0000000000511393
AUTHOR
J. Crespo
Humanα1-Antitrypsin Gene Transfer toIn VivoMouse Hepatocytes
ABSTRACT The in vivo gene transfer to mouse hepatocytes of pTG 7101, a plasmid containing the full-length gene encoding human α1-antitrypsin (α1-AT) DNA, has been studied by iv administration of recombinant DNA (100 ng/mouse) encapsulated in large and small liposomes. Our results from immunohistochemical liver sections and cytophotometric analysis of hepatocyte chromophore absorbance indicate that human α1-AT was expressed in liver parenchymal cells from mice treated (48 hr before) with DNA encapsulated in small liposomes, and this effect remained for at least 2 weeks. In contrast, the efficiency was greatly limited when large liposomes were used as a vehicle for gene transfer. Additional e…
Undetectable HCV-RNA at treatment-week 8 results in high-sustained virological response in HCV G1 treatment-experienced patients with advanced liver disease: The International Italian/Spanish Boceprevir/Peginterferon/Ribavirin Name Patients Program
In many countries, first-generation protease inhibitors (PIs)/peginterferon/ribavirin (P/R) still represent the only treatment option for HCV-infected patients. Subjects with advanced disease and previous failure to P/R urgently need therapy, but they are under-represented in clinical trials. All treatment-experienced F3/4 Metavir patients who received boceprevir (BOC)+P/R in the Italian-Spanish Name Patient Program have been included in this study. Multivariate logistic regression analysis (MLR) was used to identify baseline and on-treatment predictors of SVR and adverse events (AEs). Four hundred and sixteen patients, mean age 57.7 (range 25-78 years), 70% males, 69.5% (289/416) F4, 14% (…
Antimetastatic Effect of Immunization with Liposome-Encapsulated Tumor Cell-Membrane Proteins Obtained from Experimental Tumors
Immunization of C57BL/6 mice with tumor-derived membrane-proteins encapsulated in sized liposomes (0.2 microgram/mouse) and composed by phosphatidylcholine or sphingomyelin, significantly reduced the mean values of spontaneous lung metastasis from both B16 (0.7 +/- 0.5 and 1.2 +/- 0.6, respectively) and 3LL (4.8 +/- 2.5 and 7.2 +/- 4.1, respectively) tumors, with respect to control (HEPES) groups (4.8 +/- 1.1 and 19.0 +/- 4.4, respectively). However, no significant antimetastatic effect was observed using free tumor-derived proteins (2 micrograms/mouse) or liposome vehicle alone. Specific humoral immune response after the vaccination was studied by flow cytometry of tumor cells incubated wi…
Asialofetuin Liposomes for Receptor-Mediated Gene Transfer into Hepatic Cells
Publisher Summary The liver is an excellent organ for gene transfer in treating a wide variety of diseases that affect liver function. It is an ideal organ for a high amount of expression of therapeutic genes and efficient systemic distribution of the resulting therapeutic proteins secreted into the bloodstream. For strategies of liver-destined gene therapy, the liver sinusoid endothelium contains pores with a mean diameter of 100 nm, which allow small vectors to leave the blood circulation and reach the hepatocytes. The preparation of asialofetuin–liposomes targeted to hepatocytes can be made by covalent coupling of asialofetuin glycoprotein (ASF) onto the liposome surface, by the use of h…
EFFICACY AND SAFETY OF BOCEPREVIR-BASED THERAPY IN HCVG1 TREATMENT-EXPERIENCED PATIENTS WITH ADVANCED FIBROSIS/CIRRHOSIS: THE ITALIAN AND SPANISH NPP EARLY ACCESS PROGRAM
Background and Aims: To maximize cost/efficay of boceprevirbased triple therapy (BOC) in patients with HCV-related advanced fibrosis/cirrhosis. Methods: ITT SVR12, safety and futility rules value were evaluated in the multicenter national Italian and Spanish early access Name- Patient-Program which includes treatment-experienced patients with HCVG1-related advanced fibrosis/cirrhosis (Metavir F3/4) treated with BOC in both countries. Results: 402 patients (mean age 55 years; range 22–75), 316 (78.6%) G1b, 255 (63.4%) F4, 60 (30.9%) with oesophageal varices, 137 (34.1%) relapsers, 95 (23.6%) partial and 168 (41.8%) null responders were enrolled. Platelets count <100,000 and albumin levels <3…
Effect of the protein kinase inhibitors, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine H-7 and N-(2-[methylamino]ethyl)-5-isoquinoline-sulfonamide H-8 on Lewis lung carcinoma tumor progression.
The effects of 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine H-7 (a cAMP-dependent protein kinase and protein kinase C inhibitor), n-(2-[methylamino]ethyl)-5-isoquinoline-sulfonamide H-8 (a cAMP- and cGMP-dependent protein kinase inhibitor) and indomethacin (IND, a cyclooxygenase inhibitor) on both the spontaneous metastatic ability of 3LL (Lewis lung carcinoma) tumor cells and anti-tumor host response were studied. The study of tumor progression showed that H-7 and H-8 (2 mg kg(-1) day(-1) , i.p., for 8 days) significantly reduced the mean number of metastases (0.8 +/- 0.2 and 1.0 +/- 0.7, respectively, P0.05) with respect to the number of lung metastases (4.2 +/- 2.1) observed in the con…