Combination of Peglated-H1/HGFK1 Nanoparticles and TAE in the Treatment of Hepatocellular Carcinoma.

Transarterial embolization (TAE) constitutes the gold standard for the treatment of hepatocellular carcinoma. The effect of combination of TAE and peglated-H1/HGFK1 nanoparticles was explored on hepatocellular carcinoma. MTT and Annexin V-FITC were used to determine the cell viability and apoptosis of HepG2, ml-1, LO2, and VX2 cells after the treatment of HGFK1. Next, the orthotopic rabbit was selected to establish the in situ models of VX2 hepatocellular carcinoma. Nanoparticles were synthesized with peglated-PH1 and used to deliver HGFK1 overexpressing plasmids. MRI was performed to monitor tumor volume after being treated with TAE. The protein expression levels of CD31, CD90, and Ki67 were determined by immunohistochemistry. H&E and TUNEL staining were used to determine the necrosis and apoptosis in vivo. HGFK1 significantly inhibited the proliferation and increased the apoptosis of HepG2 and ml-1 cells (P < 0.05). MRI on 14 days after modeling suggested that the tumor showed ring enhancement. MRI on 7 days and 14 days after interventional therapy showed that tumor volume was significantly inhibited after the treatment with TAE and HGFK1 (P < 0.05). The immunohistochemical results 7 days after interventional therapy indicated that the expressions of CD31, CD90, and Ki67 were significantly lower after treatment with TAE and HGFK1 (P < 0.05). TAE and HGFK1 all extended the survival period of rabbits (P < 0.05). PH1/HGFK1 nanoparticle is an innovative and effective embolic agent, which could limit angiogenesis post-TAE treatment. The combination of TAE with PH1/HGFK1 is a promising strategy and might alter the way that surgeons manage hepatocellular carcinoma (HCC).

Automated quantitative lesion water uptake in acute stroke is a predictor of malignant cerebral edema.

OBJECTIVES: Net water uptake (NWU) has been shown to have a linear relationship with brain edema. Based on an automated-Alberta Stroke Program Early Computed Tomography Score (ASPECTS) technique, we automatically derived NWU from baseline multimodal computed tomography (CT), namely ASPECTS-NWU. We aimed to determine if ASPECTS-NWU can predict the development of malignant cerebral edema (MCE). METHODS: One hundred and forty-six patients with large-vessel occlusion were retrospectively enrolled. Quantitative NWU based on automated-ASPECTS was measured both on nonenhanced CT (NECT) and CT angiography (CTA), namely NECT-ASPECT-NWU and CTA-ASPECTS-NWU. The correlation between ASPECTS-NWU and cerebral edema (CED) grades was calculated using Spearman rank correlation. Univariate logistic regression was used to assess the effect of radiological and clinical features on MCE, and a multivariable model with significant factors from the univariate regression analysis was built. Receiver operating characteristic (ROC) was obtained and area under curve (AUC) was compared. RESULTS: CTA-ASPECTS-NWU had a moderate positive correlation with CED grades (r = 0.62; 95% confidence interval [CI], 0.51-0.71; p < 0.001). The CTA-ASPECTS-NWU performed better than the NECT-ASPECTS-NWU with AUC: 0.88 vs. 0.71 (p < 0.001). Multivariable logistic regression model integrating CTA-ASPECTS-NWU, collateral score, and age showed the CTA-ASPECTS-NWU was an independent predictor of MCE with an AUC of 0.94 (95% CI: 0.90-0.98; p < 0.001). CONCLUSIONS: This study demonstrates that ASPECTS-NWU is a quantitative predictor of MCE after large-vessel occlusion of the middle cerebral artery territory. The multivariable logistic regression model may enhance the identification of patients with MCE needing anti-edematous treatment. KEY POINTS: • The automated-ASPECTS technique can automatically detect the affected regions with early ischemic changes and NWU could be manually calculated. • The CTA-ASPECTS-NWU performs better than the NECT-ASPECTS-NWU on predicting the development of MCE. • The multivariable logistic regression model may enhance the identification of patients with MCE needing anti-edematous treatment.

Survival Response of Patients With Gastric Cancer Treated With Regional Arterial-Perfusion Chemotherapy Is Correlated With Borrmann Classification.

BACKGROUND/AIM: The aim of the present study was to correlate the survival response to regional arterial-perfusion chemotherapy (RAPC) with Borrmann classification in patients with gastric cancer. PATIENTS AND METHODS: The survival response of 270 patients with advanced gastric cancer treated with RAPC was analyzed and Borrmann classification of the tumors was retrospectively correlated to survival. RESULTS: The median survival time of RAPC-treated patients with Borrmann type I/II was 53 months compared with 19 and 12 months for those with Borrmann type III and IV, respectively (p<0.001). CONCLUSION: Borrmann classification is a potential indicator to predict prognosis of patients with advanced gastric cancer treated with RAPC.

Magnetic mesoporous embolic microspheres in transcatheter arterial chemoembolization for liver cancer.

Transcatheter arterial chemoembolization (TACE) is the main treatment for liver cancer. Although many embolic agents have been exploited in TACE, embolic agents combining embolization, drug loading, and imaging properties have not yet been constructed. Herein, we report a new magnetic mesoporous embolic microsphere that can simultaneously be loaded with doxorubicin (Dox), block vessels, and be observed by magnetic resonance imaging (MRI). The microspheres were prepared by decorating magnetic polystyrene/Fe3O4 particles with mesoporous organosilica microparticles (denoted as PS/Fe3O4@MONs). The PS/Fe3O4@MONs were uniformly spherical and large (50 µm), with a high specific surface area, uniform mesopores, and a Dox loading capacity of 460.8 µg mg-1. Dox-loaded PS/Fe3O4@MONs (PS/Fe3O4@MON@Dox) effectively inhibited liver cancer cell growth. A VX2 rabbit liver tumor model was constructed to study the efficacy of TACE with PS/Fe3O4@MON@Dox. In vivo, PS/Fe3O4@MON@Dox could be smoothly delivered through an arterial catheter to achieve chemoembolization. Moreover, PS/Fe3O4@MON@Dox and residual tumor parenchyma could be distinguished on MRI, which is of great significance for evaluating the efficacy of TACE. Histopathology showed that PS/Fe3O4@MON@Dox could be deposited in the tumor vessels, completely blocking the blood supply. Overall, PS/Fe3O4@MON@Dox showed good drug loading, embolization and imaging performance as well as potential for use in TACE. STATEMENT OF SIGNIFICANCE: Transcatheter arterial chemoembolization (TACE) is the main treatment for liver cancer. Although many embolic agents have been exploited in TACE, embolic agents combining embolization, drug-loading, and imaging properties have not yet been constructed. In this work, we prepared magnetic mesoporous microspheres as a new embolic agent that can simultaneously load doxorubicin (Dox), block blood vessels and enable magnetic resonance imaging. Overall, this new embolic microsphere-mediated TACE strategy for liver cancer showed good therapeutic effects, and the PS/Fe3O4@MON@Dox embolic microspheres provide a new avenue for improving the efficacy of TACE for liver cancer and postoperative evaluation.

Periodic mesoporous organosilica-coated magnetite nanoparticles combined with lipiodol for transcatheter arterial chemoembolization to inhibit the progression of liver cancer.

Transcatheter arterial chemoembolization (TACE) is standard locoregional therapy for hepatocellular carcinoma (HCC) that involves the injection of chemotherapeutic drugs with embolic agents into tumor tissues through intra-arterial transcatheter infusion. TACE technology using lipiodol emulsion has been most widely used in the treatment of human HCC. However, lipiodol emulsions with anticancer drugs do not stably maintain high drug concentrations at tumor sites. Herein, we developed a dual-modality imaging nanoplatform for the TACE treatment of liver cancer by integrating periodic mesoporous organosilica (PMO) with magnetite (Fe3O4) nanoparticles and Cy5.5 molecules (denoted as Fe3O4@PMO-Cy5.5). Fe3O4@PMO-Cy5.5 showed an excellent doxorubicin (Dox)-loading capacity, sensitive drug release behavior under acidic conditions, and good biocompatibility. Moreover, Cy5.5-mediated optical imaging showed that Dox-loaded Fe3O4@PMO-Cy5.5 (Fe3O4@PMO-Cy5.5-Dox) could enter liver cancer cells and effectively inhibit their growth. In addition, Fe3O4@PMO-Cy5.5-Dox was used in combination with transarterial embolization for the treatment of in situ VX2 liver tumors in rabbits. Magnetic resonance imaging (MRI) evaluation showed that Fe3O4@PMO-Cy5.5-Dox perfused through arteries was deposited into liver tumors, and Fe3O4@PMO-Cy5.5-Dox combined with lipiodol to control liver tumors yielded the optimal therapeutic effect. In addition, histological analysis showed that compared with both lipiodol embolization and traditional lipiodol combined with Dox chemoembolization, Fe3O4@PMO-Cy5.5-Dox combined with lipiodol chemoembolization induced more complete tumor tissue necrosis. In summary, these results indicate that the Fe3O4@PMO-Cy5.5-Dox platform has the potential to become an advanced tool for the transarterial treatment of unresectable liver cancer.

ß-Catenin Expression Correlates With Prognosis in Hepatocellular Carcinoma Patients Treated With Transcatheter Arterial Chemoembolization.

BACKGROUND/AIM: Transcatheter arterial chemoembolization (TACE) is one of the most widely used palliative therapies for the unresectable hepatocellular carcinoma (HCC). However, a large difference is found in prognosis among patients treated with TACE. The aim of the present study was to investigate the prognostic value of ß-catenin in HCC patients treated with TACE. MATERIALS AND METHODS: Seventy patients with HCC were included in this study. Expression of ß-catenin was determined by immunohistochemistry in biopsy samples taken before TACE. The patients were treated with TACE and followed-up. Clinicopathological parameters, progression-free survival (PFS) and overall survival (OS) were evaluated to analyze the association of ß-catenin expression with prognosis for HCC patients after TACE. RESULTS: HCC patient biopsies exhibited a significantly higher positive rate of ß-catenin expression (72.86%) compared to paracancer normal tissues (19.44%) (p<0.01). ß-Catenin expression was closely correlated with tumor differentiation, tumor size, serum α-fetoprotein (AFP) level and TACE treatment frequency (all p<0.05). Patients with negative ß-catenin expression had longer PFS and OS after TACE compared to those with positive ß-catenin expression (PFS: 44.2 vs. 14.1 months, p=0.004; OS: 56.4 vs. 35.9 months, p<0.001). Multivariate Cox regression analysis indicated that ß-catenin expression in HCC patients treated with TACE was an independent prognostic factor for higher PFS and OS. CONCLUSION: The HCC patients with increased ß-catenin expression have a poor prognosis with lower survival rate.