Recently, two novel concepts have emerged in cancer biology: the role of so-called “cancer stem cells” in tumor initiation, and the involvement of an epithelial-mesenchymal transition (EMT) in the metastatic dissemination of epithelial cancer cells. Using a mammary tumor progression model, we show that cells possessing both stem and tumorigenic characteristics of “cancer stem cells” can be derived from human mammary epithelial cells following the activation of the Ras-MAPK pathway. The acquisition of these stem and tumorigenic characters is driven by EMT induction.

HCV particles were isolated from the plasma of chronically infected patients. The virus was analysed by sucrose density gradient centrifugation. The fractions were tested for viral RNA, core antigen and envelope proteins by using a monoclonal antibody directed against the natural E1E2 complex (D32.10). Two populations of particles containing RNA plus core antigen were separated: the first with a density of 1.06-1.08 g/ml did not contain the envelope proteins; the second with a density between 1.17 and 1.21 g/ml expressed both E1 and E2 glycoproteins. Electron microscopy of the enveloped population after immunoprecipitation with D32.10 showed spherical particles with a rather featureless surface and with a diameter around 40 nm. Immuno-gold staining gave evidence that the E1E2 complex was indeed positioned at the surface of these particles.

When a candidate drug is likely to become available to prescribers and healthcare policy makers, evaluation of therapeutic progress moves forward in two stages. First, the level of expected therapeutic progress must be established. This first stage requires the determination of therapeutic needs and the comparison of these against the results of the clinical studies that will form the basis of the marketing authorisation of the drug. This determination helps anticipate the therapeutic progress that is attributable to the approved use of the new drug. The second stage of the process, the evaluation of the actual therapeutic progress, involves therapeutic drug monitoring and bases itself on observation. Since such observational data are intended to challenge the initial hypotheses and uncertainties (in terms of benefits and risks), goals and methods must be laid out before the drug becomes available to the general public. Keywords: therapeutic progress, epidemiology, evaluation When penicillin G was introduced as a therapeutic drug for human use, the therapeutic progress was so clear that no one envisaged measuring it objectively. Moreover, this question apparently sparked no interest in either physicians or scientists at that time, because of the major innovation of the antibiotic and the tangible medical progress it represented. Clinical studies were sufficient for observing that its administration cured certain infections that, until that time, systematically killed the afflicted. Although the question of therapeutic progress went unaddressed, as important as it seemed, it was, nonetheless, important to demonstrate the efficacy of the drug. In addition, the implementation of an experimental protocol defining a random controlled study was not required for this molecule to receive marketing authorisation. PHARMACOLOGIE CLINIQUESince then, the context has changed. Today, no one would consider introducing a new therapeutic molecule onto the market without data on its efficacy, based on the results of clinical trials. In the same way, anticipating the therapeutic gain of a candidate drug and measuring real therapeutic progress, obtained through its use, have become indispensable.

M e d i c a 234Metodi Il paziente viene quindi indagato, nel sospetto clinico di subocclusione intestinale, con Rx addome, ecografia addome, valutazione chirurgica ed esami ematochimici di routine. Risultati Rx addome: esclude la presenza di aria libera e di evidenti livelli idroarei; assenza di immagini radiopache da formazioni litiasiche a carico dell'apparato urinario; importante distensione gassosa delle anse mesenteriali e coprostasi; non segni di occlusione. Eco addome: nella norma fegato, vie biliari e colecisti; non versamenti liberi peritoneali; tra rene e milza presenza di anse mesenteriali distese da materiale corpuscolato e peristalsi torpida. Visita chirurgica: esclude un quadro occlusivo e consiglia osservazione. Esame emocromocitometrico: la formula leucocitaria evidenzia il 24 % di granulociti eosinofili. Esegue esame coproparassitologico (PARAPAK SAF FORMALIN, Meridian) che evidenzia numerose uova di A. lumbricoides, numerose larve di S. stercoralis, rare uova di T. trichiura e rare cisti di E. coli; allo sotch-test: rare uova di T. trichiura. Il paziente, tenuto sotto stretta osservazione clinica e in terapia infusionale con soluzione glucosalina, viene successivamente trattato con mebendazolo (100 mgx2 al dì per 3 giorni). Segue eliminazione di verme di A. lumbricoides della lunghezza di 27 cm. Progressiva risoluzione della sintomatologia clinica. Conclusioni Il quadro clinico iniziale, riferibile a sospetta subocclusione intestinale, ed il reperto ecografico di dubbia interpretazione sono stati quindi chiariti alla luce del riscontro di importante parassitosi intestinale. Si sottolinea l'importanza di un accurato raccordo anamnestico (recente immigrazione) ai fini diagnostici di patologie infettive di raro riscontro nella pratica clinica quotidiana.