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Disintegrins (0):
Recent article
Disintegrins
Abstract
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Abstract
We have used various methanol feeding strategies to enhance the production of saxatilin. Saxatilin is a novel snake venom-derived disintegrin that inhibits tumor angiogenesis and metastasis and has been shown to suppress ovarian cancer cell invasion. A two-step increase feeding strategy to control t...
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PMID: 20547360
PDF is available here.
PDF is available here.
Abstract
Cell culture experiments indicate that the combination of docetaxel and CN inhibits growth in an additive fashion. FACS analysis of PC-3 cells shows expression of alpha5beta1 and alphavbeta5 integrins, but little expression of the alphavbeta3. CN showed complete inhibition of PC-3 migration in cultu...
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PMID: 20623636
PDF is available here.
PDF is available here.
Biochimica et Biophysica Acta (1803)7 2010
Abstract
We sought to investigate the main signaling events triggered by alpha(9)beta(1) integrin engagement and how these signaling pathways modulate the apoptotic program of human neutrophils. Using VLO5, a snake venom disintegrin shown to bind to alpha(9)beta(1) integrin in neutrophils, we demonstrate tha...
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PMID: 20362630
PDF is available here.
PDF is available here.
Abstract
The ADAM28 eukaryotic plasmid group showed the highest expression level in HPDLSCs, whereas the AS-ODN group displayed the lowest. Furthermore, the overexpression of ADAM28 enhanced the proliferation of HPDLSCs and inhibited the specific differentiation of HPDLSCs, whereas the inhibition of ADAM28 p...
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PMID: 20450360
PDF is available here.
PDF is available here.
Matrix Biology (29)4 2010
Abstract
Venoms are cocktails containing pharmacologically active compounds, which drastically affect essential functions of the neuromuscular and cardiovascular system, as well as of blood, kidney and other organs. As the extracellular matrix and its contacts with cells are responsible for maintaining the i...
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PMID: 20079834
PDF is available here.
PDF is available here.
Abstract
We designed and examined several ADAM22 variants. We discovered that the ADAM22 P81R variant, the most common polymorphic variation, works as well as the wild-type ADAM22. We also showed that mutations in the disintegrin domain cause a marked decrease in the processing of ADAM22 preproteins, and res...
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PMID: 20156119
PDF is available here.
PDF is available here.
Abstract
Journal of Neurochemistry (108)6 2009
Abstract
We demonstrate that ADAM10 itself is subject to shedding by one or more ADAMs. Expression of epitope-tagged wild-type ADAM10 in SH-SY5Y cells enabled the detection of a soluble ectodomain in conditioned medium. Shedding of the ADAM10 ectodomain was inhibited by a known ADAM inhibitor with a reciproc...
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PMID: 19183255
PDF is available here.
PDF is available here.
Archives of Toxicology (83)3 2009
Abstract
Snake venoms are complex mixtures of proteins, which affect the vital biologic systems of prey, as well as humans. Envenomation leads to immobilization by paralysis, cardiac, and circulatory failure. These same venom proteins that cause havoc in the physiologic system could be used as therapeutic ag...
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PMID: 18830584
PDF is available here.
PDF is available here.
Biochemical Journal (417)1 2009
Abstract
We have produced recombinant full-length wild-type and site-directed mutants of obtustatin to assess the role of the K(21)TS(23) tripeptide and C-terminal residues for specific inhibition of the alpha(1)beta(1) integrin. Thr(22) appeared to be the most critical residue for disintegrin activity, wher...
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PMID: 18774946
PDF is available here.
PDF is available here.
Oncology Research (18)5-6 2009
Abstract
Recently, a number of reports have demonstrated that coexpression of therapeutic genes having different anticancer mechanisms is a more effective strategy for anticancer gene therapy than single gene expression. Saxatilin, a novel disintegrin from snake venom, has recently been shown to have potent...
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PMID: 20225758
PDF is available here.
PDF is available here.
Abstract
We show that specific amino acid changes in the ECM proteins fibulin-1C (FBL-1C) and type IV collagen (LET-2) result in bypass of the requirement for MIG-17 activity in gonadal leader cell migration in a nidogen (NID-1)-dependent and -independent manner, respectively. The MIG-17, FBL-1C and LET-2 ac...
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PMID: 19104038
PDF is available here.
PDF is available here.
Abstract
We present the crystal structure of bothropasin complexed with the inhibitor POL647. The catalytic domain consists of a scaffold of two subdomains organized similarly to those described for other SVMPs, including the zinc and calcium-binding sites. The free cysteine residue Cys189 is located within...
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PMID: 18831982
PDF is available here.
PDF is available here.
Experimental Hematology (36)12 2008
Abstract
We hypothesize that disintegrin initially binds to specific epitope of GPIIb/IIIa, causing conformational change, and the recruitment of FcgammaRII, which can be bound by AP2, and finally triggering platelet aggregation....
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PMID: 18809237
PDF is available here.
PDF is available here.
Obstetrics & Gynecology (112)5 2008
Abstract
In the control group the concentration of ADAM12 increased with fetal crown rump length, decreased with maternal weight and was higher in African-American than in white women. There was a significant association between ADAM12 and pregnancy-associated plasma protein A (r=0.417, P<.001) and between e...
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PMID: 18978109
PDF is available here.
PDF is available here.
Abstract
PII-disintegrins, cysteine-rich polypeptides broadly distributed in the venoms of geographically diverse species of vipers and rattlesnakes, antagonize the adhesive functions of beta(1) and beta(3) integrin receptors. PII-disintegrins evolved in Viperidae by neofunctionalization of disintegrin-like...
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PMID: 18701431
PDF is available here.
PDF is available here.
Abstract
We describe the expression of GPCR, ADAMs and EGFR ligands in human glioma brain tumors and the characteristics of small molecule ADAMs inhibitors. The addition of ADAM inhibitors to our pharmacological arsenal could enhance the outcome of combination therapies when using EGFR inhibitors against hum...
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PMID: 18991757
PDF is available here.
PDF is available here.
Abstract
This study evaluated the effects of alternagin-C (ALT-C) on mRNA levels of VEGF, MyoD and matrix metalloproteinase 2 (MMP-2) and on activity of MMPs in injured tibialis anterior (TA) muscle induced by cryolesioning in rats. Thirty-six Wistar rats (3 months old, 258.9+/-27 g) were divided into five g...
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PMID: 18761031
PDF is available here.
PDF is available here.
Abstract
We characterized a second site of interaction between vitronectin and its integrin partner. We determined that amino acids within the heparin-binding domain of vitronectin bind to a cysteine loop (C-loop) region of beta3 and that this interaction is required for the positive effects of alphaVbeta3 l...
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PMID: 18615592
PDF is available here.
PDF is available here.
Cancer Research (68)17 2008
Abstract
These results suggest that there may be an additional clinical benefit of combining agents that target the ErbB pathways at multiple points....
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PMID: 18757423
PDF is available here.
PDF is available here.
Abstract
These results may have significant implications for integrin antagonistic therapy used for the treatment of atherosclerosis and restenosis....
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PMID: 18625263
PDF is available here.
PDF is available here.
Abstract
(1) 298 mg/L GST (Glutathione-S-transferase)-ADAM15 and 42 mg/L rhADAM15 were achieved when choosing E. coli Rosetta (DE3) as the expression host that could supply additional tRNA for rare codons. (2) The GST-ADAM15 expression level increased to 326 mg/L after changing the rare codon GGA (Gly425) to...
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PMID: 18956757
PDF is available here.
PDF is available here.
Abstract
We show that Kuz regulates Notch signaling primarily by activating the receptor and has little overall effect on signaling via disabling Delta. We confirm that Kuz-dependent activation of Notch requires stimulation of Notch by Delta. However, over-expression of Kuz gives ligand-independent Notch act...
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PMID: 18535782
PDF is available here.
PDF is available here.
Reproduction (136)1 2008
Abstract
Successful fertilization requires gametes to complete several stages, beginning with maturation and transport along the male and female reproductive tracts and ending with the interaction between the sperm and the egg. This last step involves sperm-egg adhesion and membrane fusion. ADAMs (disintegri...
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PMID: 18390692
PDF is available here.
PDF is available here.
Abstract
Our data suggest that while crotatroxin 2 inhibits platelet aggregation, cancer cell migration, and lung tumor colonization, it is done via different integrins....
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PMID: 18387648
PDF is available here.
PDF is available here.
Acta Crystallographica Section D (64)Pt 4 2008
Abstract
Disintegrins are a family of small (4-14 kDa) proteins that bind to another class of proteins, integrins. Therefore, as integrin inhibitors, they can be exploited as anticancer and antiplatelet agents. Acostatin, an alphabeta heterodimeric disintegrin, has been isolated from the venom of Southern co...
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PMID: 18391413
PDF is available here.
PDF is available here.
Abstract
We observed a decrease in locomotor activity, piloerection, and crouching in clinical findings, a decrease of red blood cells (RBCs) in hematology, and hyperplasia of the spleen in histology related to administration of the test item. These results suggest that the target organ of intravenous admini...
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PMID: 18155118
PDF is available here.
PDF is available here.
Trends in Immunology (29)2 2008
Abstract
We discuss how two specific classes of metal-dependent proteinases, the matrix metalloproteinases and the disintegrin metalloproteinases, have consequences well beyond classical cell-matrix and cell-cell interactions and motility, and we review their roles in immune-cell maturation, clonal expansion...
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PMID: 18182322
PDF is available here.
PDF is available here.
Cancer Science (99)2 2008
Abstract
We focus on ectodomain shedding of the EGF family ligands, especially HB-EGF by disintegrin and metalloproteases, which are not only key events of receptor cross talk, but also novel intercellular signaling by their carboxy-terminal fragments to regulate gene expression directly....
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PMID: 18271917
PDF is available here.
PDF is available here.
Abstract
We studied the effects of dextran, dextrin, and disintegrants on the chemical stability of Opalmon tablets containing Limaprost-alfadex (Limaprost/alpha-cyclodextrin complex) and found that the addition of dextran or dextrin significantly improved the chemical stability of Opalmon tablets under high...
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PMID: 18175966
PDF is available here.
PDF is available here.
Abstract
Few of the proteins isolated and characterized from snake venom have proven to be more chemically diverse, exquisitely specific or promiscuously active than the family known as disintegrins. These small proteins have shown structural homology with hundreds of cell surface molecules from plants and a...
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PMID: 18508683
PDF is available here.
PDF is available here.
Abstract
We report here on the production, the characterization and the in vivo anti-angiogenic and anti-metastatic properties of a novel alpha(v)beta(3)-binding disintegrin, DisBa-01, isolated from a cDNA library made with RNAs from the venom gland of Bothrops alternatus. The 11,637 Da-recombinant monomeric...
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PMID: 17952617
PDF is available here.
PDF is available here.
Abstract
Disintegrins are snake venom-derived, RGD- or KGD-containing peptides that can inhibit integrin-mediated platelet aggregation and cell-matix interactions. The aim of this study is to analyze the full-length cDNA sequence of a snake venom metalloprotease (SVMP) from green pit viper (Trimeresurus albo...
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PMID: 17870140
PDF is available here.
PDF is available here.
Abstract
The effects and molecular mechanisms of RGD-disintegrins isolated from snake venoms on the growth and metastatic potential of B16F10-melanoma cells were investigated. Jarastatin (JT) from Bothrops jararaca is a ligand of alpha(5)beta(1), alpha(v)beta(3) and alpha(m)beta(2) integrins, flavoridin (FL)...
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PMID: 17854854
PDF is available here.
PDF is available here.
Journal of Biological Chemistry (282)49 2007
Abstract
We report that the recombinant mouse ADAM10 prodomain, purified from Escherichia coli, is a potent competitive inhibitor of the human ADAM10 catalytic/disintegrin domain, with a K(i) of 48 nM. Moreover, the mouse ADAM10 prodomain is a selective inhibitor as it only weakly inhibits other ADAM family...
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PMID: 17895248
PDF is available here.
PDF is available here.
Endocrinology (148)12 2007
Abstract
We previously found that Janus kinase 2 (JAK2)-deficient GHR-expressing cells have a greater precursor/mature GHR ratio, exhibit diminished inducible metalloproteolysis, and have a cytoplasmic domain-containing GHR fragment called the basal remnant (by virtue of comigration on SDS-PAGE with the indu...
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PMID: 17761766
PDF is available here.
PDF is available here.
Journal of Molecular Biology (373)4 2007
Abstract
We report the first crystal structures for a member of the ADAMTS family, ADAMTS-1. Originally cloned as an inflammation-associated gene, ADAMTS-1 has been shown to be involved in tissue remodelling, wound healing and angiogenesis. The crystal structures contain catalytic and disintegrin-like domain...
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PMID: 17897672
PDF is available here.
PDF is available here.
Journal of Biological Chemistry (282)42 2007
Abstract
We report that ADAM-9 functions as a cell adhesion molecule via its disintegrin-cysteine-rich domain. Using solid phase binding assays and antibody inhibition experiments, we demonstrated that the recombinant disintegrin-cysteine-rich domain of ADAM-9 specifically interacts with the beta1 integrin s...
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PMID: 17704059
PDF is available here.
PDF is available here.
Abstract
One year of lifestyle intervention reduced the level of sICAM-1 in sedentary, drug-treated hypertensives, in spite of no impact on traditional risk factors. Low dose fluvastatin had no beneficial effect on the measured markers....
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PMID: 17852781
PDF is available here.
PDF is available here.
Abstract
We examined the expression, localization and effect on growth of ADAMTS-1 in a normal rat kidney cell line (NRK-49F). Increased ADAMTS-1 mRNA expression was observed in the kidney by in situ hybridization after induction of unilateral ureteral obstruction (UUO) in male Wistar rats, the mRNA was loca...
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PMID: 17583485
PDF is available here.
PDF is available here.
Journal of Immunology (178)12 2007
Abstract
We introduce the calcium-ionophore ionomycin as a novel, very rapid, and efficient inducer of CX3CL1 and CXCL16 shedding. By transfection in COS-7 cells and ADAM10-deficient murine embryonic fibroblasts combined with the use of selective metalloproteinase inhibitors, we demonstrate that the inducibl...
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PMID: 17548644
PDF is available here.
PDF is available here.
EMBO Journal (26)11 2007
Abstract
We show that MIG-17, an ADAMTS family protein required for gonadal leader cell migration in Caenorhabditis elegans, is recruited to the gonadal basement membrane in a prodomain-dependent manner. The activation of MIG-17 to control leader cell migration requires prodomain removal, which is suggested...
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PMID: 17491590
PDF is available here.
PDF is available here.
Abstract
We report here that saxatilin, a snake venom-derived disintegrin, suppresses the angiogenesis-inducing properties of NCI-H460 human lung cancer cells. Culture supernatants of NCI-H460 cells are able to induce human umbilical vascular endothelial cell (HUVEC) invasion and tube formation. However, tre...
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PMID: 17562297
PDF is available here.
PDF is available here.
Abstract
These data suggest that radiolabeled kistrin, flavoridin and VLO4 may have advantages over labeled bitistatin and small cyclic peptides for targeting alphavbeta3 in vivo. Since receptor-bound radioligand is not internalized by endothelial cells, disintegrins may provide an advantage for targeting al...
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PMID: 17499726
PDF is available here.
PDF is available here.
Abstract
We have previously demonstrated that alternagin-C (ALT-C), a disintegrin-like protein from the venom of the Brazilian snake Bothrops alternatus, induces human vascular endothelial cell (HUVEC) proliferation by up-regulating the expression of vascular endothelial growth factor (VEGF). Here, we show t...
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PMID: 17428438
PDF is available here.
PDF is available here.
Abstract
These results indicate that transcriptional regulation of MMP-9 is an important mechanism for the tumor suppressive effects of saxatilin in MDAH 2774 human ovarian cancer cells....
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PMID: 17394781
PDF is available here.
PDF is available here.
Abstract
We isolated six cDNAs from snake venom glands using RT-PCR. Three RGD disintegrins (atroxatin, mojastin, and viridistatin) and three PIII-SVMPs (catroriarin, scutiarin, and viristiarin) cDNAs were isolated from the rattlesnakes Crotalus atrox, Crotalus scutulatus scutulatus, and Crotalus viridis vir...
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PMID: 17112685
PDF is available here.
PDF is available here.
Molecular Immunology (44)6 2007
Abstract
Tumor necrosis factor-alpha (TNF-alpha)-induced proliferation of cancer cell line MDAH 2774 was significantly suppressed by treating the cells with saxatilin, a snake venom disintegrin. The suppressed proliferation was found to be associated with the level of interleukin-8 (IL-8) expression in the c...
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PMID: 16806476
PDF is available here.
PDF is available here.
Abstract
We now report the sequence analysis of disintegrin-coding genes from these two vipers. Genomic DNAs for dimeric disintegrin subunits Ml_G1 and Ml_G2 (Mlt) and Eo_D3 (Eo) contain single 1-kb introns exhibiting the 5'-GTAAG (donor)/3'-AG (acceptor) consensus intron splicing signature. On the other han...
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PMID: 17177090
PDF is available here.
PDF is available here.
Biochimica et Biophysica Acta (1773)2 2007
Abstract
We have investigated the ability of three RGD-disintegrins, ligands of alpha(5)beta(1) and alpha(v)beta(3), Flavoridin (Fl), Kistrin (Kr) and Echistatin (Ech), in modulating the activation of human T lymphocyte. The disintegrins induced T cell proliferation and CD69 expression. This activation paral...
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PMID: 17081636
PDF is available here.
PDF is available here.
Developmental Biology (301)2 2007
Abstract
We show the Notch activity pattern during oogenesis. Notch activation was found in many follicle cells at stage 6 but then at stage 9 was restricted to migrating border cells, despite uniform expression of Delta. Expression of Kuzbanian (KUZ), a metalloproteinase that can activate Notch as well as c...
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PMID: 17010965
PDF is available here.
PDF is available here.
Abstract
We will briefly discuss tumor angiogenesis and molecules implicated in the angiogenic process, with a special focus on the role of integrins. We will also discuss therapeutic approaches towards the treatment of tumor angiogenesis, including non-integrin-targeted agents currently in clinical trials....
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PMID: 17979731
PDF is available here.
PDF is available here.
Abstract
We discuss structure-function correlations of the novel group of specific (K/R)TS-disintegrins targeting the alpha(1)beta(1) integrin....
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PMID: 17979730
PDF is available here.
PDF is available here.
Abstract
Basic research over the last two decades has identified a large number of molecules pertinent to the atherosclerotic process, which have clearly improved our understanding of the underlying pathology. It is now well established that inflammation represents a major feature which is present in the ves...
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PMID: 17082488
PDF is available here.
PDF is available here.
Abstract
Platelet activation results in platelet aggregation and the secretion of granules, which contain a variety of constituents including nonprotein molecules, adhesive proteins and hydrolases. The platelet-derived supernatant (PDS), which contains these granules, is known to trigger the activation of end...
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PMID: 17215584
PDF is available here.
PDF is available here.
Abstract
We report classification and therapeutic implications of disintegrins. In particular the structural and the functional characteristics of lebestatin; a short disintegrin isolated from Tunisian Macrovipera lebetina snake venom....
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PMID: 19388581
PDF is available here.
PDF is available here.
Abstract
The protein composition of the venom of the East African Gaboon viper (Bitis gabonica gabonica) was analyzed using RP-HPLC, N-terminal sequencing, MALDI-TOF peptide mass fingerprinting, and CID-MS/MS. In total, 35 proteins of molecular masses in the range of 7-160 kDa and belonging t...
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PMID: 17203976
PDF is available here.
PDF is available here.
Abstract
We briefly explain how integrins can affect the multitude of signal transduction cascades in control of survival, proliferation, and differentiation. Subsequently, we primarily focus on targeting integrins alpha5beta1 and alphanubeta3 in disease and we discuss how antagonists of these integrins, inc...
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PMID: 17852562
PDF is available here.
PDF is available here.
Abstract
A novel disintegrin, stejnin, was purified from the Trimeresurus stejnegeri venom by gel filtration and reverse phase high performance liquid chromatography. The molecular weight of stejnin was determined to be 7428 Da by MALD-TOF MS analysis. The cDNA encoding the precursor of stejnin was cloned fr...
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PMID: 17584163
PDF is available here.
PDF is available here.