Purpose: Replication-selective tumor-specific viruses present a novel approach for treating neoplastic disease. These vectors are designed to induce virus-mediated lysis of tumor cells after selective viral propagation within the tumor. Telomerase activation is considered to be a critical step in carcinogenesis, and its activity is closely correlated with human telomerase reverse transcriptase (hTERT) expression. We investigated the antitumor effect of the hTERT-specific replication-competent adenovirus on human cancer cells. Experimental Design: We constructed an adenovirus 5 vector [tumor- or telomerase-specific replication-competent adenovirus (TRAD)], in which the hTERT promoter element drives expression of E1A and E1B genes linked with an internal ribosome entry site, and we examined the selective replication and antitumor effect in human cancer cells in vitro and in vivo. Results: TRAD induced selective E1A and E1B expression in human cancer cells, but not in normal cells such as human fibroblasts. TRAD replicated efficiently and induced marked cell killing in a panel of human cancer cell lines, whereas replication as well as cytotoxicity was highly attenuated in normal human fibroblasts lacking telomerase activity. In nu/nu mice carrying s.c. human lung tumor xenografts, intratumoral injection of TRAD resulted in a significant inhibition of tumor growth. No evidence of TRAD was identified in tissues outside of the tumors, despite the presence of TRAD in the circulation. Moreover, TRAD replication in the distant, noninjected tumors was demonstrated. Conclusions: Our results suggest that the hTERT promoter confers competence for selective replication of TRAD in human cancer cells, an outcome that has important implications for the treatment of human cancers.

PURPOSE: To determine the effectiveness of computed tomography (CT)-guided radiofrequency (RF) ablation of malignant thoracic tumors. MATERIALS AND METHODS: CT-guided RF ablations of 99 malignant thoracic tumors (3–80 mm in largest diameter; mean, 19.5 mm) were performed in 35 patients in 54 sessions. Ablation was performed with an RF generator by using a single internally cooled electrode. Tumors were both primary (three lesions) and secondary (pulmonary or pleural metastases, 96 lesions). Follow-up was 1–17 months (mean, 7.1 months). Follow-up CT and histopathologic examinations were evaluated. Univariate analysis was performed with the Fisher exact test, and Welch t test was used to evaluate differences between group means. P < .05 represented a significant difference. The maximal diameter of each residual tumor or local recurrence or the proportion of primary lesions of pulmonary metastatic tumors with recurrence after RF ablation were analyzed. Complications, management, and outcomes of the complicat...