Hydrolysis of oleuropein by recombinant beta-glycosidase from hyperthermophilic archaeon Sulfolobus solfataricus immobilised on chitosan matrix.

The recombinant beta-glycosidase (EcS beta gly) from Sulfolobus solfataricus was immobilised on chitosan to perform the enzymatic hydrolysis of commercial oleuropein (heterosidic ester of elenolic acid and 3,4-dihydroxy-phenylethanol (hydroxytyrosol)) at two temperatures (60 and 70 degrees C). Interestingly, on the basis of the reasonable assumption that the enzyme hydrolyses only the sugar linkage, the biotransformation produces unstable aglycone species formed by oleuropein hydrolysis that, differently from some commercially available beta-glucosidases tested, give rise to the formation of hydroxytyrosol, at the operative temperatures of the bioreactor. The results of the biotransformation at 70 degrees C showed that the main products are hydroxytyrosol, and glucose, being the oleuropein aglycone present in low amount at the end of reaction. Both in single step approach or in recycle approach the amounts of glucose and oleuropein aglycone were lightly dependent from flow rate. The amount of hydroxytyrosol, increased on decreasing the flow rate of bioreactor in recycle approach, following a non-linear trend and obtaining the highest value at a flow rate of 15 ml h-1 while in the single step approach the 3,4-dihydroxy-phenylethanol was at its maximum at higher flow rate (16 ml h-1). For the hydrolysis of the oleuropein by bioreactor at 60 degrees C we used lower molar ratio oleuropein/enzyme only by the single step approach. In these conditions it is possible to obtain high amounts of only two products (glucose and hydroxytyrosol) in short time (2 h). The stability of the bioreactor at the operative temperatures showed a t1/2 of 30 days at 70 degrees C and a t1/2 of 56 days at 60 degrees C.

Adriamycin and cis-dichlorodiammineplatinum in nonresectable and metastatic carcinoma of the lung.

The combination of adriamycin and cis-dichlorodiammineplatinum (DDP) was evaluated in 20 patients with nonresectable and metastatic carcinoma of the lung. Both drugs were administered at a dosage of 60 mg/m2 intravenously every 3 weeks. The overall objective response rate was 40% (eight of 20 patients) with two complete responses (CR) and six partial responses (PR). Four of eight patients with small cell carcinoma responded (1 CR and 3 PR) and four of 12 patients with nonsmall cell carcinoma responded (1 CR and 3 PR). The median duration of response was greater than 36 weeks. The median survival of responders was 54 weeks. Nausea and vomiting were major side effects but rarely lasted longer than 2 days. Renal and bone marrow toxicities were generally minimal and controlled by dosage reduction. However, there was one death secondary to severe myelosuppression.