Treatment of peritoneal carcinomatosis with intraperitoneal administration of Ad-hARF.
J Surg Res
; 197(1): 85-90, 2015 Jul.
Article
in En
| MEDLINE
| ID: mdl-25935465
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 ANDMETHODS:
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 × 10(6) viral particles) suppressed the progression of peritoneal disease. Weekly (six times) administration of the Ad-hARF at a lower dose (3 × 10(6) 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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Peritoneal Neoplasms
/
Colorectal Neoplasms
/
Genetic Therapy
/
Genes, p16
/
Tumor Suppressor Protein p14ARF
/
Antineoplastic Agents
Type of study:
Clinical_trials
/
Evaluation_studies
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
J Surg Res
Year:
2015
Document type:
Article