule is inactive as second line therapy for small-cell lung cancer
Brain metastases at the time of presentation of non-small cell lung cancer: a multi-centric AERIO analysis of prognostic factors
A multi-centre retrospective study involving 4 French university institutions has been conducted in order to identify routine pre-therapeutic prognostic factors of survival in patients with previously untreated non-small cell lung cancer and brain metastases at the time of presentation. A total of 231 patients were recorded regarding their clinical, radiological and biological characteristics at presentation. The accrual period was January 1991 to December 1998. Prognosis was analysed using both univariate and multivariate (Cox model) statistics. The median survival of the whole population was 28 weeks. Univariate analysis (log-rank), showed that patients affected by one of the following characteristics proved to have a shorter survival in comparison with the opposite status of each variable: male gender, age over 63 years, poor performance status, neurological symptoms, serum neuron-specific enolase (NSE) level higher than 12.5 ng ml−1, high serum alkaline phosphatase level, high serum LDH level and serum sodium level below 132 mmol l−1. In the Cox's model, the following variables were independent determinants of a poor outcome: male gender: hazard ratio (95% confidence interval): 2.29 (1.26–4.16), poor performance status: 1.73 (1.15–2.62), age: 1.02 (1.003–1.043), a high serum NSE level: 1.72 (1.11–2.68), neurological symptoms: 1.63 (1.05–2.54), and a low serum sodium level: 2.99 (1.17–7.62). Apart from 4 prognostic factors shared in common with other stage IV NSCLC patients, whatever the metastatic site (namely sex, age, gender, performance status and serum sodium level) this study discloses 2 determinants specifically resulting from brain metastasis: i.e. the presence of neurological symptoms and a high serum NSE level. The latter factor could be in relationship with the extent of normal brain tissue damage caused by the tumour as has been demonstrated after strokes. Additionally, the observation of a high NSE level as a prognostic determinant in NSCLC might reflect tumour heterogeneity and understimated neuroendocrine differentiation. © 2001 Cancer Research Campaignhttp://www.bjcancer.co
Effect of grain orientation and magnesium doping on β-tricalcium phosphate resorption behavior
The efficiency of calcium phosphate (CaP) bone substitutes can be improved by tuning their resorption rate. The influence of both crystal orientation and ion doping on resorption is here investigated for beta-tricalcium phosphate (β-TCP). Non-doped and Mg-doped (1 and 6 mol%) sintered β-TCP samples were immersed in acidic solution (pH 4.4) to mimic the environmental conditions found underneath active osteoclasts. The surfaces of β-TCP samples were observed after acid-etching and compared to surfaces after osteoclastic resorption assays. β-TCP grains exhibited similar patterns with characteristic intra-crystalline pillars after acid-etching and after cell-mediated resorption. Electron BackScatter Diffraction analyses, coupled with Scanning Electron Microscopy, Inductively Coupled Plasma–Mass Spectrometry and X-Ray Diffraction, demonstrated the influence of both grain orientation and doping on the process and kinetics of resorption. Grains with c-axis nearly perpendicular to the surface were preferentially etched in non-doped β-TCP samples, whereas all grains with simple axis (a, b or c) nearly normal to the surface were etched in 6 mol% Mg-doped samples. In addition, both the dissolution rate and the percentage of etched surface were lower in Mg-doped specimens. Finally, the alignment direction of the intra-crystalline pillars was correlated with the preferential direction for dissolution. Statement of significance: The present work focuses on the resorption behavior of calcium phosphate bioceramics. A simple and cost-effective alternative to osteoclast culture was implemented to identify which material features drive resorption. For the first time, it was demonstrated that crystal orientation, measured by Electron Backscatter Diffraction, is the discriminating factor between grains, which resorbed first, and grains, which resorbed slower. It also elucidated how resorption kinetics can be tuned by doping β-tricalcium phosphate with ions of interest. Doping with magnesium impacted lattice parameters. Therefore, the crystal orientations, which preferentially resorbed, changed, explaining the solubility decrease. These important findings pave the way for the design of optimized bone graft substitutes with tailored resorption kinetics
Application de la borne de Cramer-Rao dans le cas de systèmes antennaires complexes de goniométrie
Généralement, la borne de Cramer-Rao des directions d'arrivée de signaux sur un réseau de capteurs est calculée de façon théorique [1] [2] [3]. Or dès que l'on désire effectuer une application numérique de la borne de Cramer-Rao pour un système donné, on est souvent amené à effectuer des suppositions et/ou des simplifications. En effet, il est souvent très difficile de tenir compte et de modéliser l'environnement et les différents phénomènes pouvant perturber le réseau de capteurs, comme le couplage entre antennes, l'influence d'un porteur (mat ou véhicule) en termes de diffraction, de réflexion ou même la présence d'un sol. Dans ce travail, nous utilisons un logiciel de simulation électromagnétique pour estimer l'impact de l'environnement réel sur le vecteur direction d'un système antennaire complexe de goniométrie. La borne de Cramer-Rao déterministe des directions d'arrivée de signaux est ensuite déterminée pour le réseau de capteurs de goniométrie soumis à des perturbations. Les résultats montrent que la précision dépend fortement de la prise en compte des couplages et perturbations du système antennaire. On montre ainsi que l'environnement a un impact non négligeable et que l'on peut calculer une borne de Cramer Rao des directions d'arrivée plus réaliste et ainsi optimiser dans certains cas le système antennaire de goniométrie en fonction de son environnement
Phase II study of gemcitabine plus oxaliplatin as first-line chemotherapy for advanced non-small-cell lung cancer
This phase II study evaluated the response rate and tolerability of gemcitabine–oxaliplatin chemotherapy in non-small-cell lung cancer (NSCLC) patients. Chemonaive patients with stage IIIB or IV NSCLC received gemcitabine 1000 mg m−2 on days 1 and 8, followed by oxaliplatin 130 mg m−2 on day 1. Cycles were repeated every 21 days for up to six cycles. From February 2002 to May 2004, 60 patients were enrolled into the study in seven Italian institutions. We observed one complete response (1.7%) and 14 partial responses (23.3%), for an overall response rate of 25.0% (95% confidence interval, 14.7–37.9%). The median duration of response was 5.9 months (range 1.5–17.1 months). With a median follow-up of 6.7 months, median time to progressive disease and overall survival were 2.7 (range 1.9–3.4 months) and 7.3 months (range 7.2–8.6 months), respectively. The main grade 3–4 haematological toxicities were transient neutropenia in 11.7% and thrombocytopenia in 8.3% of the patients. Nausea/vomiting was the main grade 3–4 nonhaematological toxicity, occurring in 10.0% of the patients. Two (3.3%) patients developed grade 3 neurotoxicity. Our results show that gemcitabine–oxaliplatin chemotherapy is active and well tolerated in patients with advanced NSCLC, deserving further study, especially for patients not eligible to receive cisplatin
Ancient hybridization and adaptive introgression of an invadolysin gene in schistosome parasites
Introgression among parasite species has the potential to transfer traits of biomedical importance across species boundaries. The parasitic blood fluke Schistosoma haematobium causes urogenital schistosomiasis in humans across sub-Saharan Africa. Hybridization with other schistosome species is assumed to occur commonly, because genetic crosses between S. haematobium and livestock schistosomes, including S. bovis, can be staged in the laboratory, and sequencing of mtDNA and rDNA amplified from microscopic miracidia larvae frequently reveals markers from different species. However the frequency, direction, age and genomic consequences of hybridization are unknown. We hatched miracidia from eggs, and sequenced the exomes from 96 individual S. haematobium miracidia from infected patients from Niger and the Zanzibar archipelago. These data revealed no evidence for contemporary hybridization between S. bovis and S. haematobium in our samples. However, all Nigerien S. haematobium genomes sampled show hybrid ancestry, with 3.3-8.2% of their nuclear genomes derived from S. bovis, providing evidence of an ancient, introgression event that occurred at least 108-613 generations ago. Some S. bovis derived alleles have spread to high frequency or reached fixation and show strong signatures of directional selection; the strongest signal spans a single gene in the invadolysin gene family (Chr. 4). Our results suggest that S. bovis/S. haematobium hybridization occurs rarely, but demonstrate profound consequences of ancient introgression from a livestock parasite into the genome of S. haematobium, the most prevalent schistosome species infecting humans
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