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1.
immunocytochemical localization of urokinase-type plasminogen activator in lewis lung carcinoma 总被引:1,自引:0,他引:1 下载免费PDF全文
L Skriver LI Larsson V Kielberg LS Nielsen PB Andresen P Kristensen K Dano 《The Journal of cell biology》1984,99(2):753-758
The invasively growing and metasizing Lewis lung carcinoma consistently contained urokinase-type plasminogen activator (u-PA) enzyme activity. When investigated immunocytochemically with antibodies against u-PA, different parts of individual tumors showed a pronounced heterogeneity in staining intensity. Strong staining was found in areas with invasive growth and degradation of surrounding normal tissue, while other areas were completely devoid of staining. Immunoreactivity occurred both with a perinuclear cytoplasmic localization in tumor cells and associated with apparently extracellular material. SDS PAGE of tumor extracts, under both reducing and nonreducing conditions, followed by immunoblotting, showed only one immunocytochemically stainable band with an electrophoretic mobility corresponding to that of purified proenzyme to u-PA, while no two-chain u-PA was detected. This indicates that the major part of the activator in Lewis lung carcinoma is present as one-chain pro-u-PA. 相似文献
2.
A de novo peptide that self-assembles into fibrillar structures and serves as a substrate for the cross-linking enzyme tissue transglutaminase was developed (Ac-QQKFQFQFEQQ-Am). Congo red staining, circular dichroism, and FTIR spectroscopy showed that this 11-amino acid peptide produced predominantly beta-sheet structures. TEM with negative staining and quick-freeze deep etch (QFDE) TEM showed that the peptide structures were composed of a highly entangled fibrillar network. These beta-sheet fibrillar nanostructures were then covalently coupled to pendant amine-containing biomolecules via tissue transglutaminase. MALDI-TOF mass spectrometry and HPLC were utilized to monitor the extent of the transglutaminase modification of the peptide, showing that as many as five glutamines in the peptide were reactive via transglutaminase for covalent conjugation. This strategy, based on the post-assembly modification of a self-assembling peptide, has potential applications for tailoring supramolecular structures for drug delivery, tissue engineering, or other biomedical applications. 相似文献
3.
Black AP Bhayani H Ryder CA Pugh MT Gardner-Medwin JM Southwood TR 《Arthritis research & therapy》2003,5(5):R277-R284
The aim of this research was to determine whether all memory T cells have the same propensity to migrate to the joint in patients
with juvenile idiopathic arthritis. Paired synovial fluid and peripheral blood mononuclear cell proliferative responses to
a panel of antigens were measured and the results correlated with a detailed set of laboratory and clinical data from 39 patients
with juvenile idiopathic arthritis. Two distinct patterns of proliferative response were found in the majority of patients:
a diverse pattern, in which synovial fluid responses were greater than peripheral blood responses for all antigens tested;
and a restricted pattern, in which peripheral blood responses to some antigens were more vigorous than those in the synovial
fluid compartment. The diverse pattern was generally found in patients with a high acute phase response, whereas patients
without elevated acute phase proteins were more likely to demonstrate a restricted pattern. We propose that an association
between the synovial fluid T cell repertoire and the acute phase response suggests that proinflammatory cytokines may influence
recruitment of memory T cells to an inflammatory site, independent of their antigen specificity. Additionally, increased responses
to enteric bacteria and the presence of αEβ7 T cells in synovial fluid may reflect accumulation of gut associated T cells
in the synovial compartment, even in the absence of an elevated acute phase response. This is the first report of an association
between the acute phase response and the T cell population recruited to an inflammatory site. 相似文献
4.
Narayana PB Fazolini André LS Cruz Miriam BF Werneck Jo?o PB Viola Clarissa M Maya-Monteiro Patrícia T Bozza 《Cell cycle (Georgetown, Tex.)》2015,14(16):2667-2676
Accumulating evidence suggests that obesity and enhanced inflammatory reactions are predisposing conditions for developing colon cancer. Obesity is associated with high levels of circulating leptin. Leptin is an adipocytokine that is secreted by adipose tissue and modulates immune response and inflammation. Lipid droplets (LD) are organelles involved in lipid metabolism and production of inflammatory mediators, and increased numbers of LD were observed in human colon cancer. Leptin induces the formation of LD in macrophages in a PI3K/mTOR pathway-dependent manner. Moreover, the mTOR is a serine/threonine kinase that plays a key role in cellular growth and is frequently altered in tumors. We therefore investigated the role of leptin in the modulation of mTOR pathway and regulation of lipid metabolism and inflammatory phenotype in intestinal epithelial cells (IEC-6 cells). We show that leptin promotes a dose- and time-dependent enhancement of LD formation. The biogenesis of LD was accompanied by enhanced CXCL1/CINC-1, CCL2/MCP-1 and TGF-β production and increased COX-2 expression in these cells. We demonstrated that leptin-induced increased phosphorylation of STAT3 and AKT and a dose and time-dependent mTORC activation with enhanced phosphorilation of the downstream protein P70S6K protein. Pre-treatment with rapamycin significantly inhibited leptin effects in LD formation, COX-2 and TGF-β production in IEC-6 cells. Moreover, leptin was able to stimulate the proliferation of epithelial cells on a mTOR-dependent manner. We conclude that leptin regulates lipid metabolism, cytokine production and proliferation of intestinal cells through a mechanism largely dependent on activation of the mTOR pathway, thus suggesting that leptin-induced mTOR activation may contribute to the obesity-related enhanced susceptibility to colon carcinoma. 相似文献
5.
Douglas TE Messersmith PB Chasan S Mikos AG de Mulder EL Dickson G Schaubroeck D Balcaen L Vanhaecke F Dubruel P Jansen JA Leeuwenburgh SC 《Macromolecular bioscience》2012,12(8):1077-1089
Alkaline phosphatase (ALP), an enzyme involved in mineralization of bone, is incorporated into three hydrogel biomaterials to induce their mineralization with calcium phosphate (CaP). These are collagen type I, a mussel-protein-inspired adhesive consisting of PEG substituted with catechol groups, cPEG, and the PEG/fumaric acid copolymer OPF. After incubation in Ca-GP solution, FTIR, EDS, SEM, XRD, SAED, ICP-OES, and von Kossa staining confirm CaP formation. The amount of mineral formed decreases in the order cPEG?>?collagen?>?OPF. The mineral:polymer ratio decreases in the order collagen?>?cPEG?>?OPF. Mineralization increases Young's modulus, most profoundly for cPEG. Such enzymatically mineralized hydrogel/CaP composites may find application as bone regeneration materials. 相似文献
6.
Multicellular organization and tissue construction has evolved along essentially different lines in plants and animals. Since plants do not run away, but are anchored in the soil, their tissues are more or less firm and stiff. This strength stems 相似文献
7.
Ma WW Herman JM Jimeno A Laheru D Messersmith WA Wolfgang CL Cameron JL Pawlik TM Donehower RC Rudek MA Hidalgo M 《Translational oncology》2010,3(6):373-379
BACKGROUND: Erlotinib is approved for the treatment of advanced pancreas cancer. We conducted a prospective trial to determine the safety profile and recommended phase 2 dose of erlotinib and capecitabine given concurrently with intensity-modulated radiation therapy (IMRT) in resected pancreatic cancer patients. The pharmacokinetic profile of this combination was also evaluated. METHODS: Patients with resected pancreatic adenocarcinoma received erlotinib and capecitabine concurrently with IMRT delivered at 1.8 Gy daily in 28 fractions (total = 50.4 Gy). The starting dose level (DL 1) was erlotinib 150mgdaily and capecitabine 800 mg/m2 twice daily without interruption. The next lower dose level (DL -1) was erlotinib 100 mg daily and capecitabine 800 mg/m2 twice daily (Monday to Friday). Plasma samples were obtained for pharmacokinetic analysis. RESULTS: Thirteen patients were enrolled in total. At DL 1, six of the seven treated patients were evaluable for toxicities. Four completed planned treatment, but all required treatment interruption or dose reduction. The dose-limiting toxicities were neutropenia, diarrhea, and rash. Six patients were subsequently enrolled to and completed planned treatment in DL-1. Themost common toxicities were fatigue, elevated liver enzymes, and anorexia. The pharmacokinetic parameters of erlotinib and OSI-420 were not significantly different in the presence or absence of capecitabine and were consistent with historical controls. CONCLUSIONS: When administered concurrently with IMRT, erlotinib 100 mg daily and capecitabine 800 mg/m2 twice daily (Monday to Friday) can be administered safely in resected pancreas cancer patients, and is the recommended regimen for efficacy studies using this regimen. 相似文献
8.
Rudek MA Zhao M He P Zabelina Y Jin R Messersmith WA Wolff AC Baker SD 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2005,828(1-2):41-54
A method has been developed for the quantitation of N-[4-(5-bromo-2-pyrimidinyloxy)-3-methylphenyl]-N'-(2-dimethylamino-benzoyl)urea (BPU) and its metabolites in human plasma and urine. BPU and metabolites were separated on a C18 column with acetonitrile-water mobile phase containing 0.1% formic acid using isocratic flow for 5 min. The analytes were monitored by tandem mass spectrometry. Calibration curves were generated over the range of 2.5-500 ng/mL for BPU, mmBPU, and aminoBPU in plasma; and 0.1-20, 0.1-20, 0.5-100, 10-2000, 1-200, and 3-600 ng/mL for BPU, mmBPU, aminoBPU, G280, G308, and G322 in urine, respectively. The method has been successfully applied to study the pharmacokinetics of BPU. 相似文献
9.
Mussel-inspired adhesive hydrogels represent innovative candidate medical sealants or glues. In the present work, we describe an enzyme-degradable mussel-inspired adhesive hydrogel formulation, achieved by incorporating minimal elastase substrate peptide Ala-Ala into the branched poly(ethylene glycol) (PEG) macromonomer structure. The system takes advantage of neutrophil elastase expression upregulation and secretion from neutrophils upon recruitment to wounded or inflamed tissue. By integrating adhesive degradation behaviors that respond to cellular cues, we expand the functional range of our mussel-inspired adhesive hydrogel platforms. Rapid (<1 min) and simultaneous gelation and adhesion of the proteolytically active, catechol-terminated precursor macromonomer was achieved by addition of sodium periodate oxidant. Rheological analysis and equilibrium swelling studies demonstrated that the hydrogel is appropriate for soft tissue-contacting applications. Notably, hydrogel storage modulus (G') achieved values on the order of 10 kPa, and strain at failure exceeded 200% strain. Lap shear testing confirmed the material's adhesive behavior (shear strength: 30.4 ± 3.39 kPa). Although adhesive hydrogel degradation was not observed during short-term (27 h) in vitro treatment with neutrophil elastase, in vivo degradation proceeded over several months following dorsal subcutaneous implantation in mice. This work represents the first example of an enzymatically degradable mussel-inspired adhesive and expands the potential biomedical applications of this family of materials. 相似文献
10.
Ying-zi Xu Andrei W. Konradi Frederique Bard Michael Dappen Lilibeth Dofiles Mark Dreyer Ian Gallager Caroline Garrido Mike Krimm Zhenmei Liao Elizabeth Messersmith Linda Mutter Michael A. Pleiss Bhushan Samant Christopher M. Semko Jennifer Smith Frank Stappenbeck Brian Stupi Ted Yednock 《Bioorganic & medicinal chemistry letters》2013,23(10):3070-3074
A series of (S)-2-(2-(diethylamino)-5-(N-alkyl-N-sulfonamido)pyrimidin-4-ylamino)-3-(4-(carbamoyloxy)phenyl)propanoic acid is discovered as orally available VLA-4 antagonists. Representative compounds 11b and 11p showed efficacy in multiple in vivo animal models. The in vitro selectivity of 11p is also described. 相似文献