1. Treatment of peritoneal carcinomatosis with intraperitoneal administration of Ad-hARF.
- Author
-
Rajeshkumar, Barur R., Paliwal, Seema, Lambert, Laura, Grossman, Steven R., and Whalen, Giles F.
- Subjects
- *
PERITONEAL cancer , *DRUG administration , *GENE therapy , *TUMOR suppressor genes , *AMINO acid sequence , *CELL lines , *CANCER treatment - Abstract
Background Peritoneal dissemination of cancer is a terminal condition with limited therapeutic options. Because the peritoneal cavity is a single enclosed space, regional treatment approaches for isolated peritoneal cancrinomatosis are appealing. There is a potential role for gene therapy in the management of peritoneal cancrinomatosis. Materials and methods An adenoviral construct of the human p14ARF gene (a tumor suppressor) and a 22 amino acid sequence of the ARF gene product, which has cell membrane penetrating properties, were assayed for proapoptotic properties in a human colorectal cancer cell line (Clone A) cells in vitro. Peritoneal carcinomatosis derived from Clone A cells was also established in nude mice and then treated with intraperitoneal administration of an adenoviral construct of the human p14ARF gene. Results Treatment of ARF-negative Clone A cells with Ad-hARF in vitro reestablished ARF function. However, the cell penetrating ARF-related peptide did not restore ARF function in Clone A cells. Treatment of Clone A peritoneal xenografts with a single intraperitoneal dose of Ad-hARF (9 x 106 viral particles) suppressed the progression of peritoneal disease. Weekly (six times) administration of the Ad-hARF at a lower dose (3 x 106 viral particles) also suppressed tumor progression. Conclusions Treatment of peritoneal carcinomatosis by intraperitoneal administration of adenoviral constructs of inactivated tumor suppressor genes may be a feasible clinical approach, and ARF may represent a suitable molecular target for tumors where the ARF gene is inactivated. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF