Melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL24), selectively induces apoptosis in cancer cells without harming normal cells. It also exerts immunomodulatory and antiangiogenic effects, as well as potent antitumor bystander effects, making it an ideal candidate for a new anticancer gene therapy. Here, we examined the feasibility of adeno-associated virus type 1 (AAV1) vector-mediated systemic gene therapy using mda-7/IL24. In vitro studies showed that medium conditioned by AAV1-mda7-transducedC2C12 cells induces tumor cell-specific apoptosis and inhibits angiogenesis in a human umbilical vein endothelial cell tube formation assay. To assess the in vivo effects of AAV1-mediated systemic delivery of MDA-7/IL24, we generated a subcutaneous tumor model by injecting Ehrlich ascites tumor cells into the dorsum of DDY mice. A single intravenous injection of AAV1-mda7 (2.0 x 10(11) viral genomes) significantly inhibited tumor growth. In addition, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), and immunohistochemical analyses showed significant induction of tumor-cell-specific apoptosis and reduction of microvessel formation within the tumors, and there was a significant increase in survival among the AAV1-mda7-treated mice. These results clearly demonstrate that continuous systemic delivery of MDA-7/IL24 can serve as an effective treatment for cancer. Thus, AAV1 vector-mediated systemic delivery of MDA-7/IL24 represents a potentially important new approach to anticancer therapy.
The intracranial pressure decreased in a)) cases. EEG revealed slight improvement. The diameter of cortical and peripheral vessels did not change during the experimental period. These results suggested that the administration of mannitol brought about a beneficial effect on cerebral edema.
Experimental brain edema was prepared by the expradural balloon method with rabbit. Intravenous injection of trasylol (25,000 uts) was carried out twice; the first, at the filling of the. extradurally introduced balloon with saline solution and the second, at the emptying this balloon after 24 hours. Then 24 hours later from the last injection, the experimenal animals were sacrificed and the destruction of the blood brain barrier was examined with fluorescein method.7 rabbits were used in this experiment. Of the 4 cases no fluorescein was observed, and of the 2 cases slight staining was found. Last one case was stained by dye as same grade in control. Therefore, it seems that the trasylol has the protective effect on the blood brain barrier in this type of brain edema since in about 68% cars the staining of the brain was inhibited.Trasylol is the inhibitor for the many kinds of proteolytic enzymes. It has been accepted that this drug has three main sites of action such as kinin system, plasmin system and blood coagulation system. On the other hand, the action mechanismus of this drug on the blood brain barrier is very interest problem which should be elucidated.
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