Persistent transgene expression following intravenous administration of a liposomal complex: role of interleukin-10-mediated immune suppression.

Studies conducted in non-tumor-bearing, immunocompetent mice have shown that intravenous administration of liposome-DNA complex elicits an inflammatory response that results in a failure to sustain adequate transgene expression. In the present study, however, we investigated the effects of a cationic liposomal DOTAP:cholesterol (DOTAP:Chol)-DNA complex on cytokine production and transgene expression in both experimental lung tumor-bearing (TB) mice and non-tumor-bearing (NTB) syngeneic mice and nude mice. Intravenous injection of DOTAP:Chol-luciferase (luc) DNA complex resulted in tumor necrosis factor-alpha levels that were 50% lower and interleukin-10 levels that were 50-60% higher in TB mice than in NTB mice.

Adenoviral transfer of mda-7 leads to BAX up-regulation and apoptosis in mesothelioma cells, and is abrogated by over-expression of BCL-XL.

Background: Malignant pleural mesothelioma (MPM) is unresponsive to conventional therapies. Forced expression of the novel tumor suppressor mda-7 gene in other cell types has resulted in decreased growth and apoptosis. We evaluated cell growth, apoptosis and tumor suppressor characteristics following forced expression of this gene in mesothelioma cell lines.

Antisense therapy for malignant mesothelioma with oligonucleotides targeting the bcl-xl gene product.

Objective: Malignant pleural mesothelioma is resistant to conventional therapies and to apoptosis. The bcl-2 family genes are major determinants of apoptotic homeostasis. Malignant pleural mesothelioma lines and tumors rarely express the antiapoptotic Bcl-2 protein but routinely express the antiapoptotic protein Bcl-xl and the proapoptotic proteins Bax and Bak.