992 resultados para c-Met


Relevância:

60.00% 60.00%

Publicador:

Resumo:

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Relevância:

60.00% 60.00%

Publicador:

Resumo:

Un document accompagne le mémoire et est disponible pour consultation au Centre de conservation des bibliothèques de l'Université de Montréal (http://www.bib.umontreal.ca/conservation/).

Relevância:

60.00% 60.00%

Publicador:

Resumo:

Un document accompagne le mémoire et est disponible pour consultation au Centre de conservation des bibliothèques de l'Université de Montréal (http://www.bib.umontreal.ca/conservation/).

Relevância:

60.00% 60.00%

Publicador:

Resumo:

Background: There is an urgent need to identify molecular signatures in small cell lung cancer (SCLC) that may select patients who are likely to respond to molecularly targeted therapies. In this study, we investigate the feasibility of undertaking focused molecular analyses on routine diagnostic biopsies in patients with SCLC.

Methods: A series of histopathologically confirmed formalin-fixed, paraffin-embedded SCLC specimens were analysed for epidermal growth factor receptors (EGFR), KRAS, NRAS and BRAF mutations, ALK gene rearrangements and MET amplification. EGFR and KRAS mutation testing was evaluated using real time polymerase chain reaction (RT-PCR cobas®), BRAF and NRAS mutations using multiplex PCR and capillary electrophoresis-single strand conformation analysis, and ALK and MET aberrations with fluorescent in situ hybridization. All genetic aberrations detected were validated independently.

Results: A total of 105 patients diagnosed with SCLC between July 1990 and September 2006 were included. 60 (57 %) patients had suitable tumour tissue for molecular testing. 25 patients were successfully evaluated for all six pre-defined molecular aberrations. Eleven patients failed all molecular analysis. No mutations in EGFR, KRAS and NRAS were detected, and no ALK gene rearrangements or MET gene amplifications were identified. A V600E substitution in BRAF was detected in a Caucasian male smoker diagnosed with SCLC with squamoid and glandular features.

Conclusion: The paucity of patients with sufficient tumour tissue, quality of DNA extracted and low frequency of aberrations detected indicate that alternative molecular characterisation approaches are necessary, such as the use of circulating plasma DNA in patients with SCLC.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Introduction Access to hepatitis C (hereafter HCV) antiviral therapy has commonly excluded populations with mental health and substance use disorders because they were considered as having contraindications to treatment, particularly due to the neuropsychiatric effects of interferon that can occur in some patients. In this review we examined access to HCV interferon antiviral therapy by populations with mental health and substance use problems to identify the evidence and reasons for exclusion. Methods We searched the following major electronic databases for relevant articles: PsycINFO, Medline, CINAHL, Scopus, Google Scholar. The inclusion criteria comprised studies of adults aged 18 years and older, peer-reviewed articles, date range of (2002--2012) to include articles since the introduction of pegylated interferon with ribarvirin, and English language. The exclusion criteria included articles about HCV populations with medical co-morbidities, such as hepatitis B (hereafter HBV) and human immunodeficiency virus (hereafter HIV), because the clinical treatment, pathways and psychosocial morbidity differ from populations with only HCV. We identified 182 articles, and of these 13 met the eligibility criteria. Using an approach of systematic narrative review we identified major themes in the literature. Results Three main themes were identified including: (1) pre-treatment and preparation for antiviral therapy, (2) adherence and treatment completion, and (3) clinical outcomes. Each of these themes was critically discussed in terms of access by patients with mental health and substance use co-morbidities demonstrating that current research evidence clearly demonstrates that people with HCV, mental health and substance use co-morbidities have similar clinical outcomes to those without these co-morbidities. Conclusions While research evidence is largely supportive of increased access to interferon by people with HCV, mental health and substance use co-morbidities, there is substantial further work required to translate evidence into clinical practice. Further to this, we conclude that a reconsideration of the appropriateness of the tertiary health service model of care for interferon management is required and exploration of the potential for increased HCV care in primary health care settings.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

The tetrapeptide t-butyloxycarbonyl--aminoisobutyryl--aminoisobutyryl-L- phenylalanyl-L-methionyl amide crystallizes in the orthorhombic space group P212121 with a= 9.096, b= 18.067, c= 21.701 Å and Z= 4. The crystals contain one molecule of dimethyl sulphoxide (DMSO) associated with each peptide. The structure has been solved by direct methods and refined to an R value of 0.103 for 2 672 observed reflections. The peptide adopts a distorted 310 helical structure stabilized by two intramolecular 4 1 hydrogen bonds between the Boc CO and Aib(1) CO groups and the NH groups of Phe(3) and Met(4), respectively. A long hydrogen bond (N O = 3.35 Å) is also observed between Aib(2) CO and one of the terminal amide hydrogens. The DMSO molecule is strongly hydrogen bonded to the Aib(1) NH group. The solid-state conformation agrees well with proposals made on the basis of n.m.r. studies in solution.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

The conformation of the peptide Boc-L-Met-Aib-L-Phe-OMe has been studied in the solid state and solution by X-ray diffraction and 1H n.m.r., respectively. The peptide differs only in the N-terminal protecting group from the biologically active chemotactic peptide analog formyl-L-Met-Aib-L-Phe-OMe. The molecules adopt a type-II beta-turn in the solid state with Met and Aib as the corner residues (phi Met = -51.8 degrees, psi Met = 139.5 degrees, phi Aib = 58.1 degrees, psi Aib = 37.0 degrees). A single, weak 4----1 intramolecular hydrogen bond is observed between the Boc CO and Phe NH groups (N---O 3.25 A, N-H---O 128.4 degrees). 1H n.m.r. studies, using solvent and temperature dependencies of NH chemical shifts and paramagnetic radical induced line broadening of NH resonances, suggest that the Phe NH is solvent shielded in CDCl3 and (CD3)2SO. Nuclear Overhauser effects observed between Met C alpha H and Aib NH protons provide evidence of the occurrence of Met-Aib type-II beta-turns in these solvents.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

The conformationally restricted CHO-L-Met-Xxx-L-Phe-OY (where Xxx = Aib, Ac3c, Ac5c, Ac6c, and Ac7c; Y = H, Me) tripeptides, analogs of the chemoattractant CHO-L-Met-L-Leu-L-Phe-OH, have been synthesized in solution by classical methods and fully characterized. Compounds were compared to determine the combined effect of backbone conformational preferences and side-chain bulkiness on the relation of three-dimensional structure to biological activity. Each peptide was tested for its ability to induce granule enzyme secretion from rabbit peritoneal polymorphonuclear leukocytes. In parallel, a conformational analysis on the CHO-blocked peptide and their tertbutyloxycarbonylated synthetic precursors was performed in the crystal state and in solution using X-ray diffraction, infrared absorption, and 1H nuclear magnetic resonance. The biological and conformational data are discussed in relation to the proposed model of the chemotactic peptide receptor of rabbit neutrophils.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

[ES] El análisis de una serie industrial correspondiente a los cinco niveles arqueológicos de la trinchera C de La Quina (Charente, Francia), proveniente de las excavaciones del Dr. L. Henri-Martin y de G. Henri-Martin, pone de manifiesto, junto a la caracterización del conjunto estratigráfico por la presencia de raederas, el progresivo incremento de los denticulados en el devenir temporal. Este hecho asociado a otros particulares fenómenos secundarios (en el alargamiento de las formas, en la tipología de las raederas, en la elaboración del retoque, ... ) traducen una complicación diacrónica creciente en la dinámica de este complejo musteroide, presagiando, quizás, su relativa afinidad con el proceso leptolitizante de las series industriales evolucionadas del Paleolítico medio.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

The UV-visible, circular dichroism (CD), and resonance Raman (RR) spectra of the wild type yeast iso-1-cytochrome c (WT) and its mutant F82H in which phenylalanine-82 (Phe-82) is substituted with His are measured and compared for oxidized and reduced forms. The CD spectra in the intrinsic and Soret spectral region, as well as RR spectra in high, middle, and low frequency regions, are discussed. From the analysis of the spectra, it is determined that in the oxidized F82H the two axial ligands to the heme iron are His-18 and His-82 whereas in the reduced form the sixth ligand switches from His-82 to Met-80 providing the coordination geometry similar to that of WT. Based on the spectroscopic data, the conclusion is that the porphyrin macrocycle is less distorted in the oxidized F82H compared to the oxidized WT. Similar distortions are present in the reduced form of the proteins. Frequency shifts of Raman bands, as well as the decrease of the or-helix content in the CD spectra, indicate more open conformation of the protein around the heme. (C) 2000 John Wiley & Sons, Inc.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Experimental Raman and FT-IR spectra of solid-state non-deuterated and N-deuterated samples of cyclo(L-Met-L-Met) are reported and discussed. The Raman and FT-IR results show characteristic amide I vibrations (Raman: 1649 cm-1, infrared: 1675 cm-1) for molecules exhibiting a cis amide conformation. A Raman band, assigned to the cis amide II vibrational mode, is observed at sim1493 cm-1 but no IR band is observed in this region. Cyclo(L-Met-L-Met) crystallises in the triclinic space group P1 with one molecule per unit cell. The overall shape of the diketopiperazine (DKP) ring displays a (slightly distorted) boat conformation. The crystal packing employs two strong hydrogen bonds, which traverse the entire crystal via translational repeats. B3-LYP/cc-pVDZ calculations of the structure of the molecule predict a boat conformation for the DKP ring, in agreement with the experimentally determined X-ray structure. Copyright © 2009 John Wiley & Sons, Ltd.