Uterine perfusion model for analyzing barriers to transport in fibroids.

This project uses an ex vivo human perfusion model for studying transport in benign, fibrous tumors. The uterine arteries were cannulated to perfuse the organ with a buffer solution containing blood vessel stain and methylene blue to analyze intratumoral transport. Gross examination revealed tissue expansion effects and a visual lack of methylene blue in the fibroids.

Combination of local, non-viral IL12 gene therapy and systemic paclitaxel chemotherapy in a syngeneic ID8 mouse model for human ovarian cancer.

The in vivo feasibility of the previously established ID8 and ID8-VEGF ovarian cancer models for non-viral IL-12 gene delivery by itself or in combination with paclitaxel chemotherapy, was investigated in C57BL/6 black mice. The syngeneic mouse ovarian epithelium (MOSE) cancer cell line and its more aggressive variant, a VEGF-modified strain, were used to perform these experiments. Tumor growth and survival were observed in C57/BL6 mice, inoculated with both ID8 substrains.

Comparison of ID8 MOSE and VEGF-modified ID8 cell lines in an immunocompetent animal model for human ovarian cancer.

Attempts to develop novel immunotherapeutic mouse models have been hampered by the lack of an adequate in vivo system. This study was performed to establish an immunocompetent mouse model for the testing of immunotherapy concepts. The in vivo system was based on a svngeneic mouse ovarian surface epithelium (MOSE) cancer, physiologically and biologically closely resembling human epithelial ovarian cancer.

Long-circulating DNA-complexed biodegradable multiblock copolymers for gene delivery: degradation profiles and evidence of dysopsonization.

Biodegradable cationic polymers have become promising alternatives to traditional polycationic gene delivery systems in which the high charge densities of high molecular weight polymers contribute significantly to cellular toxicities. Previous research has shown that biodegradable, multiblock copolymers (MBC), PEG-PLL-g-16% His, are efficient gene carriers with negligible cellular toxicities. The present research was designed to characterize the polymer degradation as well as to determine the biodistribution of the MBC after systemic administration.

Local, non-viral IL-12 gene therapy using a water soluble lipopolymer as carrier system combined with systemic paclitaxel for cancer treatment.

Development of improved gene transfer methods is needed for gene therapy to achieve its clinical potential. The use of biocompatible polymeric gene carriers has shown effectiveness in overcoming the current problems associated with viral vectors in safety, immunogenicity and mutagenesis. Previous work has demonstrated that repeated, local, non-viral interleukin-12 (IL-12) gene delivery successfully slows down tumor progression, while improving immunogenicity.

Combination of local, nonviral IL12 gene therapy and systemic paclitaxel treatment in a metastatic breast cancer model.

Repeated, local, nonviral IL12 (interleukin-12) gene delivery decreased tumor progression and increased immunogenicity. We combined our IL12 gene delivery with systemic paclitaxel chemotherapy as a treatment for paclitaxel (PCT)-resistant 4T1 subcutaneous mouse mammary carcinomas and PCT-sensitive, immunogenic/nonimmunogenic tumors. We mixed PCT with either a biodegradable polymeric solubilizer, HySolv, or Cremophor EL for bimonthly systemic treatments and injected water-soluble lipopolymer (WSLP)/p2CMVmIL-12 (plasmid encoding IL12 gene) complexes locally every week.