Abstract
AIM: To evaluate the effect of interleukin-12 (IL-12) gene ther apyon microvessel density and microenvironment in a postchemoembolization VX2 liver cancer model, and to investigate its anti-tumor mechanism. METHODS: Rabbits with VX2 hepatic tumors were randomized into 4 groups, with eight rabbits in each group. Interventional procedure protocols were performed as follows: 0.9% saline solution (group 1, control), transcatheter arterial chemoembolization alone (group 2, lipiodol + mitomycin), intra-arterial IL-12 gene infusion (group 3, IL-12 gene therapy alone), and intraarterial IL-12 gene infusion in combination with chemoembolization (group 4, IL-12 plus chemoembolization). Fourteen days after therapy, tumor tissues of the sacrificed animals were explanted for immunohistochemistry to evaluate microvessel density, effector T cells (CD3+, CD4+, and CD8+) and regulatory T cells (FoxP3+). RESULTS: The microvessel density and FoxP3+ T cells in group 2 were significantly higher than those in group 1, but the differences in CD3+, CD4+, and CD8+ T cells between the two groups were not significant. The microvessel density in gene therapy groups (groups 3 and 4) were significantly lower, and CD3+, CD4+, and CD8+ T cells in these two groups were significantly higher than those in groups 1 and 2. The differences in CD3+, CD4+, and CD8+ T cells between the two gene therapy groups (groups 3 and 4) were not significant. The difference in FoxP3+ T cells was not significant between before and after IL-12 gene therapy. The differences in the level of FoxP3 were not significant between groups 3 and 1, as well as between groups 4 and 2. CONCLUSION: IL-12 gene therapy can inhibit angiogenesis and induce effector T cell (CD3+, CD4+, and CD8+) infiltration in the VX2 liver cancer model, but the efficacy appears to be limited by the regulatory T cells (FoxP3+) existing in the tumors and overexpressed after chemoembolization.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 97-103 |
| Number of pages | 7 |
| Journal | World Chinese Journal of Digestology |
| Volume | 24 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 8 2016 |
| Externally published | Yes |
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Keywords
- Angiogenesis
- Chemoembolization
- Gene therapy
- Interleukin 12
- Microenvironment
ASJC Scopus subject areas
- Gastroenterology
Cite this
Effect of interleukin 12 gene therapy on microvessel density and microenvironment in a rabbit model of vx2 liver cancer. / Xia, Xiang Wen; Li, Xin; Liu, Yi Ming; Liang, Bin; Zheng, Chuan Sheng; Feng, Gan Sheng; Liang, Hui Min.
In: World Chinese Journal of Digestology, Vol. 24, No. 1, 08.01.2016, p. 97-103.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effect of interleukin 12 gene therapy on microvessel density and microenvironment in a rabbit model of vx2 liver cancer
AU - Xia, Xiang Wen
AU - Li, Xin
AU - Liu, Yi Ming
AU - Liang, Bin
AU - Zheng, Chuan Sheng
AU - Feng, Gan Sheng
AU - Liang, Hui Min
PY - 2016/1/8
Y1 - 2016/1/8
N2 - AIM: To evaluate the effect of interleukin-12 (IL-12) gene ther apyon microvessel density and microenvironment in a postchemoembolization VX2 liver cancer model, and to investigate its anti-tumor mechanism. METHODS: Rabbits with VX2 hepatic tumors were randomized into 4 groups, with eight rabbits in each group. Interventional procedure protocols were performed as follows: 0.9% saline solution (group 1, control), transcatheter arterial chemoembolization alone (group 2, lipiodol + mitomycin), intra-arterial IL-12 gene infusion (group 3, IL-12 gene therapy alone), and intraarterial IL-12 gene infusion in combination with chemoembolization (group 4, IL-12 plus chemoembolization). Fourteen days after therapy, tumor tissues of the sacrificed animals were explanted for immunohistochemistry to evaluate microvessel density, effector T cells (CD3+, CD4+, and CD8+) and regulatory T cells (FoxP3+). RESULTS: The microvessel density and FoxP3+ T cells in group 2 were significantly higher than those in group 1, but the differences in CD3+, CD4+, and CD8+ T cells between the two groups were not significant. The microvessel density in gene therapy groups (groups 3 and 4) were significantly lower, and CD3+, CD4+, and CD8+ T cells in these two groups were significantly higher than those in groups 1 and 2. The differences in CD3+, CD4+, and CD8+ T cells between the two gene therapy groups (groups 3 and 4) were not significant. The difference in FoxP3+ T cells was not significant between before and after IL-12 gene therapy. The differences in the level of FoxP3 were not significant between groups 3 and 1, as well as between groups 4 and 2. CONCLUSION: IL-12 gene therapy can inhibit angiogenesis and induce effector T cell (CD3+, CD4+, and CD8+) infiltration in the VX2 liver cancer model, but the efficacy appears to be limited by the regulatory T cells (FoxP3+) existing in the tumors and overexpressed after chemoembolization.
AB - AIM: To evaluate the effect of interleukin-12 (IL-12) gene ther apyon microvessel density and microenvironment in a postchemoembolization VX2 liver cancer model, and to investigate its anti-tumor mechanism. METHODS: Rabbits with VX2 hepatic tumors were randomized into 4 groups, with eight rabbits in each group. Interventional procedure protocols were performed as follows: 0.9% saline solution (group 1, control), transcatheter arterial chemoembolization alone (group 2, lipiodol + mitomycin), intra-arterial IL-12 gene infusion (group 3, IL-12 gene therapy alone), and intraarterial IL-12 gene infusion in combination with chemoembolization (group 4, IL-12 plus chemoembolization). Fourteen days after therapy, tumor tissues of the sacrificed animals were explanted for immunohistochemistry to evaluate microvessel density, effector T cells (CD3+, CD4+, and CD8+) and regulatory T cells (FoxP3+). RESULTS: The microvessel density and FoxP3+ T cells in group 2 were significantly higher than those in group 1, but the differences in CD3+, CD4+, and CD8+ T cells between the two groups were not significant. The microvessel density in gene therapy groups (groups 3 and 4) were significantly lower, and CD3+, CD4+, and CD8+ T cells in these two groups were significantly higher than those in groups 1 and 2. The differences in CD3+, CD4+, and CD8+ T cells between the two gene therapy groups (groups 3 and 4) were not significant. The difference in FoxP3+ T cells was not significant between before and after IL-12 gene therapy. The differences in the level of FoxP3 were not significant between groups 3 and 1, as well as between groups 4 and 2. CONCLUSION: IL-12 gene therapy can inhibit angiogenesis and induce effector T cell (CD3+, CD4+, and CD8+) infiltration in the VX2 liver cancer model, but the efficacy appears to be limited by the regulatory T cells (FoxP3+) existing in the tumors and overexpressed after chemoembolization.
KW - Angiogenesis
KW - Chemoembolization
KW - Gene therapy
KW - Interleukin 12
KW - Microenvironment
UR - http://www.scopus.com/inward/record.url?scp=84953790793&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84953790793&partnerID=8YFLogxK
U2 - 10.11569/wcjd.v24.i1.97
DO - 10.11569/wcjd.v24.i1.97
M3 - Article
AN - SCOPUS:84953790793
VL - 24
SP - 97
EP - 103
JO - World Chinese Journal of Digestology
JF - World Chinese Journal of Digestology
SN - 1009-3079
IS - 1
ER -