Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

High affinity polyclonal rabbit antibodies to ovine (o) pituitary LH [anti-oLH-immunoglobulin G (IgG) Ab1] were used to immunize young Southdown lambs. Their serum samples as well as those from controls receiving normal rabbit IgG were studied for the presence of anti-Ab1 antibodies. In RIAs using [125I]oLH and affinity-purified Ab1, sera from experimental sheep showed high activity, as expressed in oLH equivalents. These sera also showed ability to compete with [125I]oLH for binding to receptor on pig ovarian and testicular membranes. The antiidiotypic antibodies (Ab2) in experimental sheep sera were purified by successive affinity chromatography on immobilized rabbit normal IgG and immobilized oLH-IgG columns. Ab2-IgG eluted from the latter mimicked oLH in RIAs and RRAs. These purified Ab2 antibodies were also of a stimulatory type, because they elicited progesterone production in rat granulosa cells and collagenase-dispersed rat Leydig cells. This stimulatory action was counteracted by coincubation with anti-oLH-IgG, which would also terminate (oLH) hormone action in a similar manner. The Ab2 antibodies had no effect on oFSH RIA or on the binding of [125I]oFSH to pig ovarian receptors, indicating specificity with respect to LH antigenic structure and function. As can be expected from the choice of the immunogen (polyclonal anti-oLH-IgG), only a small percentage of the true Ab2 population could display biological mimicry of the original antigen (oLH). Their presence in circulation during 6-8 months had no effect on testicular size or body growth. The formation of Ab2 antibodies to rabbit anti-oLH-IgG was also demonstrated in male rats, but these were not purified. In this instance also there was no effect on testicular weight after 6 months of immunization. These results show the feasibility of producing antiidiotypic antibodies that stimulate gonadal function in a manner much like the pituitary gonadotropin (oLH).
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PMID:Biological mimicry of gonadotropin action by antiidiotypic antibodies to luteinizing hormone: characterization and biological properties. 150 61

Drug-induced liver injury is a major cause of drug development failures and postmarket withdrawals. In vitro models that incorporate primary hepatocytes have been shown to be more predictive than model systems which rely on liver microsomes or hepatocellular carcinoma cell lines. Methods to phenotypically stabilize primary hepatocytes ex vivo often rely on mimicry of hepatic microenvironmental cues such as cell-cell interactions and cell-matrix interactions. In this work, we sought to incorporate phenotypically stable hepatocytes into three-dimensional (3D) microtissues, which, in turn, could be deployed in drug-screening platforms such as multiwell plates and diverse organ-on-a-chip devices. We first utilize micropatterning on collagen I to specify cell-cell interactions in two-dimensions, followed by collagenase digestion to produce well-controlled aggregates for 3D encapsulation in polyethylene glycol (PEG) diacrylate. Using this approach, we examined the influence of homotypic hepatocyte interactions and composition of the encapsulating hydrogel, and achieved the maintenance of liver-specific function for over 50 days. Optimally preaggregated structures were subsequently encapsulated using a microfluidic droplet-generator to produce 3D microtissues. Interactions of engineered hepatic microtissues with drugs was characterized by flow cytometry, and yielded both induction of P450 enzymes in response to prototypic small molecules and drug-drug interactions that give rise to hepatotoxicity. Collectively, this study establishes a pipeline for the manufacturing of 3D hepatic microtissues that exhibit stabilized liver-specific functions and can be incorporated into a wide array of emerging drug development platforms.
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PMID:Micropatterned cell-cell interactions enable functional encapsulation of primary hepatocytes in hydrogel microtissues. 2449 10

The phenomenon of vasculogenic mimicry in melanoma has been recently described to be an important factor relating to melanoma progression. Large scale gene expression profiling by real-time quantitative RT-QPCR of a panel of 40 normal tissues and 54 cancer cell lines revealed that two genetically related melanoma cell lines, one derived from a primary lesion Hs.688(A) and one derived from a lymph node metastasis Hs.688(B), displayed a unique expression pattern when compared to other cancer cell lines and tissue samples in the panel. Quantitative-RT-PCR data indicated that these melanoma cells expressed a number of activated endothelial cell-associated genes such as tissue inhibitors of matrix metalloproteinases TIMP-2, matrix metalloproteinase (MMP-1, MMP-2), thrombospondin 1 (TSP1), proto-oncogene c-MET and vascular endothelial growth factor (VEGF). To examine the gene expression profile of these unique melanoma cells in greater depth, cDNA libraries were made from isolated microsome complexes to enrich those transcripts that were destined to be translated into cell surface or secreted proteins. High throughput sequencing analysis revealed that this library contained over 7000 cDNAs and was enriched by over 80% of secreted or membrane-bound proteins. The presence in the cDNA library of genes such as acetyl LDL receptor, tumor endothelial markers-1, 5 and 8 (TEMs), flow-induced endothelial G protein coupled receptor-1 and VEGF-related protein (VRP), all of which are known to be expressed uniquely by endothelial cells, supported the hypothesis that Hs.688(A) and Hs.688(B) cells were mimicking an activated vascular phenotype. Ultimately the goal is to investigate the biological roles of endothelial cell-associated genes in the behavior of Hs.688(A) and Hs.688 (B) melanoma cells.
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PMID:The Melanoma Vascular Mimicry Phenotype Defined in Gene Expression and Microsome Sequencing Analysis. 3139 28