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1.

Background  

Hepatoma-derived growth factor (HDGF) belongs to a polypeptide family containing five additional members called HDGF related proteins 1–4 (HRP-1 to -4) and Lens epithelial derived growth factor. Whereas some family members such as HDGF and HRP-2 are expressed in a wide range of tissues, the expression of others is very restricted. HRP-1 and -4 are only expressed in testis, HRP-3 only in the nervous system. Here we investigated the expression of HDGF, HRP-2 and HRP-3 in the central nervous system of adult mice on the cellular level by immunohistochemistry. In addition we performed Western blot analysis of various brain regions as well as neuronal and glial cell cultures.  相似文献   

2.
Dynamic contrast-enhanced MRI (DCE-MRI) was used to noninvasively evaluate the effects of AG-03736, a novel inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinases, on tumor microvasculature in a breast cancer model. First, a dose response study was undertaken to determine the responsiveness of the BT474 human breast cancer xenograft to AG-013736. Then, DCE-MRI was used to study the effects of a 7-day treatment regimen on tumor growth and microvasculature. Two DCE-MRI protocols were evaluated: (1) a high molecular weight (MW) contrast agent (albumin-(GdDTPA)(30)) with pharmacokinetic analysis of the contrast uptake curve and (2) a low MW contrast agent (GdDTPA) with a clinically utilized empirical parametric analysis of the contrast uptake curve, the signal enhancement ratio (SER). AG-013736 significantly inhibited growth of breast tumors in vivo at all doses studied (10-100 mg/kg) and disrupted tumor microvasculature as assessed by DCE-MRI. Tumor endothelial transfer constant (K(ps)) measured with albumin-(GdDTPA)(30) decreased from 0.034+/-0.005 to 0.003+/-0.001 ml min(-1) 100 ml(-1) tissue (P<.0022) posttreatment. No treatment-related change in tumor fractional plasma volume (fPV) was detected. Similarly, in the group of mice studied with GdDTPA DCE-MRI, AG-013736-induced decreases in tumor SER measures were observed. Additionally, our data suggest that 3D MRI-based volume measurements are more sensitive than caliper measurements for detecting small changes in tumor volume. Histological staining revealed decreases in tumor cellularity and microvessel density with treatment. These data demonstrate that both high and low MW DCE-MRI protocols can detect AG-013736-induced changes in tumor microvasculature. Furthermore, the correlative relationship between microvasculature changes and tumor growth inhibition supports DCE-MRI methods as a biomarker of VEGF receptor target inhibition with potential clinical utility.  相似文献   

3.
随着核磁共振技术的不断创新及分子模拟计算的长足进步,用NMR结合电脑计算已成为研究蛋白质结构及功能的主要方法,本文以实际的范例,介绍台湾眼镜蛇毒的NMR研究成果,台湾NMR的研究工作正在蓬勃发展,目前最高磁场为600MHz,分别装置在中研院生物医学研究所(台北)及清华大学化学系(新竹)。  相似文献   

4.
Erabutoxins a and b are neurotoxins isolated from venom of a sea snake Laticauda semifasciata (erabu-umihebi). Amino acid sequences of the toxins indicated that the toxins are members of a superfamily consisting of short and long neurotoxins and cytotoxins found in sea snakes and terrestrial snakes. The short neurotoxins to which erabutoxins belong act by blocking the nicotinic acetylcholine receptor on the post synaptic membrane in a manner similar to that of curare. X-ray crystallography and NMR analyses showed that the toxins have a three-finger structure, in which three fingers made of three loops emerging from a dense core make a gently concave surface of the protein. The sequence comparison and the location of essential residues on the protein suggested the mechanism of binding of the toxin to the acetylcholine receptor. Classification of snakes by means of sequence comparison and that based on different morphological features were inconsistent, which led the authors to propose a hypothesis "Evolution without divergence."  相似文献   

5.
The European eelpout Zoarces viviparus is a common inhabitant in the coastal areas of the eastern Atlantic Ocean and the Baltic region. At least 3 different antifreeze proteins were purified from Z. viviparus serum but more isoforms are most likely present. Two antifreeze proteins with molecular weights of approx. 6.5-7 kDa were characterised and found to share high similarity to the type III antifreeze proteins found in other members of the family Zoarcidae. The antifreeze activity of Z. viviparus antifreeze proteins is concentration dependent and showed a saturation effect when the protein concentration reached 30 mg.ml-1 (crude serum) and 8 mg.ml-1 (partly purified serum) respectively. Further the antifreeze activity was found to be dependent of the buffer osmolality resulting in increasing thermal hysteresis when buffer osmolality was raised from 0 to 1M.  相似文献   

6.
台湾眼镜蛇毒的NMR研究   总被引:1,自引:0,他引:1  
余靖 《波谱学杂志》1995,12(4):357-372
随着核磁共振技术的不断创新及分子模拟计算的长足进步,用NMR结合电脑计算已成为研究蛋白质结构及功能的主要方法,本文以实际的范例,介绍台湾眼镜蛇毒的NMR研究成果,台湾NMR的研究工作正在蓬勃发展,目前最高磁场为600MHz,分别装置在中研院生物医学研究所(台北)及清华大学化学系(新竹)。  相似文献   

7.
Electrospun blended nanofibrous scaffolds were fabricated from an synthetic biodegradable polymer (poly(ethylene carbonate-?-caprolactone) (poly(EC-CL)) and vascular endothelial growth factor with different weight ratios. Results showed that the diameter of blended scaffolds was 440 ± 55 nm. VEGF on the surface of the blended scaffolds was identified by immunofluorescence. In vitro cell proliferation, viability assay results showed that human umbilical vein endothelial cells (HUVECs) had a good growth and spread morphology on the blended scaffolds. Scaffolds electrospun from this polymer contained VEGF had a good application in tissue engineering.  相似文献   

8.
Summary Multiple protein expression forms (MPEFs) presenting splicing forms or co- and posttranslation modifications, account for the vast diversity, the myriad of gene products and clearly indicate problems which proteomics research is facing. In the present study, we generated a rat brain map representing MPEFs by the use of an analytical method based on two-dimensional electrophoresis combined with mass spectrometry. Forty-nine individual proteins were selected that showed more than two spots, resulting altogether into a total number of 357 expression forms. Some proteins showed large MPEFs numbers as e.g. tubulin alpha-1 chain (24 spots), ATP synthase alpha-chain (28), beta chain (17) or septin 7 (13). The molecular diversity observed in this map clearly shows that immunochemical or even protein chemical results from expressional studies have to be interpreted with caution, in particular if one dimensional electrophoretic or western blot techniques are applied and MPEFs are poorly resolved.  相似文献   

9.
A novel approach to the study of venoms characterizes and compares the venom structure of genus Dendroaspis presented in this work. The complex molecular structure of individual venoms of genus Dendroaspis was defined graphically as a record of synchronous fluorescence fingerprint and atomic force microscopy. Simple comparison of these methods mentioned above of individual analyzed venom samples will immediately reveal changes in each venom composition. Application of these methods with electrophoresis and total protein concentration are new alternatives that were used for monitoring venom composition in selected snakes. Electrophoretogram of black mamba with very low content of total proteins contained the largest number of separated fractions, whereas synchronous fluorescence analysis showed that the highest endogenous fluorescence was found in the venom of black mamba compared with the venom of green mambas, respectively. Our results confirmed different molecular structure in the venom of the genus Dendroaspis. The practical advantages of the selected techniques are high sensitivity and minimal quantity of venom required for the assay. These novel methods show that the least toxic Dendroaspis intermedius contained the greatest amount of proteins contrary to Dendroaspis polylepis with a considerably lower content of proteins but the highest toxic bioactivity.  相似文献   

10.
Vascular endothelial growth factor (VEGF) and its receptor tyrosine kinase VEGFR-2 or kinase insert domain receptor (KDR) have been identified as promising targets for novel anticancer agents. To achieve new potent inhibitors of KDR, we conducted molecular fragment replacement (MFR) studies for the understanding of 3D-QSAR modeling and the docking investigation of arylphthalazines and 2-((1H-Azol-1-yl)methyl)-N-arylbenzamides-based KDR inhibitors. Two favorable 3D-QSAR models (CoMFA with q 2, 0.671; r 2, 0.969; CoMSIA with q 2, 0.608; r 2, 0.936) have been developed to predict the biological activity of new compounds. The new molecular database generated by MFR was virtually screened using Glide (docking) and further evaluated with CoMFA prediction, protein?Cligand interaction fingerprint (PLIF) and ADMET analysis. 44 N-(pyridin-4-ylmethyl)aniline derivatives as novel potential KDR inhibitors were finally obtained. In this paper, the work flow developed could be applied to de novo drug design and virtual screening potential KDR inhibitors, and use hit compounds to further optimize and design new potential KDR inhibitors.  相似文献   

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