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The 2020 Nobel Prize in Chemistry was awarded to Emmanuelle Charpentier and Jennifer Doudna for the development of the Clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease9 (CRISPR/Cas9) gene editing technology that provided new tools for precise gene editing. It is possible to target any genomic locus virtually using only a complex nuclease protein with short RNA as a site-specific endonuclease. Since cancer is caused by genomic changes in tumor cells, CRISPR/Cas9 can be used in the field of cancer research to edit genomes for exploration of the mechanisms of tumorigenesis and development. In recent years, the CRISPR/Cas9 system has been increasingly used in cancer research and treatment and remarkable results have been achieved. In this review, we introduced the mechanism and development of the CRISPR/Cas9-based gene editing system. Furthermore, we summarized current applications of this technique for basic research, diagnosis and therapy of cancer. Moreover, the potential applications of CRISPR/Cas9 in new emerging hotspots of oncology research were discussed, and the challenges and future directions were highlighted.

Cisplatin is a widely used platinum-based chemotherapeutic agent for hypopharyngeal squamous cell carcinoma (HSCC). However, resistance to cisplatin limits its use for the treatment of HSCC, and the underlying molecular mechanism requires further investigation. The present study performed functional assays to determine whether the expression of plant homeodomain finger protein 20 (PHF20) may be involved in the apoptosis and cisplatin resistance of HSCC. The expression levels of PHF20 were higher in cisplatin-resistant HSCC cells compared with those in cisplatin-sensitive cells. The inhibition of PHF20 suppressed cell viability but did not affect the migratory and invasive abilities of HSCC cells compared with those of negative control-transfected cells. Furthermore, PHF20 inhibition reduced cell viability by enhancing apoptosis compared with those in the control cells in vitro. Notably, the inhibition of PHF20 sensitized HSCC cells to cisplatin, thus increasing apoptosis via the signal transducer and activator of transcription 3 (STAT3)-myeloid cell leukemia-1 (MCL1) pathway. Octamer-binding transcription factor 4 (OCT4) overexpression restored phosphorylated STAT3-MCL1-mediated apoptosis induced by PHF20 inhibition. In vivo experiments confirmed that PHF20 silencing induced tumor growth and increased apoptosis in HSCC cells compared with those in the control cells. Thus, PHF20 inhibition may promote apoptosis and improve cisplatin chemosensitivity via the OCT4-p-STAT3-MCL1 signaling pathway in HSCC.

Vasculogenic mimicry (VM) refers to vessel-like structures formed by aggressive tumor cells and is closely associated with cancer invasion and metastasis. Here, we investigated the effect of macrophage-derived MTDH on VM formation in head and neck squamous cell carcinoma (HNSCC) and its underlying mechanism. Macrophages with MTDH overexpression (Mac-MTDH) promoted cancer cell VM formation, migration, and invasion in vitro. Moreover, MTDH overexpression triggered macrophage polarization into M2 type tumor-associated macrophages. Analysis of HNSCC clinical samples revealed that MTDH+ macrophages were predominantly located in the tumor-stromal region in proximity to VM and correlated with lymph node metastasis. Mechanistically, Mac-MTDH enhanced the expression and secretion of VEGFA-165 rather than other VEGFA isoforms via s-catenin. The VEGFA-165/Flt-1 axis was responsible for Mac-MTDH’s effects in cancer cells through p-STAT3/Twist1/VE-cadherin pathway. Using mouse model, we further confirmed that Mac-MTDH increased VM formation and cancer metastasis in vivo. Furthermore, in subcutaneous xenograft mouse model, HN6 + Mac-MTDH tumor exhibited elevated expression of p-STAT3 and Twist1 than HN6 + Mac-NC tumors. This study revealed that Mac-MTDH promoted VM formation, cancer cell migration and invasion, and cancer metastasis through VEGFA-165/Flt-1 axis, and that macrophage-derived MTDH could be a potential therapeutic target in HNSCC.

This paper examined the effect of basalt fibers of varied lengths (6 mm, 9 mm and 15 mm) and contents (3–10%) on the properties of asphalt mastics. For comparison, three asphalt mastics reinforced with basalt fiber, lignin fiber or polyester fiber were investigated. The asphalt adsorptivity, shear behavior, crack resistance and high-temperature rheological property were evaluated by leakage test, cone penetration test, strip-tensile test and dynamic shear rheometer test, respectively. In order to understand the reinforcement mechanism, the microstructure and morphology of basalt fiber-asphalt mastics were studied through using scanning electron microscopy (SEM). It was shown that the addition of basalt fibers generally improved the properties of asphalt mastics especially the crack resistance. The asphalt adsorption and strength behavior of asphalt mastic with 6 mm basalt fiber excelled that with 9 mm or 15 mm due to its largest contact area with asphalt mastic. The crack resistance and high-temperature rheological property of asphalt mastics were influenced by the adsorption and content of fibers. The asphalt mastic with basalt fiber showed the best comprehensive performance among all types of fiber-reinforced asphalt mastics. Basalt fibers could form a stable three-dimensional network in the asphalt mastic, which was able to disperse the stress and suppress the development of cracks of asphalt mastic effectively.

The catalytic properties of small-molecule proteolysis targeting chimeras (PROTACs) may lead to uncontrolled degradation. Therefore, the main disadvantages of PROTACs are non-cancer specificity and relatively high toxicity, which limit the clinical application of PROTACs. The photocontrolled PROTACs (photoPROTACs) were proposed to overcome this issue, in which they can be triggered by ultraviolet A (UVA) or visible light to induce the degradation of the target protein. Herein, we designed several photoPROTACs to cause the degradation of bromodomain-containing protein 4 (BRD4) on-demand using 365 nm light. The representative compound N2 is proved to induce the degradation of BRD4 upon irradiation. Moreover, compound N2 was successfully applied in vivo to inhibit tumor growth in a zebrafish xenograft model of skin cancer tongue squamous cell carcinoma (TSCC) in a photocontrol manner.

// Xiuxiu Liu 1, 2, * , Zhenghua Lv 1, * , Jidong Zou 1 , Xianfang Liu 1, 2 , Juke Ma 1 , Chengtao Sun 1 , Na Sa 1 , Wei Xu 1, 2 1 Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China 2 Shandong Provincial Key Laboratory of Otology, Jinan, Shandong, China * These authors contributed equally to this work Correspondence to: Wei Xu, email: xuwhns@126.com Keywords: macrophages, cancer invasion, AEG-1, MMP-9, hypopharyngeal cancer Received: July 11, 2016 Accepted: October 14, 2016 Published: October 25, 2016 ABSTRACT Macrophages play a critical role in tumor invasion and metastasis, which remain major causes of mortality in patients with hypopharyngeal cancer. Here we investigate the effect of an oncogene, AEG-1 expressed in macrophages on the invasion of hypopharyngeal cancer cells. AEG-1 is more highly expressed in macrophages of human hypopharyngeal cancer samples compared with adjacent non-tumor controls. Using matrigel invasion assay system, THP-1-derived macrophages with forced AEG-1 overexpression enhance FaDu cell invasion whereas macrophages with AEG-1 silence inhibit. Matrix metalloproteinase 9 (MMP-9), which is important in tumor invasion and metastasis through degrading extracellular matrix, is up-reulated by AEG-1 partly through NF-κB p65 in macrophages. Intriguingly, macrophage AEG-1 also induces MMP-9 up-regulated expression in FaDu cells. Furthermore, macrophage AEG-1 activates signal transducer and activator of transcription 3 (STAT3) in FaDu cells, which is responsible for macrophage AEG-1-induced an increase in MMP-9 expression and invasion of FaDu cells. This is the first to demonstrate that macrophage AEG-1 promotes tumor invasion through up-regulation of MMP-9 in both macrophages and cancer cells. Thus, the results provide evidences that macrophage AEG-1 contributes to promotion of tumor invasion, and represents as a potential target in hypopharyngeal cancer therapy.

Background Distant metastasis is the major cause of death in patients with hypopharyngeal squamous cell carcinoma (HSCC). CDH1 is correlated with tumor invasion and metastasis; however, its function in HSCC remains unclear. Methods We used immunohistochemistry (IHC) staining to evaluate the expression of CDH1 in 31 and 78 specimens from primary HSCC patients with and without postoperative lung metastases respectively. Sulforhodamine B (SRB) and CCK-8 assays were used to test the proliferation of HSCC cells. Motility of HSCC cells was investigated by migration and invasion assays. Western blot analysis was used to measure the levels of CDH1 and other proteins. Results We found that the low expression of CDH1 was significantly associated with postoperative lung metastasis in HSCC (P

This paper examines the physical and mechanical properties of asphalt mortar containing basalt fiber and other kinds of fibers as comparison by using different macroscopic and microscopic experimental methods. Experimental comparisons were made, in terms of adsorption performance, shear performance, crack resistance property and high temperature rheological property, between the innovative asphalt mortar made with basalt fiber and asphalt mortars made with two commonly used fibers. Then, the reinforcing mechanisms was explored by using SEM. Different types of samples with varying dosages and dimensions of the additives were studied, namely asphalt mortar with 3%, 5%, 7% and 10% of basalt fiber and that with 6mm and 9mm of basalt fiber. Laboratory test results indicate that basalt fiber have great effect on the ultimate tension and rheological properties of asphalt mortars, which derived from that basalt fibers make them forming a network structure to disperse stress and made a contribution to the stability of asphalt mixture.

In order to reverse the malignant characteristics of hypopharyngeal cancer, the proteasome inhibitor MG132 was introduced into FaDu/T cells and the mechanisms underlying its effects were investigated. The multi-drug resistance (MDR) sensitivities of FaDu/T and FaDu/T-MG132 cancer cells to several chemotherapeutics were investigated by a 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide (MTT) assay. Apoptosis was measured by staining cells with Annexin V and propidium iodide (PI) double staining. Reverse transcription-polymerase chain reaction and western blot analysis were conducted to detect mRNA and corresponding protein levels of the MDR- and apoptosis-related genes P-glycoprotein (P-gp), caspase-3, Bcl-2 and Bax. The nuclear protein of nuclear factor κ-light-chain-enhancer of activated B cells. (NF-κB) and p53 were also investigated via western blot analysis. Compared with FaDu/T cells, the drug resistance of FaDu/T + MG132 cells to cisplatin (DDP), 5-fluorouracil (5-FU), doxorubicin (Dox) and vincristine (VCR) decreased. With increased expression of caspase-3 and Bax and decreased expression of Bcl-2, the anti-apoptotic ability markedly decreased in FaDu/T + MG132 cells. P-gp and NF-κB significantly decreased; however, p53 increased in FaDu/T + MG132 cells. These results suggested that the proteasome inhibitor MG132 reversed the malignant characteristics of FaDu/T by enhancing apoptosis and inhibiting P-gp. MG132 was also able to inhibit the nuclear translocation of NF-κB and increase the expression of p53.

The aim of this study was to investigate the possible influence of different genotypes of the lead single nucleotide polymorphisms (SNPs) rs10917468 and rs12045440 in the CAPZB gene on the thyroid function in papillary thyroid carcinoma (PTC) and benign thyroid neoplasm (BN) patients. In the study, a significant association was detected between rs12045440 and serum TSH concentrations in thyroid tumor patients (p=0.001). After the adjustment of relevant covariates, the difference between the mean serum TSH levels in different genotypes of rs12045440 was still significant in the BN group (p=0.003) but was not significant in the PTC cases (p=0.115). No significant association of rs10917468 with TSH levels was found. The SNP rs12045440 was associated with the serum TSH concentrations in Chinese thyroid tumor patients, especially in benign thyroid tumor cases.

Summary Objectives To investigate whether patients with Reinke edema are more extrovertive than patients with carcinoma and, whether cyclic tensile strain (CTS) attenuates cigarette smoke condensate (CSC)-induced inflammation in human vocal fold fibroblasts (HVFF). Study Design In vitro and ex vivo study. Methods Clinical investigation and Eysenck personality questionnaire were performed to evaluate the personality and smoking status in individuals among groups. 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay was applied to test the viabilities of cultured HVFF exposed to CSC and/or CTS. The messenger RNA (mRNA) and protein expressions of cluster of differentiation 44 (CD44), cyclooxygenase-2 (COX-2), and matrix metalloproteinase-9 (MMP-9) in tissues from Reinke edema, paracancerous site, normal vocal fold, and in HVFF with different treatments were measured by reverse transcriptase polymerase chain reaction or western blot, respectively. Results Patients with either Reinke edema or carcinoma were moderate/heavy smokers; the extraversion score, however, was higher in Reinke edema patients than that in carcinoma patients. CD44 mRNA and protein expressions were significantly higher, whereas, COX-2 and MMP-9 expressions were significantly lower in Reinke edema tissues than those in paracancerous tissues. Treatment of HVFF with CSC led to the decrease in cell viability, the reduction in CD44 expression, but, the increase in COX-2 and MMP-9 expressions and, moreover, administration of CTS inhibited such effects of CSC on HVFF. Conclusions Our results demonstrate that Reinke edema patients have more extrovert personality characteristics in comparison to carcinoma patients and, importantly, CTS attenuates CSC-induced inflammation in HVFF. Phonatory vibration may be a mechanism for lower expression of proinflammatory mediators in Reinke edema tissues in spite of cigarette smoke exposure.

This paper describes the architecture and the implementation of a spectrum sensing platform based on cloud computing. The system collects information from distributed sensors scattered around a specific area for further analysis. The system is designed in layers, including layers of sensor device, console terminal, cloud server management, application development and consumers from bottom to up. Data-directed method is taken to ensure the extendibility of the system. The TCP/IP is wrapped by AMQP for simple and reliable network connection. Finally, we introduce some practical applications running on the cloud platform.