scholarly journals Hepatic Radiofrequency Ablation–induced Stimulation of Distant Tumor Growth Is Suppressed by c-Met Inhibition

Radiology ◽  
2016 ◽  
Vol 279 (1) ◽  
pp. 103-117 ◽  
Author(s):  
Muneeb Ahmed ◽  
Gaurav Kumar ◽  
Marwan Moussa ◽  
Yuanguo Wang ◽  
Nir Rozenblum ◽  
...  
Keyword(s):  
Radiofrequency Ablation ◽  
Tumor Growth ◽  
Distant Tumor ◽  
Stimulation Of

Effect of radiofrequency ablation (RFA) combined with anti-CTLA-4 and anti-PD1 in a preclinical melanoma model.

2019 ◽  
Vol 37 (8_suppl) ◽  
pp. 143-143
Author(s):  
Olga L. Franco-Mahecha ◽  
Anna Christou ◽  
Michal Mauda-Havakuk ◽  
Prateek Katti ◽  
William F. Pritchard ◽  
...  
Keyword(s):  
T Cells ◽  
Radiofrequency Ablation ◽  
T Cell ◽  
Immune Responses ◽  
Tumor Growth ◽  
Cell Fraction ◽  
Primary Tumors ◽  
Syngeneic Mouse Model ◽  
Distant Tumor

143 Background: The aim is to characterize the effect of Radiofrequency Ablation (RFA) with anti-CTLA-4 and anti-PD1 checkpoint inhibitors, on tumor growth and immune responses against B16-OVA melanoma tumors implanted in a syngeneic mouse model. Methods: Adult c57BL/6J female mice were distributed among a non-tumor placebo group (n=5) and four experimental tumor groups: no RFA (n=10); RFA alone (n=5); CPI post-RFA (n=5); and CPI pre-and-post-RFA (n=5). On day 0, mice were inoculated SQ with 2.5x105 B16-OVA cells. RFA was performed at day 15. Three doses of anti-mouse CTLA-4 and anti-mouse PD-1 (200 µg/dose each, every 24 h) were given IP to the appropriate groups. To evaluate the effect of the therapy on a distant tumor, each tumor group was re-inoculated SQ at day 20 with 2.5x105 B16-OVA cells. Serum samples were collected to measure concentration of cytokines. Mice were euthanized at day 36. T-cell and non-T cell fractions were collected from splenocytes for co-culture and evaluation of killing in vitro. Results: Mice that received RFA alone or RFA plus CPI showed significantly smaller primary tumors and minimal growth of secondary tumors compared to untreated mice, suggesting that these therapies may have an abscopal effect. Based on the cytokine profile in serum, mice treated with CPI pre-and-post-RFA showed balanced and sustained concentrations of IFNγ and IL-2 (T cell activation) and controlled inflammatory responses. In vitro experiments showed that T cells from mice treated with CPI pre-and-post-RFA produced significantly more IFNγ when co-cultured with B16-OVA cells. However, these T cells did not demonstrate a high killing activity on the tumor cells. The killing capacity of T cells from mice treated with RFA alone or with CPI pre-and-post-RFA increased significantly when the non-T cell fraction (dendritic cells, macrophages, NK cells, and B cells) was added to the co-culture. Conclusions: RFA therapy combined with CPI given to mice bearing B16-OVA tumors may induce systemic immune responses capable of improving control of distant tumor growth. In culture, primed T cells are not able to kill B16-OVA by themselves, but the addition of the non-T cell fraction may improve T cell killing capacity.

scholarly journals Targetting an LncRNA P5848-ENO1 axis inhibits tumor growth in hepatocellular carcinoma

2019 ◽  
Vol 39 (11) ◽  
Author(s):  
Xidan Zhu ◽  
Hui Yu ◽  
Baolin Li ◽  
Jing Quan ◽  
Zhangrui Zeng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Radiofrequency Ablation ◽  
Cell Growth ◽  
Tumor Growth ◽  
Cell Survival ◽  
Cancer Cell ◽  
Expression Level ◽  
High Recurrence Rate ◽  
Gene And Protein Expression ◽  
And Migration

Abstract Hepatocellular carcinoma (HCC) has a high recurrence rate and poor clinical outcome after currently used therapies, including radiofrequency ablation. To explore the possible mechanisms for the relapse of HCC, in the present study we focussed on long non-coding RNA (LncRNA), which has been reported to be involved in tumorigenesis. We identified an LncRNA P5848, whose expression level was up-regulated in tumor samples from HCC patients after radiofrequency ablation. As such, we speculated that LncRNA P5848 may play a role in tumor growth. Here we showed that LncRNA P5848, whose up-regulation can lead to HCC cancer cell proliferation and migration. In vitro and in vivo overexpression of LncRNA P5848 promoted cell growth, cell survival, and cell invasion, whereas LncRNA P5848 depletion exerts opposite effects. Mechanistically, we have found that ENO1 was the target of LncRNA P5848. LncRNA P5848 up-regulated the gene and protein expression level of ENO1, promoting tumor growth and cell survival. However, siRNA-mediated knockdown of ENO1 counteracted the effects of LncRNA P5848 on cancer cell growth, cell survival, and migration. Taken together, LncRNA P5848 promotes HCC development by up-regulating ENO1, indicating that LncRNA P5848-ENO1 axis is a potential therapeutic target for the treatment of HCC.

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