[Extreme hypofractionation: New indications for breast cancer radiotherapy]. / Hypofractionnement extrême en pratique : les nouvelles indications dans les cancers du sein.

Due to the continuously increasing number of newly diagnosed breast cancer and limited health resources hypofractionated radiotherapy is a major topic. Recent results from randomized clinical trials assessing extreme hypofractionated radiotherapy for whole or partial breast radiotherapy are practice changing. Here we report toxicity and oncological outcomes from major recent trials of extreme hypofractionated breast irradiation and present an ongoing prospective implementation program. For whole breast irradiation, with a 10 years follow up, the UK-FAST trial demonstrated no significant difference in toxicity between a once weekly 5 fractions (5,7Gy/fr) regimen and a conventional 50Gy/25fr regimen. With a 5 years follow up, the FAST-Forward trial showed non inferiority on local control for a 5 fractions over 1 week (5,2Gy/fr) regimen versus standard 40Gy/15fr over 3 weeks with safe toxicity profile. For accelerated partial breast irradiation, in low-risk breast cancers patients, several phase III randomized trials confirmed that extreme hypofractionation is a valid option. With our "One Week Breast Radiotherapy" program, we propose the implementation of a one-week full workflow preparing and delivering 5 fractions over 1 week (26Gy) in selected patients with prospective follow-up. Several extreme hypofractionated breast radiotherapy regimens are validated and can be routinely discussed with patients in a share decision-making process following patient selection criteria and dosimetric constraints.

[Margin determination from clinical to planning target volume for lung cancer treated with conformal or intensity-modulated irradiation]. / Détermination des marges du volume cible anatomoclinique au volume cible prévisionnel des cancers bronchiques en radiothérapie conformationnelle tridimensionnelle ou avec modulation d'intensité.

Technological progress in radiotherapy enables more precision for treatment planning and delivery. The margin determination between the clinical target volume and the planning target volumes stem from the estimation of geometric uncertainties of the tumour localization into the radiation beam. The inner motion complexity of lung tumours has led to the use of 4D computed tomography and nurtures specific dosimetric concerns. Few strategies consisting in integrating tumour motion allow margin reduction regarding inner movements. The patient immobilization and onboard imagery improvement decrease the setup uncertainties. Each step between the initial planning imagery and treatment delivery has to be analysed as systematic or random errors to calculate the optimal planning margin.

Probing the kinetics of lipid membrane formation and the interaction of a nontoxic and a toxic amyloid with plasmon waveguide resonance.

The kinetics of formation of solid-supported lipid model membranes were investigated using a home-made plasmon waveguide resonance (PWR) sensor possessing enhanced properties relative to classic surface plasmon resonance sensors. Additionally, the kinetics of interaction of two amyloid peptides with zwitterionic and anionic membranes and their effect on lipid organization were followed.

A second eIF4E protein in Schizosaccharomyces pombe has distinct eIF4G-binding properties.

The eukaryotic cap-binding proteins belonging to the eIF4E family are generally involved in mediating the recruitment of ribosomes to capped mRNA. We described previously a cap-binding protein (now called eIF4E1) in Schizosaccharomyces pombe that appears to have all of the usual structural and functional attributes of an eIF4E. We have now characterised a new type of cap-binding protein (eIF4E2) from this organism, which at the amino acid sequence level, is 52% identical and 59% similar to eIF4E1. eIF4E2 is not essential in S.pombe but has some novel properties that may be related to a special function in the cell. The ratio of eIF4E2:eIF4E1 in the cell shifts in favour of eIF4E2 at higher temperatures. Despite having all of the dorsal face amino acids that have so far been associated with eIF4G binding to eIF4E1, eIF4E2 binds the eIF4E-binding domain of S.pombe eIF4G >10(2)-times weaker than eIF4E1 in vitro. The eIF4E2 cap-binding affinity is in the typical micromolar range. The results suggest that eIF4E2 is not active on the main pathway of translation initiation in fission yeast but might play a role in the adaptation strategy of this organism under specific growth conditions. Moreover, they provide insight into the molecular characteristics required for tight binding to eIF4G.

Purification and characterization of an alpha-glucosidase from Rhizobium sp. (Robinia pseudoacacia L.) strain USDA 4280.

A novel alpha-glucosidase with an apparent subunit mass of 59 +/- 0. 5 kDa was purified from protein extracts of Rhizobium sp. strain USDA 4280, a nodulating strain of black locust (Robinia pseudoacacia L), and characterized. After purification to homogeneity (475-fold; yield, 18%) by ammonium sulfate precipitation, cation-exchange chromatography, hydrophobic chromatography, dye chromatography, and gel filtration, this enzyme had a pI of 4.75 +/- 0.05. The enzyme activity was optimal at pH 6.0 to 6.5 and 35 degrees C. The activity increased in the presence of NH4+ and K+ ions but was inhibited by Cu2+, Ag+, Hg+, and Fe2+ ions and by various phenyl, phenol, and flavonoid derivatives. Native enzyme activity was revealed by native gel electrophoresis and isoelectrofocusing-polyacrylamide gel electrophoresis with fluorescence detection in which 4-methylumbelliferyl alpha-glucoside was the fluorogenic substrate. The enzyme was more active with alpha-glucosides substituted with aromatic aglycones than with oligosaccharides. This alpha-glucosidase exhibited Michaelis-Menten kinetics with 4-methylumbelliferyl alpha-D-glucopyranoside (Km, 0.141 microM; Vmax, 6.79 micromol min-1 mg-1) and with p-nitrophenyl alpha-D-glucopyranoside (Km, 0.037 microM; Vmax, 2.92 micromol min-1 mg-1). Maltose, trehalose, and sucrose were also hydrolyzed by this enzyme.

Collaborative home practice: nursing and occupational therapy ensure appropriate medication administration.

Interdisciplinary collaboration in home healthcare practice can help to generate successful outcomes for patients. However, effective collaboration requires that disciplines have a thorough understanding of team members' respective roles, use their team members' expertise effectively, and have a willingness to work together to solve problems and integrate interventions. In this case study, nursing and occupational therapy collaborated to maximize one patient's independence in medication administration.

vir-Gene-inducing activities of hydroxycinnamic acid amides in Agrobacterium tumefaciens.

Expression of Agrobacterium tumefaciens virulence genes and transformation of dicots by this organism are dependent upon host plant phenolic compounds. Several alkylsyringamides have recently been shown to be powerful inducers of these vir-genes. These synthetic amides, and especially ethylsyringamide, are much stronger inducers than syringic acid. In this work, four alkylamides derived from ferulic or sinapic acids were synthesized by a dicyclohexylcarbodiimide method and tested for their potential to induce vir-gene expression on A. tumefaciens strains harbouring virB::lacZ or virE::lacZ fusion plasmids. Their effectiveness was compared to that of ethylsyringamide and tyraminylferulamide, a naturally occurring amide in plants. Whatever the amine moiety of the amide (ethylamine, propylamine, tyramine or beta-alanine ethyl ester) conjugation of the acid functional group clearly diminished the toxicity to the bacteria of the respective acid at high concentration and thereby increased the vir-inducing potential. However, none of the inducers tested exhibited higher activity than acetosyringone, the reference compound for vir-gene induction, with the exception of ethylsyringamide at concentrations above 1mM. When tested on Agrobacterium tumefaciens strain A348(pSM243cd), ethylferulamide and ethylsinapamide were more efficient than the corresponding phenolic acids but only above 100 microM.

Reduction of restenosis after angioplasty in an atheromatous rabbit model by suicide gene therapy.

BACKGROUND: Gene delivery of the thymidine kinase (tk) gene combined with ganciclovir (GCV) limits intimal hyperplasia after abrasion of normal arteries. However, the low efficiency of adenoviral-mediated gene transfer to atherosclerotic arteries has raised concerns about the applicability of this strategy to the prevention of restenosis. METHODS AND RESULTS: A replication-defective adenoviral vector expressing tk (Ad-RSVtk) demonstrated selective toxicity toward GCV-treated arterial smooth muscle cells, with oligonucleolytic cleavage suggesting apoptosis. In vivo, after demonstration of tk expression after Ad-RSVtk delivery, the combination of Ad-RSVtk followed by GCV was tested in a rabbit model of angioplasty of atheromatous iliac arteries. Angioplasty (8 atm, 20 minutes) was performed by use of a hydrogel balloon coated with Ad-RSVtk (4x10(9) plaque forming units). GCV was infused (25 mg.kg(-1) I.V. BID) from days 2 through 7 after angioplasty in 8 of 12 rabbits. Four weeks later, morphometric analysis demonstrated a reduced intima-to-media ratio in the group receiving combination therapy compared with Ad-RSVtk alone (3.0+/-1.2 versus 5.2+/-0.5, P<.018). GCV per se had no effect on intimal hyperplasia after arterial injury. CONCLUSIONS: In vitro, Ad-RSVtk demonstrates selective toxicity toward GCV-treated arterial smooth muscle cells involving apoptosis. In vivo, GCV conditions reduction of neointimal formation after percutaneous delivery of Ad-RSVtk during angioplasty of atheromatous arteries.

Alkylsyringamides, new inducers of Agrobacterium tumefaciens virulence genes.

The virulence genes of Agrobacterium tumefaciens are specifically activated by plant phenolic compounds and allow this organism to genetically transform plant cells. New types of phenolic compounds, three phenol amides derived from syringic acid, were synthesized. Introduction of an amide group in syringic acid strongly enhances its vir gene inducing activity.

Opposite in vitro and in vivo regulation of hepatic apolipoprotein A-I gene expression by retinoic acid. Absence of effects on apolipoprotein A-II gene expression.

We studied the pharmacological potential of retinoids to modulate apolipoprotein (apo) A-I and apoA-II gene expression and production in vitro in the human cell line HepG2 as well as in primary cultures of adult rat hepatocytes and in vivo in the rat. In HepG2 cells, addition of all-trans retinoic acid (RA) doubled apoA-I mRNA within 24 hours and protein secreted in the culture medium after 48 hours. The induction of apoA-I mRNA by RA was completely blocked by actinomycin D, suggesting that RA acts at the transcriptional level in HepG2 cells. In primary cultures of rat hepatocytes, addition of RA increased apoA-I mRNA in a dose- and time-dependent manner as well as the secretion of apoA-I protein. Similar changes in apoA-I mRNA were observed with 9-cis RA. However, in vivo, hepatic apoA-I mRNA levels decreased after a single administration of RA at 10 mg/kg and remained low after prolonged treatment or at a higher dose, and serum apoA-I concentrations did not change. Furthermore, RA treatment did not substantially affect apoA-II mRNA levels or protein secretion either in vitro or in vivo. As a control, RA receptor-beta mRNA levels increased after RA both in vitro and in vivo. In conclusion, RA treatment selectively induces apoA-I and not apoA-II expression in vitro but not in vivo. These results therefore show additional regulatory effects of RA on apoA-I gene expression in vivo and raise questions about the usefulness of RA in the treatment of atherosclerosis.