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Bernard Meunier

Publications and source records attributed to Bernard Meunier.

At least 37 records · Page 2Linked to original sources
PubMed2005

Accuracy of preoperative imaging methods in a retrospective series of 14 patients with operated intraductal papillary mucinous tumors of the pancreas.

UNLABELLED: Accuracy of preoperative imaging methods for the diagnosis of intraductal papillary mucinous tumor of the pancreas (IPMT) is not well known. AIMS: To compare diagnostic accuracy of various preoperative imaging methods with pathology data following surgical resection. PATIENTS AND METHODS: Fourteen consecutive patients underwent pancreatic surgical resection for IPMT between January 1988 and May 2002. Imaging methods included endoscopic retrograde cholangiopancreatography and/or magnetic resonance cholangiopancreatography and/or endoscopic ultrasonography. Results of preoperative morphological examinations were compared with histopathological findings from surgical specimens. RESULTS: IPMT was located to the pancreatic head or body in 72% of patients and involved the main pancreatic duct (MPD) in 79% of cases Carcinoma was diagnosed in 35% of the cases. Sensitivity of imaging methods varied from 64 to 80% to accurately locate the tumor and from 73 to 80% in distinguishing between types involving the MPD or the accessory ducts. Planned surgical resection based on preoperative imagery correlated with final surgery in 57% of the patients. Histological study of whole pancreas specimens revealed lesions in undilated ducts, and also dilated ducts without histological lesions. CONCLUSION: The sensitivity of preoperative imaging methods is moderate in defining intraductal extension of IPMT. Duct dilatation is not predictive of histological involvement by tumors and ducts may be pathological without dilatation.

Aged↗
PubMed2005

New drugs for colorectal cancer (irinotecan, oxaliplatin, raltitrexed) meet expectations in routine practice: a single center's experience before and after their introduction.

BACKGROUND AND AIMS: Treatment of metastatic colorectal cancer with new drugs (NDs) as oxaliplatin and irinotecan had improved response and survival. In order to check whether the promising achievements of the trials are obtained in routine clinical practice, we have reviewed retrospectively our results for two periods, before (period A: 1993-1995, n=63) and after (period B:1998-2000 n=103) the introduction of these NDs. Patients characteristics, treatment modalities, survival, and prognostic factors were compared. PATIENTS: There were 74 women and 92 men, aged 60.8+/-11.6 yr, 7 patients received best supportive care only, 91 had synchronous metastasis. RESULTS: Period B patients were older, with WHO score>1 more often, more adjuvant treatment, more metachronous metastasis, and NDs used more frequently (24% vs 59%). Median survival was similar (16 vs 15 mo). But when looking at the population aged<75 years with WHO score<2, median survival was 13 mo (period A) vs 21 mo (period B); survival at 1, 2, and 3 yr were respectively 59.5+/-8%, 16.2+/-6 %, 13.5+/-6 % vs 69.8+/-6%, 49.6+/-7%, 29.8+/-7%, p<0.01). In multiparametric analysis, factors correlated with survival were the absence of elevated serum alkaline phosphatase, a unique metastatic organ, and administration of NDs. CONCLUSION: In our routine clinical experience the use of NDs for metastatic CRC has allowed a significant improvement in survival among patients with unresectable tumors.

Age Factors↗
PubMed2004

Synthesis and antimalarial activity of trioxaquine derivatives.

Trioxaquines are dual molecules that contain a trioxane motif linked to an aminoquinoline entity. Among the different compounds of this series, trioxaquine cis-15 (DU1302 c), prepared from alpha-terpinene, a cheap natural product, showed efficient antimalarial activity in vitro on both sensitive and resistant strains of Plasmodium falciparum (IC(50)=5-19 nM). A stereochemical description of this stable, nontoxic, and non-genotoxic antimalarial agent is detailed. Mice infected with P. vinckei were successfully treated with cis-15 in a four-day suppressive test. The doses required to decrease parasitemia by 50 % (ED(50)) were 5 and 18 mg kg(-1) d(-1) after intraperitoneal and oral administration, respectively. Parasitemia clearance was complete without recrudescence at an intraperitoneal dose of 20 mg kg(-1) d(-1).

Aminoquinolines↗
PubMed2004

Alkylation of human hemoglobin A0 by the antimalarial drug artemisinin.

In vitro, the heme cofactor of human iron(II) hemoglobin was efficiently and quickly alkylated at meso positions by the peroxide-based antimalarial drug artemisinin, leading to heme-artemisinin-derived covalent adducts. This reaction occurred in the absence of any added protease or in the presence of an excess of an extra non-heme protein, or even when artemisinin was added to hemolysed human blood. This activation of artemisinin by the heme moiety of non-digested hemoglobin clearly indicates the high affinity of this drug for heme, and its efficient alkylating ability under very mild conditions.

Alkylation↗
PubMed2004

Cationic phosphorus-containing dendrimers reduce prion replication both in cell culture and in mice infected with scrapie.

Over the last 30 years, many drugs have been tested both in cell culture and in vivo for their ability to prevent the generation of prions and the development of transmissible spongiform encephalopathies. Among the compounds tested, dendrimers are defined by their branched and repeating molecular structure. The anti-prion activity of new cationic phosphorus-containing dendrimers (P-dendrimers) with tertiary amine end-groups was tested. These molecules had a strong anti-prion activity, decreasing both PrP(Sc) and infectivity in scrapie-infected cells at non-cytotoxic doses. They can bind PrP and decrease the amount of pre-existing PrP(Sc) from several prion strains, including the BSE strain. More importantly, when tested in a murine scrapie model, the dendrimers were able to decrease PrP(Sc) accumulation in the spleen by more than 80 %. These molecules have a high bio-availability and therefore exhibit relevant potential for prion therapeutics for at least post-exposure prophylaxis.

Animals↗
PubMed2003

Dendrimeric coating of glass slides for sensitive DNA microarrays analysis.

Successful use and reliability of microarray technology is highly dependent on several factors, including surface chemistry parameters and accessibility of cDNA targets to the DNA probes fixed onto the surface. Here, we show that functionalisation of glass slides with homemade dendrimers allow production of more sensitive and reliable DNA microarrays. The dendrimers are nanometric structures of size-controlled diameter with aldehyde function at their periphery. Covalent attachment of these spherical reactive chemical structures on amino-silanised glass slides generates a reactive approximately 100 A layer onto which amino-modified DNA probes are covalently bound. This new grafting chemistry leads to the formation of uniform and homogenous spots. More over, probe concentration before spotting could be reduced from 0.2 to 0.02 mg/ml with PCR products and from 20 to 5 micro M with 70mer oligonucleotides without affecting signal intensities after hybridisation with Cy3- and Cy5-labelled targets. More interestingly, while the binding capacity of captured probes on dendrimer-activated glass surface (named dendrislides) is roughly similar to other functionalised glass slides from commercial sources, detection sensitivity was 2-fold higher than with other available DNA microarrays. This detection limit was estimated to 0.1 pM of cDNA targets. Altogether, these features make dendrimer-activated slides ideal for manufacturing cost-effective DNA arrays applicable for gene expression and detection of mutations.

DNA, Complementary↗
PubMed2003

1H and 13C NMR characterization of hemiamidal isoniazid-NAD(H) adducts as possible inhibitors of InhA reductase of Mycobacterium tuberculosis.

Isoniazid (INH) is easily oxidized with manganese(III) pyrophosphate, a chemical model of the KatG protein involved in activation of INH inside the bacteria Mycobacterium tuberculosis. Performed in the presence of NAD(+), this oxidation generates a family of isomeric INH-NAD(H) adducts, which have been shown to be effective inhibitors of InhA, an enzyme essential in mycolic acid biosynthesis. In this work, we fully characterized by (1)H and (13)C NMR spectroscopy four main species of INH-NAD(H) adducts that coexist in solution. Two of them are open diastereoisomers consisting of the covalent attachment of the isonicotinoyl radical at position four of the nicotinamide coenzyme. The other two result from a cyclization involving the amide group from the nicotinamide and the carbonyl group from the isonicotinoyl radical to give diastereoisomeric hemiamidals. Although an INH-NAD(H) adduct with a 4S configuration has been characterized within the active site of InhA from Xray crystallography and this bound adduct interpreted as an open form (Rozwarski et al., Science 1998, 279, 98-102), it is legitimate to raise the question about the effective active form(s), open or cyclic, of INH-NAD(H) adduct(s). Is there a single active form or are several forms able to inhibit the InhA activity with different levels of inhibitory potency?

Bacterial Proteins↗
PubMed2003

DNA cleavage studies of mononuclear and dinuclear copper(II) complexes with benzothiazolesulfonamide ligands.

Copper-based transition metal complexes performing single- and double-strand scission of DNA have been studied. The dinuclear complexes [Cu(2)(L)(2)(OCH(3))(2)(NH(3))(2)] and [Cu(2)(L)(2)(OCH(3))(2)(DMSO)(2)] are more active than the corresponding mononuclear [Cu(L)(2)(py)(2)] (where HL= N-(4-methylbenzothiazol-2-yl)benzenesulfonamide), suggesting that the dinuclearity is an important factor in the oxidative cleavage of DNA. The cleavage efficiency of the complexes depends on the reducing agent used in the process, the tandem ascorbate/H(2)O(2) being the most efficient. PAGE analyses have shown that these complexes cleave DNA without sequence selectivity. The DNA degradation process takes place mainly by C1' oxidation, but C4' and C5' oxidations cannot be ruled out as minor pathways. These copper complexes preferably oxidize guanine under mild conditions, but under more drastic conditions the oxidation reactivity appears to be T>G>C>A, suggesting the intervention of hydroxyl radicals as active species.

Chromatography, High Pressure Liquid↗
PubMed2003

Injection by various routes of melanoma antigen-associated macrophages: biodistribution and clinical effects.

Patients' autologous macrophages (AM) were used as antigen-presenting cells (APC) in a vaccination protocol against malignant melanoma. AM were administered by various routes, including intralymphatic, since these cells did not express CCR7, a molecule required for APC migration to lymph nodes. Seven HLA-A2 patients with metastatic melanoma-two classified as M1 and five as M3-were included in the study. AM were produced from leukapheresis-separated mononuclear cells by 7-day culture with granulocyte-macrophage colony-stimulating factor. After separation by elutriation, AM were frozen in aliquots and subsequently thawed at monthly intervals, exposed to MAGE-3(271-279) peptide and injected subcutaneously into lymph nodes or into one peripheral lymph vessel. Intradermal tests were performed before and after treatment to determine peptide reactivity. No acute toxicity was observed following injection. One M1 patient had a 7-mm induration intradermal reaction response and was stabilized for 64 weeks. The M3 patients did not show any immunological or clinical response. In 11 patients, the biodistribution of 111In-labeled AM was investigated. There was no clear evidence that AM injected intradermally or subcutaneously left the site of injection. After injection into a lymph vessel of the foot region, scintigraphs showed five to ten popliteal and inguinocrural lymph nodes. This appeared to be the most efficient way to administer rapidly and safely large amounts of peptide-loaded APC into lymph nodes.

Adult↗
PubMed2003

Porphyrin-aminoquinoline conjugates as telomerase inhibitors.

A series of metalloporphyrins was prepared in order to target the G-quadruplex structure of telomeric DNA for the design of antitelomerase compounds. The initial cationic tetramethylpyridiniumyl porphyrin was modified by the replacement of one or two methylpyridiniumyl groups by one or two 4-aminoquinoline moieties, at the meso position, in order to increase the cell penetration and the quadruplex affinity. The porphyrins were either metallated by manganese or by nickel. The degradation of quadruplex DNA was assayed in vitro with the manganese redox-active derivatives. All porphyrins complexes were capable of inhibiting the telomerase enzyme with IC50 values in the micromolar range (TRAP assay).

Aminoquinolines↗
PubMed2003

Theoretical study of the interaction between a high-valent manganese porphyrin oxyl-(hydroxo)-Mn(IV)-TMPyP and double-stranded DNA.

Cationic porphyrin derivatives such as meso-tetrakis(4-N-methylpyridinium)porphyrin, TMPyP, have been shown to interact with double-stranded DNA. The manganese derivative, Mn(III)-TMPyP, activated by an oxygen donor like potassium monopersulfate, provides an efficient DNA-cleaving system. Previous experimental work1 has shown that DNA cleavage by the Mn(III)-TMPyP/KHSO(5) system was due to an oxidative attack, within the minor groove of B-DNA, at the C5' or C1' carbons of deoxyribose units. The aim of this study was to use molecular modeling to elucidate the specificity of the interactions between the transient active species oxyl-Mn(IV)-TMPyP and the DNA target. Geometric parameters, charges, and force field constants consistent with the AMBER 98 force field were calculated by DFT methods. Molecular modeling (mechanics and dynamic simulations) were performed for oxyl-(hydroxo)-Mn(IV)-TMPyP bound in the minor groove of the dodecamer d(5'-TCGTCAAACCGC)-d(5'-GCGGTTTGACGA). Geometry, interactions, and binding energy of the metalloporphyrin located at the A.T triplet region of the dodecamer were analyzed. These studies show no significant structural change of the DNA structure upon ligand binding. Mobility of the metalloporphyrin in the minor groove was restrained by the formation of a hydrogen bond between the hydroxo ligand trans to the metal-oxyl and a DNA phosphate, restricting the access of the oxyl group to the (pro-S) H atom at C5'.

Base Sequence↗
PubMed2003

Adjuvant intra-arterial injection of iodine-131-labeled lipiodol after resection of hepatocellular carcinoma.

The high rate of recurrence after surgical resection of hepatocellular carcinoma (HCC) is a major therapeutic challenge. Postoperative injection of 131-iodine-labeled lipiodol (131I-Lip) into the hepatic artery has been proposed as adjuvant treatment (Lau et al.). We analyzed 2 retrospective series of matched patients treated in our unit before and after addition of 131I-Lip adjuvant therapy to our standard surgical strategy. Thirty-eight patients who had undergone surgical resection of HCC after January 1999 were given adjuvant intra-arterial injection of 131I-Lip after surgery. These patients were matched with 38 other patients who had undergone surgical resection only between January 1997 and January 1999. The frequency of recurrences, disease-free rates, and overall survival rates were compared. The 2 groups were similar for clinical, biologic, or histologic parameters studied and Cancer Liver Italian Program scores. There were 15 recurrences in the group without adjuvant treatment and 9 in the group with 131I-Lip adjuvant treatment. The 1-, 2-, and 3-year disease-free survival rates (+/-95% confidence interval) were different (P <.02): 94.7% +/- 3.6%, 83.7% +/- 6.1%, and 68.4% +/- 9.7%, respectively, in the 131I-Lip group versus 73.7% +/- 7.1%, 54.3% +/- 8.2%, and 41.5% +/- 10.5% in the surgery group. The 1-, 2-, and 3-year survival rates (+/-95% confidence interval) also were different (P <.02): 94.7% +/- 3.6%, 91.7% +/- 4.6%, and 91.7% +/- 4.6%, respectively, in the 131I-Lip group versus 94.7% +/- 3.6%, 71.3% +/- 7.8%, and 49.9% +/- 10% in the surgery group. In conclusion, this retrospective analysis supports the promising contribution of postoperative injection of 131I-Lip after resection of HCC. A randomized study including more patients would be necessary to confirm its contribution to therapeutic management.

Aged↗
PubMed2003

Chloroquine and artemisinin: six decades of research--what next?

Over the next decade drugs will remain the focus of continuous efforts to control malaria, with a contribution from pharmacogenomic development. Quinine, extracted from Cinchona bark, has been the source for aminoquinoline drugs such as chloroquine; more recently, artemisinin extracted from Artemisia allowed the design of artemisinin mimics containing a trioxane structure. Here, we examine parallels between chloroquine and artemisinin in terms of pharmacological target discovery, mechanism of action and parasite resistance. The widespread use of chloroquine has dramatically reduced its therapeutic response, thus recent strategies are based on artemisinin combinations.

Animals↗