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A dynamic three-dimensional finite element analysis model for the stability of the reaction wall of a working well during pipe jacking is established on the basis of the rectangular pipe jacking project of No. 2 Shangdu Road Station on line 4 of the Zhengzhou rail transit system. A comparison of the simulation data with field monitoring data verifies the correctness of the model. Using the model, the effects of the elastic modulus of soil, thickness of solid, and depth of solid on the horizontal displacement of soil behind the reaction wall are analyzed. The results show that the elastic modulus of soil strongly affects the lateral displacement of the soil whereas the solid depth and thickness have a slight effect. The results of the study provide a theoretical basis for the structural design of a large rectangular-pipe jacking starter well. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to assess whether objectively measured hearing loss and self-perceived hearing handicap in adults are independently associated with food insecurity, and vice versa. Design: Cross-sectional population-based study. Population: 2,500 participants aged 50+ years from the Blue Mountains Hearing Study, with both complete pure-tone audiometry data and information on food security status. Measurements: The pure-tone average of frequencies 0.5, 1.0, 2.0 and 4.0 kHz (PTA0.5-4KHz) >25 dB HL in the better ear, established the presence of hearing loss. Self-perceived hearing handicap was assessed by administering the Hearing Handicap Inventory for Elderly Screening (HHIE-S total scores of ≥8 indicates hearing handicap). A 12-item food security survey was administered, comprising statements related to individual and household food situations. Results: Food insecurity was reported by 12.8% of study participants. After adjusting for all potential confounders, any self-perceived hearing handicap significantly increased the likelihood of participants reporting food insecurity by 94% (p<0.0001). Participants reporting any, mild or severe self-perceived hearing handicap had around 2-fold greater odds of experiencing food insecurity. Objectively measured hearing loss did not significantly influence the food security status of study participants. Conversely, food insecurity was significantly associated with both objectively measured hearing loss and self-perceived hearing handicap: multivariate-adjusted OR 1.37 (95% CI 1.01–1.88) and OR 1.83 (95% CI 1.40–2.39), respectively. Conclusions: Food insecurity was an important social determinant of hearing health among community-dwelling adults. Conversely, participants with a significant self-perceived hearing handicap were more likely to experience food insecurity. These findings add to our understanding of the substantial public health impact of both food insecurity and hearing loss and may highlight areas for future intervention. [ABSTRACT FROM AUTHOR]

A number of aurone and aurone analogues were designed and synthesized. The anticancer activities against Cervical Cancer (HeLa), human breast cancer (MCF-7), colon cancer (HT-29) and hepatocellular carcinoma (Hep3B, HepG2, and Huh7) cells were evaluated by MTT method in vitro. The results demonstrated that several compounds exhibited anti-cancer activity. Among them, the peracetyl glycosyl aurone showed effective anti-hepatocellular carcinoma cell activity, especially against two types of Hep3B and Huh7 cells. [ABSTRACT FROM AUTHOR]

β-Lactamase inhibition is an integral part of combination therapy to tackle antibiotic resistance. So far clavulanic acid is the only β-lactamase inhibitor that exhibits oral bioavailability. We synthesized new diazabicyclooctane derivatives by replacing the SO3H with CHXCOOR moiety. The antibacterial activity of these compounds, in combination with imipenem, was determined against ten bacterial strains. All compounds showed variable profile of β-lactamase inhibition, however, most of the compounds were potent against K. pneumoniae 700603 with two- to six-fold minimization of MIC value of imipenem. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a heterogeneous disease of the intestinal epithelium and ranks the third largest diagnosed malignancy in the world. Many studies have shown that the high risk of CRC is believed to be related to the formation of biofilms. To prove causation, it will be significant to decipher which specific bacteria in biofilms initiate and maintain CRC and fully describe their underlying mechanisms. Here we introduce a bacterial driver–passenger model. This model added a novel and compelling angle to the role of microorganisms, putting more emphasis on the transformation of bacterial composition in biofilms which play different roles in the development of CRC. In this model, bacterial drivers can initiate the formation of CRC through genotoxicity, while bacterial passengers maintain the CRC process through metabolites. On the basis of these pathogens, we further turned our attention to strategies that can inhibit and eradicate these pathogenic biofilms, with the aim of finding new ways to hinder colorectal carcinogenesis. [ABSTRACT FROM AUTHOR]

Background: Aerobic glycolysis has a pivotal role in the carcinogenic process. The current understanding of the functional role and mechanism of UCHL3-related aerobic glycolysis in pancreatic cancer is far from comprehensive, therefore requires an in-depth analysis on this aspect. Methods: In the present research, the expressions of ubiquitin carboxyl-terminal hydrolase L3 (UCHL3), lactate dehydrogenase A (LDHA) and Forkhead box protein M1 (FOXM1) were detected by qRT-PCR, Western blot and immunohistochemistry. The effects of UCHL3 knockdown or overexpression on pancreatic cancer cells were examined by determining cell viability and colony formation. Aerobic glycolysis was assessed according to glucose uptake, lactic acid production, and lactate dehydrogenase (LDH) activity. Dual-luciferase reporter assay was performed to detect LDHA promoter activity. Results: The results showed that UCHL3 expression was significantly increased in the pancreatic cancer tissues and cells, and that knocking down UCHL3 noticeably inhibited cell viability and aerobic glycolysis. Further investigations revealed that LDHA expression was promoted by UCHL3 and could be reduced by shFOXM1, and that low-expressed LDHA partly reversed the inhibition of aerobic glycolysis induced by overexpressed UCHL3. Conclusions: To conclude, this study demonstrates that UCHL3 plays a carcinogenic role by promoting aerobic glycolysis in pancreatic cancer, suggesting that UCHL3 may be a potential diagnostic and therapeutic target for the treatment of cancer. [ABSTRACT FROM AUTHOR]

Background: T lymphocyte are a strong indicator of treatment immune response. This study was aimed to determine the utility of T lymphocyte subsets, cytokines and inflammatory biomarkers in predicting the immunological benefits of Ganoderma spore powder (G. lucidum) in post-operative patients with breast and lung cancer. Methods: We prospectively evaluated 120 breast and lung cancer patients with or without G. lucidum. T lymphocyte subsets with relative cytokines were detected using flow cytometry and PCR and assessed by Spearman correlation analysis. The relationships between albumin-to-globulin ratio (AGR) and neutrophil–to-lymphocyte ratio (NLR) with G. lucidum treatment and prognosis were analyzed using Kaplan–Meier and Cox regression methods. Results: The prevalence of CD3 + CD4 + , CD3 + HLADR- types was higher in G. lucidum group compared to control, whilst CD4 + CD25 + Treg, CD3 + HLADR + cell types was lower. IL-12 levels were significantly higher during the treatment period which negatively impacted levels of IL-10. Other immunosuppressive factors such as COX2 and TGF-β1 had lower prevalence in treated patients. Correlation analysis showed a positive relationship between IL-10 and CD28. IL-2 was positively related to TGF-β1, whilst it was negatively related to CD3. Kaplan–Meier analysis suggested that low AGR/high NLR was related to poor progression free survival (PFS) and overall survival (OS). A combination of high AGR and low NLR may predicted treatment benefits associated with PFS and OS. Conclusions: Our findings show that T lymphocyte subsets combined with relevant cytokines and AGR/NLR inflammatory predictors may help to identify patients most likely to benefit from the immunological enhancements from G. lucidum treatment. [ABSTRACT FROM AUTHOR]

To investigate the anti-explosion behavior of high-strength reinforced concrete (RC) beam subjected to blast load, the ANSYS/LS-DYNA finite element analysis software was applied. Based on anti-explosion test results, the effects of reinforcement strength grade, reinforcement ratio and stirrup ratio on dynamic response, failure mode, resistance curve and ductility of RC beams under uniform blast load were studied. The anti-explosion performance of RC beam can be effectively improved by increasing the strength grade of the high-strength reinforcement. When the shear capacity is high enough, the ultimate capacity of high-strength RC beam can be significantly enhanced by increasing its reinforcement ratio. Anti-explosion performance may deteriorate due to the change of failure modes when the reinforcement ratio is increased to a certain extent. Increasing stirrup ratio can improve the shear capacity of high-strength RC beam to guarantee the full utilization of the advantage of high flexural capacity. For high-strength RC beam with sufficiently shear capacity, the further increase of stirrup ratio has a slight effect on the anti-explosion ability. [ABSTRACT FROM AUTHOR]

The wettability of brazing alloy on graphite surface is a key factor affecting the successful brazing of graphite to metals. By introducing active Cr, the traditional Sn0.3Ag0.7Cu brazing alloy can wet the graphite effectively. The design of active Cr introduction into SnAgCu alloy caused a significant decrease in contact angle, and the contact angle was decreased from 120° to 20° with the increasing content of active Cr. The influence of active Cr content on the wettability of SnAgCu/graphite system was investigated by sessile drop way at elevating and isothermal process in this work. Cr3C2 reaction layer formed at the interface of liquid alloy and graphite substrate, which enhanced the spreading of liquid brazing alloy and then decreased the contact angle. The thickness of Cr-C reaction layer kept identical of 2.5 μm with the further increasing content of active Cr. Finally, the wetting mechanism of SnAgCu-Cr/graphite system was proposed. [ABSTRACT FROM AUTHOR]

CuO hollow microspheres had been batch synthesized by a facile route of precipitating and annealing at 270 °C, which was derived from CuSO4·5H2O, Na2CO3 and CTAB. The morphology and structure of synthesized CuO powder were characterized by XRD, SEM, UV-Vis and BET. The formation mechanism of CuO hollow microspheres had been proposed based on the characterized structure and morphology. Firstly, the tiny Cu2(OH)2CO3 crystal strips are formed from CuSO4 and Na2CO3 aqueous solutions. Secondly, the tiny Cu2(OH)2CO3 crystal strips are assembled perpendicularly to the spherical CTA+ micelles surface due to the template of CTAB. Finally, the CuO hollow microspheres have been obtained due to the decomposition of Cu2(OH)2CO3 and burning of CTAB after annealing at 270 °C. High gas sensitivity to ethanol was achieved for the CuO hollow microspheres. The response of CuO hollow microspheres sensor is 5.6 to ethanol with the concentration of 400 ppm at 250 °C, and the responses/recover time is 17.0/11.9 s. Therefore, it indicates that the facile and batch route is a promising method to synthesize CuO hollow microspheres with excellent gas sensing properties. [ABSTRACT FROM AUTHOR]

Effect of 35BaO-35ZnO-30BO (BZB) addition on the sintering behaviors, phase evolution and microwave dielectric properties of Ti-modified BaTiNbO (BaTiNbO, BTNO) ceramics had been investigated. BZB addition effectively reduced the sintering temperature of BTNO from 1250 °C to about 900 °C. With increasing BZB addition, the crystal phase of the present ceramics changed from single phase BaTiNbO to mixing phases of BaTiNbO and BaTiNbO. And the major phase gradually became from BaTiNbO to BaTiNbO. Dielectric constant and temperature coefficient increased with the rising of BZB addition. But the Qf value gradually declined from 28000 to about 6000 GHz. The BTNO ceramics with 15% BZB addition exhibited excellent microwave dielectric properties as following: ε = 46.3, Qf = 5887 GHz and τ = 35.5 ppm/°C, which was potential of candidate materials for LTCC application. And the variation of microwave dielectric properties had been also discussed with the phase and microstructure evolution. [ABSTRACT FROM AUTHOR]

In this paper, influence of void ratio on phase change of thermal storage unit for heat pipe receiver under microgravity is numerically simulated. Accordingly, mathematical model is set up. Numerical method is offered. The liquid fraction distribution of thermal storage unit of heat pipe receiver is shown. Numerical results are compared with experimental ones in Japan. Numerical results show that void cavity prevents the process of phase change greatly. PCMmelts slowly during sunlight periods and freezes slowly during eclipse periods as the void ratio increases. The utility ratio of PCM during both sunlight periods and eclipse periods decreases obviously as the void ratio increases. The thermal resistance of void cavity is much higher than that of PCMcanister wall. Void cavity prevents the heat transfer between PCM zone and canister wall. [ABSTRACT FROM AUTHOR]

Structure and dielectric properties have been investigated for CaCuTiO (CCTO) ceramics prepared by rapid sintering with relatively high sintering temperature and very short holding time. A very small amount of CuO is observed in XRD patterns of CCTO ceramics. Surface SEM of CCTO ceramics exhibits large grain and intergranular phase. Complex impedance spectra indicate that the internal barrier layer capacitor (IBLC) microstructure has been formed in the CCTO ceramics. And a giant dielectric permittivity of 8.5 × 10 at 1 kHz is achieved for the CCTO ceramics sintered at 1130 °C for 30 min. The rapid sintering method may be effective in applying these ceramics, which are expected to facilitate IBLC microstructure. [ABSTRACT FROM AUTHOR]

Ferroptosis is an iron-dependent form of non-apoptotic cell death, but its molecular mechanism remains largely unknown. Here, we demonstrate that heat shock protein beta-1 (HSPB1) is a negative regulator of ferroptotic cancer cell death. Erastin, a specific ferroptosis-inducing compound, stimulates heat shock factor 1 (HSF1)-dependent HSPB1 expression in cancer cells. Knockdown of HSF1 and HSPB1 enhances erastin-induced ferroptosis, whereas heat shock pretreatment and overexpression of HSPB1 inhibits erastin-induced ferroptosis. Protein kinase C-mediated HSPB1 phosphorylation confers protection against ferroptosis by reducing iron-mediated production of lipid reactive oxygen species. Moreover, inhibition of the HSF1-HSPB1 pathway and HSPB1 phosphorylation increases the anticancer activity of erastin in human xenograft mouse tumor models. Our findings reveal an essential role for HSPB1 in iron metabolism with important effects on ferroptosis-mediated cancer therapy. [ABSTRACT FROM AUTHOR]

Thermal transport in high-strength polymethacrylimide (PMI) foam insulations is described, with special emphasis on the density and temperature effects on the thermal transport performance. Measurements of the effective thermal conductivity are performed by a freestanding sensor-based $$3\omega $$ method. A linear relationship between the density and the effective thermal conductivity is observed. Based on the analysis of the foam insulation morphological structures and the corresponding geometrical cell model, the quantitative contribution of the solid conductivity and the gas conductivity as well as the radiative conductivity to the total effective thermal conductivity as a function of the density and temperature is calculated. The agreement between the curves of the results from the developed model and experimental data indicate the model can be used for PMI foam insulating performance optimization. [ABSTRACT FROM AUTHOR]

The BMI1 protein contributes to stem cell pluripotency and oncogenesis via multiple functions, including its newly identified role in DNA damage response (DDR). Although evidence clearly demonstrates that BMI1 facilitates the repair of double-stranded breaks via homologous recombination (HR), it remains unclear how BMI1 regulates checkpoint activation during DDR. We report here that BMI1 has a role in G2/M checkpoint activation in response to etoposide (ETOP) treatment. Ectopic expression of BMI1 in MCF7 breast cancer and DU145 prostate cancer cells significantly reduced ETOP-induced G2/M arrest. Conversely, knockdown of BMI1 in both lines enhanced the arrest. Consistent with ETOP-induced activation of the G2/M checkpoints via the ATM pathway, overexpression and knockdown of BMI1, respectively, reduced and enhanced ETOP-induced phosphorylation of ATM at serine 1981 (ATM pS1981). Furthermore, the phosphorylation of ATM targets, including γH2AX, threonine 68 (T68) on CHK2 (CHK2 pT68) and serine 15 (S15) on p53 were decreased in overexpression and increased in knockdown BMI1 cells in response to ETOP. In line with the requirement of NBS1 in ATM activation, we were able to show that BMI1 associates with NBS1 and that this interaction altered the binding of NBS1 with ATM. BMI1 consists of a ring finger (RF), helix-turn-helix-turn-helix-turn (HT), proline/serine (PS) domain and two nuclear localization signals (NLS). Although deletion of either RF or HT did not affect the association of BMI1 with NBS1, the individual deletions of PS and one NLS (KRMK) robustly reduced the interaction. Stable expression of these BMI1 mutants decreased ETOP-induced ATM pS1981 and CHK2 pT68, but not ETOP-elicited γH2AX in MCF7 cells. Furthermore, ectopic expression of BMI1 in non-transformed breast epithelial MCF10A cells also compromised ETOP-initiated ATM pS1981 and γH2AX. Taken together, we provide compelling evidence that BMI1 decreases ETOP-induced G2/M checkpoint activation via reducing NBS1-mediated ATM activation. [ABSTRACT FROM AUTHOR]

Neutrophil extracellular traps (NETs) are formed when neutrophils expel their DNA, histones and intracellular proteins into the extracellular space or circulation. NET formation is dependent on autophagy and is mediated by citrullination of histones to allow for the unwinding and subsequent expulsion of DNA. NETs have an important role in the pathogenesis of several sterile inflammatory diseases, including malignancy, therefore we investigated the role of NETs in the setting of pancreatic ductal adenocarcinoma (PDA). Neutrophils isolated from two distinct animal models of PDA had an increased propensity to form NETs following stimulation with platelet activating factor (PAF). Serum DNA, a marker of circulating NET formation, was elevated in tumor bearing animals as well as in patients with PDA. Citrullinated histone H3 expression, a marker of NET formation, was observed in pancreatic tumors obtained from murine models and patients with PDA. Inhibition of autophagy with chloroquine or genetic ablation of receptor for advanced glycation end products (RAGE) resulted in decreased propensity for NET formation, decreased serum DNA and decreased citrullinated histone H3 expression in the pancreatic tumor microenvironment. We conclude that NETs are upregulated in pancreatic cancer through RAGE-dependent/autophagy mediated pathways. [ABSTRACT FROM AUTHOR]

Genome-wide gene expression measurements have enabled comprehensive studies that integrate the changes of gene expression and phenotypic information to uncover their novel associations. Here we reported the association analysis between psychophysical phenotypes and genome-wide gene expression changes in human adaptation to one of the most extreme climates on Earth, the Antarctic Dome Argus. Dome A is the highest ice feature in Antarctica, and may be the coldest, driest and windiest location on earth. It is considered unapproachable due to its hostile environment. In 2007, a Chinese team of 17 male explorers made the expedition to Dome A for scientific investigation. Overall, 133 psychophysical phenotypes were recorded, and genome-wide gene expression profiles from the blood samples of the explorers were measured before their departure and upon their arrival at Dome A. We found that mood disturbances, including tension (anxiety), depression, anger and fatigue, had a strong, positive, linear relationship with the level of a male sex hormone, testosterone, using the Pearson correlation coefficient (PCC) analysis. We also demonstrated that significantly lowest-level Gene Ontology groups in changes of gene expression in blood cells with erythrocyte removal were consistent with the adaptation of the psychophysical characteristics. Interestingly, we discovered a list of genes that were strongly related to significant phenotypes using phenotype and gene expression PCC analysis. Importantly, among the 70 genes that were identified, most were significantly related to mood disturbances, where 42 genes have been reported in the literature mining, suggesting that the other 28 genes were likely novel genes involved in the mood disturbance mechanism. Taken together, our association analysis provides a reliable method to uncover novel genes and mechanisms related to phenotypes, although further studies are needed. [ABSTRACT FROM AUTHOR]

Effects of BiVO addition on the sintering behavior, crystal structure, microstructure and microwave dielectric properties of CaLaTiO ceramics were investigated. When BiVO addition is below 3 %, the sintering temperature of CaLaTiO ceramics is reduced from 1,550 °C to about 1,400 °C. And only phase CaLaTiO is observed in the CaLaTiO ceramics. However, the secondary phase CaLaTiO appears when BiVO addition reached 3 %. It is important that a small amount of BiVO addition can not only lower the sintering temperature but also improve the microwave dielectric properties of CaLaTiO ceramics. The CaLaTiO ceramics with 1.0 % BiVO addition, which is sintered at 1,425 °C, exhibits excellent microwave dielectric properties of ε = 44.3, Q f = 51,377 GHz, τ = −9.0 ppm/°C. The variation of microwave dielectric properties had been also discussed with the structure evolution. [ABSTRACT FROM AUTHOR]

A deeper understanding of the role of autophagy, literally 'self-eating', in normal and cancer cell biology has emerged over the last few years. Autophagy serves as a vehicle for cells to respond to various stressors including genomic, hypoxic and nutrient stress, and to oppose mechanisms of 'programmed' cell death. Here, we review not only mechanisms of cell death and cell survival but also the early successes in applying autophagy inhibition strategies in solid tumors using the only currently available clinical inhibitor, oral hydroxychloroquine. In acute leukemia, currently available chemotherapy drugs promote cell death and demonstrate clinical benefit, but relapse and subsequent chemotherapy resistance is common. Increasing preclinical data suggest that autophagy is active in leukemia as a means of promoting cell survival in response to chemotherapy. We propose coupling autophagy inhibition strategies with current cytotoxic chemotherapy and discuss synergistic combinations of available anti-leukemic therapies with autophagy inhibition. Furthermore, novel autophagy inhibitors are in development and promise to provide new therapeutic opportunities for patients with leukemia. [ABSTRACT FROM AUTHOR]

Land-use spatial allocation is a multi-objective collaborative spatial optimization method for rational use of the land use. Based on global search capabilities and the information feedback mechanism of ant colony optimization (ACO), a land-use spatial allocation model (ACO-LA) is proposed. FirstlyFirst, a construction graph is built for modeling the land-use spatial allocation problem. SecondlySecond, the behaviors of artificial ants are improved so that the solution can be foundobtained quickly in the searchingsearch space. Finally, the ant colony generates optimized solutions by reconciling the conflicts between different planning objectives or by setting the relative dominance of different land-use types. Our study focuses on Gaoqiao Town of Fuyang City in Zhejiang Province, China. The model maximizes the land-use suitability and spatial compactness, and minimizes the cost of changing the land use, based on a variety of constraints, e.g., the optimal land-use structure and land-use policies. The results suggest that this model can obtain an optimized land-use spatial pattern from different sets of sub-objective weights and different development scenarios. With the constraint of the land-use structure, the land-use types can be distributed more reasonably by different sets of sub-objective weights. In different development scenarios, the model encourageencourages areas of land-use types in line with the development direction, adapting to meet different development needs by setting the relative dominance of the different land-use types, Wdominance, which is added to the component selection probability Pij. [ABSTRACT FROM AUTHOR]

Background: Recent diagnostic procedure advances have greatly improved early lung cancer detection. However, the invasive, unpleasant and inconvenient nature of current diagnostic procedures limits their application. There is a great need of novel non-invasive biomarkers for early lung cancer diagnosis. In the present study, we intend to determine whether the blood signatures of p14ARF promoter methylation are suitable for early detection of lung cancer. Methods: The study aimed to assess the probability of p14ARF promoter methylation in plasma samples to detect early lung cancer using nested methylation-specific PCR in the training set consisted of tumor tissues and paired blood. Besides, we were further to discuss the difference in time to progression between methylation and unmethylation of p14ARF promoter using univariate and multivariate analysis. Results: The methylation of p14ARF promoter was detected in 33.6 % of tumor tissues, and 12.1 and 25.2 % in distant-cancer mucosa and matched plasma, respectively, and our study has also demonstrated the positive correlation between them by Pearson's test ( r = 0.300). The tumor-free survival time of the unmethylation of p14ARF promoter is significantly longer than that of the methylation of p14ARF promoter in tumor tissues ( χ = 7.149, P = 0.008). Conclusion: The methylation of p14ARF promoter in plasma samples has strong potential as a novel non-invasive biomarker for early detection of lung cancer, and the methylation of p14ARF promoter was considered as prognostic factor in our study. [ABSTRACT FROM AUTHOR]

Background:Accumulating evidence demonstrates high levels of aldehyde dehydrogense (ALDH) activity in human cancer types, in part, because of its association with cancer stem cells. Whereas ALDH1A1 and ALDH7A1 isoforms were reported to associate with prostate tumorigenesis, whether other ALDH isoforms are associated with prostate cancer (PC) remains unclear.Methods:ALDH3A1 expression was analysed in various PC cell lines. Xenograft tumours and 54 primary and metastatic PC tumours were stained using immunohistochemistry for ALDH3A1 expression.Results:In comparison with the non-stem counterparts, a robust upregulation of ALDH3A1 was observed in DU145-derived PC stem cells (PCSCs). As DU145 PCSCs produced xenograft tumours with more advanced features compared with those derived from DU145 cells, higher levels of ALDH3A1 were detected in the former; a dramatic elevation of ALDH3A1 occurred in DU145 cell-derived lung metastasis compared with local xenograft tumours. Furthermore, while ALDH3A1 was not observed in prostate glands, ALDH3A1 was clearly present in PIN, and further increased in carcinomas. In comparison with the paired local carcinomas, ALDH3A1 was upregulated in lymph node metastatic tumours; the presence of ALDH3A1 in bone metastatic PC was also demonstrated.Conclusions:We report here the association of ALDH3A1 with PC progression. [ABSTRACT FROM AUTHOR]

This study was designed to assess the impact of premature ejaculation (PE) on a large population of men and their female partners using the instruments of intravaginal ejaculatory latency time (IELT) and patient-reported outcome (PRO) measures. A non-interventional, observational and cross-sectional field survey enrolled 2704 men with self-reported PE and their female partners from January 2010 to January 2012. PE was diagnosed by the International Society for Sexual Medicine (ISSM) criterion. IELT and sexual dysfunction were measured using a stopwatch and PRO measures, respectively. The incidence of PE in this study was 19.27%. PE negatively impacted on subjects and their partners, including reduced ejaculatory control and sexual satisfaction, and increased personal distress and interpersonal difficulty (P<0.001 for all). The severity of PE was considered worse by subjects than by their female partners (P<0.001). Reduced ejaculatory control and sexual satisfaction were considered the central themes of PE. Furthermore, a correlation was observed among the outcomes of IELT and PRO measures for subjects and their partners (absolute correlation coefficient ranged from 0.33 to 0.67). This in-depth qualitative study provides valuable insight into the PE status in Chinese men. Further research is needed to confirm and extend these results. [ABSTRACT FROM AUTHOR]

Purpose: In the present study, we intend to detect the expression of Forkhead box transcription (FOXM1) in gastric cancer tissues and cell lines, and analyze the correlation between FOXM1 expression and clinic-pathological features as well as their association with clinic outcomes in patients with resectable gastric cancers. Methods: We examined the expression of FOXM1 in 103 cancer tissues from patients who underwent gastrectomy during Jan 2007 to Nov 2007 and 68 randomly selected para-cancer tissues by immunohistochemistry. The expression of FOXM1 protein in the benign and malignant human gastric cell lines was simultaneously detected using Western blot analysis. Data on clinic-pathological features and relevant prognostic factors in these patients were then analyzed. Results: FOXM1 expression was absolutely higher in gastric cancer than para-cancer tissues ( P < 0.001) and normal gastric epithelium cell lines ( P = 0.022). No significant association was found between FOXM1 expression and any clinic-pathological parameters ( P > 0.1). FOXM1 amplification was showed to be independently associated with prognosis in gastric cancer patients ( P = 0.001), and its affection is more significant in patients with tumor size larger than 5 cm ( P = 0.004), pT3-4 ( P = 0.003) or pIII-IV ( P = 0.001) as a result of stage-stratified analysis. Conclusions: Overexpressed FOXM1 is a potential diagnostic and poor prognostic biomarker in postoperational gastric cancer patients. [ABSTRACT FROM AUTHOR]

Tumor cells require increased adenosine triphosphate (ATP) to support anabolism and proliferation. The precise mechanisms regulating this process in tumor cells are unknown. Here, we show that the receptor for advanced glycation endproducts (RAGE) and one of its primary ligands, high-mobility group box 1 (HMGB1), are required for optimal mitochondrial function within tumors. We found that RAGE is present in the mitochondria of cultured tumor cells as well as primary tumors. RAGE and HMGB1 coordinately enhanced tumor cell mitochondrial complex I activity, ATP production, tumor cell proliferation and migration. Lack of RAGE or inhibition of HMGB1 release diminished ATP production and slowed tumor growth in vitro and in vivo. These findings link, for the first time, the HMGB1-RAGE pathway with changes in bioenergetics. Moreover, our observations provide a novel mechanism within the tumor microenvironment by which necrosis and inflammation promote tumor progression. [ABSTRACT FROM AUTHOR]

A three-dimensional reticular macro-porous SiOC ceramics structure, made of spherical agglomerates, has been thermally characterized using a freestanding sensor-based $$3\omega $$ method. The effective thermal conductivity of the macro-porous SiOC ceramics, including the effects of voids, is found to be $$0.041\,\hbox { W}\cdot \hbox { m}^{-1}\cdot \hbox { K}^{-1}$$ to $$0.078\,\hbox { W}\cdot \hbox { m}^{-1}\cdot \hbox { K}^{-1}$$ at room temperature, comparable with that of alumina aerogel or carbon aerogel. These results suggest that SiOC ceramics hold great promise as a thermal insulation material for use at high temperatures. The measured results further reveal that the effective thermal conductivity is limited by the low solid-phase volume fraction for the SiOC series processed at the same conditions. For SiOC ceramics processed under different pyrolysis temperatures, the contact condition between neighboring particles in the SiOC networks is another key factor influencing the effective thermal conductivity. [ABSTRACT FROM AUTHOR]

A practical and reusable freestanding sensor based on the 3 ω technique is fabricated by encapsulating a nano-thick nickel detector between two pieces of Kapton film. Because of the protection of the Kapton layer, the mechanical strength and applicability of the sensor are greatly improved compared with the traditional 3 ω sensor. Furthermore, the nondestructive thermal-conductivity characterization for solids, liquids, and nanopowder specimens based on the 3 ω technique is first realized. However, the introduction of the additional protective film also induces an undesirable decrease in accuracy for the thermal-conductivity measurement. This article discusses the underlying reason for this decreased accuracy and accordingly proposes an error correction scheme for accurate determination of the thermal conductivity. [ABSTRACT FROM AUTHOR]

Background and aims: Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality worldwide. As CUGBP1 may also play a great role in tumor genesis and deterioration, the purpose of this study was to detect the expression of CUGBP1 mRNA and CUGBP1 and assess the prognostic significance of CUGBP1 in NSCLC. Methods: Expression of CUGBP1 mRNA and CUGBP was detected by Semi-quantitative PCR and Immunohistochemistry, respectively, from 57 NSCLC patients. The percentage of CUGBP1 mRNA and CUGBP1 expression was correlated with clinical characteristics using χ test. The prognostic significance was assessed by univariate and multivariate analyses in the Cox hazard model. Results: The expression of CUGBP1 mRNA and CUGBP1 was over-expressed in cancer group and was correlated with TNM stage and Differentiation. By both univariate and multivariate survival analyses, CUGBP1 expression ( P = 0.0074, HR = 3.701, 95 % CI 1.420-9.648), TNM-stage (HR = 4.043, 95 % CI 2.098-7.794) and age (HR = 3.207, 95 % CI 1.544-6.664) were noted to be independent indicators of a shorter postsurgical survival. Conclusions: The expression of CUGBP1 independently predicted a shorter postsurgical survival in NSCLC. [ABSTRACT FROM AUTHOR]

Acid-sensing ion channel 1a (ASIC1a) is the key proton receptor in nervous systems, mediating acidosis-induced neuronal injury in many neurological disorders, such as ischemic stroke. Up to now, functional ASIC1a has been found exclusively on the plasma membrane. Here, we show that ASIC1a proteins are also present in mitochondria of mouse cortical neurons where they are physically associated with adenine nucleotide translocase. Moreover, purified mitochondria from ASIC1a−/− mice exhibit significantly enhanced Ca2+ retention capacity and accelerated Ca2+ uptake rate. When challenged with hydrogen peroxide (H2O2), ASIC1a−/− neurons are resistant to cytochrome c release and inner mitochondrial membrane depolarization, suggesting an impairment of mitochondrial permeability transition (MPT) due to ASIC1a deletion. Consistently, H2O2-induced neuronal death, which is MPT dependent, is reduced in ASIC1a−/− neurons. Additionally, significant increases in mitochondrial size and oxidative stress levels are detected in ASIC1a−/− mouse brain, which also displays marked changes (>2-fold) in the expression of mitochondrial proteins closely related to reactive oxygen species signal pathways, as revealed by two-dimensional difference gel electrophoresis followed by mass spectrometry analysis. Our data suggest that mitochondrial ASIC1a may serve as an important regulator of MPT pores, which contributes to oxidative neuronal cell death. [ABSTRACT FROM AUTHOR]

Purpose: Current knowledge of the prognostic biomarkers of advanced non-small cell lung cancer (NSCLC) treated with gefitinib is poor. NSE mRNA as a potential prognostic biomarker of the effectiveness of gefitinib treatment in NSCLC, especially in the Chinese population, needs to be further validated. Patients and Methods: We retrospectively reviewed 168 advanced NSCLC patients treated with gefitinib between May 2006 and July 2010. NSE mRNA was measured using quantitative RT-PCR analysis for correlation with the clinical outcomes. Results: We found that NSE mRNA expression was inversely correlated with sensitivity to gefitinib in NSCLC patients. Patients without elevated NSE mRNA had a more RR (CR + RR) 45.1 % than elevated 18.9 % ( P = 0.0005). Moreover, the time to progression was 6.0 versus 4.2 months, respectively. Log-rank test was marginally significant (χ = 12.11, P = 0.0007) and Cox multivariate analysis revealed that NSE mRNA (HR = 3.076; 95 % CI 1.943-4.870; P < 0.0001) was an independent prognostic factor of NSCLC patients in the Chinese population. Conclusion: For NSCLC patients treated with gefitinib, patients without elevated NSE mRNA had a better prognosis than those with elevated NSE mRNA. Pretreatment NSE mRNA holds great potential as a prognostic biomarker in advanced NSCLC. Therefore, it is proposed that NSE mRNA should be routinely detected to screen patients who are more likely to benefit from gefitinib-based treatment. [ABSTRACT FROM AUTHOR]

Through multiple alignment analysis of mitochondrial tRNA-Thr and tRNA-Phe sequences from 161 fishes, new universal primers specially targeting the entire mitochondrial control region were designed. This new primer set successfully amplified the expected PCR products from various kinds of marine fish species, belonging to various families, and the amplified segments were confirmed to be the control region by sequencing. These primers provide a useful tool to study the control region diversity in economically important fish species, the possible mechanism of control region evolution, and the functions of the conserved motifs in the control region. [ABSTRACT FROM AUTHOR]

The effects of Ti-doping on the decomposition behavior, crystal structure, sintering behavior and dielectric properties have been investigated for the Ti-doped BiFeO ceramics derived from molten salt method. XRD reveals the almost pure phase BiFeO is synthesized in the Ti-doped BiFeO powders. And the particle size of Ti-doped BiFeO powers obviously decreases with the increase of Ti content. However, the sintering temperature elevates significantly after Ti-doping. The DC resistivity can enhance by up to four orders of magnitude (from 10 to 10 Ωm) with only 5 at% Ti doping. But the dielectric constant is suppressed from 10 to 10, and dielectric loss obviously reduces with a small amount of Ti doping. The variation of dielectric properties has been discussed from the decomposition of BiFeO phase. The Ti-doping can effectively suppress the decomposition reaction in Ti-doped BiFeO ceramics. [ABSTRACT FROM AUTHOR]

A major advancement in the treatment of chronic myeloid leukemia (CML) has been the development of imatinib and other BCR-ABL tyrosine kinase inhibitors. MicroRNAs (miRNAs) are small RNA molecules that influence gene expression by post-transcriptional regulation of messenger RNA. It is not yet clear how miRNAs are able to regulate the effectiveness of imatinib in CML. Here, we show that imatinib markedly inhibits expression of miR-30a in human CML cells. miR-30a is a potent inhibitor of autophagy by downregulating Beclin 1 and ATG5 expression. miR-30a mimic or knockdown of autophagy genes (ATGs) such as Beclin 1 and ATG5 by short hairpin RNA enhances imatinib-induced cytotoxicity and promotes mitochondria-dependent intrinsic apoptosis. In contrast, knockdown of miR-30a by antagomir-30a increases the expression of Beclin 1 and ATG5, and inhibits imatinib-induced cytotoxicity. These findings indicate that dysregulation of miR-30a may interfere with the effectiveness of imatinib-mediated apoptosis by an autophagy-dependent pathway, thus representing a novel potential therapeutic target in CML. [ABSTRACT FROM AUTHOR]

BiFeO powder was synthesized in NaCl media at temperature range from 700 to 800 °C, using BiO and FeO as raw materials. Effects of calcining temperature and salt ratios on the synthesis of BiFeO powder had been investigated. It was found that NaCl effectively promoted the formation of BiFeO. Almost pure BiFeO phase with a very small amount of BiFeO phase was synthesized at 750 °C with salt weight ratios of 1:1. A large amount of BiFeO phase decomposed to BiFeO and BiFeO phase when the temperature was up to 800 °C. In the present method, the calcining temperature played an important role in the formation of BiFeO phase. BiFeO ceramics derived from molten salt method were prepared and exhibited the higher dielectric constant. [ABSTRACT FROM AUTHOR]

Cancer cell molecular mimicry of stem cells (SC) imbues neoplastic cells with enhanced proliferative and renewal capacities. In support, numerous mediators of SC self-renewal have been evinced to show oncogenic potential. We have recently reported that short-hairpin RNA-mediated knockdown of the embryonic stem cell (ESC) self-renewal gene NANOG significantly reduced the clonogenic and tumorigenic capabilities of various cancer cells. In this study, we sought to test the potential pro-tumorigenic functions of NANOG, particularly, in prostate cancer (PCa). Using qRT-PCR, we first confirmed that PCa cells expressed NANOG mRNA primarily from the NANOGP8 locus on chromosome 15q14. We then constructed a lentiviral promoter reporter in which the −3.8-kb NANOGP8 genomic fragment was used to drive the expression of green fluorescence protein (GFP). We observed that NANOGP8-GFP+ PCa cells showed cancer stem cell (CSC) characteristics such as enhanced clonal growth and tumor regenerative capacity. To further investigate the functions and mechanisms of NANOG in tumorigenesis, we established tetracycline-inducible NANOG-overexpressing cancer cell lines, including both PCa (Du145 and LNCaP) and breast (MCF-7) cancer cells. NANOG induction promoted drug resistance in MCF-7 cells, tumor regeneration in Du145 cells and, most importantly, castration-resistant tumor development in LNCaP cells. These pro-tumorigenic effects of NANOG were associated with key molecular changes, including an upregulation of molecules such as CXCR4, IGFBP5, CD133 and ALDH1. The present gain-of-function studies, coupled with our recent loss-of-function work, establish the integral role for NANOG in neoplastic processes and shed light on its mechanisms of action. [ABSTRACT FROM AUTHOR]

The formation behavior of CaCuTiO (CCTO) had been investigated via solid state reaction from CaTiO, CuO and TiO powders. In the temperature range from 750 to 1,200 °C, the reaction sequence was traced by XRD, and the microstructure evolution of calcined powders was also investigated by SEM. CCTO began to form owing to the reaction between CaTiO, CuO and TiO at around 850 °C, and became the major phase at 1,000 °C. Finally, the single phase CCTO was obtained at 1,150 °C. However, CCTO was decomposed at CaTiO, CuO and TiO when the temperature increased to 1,200 °C. In addition, no other intermediate phases occurred in the synthesized process. The formation behaviors indicated that CaTiO prevented the formation and growth of CCTO. [ABSTRACT FROM AUTHOR]

An Nd:GYSO crystal has been grown by the Czochralski technique. The cell parameters were analyzed with X-ray diffraction (XRD). Room-temperature absorption and fluorescence spectra and fluorescence lifetime of the Nd:GYSO crystal were measured and analyzed. The Judd-Ofelt intensity parameters Ω were obtained to be 4.06, 4.65, and 3.63×10 cm, respectively. The absorption and emission cross sections and the branching ratios were calculated. The peak-emission cross section is 3.8×10 cm at 1074 nm with a FWHM of 8.8 nm. Pumped by a laser diode, a maximum 1.54 W continuous-wave (CW) laser output has been obtained with a slope efficiency of 27.4%. All the results show that Nd:GYSO crystal is a promising laser material. [ABSTRACT FROM AUTHOR]

CaO-SrO-LiO-LnO-TiO ceramics were prepared by solid state reaction method, where LnO consists of equal proportions of NdO and SmO. Dielectric properties and crystal structure were investigated with respect to the content of TiO. Single phase with an orthorhombic perovskites structure was formed within the composition range of investigation. The frequency dependence of dielectric properties of the present ceramics was extensively investigated. Dielectric constant was less sensitive to frequency. However, dielectric loss and temperature coefficients were both very sensitive to frequency and gradually decreased with increasing frequency, such as the variation was more than ten times between 1 MHz and several GHz. The relationship between the temperature coefficient and dielectric loss was also discussed at different frequencies. And the mechanism of the frequency dependence was discussed in term of the role of Li ions. [ABSTRACT FROM AUTHOR]

The thermal conductivities, thermal diffusivity, thermal anisotropy ratio, and thermal boundary resistance for the multilayered microstructure of a carbon nanotube (CNT) array are reconstructed experimentally using the 3ω method with two different width metal heaters. The thermal impedance in the frequency domain and sensitivity coefficients are introduced to simultaneously determine the multiple thermal parameters. The thermal conductivity at 295 K is 38 W · m · K along the nanotube growth direction, and two orders of magnitude lower in the direction perpendicular to the tubes with the anisotropy ratio as large as 86. Separation of the contact and CNT array resistances is realized through circuit modeling. The measured thermal boundary resistances of the CNT array/Si substrate and insulating diamond film interfaces are 3.1 m · K · MW and 18.4 m · K · MW, respectively. The measured thermal boundary resistance between the heater and diamond film is 0.085 m · K · MW using a reference sample without a CNT array. The thermal conductivity for a CNT array already exceeds those of phase-changing thermal interface materials used in microelectronics. [ABSTRACT FROM AUTHOR]

One hallmark of cancer is intrinsic or acquired resistance to apoptosis. Surprisingly, recent studies demonstrate that CD95/Fas/Apo1 and p53 upregulated mediator of apoptosis/PUMA (potent inducers of the death receptor and the mitochondrial apoptotic pathways, respectively) promote tumorigenesis. These findings provide important insights into the multifaceted roles of apoptosis in tumorigenesis. [ABSTRACT FROM AUTHOR]

passively mode-locked dual-wavelength Nd: GdVO laser with orthogonal polarizations is experimentally demonstrated. By changing the absorbed pump power, the laser can mode lock either at 1063 nm (with π polarization) or 1065 nm (with σ polarization), or simultaneously at both wavelengths with orthogonal polarizations. When mode locked at 1063 nm and 1065 nm, the laser produced pulses of 10 ps and 5.9 ps, respectively, with repetition rates of 143.7 MHz and 143.9 MHz. When simultaneously mode locked at both wavelengths, the pulsewidth was about 7 ps. The laser was demonstrated by exploiting the thermal lens and birefringence of the Nd: GdVO crystal. The laser uses one cavity and does not require the insertion of additional optical components. [ABSTRACT FROM AUTHOR]

Beclin 1, the mammalian orthologue of yeast Atg6, has a central role in autophagy, a process of programmed cell survival, which is increased during periods of cell stress and extinguished during the cell cycle. It interacts with several cofactors (Atg14L, UVRAG, Bif-1, Rubicon, Ambra1, HMGB1, nPIST, VMP1, SLAM, IP3R, PINK and survivin) to regulate the lipid kinase Vps-34 protein and promote formation of Beclin 1-Vps34-Vps15 core complexes, thereby inducing autophagy. In contrast, the BH3 domain of Beclin 1 is bound to, and inhibited by Bcl-2 or Bcl-XL. This interaction can be disrupted by phosphorylation of Bcl-2 and Beclin 1, or ubiquitination of Beclin 1. Interestingly, caspase-mediated cleavage of Beclin 1 promotes crosstalk between apoptosis and autophagy. Beclin 1 dysfunction has been implicated in many disorders, including cancer and neurodegeneration. Here, we summarize new findings regarding the organization and function of the Beclin 1 network in cellular homeostasis, focusing on the cross-regulation between apoptosis and autophagy. [ABSTRACT FROM AUTHOR]

Autophagy, a tightly regulated lysosome-dependent catabolic pathway, is important in the regulation of cancer development and progression and in determining the response of tumor cells to anticancer therapy. However, the role of autophagy in leukemia still remains largely unknown. Here we show that high-mobility group box 1 (HMGB1), the best characterized damage-associated molecular pattern, was released from leukemia cell lines after chemotherapy-induced cytotoxicity and activated autophagy to protect against injury. Treatment with HMGB1-neutralizing antibodies increased the sensitivity of leukemia cells to chemotherapy; whereas, exogenous HMGB1 rendered these cells more resistant to drug-induced cytotoxicity. Moreover, exogenous HMGB1 increased autophagy as evaluated by increased expression of the autophagic marker microtubule-associated protein light chain 3-II, degradation of sequestosome 1 (p62) and autophagosome formation. Furthermore, knockdown or pharmacological inhibition of either phosphoinositide 3-kinase-III or extracellular signal-regulated kinase kinase mitogen-activated protein kinase kinase/extracellular signal-regulated protein kinase inhibited HMGB1-induced autophagy. Taken together, these results suggest that HMGB1 release after chemotherapy is a critical regulator of autophagy and a potential drug target for therapeutic interventions in leukemia. [ABSTRACT FROM AUTHOR]

The functional relationship and cross-regulation between autophagy and apoptosis is complex. In this study we show that the high-mobility group box 1 protein (HMGB1) is a redox-sensitive regulator of the balance between autophagy and apoptosis. In cancer cells, anticancer agents enhanced autophagy and apoptosis, as well as HMGB1 release. HMGB1 release may be a prosurvival signal for residual cells after various cytotoxic cancer treatments. Diminished HMGB1 by short hairpin RNA transfection or inhibition of HMGB1 release by ethyl pyruvate or other small molecules led predominantly to apoptosis and decreased autophagy in stressed cancer cells. In this setting, reducible HMGB1 binds to the receptor for advanced glycation end products (RAGEs), but not to Toll-like receptor 4, induces Beclin1-dependent autophagy and promotes tumor resistance to alkylators (melphalan), tubulin disrupting agents (paclitaxel), DNA crosslinkers (ultraviolet light) and DNA intercalators (oxaliplatin or adriamycin). On the contrary, oxidized HMGB1 increases the cytotoxicity of these agents and induces apoptosis mediated by the caspase-9/-3 intrinsic pathway. HMGB1 release, as well as its redox state, thus links autophagy and apoptosis, representing a suitable target when coupled with conventional tumor treatments. [ABSTRACT FROM AUTHOR]

15-Lipoxygenase 2 (15-LOX2), a lipid-peroxidizing enzyme, is mainly expressed in the luminal compartment of the normal human prostate, and is often decreased or lost in prostate cancer. Previous studies from our lab implicate 15-LOX2 as a functional tumor suppressor. To better understand the biological role of 15-LOX2 in vivo, we generated prostate-specific 15-LOX2 transgenic mice using the ARR2PB promoter. Unexpectedly, transgenic expression of 15-LOX2 or 15-LOX2sv-b, a splice variant that lacks arachidonic acid-metabolizing activity, resulted in age-dependent prostatic hyperplasia and enlargement of the prostate. Prostatic hyperplasia induced by both 15-LOX2 and 15-LOX2sv-b was associated with an increase in luminal and Ki-67+ cells; however, 15-LOX2-transgenic prostates also showed a prominent increase in basal cells. Microarray analysis revealed distinct gene expression profiles that could help explain the prostate phenotypes. Strikingly, 15-LOX2, but not 15-LOX2sv-b, transgenic prostate showed upregulation of several well-known stem or progenitor cell molecules including Sca-1, Trop2, p63, Nkx3.1 and Psca. Prostatic hyperplasia caused by both 15-LOX2 and 15-LOX2sv-b did not progress to prostatic intraprostate neoplasia or carcinoma and, mechanistically, prostate lobes (especially those of 15-LOX2 mice) showed a dramatic increase in senescent cells as revealed by increased SA-βgal, p27Kip1 and heterochromatin protein 1γ staining. Collectively, our results suggest that 15-LOX2 expression in mouse prostate leads to hyperplasia and also induces cell senescence, which may, in turn, function as a barrier to tumor development. [ABSTRACT FROM AUTHOR]

Ultrahigh-repetition-rate (over 100 GHz) bound-soliton pulses were experimentally generated in a fiber laser. Through incorporating a Loyt-type filter made of a piece of high birefringent fiber and an intracavity polarizer in a fiber laser, we found that not only ultrahigh-repetition-rate single-pulse soliton but also bound-soliton trains could be generated. Numerical simulations confirm the experimental observations. [ABSTRACT FROM AUTHOR]

Activation of the induced receptor for advanced glycation end products (RAGE) leads to initiation of NF-κB and MAP kinase signaling pathways, resulting in propagation and perpetuation of inflammation. RAGE-knockout animals are less susceptible to acute inflammation and carcinogen-induced tumor development. We have reported that most forms of tumor cell death result in release of the RAGE ligand, high-mobility group protein 1 (HMGB1). We now report a novel role for RAGE in the tumor cell response to stress. Targeted knockdown of RAGE in the tumor cell, leads to increased apoptosis, diminished autophagy and decreased tumor cell survival . In contrast, overexpression of RAGE is associated with enhanced autophagy, diminished apoptosis and greater tumor cell viability. RAGE limits apoptosis through a p53-dependent mitochondrial pathway. Moreover, RAGE-sustained autophagy is associated with decreased phosphorylation of mammalian target of rapamycin (mTOR) and increased Beclin-1/VPS34 autophagosome formation. These findings show that the inflammatory receptor, RAGE, has a heretofore unrecognized role in the tumor cell response to stress. Furthermore, these studies establish a direct link between inflammatory mediators in the tumor microenvironment and resistance to programmed cell death. Our data suggest that targeted inhibition of RAGE or its ligands may serve as novel targets to enhance current cancer therapies. [ABSTRACT FROM AUTHOR]

Bcl-2 proteins are over-expressed in many tumors and are critically important for cell survival. Their anti-apoptotic activities are determined by intracellular localization and post-translational modifications (such as phosphorylation). Here, we showed that WAVE1, a member of the Wiskott-Aldrich syndrome protein family, was over-expressed in blood cancer cell lines, and functioned as a negative regulator of apoptosis. Further enhanced expression of WAVE1 by gene transfection rendered leukemia cells more resistant to anti-cancer drug-induced apoptosis; whereas suppression of WAVE1 expression by RNA interference restored leukemia cells' sensitivity to anti-drug-induced apoptosis. WAVE1 was found to be associated with mitochondrial Bcl-2, and its depletion led to mitochondrial release of Bcl-2, and phosphorylation of ASK1/JNK and Bcl-2. Furthermore, depletion of WAVE1 expression increased anti-cancer drug-induced production of reactive oxygen species in leukemia cells. Taken together, these results suggest WAVE1 as a novel regulator of apoptosis, and potential drug target for therapeutic intervention of leukemia. [ABSTRACT FROM AUTHOR]