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91.
Pascal Sève Sylvie Isaac Olivier Trédan Pierre-Jean Souquet Yves Pachéco Maurice Pérol Laurence Lafanéchère Aurélie Penet Eva-Laure Peiller Charles Dumontet 《Clinical cancer research》2005,11(15):5481-5486
PURPOSE: To determine the prevalence and the prognostic value of microtubule component expression in tumors of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Expression of microtubular components was immunohistochemically examined in 93 tumor samples from untreated patients with stage III and IV NSCLC. All patients received vinorelbine-based chemotherapy. Response to chemotherapy, progression-free survival, and overall survival were correlated with the expression of microtubule proteins. RESULTS: The response rate was 27.3% (21 partial responses among 77 valuable patients). Although expression of microtubule components was not associated with the response rate, high class III beta-tubulin expression was correlated with resistance to vinorelbine, defined as disease progression under treatment. Patients whose tumors expressed high levels of class III beta-tubulin isotype had shorter progression-free survival and overall survival (P = 0.002 and 0.001, respectively). High Delta2 alpha-tubulin expression was associated with a shorter overall survival (P = 0.018). Tubulin II levels were not found to be correlated with patient outcome. A multivariate analysis, taking into account sex, age, histology, stage, weight loss, and class II beta-tubulin, class III beta-tubulin, and Delta2 alpha-tubulin levels, confirmed that class III beta-tubulin expression was independently correlated with progression-free survival (P = 0.04) and overall survival (P = 0.012). CONCLUSIONS: These findings suggest that a high level of expression of class III beta-tubulin in tumor cells is associated with resistance to vinorelbine and a poor prognosis in patients with NSCLC receiving vinorelbine-based chemotherapy. 相似文献
92.
Simon P. Jochems Karin de Ruiter Carla Solrzano Astrid Voskamp Elena Mitsi Elissavet Nikolaou Beatriz F. Carniel Sherin Pojar Esther L. German Jesús Rein Alessandra Soares-Schanoski Helen Hill Rachel Robinson Angela D. Hyder-Wright Caroline M. Weight Pascal F. Durrenberger Robert S. Heyderman Stephen B. Gordon Hermelijn H. Smits Britta C. Urban Jamie Rylance Andrea M. Collins Mark D. Wilkie Lepa Lazarova Samuel C. Leong Maria Yazdanbakhsh Daniela M. Ferreira 《The Journal of clinical investigation》2022,132(11)
93.
Ulrich Hegerl Roland Mergl Christian Sander Jens Dietzel Istvan Bitter Koen Demyttenaere Ricardo Gusmão Ana González-Pinto Iñaki Zorrilla Adriana García Alocén Victor Perez Sola Eduard Vieta Georg Juckel Ulrich S. Zimmermann Michael Bauer Pascal Sienaert Sónia Quintão Marc-Andreas Edel Michael Kluge 《European neuropsychopharmacology》2018,28(1):185-194
Based on many clinical and preclinical findings the ‘vigilance regulation model of mania’ postulates that an unstable regulation of wakefulness is a pathogenetic factor in both mania and Attention Deficit Hyperactivity Disorder (ADHD) and induces hyperactivity and sensation seeking as an autoregulatory attempt to stabilize wakefulness. Accordingly, stimulant medications with their vigilance stabilizing properties could have rapid antimanic effects similar to their beneficial effects in ADHD. The MEMAP study – a multi-center, double-blind, placebo-controlled and randomized clinical trial (RCT) – assessed the antimanic efficacy and safety of a 2.5-day treatment with methylphenidate (20–40 mg/day). Of 157 screened patients with acute mania, 42 were randomly assigned to receive 20–40 mg per day of methylphenidate in one or two applications, or placebo. The primary outcome was the change in Young Mania Rating Scale (YMRS) sum scores from baseline to day 2.5 in the methylphenidate group compared to the placebo group. A group sequential design was chosen to justify early RCT termination based on efficacy or futility at an interim analysis after inclusion of 40 patients. In the interim analysis, the change from baseline in the YMRS total score at day 2.5 was not significantly different between both groups (F(1,37)=0.23; p=0.64). Thus, futility was declared for methylphenidate and the RCT was stopped. In summary, although methylphenidate was well tolerated and safe in the full analysis set, it failed to show efficacy in the treatment of acute mania. Trial registration: clinicaltrials.gov (URL: http://www.clinicaltrials.gov; registration number: NCT01541605). 相似文献
94.
J Michael Conlon Jolanta Kolodziejek Norbert Nowotny Jér?me Leprince Hubert Vaudry Laurent Coquet Thierry Jouenne Jay D King 《Toxicon》2008,52(3):465-473
Peptidomic analysis of norepinephrine-stimulated skin secretions from Hose's rock frog Odorrana hosii (Boulenger, 1891) led to the isolation of 8 peptides with differential antibacterial activities. Structural characterization demonstrated that the peptides belonged to the esculentin-1 (1 peptide), esculentin-2 (1 peptide), brevinin-1 (2 peptides), brevinin-2 (2 peptides), and nigrocin-2 (2 peptides) families of antimicrobial peptides. Similar analysis of skin secretions from the Malaysian fire frog Hylarana picturata (Boulenger, 1920) led to the isolation and characterization of peptides belonging to the brevinin-1 (2 peptides), brevinin-2 (5 peptides), and temporin (1 peptide) families. The differences in antimicrobial activities of paralogous peptides provide insight into structure-activity relationships, emphasizing the importance of cationicity in determining potency. The substitution Lys(11)-->Gln in brevinin-1HSa (FLPAVLRVAAKIVPTVFCAISKKC) from O. hosii abolishes growth inhibitory activity against Escherichia coli but has no effect on the high potency (MIC=8mug/ml) against Staphylococcus aureus. In contrast, the substitution (Gly(4)-->Asp) in brevinin-2PTb (GFKGAFKNVMFGIAKSAGKSALNALACKIDKSC) from H. picturata reduces activity against both E. coli and S. aureus. Cladistic analysis based upon the amino acid sequences of the brevinin-2 peptides from Asian frogs provides evidence for sister taxon relationships between O. hosii and O. livida and between H. picturata and H. güntheri. 相似文献
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98.
Hanzhi Yu Runming Du Minmin Wang Fengyun Yu Juntao Yang Lirui Jiao Zhuoran Wang Haitao Liu Peixin Wu Till Brnighausen Lan Xue Chen Wang Shannon McMahon Pascal Geldsetzer Simiao Chen 《JMIR Public Health and Surveillance》2022,8(6)
BackgroundCOVID-19 vaccines are in short supply worldwide. China was among the first countries to pledge supplies of the COVID-19 vaccine as a global public product, and to date, the country has provided more than 600 million vaccines to more than 200 countries and regions with low COVID-19 vaccination rates. Understanding the public’s attitude in China toward the global distribution of COVID-19 vaccines could inform global and national decisions, policies, and debates.ObjectiveThe aim of this study was to determine the attitudes of adults living in China regarding the global allocation of COVID-19 vaccines developed in China and how these attitudes vary across provinces and by sociodemographic characteristics.MethodsWe conducted a cross-sectional online survey among adults registered with the survey company KuRunData. The survey asked participants 31 questions about their attitudes regarding the global allocation of COVID-19 vaccines developed in China. We disaggregated responses by province and sociodemographic characteristics. All analyses used survey sampling weights.ResultsA total of 10,000 participants completed the questionnaire. Participants generally favored providing COVID-19 vaccines to foreign countries before fulfilling domestic needs (75.6%, 95% CI 74.6%-76.5%). Women (3778/4921, 76.8%; odds ratio 1.18, 95% CI 1.07-1.32; P=.002) and those living in rural areas (3123/4065, 76.8%; odds ratio 1.13, 95% CI 1.01-1.27; P=.03) were especially likely to hold this opinion. Most respondents preferred providing financial support through international platforms rather than directly offering support to individual countries (72.1%, 95% CI 71%-73.1%), while for vaccine products they preferred direct provision to relevant countries instead of via a delivery platform such as COVAX (77.3%, 95% CI 76.3%-78.2%).ConclusionsAmong our survey sample, we found that adults are generally supportive of the international distribution of COVID-19 vaccines, which may encourage policy makers to support and implement the distribution of COVID-19 vaccines developed in China worldwide. Conducting similar surveys in other countries could help align policy makers’ actions on COVID-19 vaccine distribution with the preferences of their constituencies. 相似文献
99.
Maja C. Mezger Carina Conzelmann Tatjana Weil Pascal von Maltitz Dan P. J. Albers Jan Münch Thomas Stamminger Eva-Maria Schilling 《Viruses》2022,14(6)
Screening of a protein kinase inhibitor library identified SB431542, targeting activin receptor-like kinase 5 (ALK5), as a compound interfering with SARS-CoV-2 replication. Since ALK5 is implicated in transforming growth factor β (TGF-β) signaling and regulation of the cellular endoprotease furin, we pursued this research to clarify the role of this protein kinase for SARS-CoV-2 infection. We show that TGF-β1 induces the expression of furin in a broad spectrum of cells including Huh-7 and Calu-3 that are permissive for SARS-CoV-2. The inhibition of ALK5 by incubation with SB431542 revealed a dose-dependent downregulation of both basal and TGF-β1 induced furin expression. Furthermore, we demonstrate that the ALK5 inhibitors SB431542 and Vactosertib negatively affect the proteolytic processing of the SARS-CoV-2 Spike protein and significantly reduce spike-mediated cell–cell fusion. This correlated with an inhibitory effect of ALK5 inhibition on the production of infectious SARS-CoV-2. Altogether, our study shows that interference with ALK5 signaling attenuates SARS-CoV-2 infectivity and cell–cell spread via downregulation of furin which is most pronounced upon TGF-β stimulation. Since a TGF-β dominated cytokine storm is a hallmark of severe COVID-19, ALK5 inhibitors undergoing clinical trials might represent a potential therapy option for COVID-19. 相似文献