BackgroundTo assess whether intraoperative use of contrast-enhanced ultrasound (CEUS)-CT/MR image fusion can accurately evaluate ablative margin (AM) and guide supplementary ablation to improve AM after hepatocellular carcinoma (HCC) ablation.MethodsNinety-eight patients with 126 HCCs designated to undergo thermal ablation treatment were enrolled in this prospective study. CEUS-CT/MR image fusion was performed intraoperatively to evaluate whether 5-mm AM was covered by the ablative area. If possible, supplementary ablation was applied at the site of inadequate AM. The CEUS image quality, the time used for CEUS-CT/MR image fusion and the success rate of image fusion were recorded. Local tumor progression (LTP) was observed during follow-up. Clinical factors including AM were examined to identify risk factors for LTP.ResultsThe success rate of image fusion was 96.2 % (126/131), and the duration required for image fusion was 4.9 ± 2.0 (3–13) min. The CEUS image quality was good in 36.1 % (53/147) and medium in 63.9 % (94/147) of the cases. By supplementary ablation, 21.8 % (12/55) of lesions with inadequate AMs became adequate AMs. During follow-up, there were 5 LTPs in lesions with inadequate AMs and 1 LTP in lesions with adequate AMs. Multivariate analysis showed that AM was the only independent risk factor for LTP (hazard ratio, 9.167; 95 % confidence interval, 1.070–78.571; p = 0.043).ConclusionCEUS-CT/MR image fusion is feasible for intraoperative use and can serve as an accurate method to evaluate AMs and guide supplementary ablation to lower inadequate AMs.
3D US-CEUS fusion imaging is a feasible and valuable technique for the immediate evaluation and guidance of supplementary ablation during the liver cancer thermal ablation procedure.
Rationale
: Current therapies for hepatocellular carcinoma (HCC) are hampered by treatment failure and recurrence due to the remaining treatment-resistant liver cancer stem cells (CSCs). Stemness and epithelial-mesenchymal transition (EMT) are regarded as two fundamental characteristics of liver CSCs necessary for cancer progression; thus, drugs that simultaneously target both characteristics should prove effective in eliminating HCC and impeding recurrence. In this study, we developed new arsenic trioxide (ATO)-based nanoparticles (NPs), which are expected to be more effective than the current HCC therapy, and explored their potential mechanism.
Methods
: A “one-pot” reverse emulsification approach was employed to prepare the ZnAs@SiO
2
NPs. HCC cell lines, MHCC97L and Hep3b, were used to analyze the antitumor activity of ZnAs@SiO
2
NPs
in vitro
and
in vivo
by quantifying cell growth and metastasis as well as to study the effect on stemness and EMT. SHP-1 siRNA was used to validate the role of the SHP-1/JAK2/STAT3 signaling pathway in mediating inhibition of stemness and EMT by ZnAs@SiO
2
.
Results
: Compared with the current ATO treatment, ZnAs@SiO
2
NPs promoted apoptosis and significantly inhibited proliferation, migration, and invasion of both MHCC97L and Hep3b cells. In the
in vivo
assay, ZnAs@SiO
2
NPs inhibited tumor growth by 2.2-fold and metastasis by 3.5-fold as compared to ATO. The ZnAs@SiO
2
NPs also inhibited tumor spheroid formation
in vitro
and tumor initiation
in vivo
and induced significant changes in the expression of stemness markers (CD133, Sox-2, and Oct-4) and EMT markers (E-cadherin, Vimentin, and Slug) both
in vitro
and
in vivo.
These effects of ZnAs@SiO
2
that correlated with prognosis of HCC were mediated by the SHP-1/JAK2/STAT3 signaling.
Conclusions
: ZnAs@SiO
2
NPs can effectively suppress tumor initiation, growth, metastasis, and inhibit stemness and EMT through regulation of SHP-1/JAK2/STAT3 signaling pathway in liver cancer cells
in vitro
and
in vivo
. Thus, ZnAs@SiO
2
NPs have immense potential for HCC treatment in the future.
Chemoresistance and epithelial-mesenchymal transition (EMT) in cancer are linked phenomena. EMT contributes to chemoresistance, however, little is known about whether chemotherapy can induce EMT in cancer cells. Here, we found that miR-101 expression was downregulated in cisplatin-resistant non-small cell lung cancer (NSCLC) cells. Restoration of miR-101 expression inhibited EMT and increased the sensitivity of cisplatin-resistant NSCLC cells to cisplatin in vitro by targeting ROCK2. Furthermore, ROCK2 protein level was inversely correlated with miR-101 level in NSCLC tissue samples. Kaplan-Meier analysis revealed that low miR-101 expression in NSCLC was correlated with poor survival time. In summary, our results provide novel mechanistic insights into the role of miR-101/ROCK2 signaling in the cisplatin resistance of NSCLC cells. Targeting of miR-101 is a potential therapeutic approach for NSCLC.
Aim
To retrospectively compare the treatment effect of intraprocedural computed tomography/magnetic resonance–contrast‐enhanced ultrasound (CT/MR‐CEUS) fusion imaging (FI) with that of conventional ultrasound (US) in the guidance and assessment of thermal ablation of hepatocellular carcinoma (HCC).
Methods
The FI group (112 patients with 129 HCC) was treated between April 2010 and December 2012, whereas the US group (83 patients with 90 HCC) was treated between January 2008 and March 2010. Either CT/MR‐CEUS FI or US was used to guide puncture, provide immediate assessment, and guide supplementary ablation. Technical efficacy, cumulative local tumor progression rate (LTP), recurrence‐free survival (RFS), and overall survival (OS) were evaluated and compared during follow‐up. Technical success rate of CT/MR‐CEUS FI was also recorded.
Results
Technical efficacy was significantly higher in the FI group than in the US group (100% vs. 86.7%, P < 0.001). The 1‐, 2‐, 3‐, 4‐, 5‐, and 6‐year cumulative LTP rates in the FI group were significantly lower than in the US group (3.8%, 4.9%, 6.0%, 6.0%, 7.2%, and 7.2% vs. 16.9%, 20.1%, 25%, 25%, 25%, and 25%, respectively; P < 0.001); RFS and OS were significantly higher in the FI group than in the US group (P = 0.027 and P = 0.049, respectively). The technical success rate of FI was 85.3%.
Conclusions
Intraprocedural CT/MR‐CEUS FI improved the treatment effect of thermal ablation of HCC by immediately assessing treatment response and guiding supplementary ablation relative to those resulting from the use of conventional US.
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