Approximately 30-40% of estrogen receptor a (ERa)-positive breast tumors express high levels of the cyclooxygenase-2 (COX-2) protein, and these high levels have been associated with a poorer prognosis in breast cancer patients. We speculate that high levels of COX-2 induce drug resistance in ERa-positive breast tumors, thus reducing the survival rate of patients with such tumors. Human breast cancer cell lines that express high levels of COX-2 are generally ERa negative. To determine whether COX-2 induces drug resistance, plasmids encoding the COX-2 gene were stably transfected into ERa-positive MCF-7 human breast cancer cells (MCF-7/COX-2). MCF-7/COX-2 cells were resistant to the selective estrogen receptor modulator tamoxifen but not to its analog, raloxifene. MCF-7/COX-2 cells were also resistant to the retinoid N-(4-hydroxyphenyl)retinamide (4-HPR) but not to its analog, all-trans retinoic acid. In contrast, the sensitivities of MCF-7/COX-2 cells to doxorubicin and paclitaxel were similar to those of the parental MCF-7 cells. We then determined which COX-2 product, prostaglandin E 2 (PGE 2 ) or prostaglandin F 2a is involved in the COX-2-mediated drug resistance. PGE 2 , but not PGF 2a , blocked the antiproliferative effects of tamoxifen and 4-HPR. Agonists that activate PGE 2 receptors and their downstream kinase effectors, protein kinases A and C, also blocked the growth inhibitory effects of these drugs. Increased levels of Bcl-2 and Bcl-X L proteins have been reported in mammary tumors of COX-2 transgenic mice and in human colon cancer cell lines that have high levels of COX-2. However, we did not observe any changes in Bcl-2, Bcl-X L , or Bax expression induced by COX-2 or PGE 2 . Here we report the novel findings that COX-2 uses PGE 2 to stimulate the activities of protein kinases A and C to induce selectively tamoxifen and 4-HPR resistance in ERa-positive breast cancer cells. Laboratory Investigation ( The cyclooxygenase-2 (COX-2) protein is the inducible form of the COX enzymes. Functionally, the COX-2-derived prostaglandins (PGs) have been shown to block apoptosis, induce invasion, and promote angiogenesis. High levels of COX-2 and its products prostaglandin E 2 (PGE 2 ) and prostaglandin F 2a (PGF 2a ) have been found in human mammary tumor tissues.1-9 Elevated COX-2 expression had been associated with breast tumors of an estrogen receptor a (ERa)-negative status, large tumor size, high histological grade, high proliferation rate, high p53 expression, and the presence of the amplification of the HER2/neu oncogene.2,4,7 High expression of COX-2 was associated with reduced disease-free survival in breast cancer patients with ERa-negative tumors.10
Spinocerebellar ataxia type 10 (SCA10) is a dominantly inherited disorder caused by an intronic ATTCT pentanucleotide repeat expansion. The ATXN10 gene encodes a novel protein, ataxin 10, known previously as E46L, which is widely expressed in the brain. Ataxin 10 deficiency has been shown recently to cause increased apoptosis in primary cerebellar cultures, thus implicated in SCA10 pathogenesis. The biologic functions of ataxin 10 remain largely unknown. By using yeast-two-hybrid screening of a human brain cDNA library, we identified the G-protein beta2 subunit (Gbeta2) as an ataxin 10 binding partner, and the interaction was confirmed by coimmunoprecipitation and colocalization in mammalian cells in culture. Overexpression of ataxin 10 in PC12 cells induced neurite extension and enhanced neuronal differentiation induced by nerve growth factor (NGF). Moreover, coexpression of ataxin 10 and Gbeta2 potently activated the Ras-MAP kinase-Elk-1 cascade. Dominant negative Ras or inhibitor of MEK-1/2 (U0126) aborted this activation, and blocked morphologic changes, whereas inhibition of TrkA receptor by K252a had no effects. Our data suggest that the ataxin 10-Gbeta2 interaction represents a novel mechanism for inducing neuritogenesis in PC12 cells by activating the Ras-MAP kinase-Elk-1 cascade.
A leaching solution of white mud was prepared from this waste material of soda production, and used for treatment of waste cutting oil emulsion. In alkaline conditions, the leaching solution of white mud generates hydroxide precipitates, which have relatively high specific surface area and excess surface energy, and readily adsorb the pollutants in waste cutting oil emulsion. The chemical composition of the white mud was determined and the hydroxide precipitates were characterized. The maximum removal efficiency (of turbidity, oil contents and TOC) was obtained at an adsorbent dosage of 4.0 g/L, pH 12.0 and 25°C. Leaching solutions of white mud could be used as an effective and low-cost material for treatment of waste cutting oil emulsion by the precipitation method.
Fe1.125Te alloys had been synthesized by solid state reaction methods. The effects of nitrogen annealing on Fe1.125Te lattice structure and physical properties had been studied. It was found that the lattice constants a and c increased after annealed at temperature 400~600 oC. When the temperature is above 850 oC, the size of the unit cell returns to the similar size of original samples. The step-like magnetic-thermal curves were observed after annealed at 900 oC, which is associated with two magnetic transitions. In vacuum, the transition temperatures are 122 K and 128 K, while in the nitrogen, they are 122 K and 138 K. The resistance-temperature curves indicate a semiconductor to metal transition around 69 K for N2 atmosphere.
This paper uses the PHOENICS software to discusses a screen set mode's influence on the indoor mechanical ventilation, then calculated face wind speed, air temperature, air age and PMV. And analyzes the comparison of data, therefore concluded a reasonable way of setting screen in the office building.
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