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Cisplatin (DDP) is the first-line chemotherapy drug widely used for the treatment of lung cancer patients, whereas the majority of cancer patients will eventually show resistance to DDP. The mechanisms responsible for DDP resistance are not fully understood. Tongue cancer resistance-associated protein 1 (TCRP1) gene was recently cloned and reported to specially mediate DDP resistance in human oral squamous cell carcinoma (OSCC) cells. However, the mechanisms of TCRP1-mediated DDP resistance are far from clear, and whether TCRP1 participates in DDP resistance in lung cancer cells remains unknown. Here, we show that TCRP1 contributes to DDP resistance in lung cancer cells. Knockdown of TCRP1 sensitizes the cells to DDP and increases the DDP-induced DNA damage. We have identified that Pol β is associated with DDP resistance, and Pol β knockdown delays the repair of DDP-induced DNA damage in A549/DDP cells. We find TCRP1 interacts with Pol β in lung cancer cells. Moreover, TCRP1 knockdown decreases the level of Pol β and increases the level of its ubiquitination. These results suggest that TCRP1 contributes to DDP resistance through the prevention of Pol β degradation in lung cancer cells. These findings provide new insights into chemoresistance and may contribute to prevention and reversal of DDP resistance in treatment of lung cancer in the future.

A movement planning method for attitude adjustment of a drilling robot is presented in this paper. The double eccentric discs normal adjustment mechanism is used in the robot to adjust the attitude of the drill axis. To improve the adjustment efficiency, the robot should rotate the eccentric discs to the target point in a most effective way. But there are two available directions and attitudes to rotate, while the anti-trigonometric functions also have two solutions, the key problem of the movement planning is how to choose the optimal solutions from these calculated solutions to rotate the eccentric discs to improve the rotary efficiency. The principle of choosing the solutions is that the eccentric discs should rotate in the minimum absolute angle values to move to the target point. Finally, the movement loci from the initial position and a specific attitude to some different points in different quadrants are simulated in Mat lab to verify the feasibility of the rotary angle calculation method.

Aiming at the drilling verticality in aircraft assembly, this paper presents a design method of a Double-Eccentricdisc Normal-Adjustment (DENA) mechanism; it can adjust the two rotational degrees of freedom by the interaction of two eccentric discs, and make the drill axis coincide with the normal direction of the drilling point. This method ensures that the position of the drill vertex can be kept static during the attitude adjustment process. In addition, it can avoid position compensation and secondary positioning, and then improve the drilling efficiency. Using pressure sensor, the robot can control the countersink depth by detecting the states of the drill and the pressing force of the cylinder. It can eliminate the influence of the deformation under the compression to the countersink depth precision and make the countersink precision accuracy within 0.05mm. Finally, the experimental results are addressed to verify the rationality of DENA mechanism and the feasibility of using pressure sensor to control the countersink depth.

The paper describes a video detection method for two-wheeled vehicles appearing especially in the small-medium cities. The multi Gaussian mixture model is used to build the background and foreground. The single threshold method is efficiently used in shadow removal. Then Gaussian smooth filter processing and morphological image processing are used to filter out the noises in the foreground. The target region is obtained by comparing the difference of physical characteristics computed by labeled connecting area between general vehicles (cars) and two-wheeled vehicles. In the target region, the offline classifier based trained with local binary pattern (LBP) feature and AdaBoost algorithm, is used to accurate object detection. Experimental results show that the proposed method has a good performance in real-time and accurate detection of two-wheeled vehicles.

Cisplatin is one of the major chemotherapeutic agents used against different human cancers. A better understanding of the downstream cellular targets of cisplatin will provide information on its mechanism of action. FOXO3a is a member of the FOXO transcription factor family, which modulates the expression of genes involved in cell cycle arrest, apoptosis, and other cellular processes. In this study, we have investigated the effects of cisplatin in a panel of lung cancer cell lines. The results showed that cisplatin inhibited the proliferation of these lung cancer cell lines by inhibiting the PI3K/AKT pathway, with evidence of decreasing phosphorylation of PI3K and AKT under cisplatin treatment, and constitutively activating AKT1 could reduce cisplatin-induced cell apoptosis. More importantly, cisplatin significantly inhibited FOXO3a phosphorylation (at Thr32, AKT phosphorylation site) and induced FOXO3a nuclear accumulation, which in turn increased the expression of FOXO3a-dependent apoptotic protein Bim. Knockdown of FOXO3a expression using small interfering RNA attenuated cisplatin-induced apoptosis. Furthermore, activation of FOXO3a induced cell apoptosis irrespective of p53 status, whereas p53 may act as FOXO3a downstream molecules involved in cisplatin-induced cell apoptosis. Together, our findings suggested that FOXO3a is a relevant mediator of the cytotoxic effects of cisplatin in lung cancer cells.

miRNAs have been proposed to be key regulators of progression and metastasis in cancer. However, an understanding of their roles and molecular mechanisms is needed to provide deeper insights for better therapeutic opportunities. In this study we investigated the role and mechanism of miR-493 in the development and progression of nonsmall-cell lung cancer (NSCLC). Our data indicated that the expression of miR-493 was markedly reduced in pulmonary carcinoma. The ectopic expression of miR-493 impaired cell growth and invasion in vitro and in vivo. Mechanically, miR-493 commonly directly targeted E2F1, which resulted in a robust reduction of the expression of mRNA and protein. This effect, in turn, decreased the growth, invasion and metastasis of lung cancer cells. Our findings highlight the importance of miR-493 dysfunction in promoting tumor progression, and implicate miR-493 as a potential therapeutic target in lung cancer.

It is very important to identify the dominant precursors for N-nitrosamine formation from bulk organic matter, to enhance the understanding of N-nitrosamine formation pathways in water treatment plants and allow the development of practical treatment technologies. In this study, dissolved organic matter (DOM) from two source waters was fractionated with XAD resins and ultrafiltration membranes. The N-nitrosamine formation potential (FP) (ng of N-nitrosamines formed per mg of dissolved organic carbon (DOC)) from raw water and each fraction were measured and correlated with the fluorescence excitation-emission matrix (EEM), molecular weight (MW) and other assays. The results showed that the hydrophilic fraction had N-nitrosamine FP 1.3 to 3.5 times higher than the hydrophobic fraction from both source waters. The DOM fraction with low MW was the dominant fraction in these two source waters and contributed more precursors for N-nitrosamine formation than the larger MW fraction. The EEM spectra indicated there were notable amounts of soluble microbial products (SMPs) and aromatic proteins in the two studied rivers, which probably originated from wastewater discharge. The SMPs tended to be more closely correlated with N-nitrosodimethylamine formation potential than the other DOM components. Higher N-nitrosamine FP were also related to fractions with lower DOC/DON ratios and lower SUVA254 values.

article i nfo Knowledge of N-nitrosamine precursors from dissolved organic matter (DOM) is important for water profes- sionals to better control N-nitrosamine formation. The characterization of DOM from the Luan River in Northern China was conducted using Amberlite XAD resins and ultra-filtration methods. N-nitrosamine formation poten- tials were investigated for various DOM fractions. The removal of the DOM during water treatment were evaluated using dissolved organic carbon (DOC) and ultraviolet absorbance at 254 nm (UV254) bulk parameters as well as size exclusion chromatography and fluorescence spectroscopy. The results indicated that the XAD-4 hydrophilic fraction, with normalized yields of N-nitrosodimethylamine (NDMA), N-nitrosopyrrolidine (NPYR), N-nitrosomorpholine (NMOR), and N-nitrosopiperidine (NPIP) of 27.2, 5.2, 5.9, and 6.1 ng/mg-DOC, respectively, tended to form more N-nitrosamines than the hydrophobic and the transphilic fractions. The DOM fraction with a molecular weight (MW) below 1 kDa, with normalized yields of NDMA, NPYR, NMOR, and NPIP of 39.6, 8.1, 14.7, and 3.3 ng/mg-DOC, respectively, tended to form more N-nitrosamines than those with a higher MW. The limited removal of the hydrophilic fraction and the lower MW DOM faction during con- ventional water treatment processes suggests that the process may not effectively remove the nitrosamine precursors.

This paper addresses the design of a small humanoid robot BJHR-I with 19 degrees of freedom, including the allocation of degrees of freedom, prototype structure design, Adams and Solidworks modeling and simulation based on virtual prototyping technology, gait planning, the ARM11 + Single Chip system based on the hierarchical control system, finally, to achieve the walking experiment with the height of step 20mm, the distance of one step 85mm, and the walking period 12s through the physical prototype, and to prove that this design is stable and reliable, as well as to provide a basis for the following research projects related to the platform.

Street dust was collected from five roads with different traffic volumes in the metropolitan area of Beijing and separated into five size fractions. Concentrations of polycyclic aromatic hydrocarbons (PAHs) adsorbed on street dust in different size ranges and their correlation with specific surface area and total organic carbon (TOC) were investigated. Results show that the concentration of 16-PAHs of sieved samples ranges from 0.27 to 1.30 mg/kg for all the sampling sites. Particles smaller than 40 mum in diameter have the highest 16-PAHs concentration among all of the size ranges for street dust from the four sampling sites with vehicles running on. PAHs with three or four rings account for 68% of the overall 16-PAHs on average. Remarkable positive correlation exists between 16-PAHs concentration and specific surface area with R(2) values from 0.7 to 0.96 for the four sampling sites with vehicles running on. The relationship between the concentration of 16-PAHs and TOC is less clear.

Chemotherapy is not only important but also necessary for the patient of breast cancer. Breast cancer resistance protein (BCRP), an atypical drug efflux pump, mediates multidrug resistance in breast cancer. The aim of this study is to search new substrate of BCRP. The result will guide the drug selection of chemotherapy in BCRP-positive breast cancer. PA317/Tet-on/TRE-BCRP cell induced with doxycycline was used to screen the possible substrates of BCRP by MTT assay. The suspicious substrate [5-fluorouracil (5-Fu)] was further confirmed in PA317 and breast cancer cell MCF-7 by HLCP, apoptosis assay (staining and FACS) and RNAi technique. Mitoxantrone, 5-Fu, adriamycin, Methotrexate, Pirarubicin, and Etoposide were identified as substrates of BCRP. However, Paclitaxel, Vincristine, Vindesine, Mitomycin C, and cisplatin were not mediated by BCRP. 5-Fu was identified as substrate of BCRP for the first time. The further study showed that the intracellular retention dose of 5-Fu and the 5-Fu induced cellular apoptosis all decreased when BCRP highly expressed. Furthermore, 5-Fu accumulation and 5-Fu induced DNA damage increased when BCRP was silenced by RNAi in breast cancer cells. 5-Fluorouracil may be a specific substrate which can be bound by BCRP. BCRP can predict the sensitivity of breast cancer to 5-Fu. And BCRP-targeted therapy will reverse the resistance of breast cancer to 5-Fu.

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA TCRP-1 (Tongue Cancer Resistance-related Protein-1) gene was recently cloned from the multidrug resistance tongue cancer cell (Tca8113/PYM) which developed by ourselves team (GeneBank accession number: [EF36480][1]). Subsequently we found that the gene can mediate tongue cancer cells to specific cisplatin chemotherapy tolerance and radiotherapy tolerance, and its mechanism may be caused at least in part by TCRP1 induced activation of the PI3K/Akt/NF-κB signaling pathway and promotes cell survival. Recently, using real-time quantitative PCR and immunohistochemical method to detect various types of tumors and control normal tissue, we found that expression of TCRP1 in lung cancer, ovarian cancer and glioma were significantly higher than that of normal tissue. These results suggest that TCRP1 gene may be closely related to the carcinogenesis. In the present study we constructed a lentiviral vector expressing TCRP1 to transfect NIH/3T3 cells, and found proliferation rate of NIH/3T3/TCRP1 cells was significantly improved compared with NIH/3T3 cells and NIH/3T3/vector cells by detection with the CellTiter-Glo Assay. Clonogenic capacity of NIH/3T3/TCRP1 cells was 5.39 times and 20.18 times higher than the control group in plate cloning and soft agar cloning assay. Subcutaneous tumorigenicity experiment with self-controlled in 10 nude mice found only the injected site of NIH/3T3/TCRP1 cell emergence nodular masses about 1cm diameter after 3 weeks, and the tumorigenic rate was 90%. Pathological diagnosis of mass was fibrosarcoma. These results suggest that TCRP1 gene own an oncogene-like effect. In order to study the TCRP1 tumorigenic mechanisms, gene chips were used and showed that expression of total of 1894 genes were up-regulated and 3626 genes were down-regulated. Among these genes, the verification results of PDPK1, Akt, GSK3β and cyclinD1 were consistent with microarray results. Co-immunoprecipitation assay indicate that TCRP1 interact with PDPK1; FRET(Fluorescence Resonance Energy Transfer)experiments shows that TCRP1 can directly bind to PDPK1. On the other hand, the growth rate and in vitro colony forming ability of NIH/3T3/TCRP1 cells was significantly inhibited after using PDPK1 inhibitor AR-12 and TCRP1 interference. These data suggest that TCRP1 mediated PI3K/Akt pathway to the excessive activation by recruiting recruitment and activating of PDPK1, resulting in a series of growth and proliferation and cell transformation related factor expression or activation of its downstream. This may be the possible mechanism of cell malignant transformation induced by TCRP1. {This study was supported by grant from National Natural Science Foundation (81472184) of China.} Citation Format: Chengkun Wang, Xiaorong Liu, Qinwei Qiu, Zhijie Zhang, Jiang Yin, Guopei Zheng, Zhimin He. TCRP1 gene promotes NIH/3T3 cell transformation by over-activating PDPK1 and Akt. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2719. doi:10.1158/1538-7445.AM2015-2719 [1]: /lookup/external-ref?link_type=GEN&access_num=EF36480&atom=%2Fcanres%2F75%2F15_Supplement%2F2719.atom

Breast cancer resistance protein (BCRP) has been shown to confer multidrug resistance, but the mechanisms of its regulation are poorly understood. Here, we investigate the effects of wild-type and mutant p53, and nuclear factor kappa-B (NF-kappaB) (p50) on BCRP promoter activity in MCF-7 cells. Our results demonstrated that wild-type p53 markedly suppressed BCRP activity and enhanced the chemosensitivity of cells to mitoxantrone, whereas mutant p53 had little inhibitory effect. After inhibition of NF-kappaB, similar results were obtained. Following knockdown of endogenous p53, BCRP and p50 expressions were increased, and the chemosensitivity of the cells to mitoxantrone was decreased. We conclude that wild-type p53 acts as a negative regulator of BCRP gene transcription.