The Experts below are selected from a list of 65481 Experts worldwide ranked by ideXlab platform
William J Muller - One of the best experts on this subject based on the ideXlab platform.
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targeted disruption of β1 integrin in a transgenic mouse model of human breast cancer reveals an essential role in mammary tumor induction
Cancer Cell, 2004Co-Authors: Donald E White, Natasza A Kurpios, Dongmei Zuo, John A Hassell, Sandra Blaess, Ulrich Mueller, William J MullerAbstract:Despite evidence demonstrating the role of beta1-integrin in the regulation of cancer cell proliferation in vitro, the importance of this cell Adhesion Receptor during the initiation and progression of epithelial tumors in vivo remains unclear. Here we have used the Cre/LoxP1 recombination system to disrupt beta1-integrin function in the mammary epithelium of a transgenic mouse model of human breast cancer. Using this approach, we show that beta1-integrin expression is critical for the initiation of mammary tumorigenesis in vivo, and for maintaining the proliferative capacity of late-stage tumor cells. These observations provide a direct demonstration that beta1-integrin plays a critical role in both the initiation and maintenance of mammary tumor growth in vivo.
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targeted disruption of β1 integrin in a transgenic mouse model of human breast cancer reveals an essential role in mammary tumor induction
Cancer Cell, 2004Co-Authors: Donald E White, Natasza A Kurpios, John A Hassell, Sandra Blaess, Ulrich Mueller, William J MullerAbstract:Abstract Despite evidence demonstrating the role of β1-integrin in the regulation of cancer cell proliferation in vitro, the importance of this cell Adhesion Receptor during the initiation and progression of epithelial tumors in vivo remains unclear. Here we have used the Cre/LoxP1 recombination system to disrupt β1-integrin function in the mammary epithelium of a transgenic mouse model of human breast cancer. Using this approach, we show that β1-integrin expression is critical for the initiation of mammary tumorigenesis in vivo, and for maintaining the proliferative capacity of late-stage tumor cells. These observations provide a direct demonstration that β1-integrin plays a critical role in both the initiation and maintenance of mammary tumor growth in vivo.
Markus Schwaiger - One of the best experts on this subject based on the ideXlab platform.
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noninvasive imaging of αvβ3 integrin expression using 18f labeled rgd containing glycopeptide and positron emission tomography
Cancer Research, 2001Co-Authors: Roland Haubner, Hansjurgen Wester, Wolfgang A Weber, Christian Mang, Sibylle Ziegler, Simon L Goodman, Reingard Senekowitschschmidtke, Horst Kessler, Markus SchwaigerAbstract:The alpha(v)beta3 integrin is an important cell Adhesion Receptor involved in tumor-induced angiogenesis and tumor metastasis. Here we describe the 18F-labeling of the RGD-containing glycopeptide cyclo(-Arg-Gly-Asp-D-Phe-Lys(sugar amino acid)-) with 4-nitrophenyl 2-[18F]fluoropropionate and the evaluation of this compound in vitro and in tumor mouse models. Binding assays with isolated immobilized alpha(v)beta3, alpha(v)beta5, and alpha(IIb)beta3 as well as in vivo studies using alpha(v)beta3-positive and -negative murine and xenotransplanted human tumors demonstrated Receptor-specific binding of the radiolabeled glycopeptide yielding high tumor:background ratios (e.g., 120 min postinjection: tumor:blood, 27.5; tumor:muscle, 10.2). First imaging results using a small animal positron emission tomograph suggest that this compound is suitable for noninvasive determination of the alpha(v)beta3 integrin status and therapy monitoring.
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noninvasive imaging of αvβ3 integrin expression using 18f labeled rgd containing glycopeptide and positron emission tomography
Cancer Research, 2001Co-Authors: Roland Haubner, Hansjurgen Wester, Wolfgang A Weber, Christian Mang, Sibylle Ziegler, Simon L Goodman, Reingard Senekowitschschmidtke, Horst Kessler, Markus SchwaigerAbstract:The α v β 3 integrin is an important cell Adhesion Receptor involved in tumor-induced angiogenesis and tumor metastasis. Here we describe the 18 F-labeling of the RGD-containing glycopeptide cyclo(-Arg-Gly-Asp-d-Phe-Lys(sugar amino acid)-) with 4-nitrophenyl 2-[ 18 F]fluoropropionate and the evaluation of this compound in vitro and in tumor mouse models. Binding assays with isolated immobilized α v β 3 , α v β 5 , and α IIb β 3 as well as in vivo studies using α v β 3 -positive and -negative murine and xenotransplanted human tumors demonstrated Receptor-specific binding of the radiolabeled glycopeptide yielding high tumor:background ratios ( e.g. , 120 min postinjection: tumor:blood, 27.5; tumor:muscle, 10.2). First imaging results using a small animal positron emission tomograph suggest that this compound is suitable for noninvasive determination of the α v β 3 integrin status and therapy monitoring.
Donald E White - One of the best experts on this subject based on the ideXlab platform.
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targeted disruption of β1 integrin in a transgenic mouse model of human breast cancer reveals an essential role in mammary tumor induction
Cancer Cell, 2004Co-Authors: Donald E White, Natasza A Kurpios, Dongmei Zuo, John A Hassell, Sandra Blaess, Ulrich Mueller, William J MullerAbstract:Despite evidence demonstrating the role of beta1-integrin in the regulation of cancer cell proliferation in vitro, the importance of this cell Adhesion Receptor during the initiation and progression of epithelial tumors in vivo remains unclear. Here we have used the Cre/LoxP1 recombination system to disrupt beta1-integrin function in the mammary epithelium of a transgenic mouse model of human breast cancer. Using this approach, we show that beta1-integrin expression is critical for the initiation of mammary tumorigenesis in vivo, and for maintaining the proliferative capacity of late-stage tumor cells. These observations provide a direct demonstration that beta1-integrin plays a critical role in both the initiation and maintenance of mammary tumor growth in vivo.
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targeted disruption of β1 integrin in a transgenic mouse model of human breast cancer reveals an essential role in mammary tumor induction
Cancer Cell, 2004Co-Authors: Donald E White, Natasza A Kurpios, John A Hassell, Sandra Blaess, Ulrich Mueller, William J MullerAbstract:Abstract Despite evidence demonstrating the role of β1-integrin in the regulation of cancer cell proliferation in vitro, the importance of this cell Adhesion Receptor during the initiation and progression of epithelial tumors in vivo remains unclear. Here we have used the Cre/LoxP1 recombination system to disrupt β1-integrin function in the mammary epithelium of a transgenic mouse model of human breast cancer. Using this approach, we show that β1-integrin expression is critical for the initiation of mammary tumorigenesis in vivo, and for maintaining the proliferative capacity of late-stage tumor cells. These observations provide a direct demonstration that β1-integrin plays a critical role in both the initiation and maintenance of mammary tumor growth in vivo.
Denisa D. Wagner - One of the best experts on this subject based on the ideXlab platform.
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A new role in hemostasis for the Adhesion Receptor P-selectin.
Trends in molecular medicine, 2004Co-Authors: Béatrice Cambien, Denisa D. WagnerAbstract:The Adhesion Receptor P-selectin has long been known to support leukocyte rolling and emigration at sites of inflammation. Recently, P-selectin was also revealed to be a key molecule in hemostasis and thrombosis, mediating platelet rolling, generating procoagulant microparticles containing active tissue factor and enhancing fibrin deposition. Elevated levels of plasma P-selectin are indicative of thrombotic disorders and predictive of future cardiovascular events. Because the interaction between P-selectin and its Receptor P-selectin glycoprotein ligand-1 (PSGL-1) represents an important mechanism by which P-selectin induces the formation of procoagulant microparticles and recruits the microparticles to thrombi, anti-thrombotic strategies are currently aimed at inhibiting this interaction. Recent developments also suggest that the procoagulant potential of P-selectin could be used to treat coagulation disorders such as hemophilia A.
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prominent role of p selectin in the development of advanced atherosclerosis in apoe deficient mice
Circulation, 2000Co-Authors: Zhao Ming Dong, Allison A Brown, Denisa D. WagnerAbstract:Background—Adhesive interactions between leukocytes and endothelial cells are characteristic of the development of atherosclerotic lesions, but the Receptors involved remain to be defined. P-selectin is an Adhesion Receptor expressed on activated endothelial cells or platelets and was shown to be involved in fatty streak formation in LDL Receptor–deficient mice on an atherogenic diet. The main purpose of this study is to examine the role of P-selectin in the spontaneous development of advanced atherosclerosis in apoE-deficient mice. Methods and Results—We intercrossed P-selectin–deficient mice with mice lacking apoE and compared lesion development in apoE-deficient mice with P-selectin (apoE−/− P+/+) and without P-selectin (apoE−/− P−/−) that were fed normal mouse chow. At 4 months of age, apoE−/− P−/− mice had 3.5-fold smaller aortic sinus lesions than apoE−/− P+/+ mice. These were limited to fatty streaks in the apoE−/− P−/− mice, whereas 70% of apoE−/− P+/+ lesions contained smooth muscle cells. Signif...
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leukocyte rolling and extravasation are severely compromised in p selectin deficient mice
Cell, 1993Co-Authors: Tanya N Mayadas, Robert C Johnson, Helen Rayburn, Richard O Hynes, Denisa D. WagnerAbstract:P selectin, expressed on surfaces of activated endothelial cells and platelets, is an Adhesion Receptor for leukocytes. We report that P selectin-deficient mice, generated by gene targeting in embryonic stem cells, exhibit a number of defects in leukocyte behavior, including elevated numbers of circulating neutrophils, virtually total absence of leukocyte rolling in mesenteric venules, and delayed recruitment of neutrophils to the peritoneal cavity upon experimentally induced inflammation. These results clearly demonstrate a role for P selectin in leukocyte interactions with the vessel wall and in the early steps of leukocyte recruitment at sites of inflammation. These mutant mice should prove useful in deciphering the contributions of P selectin in various inflammatory responses as well as in platelet functions.
Stefan Meuer - One of the best experts on this subject based on the ideXlab platform.
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a soluble form of the Adhesion Receptor cd58 lfa 3 is present in human body fluids
European Journal of Immunology, 1993Co-Authors: Jorg C Hoffmann, Thomas J Dengler, Percy A Knolle, Marion Albertwolf, Matthias Roux, Reinhard Wallich, Stefan MeuerAbstract:The human Adhesion Receptor CD58 (LFA-3) is expressed on most human cell types. Here we report on a soluble form of CD58 (sCD58) in human serum, human urine, and culture supernatants of several cell lines. sCD58 partially purified from human serum, from supernatant of the Hodgkin cell line L428, and purified sCD58 from human urine were found to have a molecular mass of 40-70 kDa under denaturating conditions (sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting). However, gel filtration of sCD58 purified from human urine gave a molecular mass of 118-166 kDa, suggesting a noncovalent homotrimer conformation or its association with other molecules. Using an enzyme-linked immunosorbent assay specific for CD58 we found that sera from patients suffering from different forms of hepatitis contained elevated sCD58 levels (n = 108). Accordingly, there was a fivefold increase of supernatant sCD58 when the hepatocellular carcinoma cell line Hep G2 was incubated with 25 ng/ml recombinant tumor necrosis factor-alpha in vitro. In contrast, sCD58 serum levels of 337 additional patients suffering from various other immunological disorders were not found to be raised. At high concentrations sCD58 binds to CD2-positive cells and inhibits rosette formation of human T cells to human erythrocytes. Thus, local release of large quantities of naturally occurring sCD58 may interfere with intercellular Adhesion in vivo.
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structural and functional epitopes of the human Adhesion Receptor cd58 lfa 3
European Journal of Immunology, 1992Co-Authors: Thomas J Dengler, Jorg C Hoffmann, Percy A Knolle, Marion Albertwolf, Matthias Roux, Reinhard Wallich, Stefan MeuerAbstract:CD58 (LFA-3), a heavily glycosylated protein of 40-70 kDa, is expressed on a broad range of hematopoietic and non-hematopoietic cells. It serves as a physiological ligand of the CD2 Receptor, present on T cells and natural killer cells, and plays, thus, an important role in lymphocyte Adhesion and T cell activation through CD2. Whereas several epitopes and their respective function are known for CD2, a similarly detailed characterization of CD58 is still lacking. We raised a panel of novel murine monoclonal antibodies (mAb) against recombinant human CD58 and describe here the identification of six structurally and/or functionally distinct epitopes on the CD58 molecule. All epitopes were found to be present in equal numbers on a wide range of CD58+ cells, none of them being differentially up-regulated following cell activation or malignant transformation. Two of these epitopes represent functionally relevant sites, involved in binding of CD58 to CD2 and T cell activation via CD2. One further epitope appears to be selectively involved in CD58-mediated activation, whereas the other three displayed no functional effects. The new mAb allow for the first time the detection of CD58 in enzyme-linked immunosorbent assays and immunofluorescence while bound to its Receptor CD2 in human serum or on freshly isolated blood cells. Finally, one mAb was found to specifically cross-react with T11TS, the equivalent of CD58 in sheep.