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Investigation Of Principal Pharmacodynamics Of Malignant Tumor Therapeutic Action And Comparison Of Phosphorylation Of Signaling Proteins By Vascular Basement Membrance Derived Multifunctional Peptide

Posted on:2007-06-19Degree:DoctorType:Dissertation
Country:ChinaCandidate:J G CaoFull Text:PDF
GTID:1104360185986771Subject:Pharmacology
Abstract/Summary:PDF Full Text Request
It has been reported that tumstatin and tumstatin's 74-98aa peptide possess significant anti-angiogenic activity. Tumstatin and tumstatin's 74-98aa peptide have been shown inhibiting activation of FAK,PI3-kinase, protien kinase B (PKB/Akt), and mammalian target of rapamycin (mTOR) in endothelial cells. Furthermore, those prevents the dissociation of eukaryotic initiation factor 4E protien (eIF4E) from 4E-binding protien 1 , leading to the inhibition of cap-dependent translation. The study indicates those are an α v β3 integrin-dependent angiogenic inhibitor.In earlier period the study had shown that synthetic peptide-derived encoding amino acids 185-203 of a noncollagenous domain (NCI) of the α 3 chain of type IV collage (tumstatin 197-215 peptide,tumstatin total length 244 amino acids) inhibits the activation of polymorphonuclear leukocytes. Then the 197-215 peptide of tumstatin also were demonstrated that promotes adhesion of human melanoma cells and inhibits proliferation of the cells potentially medited via binding to α v β3 integrin. The antitumor cell activity of tumstatin 197-215 peptide is not realized until the peptide region is exposed by truncation of tumstain, a requirement not essential for the anti-angiogenic activity of this domain.One way to detect the expression of proteins in a complex mixtureis to use immobilized antibodies as probes. The feasibility of developing such an array-based platform to study protein expression has been indicated by several reports. These include the use of membrane based arrays to screen for DNA, RNA, or protein-binding targets in bacterial expression libraries and filter-based ELISAs to characterize single-chain antibody libraries. Array formats have also been used to monitor protein-protein interactions, quantitate auto-antibodies, detect enzyme targets, and analyze interactions between proteins and small molecule drugs. Recently, Sreekumar A,et al. used antibody microarrays to monitor proteomic profiles of LoVo colon carcinoma cells exposed to ionizing radiation. This approach yielded both known radiation-regulated proteins such as p53 and DR5,3 and several novel associations such as DFF40/CAD and CEA.Vascular basement membrane-derived multifunctional peptide (VBMDMP) sequence (fusion gene of human IgG3 upper hinge region and two tumstatin-derived...
Keywords/Search Tags:neoplasm, recombinant vascular basement-derived multifunctional peptide, angiogenesis, signal protein, phosphorylation, therapeutic action
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