| RRC ID |
3814
|
| 著者 |
Tanaka F, Tominaga K, Shiota M, Ochi M, Kuwamura H, Tanigawa T, Watanabe T, Fujiwara Y, Oshitani N, Higuchi K, Iwao H, Arakawa T.
|
| タイトル |
Interleukin-10 gene transfer to peritoneal mesothelial cells suppresses peritoneal dissemination of gastric cancer cells due to a persistently high concentration in the peritoneal cavity.
|
| ジャーナル |
Cancer Gene Ther
|
| Abstract |
Interleukin (IL)-10 has potent biological properties including an inhibitory action on the proliferation and metastasis of various cancer cells. However, it is difficult to maintain a high concentration of this cytokine as it has a short half life. In this study, we evaluated whether peritoneal mesothelial cells (PMCs) could be suitable for maintaining a high concentration of IL-10 using adenoviral gene transfer. We also evaluated the therapeutic effects of an intraperitoneal injection with adenoviral vector containing mouse IL-10 gene (Ad-mIL-10) using a mouse peritoneal dissemination model of MKN45 gastric cancer cells. We demonstrated that in vitro transfection efficiency of a recombinant adenovirus containing the bacterial beta-galactosidase gene (Ad-LacZ) was approximately 10-fold higher for primarily isolated PMCs than MKN45. The entire peritoneum was transfected until 3 weeks after an intraperitoneal Ad-LacZ injection. Ad-mIL-10 treatment increased intraperitoneal IL-10 levels until 3 weeks after treatment, and then significantly inhibited peritoneal cancer growth by inhibiting angiogenesis. This treatment also improved cachexia and prolonged mice survival. We thus concluded that IL-10 gene transfer in PMCs could be a new strategy for the prevention of peritoneal dissemination of gastric cancer due to the resulting persistently high IL-10 concentration in the peritoneal cavity.
|
| 巻・号 |
15(1)
|
| ページ |
51-9
|
| 公開日 |
2008-1-1
|
| DOI |
10.1038/sj.cgt.7701104
|
| PII |
7701104
|
| PMID |
17992202
|
| MeSH |
Adenoviridae*
Animals
Cachexia / genetics
Cachexia / metabolism
Cachexia / therapy
Epithelium / metabolism
Humans
Interleukin-10 / biosynthesis*
Interleukin-10 / genetics
Lac Operon / genetics
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasms, Experimental / genetics
Neoplasms, Experimental / metabolism
Neoplasms, Experimental / therapy
Peritoneal Cavity
Peritoneal Neoplasms / genetics
Peritoneal Neoplasms / metabolism
Peritoneal Neoplasms / secondary
Peritoneal Neoplasms / therapy*
Rats
Rats, Wistar
Stomach Neoplasms / genetics
Stomach Neoplasms / metabolism
Stomach Neoplasms / therapy*
Time Factors
Transduction, Genetic*
Transfection
|
| IF |
4.534
|
| 引用数 |
15
|
|
WOS 分野
|
MEDICINE, RESEARCH & EXPERIMENTAL
BIOTECHNOLOGY & APPLIED MICROBIOLOGY
ONCOLOGY
GENETICS & HEREDITY
|
| リソース情報 |
| 遺伝子材料 |
AxCAmIL10 (RDB1410) |
| ヒト・動物細胞 |
MKN45(RCB1001) |
