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11.
Cristina Firanescu Paul NM Lohle Jolanda de Vries Caroline A Klazen Job R Juttmann William Clark Willem Jan van Rooij 《Trials》2011,12(1):1-5
Background
Combination of erlotinib and bevacizumab is a promising regimen in advanced non-squamous non-small-cell lung cancer (NSCLC). We are conducting a single arm phase II trial which aims to evaluate the efficacy and safety of this regime as a second- or third-line chemotherapy.Methods
Key eligibility criteria were histologically or cytologically confirmed non-squamous NSCLC, stage III/IV or recurrent NSCLC not indicated radical chemoradiation, prior one or two regimen of chemotherapy, age 20 years or more, and performance status of two or less. The primary endpoint is objective response rate. The secondary endpoints include overall survival, progression-free survival, disease control rate and incidence of adverse events. This trial plans to accrue 80 patients based on a two-stage design employing a binomial distribution with an alternative hypothesis response rate of 35% and a null hypothesis threshold response rate of 20%. A subset analysis according to EGFR mutation status is planned.Discussion
We have presented the design of a single arm phase II trial to evaluate the efficacy and safety of combination of bevacizumab and erlotinib in advanced non-squamous NSCLC patients. In particular we are interested in determining the merit of further development of this regimen and whether prospective patient selection using EGFR gene is necessary in future trials.Trial registration
This trial was registered at the UMIN Clinical Trials Registry as UMIN000004255 (http://www.umin.ac.jp/ctr/index.htm). 相似文献12.
Afforestation is a recommended practice to mitigate global warming. However, their implementation may generate undesirable impacts, mostly if exotic species are used. Plantations of Pinus radiata D Don in Ventania (Bs. As., Argentina) soils showed notorious increments of extractable P (Pe), which could affect the dynamic of this element as well as the degree of phosphorus saturation (GSPBray). The objectives of this study were: i) to quantify the GSPBray in Mollisols afforested with P. radiata comparing the results with those coming from adjacent, natural grassland areas (base line); ii) to evaluate the potential environmental risk induced by afforestation through the identification of a change point (PC) in the GSPBray indicative of a phosphate leaching increment. Treatments included mature stands of P. radiata (TB) and adjacent areas with natural grassland vegetation (TP). Samples were taken at 0-15; 15-30 and 30-45 cm soil depth, and texture, pH, total organic carbon (COT), Pe, soluble reactive phosphorus (PSR), phosphorus sorption index (ISP) and GSPBray were determined. The results showed a significant acidification in TB and an increase in the COT stock, indicating an additional atmospheric CO2 sequestration by the trees. The Pe and PSR values were notoriously higher in TB, and they were reflected in a significant increment in the GSPBray with respect to TP. The detection of a significant PC in the GSPBray-PSR regression indicates higher chances of phosphate leaching in the forest stands, which could reach water courses, lakes and artificial reservoirs promoting their eutrophication. Because of the potential environmental pollution risk of biologic origin derived from the afforestation with P. radiata in Mollisols areas, their inclusion in clean development practices must be reconsidered. 相似文献
13.
A V Grinberg N M Gevondyan N V Grinberg V Y Grinberg 《European journal of biochemistry》2001,268(19):5027-5036
The thermal unfolding and domain structure of Na+/K+-ATPase from pig kidney were studied by high-sensitivity differential scanning calorimetry (HS-DSC). The excess heat capacity function of Na+/K+-ATPase displays the unfolding of three cooperative domains with midpoint transition temperatures (Td) of 320.6, 327.5, 331.5 K, respectively. The domain with Td = 327.5 K was identified as corresponding to the beta subunit, while two other domains belong to the alpha subunit. The thermal unfolding of the low-temperature domain leads to large changes in the amplitude of the short-circuit current, but has no effect on the ATP hydrolysing activity. Furthermore, dithiothreitol or 2-mercaptoethanol treatment causes destruction of this domain, accompanied by significant disruption of the ion transporting function and a 25% loss of ATPase activity. The observed total unfolding enthalpy of the protein is rather low (approximately 12 J.g-1), suggesting that thermal denaturation of Na+/K+-ATPase does not lead to complete unfolding of the entire molecule. Presumably, transmembrane segments retain most of their secondary structure upon thermal denaturation. The binding of physiological ligands results in a pronounced increase in the conformational stability of both enzyme subunits. 相似文献
14.
I. I. Babichenko A. A. Kazantsev D. L. Titarov K. A. Shemyatovskii N. M. Gevondyan D. S. Melchenko A. I. Alekhin 《Cell and Tissue Biology》2016,10(4):332-339
A comparative analysis of the proliferative activity of inflammatory infiltrate cells and the distribution of collagen type I and III in granulomas formed in the area of contact of mesh materials made of polypropylene (PP Std Light) and titanium-coated polypropylene (TiMesh) was performed via polarized microscopy and immunohistochemical detection of Ki-67 protein. Mesh materials were implanted in the soft tissues of the lumbar region of rats. The number of proliferative cells around implants made of the standard polypropylene (PP Std Light) 7 days after the operation was detected with the use of antibodies to Ki-67 protein to be less than the number of those around titanium-coated polypropylene (TiMesh) (29.1 ± 5.7 and 33.6 ± 3.1%, respectively, p < 0.001). The similar differences were revealed 1 month after the beginning of the experiment (15.9 ± 4.3 and 26.9 ± 3.6%, respectively, p < 0.001). Various types of collagen fibers in granulomas around the implanted mesh materials were detected in polarized light with the use of sections stained with Sirius Red. The ratios between collagen fibers type I and III in granulomas around PP Std Light and TiMesh materials determined 7 days after the operation were 1.085 ± 0.022 and above 1.107 ± 0.013, respectively (p = 0.017). The ratio increased to 1.174 ± 0.036 and 1.246 ± 0.102, respectively (p = 0.045) 1 month after the operation. The obtained results suggest that the titanium coating of polypropylene stimulates the formation of collagen type I and more mature connective tissue around mesh endoprostheses. 相似文献
15.
Topology of Na+,K+-ATPase. Identification of the extra- and intracellular hydrophilic loops of the catalytic subunit by specific antibodies 总被引:1,自引:0,他引:1
N M Ovchinnikov YuALuneva E A Arystarkhova N M Gevondyan N M Arzamazova A T Kozhich V A Nesmeyanov N N Modyanov 《FEBS letters》1988,227(2):230-234
To study the topology of Na+,K+-ATPase monoclonal antibodies (MAbs) specific for membrane-bound enzyme were produced. Using immunofluorescence staining of viable cells or smears of a pig kidney embryonic (PKE) cell line, two groups of MAbs were selected, namely those binding to extra- or intracellular portions of the alpha-subunit. The extracellular location of peptide loop 804-841 linking the Vth and VIth intramembrane hydrophobic segments was proved using MAb VG2. Another MAb, IIC9, interacting with PKE cells only after membrane perforation (4% formaldehyde and 0.1% Tween-20), was shown to bind to the hydrophilic loop 868-945. The antigenic determinants recognized by MAb IIC9 and VG2 are located in peptides 887-904 and 810-825, respectively. The C-terminus of the alpha-subunit molecule was positioned on the outer side of the cytoplasmic membrane utilizing affinity-purified antibodies to the synthetic peptide corresponding to fragment 999-1008. 相似文献
16.
17.
MP Lisovoi NM Lesovoy GI Vasechko 《Archives Of Phytopathology And Plant Protection》2013,46(2):123-127
A new method of selection of the winter wheat varieties has been tested for resistance to the pest insects' complex by the traits of plants that are the markers of plant resistance. It makes it possible to use this method from year to year independently of the pests' density. 相似文献
18.
Adriaan D Bins Jacco van Rheenen Kees Jalink Jonathan R Halstead Nullin Divecha David M Spencer John BAG Haanen Ton NM Schumacher 《BMC biotechnology》2007,7(1):2
Background
Advances in fluorescence microscopy and mouse transgenesis have made it possible to image molecular events in living animals. However, the generation of transgenic mice is a lengthy process and intravital imaging requires specialized knowledge and equipment. Here, we report a rapid and undemanding intravital imaging method using generally available equipment. 相似文献19.
Background
The frequency of a haplotype comprising one allele at each of two loci can be expressed as a cubic equation (the 'Hill equation'), the solution of which gives that frequency. Most haplotype and linkage disequilibrium analysis programs use iteration-based algorithms which substitute an estimate of haplotype frequency into the equation, producing a new estimate which is repeatedly fed back into the equation until the values converge to a maximum likelihood estimate (expectation-maximisation). 相似文献20.
Purified chloroplast tRNAs were isolated fromPisum sativum leaves and radioactively labeled at their 3′ end using tRNA nucleotidyl transferase and α32P-labeled CTP. Pea ctDNA was fragmented using a number of restriction endonucleases and hybridized with thein vitro labeled chloroplast tRNAs by DNA transfer method. Genes for tRNAs have been found to be dispersed throughout the chloroplast
genome. A closer analysis of the several hybrid regions using recombinant DNA plasmids have shown that tRNA genes are localized
in the chloroplast genome in both single and multiple arrangements. Two dimensional gel electrophoresis of total ct tRNA have
identified 36 spots. All of them have been found to hybridize withPisum sativum ctDNA. Using recombinant clones, 30 of the tRNA spots have been mapped inPisum sativum ctDNA. 相似文献