Phase II study of imatinib in patients with recurrent gliomas of various histologies: a European Organisation for Research and Treatment of Cancer Brain Tumor Group Study.

PURPOSE: To evaluate the safety and the efficacy of imatinib in recurrent malignant gliomas. PATIENTS: AND METHODS: This was a single-arm, phase II study. Eligible patients had recurrent glioma after prior radiotherapy with an enhancing lesion on magnetic resonance imaging. Three different histologic groups were studied: glioblastomas (GBM), pure/mixed (anaplastic) oligodendrogliomas (OD), and low-grade or anaplastic astrocytomas (A). Imatinib was started at a dose of 600 mg/d with dose escalation to 800 mg in case of no toxicity; during the trial this dose was increased to 800 mg/d with escalation to 1,000 mg/d. Trial design was one-stage Fleming; both an objective response and 6 months of progression-free survival (PFS) were considered a successful outcome to treatment. RESULTS: A total of 112 patients (51 patients with GBM, 25 patients with A, and 36 patients with OD) were enrolled. Imatinib was in general well tolerated. The median number of cycles was 2.0 (range, 1 to 43 cycles). Five patients had an objective partial response, including three patients with GBM; all had 6 months of PFS. The 6-month PFS rate was 16% (95% CI, 8.0% to 34.0%) in GBM, 4.0% (95% CI, 0.3% to 15.0%) in OD, and 9% (95% CI, 2.0% to 25.0%) in A. The exposure to imatinib was significantly lower in patients using enzyme-inducing antiepileptic drugs. The presence of ABCG2 point mutations were not correlated with pharmacokinetic findings. No somatic activating mutations of KIT or platelet-derived growth factor receptor-A or -B were found. CONCLUSION: In the dose range of 600 to 1,000 mg/d, single-agent imatinib is well tolerated but has limited antitumor activity in patients with recurrent gliomas.

Estructura, distribución y abundancia de peces demersales: Crucero: Tareq II, 7605 (13 de mayo - 3 de junio 1976)

Presenta los resultados obtenidos a bordo del BI-TAREQ-II en el otoño de 1976, cuyo objetivo fue realizar un diagnóstico del estado de los stocks de peces para consumo humano, con la finalidad de ayudar a definir estrategias especificas para mejorar los niveles de explotación.

Situación del recurso merluza y sus características biológicas en la primavera de 1978 crucero 7811-II TAREQ II (18 de octubre - 8 de noviembre 1978)

Evalúa el stock de la merluza y de otros recursos dermesales, determina la intensidad del desove y la distribución del stock reproductivo, así como las condiciones ambientales que están influyendo en la distribución y concentración del recurso.

Institutes de Justinien. I. Livres I-II / nouvellement expliquées par A.-M. Du Caurroy,...

[Institutes (français). 1841]

Institutes de Justinien. II. Livres III-IV / nouvellement expliquées par A.-M. Du Caurroy,...

[Institutes (français). 1841]

Biomasa y distribución del krill (euphausia superba) en el estrecho de Bransfield durante las operaciones Perú Antar I, II y III.

Describe las operaciones Perú Antar I, II y III que se ejecutaron entre los meses de enero y febrero de 1988, 1989 y 1991, respectivamente, a bordo del BIC Humboldt en el estrecho de Bransfield, ampliandose el área de estudio, en Antar III, a los alrededores de la isla Elefante. Se presenta la distribución horizontal y vertical así como los estimados de biomasa del krill (Euphausia superba) determinados en el área de estudio en tales expediciones. En todos los casos se emplearon los mismos equipos y similares metodologías. Se incluye una revisión de los antecedentes de evaluación acústica del krill tendientes al cálculo de su biomasa en la zona del Estrecho de Bransfield e Isla Elefante. Los estimados de biomasa fueron los siguientes: ANTAR I, 17.0x106 t (±29,41%) con una densidad de 536,05 g/m2; en ANTAR II, 5,67 x 106 t (±16,66%) con una densidad de 176,66 g/m2 ; en ANTAR III, 8,43 x 106 t (±12,0%) con una densidad de 200,93 g/m2 . Las principales zonas de concentración del krill se observaron entre la Isla Rey Jorge e Isla Elefante en ANTAR I; entre las Islas Bravante y Livingstone en ANTAR II; y, entre las Islas Decepción y Trinidad, y al norte de la Isla Elefante, en ANTAR III.

Monitoring of NY-ESO-1 specific CD4+ T cells using molecularly defined MHC class II/His-tag-peptide tetramers.

MHC-peptide tetramers have become essential tools for T-cell analysis, but few MHC class II tetramers incorporating peptides from human tumor and self-antigens have been developed. Among limiting factors are the high polymorphism of class II molecules and the low binding capacity of the peptides. Here, we report the generation of molecularly defined tetramers using His-tagged peptides and isolation of folded MHC/peptide monomers by affinity purification. Using this strategy we generated tetramers of DR52b (DRB3*0202), an allele expressed by approximately half of Caucasians, incorporating an epitope from the tumor antigen NY-ESO-1. Molecularly defined tetramers avidly and stably bound to specific CD4(+) T cells with negligible background on nonspecific cells. Using molecularly defined DR52b/NY-ESO-1 tetramers, we could demonstrate that in DR52b(+) cancer patients immunized with a recombinant NY-ESO-1 vaccine, vaccine-induced tetramer-positive cells represent ex vivo in average 1:5,000 circulating CD4(+) T cells, include central and transitional memory polyfunctional populations, and do not include CD4(+)CD25(+)CD127(-) regulatory T cells. This approach may significantly accelerate the development of reliable MHC class II tetramers to monitor immune responses to tumor and self-antigens.

Plan II Proyecto para la ampliación de investigaciones de peces de consumo Desarrollo de los programas: reproducción, nutrición y crecimiento, comportamiento, población y explotación

Describe los recursos marinos, el consumo de peces orientado hacia la evaluación de los recursos pesqueros y su explotación racional.

Angiotensin II receptor blockade in normotensive subjects: A direct comparison of three AT1 receptor antagonists.

Use of angiotensin (Ang) II AT1 receptor antagonists for treatment of hypertension is rapidly increasing, yet direct comparisons of the relative efficacy of antagonists to block the renin-angiotensin system in humans are lacking. In this study, the Ang II receptor blockade induced by the recommended starting dose of 3 antagonists was evaluated in normotensive subjects in a double-blind, placebo-controlled, randomized, 4-way crossover study. At 1-week intervals, 12 subjects received a single dose of losartan (50 mg), valsartan (80 mg), irbesartan (150 mg), or placebo. Blockade of the renin-angiotensin system was assessed before and 4, 24, and 30 hours after drug intake by 3 independent methods: inhibition of the blood pressure response to exogenous Ang II, in vitro Ang II receptor assay, and reactive changes in plasma Ang II levels. At 4 hours, losartan blocked 43% of the Ang II-induced systolic blood pressure increase; valsartan, 51%; and irbesartan, 88% (P<0.01 between drugs). The effect of each drug declined with time. At 24 hours, a residual effect was found with all 3 drugs, but at 30 hours, only irbesartan induced a marked, significant blockade versus placebo. Similar results were obtained when Ang II receptor blockade was assessed with an in vitro receptor assay and by the reactive rise in plasma Ang II levels. This study thus demonstrates that the first administration of the recommended starting dose of irbesartan induces a greater and longer lasting Ang II receptor blockade than that of valsartan and losartan in normotensive subjects.