Weak expression of cyclooxygenase-2 is associated with poorer outcome in endemic nasopharyngeal carcinoma: analysis of data from randomized trial between radiation alone versus concurrent chemo-radiation (SQNP-01)

<p>Abstract</p> <p>Background</p> <p>Over-expression of cyclooxygenase-2 (COX-2) enzyme has been reported in nasopharyngeal carcinoma (NPC). However, the prognostic significance of this has yet to be conclusively determined. Thus, from our randomized trial of radiation versus concurrent chemoradiation in endemic NPC, we analyzed a cohort of tumour samples collected from participants from one referral hospital.</p> <p>Methods</p> <p>58 out of 88 patients from this institution had samples available for analysis. COX-2 expression levels were stratified by immunohistochemistry, into negligible, weak, moderate and strong, and correlated with overall and disease specific survivals.</p> <p>Results</p> <p>58% had negligible or weak COX-2 expression, while 14% and 28% had moderate and strong expression respectively. Weak COX-2 expression conferred a poorer median overall survival, 1.3 years for weak versus 6.3 years for negligible, 7.8 years, strong and not reached for moderate. There was a similar trend for disease specific survival.</p> <p>Conclusion</p> <p>Contrary to literature published on other malignancies, our findings seemed to indicate that over-expression of COX-2 confer a better prognosis in patients with endemic NPC. Larger studies are required to conclusively determine the significance of COX-2 expression in these patients.</p

Biomimetic Oxidative Dimerization of Anodically Generated Stilbene Radical Cations: Effect of Aromatic Substitution on Product Distribution and Reaction Pathways

A systematic study of the electrochemical oxidation of 1,2-diarylalkenes was carried out with the focus on detailed product studies and variation of product type as a function of aromatic substitution. A reinvestigation of the electrochemical oxidation of 4,4′-dimethoxystilbene under various conditions was first carried out, and all products formed were fully characterized and quantitated. This was followed by a systematic investigation of the effect of aromatic substitution on the nature and distribution of the products. The aromatic substituents were found to fall into three main categories, viz., substrates in which the nature and position of the aromatic substituents gave rise to essentially the same products as 4,4′-dimethoxystilbene, for example, tetraaryltetrahydrofurans, dehydrotetralins, and aldehydes (<i>p</i>-MeO or <i>p</i>-NMe₂ on one ring and X on the other ring, where X = <i>o</i>-MeO or <i>p</i>-alkyl, or <i>m</i>- or <i>p</i>-EWG; e.g., 4-methoxy-4′-trifluoromethylstilbene); those that gave rise to a mixture of indanyl (or tetralinyl) acetamides and dehydrotetralins (or pallidols) (both or one ring substituted by alkyl groups, e.g., 4,4′-dimethylstilbene); and those where strategic placement of donor groups, such as OMe and OH, led to the formation of ampelopsin F and pallidol-type carbon skeletons (e.g., 4,3′,4′-trimethoxystilbene). Reaction pathways to rationalize the formation of the different products are presented

Verso sistemi sanitari orientati alle patologie croniche: il caso spagnolo

Le crescenti spese della sanità destano grande preoccupazione in particolare nei paesi Ocse, soprattutto in relazione ai driver alla base di tale incremento tra cui l’invecchiamento della popolazione, l’innovazione medica e i cambiamenti nelle priorità e nel carico di malattia, che vede una costante crescita nella prevalenza di patologie croniche. La maggior parte dei sistemi sanitari nei paesi sviluppati è stata creata per ‘curare’ episodi acuti piuttosto che ‘gestire’ condizioni croniche e, di conseguenza, non è adeguatamente ed efficientemente organizzata per rispondere alle esigenze e alle preferenze, in costante cambiamento ed evoluzione, dei consumatori. Nuovi modelli per meglio rispondere ai bisogni dei pazienti cronici sono stati proposti e sviluppati e vi sono già esperienze pratiche in diversi paesi che ne dimostrano i vantaggi, ma anche le difficoltà di implementazione. In questo articolo ci focalizziamo sull’esperienza spagnola, ed in particolare sulle politiche e gli studi pilota atti a testare la fattibilità del passaggio da modelli di ‘cura’ a modelli di ‘gestione’ delle patologie croniche. In particolare, utilizziamo una struttura concettuale che identifica e analizza 10 prerequisiti dei sistemi sanitari basati sulla gestione delle patologie croniche con prestazioni di alta qualità e li applichiamo all’attuale sistema sanitario nazionale spagnolo. Dalla nostra analisi emerge che il sistema sanitario spagnolo soddisfa già alcuni prerequisiti. Tuttavia, altri prerequisiti sono ancora in fase embrionale di sviluppo o vengono applicati in contesti clinici o geografici limitati. Proponiamo, quindi, un percorso per delineare i passaggi cruciali verso un sistema sanitario orientato alla cura delle patologie croniche

Electrochemically Mediated Oxidative Transformations of Substituted 4‑Methoxystilbenes: Effect of Ortho-Substituted Nucleophilic Groups

A systematic study was undertaken to determine the influence of ortho′-substituted nucleophilic groups (OH, NH₂, or NHR) on the reactivity of anodically generated 4-methoxy- and 3,4-dimethoxystilbene cation radicals. The results showed that when ortho-substituted nucleophilic groups such as OH and NHR are present in the other ring, both direct and crossover intramolecular cation–nucleophile reactions occur to give bisbenzofurans/bisindoles or fused bisbenzopyrans/bisquinolines, respectively. Where an additional 3-methoxy substituent is present, bridged oxocine/azocine products are formed in addition to the bisbenzopyrans/bisquinolines and bisbenzofurans/bisindoles. Mechanistic rationalization of the observed behavior is presented based on a generalized pathway involving fast cation radical dimerization following electron transfer, followed by direct and crossover trapping of the benzylic cations by the ortho-substituted oxygen and nitrogen nucleophilic groups. In the instances where an additional 3-methoxy group is present, the bridged oxocine/azocine products are also formed as a result of competing aromatic substitution (Friedel–Crafts reaction). The results have shed further light and provided additional clarification on the reactivity of anodically generated stilbene cation radicals