Journals
2009 EN
Robert Dominique · Abinet Elise · Spaniol Thomas P.
+1 more
Monocationic bis‐allyl complexes [Ln(η 3 ‐C 3 H 5 ) 2 (thf) 3 ] + [B(C 6 X 5 ) 4 ] − (Ln=Y, La, Nd; X=H, F) and dicationic mono‐allyl complexes of yttrium and the early lanthanides [Ln(η 3 ‐C 3 H 5 )(thf) 6 ] 2+ [BPh 4 ] 2 − (Ln=La, Nd) were prepared by protonolysis of the tris‐allyl complexes [Ln(η 3 ‐C 3 H 5 ) 3 (diox)] (Ln=Y, La, Ce, Pr, Nd, Sm; diox=1,4‐dioxane) isolated as a 1,4‐dioxane‐bridged dimer (Ln=Ce) or THF adducts [Ln(η 3 ‐C 3 H 5 ) 3 (thf) 2 ] (Ln=Ce, Pr). Allyl abstraction from the neutral tris‐allyl complex by a Lewis acid, ER 3 (Al(CH 2 SiMe 3 ) 3 , BPh 3 ) gave the ion pair [Ln(η 3 ‐C 3 H 5 ) 2 (thf) 3 ] + [ER 3 (η 1 ‐CH 2 CHCH 2 )] − (Ln=Y, La; ER 3 =Al(CH 2 SiMe 3 ) 3 , BPh 3 ). Benzophenone inserts into the LaC allyl bond of [La(η 3 ‐C 3 H 5 ) 2 (thf) 3 ] + [BPh 4 ] − to form the alkoxy complex [La{OCPh 2 (CH 2 CHCH 2 )} 2 (thf) 3 ] + [BPh 4 ] − . The monocationic half‐sandwich complexes [Ln(η 5 ‐C 5 Me 4 SiMe 3 )(η 3 ‐C 3 H 5 )(thf) 2 ] + [B(C 6 X 5 ) 4 ] − (Ln=Y, La; X=H, F) were synthesized from the neutral precursors [Ln(η 5 ‐C 5 Me 4 SiMe 3 )(η 3 ‐C 3 H 5 ) 2 (thf)] by protonolysis. For 1,3‐butadiene polymerization catalysis, the yttrium‐based systems were more active than the corresponding lanthanum or neodymium homologues, giving polybutadiene with approximately 90 % 1,4‐ cis stereoselectivity.
Journals
2009 EN
Sameni Soheila · Jeunesse Catherine · Matt Dominique
+1 more
The first diphosphines based on a double calixarene, namely 1,4 (or 1,3)‐bis‐(5‐diphenylphosphino‐25,26,27,28‐tetrapropoxycalix[4]aren‐17‐yl)benzene ( L 2 , L 3 ) were each prepared in four steps starting from 5,17‐dibromo‐25,26,27,28‐tetrapropoxycalix[4]arene. Upon reaction of L 2 with [Au(tht)(thf)]BF 4 , (tht=C 4 H 8 S) a rigid metallo‐capsule was quantitatively formed, which adopts an oblique form owing to the distinct nature of the spacers linking the two calixarene half‐spheres. In the solid state, the 1,4‐substituted phenylene linker is turned towards the gold ion, suggesting the existence of weak bonding interactions between two aromatic CH protons of this ring and the metal centre (Au⋅⋅⋅H=2.67 Å). In contrast to this gold complex, the related silver complex shows dynamic behaviour in solution, the exchange between two enantiomeric oblique forms being facilitated by the greater stereochemical flexibility of Ag I vs. Au I . A heteronuclear 109 Ag{ 1 H} HMQC experiment established strong correlations between the CH protons of the phenylene linker and the 109 Ag ion. Dynamic behaviour similar to that observed for the silver complex was further observed in trans ‐[PtCl 2 ⋅ L 2 ], a chelate complex that could be obtained quantitatively from L 2 and [PtCl 2 (PhCN) 2 ]. The intended formation of a chelate complex leading to a capsule with an endo ‐oriented metal centre was achieved by reacting L 3 with [Pd(allyl)(thf) 2 ]BF 4 . The complex thus formed constitutes the first organometallic transition metal complex embedded in a cavity with large portals. Binding of [RuCl 2 ( p ‐cymene)] to L 2 and L 3 resulted in self‐compacting bimetallic complexes in which each calixarene basket entraps a Ru( p ‐cymene) unit, thereby forming molecules occupying a minimal volume.
Journals
2009 EN
Brizard Aurélie · Berthier Damien · Aimé Carole
+5 more
This contribution presents an application of electronic circular dichroism (ECD) and vibrational circular dichroism (VCD) to study the molecular and supramolecular chirality in assemblies of gemini‐tartrate amphiphiles. Nonchiral dicationic n ‐2‐ n amphiphiles ( n = 14–20) can self‐organize into right‐ or left‐handed structures upon interacting with chiral tartrate counterions. Micellar solutions can also be obtained for shorter alkyl chains ( n = 12). First, the conformation of tartrate counterions has been investigated in various environments (micellar solutions and chiral ribbons). ECD and VCD spectra recorded in micellar solutions are independent from the solvent and from the nature of the cations (sodium, cetyl‐trimethylammonium, or dimeric surfactant 12‐2‐12) used and are representative of the anticonformation of the tartrate dianions. On the other hand, drastic changes in the ECD and VCD spectra have been observed in multilayered chiral assemblies of 16‐2‐16 tartrate. These strong spectral modifications are associated with the chiral arrangement of the tartrate molecules at the surface of the bilayers. Moreover, chirality transfer from counterions to achiral amphiphiles has been clearly evidenced by VCD since circular dichroism has been observed on vibrations related to alkyl chains and gemini headgroups. Finally, ECD and VCD experiments were performed varying the enantiomeric excess of the tartrate. The ECD and VCD intensities do not vary linearly with the enantiomeric excess of the anion and different behaviors have been observed from the two spectroscopic methods: ECD intensities are correlated to the pitch of the ribbons, whereas the VCD intensities are correlated to the dimension of the chiral ribbons. Chirality 21:E153–E162, 2009. © 2009 Wiley‐Liss, Inc.
Wiley Subscription Services
Journals
2009 EN
Palm Thomas · FigarellaBranger Dominique · Chapon Françoise
+7 more
BACKGROUND: Ependymomas derive from ependymal cells that cover the cerebral ventricles and the central canal of the spinal cord. The molecular alterations leading to ependymomal oncogenesis are not completely understood. METHODS: The authors performed array‐based expression profiling on a series of 34 frozen ependymal tumors with different localizations and histologic grades. Data were analyzed by nonsupervised and supervised clustering methods along with Gene Ontology and Pathway Analyzer tools. RESULTS: Class discovery experiments indicated a strong correlation between profiles and tumor localization as well as World Health Organization (WHO) tumor grades. On the basis of supervised clustering, intracranial ependymomas were associated with high expression levels of Notch, Hedgehog, and bone morphogenetic protein pathway members. In contrast, most of the homeobox‐containing genes manifested high expression in extracranial ependymomas. The results also revealed that WHO grade 2 ependymomas differed from WHO grade 3 ependymomas by genes implicated in Wnt/β‐catenin signaling, cell cycle, E2F transcription factor 1 destruction, angiogenesis, apoptosis, remodeling of adherens junctions, and mitotic spindle formation. CONCLUSIONS: Taken together, the tumor localization‐related gene sets mainly implicated in stem cell maintenance, renewal, and differentiation suggest the dysregulation of localized cancer stem cells during ependymoma development. The WHO grade differentiating pathways suggested that alteration of the Wnt/β‐catenin signaling pathway is a key event in the tumorigenesis of WHO grade 3 ependymomas. On the basis of the current data, the authors suggest a developmental scheme of ependymomas that integrates tumor localization and tumor grades, and that pinpoints new targets for the development of future therapeutic approaches. Cancer 2009. © 2009 American Cancer Society.
Wiley Subscription Services
Journals
2009 EN
Metellus Philippe · Coulibaly Bema · Nanni Isabelle
+9 more
BACKGROUND: O 6 ‐methylguanine‐DNA methyltransferase (MGMT) is a key enzyme in the DNA repair process after alkylating agent action. Epigenetic silencing of the MGMT gene by promoter methylation has been associated with longer survival in patients with newly diagnosed glioblastoma multiforme (GBM) who receive alkylating agents. In this study, the authors evaluated the prognostic value of different biomarkers in recurrent GBM and analyzed the changes in MGMT status between primary tumors and recurrent tumors. METHODS: Twenty‐two patients who had recurrent GBM and who underwent surgery with carmustine wafer implantation were enrolled prospectively between 2005 and 2007. The authors investigated the correlation between MGMT silencing in the tumor at recurrence and survival taking into account other clinically recognized prognostic factors. MGMT status was determined by using methylation‐specific polymerase chain reaction analysis, a high‐throughput quantitative methylation assay, and immunohistochemistry. In addition, expression analyses of human mutL homolog 1, human mutS homolog 2, and tumor necrosis factor α‐induced protein 3 at recurrence were conducted with regard to their prognostic impact. RESULTS: The median progression‐free survival (PFS) and overall survival (OS) rates after recurrence were 3.6 months and 9.9 months, respectively, and the 6‐month PFS rate after recurrence was 27.2%. On multivariate analysis, only age ( P = .04) and MGMT promoter hypermethylation at recurrence, as determined by MethyLight technology ( P = .0012) and methylation‐specific polymerase chain reaction (MSP) analysis ( P = .004), were correlated with better PFS. On multivariate analysis, only MGMT promoter hypermethylation at recurrence, as determined by using MethyLight technology ( P = .019) and MSP analysis ( P = .046), was associated with better OS. CONCLUSIONS: MGMT methylation status was an important prognostic factor in patients with recurrent GBM who underwent surgery plus carmustine wafer implantation; therefore, it was useful in predicting the outcome of GBM therapy at recurrence. Cancer 2009. © 2009 American Cancer Society.
Wiley Subscription Services
Journals
2009 EN
Bouchahda Mohamed · Adam René · Giacchetti Sylvie
+7 more
BACKGROUND: Hepatic arterial infusion (HAI) chemotherapy delivers a high concentration of drugs both to liver metastases and to healthy liver with specific, limiting, hepatobiliary toxicities. Relevant detoxification and cellular proliferation pathways are controlled by the molecular circadian clock in normal liver but not in advanced tumors. In this article, the authors report their experience with chronomodulated HAI chemotherapy as rescue therapy in heavily pretreated patients who had metastatic colorectal cancer. METHODS: Data from all consecutive patients with colorectal cancer liver metastases who received HAI with chronomodulated, multidrug chemotherapy regimens in the authors' center after failure on standard chemotherapy were reviewed for efficacy and safety. RESULTS: Twenty‐nine patients were treated, including 76% with liver metastasis only and 24% with liver and lung metastases. Seventy‐five percent of patients had received ≥3 chemotherapy lines, including intravenous, chronomodulated chemotherapy in 59% of patients. Patients received a median of 4 HAI courses (range, 1‐9 courses). The most frequent grade (according to National Cancer Institute of Canada Common Toxicity Criteria [version 3]) 3 and 4 nonhematologic toxicities were vomiting, diarrhea, abdominal pain, and fatigue. No severe hematologic or hepatic toxicities and no chemical cholangitis were reported. An objective tumor response was observed in 10 patients (34.5%), including 4 patients who subsequently underwent R0 or R1 hepatic resection. The median progression‐free survival and overall survival were 4.5 months (95% confidence limits, 2.4‐6.5 months) and 18 months (95% confidence limits, 5.8‐30.2 months), respectively. CONCLUSIONS: HAI chronomodulated chemotherapy had well tolerated activity in selected, heavily pretreated patients, and the authors believe it deserves to be assessed prospectively in clinical trials among patients who have less advanced disease. Cancer 2009. © 2009 American Cancer Society.
Wiley Subscription Services
Journals
2009 EN
Safouane Mahassine · Langevin Dominique
Herein, we study the viscoelastic response of concentrated salt solutions using surface waves excited by electrocapillarity. We show that the hydrodynamic behaviour of the solutions is similar to that of water at concentrations up to 2 m— well above the concentration C*, at which inhibition of bubble coalescence occurs in these solutions. This result excludes the occurrence of changes in the slip conditions at C*, postulated to explain this inhibition. Our study is carried out on salts that both increase and decrease the surface tension. We observe that the salt that decreases the tension does not change the surface behaviour at all, whereas the other two salts essentially produce negative contributions to the surface viscoelasticity at very high salt concentrations. The effects observed are quite large and remain to be explained.
Journals
2009 EN
Dupres Vincent · Verbelen Claire · Raze Dominique
+2 more
New avenues in pathogenesis research: Single‐molecule measurements using AFM elucidate the specific binding forces between pathogen–host interactions. A bacterial adhesin (HBHA) on the AFM tip detects single HSPG receptors directly on living host cells (see figure). In vivo HBHA‐HSPG binding forces are similar to those measured in vitro for HBHA‐heparin complexes.Understanding the molecular interactions between bacterial adhesion proteins (adhesins) and their receptors is essential for elucidating the molecular mechanisms of bacterial pathogenesis. Here, atomic force microscopy (AFM) is used to explore the specific interactions between the heparin‐binding hemagglutinin (HBHA) from Mycobacterium tuberculosis , and heparan sulphate proteoglycan (HSPG) receptors on live A549 pneumocytes. First, we show that the specific binding forces between single HBHA‐HSPG pairs, 57±16 pN, are similar to the forces measured earlier between HBHA and heparin molecules. Second, we mapped the distribution of single HSPG receptors on the surface of A549 cells, revealing that the proteins are widely and homogeneously exposed. Third, we observed force curves with constant force plateaus at large pulling velocities, reflecting the extraction of membrane tethers or nanotubes. These single‐molecule measurements provide new avenues in pathogenesis research, particularly for elucidating the molecular basis of pathogen–host interactions.
Journals
2009 EN
Stirban Alin · Laude Dominique · Elghozi JeanLuc
+4 more
Background Sildenafil, frequently used as on demand medication for the treatment of erectile dysfunction (ED), has been suggested to improve endothelial function but also to alter blood pressure (BP) and induce sympathetic activation. In people with type 2 diabetes mellitus (T2DM), a high‐risk population, the safety profile and the effects on endothelial function of a maximal sildenafil dose (100 mg) have not been investigated and therefore constituted the aim of our study. Methods A double‐blind, placebo‐controlled, cross‐over trial using a single dose of 100 mg sildenafil or placebo has been conducted in 40 subjects with T2DM without known CVD. Haemodynamic parameters, flow mediated dilatation (FMD) in brachial artery, cardiovascular autonomic function tests and spontaneous baroreflex sensitivity (BRS) were measured. Results Sixty minutes after administration of sildenafil but not placebo, a fall of supine systolic blood pressure (SBP) (−5.41 ± 1.87 vs. + 0.54 ± 1.71 mmHg) and diastolic blood pressure (DBP) (−4.46 ± 1.13 vs. + 0.89 ± 0.94 mmHg), as well as orthostatic SBP (−7.41 ± 2.35 vs. + 0.94 ± 2.06 mmHg) and DBP (−5.65 ± 1.45 vs. + 1.76 ± 1.00 mmHg) during standing occurred, accompanied by an increase in heart rate (+1.98 ± 0.69 vs. − 2.42 ± 0.59 beats/min) (all p < 0.01 vs. placebo). Changes in BP to standing up, FMD, time domain and frequency domain indices of heart rate variability (HRV) and BRS were comparable between sildenafil and placebo. Conclusions Sildenafil administered at a maximum single dose to T2DM men results in a mild increase in heart rate and decrease in BP, but it induces neither an acute improvement of FMD nor any adverse effects on orthostatic BP regulation, HRV and BRS. Copyright © 2008 John Wiley & Sons, Ltd.
Journals
2009 EN
Wallacides Angelina · Chesnel Amand · Chardard Dominique
+2 more
Pleurodeles waltl is a urodele amphibian displaying a ZZ/ZW genetic mode of sex determination. Gonad differentiation can later be modulated by hormone treatment. To investigate germ cell differentiation, we analyzed the expression of the meiosis marker PwDmc1 and show that germ cells enter meiosis in late larval life in females, and 2 months after metamorphosis in males. Organotypic cultures of gonad–mesonephros complexes demonstrated that retinoic acid triggers meiosis entry in P. waltl . In vivo analyses of both PwRaldh2 and PwCyp26b1 expressions, the enzymes required for RA synthesis and degradation respectively, indicate that meiosis onset depends on PwCyp26b1 repression in the gonad during normal or steroid‐induced sex‐reversed development. Taken together, our results show that RA‐dependent meiosis entry could be a conserved mechanism of germ cell differentiation in vertebrates and provide evidence for crosstalk between steroid and RA signaling in the course of sex differentiation. Developmental Dynamics 238:1389–1398, 2009. © 2009 Wiley‐Liss, Inc.