Supramolecular nanoparticles for photothermal therapy (PTT) have shown promising therapeutic efficacy in the primary tumor and great potential for turning the whole-body immune microenvironment from "cold" to "hot," which allows for the simultaneous treatment of the primary tumor and the metastatic site. In this work, we develop a liposome-based PTT nanoparticle through the self-assembly of FDA-approved intravenous injectable lipids and a photothermal agent, indocyanine green (ICG). The obtained ICG-liposome shows long-term storage stability, high ICG encapsulation efficiency (>95%), and enhanced near-infrared (NIR) light-triggered photothermal reaction both in vitro and in vivo. The ICG-liposome efficiently eradicated the primary tumor upon laser irradiation in two colon cancer animal models (CT26 and MC38) and promoted the infiltration of CD8 T cells to distant tumors. However, PTT from ICG-liposome shows only a minimal effect on the inhibition of distant tumor growth in long-term monitoring, predicting other immunosuppressive mechanisms that exist in the distant tumor. By immune-profiling of the tumor microenvironment, we find that the distant tumor growth after PTT highly correlates to compensatory upregulation of immune checkpoint biomarkers, including program death-1 (PD-1), T-cell immunoglobulin, and mucin domain-containing protein 3 (TIM-3), in tumor-infiltrating CD8 T cells. Based on this mechanism, we combine dual PD-1 and TIM-3 blockade with PTT in an MC38 tumor model. This combo successfully clears the primary tumor, generates a systemic immune response, and inhibits the growth of the distant tumor. The ICG-liposome-combined PD-1/TIM-3 blockade strategy sheds light on the future clinical use of supramolecular PTT for cancer immunotherapy.
The aim of this meta-analysis was to estimate the diagnostic performance of shear wave elastography (SWE) in differentiating malignant from benign breast lesions. A literature search of PubMed, Web of Science and Scopus up to November 2014 was conducted. A summary receiver operating characteristic curve was constructed, and pooled weighted estimates of sensitivity and specificity were calculated using a bivariate mixed-effects regression model. Thirty-three studies, which included a total of 5838 lesions (2093 malignant, 3745 benign) from 5397 patients, were finally analyzed. Summary sensitivity and specificity were 0.886 (95% confidence interval [CI], 0.858-0.909) and 0.866 (95% CI, 0.833-0.894), respectively. The pooled diagnostic odds ratio was 50.410 (95% CI, 34.972-72.664). And the area under the receiver operating characteristic curve of SWE was 0.94 (95% CI, 0.91-0.96). No publication bias existed among these studies (p = 0.245). In the subgroup analysis, sensitivity and specificity were 0.862 (95% CI, 0.811-0.901) and 0.875 (95% CI, 0.793-0.928) among 1552 lesions from 1429 patients in the 12 studies using acoustic radiation force impulse imaging and 0.897 (95% CI, 0.863-0.923) and 0.863 (95% CI, 0.831-0.889) among another 4436 lesions from 4097 patients in the 21 studies using supersonic shear imaging. When analysis confined to 9 studies evaluated the diagnostic performance of combination SWE and conventional ultrasound, the area under the curve was 0.96 (95% CI, 0.94-0.97), yielding a sensitivity of 0.971 (95% CI, 0.941-0.986) and specificity of 0.801 (95% CI, 0.733-0.856). SWE seems to be a good quantitative method for differentiating breast lesions, with promise for integration into routine imaging protocols.
Background: We aimed to evaluate the performance of a deep learning (DL)-based Radiomics strategy designed for analyzing contrast-enhanced ultrasound (CEUS) to not only predict the progression-free survival (PFS) of radiofrequency ablation (RFA) and surgical resection (SR) but also optimize the treatment selection between them for patients with very-early or earlystage hepatocellular carcinoma (HCC). Methods: We retrospectively enrolled 419 patients examined by CEUS within 1 week before receiving RFA or SR (RFA: 214, SR: 205) from January 2008 to 2016. Two Radiomics signatures were constructed by the Radiomics model R-RFA and R-SR to stratify PFS of different treatment groups. Then, RFA and SR nomograms were built by incorporating Radiomics signatures and significant clinical variables to achieve individualized 2-year PFS prediction. Finally, we applied both Radiomics models and both nomograms to each enrolled patient to investigate whether there were space for treatment optimization and how much prognostic improvement could be expected.
Background
The prognosis of adrenal metastases (AM) from hepatocellular carcinoma (HCC) with surgical contraindication was poor. This study evaluated the feasibility, safety and treatment efficacy of percutaneous ultrasound (US)-guided radiofrequency ablation (RFA) for the local treatment of AM originated from HCC.
Methods
A retrospective study was carried out on 22 patients (21 male and 1 female, mean age, 53.0 ± 13.0 years) who had single AM (mean diameter, 4.0 ± 1.8 cm, range, 1.7–8.0 cm) originated from HCC and received US-guided percutaneous RFA at our institution. The diagnosis was established on typical radiologic findings. The primary technical success was defined as the tumour being completely ablated in the first RFA session. The secondary technical success was defined as tumour residual left from the first ablation was completely ablated by a second ablation session. Local tumour progression (LTP) and overall survival (OS) were estimated by using Kaplan-Meier analysis.
Results
A total of 25 ablation sessions were performed. The primary technical success and the secondary technical success were 77.3% (17 of 22) and 86.4% (19 of 22), respectively, with the major complication rate at 4.5% (1 of 22). The median follow-up period after RFA was 10 months (3–55 months). During the follow-up period, five patients were detected LTP. The LTP at 3, 6, and 12 months were 15.8, 26.3, and 26.3%, respectively. Nine patients died of distant extra-adrenal metastases and another five of liver failure due to HCC. The OS at 6, 12, 24 months after RFA for AM were at 79.7, 52.6, and 32.9%, respectively.
Conclusion
Percutaneous US-guided RFA in the treatment of AM originated from HCC is feasible, safe and effective.
Background: Radiofrequency ablation (RFA) is a widely applied treatment for hepatocellular carcinoma (HCC), but insufficient RFA can promote rapid progression of the residual tumor through the hypoxia inducible factor-1a (HIF-1a)/vascular endothelial growth factor A (VEGFA) pathway. Although sorafenib has been successfully applied to advanced HCC, the use of sorafenib in residual tumor cells after RFA has rarely been tested. Purpose: To evaluate the potential role of sorafenib as an adjunct to RFA to reduce the recurrence rate after insufficient RFA. Material and Methods: Xenograft tumors of SMMC 7721 were created by subcutaneously inoculating nude mice with hepatoma cells (5 Â 10 6 cells per mouse). Fourteen days after inoculation, all mice were divided into three groups (control group [sham puncture], RFA group, and RFA combined with sorafenib treatment group) with six mice in each group. Each group was given a different treatment procedure. After treatment, the volume of the tumors was calculated from the resected specimens. The mRNA and protein expression of HIF-1a and VEGFA was quantified by real-time PCR and immunohistochemistry analysis. The micro-vessel density (MVD) was determined by CD34 immunohistochemistry. Results: Real-time PCR and immunohistochemistry analysis showed that, compared to the RFA group, HIF-1a and VEGFA expression were significantly decreased in the group that received RFA combined with sorafenib treatment (P , 0.05). By comparing the control group with the RFA group, we found that insufficient RFA promoted HIF-1a and VEGFA expression (P , 0.05). Similar results were obtained for MVD expression. Additionally, the combination of RFA with sorafenib therapy resulted in a synergistic reduction in tumor growth compared to insufficient RFA and sham puncture (P , 0.05). Conclusion: Sorafenib was able to inhibit the expression of HIF-1a and VEGFA, and sorafenib was able to increase time to recurrence when used as an adjunct to RFA.
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