Prevalence and clinical outcomes for patients with MET protein expression in patients with non-small cell lung cancer in Europe: Results from the European Thoracic Oncology Platform Lungscape Project.

Aim The reported prevalence of MET overexpression varies from 25-55% in non-small cell lung cancer (NSCLC) and clinical correlations are emerging slowly. In a well-defined NSCLC cohort of the Lungscape program, we explore the epidemiology, the natural history of IHC MET positivity and its association to OS, RFS and TTR. Methods Resected stage I-III NSCLC identified based on the quality of clinical data and FFPE tissue availability were assessed for MET expression using immunohistochemistry (IHC) on TMAs (CONFIRM anti total c-MET assay, clone SP44, Ventana BenchMark platform). All cases were analysed at participating pathology laboratories using the same protocol, after passing an external quality assurance program. MET positive status is defined as ≥ 50% of tumor cells staining with 2+ or 3+ intensity. Results A total of 2709 cases are included in the iBiobank and will be analysed. IHC MET expression is currently available for 1552 patients, with positive MET IHC staining in 380 cases [24.5%; IHC 3+ in 157 cases (41.3%) and 2+ in 223 cases (58.7%)]. The cohort of 1552 patients includes 48.2%, 44.7% and 4.4% cases of adenocarcinoma, squamous and large cell histologies, respectively. IHC MET status was independent of stage, age and smoking history. Significant differences in MET positivity were associated with gender (32% vs. 21% for female vs. male, p < 0.001), with performance status (25% vs. 18% for 0 vs. 1-3, p = 0.006), and histology (34%, 14% and 24% for adenocarcinoma, squamous and large cell carcinoma, p < 0.001). IHC MET positivity was independent of the IHC ALK status (p = 0.08). At last FU, 52% of patients were still alive, with a median FU of 4.8 yrs. No association of IHC MET was found with OS, RFS or TTR. Conclusions The preliminary results for this large multicentre European cohort describe a prevalence of MET overexpression that seems lower than previous observations in NSCLC, such as reported for the OAM4971g trial, suggesting potential biological differences between surgically resected and metastatic disease. Analysis for the full cohort is ongoing and results will be presented. Disclosure L. Bubendorf: Disclosures: Stock ownership: Roche Advisory boards: Roche, Pfizer Research support: Roche; K. Schulze: Full time employee of Roche; A. Das-Gupta: I am a full time employee of Roche. All other authors have declared no conflicts of interest.

Synthesis of a tetrahydroimidazo-[2',1':2,3]thiazolo[5,4-c]pyridine derivative with Met inhibitory activity

A straightforward synthesis of the Met antagonist JLK1360 involving an alkylationcyclocondensation process using aminothiazole 1 and nitrophenacyl bromide 2, reduction of the nitro group, and coupling of the resulting tetracyclic aniline 5 with an appropriate N-acyl alanine derivative, is reported.

Synthesis of a tetrahydroimidazo-[2',1':2,3]thiazolo[5,4-c]pyridine derivative with Met inhibitory activity

A straightforward synthesis of the Met antagonist JLK1360 involving an alkylationcyclocondensation process using aminothiazole 1 and nitrophenacyl bromide 2, reduction of the nitro group, and coupling of the resulting tetracyclic aniline 5 with an appropriate N-acyl alanine derivative, is reported.

Waarachtige en aen-merkens-waardige historie van Lapland: ofte een Beschrijving van desselfs oorspronk, landschappen, geberchten, gewassen, gedierten, metalen, steenen, wateren, en voornaemste geschiedenissen. Benessens der inwoonderen zeden, regeering, godtsdiensten, oorlogen, drachten, koophandel, gebouwen, van tenten, schepen, sleden, &c. Als ook van hare tover-trommelen, en wind-koopery. Met noch een kort bericht van den toestand der Finnen. Nieuwelijks uit het frans van den Heer Scheffer vertaalt. Met kurieuse kopere Plaaten

Added engraved title page: Waragtige en aanmerkenswaardige historie van Lapland en Finland.

Mäet pois

kuv., 13 x 19 cm

Produção e purificação parcial de PPD-maleína para diagnóstico do mormo em equídeos

Objetivou-se com este estudo produzir e purificar parcialmente a PPD-maleína a partir de amostras de Burkholderia mallei isoladas de equídeos no Brasil com potencial para uso no diagnóstico do mormo. As linhagens de B. mallei fenotipicamente caracterizadas e de virulência comprovada foram inoculadas em caldo Dorset-Henley para crescer e metabolizar. Em seguida, as proteínas foram separadas por precipitação com ácido tricloroacético e precipitadas com sulfato de amônia. As PPDs-maleínas foram concentradas em 1,0mg/mL e na avaliação realizada em cobaios foi eficaz no desenvolvimento da hipersensibilidade do tipo tardia e consequentemente na identificação de animais verdadeiro positivos e exclusão dos verdadeiro negativos, sendo uma possibilidade em potencial para utilização no diagnóstico do mormo.

Detection of specific antibodies in cows after injection of PPD

The diagnosis of bovine tuberculosis aims to identify the immune response against mycobacterial antigens. Although Single Intradermal Comparative Cervical Tuberculin test (SICCT) is broadly used for first identification of the disease, the performance of ELISAs has been investigated for diagnosis improvement. The present study expected to find out the influence of intradermal skin tests on the results of ELISAs using the recombinant proteins MPB70 and MPB83 as antigens on cows from a naturally infected herd. Results were analyzed by the F-test, Mann-Whitney and Friedman tests Although comparable to both proteins, results showed that positive animals presented a tendency of augment reactivity to MPB70, representing a tendency for a booster effect, but not to MPB83.

Hb Köln [a2b298(FG5) val-met] identified by DNA analysis in a Brazilian family

Hb Köln was identified by DNA analysis in a Brazilian patient. A four-year old Brazilian female, with jaundice since birth, presented an abnormal band, between A2 and S, in hemoglobin electrophoresis on a cellulose acetate membrane, and a band with electrophoretic migration similar to Hb C on agar gel. Thermic instability and isopropanol precipitation tests were positive. Heinz bodies were observed in the patient’s peripheral blood. Sequencing of the three exons of the b globin gene detected a transition from G to A in the first position of codon 98. This alteration does not create or abolish any known restriction site. In this case, confirmation of the mutation was accomplished by allele-specific oligonucleotide hybridization, which is a simple and fast identification method when the clinical data and hematological and electrophoretic patterns are suggestive of Hb Köln.

Die custe va Lijfflandt met de eijlanden daer beneffens ... tot Sijburgs ness tho : tractus littoralis Livoniae ab Ekeholmis ad Siburghnessam ... diligentissima descriptio

Julkaisussa: Speculum nauticum super navigatione maris Occidentalis confectum. - Vol. II: Pars altera speculi marini, integram cum borealis tum orientalis oceani navigationem

Pas-kaart van Europa met een gedeelte van de kust van Africa tot aen Cabo Verde

Julkaisussa: De zee-atlas ofte water-waereld, vertoonende alle de zee-kusten van het bekende deel des aerd-bodems, met een generale bechrijvinge van dien

Nieuwe kaart van Oostindie met alle desselfs omleggende eylanden etc

Irtokartta

Caerte van Nova Zembla, de Weygats, de custe van Tartarien en Ruslandt tot Kilduyn toe : met anwysinge van de weeder vaert lancx de noortcust van Nova Zembla, en de overvaert omtrent de Weygats na Ruslandt tot de hoeck van Candenos, en de mont van de Witte Zee

Julkaisussa: Diarium Nauticum, seu vera descriptio trium navigationum admirandarum

Paskaart voor een gedeelte der Oost Zee beginnende van Lemsaal tot beooste Kok als mede de kust van oost Finlandt, van 't Alandse haff, tot Parna, waar in ook vervat is, d'eylande Oesel, en Dagho : naaukeurig opgestelt en van veel fouten verbetert, met privilegie voor 15 iaaren

Julkaisussa: De groote nieuwe vermeerderde zee-atlas of te water-werelt

Typus orarum maritimarum Guinae, Manicongo & Angôlae ultra promontorium Bonae Spei : usque cum omnibus portubus, insulis, scopulis, pluvinis & vadis, veraque latitudine Oceani Aethiopici ... = Afbeeldinghe der custen des landts Guinea, Manicongo, ende Angôla, ende voorts tot vooby de C. de Boa Esperança : met alle de havenen, eylanden, clippen, droochten, ende ondiepten, met de gheheele breede des Aethiopischen Oceani ...

Kartta kuuluu A. E. Nordenskiöldin kokoelmaan

Nieuwe pascaerte van alle de zeecusten van geheel Europa, streckende omde noordt tot Nova Zemla, Spitsbergen, ende Groenlandt, en na het westen tot de Vlaemsche Eijlanden, mitsgaders suijdwaerts tot de Canarische Eijlanden, ende de Custen van Barbarijen, met alle de custen en eijlanden vande Middelantsche Zee, tot de custen van Soria toe

Kartta kuuluu A. E. Nordenskiöldin kokoelmaan