Clinicopathologic idiosyncrasies of nasopharyngeal cancer in a moderate-risk Mediterranean region

Il carcinoma del rinofaringe presenta una notevole eterogeneità per quanto riguarda le caratteristiche epidemiologiche, patogenetiche, cliniche e prognostiche sulla base dellarea geografica considerata. Lincidenza registrata nel Mediterraneo per tale patologia si colloca fra quella delle forme epidemiche e sporadiche registrate rispettivamente nel Sud Est Asiatico e nel Nord America. Il presente studio descrive le caratteristiche di questa patologia per quanto riguarda lovest della Grecia. Sono stati analizzati i dati relativi a 70 pazienti affetti da carcinoma del rinofaringe la cui diagnosi è stata posta presso un singolo centro fra il 1994 e il 2014. Il trattamento primario si è basato sulla radioterapia con o senza chemioterapia associata. Sono stati raccolti ai fini dellanalisi statistica i dati demografici, i fattori di rischio, le caratteristiche della neoplasia, la presentazione clinica e loutcome. Sono state calcolate sia la sopravvivenza globale (OS) che la sopravvivenza specifica per malattia (DSS) a 5 anni. Tutti i fattori potenzialmente predittori di sopravvivenza sono stati testati a unanalisi univariata e multivariata. La variante maggiormente diagnosticata allanalisi istopatologica è stato il tipo 3 secondo la WHO (74,3%) che si è associato in modo significativo con sintomatologia nasale alla presentazione (p = 0,050), linfoadenopatie metastatiche (p = 0,028), stage clinico avanzato (p = 0,009) e risposta completa al trattamento iniziale (p = 0,018). Lanalisi univariata ha evidenziato un impatto negativo in termini prognostici per letà avanzata (OS p = 0,029, DSS p = 0,041), la mancata risposta ai trattamenti (OS & DSS p < 0,001) e la recidiva di malattia (OS p = 0,003, DSS p = 0,001). A unanalisi multivariata la recidiva di malattia ha mantenuto un impatto prognostico negativo (HR 7,442, 95% IC 2,199-25,187, p = 0,001). In conclusione, fra i carcinomi nasofaringei diagnosticati nellovest della Grecia, il linfoepitelioma mostra caratteristiche peculiari sotto il profilo clinico, tali per cui la sua inclusione assieme alle neoplasie tipo 2 secondo la WHO nel gruppo di carcinomi rinofaringei non cheratinizzanti potrebbe risultare inappropriata. Infine, la recidiva di malattia, indipendentemente dagli altri fattori in gioco, appare essere un evento gravemente avverso

Tanzania: Recent Economic Developments

https://www.elibrary.imf.org/doc/IMF002/06676-9781451838282/06676-9781451838282/Other_formats/Source_PDF/06676-9781463912642.pd

Extracellular proteolytic cascade in tomato activates immune protease Rcr3

Proteolytic cascades regulate immunity and development in animals, but these cascades in plants have not yet been reported. Here we report that the extracellular immune protease Rcr3 of tomato is activated by P69B and other subtilases (SBTs), revealing a proteolytic cascade regulating extracellular immunity in solanaceous plants. Rcr3 is a secreted papain-like Cys protease (PLCP) of tomato that acts both in basal resistance against late blight disease (Phytophthora infestans) and in gene-for-gene resistance against the fungal pathogen Cladosporium fulvum (syn. Passalora fulva) Despite the prevalent model that Rcr3-like proteases can activate themselves at low pH, we found that catalytically inactive proRcr3 mutant precursors are still processed into mature mRcr3 isoforms. ProRcr3 is processed by secreted P69B and other Asp-selective SBTs in solanaceous plants, providing robust immunity through SBT redundancy. The apoplastic effector EPI1 of P. infestans can block Rcr3 activation by inhibiting SBTs, suggesting that this effector promotes virulence indirectly by preventing the activation of Rcr3(-like) immune proteases. Rcr3 activation in Nicotiana benthamiana requires a SBT from a different subfamily, indicating that extracellular proteolytic cascades have evolved convergently in solanaceous plants or are very ancient in the plant kingdom. The frequent incidence of Asp residues in the cleavage region of Rcr3-like proteases in solanaceous plants indicates that activation of immune proteases by SBTs is a general mechanism, illuminating a proteolytic cascade that provides robust apoplastic immunity

The rice NLR pair Pikp-1/Pikp-2 initiates cell death through receptor cooperation rather than negative regulation

Plant NLR immune receptors are multidomain proteins that can function as specialized sensor/helper pairs. Paired NLR immune receptors are generally thought to function via negative regulation, where one NLR represses the activity of the second and detection of pathogen effectors relieves this repression to initiate immunity. However, whether this mechanism is common to all NLR pairs is not known. Here, we show that the rice NLR pair Pikp-1/Pikp-2, which confers resistance to strains of the blast pathogen Magnaporthe oryzae (syn. Pyricularia oryzae) expressing the AVR-PikD effector, functions via receptor cooperation, with effector-triggered activation requiring both NLRs to trigger the immune response. To investigate the mechanism of Pikp-1/Pikp-2 activation, we expressed truncated variants of these proteins, and made mutations in previously identified NLR sequence motifs. We found that any domain truncation, in either Pikp-1 or Pikp-2, prevented cell death in the presence of AVR-PikD, revealing that all domains are required for activity. Further, expression of individual Pikp-1 or Pikp-2 domains did not result in cell death. Mutations in the conserved P-loop and MHD sequence motifs in both Pikp-1 and Pikp-2 prevented cell death activation, demonstrating that these motifs are required for the function of the two partner NLRs. Finally, we showed that Pikp-1 and Pikp-2 associate to form homo- and hetero-complexes in planta in the absence of AVR-PikD; on co-expression the effector binds to Pikp-1 generating a tri-partite complex. Taken together, we provide evidence that Pikp-1 and Pikp-2 form a fine-tuned system that is activated by AVR-PikD via receptor cooperation rather than negative regulation

Epidemiologische und klinische Charakteristika des Nasopharyngeal-Karzinoms in Beziehung zu EBV-Immunstatus

Einleitung: Dem Epstein-Barr-Virus (EBV) wird unter anderem eine wesentliche Rolle bei der Entstehung des Nasopharyngeal-Karzinoms (NPC) zugesprochen. Die vorliegende Studie untersucht die Einbeziehung einer latenten EBV-Infektion bei der Entstehung des NPC, sowie die Möglichkeit der Diagnosesicherung und der Kontrolle des Therapieerfolges. Methoden: In die Studie wurden 37 Patienten, bei denen im Zeitraum von 1990-2005 in der HNO-Universitätsklinik Patras NPC diagnostiziert und histologisch gesichert wurde, einbezogen, sowie 11 Kontrollpersonen, davon 3 mit anderorts gesichertem Karzinom. Mittels eines standardisierten Fragebogens wurden demographische und klinische Daten sowie Informationen zu Risikofaktoren (Rauchen, Alkohol, berufliche Exposition) erhoben. Bei 11 Patienten mit NPC und allen Kontrollpersonen wurden Titerbestimmungen verschiedener EBV-Antikörper (gegen Early-Antigen (EA) und Virus-Capsid-Antigen (VCA)) im Serum durchgeführt. Die statistische Analyse erfolgte mittels SPSS v. 12.0.Ergebnisse: In 84% der Patienten wurde Rauchen im Zusammenhang mit beruflicher Exposition als wesentlicher Risikofaktor bestimmt. Die 3-Jahres-Überlebensrate betrug 42%. In der Gruppe der NPC wurden im Vergleich zu der Kontrollgruppe statistisch signifikante Unterschiede hinsichtlich der Titerhöhe der IgG anti VCA sowie IgG anti EA nachgewiesen, während IgM-Antikörper gegen VCA in keiner Gruppe feststellbar waren.Schlussfolgerung: Berufliche Exposition, Rauchen sowie Infektion mit EBV sind als wesentliche Risikofaktoren bei der Entstehung des NPC zu werten. Daraus ergibt sich das Postulat nach einer strengeren Beobachtung dieser Risikogruppe unter Einbezug der EBV-Serologie, damit NPC im Frühstadium entdeckt und effektiver therapiert werden kann