Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In halothane-anesthetized and -ventilated cynomologus macaque monkeys, the effects of administering vehicle (n = 3) or the neutral endopeptidase inhibitor N-[L-(1-carboxy-2-phenyl)ethyl]-L-phenylalanyl-beta-alanine (16 mg/kg, n = 5; or 100 mg/kg, n = 3, intravenously) was examined. Cisternal CSF aliquots were examined by radioimmunoassay: 1) for Met enkephalin; 2) after trypsin and carboxypeptidase B treatment for encrypted enkephalin (X-ENK); 3) for substance P; and 4) for unmetabolized drug. Similar measures were carried out in femoral artery and femoral venous plasma, except that substance P was not assayed. In CSF, prior to drug, low, but measurable levels of enkephalin (61 pg/ml), X-ENK (285 pg/ml) and substance P (16 pg/ml) were observed. Vehicle-injected animals showed no change from baseline levels over a 4-hr sampling period in either plasma or CSF levels. In contrast, following 16 mg/kg, in CSF, there was a significant 9-fold increase in MET and 11-fold increase in X-ENK at 30 min. CSF-substance P levels rose also by a factor of 2, with the peak effect observed at 60 min. All levels displayed a significant reduction by 4 hr. There was no statistical difference between the maximum effects observed with either the 16- or 100-mg/kg dose. Plasma peptide levels of enkephalin and X-ENK were not altered by drug. CSF displayed significant drug levels by 30 min, which were between 0.1 and 1% of levels observed concurrently in plasma.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of [N-(L-(1-carboxy-2-phenyl)ethyl]-L-phenylalanyl-beta-alanine (SCH32615), a neutral endopeptidase (enkephalinase) inhibitor, on levels of enkephalin, encrypted enkephalins and substance P in cerebrospinal fluid and plasma of primates. 170 28

A better molecular characterization of breast cell lines (BCL) may help discover new markers to apply to tumour samples. We performed gene and protein expression profiling of 31 BCL using whole-genome DNA microarrays and immunohistochemistry (IHC) on 'cell microarrays' (CMA), respectively. Global hierarchical clustering discriminated two groups of BCL: group I corresponded to luminal cell lines, group II to basal and mesenchymal cell lines. Correlations with centroids calculated from a published 'intrinsic 500-gene set' assigned 15 cell lines as luminal, eight as basal and four as mesenchymal. A set of 1.233 genes was differentially expressed between basal and luminal samples. Mesenchymal and basal subtypes were rather similar and discriminated by only 227 genes. The expression of 10 proteins (CAV1, CD44, EGFR, MET, ETS1, GATA3, luminal cytokeratin CK19, basal cytokeratin CK5/6, CD10, and ERM protein moesin) encoded by luminal vs basal discriminator genes confirmed the subtype classification and the validity of the identified markers. Our BCL basal/luminal signature correctly re-classified the published series of tumour samples that originally served to identify the molecular subtypes, suggesting that the identified markers should be useful for tumour classification and might represent promising targets for disease management.
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PMID:Gene expression profiling of breast cell lines identifies potential new basal markers. 1628 5

Pseudomyxoma (PM) implies an accumulation of a large amount of mucins which show myxomatous appearances. PM Peritonei (PMP) is famous and the only example of PM. PMP means excessive accumulation of mucins and mucin-secreting cells in the peritoneal cavity. The causes of PMP are mostly mucinous tumors, both benign and malignant, of ovaries and vermiform appendix. The author experienced excessive accumulation of mucins and mucin-producing cells in the subcutis and deep soft tissue. This situation very resembled PMP. Thus, the author termed the lesion as PM cutis (PMC). A 57-year-old man admitted to our hospital because of multiple subcutaneous large tumors in the perianal skin. The tumors were deeply seated and soft. No biopsy was performed. Very large skin and subcutis resection of the perianal region was done. Grossly, the material was skin and sot tissue flap measuring 25x25x5cm. The subcutis and deep soft tissue were resected. On cut surface, the tumor was slimy liquid. Microscopical examination revealed a large amount of mucins pools and mucin-producing intestinal epithelium with mild atypia. The author diagnosed it metastatic extremely well differentiated adenocarcinoma producing mucins, and pointed out anorectal primary. Thus, Miles operation was performed, which showed tumor formation in the anus. The tumor was located from the submucosa to adventitia, and composed of mucin pools and mucins producing intestinal-type epithelium with atypia. Mucins histochemistry showed that the mucin pools and epithelial cytoplasm contained neutral, carboxylated, and sulfated mucins. Immunohistochemically, the tumor cells were positive for CKAE1/3, CKCAM5.2, CK7, CK8, CK19, CK20, CEA, CA19-9,CD68, MET, p53, MUC2, MUC5AC, KIT, PDGFRA, chromogranin, and Ki-67 (76%). They were negative for CK34BE12, CK5/6, CK14, CK18, EMA, vimentin, desmin, smooth muscle actin, p63, CD34, ER, PgR, CA125, MUC1, MUC6, CD45, CD10, synaptophysin, surfactant Apo-A, TTF-1, NCAM, bcl-2, CDX-2. Although the atypia is mild, the author diagnosed primary anorectal extremely well differentiated adenocarcinoma with excessive production of mucins. The author considers the cutaneous mucins and tumor cells are metastatic or directly invading lesions of the anal tumor. Thus, the author termed pseudomyxoma cutis (PMC) for the cutaneous lesion.
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PMID:Pseudomyxoma cutis; a new entity. 2369 38

Papillary renal cell carcinoma (PRCC) is traditionally classified into type 1 and type 2. Recently, an oncocytic variant of PRCC has been described. We report a series of 6 oncocytic renal papillary tumors (OPRCC) which tended to occur in older patients (mean, 56.8 years) with a male preference (male-to-female ratio is 5:1). All 6 patients are alive with no evidence of disease after initial resection, showing an indolent clinical behavior. Histologically, tumors exhibited predominant papillary structure with delicate fibrovascular cores. Papillae were lined by single layers of cells with large, deeply eosinophilic and finely granular cytoplasms and round regular nucleus. The phagocytosis of tumor cells was frequently and evidently seen in our cases that hemosiderin-laden tumor cells and foamy tumor cells were noticed in five and four cases respectively. All tumors were immunoreactive for racemase, vimentin, CD10, and MET and negative for CD117. While E-cadherin, EMA, and cytokeratin 7 exhibited variable immunopositivity. FISH analysis was performed in five of six cases and found heterogeneous results. Trisomy of chromosomes 7 was found in three cases and trisomy of chromosomes 17 in two cases. Loss of chromosome Y was noted in one of four tumors in male patients. MET gene status was also investigated by direct sequencing in all 6 cases and found no distinct mutation in any case. These results suggest that OPRCC shows distinct morphology, indolent clinical behavior, and similar immunohistochemical and cytogenetic features with PRCC, seems to be a variant in the PRCC group. Whether the strong expression of MET indicates a potential therapeutic target is still unknown and requires further investigation in clinical trials.
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PMID:Oncocytic papillary renal cell carcinoma: a clinicopathological study emphasizing distinct morphology, extended immunohistochemical profile and cytogenetic features. 2382 21

Hepatocyte growth factor (HGF) promotes pleiotropic signaling through its specific receptor tyrosine kinase, MET. As such, it has important roles in the regeneration of injured tissues. Since HGF is produced mainly by mesenchymal cells and MET is expressed in most epithelial, endothelial and somatic stem cells, HGF functions as a typical paracrine growth factor. HGF is secreted as an inactive precursor (proHGF) and requires proteolytic activation to initiate HGF-induced MET signaling. HGF activator (HGFAC) is a serum activator of proHGF and produces robust HGF activities in injured tissues. HGFAC is a coagulation factor XII-like serine endopeptidase that circulates in the plasma as a zymogen (proHGFAC). Thrombin, kallikrein-related peptidase (KLK)-4 or KLK-5 efficiently activates proHGFAC. The activated HGFAC cleaves proHGF at Arg494-Val495, resulting in the formation of the active disulfide-linked heterodimer HGF. Macrophage stimulating protein, a ligand of RON, is also activated by HGFAC in vivo. Although HGFAC functions primarily at the site of damaged tissue, a recent report has suggested that activated HGFAC relays a signal to stem cells in non-injured tissues via proHGF activation in the stem cell niche. This review focuses on current knowledge regarding HGFAC-mediated proHGF activation and its roles in tissue regeneration and repair.
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PMID:Hepatocyte Growth Factor Activator: A Proteinase Linking Tissue Injury with Repair. 3038 69