Specific Inhibitor of Matrix Metalloproteinase Decreases Tumor Invasiveness After Radiofrequency Ablation in Liver Tumor Animal Model

Jiang, Anna; Liu, Jingtao; Zhao, Kun; Wu, Huizi; Wang, Song; Yan, Kun; Yang, Wei

doi:10.3389/fonc.2020.561805

Cited by 6 publications

(5 citation statements)

References 36 publications

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“…Although several studies have aimed to elucidate the mechanism of worse malignancy for recurrent residual liver tumor, more specific molecular indicators still await exploration [38][39][40]. In the current study, overexpressed NR2F6 in hepatoblastoma tissues was confirmed through 440 samples.…”

Section: Discussionmentioning

confidence: 55%

Incomplete thermal ablation-induced up-regulation of transcription factor nuclear receptor subfamily 2, group F, member 6 (NR2F6) contributes to the rapid progression of residual liver tumor in hepatoblastoma

Pang

Wen

et al. 2021

Bioengineered

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Section: Discussionmentioning

confidence: 55%

Incomplete thermal ablation-induced up-regulation of transcription factor nuclear receptor subfamily 2, group F, member 6 (NR2F6) contributes to the rapid progression of residual liver tumor in hepatoblastoma

Pang

Wen

et al. 2021

Bioengineered

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“…Twenty-four mice with H22 tumors were used in this phase, and the effect of the two different manners on the growth of the unablated half of the tumor after RFA was analyzed. On the basis of our previous work [16,17], the average diameter of tumor destruction after RFA was around 7 mm, while the risk of spontaneous necrosis was higher when the tumor was larger than 15 mm. Accordingly, the range of 7-15 mm diameter was selected as an appropriate tumor size for RFA.…”

Section: Comparison Of Tumor Growth Ratesmentioning

confidence: 87%

The study of direct and indirect effects of radiofrequency ablation on tumor microenvironment in liver tumor animal model

Jiang

Wang

et al. 2022

BMC Cancer

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Background Direct and indirect effects of radiofrequency ablation (RFA) on tumor microenvironment of the liver tumor have been noted, which was reported to be related to a variety of tyrosine protein kinase or cytokinetic pathway, but have not been thoroughly investigated and conclusive. Purpose To elucidate direct and indirect effects of RFA on tumor microenvironment in the liver tumor model, and to explore the role of the specific inhibitor in tumor growth by targeting the key pathway of RFA. Materials and methods One hundred and ten mice with H22 liver tumor were used in animal experiments. Eighty-four mice were randomized into three groups: control, direct RFA and indirect RFA (a block slide was inside the middle of the tumor). The growth rate of the residual tumor after RFA was calculated (n = 8 each group) and the pathologic changes at different time points (6 h, 24 h, 72 h and 7d after RFA) were evaluated (n = 5 in each subgroup). After semi-quantitative analysis of the pathological staining, the most significant marker after RFA was selected. Then, the specific inhibitor (PHA) was applied with RFA and the tumor growth and pathological changes were evaluated and compared with RFA alone. The Kruskal-Wallis test was used for evaluating the significance of different treatments in the pathological positive rate of specific markers in tumor. The two-way analysis of variance was used to determine the significance of treatment in tumor growth or body weight. Results The growth rate of the residual tumor in the direct RFA group was faster than the indirect RFA group (P = 0.026). The pathological analysis showed the expression of HSP70 (73 ± 13% vs 27 ± 9% at 24 h, P < 0.001), SMA (70 ± 18% vs 18 ± 7% at 6 h, P < 0.001) and Ki-67 (51 ± 11% vs 33 ± 14% at 7d, P < 0.001) in the direct RFA group was higher than those in the indirect RFA group after RFA. On the other hand, the expression of c-Met (38 ± 11% vs 28 ± 9% at 24 h, P = 0.01), IL-6 (41 ± 10% vs 25 ± 9% at 24 h, P < 0.001) and HIF-α (48 ± 10% vs 28 ± 8% at 24 h, P < 0.001) in the indirect RFA group was higher than those in the direct RFA group. And the expression of c-Met increased mostly in both direct and indirect RFA group compared to the baseline (53 and 65% at 72 h). Then the specific inhibitor of c-Met-PHA was applied with RFA. The growth rate of the tumor was significantly slower in the RFA + PHA group than the RFA alone group (1112.9 ± 465.6 mm3 vs 2162.7 ± 911.1 mm3 at day 16, P = 0.02). Conclusion Direct and indirect effects of RFA on tumor microenvironment changed at different time points and resulted in increased residual tumor growth in the animal model. It can be potentially neutralized with specific inhibitor of related pathways, such as tyrosine-protein kinase c-Met.

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“…Insufficient RFA has been also shown to upregulate the AKT pathway, promoting neoplastic proliferation and survival through the epithelial-mesenchymal transition pathway, driving cancer metastasis ( 39 ). Additional important players found in insufficient RFA of cancer tissue include c-Met, a tyrosine kinase receptor that upregulates embryogenesis, potentially implicating a mechanism that may promote novel neoplastic growth after the RFA procedure, and MMPs, which facilitate wound healing and tissue remodeling following injury, which establish a peripherally reactive cellular environment after RFA ( 37 , 52 ).…”

Section: Discussionmentioning

confidence: 99%

Clinical outcomes and tumor microenvironment response to radiofrequency ablation therapy: a systematic review and meta-analysis

Mueller,

Issa,

Hussein

et al. 2024

Gland Surg

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Background Radiofrequency ablation (RFA) utilizes minimally invasive high-energy current to precisely ablate tumor cells. It has been utilized in many cancer types including thyroid, lung, and liver cancer. It has been shown to provide adequate ablative margins with minimal complications; however, incomplete RFA may lead to recurrence of tumor. The underlying cellular mechanism and behavior of ablated cancer tissue is poorly understood. Methods A systematic review was performed, searching EMBASE, Web of Science, PubMed, and Scopus for studies published up to March 2022 and reported following PRISMA guidelines. Collection was performed by two groups of investigators to avoid risk of bias. The Cochrane Collaboration’s tool was used for assessing risk of bias. We identified human, in vivo , and in vitro research studies utilizing RFA for tumor tissues. We required that the studies included at least one of the following: complications, recurrence, or survival, and took interest to studies identifying cellular signaling pathway patterns after RFA. Descriptive statistical analysis was performed in ‘R’ software including mean and confidence interval. Results The most frequent cancers studied were liver and lung cancers accounting for 57.4% (N=995) and 15.4% (N=267), followed by esophageal (N=190) and breast cancer (N=134). The most common reported complications were bleeding (19%) and post-operative pain (14%). In our literature search, four independent studies showed upregulation and activation of the VEGF pathway following RFA, four showed upregulation and activation of the AKT pathway following RFA, three studies demonstrated involvement of matrix metalloproteinases, and four showed upregulation of c-Met protein following RFA. Conclusions In our review and meta-analysis, we identify several proteins and pathways of interest of which are important in wound healing, angiogenesis, and cellular growth and survival. These proteins and pathways of interest may implicate areas of research towards RFA resistance and cancer recurrence.

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Specific Inhibitor of Matrix Metalloproteinase Decreases Tumor Invasiveness After Radiofrequency Ablation in Liver Tumor Animal Model

Cited by 6 publications

References 36 publications

Incomplete thermal ablation-induced up-regulation of transcription factor nuclear receptor subfamily 2, group F, member 6 (NR2F6) contributes to the rapid progression of residual liver tumor in hepatoblastoma

Incomplete thermal ablation-induced up-regulation of transcription factor nuclear receptor subfamily 2, group F, member 6 (NR2F6) contributes to the rapid progression of residual liver tumor in hepatoblastoma

The study of direct and indirect effects of radiofrequency ablation on tumor microenvironment in liver tumor animal model

Clinical outcomes and tumor microenvironment response to radiofrequency ablation therapy: a systematic review and meta-analysis

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