Transarterial Chemoembolization (TACE) Combined with Lenvatinib versus TACE Alone in Intermediate-Stage Hepatocellular Carcinoma Patients Beyond Up-To-Seven Criteria: A Retrospective, Propensity Score-Matched Analysis.

RATIONALE AND OBJECTIVES: To compare the treatment efficacy and safety of transarterial chemoembolization (TACE) combined with lenvatinib versus TACE alone in patients with intermediate-stage hepatocellular carcinoma (HCC) beyond up-to-seven criteria. MATERIALS AND METHODS: A total of 107 newly diagnosed HCC patients with Barcelona Clinic Liver Cancer stage B HCC beyond up-to-seven criteria were included in this retrospective cohort study. These patients were divided into two groups: TACE-Lenv group and TACE alone group. Propensity score matching was used to account for potential confounding factors. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), downstaging rate, liver function, and adverse events (AEs) were recorded and evaluated. RESULTS: Both the median OS and median PFS were significantly longer in the TACE-Lenv group compared to the TACE alone group (median OS: 28.0 vs 12.0 months, P = 0.017; median PFS [mRECIST]: 8.2 vs 3.7 months, P = 0.018; median PFS [RECIST v1.1]: 8.9 vs 3.7 months, P = 0.003). Furthermore, the ORR and DCR were also significantly higher in TACE-Lenv group (ORR: 94% [30/32] vs 47% [15/32], P < 0.001; DCR: 97% [31/32] vs 62% [20/32], P < 0.001). There were no significant differences in terms of liver function and grade 3 or 4 AEs rate between two groups. CONCLUSION: The combination of TACE and lenvatinib provides clinical benefits for patients with intermediate HCC beyond the up-to-seven criteria, has an acceptable safety profile, shows a trend towards improving liver function, and does not increase the occurrence of grade 3-4 AEs. KEY POINTS: The efficacy of transarterial chemoembolization in intermediate-stage hepatocellular carcinoma patients is partially unsatisfactory. Addition of lenvatinib to transarterial chemoembolization improves OS, PFS, ORR, and DCR for patients with intermediate-stage hepatocellular carcinoma beyond the up-to-seven criteria. This combination therapy is a superior treatment option for intermediate-stage hepatocellular carcinoma patients with high tumor burden.

Double Carbon Networks Reinforce the Thermal Storage and Thermal Transfer Properties of 1-Octadecanol Phase Change Materials.

Using thermal storage materials with excellent thermal properties in the energy utilization system enables efficient use of renewable energy sources. Organic phase change materials (PCMs) have the advantages of high heat storage density, no corrosion, and low cost, but low thermal conductivity and insufficient heat transfer capacity have always been the bottlenecks in their application. In this paper, melamine foam@ reduction graphene oxide (MF@rGO) and carbon foam@ reduction graphene oxide (CF@rGO) composite foams with double carbon networks were prepared by self-assembly method and further employed in 1-octadecinal (OD) PCMs. The microstructure, chemical composition, phase change behavior, thermal conductivity, and photothermal conversion performance of MF@rGO/OD and CF@rGO/OD were studied in detail using SEM, FTIR, Raman DSC, and LFA. The melting and solidification enthalpies of CF@rGO/OD composite PCMs were 208.3 J/g and 191.4 J/g, respectively, its thermal conductivity increased to 1.54 W/m·K, which is 6.42 times that of pure OD. The porous structure and high thermal conductivity of the double carbon network substantially enhance the efficiency of energy storage and release in composite PCMs. CF@rGO/OD composite PCMs have excellent heat storage performance and heat transfer capacity, and a wide range of application prospects in the fields of low-temperature solar heat storage, precision instrument temperature control, and intelligent buildings.

Rare-earth hydroxide/MXene hybrid: a promising agent for near-infrared photothermy and magnetic resonance imaging.

Layered gadolinium hydroxide (LGdH) and Ti3C2 monolayers were assembled into a LGdH/Ti3C2 (GTC) hybrid. The hybrid demonstrated enhanced near-infrared (NIR) light absorption properties and superior photothermal performance. Moreover, the GTC hybrid achieved an excellent T1-weighted magnetic resonance imaging (MRI) effect.

Tb3+/Sm3+ co-doped double perovskite: synthesis, exfoliation and luminescence properties.

Tb3+/Sm3+ co-doped double perovskite K[K1.5(Tb1-xSmx)0.5]Ta3O10 (denoted as KKT1-xSxTO) was prepared, which exhibited typical Tb3+ and Sm3+ photoluminescence emissions and tunable colours. After protonation and subsequent exfoliation processes, unilaminar KT1-xSxTO nanosheets with a lateral size of ∼300 nm and thickness of ∼2.7 nm were obtained.

Synthesis of Fluorinated Imidazole[4,5f][1,10]phenanthroline Derivatives as Potential Inhibitors of Liver Cancer Cell Proliferation by Inducing Apoptosis via DNA Damage.

Phenanthroline derivatives containing fluorinated imidazole ring are effective anti-neoplastic agents. Herein, a series of four fluorinated imidazole[4,5f][1,10]phenanthroline derivatives were synthesized and investigated as potential inhibitors to fight against the growth of liver cancer cells. The in vitro antitumor activity of targeted compounds have been evaluated by using MTT assay, and results showed that compound 4 (2-(2,3-difluorophenyl)-1H-imidazo[4,5-f][1,10]phenanthroline) exhibited excellent inhibitory effect against the growth of various tumor cells, particularly for HepG2 cells, with IC50 value of approximately 0.29 µM. This result has been further confirmed by colony formation assay, showing that compound 4 suppressed the proliferation of HepG2 cells. Moreover, cell apoptosis (AO/PI dual staining and flow cytometry) analyses as well as comet assay showed that compound 4 may induce apoptosis of HepG2 cells through triggering DNA damage. Furthermore, the in vivo anti-tumor activity were evaluated on zebrafish bearing HepG2 cells showed that compound 4 can observably block the growth of liver cancer cells. All in together, these compounds, particularly compound 4, may be developed as a potential agent to treat liver cancer in the future.

General Synthesis of Layered Rare-Earth Hydroxides (RE = Sm, Eu, Gd, Tb, Dy, Ho, Er, Y) and Direct Exfoliation into Monolayer Nanosheets with High Color Purity.

Layered rare-earth hydroxides (LREHs) are promising optical and magnetic materials, while it is hard to obtain monolayer nanosheets through a direct exfoliation. In this study, organic dodecyl sulfate (C12H25SO4-, DS-) was used to prepare LREHs. In-plane lattice parameters of the LREHs decreased from Sm3+ to Er3+, correlating well with the monotonically decreasing ionic radius. Conversely, the interlayer spacing slightly increased with the increase of host layer charge density and corresponding intercalated DS- contents. By a direct sonication of the LREHs in formamide, nanosheets were obtained with a thickness of ∼1 nm and size of ∼500 nm. Compared to the bulk crystals, exfoliation resulted in a slight elongation of in-plane lattice constants and a more asymmetric coordination environment. The suspension of europium hydroxide nanosheets exhibited a remarkably high red-light emission purity (91.4%). This work demonstrated an important strategy toward an efficient synthesis of well-defined LREH nanosheets with high color purity.

Aspirin-induced long-term tumor remission in hepatocellular carcinoma with adenomatous polyposis coli stop-gain mutation: A case report.

BACKGROUND: Targeted therapy based on pathway analysis of hepatitis B-related hepatocellular carcinoma (HCC) may be a promising remedy. CASE SUMMARY: The present case involved an advanced hepatocellular carcinoma (HCC) patient who did not receive local regional therapy and was intolerant to sorafenib. Total RNA extracted from the patient's tumor tissue was used to obtain the gene mutation profile. The c.3676A>T and c.4402A>T stop-gain mutations in adenomatous polyposis coli (APC) were the most prevalent (42.2% and 35.1%, respectively). MutationMapper analysis indicated that the functional domain of APC was lost in the two APC mutant genes. APC is a major suppressor of the Wnt signaling pathway. Thus, the Wnt pathway was exclusively activated due to APC dysfunction, as other elements of this pathway were not found to be mutated. Aspirin has been reported to suppress the Wnt pathway by inducing ß-catenin phosphorylation through the activation of glycogen synthase kinase 3 beta via cyclooxygenase-2 pathway inhibition. Therefore, aspirin was administered to the patient, which achieved four years of disease control. CONCLUSION: Exclusive mutations of APC of all the Wnt pathway elements could be a therapeutic target in HCC, with aspirin as an effective treatment option.

Neutrophil-to-Apolipoprotein A1 Ratio Predicted Overall Survival in Hepatocellular Carcinoma Receiving Transarterial Chemoembolization.

PURPOSE: The purpose of this study was to investigate the predictive capability of neutrophil-to-apolipoprotein A1 ratio (NAR) for predicting overall survival (OS) among patients with hepatocellular carcinoma (HCC) receiving transarterial chemoembolization (TACE). PATIENTS AND METHODS: We investigated the clinical features of 554 patients with HCC receiving TACE and assessed NAR's predictive value for OS with 222 patients (the discovery cohort) and 332 patients (the validation cohort). The association of NAR with circulation lectin-type oxidized low-density lipoprotein receptor-1-positive (LOX-1+ ) polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) was illustrated. RESULTS: Multivariate Cox regression revealed that lymphocyte count; Tumor, Node, Metastasis (TNM) stage; and NAR were independent prognostic factors in the discovery cohort. The validation cohort confirmed the independent prognostic value of TNM stage and NAR. Patients with low NAR (<2.7) displayed significantly increased OS in the discovery cohort (59.8 months vs. 21 months), the validation group (38.0 months vs. 23.6 months), and the total cohort (44.1 months vs. 22.0 months). A Cox proportional hazards model was used to combine Cancer of the Liver Italian Program (CLIP) score with discretized NAR. C-index illustrated that NAR-integrated CLIP score was the best model compared with NAR and CLIP score. Furthermore, NAR-CLIP presented superior predictive capacity for 10-, 20-, 30-, 40-, 50-, and 60-month survival compared with CLIP score by survival receiver-operator characteristic analysis in the discovery cohort, validation cohort, and total cohort. NAR was significantly associated with LOX-1+ PMN-MDSCs by linear regression. CONCLUSION: This study identified NAR as an independent predictor for OS among patients with HCC receiving TACE. NAR reflected circulation LOX-1+ PMN-MDSC level. IMPLICATIONS FOR PRACTICE: The present study identified neutrophil-to-apolipoprotein A1 ratio (NAR) as an independent predictor for overall survival among patients with hepatocellular carcinoma receiving transarterial chemoembolization. NAR reflected circulation level of lectin-type oxidized low-density lipoprotein receptor-1-positive polymorphonuclear myeloid-derived suppressor cells.

Superlattice films of semiconducting oxide and rare-earth hydroxide nanosheets for tunable and efficient photoluminescent energy transfer.

Europium and terbium doped layered gadolinium hydroxides were prepared by microwave assisted hydrothermal precipitation. They were subsequently exfoliated into nanosheets by sonication treatment in formamide. The thickness of the nanosheets (LGdH:Eu and LGdH:Tb) was found to be approximately 1 nm, exemplifying a single-layer feature. Multilayer and superlattice films were prepared through layer-by-layer (LbL) deposition of exfoliated hydroxide nanosheets with a polyanionic electrolyte (polystyrene sulfonate, PSS) and heteroassembly with semiconducting oxide nanosheets (Ti0.87O20.52- and TaO3-), respectively. Compared to the multilayers of (LGdH:Eu/PSS)n and (LGdH:Tb/PSS)n, the superlattices of (LGdH:Eu/Ti0.87O20.52-)n and (LGdH:Tb/TaO3-)n exhibited significantly enhanced photoluminescence intensity, ∼14 times and ∼5 times, respectively. The photoenergy absorbed by the semiconducting nanosheets can be transferred to the excited states of rare-earth hydroxide nanosheets for enhanced photoluminescence emission. Further investigation on the stacking sequence of the nanosheets revealed that direct neighboring and energy level matching with semiconducting nanosheets was essential for realizing efficient energy transfer across the nanosheet interface. Annealing at 600 °C could further enhance the emission intensity of the superlattice structured films. The current work demonstrates an important strategy for hetero-assembling nanosheets at the molecular level with a carefully designed interface for tunable and enhanced functionalities.

Thymic lymphoid hyperplasia with Graves' disease in a 28-year-old female: a case report.

Thymic lymphoid hyperplasia with Graves' disease (GD) is not uncommon in adults. Generally, cases are newly diagnosed with GD when they refer to the department of endocrinology in hospital, and an anterior mediastinal mass is found on a computed tomography scan by accident. Almost half of them receive thymectomy due to the concern about thymoma or thymic carcinoma. In the past literature, an enlarged thymus can gradually shrink after treatment of antithyroid drugs. In this paper, a 28-year-old woman presented to our hospital with a 11-month history of dizziness, left hand convulsion and paralysis, without chest pain, difficulty swallowing, dyspnea. Chest computed tomography revealed an anterior mediastinal mass without obvious nodules. However, in this case, the mass did not shrink obviously after regularly taking antithyroid drugs. In order to figure out the diagnosis of the mass, we performed a thoracoscopic thymic resection, and the pathologic result was thymic lymphoid hyperplasia. There is no thymus gland tissue left on a repeated CT scan four months later after surgery. In this report, we discuss the optimal therapeutic strategy for this rare case. In conclusion, if an anterior mediastinal mass in GD patients did not shrink obviously upon treatment of antithyroid drugs, minimally invasive surgery should be taken into consideration seriously to exclude the possibility of malignancy.

Exosome-mediated miRNA delivery promotes liver cancer EMT and metastasis.

The deregulation of exosomal microRNAs (miRNAs) plays an important role in the progression of hepatocarcinogenesis. In this study, we highlight exosomes as mediators involved in modulating miRNA profiles in liver cancer cells after induction of the epithelial-mesenchymal transition (EMT) and metastasis. Initially, we induced EMT in a hepatocellular carcinoma cell (HCC) line (Hep3B) by stimulation with transforming growth factor-ß (TGF-ß) and confirmed by western blot detection of EMT markers such as vimentin and E-cadherin. Exosomes were then isolated from the cells and identified by nanoparticle tracking analysis (NTA). The isolated exosomal particles from unstimulated Hep3B cells (Hep3B exo) or TGF-ß-stimulated EMT Hep3B cells (EMT-Hep3B exo) contained higher levels of exosome marker proteins, CD63 and TSG101. After incubation with EMT-Hep3B exo, Hep3B cell proliferation increased. EMT-Hep3B exo promoted the migration and invasion of Hep3B and 7721 cells. High-throughput sequencing of miRNAs and mRNA within the exosomes showed 119 upregulated and 186 downregulated miRNAs and 156 upregulated and 166 downregulated mRNA sequences in the EMT-Hep3B exo compared with the control Hep3B exo. The most differentially expressed miRNAs and target mRNA sequences were validated by RT-qPCR. Based on the known miRNA targets for specific mRNA sequences, we hypothesized that GADD45A was regulated by miR-374a-5p. Inhibition of miR-374a-5p in Hep3B cells resulted in exosomes that inhibited the proliferation, migration, and invasion of HCC cells. These results enhance our understanding of metastatic progression of liver cancer and provide a foundation for the future development of potential biomarkers for diagnosis and prognosis of hepatic cancer.

2D Layered Double Hydroxide Nanosheets and Their Derivatives Toward Efficient Oxygen Evolution Reaction.

Layered double hydroxides (LDHs) have attracted tremendous research interest in widely spreading applications. Most notably, transition-metal-bearing LDHs are expected to serve as highly active electrocatalysts for oxygen evolution reaction (OER) due to their layered structure combined with versatile compositions. Furthermore, reducing the thickness of platelet LDH crystals to nanometer or even molecular scale via cleavage or delamination provides an important clue to enhance the activity. In this review, recent progresses on rational design of LDH nanosheets are reviewed, including direct synthesis via traditional coprecipitation, homogeneous precipitation, and newly developed topochemical oxidation as well as chemical exfoliation of parent LDH crystals. In addition, diverse strategies are introduced to modulate their electrochemical activity by tuning the composition of host metal cations and intercalated counter-anions, and incorporating dopants, cavities, and single atoms. In particular, hybridizing LDHs with conductive components or in situ growing them on conductive substrates to produce freestanding electrodes can further enhance their intrinsic catalytic activity. A brief discussion on future research directions and prospects is also summarized.

Recurrent transmural tracheal schwannoma resected by video-assisted thoracoscopic window resection: A case report.

RATIONALE: Primary schwannoma is extremely rare in the trachea, and its optimal treatment has not yet been established. Previous literature have indicated that traditional resection by thoracotomy is an effective surgical procedure but with huge trauma, and endoscopic excision is a minimally invasive surgical method but with possibility of recurrence. Window resection was usually utilized for selected patients with trachea invasion by thyroid carcinoma, but video-assisted thoracoscopic window resection for trachea schwannoma has not been reported previously. PATIENT CONCERNS: A 23-year-old woman was admitted to hospital due to dyspnea, coughing and wheezing that had persisted for 2 months with aggravation for 1 week. DIAGNOSES: Chest computed tomography (CT) scan revealed a well-circumscribed soft-tissue mass located on the right lateral posterior wall of the trachea. Bronchofibroscopy (BFS) showed a whitish, smooth and round mass with a wide base in the trachea. Immunohistochemical staining demonstrated cells labeled with Vim (+), S-100 (+), SOX-10 (+), SMA (-), CK (-). Histopathological examinations showed that the mass was a schwannoma. INTERVENTIONS: The tumor was nearly completely excised via BFS, but relapsed 2 times at 12 days and 3 weeks after endoscopic resection. Finally, the patient underwent video-assisted thoracoscopic window resection of trachea. OUTCOMES: The patient recovered rapidly and no recurrence was observed over 6 months of follow-up. LESSONS: The treatment of tracheal schwannoma depends on the characteristics of tumor and the condition of patient. Surgical resection is a preferred alternative for sessile or transmural tumors and recurrence after endoscopic excision. Tracheal window resection by video-assisted thoracoscopy is beneficial for some appropriate patients with a small and sessile tumor.

LncRNA DLEU2 aggravates the progression of hepatocellular carcinoma through binding to EZH2.

To explore whether lncRNA deleted in lymphocytic leukemia 2 (DLEU2) could accelerate the migratory, invasive and proliferative abilities, thus influencing the progression of HCC. DLEU2 level in HCC tissues and adjacent normal tissues was firstly determined. Its level in HCC tissues with different tumor sizes (≤ 5 cm or > 5 cm), different tumor stages (stage I-II or III-IV) and either with vascular invasion or not was determined. Potential influences of DLEU2 on proliferative, migratory and invasive abilities of SMMC7721 and HCLM3 cells were assessed. The interaction between DLUE2 and enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) was evaluated by RNA Binding Protein Immunoprecipitation (RIP) assay. Finally, the effect of DLEU2/EZH2 regulatory loop on proliferative ability of HCC cells was detected. DLEU2 was upregulated in HCC tissues, especially in those larger than 5 cm in tumor size, accompanied with vascular invasion and in worse tumor stage. Knockdown of DLEU2 attenuated proliferative, migratory and invasive abilities of SMMC7721 and HCLM3 cells. RIP assay proved that DLEU2 could interact with EZH2. Knockdown of EZH2 attenuated the inhibited proliferation in HCC cells with DLEU2 knockdown. DLEU2 accelerates the proliferative, migratory and invasive abilities of HCC cells via binding to EZH2, thus aggravating the progression of HCC.

Long noncoding RNA LINC00511 promotes cell growth and invasion in triple-negative breast cancer by interacting with Snail.

Purpose: Aberrant long noncoding RNA expression has been frequently reported in cancer research, including in triple-negative breast cancer (TNBC). The aim of the present study was to investigate the involvement of LINC00511 in the progression and prognosis of TNBC. Materials and methods: The expression level of LINC00511 was examined by RT-PCR in TNBC tissues and in cell lines. MTT and colony formation assays were used to examine the cell growth ability. A Boyden assay was used to examine the cell invasion ability. RNA pull-down and RNA immunoprecipitation (RIP) assays were used to examine the proteins that interacted with LINC00511. Results: We demonstrated that the LINC00511 expression level was elevated in TNBC tissues when compared with that in normal breast tissues. The downregulation of LINC00511 decreased TNBC cell growth and invasion compared to those of the controls. To explore the molecular mechanisms underlying the biological activity of LINC00511, we identified proteins that bound to LINC00511 with RNA pull-down experiments. We showed that LINC00511 binds to the ß-transducin repeat containing (BTRC) E3 ubiquitin protein. Mechanistically, LINC00511 maintained the stability of Snail by impeding its ubiquitination and degradation by the BTRC E3 ubiquitin protein. Conclusion: Our data suggested that LINC00511 might serve as a novel molecular target for the treatment of TNBC.

Safety and efficacy of 125I brachytherapy for bilateral lung recurrences from hepatocellular carcinoma after resection or ablation.

PURPOSE: To evaluate the safety and efficacy of 125I brachytherapy to treat bilateral lung recurrences from hepatocellular carcinoma (HCC) after resection or ablation. MATERIALS AND METHODS: We retrospectively recruited 95 patients with bilateral lung recurrences from hepatocellular carcinoma (HCC) after resection or ablation who had received 3-6-month sorafenib with or without stereotactic body radiotherapy (SBRT), from October 2011 to January 2015; patients were then randomly divided into two groups, 44 patients received computed tomography (CT)-guided 125I brachytherapy (group A), and 51 patients were treated with supportive and symptomatic treatments (group B). RESULTS: The median survival time was 19 months (range of 3-36 months). The local response rate (LRR) at 3, 6, 12, 18, 24, 30 and 36 months in group A was 81.8%, 65.9%, 59.1%, 45.0%, 38.6%, 22.7%, 11.4%, respectively, and 64.7%, 47.1%, 33.3%, 25.4%, 15.7%, 11.7%, 7.8%, respectively, in group B (P < 0.05). The mean progression-free survival time (PFST) and overall survival (OS) of group A were significantly longer than those of group B. Alpha fetoprotein (AFP) and tumor size were independent factors that affected the PFST and OS, normal AFP levels and less than 1-cm tumor diameter had better PFST and OS (P < 0.05). No massive bleeding or serious complications occurred. CONCLUSION: CT-guided 125I brachytherapy is safe and effective for the treatment of bilateral lung recurrences from HCC after resection or ablation.

A flexible and conductive metallic paper-based current collector with energy storage capability in supercapacitor electrodes.

The development of flexible current collectors as an indispensable component in energy storage devices has been in strong demand for the ever-growing market of flexible and wearable electronics. Herein, flexible and conductive paper-based current collectors are fabricated by directly depositing a metallic Ni layer composed of spiny Ni nanospheres of 400 nm diameter on the surface of filter paper via electroless deposition. The metallic paper shows excellent electric and mechanical properties: the sheet resistance is 2.7 Ω cm-2 (R0 = 0.8 Ω cm-2) after 5000 bending cycles and the mass density is only 0.35 g cm-3. MnO2 is selected as an electrode active material to explore the role of flexible and conductive paper-based current collectors in supercapacitors. Electrochemical results reveal that the largest areal specific capacitance is 1095 mF cm-2 at 1 mA cm-2 and the excellent electrochemical performance can be attributed to the hierarchical porous fibre structure of paper and the lower contact resistance between the active material and the current collector. Note that the approach can be applied to an enlarged size of metallic conductive paper or textile, presenting a simple and feasible method to fabricate flexible current collectors in a large scale.

Chiral ruthenium(II) complex Δ-[Ru(bpy)2(o-FMPIP)] (bpy = bipyridine, o-FMPIP = 2-(2'-trifluoromethyphenyl) imidazo[4,5-f][1,10]phenanthroline) as potential apoptosis inducer via DNA damage.

Chiral ruthenium(II) complexes have long been considered as potential anticancer agents. Herein, in vivo inhibitory activity of a chiral ruthenium(II) complex coordinated by ligand 2-(2'-trifluoromethyphenyl) imidazo [4,5-f][1,10]phenanthroline, Δ-[Ru(bpy)2(o-FMPIP)] (D0402) on Kunming(KM) mice bearing tumor (H22 hepatic cancer) has been evaluated, and the results showed that the tumor weight of mice treated with 0.22 mg/(kg·day) D0402 via i.v. administration for 7 days decreased about 31.79% compared to the control group, while the body weight, as well as the thymus, spleen, liver, lung, and kidney indices of mice treated with D0402 observed almost no loss compared to the control group. Furthermore, the mechanism studies on anti-angiogenic showed that D0402 could inhibit the formation of angiogenesis in the transgenic Tg(fli1a: EGFP) zebrafish. After treated with D0402, the sub-intestinal vessels(SIVs) of the zebrafish became disordered and chaotic, and was dosage dependent. Moreover, the TUNEL analysis and comet assays revealed that D0402 can induce apoptosis of HepG2 cell through DNA damage, and this was further demonstrated by immunofluorescence analysis with the number of γ-H2AX increased following the increasing amount of D0402. Besides, in vivo toxicity of D0402 has also been investigated on the development of zebrafish embryo, and the results showed that there were no death or development delay occurred for zebrafish embryo treated with D0402 up to concentration of 60 µM. All in together, this study suggested that D0402 can be developed as a potential inhibitor against liver cancer through co-junction of anti-angiogenesis and apoptosis-inducing via DNA damage in the near future.

Transarterial chemoembolization with pirarubicin-eluting microspheres in patients with unresectable hepatocellular carcinoma: Preliminary results.

PURPOSE: To present the early results of pirarubicin-eluting microsphere transarterial chemoembolization (PE-TACE) for patients with unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: We retrospectively analyzed 55 consecutive patients with HCC who received PE-TACE between April 1, 2015 and August 30, 2016. The complication rate, tumor response rate, progression-free survival (PFS), and overall survival (OS) were analyzed. RESULTS: Adverse events were generally mild and included abdominal pain and fever, although a major complication was reported in 1 patient (1.8%). During a median follow-up of 10.0 months (range, 3.0-24.0 months), 14 patients (25.5%) achieved a complete tumor response, 25 (45.5%) had a partial response, 9 (16.4%) showed stable disease, and 7 (12.7%) had disease progression. The 1-month overall response rate was 70.9%, and the local tumor response rate was 89.0%. The 1-month tumor response rate was 100% for Barcelona Clinic Liver Cancer (BCLC) stage A or B disease and 62.8% for BCLC stage C disease. The median PFS was 6.1 months (95% confidence interval [95%CI], 3.4-8.8 months; range, 1.0-24.0 months). The median OS was 11.0 months (95%CI, 7.1-14.9 months; range, 2.0-24.0 months). Kaplan-Meier analysis (log-rank test) found significant differences in OS between patients grouped by tumor number (P = 0.006), tumor size (P = 0.035), and Eastern Cooperative Oncology Group (ECOG) score (P = 0.005). The tumor number (1 vs. ≥2) was the only factor independently associated with OS (hazard ratio [HR], 2.867; 95%CI, 1.330-6.181; P = 0.007). CONCLUSIONS: PE-TACE for unresectable HCC may be safe, with favorable tumor response rates and survival time, especially in patients with a single large tumor. Longer follow-up using a larger series is necessary to confirm these preliminary results.

Albumin-to-Alkaline Phosphatase Ratio as an Independent Prognostic Factor for Overall Survival of Advanced Hepatocellular Carcinoma Patients without Receiving Standard Anti-Cancer Therapies.

Background Albumin-to-Alkaline Phosphatase Ratio (ALB/ALP ratio, AAPR), a newly developed index of liver function, has been rarely discussed about its prognostic value in malignancies. The current study attempted to evaluate the prognostic prediction of AAPR in advanced HCC. Methods 237 advanced HCC patients who refused any standard anti-cancer therapies were retrospectively analyzed. The threshold value of AAPR was determined by receiver operating characteristic (ROC) curve. Univariate analyses using Kaplan-Meier method and log-rank test, and multivariate analysis using Cox proportional hazards regression model were conducted. Comparisons of ROC curves and likelihood ratio test (LRT) were utilized to compare the value of different factors in predicting survival. Results ROC curve analysis confirmed 0.38 as the optimal cutoff value of AAPR in evaluating overall survival (OS). Patients with an AAPR > 0.38 exhibited significantly lower frequencies of ascites, portal vein tumor thrombus, Child-Pugh grade B & C, and KPS < 70 (all P < 0.05). These patients also displayed a longer median survival time than those with an AAPR ≤ 0.38 (5.8 m vs 2.4 m, P < 0.01). Univariate and multivariate analyses identified AAPR as an independent prognostic indicator (HR = 0.592, P = 0.007). Furthermore, we integrated AAPR with TNM system and found that area under curve of AAPR-TNM system was significantly larger than that of TNM system when predicting 3-month survival (0.670 vs 0.611, P < 0.01). Moreover, LRT indicated that AAPR-TNM system had a significantly larger χ2 (26.4 vs 16.4, P < 0.01) and a significantly smaller Akaike information criterion value (1936 vs 1948, P < 0.01) comparing with TNM system. Conclusions Our study implied that AAPR was a potentially valuable prognostic index for advanced HCC patients without receiving any standard anti-cancer therapies. AAPR-TNM system preceded TNM system in predicting overall survival in this study.