It is possible that both N- and C-terminal domains are present in the same ratio in native virions but VP2 is lost during purification. It is also possible that the N- and C-terminal domains are not normally cleaved as this could simply be an artifact of purification; however this appears unlikely as the antibody to this region also detects the 44-kDa product in crude ant lysates. Previous data demonstrate that the APV ORF2-encoded polypeptide is also cleaved, as the size of the transframe fusion protein is too small to encompass the entire sequence. However it is not known whether or not the APV C-terminal domain is associated with APV virions. TRAIL acts through binding to its cognate receptors DR4 and/ or DR5. Once activated, DR4 and/or DR5 transmit apoptotic signals intracellularly. Similar to other TNF family members such as FasL and TNF-a, TRAIL activates caspase-8 as an initial apoptotic signaling event. Despite similarity in apoptotic signaling cascades activated but the mechanism largely unknown yet, TRAIL has a unique selectivity for triggering Cefetamet pivoxil HCl apoptosis in tumor cells but not most normal cells. In addition, complying with the tissue distribution of the TRAIL receptors, TRAIL has a wide range of targets. These features of TRAIL have drawn considerable attention as a promising cancer therapy. Malignant gliomas are the most common brain tumors in adults and account for more than half of all brain tumors. However, treatment of malignant gliomas with conventional approaches is largely unsuccessful because a wide resection commonly applied for other malignancies is limited and curative doses of therapeutics generally cannot be delivered to the tumor site without excessive toxicity to normal tissues. As a consequence, the mortality rate for the patients harboring malignant gliomas remains high for the past decades. Here, we present a novel TRAIL-based gene therapy for malignant gliomas. Our gene therapy approach showed Ginsenoside-F5 potent tumor suppressor activity for intracranial brain tumor with no toxic side effects. Our data indicate that this approach has great promise as a therapy toward malignant gliomas. It is thus expected that secreted soluble TRAIL should kill a larger number of cells through wider distribution. To develop a biologically active form of soluble TRAIL produced in mammalian cells, we manipulated the apoptosis-inducing moiety of TRAIL to be secreted through fusion with a secretion signal sequence. Interestingly, however, we observed that unlike recombinant soluble TRAIL produced from bacterial cells, the secreted TRAIL produced in mammalian cells maintains its apoptotic functionality only when it is fused with a trimerization-enforcing domain. This result suggested that the soluble TRAIL ectopically expressed in mammalian cells does not form the trimer quaternary structure required for apoptotic activity. Based on these observations, we have created an expression cassette that encodes a secretable form of trimeric TRAIL composed of the three functional elements including a secretion signal, a trimerization domain and an apoptosis-inducing moiety of TRAIL gene sequence. The stTRAIL is expressed as a pro-protein and converted to an active protein following a specific cleavage by Furin, a protease residing in Golgi complex, in the process of secretion. In an attempt to establish a gene therapy approach to deliver stTRAIL to tissues efficiently, we inserted our stTRAIL expression cassette to Y5, an E1/E3- doubly deleted human adenovirus type 5.