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111.
112.
Cao X You QD Li ZY Liu XR Xu D Guo QL Shang J Chern JW Chen ML 《Bioorganic & medicinal chemistry letters》2008,18(23):6206-6209
Because both c-Src and iNOS are key regulatory enzymes in tumorigenesis, a new series of 4-heterocycle amine-3-quinolinecarbonitriles as potent dual inhibitors of both enzymes were designed, synthesized and evaluated as multiple targets agents in cancer therapy. All compounds were evaluated by two related enzyme inhibition assays and an anti-proliferation assay in vitro. The results showed that most compounds inhibited c-Src and iNOS well. The best compound 8 inhibited both enzymes with the IC(50) values of 34.8 nM and 26.7 microM. Several compounds also showed moderate anti-proliferation at 10 microM against colon and liver cancer cell lines. 相似文献
113.
Yi-Chen Hsieh Jiann-Shing Jeng Huey-Juan Lin Chaur-Jong Hu Chia-Chen Yu Li-Ming Lien Giia-Sheun Peng Chin-I Chen Sung-Chun Tang Nai-Fang Chi Hung-Pin Tseng Chang-Ming Chern Fang-I Hsieh Chyi-Huey Bai Yi-Rhu Chen Hung-Yi Chiou Formosa Stroke Genetic Consortium 《PloS one》2012,7(10)
Background
Endogenous estrogens play an important role in the overall cardiocirculatory system. However, there are no studies exploring the hormone metabolism and signaling pathway genes together on ischemic stroke, including sulfotransferase family 1E (SULT1E1), catechol-O-methyl-transferase (COMT), and estrogen receptor α (ESR1).Methods
A case-control study was conducted on 305 young ischemic stroke subjects aged ≦ 50 years and 309 age-matched healthy controls. SULT1E1 -64G/A, COMT Val158Met, ESR1 c.454−397 T/C and c.454−351 A/G genes were genotyped and compared between cases and controls to identify single nucleotide polymorphisms associated with ischemic stroke susceptibility. Gene-gene interaction effects were analyzed using entropy-based multifactor dimensionality reduction (MDR), classification and regression tree (CART), and traditional multiple regression models.Results
COMT Val158Met polymorphism showed a significant association with susceptibility of young ischemic stroke among females. There was a two-way interaction between SULT1E1 -64G/A and COMT Val158Met in both MDR and CART analysis. The logistic regression model also showed there was a significant interaction effect between SULT1E1 -64G/A and COMT Val158Met on ischemic stroke of the young (P for interaction = 0.0171). We further found that lower estradiol level could increase the risk of young ischemic stroke for those who carry either SULT1E1 or COMT risk genotypes, showing a significant interaction effect (P for interaction = 0.0174).Conclusions
Our findings support that a significant epistasis effect exists among estrogen metabolic and signaling pathway genes and gene-environment interactions on young ischemic stroke subjects. 相似文献114.
Tian-Lu Cheng Bing-Mae Chen Lai-Yee Chan P.-Y. Wu Ji-Wang Chern S. R. Roffler 《Cancer immunology, immunotherapy : CII》1997,44(6):305-315
Methoxypoly(ethylene glycol) (PEG) modification of Escherichia coliβ-glucuronidase (βG) was examined as a method to improve the stability and pharmacokinetics of antibody-βG conjugates for
the targeted activation of glucuronide prodrugs at tumor cells. Introduction of 3 PEG molecules did not affect βG activity
whereas higher degrees of PEG modification produced progressively greater loss of enzymatic activity. The enzyme was found
to be stable in serum regardless of PEG modification. PEG-modified βG was coupled via a thioether bond to mAb RH1, an IgG2a antibody that binds to the surface of AS-30D hepatoma cells, to produce conjugates with 3 (RH1-βG-3PEG), 5.2 (RH1-βG-5PEG)
or 9.8 (RH1-βG-10PEG) PEG molecules per βG with retention of 75%, 45% and 40% of the combined antigen-binding and enzymatic
activity of the unmodified conjugate RH1-βG. In contrast to the rapid serum clearance of RH1-βG observed in mice, the PEG-modified
conjugates displayed extended serum half-lives. RH1-βG-3PEG and RH1-βG-5PEG also exhibited reduced spleen uptake and greater
tumor accumulation than RH1-βG. BHAMG, the glucuronide prodrug of p-hydroxyaniline mustard (pHAM), was relatively nontoxic in vivo. Injection of 6 mg/kg or 12 mg/kg pHAM i.v. depressed white
blood cell numbers by 46% and 71% whereas 80 mg/kg BHAMG reduced these levels by 22%. Although the tumor/blood ratio of RH1-βG-5PEG
was adversely affected by slow clearance from serum, combined therapy of small solid hepatoma tumors with this conjugate,
followed 4 and 5 days later with i.v. injections of BHAMG, cured all of seven mice with severe combined immunodeficiency.
Combined treatment with a control antibody-βG conjugate and BHAMG delayed tumor growth and cured two of six mice while treatment
with pHAM or BHAMG alone was ineffective.
Received: 27 February 1997 / Accepted: 6 May 1997 相似文献
115.
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Wu CS Lin JT Chien CL Chang WC Lai HL Chang CP Chern Y 《Molecular and cellular biology》2011,31(24):4874-4886
3'-5'-Cyclic AMP (cAMP) is an important second messenger which regulates neurite outgrowth. We demonstrate here that type VI adenylyl cyclase (AC6), an enzyme which catalyzes cAMP synthesis, regulates neurite outgrowth by direct interaction with a binding protein (Snapin) of Snap25 at the N terminus of AC6 (AC6-N). We first showed that AC6 expression increased during postnatal brain development. In primary hippocampal neurons and Neuro2A cells, elevated AC6 expression suppressed neurite outgrowth, whereas the downregulation or genetic removal of AC6 promoted neurite extension. An AC6 variant (AC6-N5) that contains the N terminus of AC5 had no effect, indicating the importance of AC6-N. The downregulation of endogenous Snapin or the overexpression of a Snapin mutant (Snap(Δ33-51)) that does not bind to AC6, or another Snapin mutant (Snapin(S50A)) that does not interact with Snap25, reversed the inhibitory effect of AC6. Pulldown assays and immunoprecipitation-AC assays revealed that the complex formation of AC6, Snapin, and Snap25 is dependent on AC6-N and the phosphorylation of Snapin. The overexpression of Snap25 completely reversed the action of AC6. Collectively, in addition to cAMP production, AC6 plays a complex role in modulating neurite outgrowth by redistributing localization of the SNARE apparatus via its interaction with Snapin. 相似文献
118.
Summary A simple and effective method for enzyme crystals immobilization is developed. The water- based acrylic latex mixed with enzyme crystals is coated on a porous membrane. When dried, the latex produces a continuous and strong film in which enzyme crystals are embedded. Latex of three different compositions are synthesized to immobilize urease. The urease crystals embedded in latex film shows a good thermal stability that the activity remains at 60% of its initial activity after 5 days' incubation at 50°C. The film containing amorphous urease powder, on the other hand, has a very poor thermal stability that urease activity decreases to 50% and 3% of its initial activity after 8 hrs' and 3 days' incubation, respectively. The diffusion limitation in the lattices of urease crystal is the main reason for the low activity retention of urease crystals embedded in the latex film. 相似文献
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120.
Lisa G. Riley Peter Hickey Matthew McKenzie Sze Chern Lim David Thorburn Michael T. Ryan Melanie Bahlo 《American journal of human genetics》2010,87(1):52-4343
Mitochondrial respiratory chain disorders are a heterogeneous group of disorders in which the underlying genetic defect is often unknown. We have identified a pathogenic mutation (c.156C>G [p.F52L]) in YARS2, located at chromosome 12p11.21, by using genome-wide SNP-based homozygosity analysis of a family with affected members displaying myopathy, lactic acidosis, and sideroblastic anemia (MLASA). We subsequently identified the same mutation in another unrelated MLASA patient. The YARS2 gene product, mitochondrial tyrosyl-tRNA synthetase (YARS2), was present at lower levels in skeletal muscle whereas fibroblasts were relatively normal. Complex I, III, and IV were dysfunctional as indicated by enzyme analysis, immunoblotting, and immunohistochemistry. A mitochondrial protein-synthesis assay showed reduced levels of respiratory chain subunits in myotubes generated from patient cell lines. A tRNA aminoacylation assay revealed that mutant YARS2 was still active; however, enzyme kinetics were abnormal compared to the wild-type protein. We propose that the reduced aminoacylation activity of mutant YARS2 enzyme leads to decreased mitochondrial protein synthesis, resulting in mitochondrial respiratory chain dysfunction. MLASA has previously been associated with PUS1 mutations; hence, the YARS2 mutation reported here is an alternative cause of MLASA. 相似文献