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Askoxylakis V Garcia-Boy R Rana S Krämer S Hebling U Mier W Altmann A Markert A Debus J Haberkorn U 《PloS one》2010,5(12):e15962
Carbonic anhydrase IX (CAIX) is a transmembrane enzyme found to be overexpressed in various tumors and associated with tumor hypoxia. Ligands binding this target may be used to visualize hypoxia, tumor manifestation or treat tumors by endoradiotherapy.
Methods
Phage display was performed with a 12 amino acid phage display library by panning against a recombinant extracellular domain of human carbonic anhydrase IX. The identified peptide CaIX-P1 was chemically synthesized and tested in vitro on various cell lines and in vivo in Balb/c nu/nu mice carrying subcutaneously transplanted tumors. Binding, kinetic and competition studies were performed on the CAIX positive human renal cell carcinoma cell line SKRC 52, the CAIX negative human renal cell carcinoma cell line CaKi 2, the human colorectal carcinoma cell line HCT 116 and on human umbilical vein endothelial cells (HUVEC). Organ distribution studies were carried out in mice, carrying SKRC 52 tumors. RNA expression of CAIX in HCT 116 and HUVEC cells was investigated by quantitative real time PCR.Results
In vitro binding experiments of 125I-labeled-CaIX-P1 revealed an increased uptake of the radioligand in the CAIX positive renal cell carcinoma cell line SKRC 52. Binding of the radioligand in the colorectal carcinoma cell line HCT 116 increased with increasing cell density and correlated with the mRNA expression of CAIX. Radioligand uptake was inhibited up to 90% by the unlabeled CaIX-P1 peptide, but not by the negative control peptide octreotide at the same concentration. No binding was demonstrated in CAIX negative CaKi 2 and HUVEC cells. Organ distribution studies revealed a higher accumulation in SKRC 52 tumors than in heart, spleen, liver, muscle, intestinum and brain, but a lower uptake compared to blood and kidney.Conclusions
These data indicate that CaIX-P1 is a promising candidate for the development of new ligands targeting human carbonic anhydrase IX. 相似文献2.
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Stelios Paraskevaidis Efstratios K. Theofilogiannakos Vasileios Kamperidis Yiannis S. Chatzizisis Konstantinos Tsilonis Vassilios P. Vassilikos George Dakos George Stavropoulos Antonios Ziakas Stavros Hadjimiltiades Ioannis H. Styliadis 《Indian pacing and electrophysiology journal》2013,13(5):178-180
Brugada syndrome is an inherited channelopathy associated with an increased risk of syncope and sudden cardiac death. In rare cases it can be manifested with electrical storm. We report two cases of Brugada syndrome that presented with electrical storm and were treated successfully with oral quinidine, an "endangered species" drug. 相似文献
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The polycrystalline inclusion complex of cyclomaltohexaose, (alpha-CD)(2) x NaI(5) x 8H(2)O, has been investigated via dielectric spectroscopy over a frequency range of 0-100 kHz and the temperature range of 125-450 K. Additionally, a Raman spectroscopy study was accomplished in the temperature ranges of (i) 153-298 K and (ii) 303-413 K. The ln sigma versus 1/T variation revealed the order-disorder transition of some normal hydrogen bonds to those of a flip-flop type at 200.9 K. From 278.3 up to 357.1K, the progressive transformation (H(2)O)(tightly bound)-->(H(2)O)(easily movable) takes place resulting in an Arrhenius linear increment of the ac-conductivity with activation energy E(a)=0.32 eV. In the range of 357.1-386.1K a second linear part with E(a)=0.55 eV is observed, indicating the contribution of sodium ions via the water-net.The rapid decrease of the ac-conductivity at T>386.1K is due to the removal of the water molecules from the crystal lattice, whereas the abrupt increase at T>414.9 K is caused by the sublimation of iodine.The Raman bands at 160 and 169 cm(-1) indicate the coexistence of (I(2) x I(-) x I(2)) and (I3(-) x I(2)<-->I(2) x I3(-)) units, respectively.The (I3(-) x I(2)<-->I(2) x I3(-)) units are presented as form (I), and their central I(-) ion is disordered in occupancy ratio different from 50/50 (e.g., ...60/40...70/30...).The(I(2) x I(-) x I(2)) units are displayed by the 2 equiv forms (IIa) and (IIb). In (IIa) the central I(-) ion is twofold disordered in an occupancy ratio of 50:50, whereas in (IIb) the central I(-) ion is well-ordered and equidistant from the two I(2) molecules. At low temperatures the transformation (I)-->(IIa) takes place, whereas at high temperatures the inverse one (IIa)-->(I) happens. X-ray powder diffraction and Rietveld analysis revealed a triclinic crystal form with space group P1 and lattice parameters that are in good agreement with the theoretical values. 相似文献
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Plant and Soil - Natural and managed soils have been identified as the largest sources of atmospheric nitrous oxide (N2O). However, the quantification of N2O emissions from soils under natural... 相似文献
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Vasileios Papadopoulos Ioannis Mitroulis Stavros Giaglis 《Molecular biology reports》2010,37(1):355-358
Turkey is one of the few countries in the world where Familial Mediterranean Fever (FMF), an autoinflammatory disease caused
by mutations in MEFV, the gene encoding pyrin, is not rare. Many interesting studies regarding the genetics of Familial Mediterranean Fever in
Turkey have been already published. Despite that different MEFV genetic profiles have been revealed for Turkish FMF patients, deriving from different regions of Turkey, a systematic population
genetics analysis has not been carried out yet. The present study aims to investigate the population genetics of MEFV in Turkish FMF patients so as to additionally facilitate the clinical interpretation of individualized genetic data. All
relevant studies have been recruited by searching PubMed with the terms “MEFV”, “FMF”, and “Turkey”. Seven of them, including
3,061 FMF patients, contained all necessary data concerning allelic and genotypic frequencies of the 4 commonest MEFV mutations in Turkey (M694V, V726A, M680I, E148Q). From all 6,122 MEFV alleles analyzed, the M694V mutation was recognized in 15.6–52.2% (mean 29.3%), the V726A in 1.5–9.7% (mean 4.8%), the M680I
in 1.5–15.5% (mean 7.6%), and the E148Q in 3.2–13.9% (mean 5.5%). Unidentified mutations ranged from 0–42.9% (mean 16.8%).
No mutations were found in 0–54.5% (mean 36.0%) of the patients. The allelic and genotypic frequencies of the most frequent
mutation (M694V) showed aberration of the Hardy–Weinberg law for all 7 populations studied. By application of the Arlequin
2.0 population genetics software, the Fixation index (F
ST) was found to be 0.09994, thus demonstrating that the observed variability is mainly within (90.006%) and not among (9.994%)
populations (P < 0.00001). Moreover, the global test of differentiation demonstrated that every population differs from each other (P < 0.00325). Finally, the Ewens–Watterson test of selective neutrality yielded to statistical significance in only 3 populations.
In conclusion, Turkish FMF patients are characterized by an increased genetic heterogeneity, explained by the intrapopulation
differentiation. Thus, the regional origin should be regarded as a determining factor in the diagnosis of FMF in Turkish patients. 相似文献
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Li Y Harada T Juang YT Kyttaris VC Wang Y Zidanic M Tung K Tsokos GC 《Journal of immunology (Baltimore, Md. : 1950)》2007,178(3):1938-1947
Systemic lupus erythematosus (SLE) is an autoimmune/inflammatory disease characterized by autoantibody production and abnormal T cells that infiltrate tissues through not well-known mechanisms. We report that SLE T lymphocytes display increased levels of CD44, ezrin, radixin, and moesin (ERM) phosphorylation, stronger actin polymerization, higher polar cap formation, and enhanced adhesion and chemotactic migration compared with T cells from patients with rheumatoid arthritis and normal individuals. Silencing of CD44 by CD44 small interfering RNA in SLE T cells inhibited significantly their ability to adhere and migrate as did treatment with Rho kinase and actin polymerization inhibitors. Forced expression of T567D-ezrin, a phosphorylation-mimic form, enhanced remarkably the adhesion and migration rate of normal T cells. Anti-CD3/TCR autoantibodies present in SLE sera caused increased ERM phosphorylation, adhesion, and migration in normal T cells. pERM and CD44 are highly expressed in T cells infiltrating in the kidneys of patients with lupus nephritis. These data prove that increased ERM phosphorylation represents a key molecular abnormality that guides T cell adhesion and migration in SLE patients. 相似文献