The asialoglycoprotein receptor in human hepatocellular carcinomas: its expression on proliferating cells

The expression of the asialoglycoprotein receptor (ASGP-R) on human hepatocellular carcinoma (HCC) cells might be exploited to reduce the extrahepatic toxicity of DNA synthesis inhibitors by their conjugation with galactosyl-terminating peptides. In the present study we first assessed the frequency of ASGP-R expression in 60 HCCs. Secondly, we investigated whether the receptor was maintained on the plasma membranes of DNA synthesizing cancer cells. Needle biopsies of HCC were evaluated. Diagnosis and grading of HCC were performed on routine haematoxylin and eosin-stained sections according to Edmondson and Steiner (1953). Thirty-five tumours were grade I and II and were classified as well differentiated, while 25 tumours were grade III and IV and were classified as poorly differentiated. Sections from formalin-fixed, paraffin-embedded samples were incubated, after antigen retrieval, with an anti-ASGP-R monoclonal antibody revealed by secondary biotinylated antibody and streptavidin–biotin–peroxidase–diaminobenzidine reaction. A clear immunolabelling of plasma membranes of HCC cells was observed in 28 out of 35 (80%) well differentiated (grade I and II) and in five out of 25 (20%) poorly differentiated (grade III and IV) HCCs. The presence of the ASGP-R on the surface of DNA synthesizing cancer cells was also investigated after in vitro bromodeoxyuridine (BrdU) labelling of HCC samples by immunohistochemical visualization of both the ASGP-R and incorporated BrdU on the same section. The results obtained clearly demonstrated that DNA synthesizing cancer cells expressed the ASGP-R on their surface. The presence of ASGP-R on cell plasma membrane in the majority of differentiated HCCs and its maintenance on proliferating cells encourages studies in order to restrict the action of the inhibitors of DNA synthesis of HCC cells by their conjugation with galactosyl-terminating carriers internalized through this receptor. © 1999 Cancer Research Campaig

L’efficienza operativa delle banche italiane. Un'analisi empirica di alcune relazioni.

Il lavoro analizza il tema dell’efficienza operativa delle banche italiane attraverso un'analisi specifica di diverse relazioni:1. analisi dell’efficienza tecnico-operativa attraverso l'adozione di una diversa suddivisione del processo produttivo bancario; 2. verifica di specifiche caratterizzazioni qualitative delle banche in grado di spiegare alcune diversità nei livelli di efficienza rilevati, con particolare attenzione all’utilizzo e alla gestione del fattore lavoro.Il lavoro è organizzato nel seguente modo. Il paragrafo 1 rappresenta l’introduzione al lavoro. Il paragrafo 2 illustra sinteticamente il campione di banche analizzato e le scelte compiute in termini di variabili input-output e di relativi pesi prescelti e i risultati ottenuti in termini di valori dell’efficienza, ponendo l’accento sulle principali caratterizzazioni qualitative del campione bancario analizzato. Il paragrafo 3 analizza la coerenza tra la misura di efficienza stimata ed una serie di tradizionali indicatori di bilancio, avendo riguardo alle specificità che emergono per spiegare i diversi livelli in termini di struttura dei costi e dei ricavi del campione di banche analizzato. Come anticipato, grazie ad una serie di dati aggiuntivi richiesti alle banche, è stato possibile inserire un breve approfondimento sulle principali determinanti della relazione esistente tra l’efficienza operativa e l’organizzazione e la gestione del fattore lavoro. Il paragrafo 4 esamina tale interazione approfondendo, in particolare, il caso di una banca che ha vissuto negli ultimi anni intensi fenomeni di concentrazione con conseguenti problemi di riordino e di riorganizzazione dei costi aziendali e delle risorse umane. Il paragrafo 5 offre alcuni spunti di riflessione finali al lavoro. Le due appendici al capitolo riportano rispettivamente il quadro teorico metodologico relativo al tema dell’efficienza e la metodologia DEA utilizzata, oltre ad una scomposizione delle spese amministrative diverse dal costi del lavoro rapportate al margine di intermediazione

Qualitative and quantitative analysis of AgNOR proteins in chemically induced rat liver carcinogenesis

A qualitative and quantitative analysis of silver-stained nuclear organizer regions (AgNOR) proteins was performed during hepatocarcinogenesis induced in rats initiated by diethylnitrosamine (DENA) using the resistant-hepatocyte model Nuclear proteins from control hepatocytes, hyperplastic nodules, and hepatocellular carcinomas (HCC) separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis were transferred to nitrocellulose membranes and specifically silver-stained for AgNOR proteins, No difference was observed in the distribution pattern of the silver-stained bands among control, hyperplastic, or cancer cells, The same was true if human cirrhosis and HCC were compared. The evaluation of individual AgNOR protein amounts by computerized densitometric analysis showed that 1) the integrated optical density value of the total AgNOR proteins was greatest in cancer cells, lesser in hyperplastic hepatocytes, and lowest in control hepatocytes, and 2) the amount of the two major silver-stained proteins, nucleolin (105 kd) and protein B23 (39 Sd), was always a constant percentage of total AgNOR proteins, An experiment using bromodeoxyuridine incorporation showed that, during hepatocarcinogenesis, AgNOR protein quantity progressively increased and was significantly related to the increased hepatocyte labeling index, These results show that AgNOR protein distribution changes during hepatocarcinogenesis are caused neither by the synthesis of new AgNOR proteins nor by an unbalanced synthesis of individual AgNOR proteins, but to an increased synthesis of nucleolin and protein B23, which is associated with a progressive increased hepatocyte proliferation rate