IL-12 inhibits postoperative residual tumor growth in murine models of sarcoma and renal carcinoma.

Surgical tumor removing is the most common procedure after a confirmed cancer diagnosis with no detected metastasis. Surgery can reduce tumor burden and address pathologic changes caused by local compression of tissues by the tumor. This lowers the chances of tumor cell spreading and creates more favorable conditions for further treatment. However, not all tumor cells can be eliminated through surgery. Even in the early stages of the disease, tumor cells often metastasize and cannot be identified by current detection methods. These tiny, disseminated tumors are often the cause of tumor recurrence. There is currently a lack of effective treatment options that can completely prevent tumor recurrence after surgery. To simulate the actual clinical situation, we selected murine-derived tumor cell lines S180 and Kcc853 to establish a post-transplantation residual tumor model in mice. Surgery was performed on mice inoculated with tumors. Tumor tissue was partially excised to set up the postsurgical residual tumor models. The model simulated the clinical situation where tumor cells were not completely eliminated or there were small tumors that had metastasized before surgery. IL-12 was injected to observe its effect on residual tumors or metastatic microtumors. The administration of IL-12 after surgery can significantly inhibit the growth of residual tumors and metastasis, improve the postoperative tumor-free rate and address the problem of tumor recurrence caused by the growth of residual tumors and micro-metastasis. Therefore, the use of IL-12 antitumor cytokine combined with surgery can effectively inhibit tumor recurrence. Low-dose IL-12 (1-10 ng/kg in humans) can inhibit residual tumor growth.

Enhancing Roxarsone Degradation and In Situ Arsenic Immobilization Using a Sulfate-Mediated Bioelectrochemical System.

Roxarsone (ROX) is widely used in animal farms, thereby producing organoarsenic-bearing manure/wastewater. ROX cannot be completely degraded and nor can its arsenical metabolites be effectively immobilized during anaerobic digestion, potentially causing arsenic contamination upon discharge to the environment. Herein, we designed and tested a sulfate-mediated bioelectrochemical system (BES) to enhance ROX degradation and in situ immobilization of the released inorganic arsenic. Using our BES (0.5 V voltage and 350 µM sulfate), ROX and its metabolite, 4-hydroxy-3-amino-phenylarsonic acid (HAPA), were completely degraded within 13-22 days. In contrast, the degradation efficiency of ROX and HAPA was <85% during 32-day anaerobic digestion. In a sulfate-mediated BES, 75.0-83.2% of the total arsenic was immobilized in the sludge, significantly more compared to the anaerobic digestion (34.1-57.3%). Our results demonstrate that the combination of sulfate amendment and voltage application exerted a synergetic effect on enhancing HAPA degradation and sulfide-driven arsenic precipitation. This finding was further verified using real swine wastewater. A double-cell BES experiment indicated that As(V) and sulfate were transported from the anode to the cathode chamber and coprecipitated as crystalline alacranite in the cathode chamber. These findings suggest that the sulfate-mediated BES is a promising technique for enhanced arsenic decontamination of organoarsenic-bearing manure/wastewater.

Effects of Sludge Retention Time on the Performance of Anaerobic Ceramic Membrane Bioreactor Treating High-Strength Phenol Wastewater.

Anaerobic ceramic membrane bioreactor (AnCMBR) is an attractive alternative for the treatment of high-strength phenol wastewater, but the effects of sludge retention time (SRT) on the performance and membrane fouling are still unclear. The results indicated that the AnCMBR was successfully employed to treat high-strength wastewater containing 5 g phenol L-1. The removal efficiencies of phenol and chemical oxygen demand (COD) reached over 99.5% and 99%, respectively, with long SRT and short SRT. SRT had no obvious effect on the performance of the AnCMBR treating high-strength phenol wastewater with long time operation. The strong performance robustness of AnCMBR benefited from the enrichment of hydrogenotrophic methanogens and syntrophic phenol-degrading bacteria. However, the decline of SRT led to a more severe membrane fouling in the AnCMBR, which was caused by the small size of sludge flocs and high concentration of protein in the biopolymers. Therefore, this work presented a comprehensive insight to the feasibility and robustness of the AnCMBR for treating high-strength phenol wastewater.

Synthesis, biological evaluation, and physicochemical property assessment of 4-substituted 2-phenylaminoquinazolines as Mer tyrosine kinase inhibitors.

Current results identified 4-substituted 2-phenylaminoquinazoline compounds as novel Mer tyrosine kinase (Mer TK) inhibitors with a new scaffold. Twenty-one 2,4-disubstituted quinazolines (series 4-7) were designed, synthesized, and evaluated against Mer TK and a panel of human tumor cell lines aimed at exploring new Mer TK inhibitors as novel potential antitumor agents. A new lead, 4b, was discovered with a good balance between high potency (IC50 0.68µM) in the Mer TK assay and antiproliferative activity against MV4-11 (GI50 8.54µM), as well as other human tumor cell lines (GI50<20µM), and a desirable druglike property profile with low logP value (2.54) and high aqueous solubility (95.6µg/mL). Molecular modeling elucidated an expected binding mode of 4b with Mer TK and necessary interactions between them, thus supporting the hypothesis that Mer TK might be a biologic target of this kind of new active compound.

Prognostic value of angiopoietin-2 in non-small cell lung cancer patients: a meta-analysis.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the most frequent cause of cancer deaths worldwide. The targeted therapy had made important progress in recent years, but few potential predictive biomarkers for prognosis of NSCLC patients were identified. Angiopoietin-2 (Ang-2), a cytokine upregulated in tumor endothelial cells and some tumor cells including NSCLC, is a partial agonist and antagonist of angiopoietin-1 (Ang-1). Ang-1 is another ligand for the tyrosine kinase receptor Tie2; it promotes recruitment of pericytes and smooth muscle cells, stabilizing vascular networks by binding to Tie2. Although many studies mainly considered that Ang-2 correlated with progression and prognosis of NSCLC significantly, there are much conflicting and controversial data. Therefore, we conducted a meta-analysis to assess the relationship between Ang-2 and prognosis, a clinical outcome of NSCLC. METHODS: The search was based on major databases from PubMed, Cochrane Library, EMBASE, and CNKI, and 20 eligible publications (range from 2002 to 2015) are included in our meta-analysis with 2011 NSCLC patients in total. These studies illuminated the correlation between the expression of Ang-2 and NSCLC, based on either prognostic factors or clinicopathological features. Pooled calculations were carried out on the odds ratio (OR) and the corresponding 95 % confidence interval (CI) to perform this meta-analysis, and all statistical analyses were carried out by STATA 12.0 and Review Manager 5.3. RESULTS: According to our results, the expression of Ang-2 in NSCLC tissues was significantly higher than that in normal lung tissues, indicating that Ang-2 over-expression may be a predictive marker (pooled OR = 5.09, corresponding 95 % confidence interval (95 % CI) 3.10-8.36, p = 0.000). In addition, our pooled data showed that Ang-2 expression was positively correlated with tumor stages (pooled OR = 3.58, 95 % CI 2.40-5.35, p = 0.000), differentiation (pooled OR = 0.65, 95 % CI 0.45-0.94, p = 0.02), lymphatic invasion (pooled OR = 3.15, 95 % CI 1.97-5.03, p = 0.000), and poor survival (pooled OR = 1.93, 95 % CI 1.47-2.52, p = 0.000) of NSCLC, but seems to have no significant impact on tumor size (pooled OR = 1.09, 95 % CI 0.59-2.00, p = 0.78). CONCLUSIONS: These results demonstrate that Ang-2 expression significantly correlated with poor prognosis for patients with NSCLC.

Validation and application of an analytical method for the determination of selected acidic pharmaceuticals and estrogenic hormones in wastewater and sludge.

This study was undertaken to develop an extraction method for seven acidic pharmaceuticals and five steroidal estrogens from wastewater, treated wastewater and sludge samples. The temperature and time of sample derivatization using N,O-bis(trimethylsilyl)trifluoroacetamide was optimized. Our results show that pretreatment combined with solid phase extraction (SPE) for wastewater samples (using an ENVI-C18 cartridge) and liquid-solid extraction combined with SPE (using an HLB cartridge) for sludge samples increased the analytical efficiency for acidic pharmaceuticals and estrogenic hormones using gas chromatography-mass spectrometry (GC-MS). The derivatization conditions were optimized at 40°C for 2 h. In addition, the derivatized samples were stable at ambient temperature. The new method was validated and applied to the analysis of real wastewater and discharged sludge samples from a local wastewater treatment plant. Except for 17α-ethinylestradiol, all acidic pharmaceuticals and estrogens were detected in the influent, effluent and discharged sludge samples. The concentrations of these compounds were particularly high in the discharged sludge samples.

Comparison, association, and risk assessment of phthalates in floor dust at different indoor environments in Delaware, USA.

This study aimed to compare and assess phthalate contamination in various indoor environments. In this study, 44 floor dust samples from different indoor environments in Delaware, USA were collected and analyzed for 14 phthalates using gas chromatography-mass spectrometry. Phthalates were detected in all dust samples with the total concentration ranging from 84 to 7117 mg kg(-1). DEHP (di-2-ethylhexyl phthalate), BzBP (benzylbutyl phthalate), DBP (dibutyl phthalate), and DiBP (di-isobutyl phthalate) were both the most frequently and abundantly detected phthalates. The average concentration of total phthalates in dust from offices, student dorms, gyms, stores, and daycare centers was found to be significantly or insignificantly (P = 0.05) higher than that in dust from houses and apartments. Plastic flooring materials and the application of floor care chemical products were positively associated with total phthalate concentration in floor dust. Toxicological risk assessment indicated that an investigated daycare center in this study was the only indoor environment that may cause the intake amount of DEHP of infants, toddlers, and children via dust ingestion to exceed the reference dose established by the U.S. Environmental Protection Agency (USEPA). Regular monitoring on phthalate contamination in sensitive indoor environments is recommended.

Anticancer activity of tuftsin-derived T peptide in postoperative residual tumors.

Immune adjuvants have been used in cancer biotherapies to stimulate immune response to tumor cells. Despite their potential as anticancer reagents, there are several impediments to their use in clinical applications. In this study, we aim to modify the existing tuftsin structure and evaluate its antitumor activity in preclinical models. We synthesized a novel tuftsin derivative, namely, the T peptide (TP), by linking four tuftsin peptides, which showed enhanced stability in vivo. We then evaluated its anticancer activity in a postoperative residual tumor model in mice, where we surgically removed most of the primary tumor from the host, a procedure mimicking clinically postoperative patients. Despite the limited effect in intact solid tumors, TP strongly inhibited relapsed growth of residual tumors in postsurgical mice. Surgical resection of tumors accelerated residual tumor growth, but TP slowed down this process significantly. Interestingly, TP showed similar effects in human xenograft residual models. As an immunomodulator, TP could synergize the functions of macrophages, thus inhibiting the growth of cocultured tumor cells in vitro. Furthermore, TP could shift the macrophages to the tumor-suppressive M1 type and mobilize them to produce elevated cytotoxic TNF-α and NO. As a result, TP effectively prolonged the survival time of tumor-resected mice. Using the postoperative residual tumor models, we provide a body of evidence showing the antitumor activity of TP, which causes no obvious toxicity. Our study highlights the potential of TP as a postoperative adjuvant in cancer therapies.

Electrochemical stimulation of microbial roxarsone degradation under anaerobic conditions.

Roxarsone (4-hydroxy-3-nitrophenylarsonic acid) has been commonly used in animal feed as an organoarsenic additive, most of which is excreted in manure. Roxarsone is easily biodegraded to 4-hydroxy-3-aminophenylarsonic acid (HAPA) under anaerobic conditions, but HAPA persists for long periods in the environment, increasing the risk of arsenic contamination through diffusion. We investigated the electrochemical stimulation of the microbial degradation of roxarsone under anaerobic conditions. After the carbon sources in the substrate were depleted, HAPA was slowly degraded to form arsenite under anaerobic conditions. The degradation rate of HAPA was significantly increased when 0.5 V was applied without adding a carbon source. The two-cell membrane reactor assays reveal that the HAPA was degraded in the anode chambers, confirming that the anode enhanced the electron transfer process by acting as an electron acceptor. The degradation product formed with electrochemical stimulation was arsenate, which facilitates the removal of arsenic from wastewater. Based on the high performance liquid chromatography-ultraviolet-hydride generation-atomic fluorescence spectrometry (HPLC-UV-HG-AFS) and gas chromatography-mass spectrometry (GC-MS) data, the pathway for the biodegradation of roxarsone and the mechanisms for the electrochemically stimulated degradation are proposed. This method provides a potential solution for the removal of arsenic from organoarsenic-contaminated wastewater.

Controlling carbon dioxide-to-hydrogen ratio to improve hydrogen utilization and denitrification rates of hydrogenotrophic autotrophic denitrification through homoacetogenesis-heterotrophic denitrification pathway.

Hydrogenotrophic denitrification, an environment-friendly process for organic-free influents, is limited due to poor hydrogen mass transfer efficiency and significant pH fluctuations. In this study, we manipulated the carbon dioxide-to-hydrogen ratio to improve hydrogenotrophic denitrification. When carbon dioxide-to-hydrogen ratio was 1:1 (carbon dioxide, 200 ml: hydrogen, 200 ml), the hydrogen utilization and denitrification rates were 2.4 times and 3.0 times that when carbon dioxide-to-hydrogen ratio was 0:1 (carbon dioxide, 0 ml: hydrogen, 200 ml), respectively. The pH fluctuation decreased from 3.1±0.3 to 0.2±0.1. Furthermore, the hydrogenotrophic denitrification, acetoclastic denitrification, homoacetogenic, and electron transfer activities of the sludge were improved. A high carbon dioxide-to-hydrogen ratio augmented the acid-producing and heterotrophic denitrifying microorganism populations. By maintaining a high carbon dioxide-to-hydrogen ratio, the dominant hydrogenotrophic autotrophic denitrification pathway was transformed into a homoacetogenesis-heterotrophic denitrification pathway, thereby achieving higher hydrogen utilization and denitrification rates.

Purification of dredged water by magnetic coagulation: Response surface optimization and dissolved organic matter removal characteristics.

In the present study, magnetic coagulation was used to treat dredged water and the response surface method was used to optimize process parameters. The dissolved organic matter (DOM) removal characteristics were characterized by three-dimensional fluorescence spectrometry and ultra-high resolution mass spectrometry. During the magnetic coagulation process, the suspended solids (SS) removal rate increased initially and then decreased under conditions of increasing magnetic powder dosage and stirring rate. After magnetic coagulation and precipitation for 20 min, the contents of SS, ammonia nitrogen, chemical oxygen demand, and total phosphorus in the treated dredged water met the requirements of the discharge standard (GB8978-1996, China). Three-dimensional fluorescence results showed that magnetic coagulation selectively removed fulvic acids and humic acid substances. After magnetic coagulation with precipitation for 10 min and 20 min, the total relative content of lignins, tannins, proteins, lipids, aminosugars, unsaturated hydrocarbons, condensed aromatic structures, and carbohydrates decreased by 26.3% and 39.4%, respectively. After magnetic coagulation, the distribution range of small molecule DOM shifted to the low H/C and high O/C regions. This study provides a novel perspective for studies on the removal of DOM in dredged water by magnetic coagulation. PRACTITIONER POINTS: SS and DOM removal were significantly enhanced by the use of magnetic coagulation. SS removal efficiency was affected by stirring rate and magnetic powder dosage. Magnetic coagulation selectively removed fulvic acids and humic acid substances. DOM molecule shifted to low H/C and high O/C regions after magnetic coagulation.

Exploration of the protection of riboflavin laurate on oral mucositis induced by chemotherapy or radiotherapy at the cellular level: what is the leading contributor?

Oral or gastrointestinal mucositis is a frequent phenomenon in cancer patients receiving chemotherapy or radiotherapy. In addition, several clinical investigations have demonstrated in recent years that riboflavin laurate has the potential to protect the patients from the disease induced by chemotherapy or radiotherapy. In our studies, it is observed that riboflavin laurate can ameliorate either chemotherapy- or radiotherapy-induced toxicities on Helf cells, and the effect is greater than that of riboflavin. In addition, riboflavin laurate is able to transport through the Caco-2 cell monolayer as the prototype, indicating the protective effects may be produced by the prototype of riboflavin laurate, rather than simply by the released riboflavin.

Performance of anaerobic digestion of phenol using exogenous hydrogen and granular activated carbon and analysis of microbial community.

Anaerobic conversion rate of phenol to methane was low due to its biological toxicity. In this study, the coupling of granular activated carbon (GAC) and exogenous hydrogen (EH) could enhance greatly methane production of phenol anaerobic digestion, and the metagenomic was firstly used to analyze its potential mechanism. The results indicated that a mass of syntrophic acetate-oxidizing bacteria and hydrogen-utilizing methanogens were enriched on the GAC surface, and SAO-HM pathway has become the dominant pathway. The energy transfer analysis implied that the abundance of adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide (NADH) oxidase increased. Furthermore, direct interspecies electron transfer (DIET) was formed by promoting type IV e-pili between Methanobacterium and Syntrophus, thereby improving the interspecies electron transfer efficiency. The dominant SAO-HM pathway was induced and DIET was formed, which was the internal mechanism of the coupling of GAC and EH to enhance anaerobic biotransformation of phenol.

Modification of fluorescence staining method for small-sized microplastic quantification: Focus on the interference exclusion and exposure time optimization.

Microplastics are an emerging pollutant of global concern, and fluorescence staining as an efficient method for small-sized microplastic qualification often undergoes the serious interference from external environments. The key steps affecting the accuracy of fluorescent staining and the corresponding quality assurance measures were rarely known. Therefore, this study took the Nile Red/DAPI co-staining method as an example to explore the key factors affecting its accuracy and effective measures to avoid interference. High background microplastic contamination in typical lab waters (up to 1115 MP/L), glass fiber filter membrane and glassware were identified as dominant factors affecting microplastic quantification. The background microplastics in lab waters mainly originated from the process of water production and storage. A simple filtration process removed 99% of the background microplastic in the lab waters. After burning at 500 °C for 1 h, the microplastic contamination in the filter membrane and glassware was completely eliminated. H2O2 pretreatment and exposure time caused erroneous microplastic size assessment, and were suggested to be set at 48 h and 10 ms, respectively. During the extraction process, the residue in beakers reached ~ 20% and > 50% for 5 µm and 20 µm sized microplastics, respectively, greatly contributing to the microplastic loss. The comprehensive modified measures caused microplastic concentrations in the three typical samples detected by Nile Red/DAPI co-staining method to decrease by 65.7 - 92.2% and to approach the micro-Raman results. This study clarified the reasons for interfering with quantitative microplastics by fluorescent staining and the effective measures to avoid interference, which were conducive to improving the accuracy of quantitative methods of microplastics.

Role of suspended solids on the co-precipitation of pathogenic indicators and antibiotic resistance genes with struvite from digested swine wastewater.

Struvite recovered from wastewater contains high concentration of fecal indicator bacteria (FIB), porcine adenoviruses (PAdV) and antibiotic resistance genes (ARGs), becoming potential resources of these microbial hazards. Understanding the precipitation behavior of pathogenic indicators and ARGs with suspended solids (SS) will provide the possible strategy for the control of co-precipitation. In this study, SS was divided into high-density SS (separated by centrifugation) and low-density SS (further separated by filtration), and the role of SS on the co-precipitation of FIB, PAdV and ARGs was investigated. The distribution analysis showed that 35.5-73.0% FIB, 79.6% PAdV and 64.5-94.8% ARGs existed in high-density SS, while the corresponding values were 26.9-64.4%, 11.7% and 3.5-24.3% in low-density SS. During struvite generation, 82.7-96.9% FIB, 75.5% PAdV and 56.3-86.5% ARGs were co-precipitated into struvite. High-density SS contributed 20.7-68.5% FIB, 63.9% PAdV and 38.7-87.2% ARGs co-precipitation, and the corresponding contribution of low-density SS was 31.4-79.2%, 3.9% and 6.2-54.7%. Moreover, the precipitated SS in struvite obviously decreased inactivation efficiency of FIB and ARGs in drying process. These results provide a potential way to control the co-precipitation and inactivation of FIB, PAdV and ARGs in struvite through removing high-density SS prior to struvite recovery.

Modification of TiO2 by Er3+ and rGO enhancing visible photocatalytic degradation of arsanilic acid.

As a typical wide band gap photocatalyst, titania (TiO2) cannot use the visible light and has fast recombination rate of photogenerated electron-hole pairs. Simultaneous introduction of erbium ion (Er3+) and graphene oxide (rGO) into TiO2 might overcome these two drawbacks. In this study, Er3+ and rGO were co-doped on TiO2 to synthesize Er3+-rGO/TiO2 photocatalyst through a two-step sol-gel method. Based on the UV-visible diffuse reflectance spectra and photoluminescence spectrum, the introduction of Er3+ and rGO increased the visible light absorption efficiency and enhanced the migration of photogenerated electron. Pure TiO2 has almost no photocatalytic activity for arsanilic acid (p-ASA) degradation under visible light irradiation. However, while doping with 2.0 mol% Er3+ and 10.0 mol% rGO, the p-ASA could be completely degraded within 50 min by the Er3+-rGO/TiO2 photocatalyst under visible light irradiation, and most of produced inorganic arsenic was in situ removed by adsorption from the solution. The reactive oxygen species (ROS) reacting with p-ASA was determined and superoxide radical (O2•-) and singlet oxygen (1O2) were the dominant ROS for the oxidation of p-ASA and arsenite. This work provides an approach of introducing Er3+ and rGO to enhance the visible light photocatalytic efficiency of TiO2.

Co-precipitation of heavy metals with struvite from digested swine wastewater: Role of suspended solids.

Struvite production can recover ammonia and phosphorous from digested wastewater as fertilizer. During struvite generation, most of the heavy metals was co-precipitated with ammonia and phosphorous into struvite. Understanding the precipitation behavior of heavy metals with suspended solids (SS) might provide the possible strategy for the control of co-precipitation. In this study, the distribution of heavy metals in SS and their role on the co-precipitation during struvite recovery from digested swine wastewater were investigated. The results showed that the concentration of heavy metal (including Mn, Zn, Cu, Ni, Cr, Pb and As) ranged from 0.05 to 17.05 mg/L in the digested swine wastewater. The distribution analysis showed that SS with particles > 50 µm harbored most of individual heavy metal (41.3-55.6%), followed by particles 0.45-50 µm (20.9-43.3%), and SS-removed filtrate (5.2-32.9%). During struvite generation, 56.9-80.3% of individual heavy metal was co-precipitated into struvite. The contributions of SS with particles > 50 µm, 0.45-50 µm, and SS-removed filtrate on the individual heavy metal co-precipitation were 40.9-64.3%, 25.3-48.3% and 1.9-22.9%, respectively. These finding provides potential way for controlling the co-precipitation of heavy metals in struvite.

Surface Engineering of HEK293 Cell-Derived Extracellular Vesicles for Improved Pharmacokinetic Profile and Targeted Delivery of IL-12 for the Treatment of Hepatocellular Carcinoma.

Background: Extracellular vesicles (EVs) are considered a promising drug delivery platform. Naïve EVs face numerous issues that limit their applications, such as fast clearance, hepatic accumulations, and a lack of target-specific tropism. We aimed to explore a series of surface engineering approaches to: 1) reduce the non-specific adhesion of EVs, and 2) improve their enrichment in the target tissue. As a proof-of-concept, we investigated the therapeutic potentials of a multi-modal EVs system carrying a tumor-specific nanobody and the immuno-stimulant interleukin-12 (IL12) using in vivo models of hepatocellular carcinoma. Methods: The major cell adhesion molecule on the HEK293-derived EVs, integrin ß1 (ITGB1), was knocked out (KO) by CRISPR/Cas9-mediated gene editing, followed by deglycosylation to generate ITGB1-Deg EVs for the subsequent pharmacokinetic and biodistribution analyses. ITGB1-Deg EVs were further loaded with glypican-3 (GPC3)-specific nanobody (HN3) and mouse single-chain IL12 (mscIL12) to generate ITGB1-mscIL12+HN3+Deg EVs, for evaluation of tumor tropism and therapeutic potential in a mice model of hepatocellular carcinoma. Results: Removal of ITGB1 led to the broad suppression of integrins on the EVs surface, resulting in a decrease in cellular uptake. Deglycosylation of ITGB1- EVs gave rise to inhibition of the EVs uptake by activated RAW264.7 cells. ITGB1 removal did not significantly alter the pharmacokinetic behaviors of HEK293-EVs, whereas the ITGB1-Deg EVs exhibited enhanced systemic exposure with reduced hepatic accumulation. Loading of HN3 conferred the ITGB1-Deg EVs with tumor-specific tropism for both subcutaneous and metastasized tumors in mice. The ITGB1-mscIL12+HN3+Deg EVs activated mouse splenocytes with high potency. Systemic administration of the EVs with the equivalent dose of 1.5µg/kg of exosomal IL12 achieved satisfactory tumor growth inhibition and good tolerability. Conclusion: The combinatorial approach of EVs surface engineering conferred HEK293-EVs with reduced non-specific clearance and enhanced tumor targeting efficacy, which constituted an efficient delivery platform for critical cancer therapeutics like IL12.

[Corrigendum] Fully human VEGFR2 monoclonal antibody BC001 attenuates tumor angiogenesis and inhibits tumor growth.

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that, for the scratch wound assay experiments shown in Fig. 1 on p. 2413, the panels showing the '0 h' experiments for the respective incubations with VEGF or BC001 were apparently identical. The authors were able to re­examine their original data files, and realized that this figure had been inadverently assembled incorrectly. The revised version of Fig. 1, containing the correct data for the '0 h / BC001' panel, is shown below. Note that the revisions made to this figure do not affect the overall conclusions reported in the paper. The authors are grateful to the Editor of International Journal of Oncology for allowing them the opportunity to publish this Corrigendum, and apologize to the readership for any inconvenience caused. [International Journal of Oncology 45: 2411­2420, 2014; DOI: 10.3892/ijo.2014.2690].

Design, synthesis and antitumor activities of novel bis-aryl ureas derivatives as Raf kinase inhibitors.

A series of novel bis-aryl ureas containing trifluoromethyl imidazolyl group targeting Raf kinase were designed and synthesized based on the lead compound of Sorafenib. All the prepared compounds were evaluated for their in vitro antiproliferative activities against three human cancer cell lines including MDA-MB-231 (breast), BGC-823 (gastric), and SMMC-7721 (liver). Several compounds from the series exhibited excellent antitumor activities against all three tested cancer lines. Further their inhibitory activities against Raf kinase were investigated, and three compounds (11c, 11d, and 11p) demonstrated better activities than contrast drug Sorafenib. Especially compound 11c was found to be a potent and selective Raf kinase inhibitor and could be considered as a candidate compound for further development.