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A photoinduced TBADT-catalyzed one-pot, three-component strategy for the synthesis of alkyl-alkyl sulfones was reported. The developed methodology could tolerate broad functional groups and allow for the late-stage modification of complex molecules.

Supplementary Tables 1-3 from Serglycin Is a Theranostic Target in Nasopharyngeal Carcinoma that Promotes Metastasis

Supplementary Figures 1-2 from Serglycin Is a Theranostic Target in Nasopharyngeal Carcinoma that Promotes Metastasis

Nasopharyngeal carcinoma (NPC) is known for its high-metastatic potential. Here we report the identification of the proteoglycan serglycin as a functionally significant regulator of metastasis in this setting. Comparative genomic expression profiling of NPC cell line clones with high- and low-metastatic potential revealed the serglycin gene (SRGN) as one of the most upregulated genes in highly metastatic cells. RNAi-mediated inhibition of serglycin expression blocked serglycin secretion and the invasive motility of highly metastatic cells, reducing metastatic capacity in vivo. Conversely, serglycin overexpression in poorly metastatic cells increased their motile behavior and metastatic capacity in vivo. Growth rate was not influenced by serglycin in either highly or poorly metastatic cells. Secreted but not bacterial recombinant serglycin promoted motile behavior, suggesting a critical role for glycosylation in serglycin activity. Serglycin inhibition was associated with reduced expression of vimentin but not other epithelial–mesenchymal transition proteins. In clinical specimens, serglycin expression was elevated significantly in liver metastases from NPC relative to primary NPC tumors. We evaluated the prognostic value of serglycin by immunohistochemical staining of tissue microarrays from 263 NPC patients followed by multivariate analyses. High serglycin expression in primary NPC was found to be an unfavorable independent indicator of distant metastasis-free and disease-free survival. Our findings establish that glycosylated serglycin regulates NPC metastasis via autocrine and paracrine routes, and that it serves as an independent prognostic indicator of metastasis-free survival and disease-free survival in NPC patients. Cancer Res; 71(8); 3162–72. ©2011 AACR.

Supplementary Materials and Methods from Serglycin Is a Theranostic Target in Nasopharyngeal Carcinoma that Promotes Metastasis

Wastewater treatment plants (WWTPs) are an indispensable part of the infrastructure of modern cities. However, because of the existence of many confined working spaces in them, they also pose significant risks of occupational hazards for workers. Therefore, this study was conducted on WWTP workers in Kaohsiung, Taiwan to explore the connections among the perceived control, safety attitude, and safety performance of WWTP workers. In total, 123 valid questionnaires were returned for descriptive statistical analysis, variance analysis, correlation analysis, and hierarchical regression analysis. According to the analysis results, the WWTP workers in this study indicated a mid to high level of perceived control, and they generally believed they were also responsible for industrial safety management. The variance analysis results showed that workers of a different gender, age, service unit, and seniority had significantly different safety attitudes. The hierarchical regression analysis results indicated that the perceived control of the WWTP workers had a significant influence on their safety performance through their safety attitude, which served as a mediator between perceived control and safety performance. It is hoped that these findings can provide references for WWTP managers and workers in their daily communication, operation, and safety management system introduction to ensure better safety.

Internal tandem duplication (ITD) mutation in Fms-like tyrosine kinase 3 gene (FLT3/ITD) represents an unfavorable genetic change in acute myeloid leukemia (AML) and is associated with poor prognosis. Metabolic alterations have been involved in tumor progression and attracted interest as a target for therapeutic intervention. However, few studies analyzed the adaptations of cellular metabolism in the context of FLT3/ITD mutation. Here, we report that FLT3/ITD causes a significant increase in aerobic glycolysis through AKT-mediated upregulation of mitochondrial hexokinase (HK2), and renders the leukemia cells highly dependent on glycolysis and sensitive to pharmacological inhibition of glycolytic activity. Inhibition of glycolysis preferentially causes severe ATP depletion and massive cell death in FLT3/ITD leukemia cells. Glycolytic inhibitors significantly enhances the cytotoxicity induced by FLT3 tyrosine kinase inhibitor sorafenib. Importantly, such combination provides substantial therapeutic benefit in a murine model bearing FLT3/ITD leukemia. Our study suggests that FLT3/ITD mutation promotes Warburg effect, and such metabolic alteration can be exploited to develop effective therapeutic strategy for treatment of AML with FLT3/ITD mutation via metabolic intervention.

We studied the adsorption and lateral interactions of CO molecules on Rh nanoclusters supported on an ordered thin film of Al2O3/NiAl(100) with varied surface probe techniques under ultra-high vacuum conditions and with density-functional-theory (DFT) calculations. The Rh clusters were grown with vapor deposition onto the Al2O3/NiAl(100) surface at 300 K; with increasing deposition, their mean diameter evolved from 1.0 to 3.5 nm and their height from 0.4 to 0.8 nm. The initial adsorption energy (for sparse CO coverage) and the number of adsorbed CO per surface site on the Rh clusters increased with decreasing cluster size. The former effect results from the surface structure and expanded lattice parameter of small Rh clusters, whereas the latter effect involves not only the initial adsorption energy but also altered lateral interactions among CO molecules. In contrast with CO on Rh single crystals, CO on small clusters adsorbed with their axes tilted from the surface normal, weakening the CO–CO repulsive interactions for CO coverage over a wide range. The saturated density of CO on clusters of diameter near 1.0 nm and height near 0.4 nm is 2–3 times that of large clusters (diameter ≥ 3.5 nm) or a Rh(100) surface. The CO–CO repulsive interactions on small clusters became effective at large CO densities, given that the onset of desorption of CO at saturation was 100 K lower than that of large clusters.

Sulfasalazine (SSZ) is an anti-inflammatory drug that has been demonstrated to induce apoptosis and tumor regression through inhibition of plasma membrane cystine transporter xc(-). Cysteine is a rate-limiting precursor for intracellular glutathione (GSH) synthesis, which is vital for compound detoxification and maintaining redox balance. Platinum-based chemotherapy is an important regimen used in clinics for various cancers including colorectal cancer (CRC). We hypothesized that targeting xc(-) transporter by SSZ may annihilate cellular detoxification through interruption of GSH synthesis and may enhance the anti-cancer activity of cisplatin (CDDP) by increasing drug transport. In the present study, we revealed that xCT, the active subunit of xc(-), is highly expressed in CRC cell lines and human colorectal carcinoma tissues compared with their normal counterparts. SSZ effectively depleted cellular GSH, leading to significant accumulation of reactive oxygen species and growth inhibition in CRC cells. In contrast, the normal epithelial cells of colon origin were less sensitive to SSZ, showing a moderate ROS elevation. Importantly, SSZ effectively enhanced the intracellular platinum level and cytotoxicity of CDDP in CRC cells. The synergistic effect of SSZ and CDDP was reversed by antioxidant N-acetyl-L-cysteine (NAC). Together, these results suggest that SSZ, a relatively non-toxic drug that targets cystine transporter, may, in combination with CDDP, have effective therapy for colorectal cancer.

The polyaniline/Mn0.8Zn0.2Fe2O4(PANI/MZF) nanocomposite was prepared by an in situ polymerization method. The samples were characterized by Fourier transform infrared spectrometer, X-ray diffraction, scanning electron microscope and vibrating sample magnetometer. The complex permittivity and complex permeability for the nanocomposites were measured by wave-guide method with vector network analyzer in 2.0–18.0 GHz. The reflection losses (R L ) of the nanocomposites were investigated according to the wave transmission theory. The results showed the maximum reflection loss of the PANI/MZF nanocomposite was about −20.6 dB at 14.4 GHz with a bandwidth of 5.6 GHz. In conclusion, a wider absorption frequency range could be obtained by adding polyaniline contain in the MZF ferrite. The PANI/MZF nanocomposite is a good microwave shielding and absorbing materials at higher frequency.

This paper aims at reporting the synthesis and microwave absorption characteristics of polyaniline (PANI). The PANI nanoparticles were synthesized by chemical oxidative polymerization method with ammonium persulfate ((NH4)2S2O8, APS) as oxidant and hydrochloric acid (HCl) for protonation of aniline. For APS/aniline mol ratio of 1, HCl concentration of 1 mol/L, reaction temperature of 5°C, the reaction time of 6h, the obtained PANI exhibits the highest value（30.9 S·cm-1）of the electrical conductivity. The structure and morphology of PANI were studied by X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared spectrophotometer (FT-IR), ultraviolet-visible spectrophotometer (UV-Vis) analysis ways. Microwave absorbing performances were investigated using wave-guide method with vector network analyzer in 2–18 GHz. The results showed that there is a maximum absorption peak with RL= -12.63dB at 13.61GHz，the value of RL ≤−10 dB is maintained from 11.38GHz to 18GHz for the sample of the thickness for 2mm.

To achieve high performance tracing control of the three-links spatial robot, a nonsingular terminal fuzzy sliding mode control method is proposed in this paper. Firstly, the control method can efficiently avoid the singularity of the generally terminal sliding mode controller through designing nonsingular terminal sliding mode surface. Secondly, to diminish the chattering in the control input, a fuzzy controller is designed to adjust the gain of nonsingular terminal sliding mode controller according to the normal of nonsingular terminal sliding mode surface. The stability of the control scheme is verified by using Lyapunov theory. The proposed controller is then applied to the control of a three-links spatial robot. Simulation results show the validity of the proposed control scheme.

A fuzzy adaptive terminal sliding mode control scheme for the attitude of flapping wing micro aerial vehicle is proposed in this paper. Based on the feedback linearization technique, a terminal sliding mode controller is designed. The singularity of the controller can be solved through switching between terminal sliding mode surface and linear sliding mode surface. To reduce the chattering in the control input, a fuzzy controller is designed to adaptively adjust the gain of the terminal sliding mode controller according to the normal of the terminal sliding mode surface. The stability of the control scheme is verified by using Lyapunov theory. Simulation results show that the proposed control scheme is effective.

To achieve high performance tracing control of the three-links spatial robot, a fast terminal fuzzy sliding mode control method is proposed in this paper. Firstly, the control method can efficiently solve the singularity of the controller through switching between terminal sliding mode surface and linear sliding mode surface. Secondly, to diminish the chattering in the control input, a fuzzy controller is designed to adjust the generalized gain of fast terminal fuzzy sliding mode controller according to fast terminal sliding mode surface. The stability of the control algorithm is verified by using Lyapunov theory. The proposed controller is then applied to the control of a three-links spatial robot. Simulation results show the validity of the proposed control scheme.

This papercalculated and researched equipment maintenance cycle based on Markova Chains.Taking cold reserve system as an example, maintenance information of systems was analyzed and the space figure of state transfer of parts working process was painted. State equation was listed according to the space figure. Next state equation was solved and reliability parameters were obtained. The practical application of the system’s mean time to failures (MTTF) shows the feasibility and veracity of this approach.

Nasopharyngeal carcinoma (NPC) has the highest metastatic potential among head and neck cancers. Distant metastasis is the major cause of treatment failure. The role of interleukin-8 (IL-8) in NPC progression remains unknown. Our multivariate survival analyses of 255 patients with NPC revealed that higher IL-8 expression in primary NPC tissue was an independent prognostic factor for overall survival, disease-free survival, and distant metastasis-free survival of the patients. In vitro study revealed that IL-8 was highly expressed in the established high-metastasis NPC clone S18 relative to the low-metastasis cells. Suppression of IL-8 by short-hairpin RNA reduced the expression of IL-8 in S18 cells and subsequently inhibited migration, invasion, and hepatic metastasis of the cells without influencing cellular growth. Overexpression of IL-8 in S26 cells resulted in increased migration, invasion, and metastasis capabilities of the cells without affecting cellular growth. Exogenous IL-8 enhanced the migration and invasion of low-metastasis CNE-2 cells in a dose-dependent manner. An epithelial-mesenchymal transition (EMT) could be induced by IL-8 in various NPC cell lines. The high level of phosphorylated AKT in S18 cells could be suppressed by knocking down IL-8 expression. Further, IL-8-promoted migration and invasion could be abolished by either the application of the phosphoinositide-3-kinase inhibitor LY294002 or the knock down of AKT expression by using small-interfering RNA. In summary, IL-8 serves as an independent prognostic indicator of overall survival, disease-free survival, and metastasis-free survival for patients with NPC. IL-8 promotes NPC metastasis via autocrine and paracrine means, involving activation of AKT signaling and inducing EMT in NPC cells.

A fuzzy sliding mode control scheme based on variable rate reaching law for attitude control of flapping wing micro aerial vehicle is proposed in this paper. Based on the feedback linearization technique, a sliding mode controller is designed. To faster response speed, a fuzzy controller is designed to adaptively tune the slope of sliding mode surface. To reduce the chattering, the variable rate reaching law is proposed. The variable rate reaching law is composed of the distance from current point to sliding mode surface in phase plane. The simulation studies for attitude control of a flapping wing micro aerial vehicle have been carried out. Simulation results show that the proposed control scheme is effective.

An adaptive Double Fuzzy Sliding Mode Control scheme for attitude control of Flapping Wing Micro Aerial Vehicle is proposed in this paper. Based on the feedback linearization technique, a sliding mode controller is designed. To faster response speed, a fuzzy controller is designed to adaptively tune the slope of sliding mode surface. To reduce the chattering, another fuzzy controller is designed to adaptively tune the switch part of sliding mode control. The system stability is proved by Lyapunov principle. Simulation results show that the proposed control scheme is effective.

When image digitalization device translate fastener into fastener image, the fastener image is always skewed to some extent, which will result in failure of the subsequent processing. The correction of the fastener image is the important step in its automatic recognition. In order to overcome the heavy computing burdens of hough transform, a new usage of hough transform is introduced in this paper. The algorithm works by first doing certain process on input image, the close edge of the image is gotten. Then a two-stage Hough transform algorithm is applied to the image to calculate the angle of the main edge line. This angle is thought as the declining angle of the fastener image. Lastly, the orientated image is rectified using rotation method. This algorithm is validated through experimental results.

Nasopharyngeal carcinoma (NPC) is known for its high-metastatic potential. Here we report the identification of the proteoglycan serglycin as a functionally significant regulator of metastasis in this setting. Comparative genomic expression profiling of NPC cell line clones with high- and low-metastatic potential revealed the serglycin gene (SRGN) as one of the most upregulated genes in highly metastatic cells. RNAi-mediated inhibition of serglycin expression blocked serglycin secretion and the invasive motility of highly metastatic cells, reducing metastatic capacity in vivo. Conversely, serglycin overexpression in poorly metastatic cells increased their motile behavior and metastatic capacity in vivo. Growth rate was not influenced by serglycin in either highly or poorly metastatic cells. Secreted but not bacterial recombinant serglycin promoted motile behavior, suggesting a critical role for glycosylation in serglycin activity. Serglycin inhibition was associated with reduced expression of vimentin but not other epithelial–mesenchymal transition proteins. In clinical specimens, serglycin expression was elevated significantly in liver metastases from NPC relative to primary NPC tumors. We evaluated the prognostic value of serglycin by immunohistochemical staining of tissue microarrays from 263 NPC patients followed by multivariate analyses. High serglycin expression in primary NPC was found to be an unfavorable independent indicator of distant metastasis-free and disease-free survival. Our findings establish that glycosylated serglycin regulates NPC metastasis via autocrine and paracrine routes, and that it serves as an independent prognostic indicator of metastasis-free survival and disease-free survival in NPC patients. Cancer Res; 71(8); 3162–72. ©2011 AACR.

Background: Elderly persons with acute poisoning in the emergency department (ED) and prognostic factors of outcomes have not been well addressed in previous research. This study aimed to investigate the characteristics of elderly patients with acute poisoning visiting the ED, and to identify the possible predictive factors of mortality. Methods: Patients aged ≥ 65 years with acute poisoning who visited the ED in Taipei Veterans General Hospital from January 1, 2006 through to September 30, 2008 were enrolled in the study. We collected demographic information on underlying diseases, initial presentations, causes and toxic substances, complications, dispositions, and outcomes. Analyses were conducted among different groups categorized according to age, suicide attempt, and outcome. Multiple logistic regression was applied to identify possible predictive clinical factors influencing mortality in the elderly with acute poisoning. Results: A total of 250 patients were enrolled in the study, with a mean age of 77 years and male predominance. The most common cause of intoxication was unintentional poisoning. Medication accounted for 57.6% of poisonous substances, of which benzodiazepine was the most common drug, followed by warfarin. The overall mortality rate was 9.6%. The average length of stay in the ED increased significantly in the old (65–74 years), very old (75–84 years) and extremely old (≥ 85 years) groups. Suicide attempt patients experienced more complications including respiratory failure, aspiration pneumonia, hypotension and mortality. Three clinical predictive factors of mortality were identified: herbicide poisoning, hypotension and respiratory failure upon presentation. Conclusion: Our results demonstrated that elderly patients with acute poisoning had a mortality rate of 9.6%. Suicide attempts resulted in more serious complications. The risk factors for mortality were herbicide intoxication, hypotension and respiratory failure. [J Chin Med Assoc 2010;73(2):78–87]

Dinghushan is the only nature reserve at the Tropic of Cancer in mainland China with extensive old growth monsoonal hardwood forest. We here assemble a comprehensive list, with life history notes, of amphibians and reptiles of Dinghushan. Relevant records were scattered over three centuries since the first in 1886. A total of 71 species are known to occur in the reserve, and this number of species per area far exceeds that predicted by classic island biogeographic theory. Among these 71 species, nine are new records: Five frogs (Amolops ricketti, Hylarana macrodactyla, Hylarana taipehensis, Odorrana schmackeri, and Occidozyga lima) and four snakes (Oligodon cinereus, Sinonatrix percarinata, Sinomicrurus macclellandi, and Trimeresurus stejnegeri). One undetermined skink may confound the generic definitions for the genera of Scincella and Sphenomorphus. Among these 71 species, 21 that are not closely associated with old growth forest have not been seen recently. Forest recovery and reforestation of farmland over five decades since the nature reserve was established in 1956 may have contributed to the decline of these species. Dinghushan has 97% of its species occurring strictly in the Oriental zone; among them, about 78% (55) occur both in the South China and Central China regions, 21% (15) occur only in the South China region, and one species was previously known only from the Central China region. The unique location of Dinghushan makes long-term monitoring of its herpetofaunal diversity important for future collaborative studies on a global scale.

In this paper, a 10 kV transformer's FEA model is established for studying the steady magnetic field and structure dynamic characteristic of windings. Through ANSYS Maxwell and Harmonic Response analysis, the leakage magnetic field, the electromagnetic force and the axial vibration of windings are studied. The influence factors, such as pretightening force, oil temperature and aging on mechanical characteristics of spacers are considered through a series mechanical experiments and then applied into the FEA model. The results of FEA and tests show that the vibration of winding can increase while the temperature and aging rises and the Young's modulus of spacer have a close relationship with temperature and aging.

Alterations in energy metabolism play a major role in cancer development. Aconitase (ACO2) is an essential enzyme located in the mitochondria and catalyzes the interconversion of citrate and isocitrate in the tricarboxylic acid cycle. Recent studies suggest that the expression of ACO2 may be altered in certain types of cancer. The purpose of this study was to examine ACO2 expression in clinical tumor specimens from patients with gastric cancer and to evaluate the clinical relevance of ACO2 expression in gastric cancer. A total of 456 paraffin-embedded gastric cancer tissues and 30 pairs of freshly frozen tissues were used in this study. Real-time quantitative reverse transcription polymerase chain reaction, western blotting, and immunohistochemical staining were performed to measure ACO2 expression in tumor tissues and matched adjacent non-tumorous tissues. The results showed that the expression of ACO2 was significantly down-regulated in gastric cancer tissues compared with matched adjacent nontumorous tissues and was associated with clinical stage (p = 0.001), T classification (p = 0.027), N classification (p = 0.012), M classification (p = 0.002), and pathological differentiation states (p = 0.036). Patients with lower ACO2 expression had a shorter survival time than those with higher ACO2 expression. Univariate and multivariate analyses indicated that ACO2 expression functions as an independent prognostic factor (p < 0.001). Our data suggested that ACO2 could play an important role in gastric cancer and may potentially serve as a prognostic biomarker.

The microRNA miR-138 is dysregulated in several human cancers, but the underlying mechanism remains largely unknown. Here, we report that miR-138 is commonly underexpressed in nasopharyngeal carcinoma (NPC) specimens and NPC cell lines. The ectopic expression of miR-138 dramatically suppressed cell proliferation and colony formation in vitro and inhibited tumorigenesis in vivo. Moreover, we identified the cyclin D1 (CCND1) gene as a novel direct target of miR-138. In consistent with the knocked-down expression of CCND1, overexpression of miR-138 inhibited cell growth and cell cycle progression in NPC cells. Furthermore, CCND1 was widely upregulated in NPC tumors, and its mRNA levels were inversely correlated with miR-138 expression. Taken together, our findings suggest that miR-138 might be a tumor suppressor in NPC, which is exerted partially by inhibiting CCND1 expression. The identification of functional miR-138 in NPC and its direct link to CCND1 might provide good candidates for developing diagnostic markers and therapeutic applications for NPC.

Background Fewer pauses and better chest compression quality are thought to improve overall survival following cardiac arrest. This study aimed to measure the outcomes of adult nontraumatic out-of-hospital cardiac arrests (OHCAs) treated with 5:1 compressions-to-ventilations (Thumper 1007) or continuous chest compressions with ventilation (Thumper 1008 CCV) mechanical cardiopulmonary resuscitation (CPR) within a specified period of time. Methods A retrospective observational cohort study of 515 adults with OHCA was conducted at the emergency department of an urban tertiary hospital. There were 307 patients in the Thumper 1007 phase (January 2008 to December 2009) and 208 patients in the Thumper 1008 CCV phase (January 2010 to May 2011). Return of spontaneous circulation (ROSC) and survival to hospital discharge were the primary outcome measures. Results Patients in the Thumper 1007 and Thumper 1008 CCV phases had comparable results with the following exceptions: less hypertension (42.4% vs. 62.0%), cerebrovascular accidents (11.4% vs. 25.0%), and faster emergency medical service response time intervals (mean, 3.7 vs. 4.5 minutes) with the Thumper 1007. The average ambulance transport time was 6.1 minutes in both phases. The rates of ROSC [35.1% vs. 23.5%; adjusted odds ratio (OR), 1.616; 95% confidence interval (CI), 1.073–2.432] and survival to hospital discharge (10.1% vs. 4.2%; adjusted OR 2.431; 95% CI, 1.154–5.120) were significantly higher with the Thumper 1008 CCV than with the Thumper 1007. Favorable neurologic outcome upon discharge, defined as cerebral performance category scores of 1 (good performance) or 2 (moderate disability), was not significantly different between the two phases [1.6% (5/307) vs. 1.9% (4/208); p = 0.802]. The Thumper 1008 CCV provided significantly faster average chest compression rates and shorter no-chest compression intervals than the Thumper 1007 after activation. Conclusion In an emergency department with short ambulance transport times, continuous chest compressions with ventilation through mechanical CPR showed improved outcomes, including ROSC and survival to hospital discharge, in an adult with OHCA. However, there are a variety of confounding influences that may affect the validity of conclusions that have been drawn.

Using discontinuous polyacrylamide gel electrophoresis and histochemistry methods, lactate and esterase isozyme of three species and five popalation of Lacertiformes were analysed. The interspecific zymogramatic differences are obvious. Each species possesses its specific zymogram. According to the zymogramatic similarity among these species calculated with the method of polar ordination,they can be grouped into 2 categories. Gekko chinensis and the two population of Gekko subpalmatus fall into one category. The second category contains the two population of Hemidactylus bowringii. The congsanguinity of the species and popalation has been drawn from the results.

Nasopharyngeal carcinoma (NPC) has the highest incidence of metastasis among head and neck cancers. The involvement of cancer stem cells (CSCs) in tumorigenesis has been studied in several malignancies, but their presence in NPC has not been extensively evaluated. The range of general characteristics of “stemness” includes increased side-population (SP) fraction, limited functional differentiation or dedifferentiation under the influence of the microenvironment, and expression of putative stem cell markers. We previously isolated a highly metastatic clone (Clone-18) from the NPC cell line CNE-2. Using this clone, we have sought to explore the influence of the stemness characteristics of NPC cells on tumor metastasis. Human tissue samples were collected under informed consent at the Sun Yat-sen University Cancer Center. SP cells were evaluated by flow cytometry. A Transwell assay and a wound-healing assay were used to evaluate the migratory and invasive abilities of the cells. Lung metastasis was evaluated by injecting tumor cells into the tail vein of BALB/c nude mice. Real-time PCR and western blotting were used for a protein kinase C (PKC) pathway study. Tissue microarrays and immunohistochemical staining were used to evaluate the correlation between vimentin and the survival time of patients with nasopharyngeal carcinoma. Clone-18 cells possessed a very high percentage of SP cells (62.1 ± 1.39%) relative to low-metastasis clones (Clone-22, 7.2 ± 1%; Clone-26, 3.9 ± 0.9%) or the parental CNE-2 cells (27.9 ± 2.02%), implying that there were more stem-like cells in the high-metastasis clones. Two stem cell markers, WNT5A and vimentin, were also highly expressed in the high-metastasis clone cells. To confirm the clinical relevance of these findings, human tissue samples were used. The mRNA level for WNT5A was significantly higher in regional metastatic NPC tissues (n = 4) than in primary tumors (n = 20), and it was much higher in liver metastatic NPC (n = 5) than in regional metastatic tissues. In the cohort of 282 NPC patients, a higher vimentin level in the primary tumor, as detected by IHC staining, correlated with shorter overall survival. Suppression of WNT5A by siRNA significantly reduced the migratory and invasive abilities of Clone-18 cells, and this effect was shown to be regulated by activating protein kinase C (PKC). The activated PKC further regulated the expressions of Snail and E-cadherin, which subsequently induced an EMT in NPC cells. In vivo experiments showed that the administration of recombinant WNT5A protein could promote lung metastasis by the low-metastasis Clone-26 cells in the lung metastasis mouse model. In conclusion, the stemness characteristics of NPC cells have been shown to contribute to the migratory, invasive, and metastatic phenotype of this important malignancy, with WNT5A directly regulating these properties and being a critical candidate marker of CSCs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 494. doi:10.1158/1538-7445.AM2011-494

Serglycin is a proteoglycan consisting of a core protein to which negatively charged glycoaminoglycan (GAG) chains of either chondroitin sulfate or heparin are attached. Serglycin was first shown to be essential for the maturation of mast cell secretory granules, but it has recently been shown to be present within multiple other cell types. In this study we describe for the first time the role of serglycin as a potential metastasis regulator in nasopharyngeal carcinoma (NPC), a tumor that has the highest incidence of metastasis among head and neck cancers. The recognition that serglycin plays an important role in NPC comes from our earlier genomic expression profiles comparing clones derived from the NPC cell line CNE-2, where serglycin (SRGN) was identified as one of the most up-regulated genes in the high-metastasis Clone 18. The genomic expression profiling was performed on samples collected in cultured cells and in xenograft tumors generated from Clone-18, as well as low-metastasis clones (Clone-22, Clone-26) and their parental line, CNE-2. A popliteal lymph node model was used to evaluate the metastasis ability of different cellular populations. A tissue microarray was constructed from 330 NPC tissues and a total of 263 cases were informative for assessing the patients’ survival duration. A deglycosylation assay, lentiviral transduction, quantitative PCR, proliferation assay, Transwell assay, and wound-healing assay were used for the functional studies. The serglycin protein was shown to be secreted by the high-metastasis clone, but not by any of the low-metastasis clones. Suppression of serglycin by shRNA diminished serglycin secretion and subsequently inhibited migration and invasion by the high-metastasis clone, and also significantly reduced its metastasis rate in vivo. Overexpression of serglycin in low-metastasis cells resulted in a significantly increased metastasis rate in vivo. Moreover, secreted serglycin promoted cellular motility in the wild-type low-metastasis cells. Interestingly, suppression of serglycin reduced the protein level of vimentin but did not influence the level of E-cadherin in the high-metastasis clone. Proliferation was not influenced by serglycin in either the high- or low-metastasis clones. Importantly, in direct tumor samples, serglycin expression was significantly elevated in liver metastases from NPC relative to its expression in primary tumors. In conclusion, serglycin appears to play a potentially pivotal role in regulating NPC metastasis by way of enhancing cellular migration, cellular invasiveness, vimentin expression level, and the in vivo spread of cancer cells. Moreover, a high level of serglycin expression can potentially be used to predict shorter disease-free survival and shorter metastasis-free survival of NPC patients. Targeting serglycin could be a novel option for the prevention of NPC metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1476. doi:10.1158/1538-7445.AM2011-1476

Nasopharyngeal carcinoma (NPC) has its highest incidence in southern China and Southeast Asia. In order to obtain deeper insights into the molecular mechanism of NPC tumorigenesis, we performed genome expression profiling combined with computerized pathway analyses on 18 NPC tissues and 18 age-matched tissues of non-cancerous nasopharyngeal mucosa from individuals in the endemic area, Guangdong province, China, between Dec 2007 and Oct 2010. Gene expression profiling was performed using an Agilent gene expression kit and Agilent 4×44K microarray gene chips. One-way analysis of variance was used to identify the genes differentially expressed between cancer and non-cancerous tissues. Genes with a false discovery rate of less than 0.001 and a fold-change larger than 2 or less than 0.5 were selected for in silico network mapping combined with pathway analysis using GeneGo software. Pathways were prioritized based on the gene enrichment analysis. The genes’ connectivity was also integrated to identify the regulatory hotspots in the key pathways. Genes within or surrounding these hotspots constitute potential therapeutic targets. Genes previously known to be up-regulated in NPC that were detected in our study included CCND1, CDKN1A, STAT1, BCL2A1, SGK1, RAI14, FOXM1, EPHB2, PMAIP1, COL1A1, GADD45A, ICAM1, FANC1, ZWINT, LAMB3, CKAP4, ISG15, and MMP3; known down-regulated genes included ATM and INPP5D. However, what was of interest was the identification of a series of previously unrecognized genes: those up-regulated more than 10-fold included MMP1, HOXC8, KREMEN2, and HOXA1, and those down-regulated more than 10-fold included LTF, C7, SHISA3, SKLC26A7, and C16orf89. Although the deregulated pathways in NPC encompass many cytological functions, pathway analysis has been helpful in ranking a series of the most significant deregulated pathways, which include ECM remodeling pathways; alternative complement pathway; plasmin signaling pathway; the TGF, WNT, and cytoskeletal remodeling pathways; leukocyte chemotaxis pathway; and the BAFF and PLAU signaling pathways. Results will be presented on key genetic changes within these pathways that have been verified by biologically. In conclusion, we are beginning to recognize key genes and pathways, prioritized by pathway analysis, that appear likely to identify possible novel mechanisms of NPC tumorigenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 57. doi:10.1158/1538-7445.AM2011-57

Oncogenic activation of the K-ras gene occurs in >90% of pancreatic ductal carcinoma and plays a critical role in the pathogenesis of this malignancy. Increase of reactive oxygen species (ROS) has also been observed in a wide spectrum of cancers. This study aimed to investigate the mechanistic association between K-ras–induced transformation and increased ROS stress and its therapeutic implications in pancreatic cancer. ROS level, NADPH oxidase (NOX) activity and expression, and cell invasion were examined in human pancreatic duct epithelial E6E7 cells transfected with K-ras G12V compared with parental E6E7 cells. The cytotoxic effect and antitumor effect of capsaicin, a NOX inhibitor, were also tested in vitro and in vivo. K-ras transfection caused activation of the membrane-associated redox enzyme NOX and elevated ROS generation through the phosphatidylinositol 3′-kinase (PI3K) pathway. Importantly, capsaicin preferentially inhibited the enzyme activity of NOX and induced severe ROS accumulation in K-ras–transformed cells compared with parental E6E7 cells. Furthermore, capsaicin effectively inhibited cell proliferation, prevented invasiveness of K-ras–transformed pancreatic cancer cells, and caused minimum toxicity to parental E6E7 cells. In vivo, capsaicin exhibited antitumor activity against pancreatic cancer and showed oxidative damage to the xenograft tumor cells. K-ras oncogenic signaling causes increased ROS stress through NOX, and abnormal ROS stress can selectively kill tumor cells by using NOX inhibitors. Our study provides a basis for developing a novel therapeutic strategy to effectively kill K-ras–transformed cells through a redox-mediated mechanism.

// Peng Wang 1,2,* , Chao-feng Zhu 1,* , Ming-zhe Ma 1,* , Gang Chen 3,* , Ming Song 1 , Zhao-lei Zeng 1 , Wen-hua Lu 1 , Jing Yang 1 , Shijun Wen 1 , Paul J. Chiao 4 , Yumin Hu 1 and Peng Huang 1,3 1 Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China 2 Department of Emergency Medicine, Sun Yat-sen Memorial Hospital, Guangzhou, China 3 Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 4 Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA * These authors contributed equally to this work Correspondence to: Yumin Hu, email: // Peng Huang, email: // Keywords : K-Ras, miR-155, reactive oxygen species, pancreatic cancer Received : November 05, 2014 Accepted : May 02, 2015 Published : May 12, 2015 Abstract The oncogenic K-Ras can transform various mammalian cells and plays a critical role in development of pancreatic cancer. MicroRNAs (miRNA) have been shown to contribute to tumorigenic progression. However, the nature of miRNAs involved in K-Ras transformation remains to be investigated. Here, by using microarray we identified miR-155 as the most upregulated miRNA after both acute and prolonged activation of K-Ras in a doxycyline-inducible system. Pharmacological inhibition of MAPK and NF-κB pathway blocked the induction of miR-155 in response to K-Ras activation. Overexpression of miR-155 caused inhibition of Foxo3a, leading to decrease of major antioxidants including SOD2 and catalase, and enhanced pancreatic cell proliferation induced by ROS generation. Importantly, correlations of K-Ras, miR-155 and Foxo3a were also validated in human pancreatic cancer tissues. Therefore, we propose that miR-155 plays an important role in oncogenic K-Ras transformation mediated by cellular redox regulation.