An novel role of sphingosine kinase-1 (SPHK1) in the invasion and metastasis of esophageal carcinoma

<p>Abstract</p> <p>Background</p> <p>Treatment failure for esophageal carcinoma is frequently due to lymph node metastasis and invasion to neighboring organs. The aim of the present study was to investigate invasion- and metastasis-related genes in esophageal carcinoma cells <it>in vitro </it>and <it>in vivo</it>.</p> <p>Methods</p> <p>A metastasis model using a Matrigel invasion clonal selection approach was employed to establish a highly invasive subline EC9706-P4 from the esophageal carcinoma cell (ESCC) line EC9706. The differentially expressed genes of the subline and the parental cells determined by gene microarrays were further analyzed by RT-PCR and Western blotting.</p> <p>Results</p> <p>We identified <it>sphingosine kinase 1 (SPHK1) </it>as an invasion and metastasis-related gene of esophageal cancer. <it>SPHK1 </it>was overexpressed in the EC9706-P4 subline with high invasive capacity. Among six ESCC lines tested, KYSE2 and KYSE30 cells showed the highest <it>SPHK1 </it>mRNA and protein expressions as well as the most invasive phenotype. By Western blotting, in 7/12 cases (58%), SPHK1 expression was higher in esophageal carcinomas than in the companion normal tissue. In 23/30 cases (76%), SPHK1 protein expression was upregulated in the tumors compared to matched normal tissue by immunohistochemistry (IHC). Esophageal carcinoma tissue microarray analysis indicated that SPHK1 expression correlated with the depth of tumor invasion (<it>P </it>< 0.0001) and lymph node metastasis (<it>P </it>= 0.016). By Kaplan-Meier analysis, strong SPHK1 expression was significantly associated with clinical failure (<it>P </it>< 0.01), suggesting the involvement of SPHK1 in aggressiveness of human esophageal carcinoma. <it>SPHK1 </it>overexpression significantly increased the invasiveness of EC9706 cells <it>in vitro </it>and also increased EC9706 cell growth and spontaneous metastasis <it>in vivo</it>, promoting significant increases in tumor growth, tumor burden and spontaneous lung metastasis in nude mice. <it>SPHK1 </it>expression significantly correlated with the expression of many EGFR pathway genes associated with invasion of cancer cells. SPHK1 protein expression also significantly correlated with the phosphorylation of EGFR.</p> <p>Conclusion</p> <p>In summary, our data implicate <it>SPHK1 </it>in the metastasis of esophageal cancer. Our study also identified downstream mediators of SPHK1 in esophageal cancer cells that may mediate enhanced malignant behavior, and several of these mediators may be useful as therapeutic targets.</p

ATP synthase ecto-α-subunit: a novel therapeutic target for breast cancer

<p>Abstract</p> <p>Background</p> <p>Treatment failure for breast cancer is frequently due to lymph node metastasis and invasion to neighboring organs. The aim of the present study was to investigate invasion- and metastasis-related genes in breast cancer cells <it>in vitro </it>and <it>in vivo</it>. Identification of new targets will facilitate the developmental pace of new techniques in screening and early diagnosis. Improved abilities to predict progression and metastasis, therapeutic response and toxicity will help to increase survival of breast cancer patients.</p> <p>Methods</p> <p>Differential protein expression in two breast cancer cell lines, one with high and the other with low metastatic potential, was analyzed using two-dimensional liquid phase chromatographic fractionation (Proteome Lab PF 2D system) followed by matrix-assisted laser desorption/time-of-flight mass spectrometry (MALDI-TOF/MS).</p> <p>Results</p> <p>Up regulation of α-subunit of ATP synthase was identified in high metastatic cells compared with low metastatic cells. Immunohistochemical analysis of 168 human breast cancer specimens on tissue microarrays revealed a high frequency of ATP synthase α-subunit expression in breast cancer (94.6%) compared to normal (21.2%) and atypical hyperplasia (23%) breast tissues. Levels of ATP synthase expression levels strongly correlated with large tumor size, poor tumor differentiation and advanced tumor stages (<it>P </it>< 0.05). ATP synthase α-subunit over-expression was detected on the surface of a highly invasive breast cancer cell line. An antibody against the ATP synthase α-subunit inhibited proliferation, migration and invasion in these breast cancer cells but not that of a non-tumor derived breast cell line.</p> <p>Conclusions</p> <p>Over-expression of ATP synthase α-subunit may be involved in the progression and metastasis of breast cancer, perhaps representing a potential biomarker for diagnosis, prognosis and a therapeutic target for breast cancer. This finding of this study will help us to better understand the molecular mechanism of tumor metastasis and to improve the screening, diagnosis, as well as prognosis and/or prediction of responses to therapy for breast cancer.</p

Measurement of Particulate n-alkanes and PAHs Inside and Outside a Temple in Xiamen, China

Total suspended particles samples inside and outside the South Pu-Tuo Temple (SPT), a traditional Buddhist temple in Xiamen, China were collected and further analyzed for n-alkanes and polycyclic aromatic hydrocarbons (PAHs) during the periods of worship. It was observed that the concentrations of particulate n-alkanes at SPT were abnormally higher compared to the surrounding bus terminus and campus. In addition, benzo[a]pyrene (BaP) equivalent concentrations at SPT (7.1-26.3 ng/m(3)) were significantly higher than those at the bus terminus (5.1-6.9 ng/m(3)) although the PAH concentrations were comparable. The hazard potential of PAHs in terms of the carcinogenicity of BaP inside SPT is not acceptable because the indoor air quality standard of BaP recommended by the State Environmental Protection Administration of China is 1 ng/m(3) (daily mean). Ratios of fluoranthene to fluoranthene plus pyrene, indeno[1,2,3-cd] pyrene to indeno[1,2,3-cd] pyrene plus benzo[g,h,i] perylene and 1,7-DMP (dimethylphenanthrene) to 2,6-DMP plus 1,7-DMP were further calculated; the values of these three together with the ratio of retene to phenanthrene separated the SPT samples from the bus terminus samples, in that SPT samples showed a strong influence of wood burning (such as bamboo sticks, stick coatings, and joss paper).National Science Foundation of China [20777060

Nitrogen isotope composition of ammonium in PM 2.5 in the Xiamen, China: impact of non-agricultural ammonia

Abstract(#br)Since NH 3 is a significant precursor to ammonium in PM 2.5 and contributes significantly to atmospheric nitrogen deposition but largely remains unregulated in China, the insight into the source of NH 3 emissions by the isotopic investigation is important in controlling NH 3 emissions. In this study, atmospheric concentrations of NH 3 and water-soluble ion composition in PM 2.5 as well as nitrogen isotope ratios in NH 4 + (δ 15 N-NH 4 + ) in Xiamen, China, were measured. Results showed that average NH 3 concentration for the five sites in Xiamen was 7.9 μg m −3 with distinct higher values in the warm season and lower values in the cold season, and PM 2.5 concentration for the two sites (urban and suburban) was 59.2 μg m −3 with lowest values in summer. In the PM 2.5 , NH 4 +..

Nitrogen isotope composition of ammonium in PM2.5 in the Xiamen, China: impact of non-agricultural ammonia.

Since NH3 is a significant precursor to ammonium in PM2.5 and contributes significantly to atmospheric nitrogen deposition but largely remains unregulated in China, the insight into the source of NH3 emissions by the isotopic investigation is important in controlling NH3 emissions. In this study, atmospheric concentrations of NH3 and water-soluble ion composition in PM2.5 as well as nitrogen isotope ratios in NH4+ (δ15N-NH4+) in Xiamen, China, were measured. Results showed that average NH3 concentration for the five sites in Xiamen was 7.9 μg m-3 with distinct higher values in the warm season and lower values in the cold season, and PM2.5 concentration for the two sites (urban and suburban) was 59.2 μg m-3 with lowest values in summer. In the PM2.5, NH4+ concentrations were much lower than NH3 and showed a stronger positive correlation with NO3- than that with SO42- suggesting the formation of NH4NO3 and equilibrium between NH3 and NH4+. Although the concentrations of NH3 at the urban site were significantly higher than those at the suburban site, no significant spatial difference in NH4+ and δ15N-NH4+ was obtained. The distinct heavier δ15N-NH4+ values in summer than in other seasons correlated well with the equilibrium isotopic effects between NH3 and NH4+ which depend on temperature. The initial δ15N-NH3 values were in the range of waste treatment (- 25.42‰) and fossil fuel combustion (- 2.5‰) after accounting for the isotope fractionation. The stable isotope mixing model showed that fossil fuel-related NH3 emissions (fossil fuel combustion and NH3 slip) contributed more than 70% to aerosol NH4+. This finding suggested that the reduction of NH3 emissions from urban transportation and coal combustion should be a priority in the abatement of PM2.5 pollution in Xiamen

Effect of Surfactant on the Volatilization of Organochlorine Pesticides from Still Artificial Seawater

[摘要]：研究了阴离子表面活性剂十二烷基苯磺酸钠( SDBS) 对17 种有机氯农药(OCPs) 在模拟静海水水面挥发的影响及机制. 结 果表明, 低浓度SDBS的存在能抑制OCPs 的挥发, 抑制能力有随SDBS 浓度增加而增加的趋势, 且经盐常数校正后的气2水分配 系数与挥发速率常数在对数散点图上存在很好的正相关关系. OCPs 化合物挥发阻力分析表明, 低浓度SDBS 形成的表面膜不 会对OCPs 的挥发阻力产生直接影响, 但却增加了大气中OCPs 化合物在液面的沉降, 造成净挥发量减少, 且挥发性相对较强的 化合物受表面活性膜的影响更大.[ABstract]:The effect of sodium dodecylbenzene sulfonate ( SDBS) on the volatilization of 17 organochlorine pesticides ( OCPs) from still artificial seawater has been examined. The results show that SDBS at low concentration can retard the volatilization of OCPs compared to / clean0 surface. The retarding influence ismore pronounced for high level of SDBS than it is for low level of SDBS. A good positive correlation between the gas2seawater partition coefficients and the measured volatilization rates of OCPs is observed. Although the SDBS films present no significant, direct resistance to transfer, the films can absorb more OCPs from the above atmosphere with respect to the / clean0 surface and reduce the net volatilization flux from the still artificial seawater. The effect of the film is more pronounced for volatilization of more volatile OCPs than it is for less volatile OCPs.国家自然科学基金项目( 40603020) ; 中国博士后科学基金 项目(20060390186

Diurnal Variations of Particle-bound PAHs at a Traffic Site in Xiamen, China

To improve our current understanding of the fate of particle-bound PAHs, which include potent mutagens and carcinogens, diurnal measurements of these compounds were carried out from 23 Oct to 31 Dec 2008 at a busy traffic site in Xiamen, China. The sum of 19 PAH concentrations showed a just noticeable day-night difference in the warmer period (from 23 Oct to 25 Nov) to a remarkable day-night difference in the colder period (from 26 Nov to 31 Dec). However, the average profiles of the 19 PAHs in the warmer and colder periods were very similar for both day and night samples. Atmospheric mixing seemed to have more influence on the diurnal variations in PAHs than photodecomposition resulting from solar radiation, because PAH concentrations showed negative correlation with air temperature but significantly positive correlation with the ratios of reactive to stable PAHs, such as benz[a] anthracene to chrysene and benzo[a] pyrene to benzo[e] pyrene. Based on the diagnostic ratios of indeno[1,2,3-cd]pyrene to indeno[1,2,3-cd] pyrene plus benzo[g, h, i]perylene and fluoranthene to fluoranthene plus pyrene, the results showed that no significant differences were observed in PAHs sources between the warm and cold periods and a combination of grass, wood or coal combustion and petroleum sources in airborne particles might be the most significant contributors of PAHs. Gas-phase PAHs were calculated based on the theoretical gas/particle partitioning coefficients for 19 PAHs and a high fraction of daily exposure was attributed to particle-phase PAHs in most cases. The excess lifetime cancer risk in colder period was generally higher than in the warmer period. The total uncertainties were computed based on the simpler average error transfer formula.Natural Science Foundation (NSFC) [40971257, 20777060

P ollution of an ion ic surfactan t and PCB in coasta l surfa ce seawa ter of Fujian Lprovince

[摘要]：用亚甲蓝分光光度法和GC2ECD 法分别对福建近岸表层海水中的阴离子表面活性剂和PCBs进行了分析, 初步探 讨了表层海水中这两类污染物的来源。表层海水中阴离子表面活性剂浓度范围为0. 04~ 1. 987 mg/L, 较高浓度值站点主要 位于九龙江口、闽江口和湄洲湾海域。PCBs的浓度在3. 9 ~ 367. 1 ng/L之间, 整体上近岸站点浓度值比离岸站点高, 中北部 浓度值比南部高。与其他地区的研究结果及海水水质标准进行比较, 福建沿海表层海水中阴离子表面活性剂和PCB的污染 都较为严重。[Abstract]:The an ion ic surfactant and PCB in the coasta l su rface seawater of Fu jian p rovin ce were analyzed bymethylene blue sp ectro2 photometricmethod andGC2ECD, respectively. Th e concen trations ofmethylene b lu e act ive substan ce (MBAS) in th e surface seawater ranged from 0. 04 to 1. 987mg /L with the h ighest value found at the p ipe ou tlet near X iamen Un iversity. The elevated concentrat ions ofMBASwere observed in J iu long jiang, M in jiang Estuary andMeizhou Bay, poss ib ly du e to the d ischarge of sewage. Th e concentrat ions of totalPCBs ( d issolved p lu s particu late phase) ranged from 3. 9 to 367. 1 ng/L in th e surface L seawater and increased concentrat ions were ob served from offsh ore to inshore and from sou th to north. Th e pollut ion of an ion ic surfactan ts and PCBs in the coastal su rface sea2 water of Fu j ian P rovin ce is a seriou s prob lem comparingw ith other values reported andU S and Canada seawater2qu ality criteria.中国博士后科学基金( 20060390186); 国家自然科学基金项目( 40603020

Identification of single nucleotide polymorphism markers associated with resistance to bruchids (Callosobruchus spp.) in wild mungbean (Vigna radiata var. sublobata) and cultivated V. radiata through genotyping by sequencing and quantitative trait locus analysis

Interval mapping of bruchid resistance on physical maps of populations TC1966 x NM94 and V2802. (DOCX 14 kb