Contribution of CAF-I to anaphase-promoting-complex-mediated mitotic chromatin assembly in Saccharomyces cerevisiae.

The anaphase-promoting complex (APC) is required for mitotic progression and genomic stability. Recently, we demonstrated that the APC is also required for mitotic chromatin assembly and longevity. Here, we investigated the role the APC plays in chromatin assembly.

Breast adenocarcinoma cell adhesion to the vascular subendothelium in whole blood and under flow conditions: effects of alphavbeta3 and alphaIIbbeta3 antagonists.

Tumour cell adhesion to vascular extracellular matrix (ECM), an important step of metastatic progression, is promoted by platelets. The aim of our study was to investigate, in whole blood under venous and arterial shear conditions, the respective role of tumour cell alphavbeta3 and platelet alphaIIbbeta3 integrins in MDA-MB-231 breast adenocarcinoma cell adhesion to human umbilical vein endothelial cell ECM. For that purpose, blood containing MDA-MB-231 cells was incubated with non-peptide antagonists specific for platelet alphaIIbbeta3 (lamifiban) or tumour cell alphavbeta3 (SB-273005).

Thyroid hormone signaling is highly heterogeneous during pre- and postnatal brain development.

We have generated transgenic reporter mice to analyze the spatio-temporal distribution of thyroid hormone signaling during mouse brain development. The reporter system, utilizing a chimeric yeast Gal4 DNA-binding domain-thyroid hormone alpha ligand-binding domain fusion protein to drive lacZ expression, revealed that thyroid hormone signaling starts in the midbrain roof several days before the onset of thyroid gland function, and that it remains highly heterogeneous in the central nervous system throughout pre- and postnatal development. We speculate that this heterogeneity might provide neural cells with positional information during development.

Cytostatic and pro-apoptotic effects of a novel phenylacetate-dextran derivative (NaPaC) on breast cancer cells in interactions with endothelial cells.

We have tested a novel hybrid molecule made of carboxymethylbenzylamide dextran (CMDB) and sodium phenylacetate (NaPa) groups, called the CMDB-NaPa ester (NaPaC), on the proliferation of breast cancer and endothelial cells as well as paracrine effects between these two cell types. Our results showed that NaPaC inhibited the proliferation of MDA-MB-231 cells and MCF-7 cells in a dose-dependent manner. NaPaC was 20-fold more active on highly invasive MDA-MB-231 cells than the NaPa parental molecule.

A functional analysis reveals dependence on the anaphase-promoting complex for prolonged life span in yeast.

Defects in anaphase-promoting complex (APC) activity, which regulates mitotic progression and chromatin assembly, results in genomic instability, a hallmark of premature aging and cancer. We investigated whether APC-dependent genomic stability affects aging and life span in yeast. Utilizing replicative and chronological aging assays, the APC was shown to promote longevity.

Platelet adhesion and signaling induced by the octapeptide primary binding sequence (KOGEOGPK) from type III collagen.

Platelet adhesion to vascular collagens is an essential step in the initiation of hemostasis and thrombosis. Several platelet receptors interact with type I and type III collagens, including GP Ia/IIa and GP VI. We recently described a new platelet receptor (TIIICBP) specific for a type III collagen-related primary binding sequence, the KOGEOGPK octapeptide.

Temporary cyst formation in phytoplankton: a response to allelopathic competitors?

Competition among phytoplankton for limiting resources may involve direct or indirect interactions. A direct interaction of competitors is the release of chemicals that inhibit other species, a process known as allelopathy. Here, we investigated the allelopathic effect of three toxic microalgae species (Alexandrium tamarense, Karenia mikimotoi and Chrysochromulina polylepis) on a natural population of the dinoflagellate Scrippsiella trochoidea.

Correlation between dielectric and optical measurements in the smectic-C(*)(alpha) phase.

We present optical and dielectric measurements in the smectic-C(*)(alpha) (SmC(*)(alpha)) phase of three homologues of an alkoxy benzoate series. Two different behaviors are observed depending on the values and the temperature evolution of the azimuthal angle difference alpha between two adjacent layers. For moderate values of alpha, the Goldstone mode is predominant over the whole SmC(*)(alpha) phase.

Overexpression of P70 S6 kinase protein is associated with increased risk of locoregional recurrence in node-negative premenopausal early breast cancer patients.

The RPS6KB1 gene is amplified and overexpressed in approximately 10% of breast carcinomas and has been found associated with poor prognosis. We studied the prognostic significance of P70 S6 kinase protein (PS6K) overexpression in a series of 452 node-negative premenopausal early-stage breast cancer patients (median follow-up: 10.8 years).

Hypofractionated external beam radiotherapy as retreatment for symptomatic non-small-cell lung carcinoma: an effective treatment?

Purpose: To evaluate prospectively the efficacy, toxicity, and duration of the palliative effect of retreatment with external beam radiotherapy in symptomatic patients with recurrent non-small-cell lung cancer.

Methods And Materials: Twenty-eight symptomatic patients with local recurrence of non-small-cell lung cancer underwent repeated treatment after previous radiotherapy (equivalent dose, 46-60 Gy). Reirradiation consisted of two fractions of 8 Gy on Days 1 and 8 with two opposed beams using 6-18-MV photon beams at the site of pulmonary recurrence.

Evidence of antiangiogenic and antimetastatic activities of the recombinant disintegrin domain of metargidin.

Metargidin, a transmembrane protein of the adamalysin family, and integrins, e.g., alpha5beta1 and alphav, are preferentially expressed on endothelial cells on angiogenesis.

Static and dynamic electro-optic properties of a SmC* phase in surface stabilized geometry and dispersed in the polymer matrix.

Comparative electro-optical measurements have been made on a ferroelectric liquid crystal (FLC) in surface stabilized geometry and confined to an ellipsoidal cavity within a polymer matrix. The static and dynamic electro-optical characteristics were measured for both systems and show qualitatively similar behaviours. A fast switching and important bistability were observed and characterized as a function of the applied electric field strength.

Vascular endothelial growth factor VEGF189 induces human neutrophil chemotaxis in extravascular tissue via an autocrine amplification mechanism.

Vascular endothelial growth factor (VEGF) is a potent and specific endothelial cell mitogen involved in normal and pathological angiogenesis. Our group recently reported that, among the several VEGF isoforms, VEGF189 (V189) is selectively induced in decidual endometrial cells during the mid-late phase of the menstrual cycle, together with polymorphonuclear neutrophil (PMN) influx. We thus compared the effects of various VEGF isoforms on PMN migration in vitro, and the mechanisms involved.

Transport and transformation of de-icing urea from airport runways in a constructed wetland system.

Urea, NH2-CO-NH2, is used as a de-icing agent at Kalmar Airport, southeast Sweden. During 1998-2001, urea contributed on average 30% of the yearly nitrogen (N) transport of 41,000 kg via Törnebybäcken stream to the coastal zone of the Baltic Sea. In order to reduce stream transport of N from airport, agricultural and other diffuse sources, a wetland was constructed in 1996.

Methods designed for the identification and characterization of in vitro and in vivo chromatin assembly mutants in Saccharomyces cerevisiae.

Assembly of DNA into chromatin allows for the formation of a barrier that protects naked DNA from protein and chemical agents geared to degrade or metabolize DNA. Chromatin assembly occurs whenever a length of DNA becomes exposed to the cellular elements, whether during DNA synthesis or repair. This report describes tools to study chromatin assembly in the model system Saccharomyces cerevisiae.

Regulation of myometrial phospholipase C system and uterine contraction by beta-adrenergic receptors in midpregnant rat.

We investigated whether beta-adrenergic receptors (beta-AR) regulate the phospholipase C (PLC) system in midpregnant rat myometrium. PLCbeta isoforms were characterized, and the effect of isoproterenol (beta-adrenergic agonist) was tested on myometrial inositol phosphate (InsP) production and uterine contraction. Using specific antibodies, we showed that rat myometrium expresses PLCbeta1, PLCbeta3, and PLCbeta4, and to a lesser degree PLCbeta2.

Three-arm randomized study of two cisplatin-based regimens and paclitaxel plus gemcitabine in advanced non-small-cell lung cancer: a phase III trial of the European Organization for Research and Treatment of Cancer Lung Cancer Group--EORTC 08975.

Purpose: To compare the therapeutic efficacy of paclitaxel plus cisplatin (arm A) versus gemcitabine plus cisplatin (arm B) and arm A versus paclitaxel plus gemcitabine (arm C) in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC).

Materials And Methods: Patients were randomly assigned to receive either paclitaxel 175 mg/m2 (3-hour infusion, day 1) or gemcitabine 1,250 mg/m2 (days 1 and 8) both combined with cisplatin 80 mg/m2 (day 1) or paclitaxel 175 mg/m2 (3-hour infusion, day 1) combined with gemcitabine 1,250 mg/m2 (days 1 and 8). Primary end point was comparison of overall survival for B versus A and C versus A.

Carboplatin and paclitaxol (Taxol) as an induction regimen for patients with biopsy-proven stage IIIA N2 non-small cell lung cancer. an EORTC phase II study (EORTC 08958).

The aim of this study was to document the activity and toxicity of paclitaxel (Taxol)/carboplatin when used as induction chemotherapy in patients with stage IIIA N2 non-small cell lung cancer (NSCLC) prior to definitive local treatment within a large, ongoing comparative study (EORTC 08941). 52 eligible, consenting, chemotherapy-naïve patients with NSCLC, median age of 60 years, stage IIIA N2 disease and the ability to tolerate a pneumonectomy received paclitaxel 200 mg/m2 as a 3-h infusion followed by carboplatin at an area under the concentration curve (AUC) of 6 every 3 weeks for three courses. Most patients received three courses.

Endogenous G protein-coupled receptor kinase 6 triggers homologous beta-adrenergic receptor desensitization in primary uterine smooth muscle cells.

We previously reported that G protein-coupled receptor kinase (GRK) may contribute to beta-adrenergic receptor (beta-AR) uncoupling occurring just before parturition in rat uterine muscle (myometrium). To identify the GRK involved, we set up in this study a primary cell culture retaining the morphological and functional characteristics of myometrial tissue as well as the in vivo pattern of GRK expression (GRK2, GRK5, and GRK6). In this model, homologous beta-AR desensitization was assessed by an approximately 60% decrease in cAMP production to a subsequent challenge with the beta-agonist, isoproterenol.

Static and dynamic dielectric properties of strongly polar liquids in the vicinity of first order and weakly first order phase transitions.

The paper presents the results of measurements of the linear dielectric properties of the compounds from the homologous series of alkylcyanobiphenyls (C(n)H(2n+1)PhPhCN, nCB) in the vicinity of the first order transition (from the isotropic liquid to the crystalline phase) of nonmesogenic nCB's (n=2-4) and the weakly first order transition (from the isotropic liquid to the nematic phase) of 5CB. The experimental method for the separation of the critical part of the static permittivity derivative and the activation energy for rotation of the mesogenic molecules, in the vicinity of weakly first order phase transition, is proposed. It is shown that the critical temperature dependence of the permittivity and the activation energy can be described with a function of (T-T*)(-alpha) type, with the same values of the temperature of virtual transition of the second order (T*) and the critical exponent (alpha).

Temozolomide in patients with advanced non-small cell lung cancer with and without brain metastases. a phase II study of the EORTC Lung Cancer Group (08965).

This study was performed to evaluate the activity of single-agent temozolomide in two groups of chemotherapy-naïve non-small cell lung cancer (NSCLC) patients, with (12 patients) and without (13 patients) brain metastases (BM). Patients in both groups were treated with temozolomide 200 mg/m(2)/day, administered orally for 5 consecutive days of a 28-day cycle. Treatment was continued for up to six cycles, disease progression or unacceptable toxicity.

Efficacy of Humalog injections before an afternoon meal and their acceptance by children and adolescents with type 1 diabetes.

Aims: To evaluate the acceptability and efficacy of an injection of insulin lispro, before an afternoon meal.

Methods: The subjects, 43 patients with Type 1 diabetes, 16 boys and 27 girls, aged 12.4 +/- 2.

Microarray analysis of knockout mice identifies cyclin D2 as a possible mediator for the action of thyroid hormone during the postnatal development of the cerebellum.

Thyroid hormone is a major regulator of postnatal brain development, but the precise molecular mechanisms underlying its action in this organ remain poorly understood. We used microarray analysis to identify new target genes in brain. Thyroid hormone treatment of hypothyroid Pax8(-/-) knockout mice, which lack thyroid follicular cells, had a very limited global effect on brain transcripts.

The activity of raltitrexed (Tomudex) in malignant pleural mesothelioma: an EORTC phase II study (08992).

We investigated the activity and toxicity of raltitrexed (Tomudex) as a single agent treatment in patients with Malignant Pleural Mesothelioma (MPM) in a multicentre phase II European Organization for Research and Treatment of Cancer (EORTC) study. This study enrolled chemonaíve patients with histologically-confirmed measurable MPM. Raltitrexed was administered at the dose of 3 mg/m(2) intravenous (i.

Treatment of operable breast cancer in the elderly: a randomised clinical trial EORTC 10851 comparing tamoxifen alone with modified radical mastectomy.

For treatment of early breast cancer in older women, little evidence is available from randomised trials. We conducted a randomised trial comparing modified radical mastectomy (MRM) with tamoxifen (TAM) as the sole initial therapy in 164 patients aged >/=70 years with operable breast cancer. 82 were treated by MRM and 82 with TAM.