Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.69 (APC)
 16,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A model of murine heterotopic allogeneic transplantation was used to study the rejection characteristics of three tissues--adult cornea, fetal pancreas, and fetal skin--for attributes that might explain their variation in rejection rates and help define the determinants of graft immunogenicity. Under identical conditions, tissues were transplanted to the renal subcapsular space and their base-line rejection rates compared. The expression of MHC class I and II and intercellular adhesion molecule-1 (ICAM-1), was determined for each tissue, as was their ability to produce interleukin-6, IL-3, interferon-gamma, and granulocyte-macrophage colony-stimulating factor in vitro. These studies were performed under basal conditions and after stimulation with concanavalin A-stimulated spleen cell supernatant (CAS) or INF gamma. Corneal grafts had a slow rejection rate compared with pancreas and skin. While all three tissues had low basal expression of MHC class II, both fetal skin and pancreas, but not adult cornea, were able to increase this under our experimental conditions. Pancreas and skin produced IL-6 under basal conditions and could be stimulated to increase production 2-3-fold but the cornea did not basally produce IL-6 and showed minimal upregulation. We postulate that delayed corneal rejection, compared with pancreas and skin, results from two compounding deficiencies: the relative lack of class II MHC-positive APC and the inability to overcome this deficiency by upregulating class II expression and producing accessory molecules for antigen presentation.
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PMID:A comparison of corneal, pancreas, and skin grafts in mice. A study of the determinants of tissue immunogenicity. 751 13

It has been suggested that the severity of an attack of acute pancreatitis is related to the presence of intraglandular trypsinogen activation and that disease severity is also reflected by the degree of the acute-phase protein response. In this study we examine the relationships among amylase release, the degree of trypsinogen and prophospholipase A2 activation [as measured by urinary trypsinogen activation peptide (TAP) and prophospholipase A2 activation peptide (PLAP) concentrations], and the serum concentrations of the acute phase-protein C-reactive protein (CRP) and the principal mediator of the acute-phase protein response, interleukin-6 (IL-6). Twenty-four patients (14 mild and 10 severe attacks) were studied. Peak serum amylase concentrations were seen within 12 h and peak urinary TAP/creatinine (Cr) and PLAP/Cr ratios between 12 and 24 h after the onset of symptoms, preceding those of IL-6 and CRP. The integrated TAP/Cr and PLAP/Cr responses were significantly greater in those with severe disease [95% confidence internal (CI) = 106-259.6 pmol/mmol/h, p < 0.0008; and 95.1% CI = 462.2-3887 pmol/mmol/h, p < 0.003, respectively]. The integrated amylase response was not significantly greater in those with severe disease (95.6% CI = -415 to 832 IU/L/h, p < 0.14). There was a strong correlation among the integrated IL-6, TAP/Cr (r = 0.63, p < 0.01), and PLAP/Cr (r = 0.64, p < 0.01) responses but a poor correlation with the integrated amylase response (r = 0.19, NS).(ABSTRACT TRUNCATED AT 250 WORDS)
Pancreas 1995 May
PMID:The relationship between pancreatic enzyme release and activation and the acute-phase protein response in patients with acute pancreatitis. 754 Jul 60

We performed molecular biological studies as well as immunohistochemical analysis of three cases of giant cell carcinoma of the pancreas. Histologically, one case was a pleomorphic giant cell carcinoma consisting of pleomorphic giant/ small cells and spindle cells, one an osteoclast-like giant cell tumor composed of osteoclastoid giant cells and pleomorphic small cells, and one a pleomorphic giant cell carcinoma with osteoclastoid giant cells. Immunohistochemically, pleomorphic giant cells and small pleomorphic cells were positive for epithelial and mesenchymal markers throughout the cases. Osteoclastoid cells were strongly positive for PG-M1 (CD68), but negative for lysozyme and epithelial markers. Pleomorphic spindle cells showed the same immunoreactivity as pleomorphic giant/small cells. Genetically, all cases contained a mutation in the K-ras (codons 12, 13) oncogene, but neither p53 (exons 5-8) nor p16INK4 (exons 1, 2) gene mutations were found in any case. Furthermore, Loss of heterozygosity (LOH) of the p53, p161NK4. APC, and DPC4 gene loci was not found in any of the cases. Immunohistochemical study demonstrated this tumor to be of epithelial origin with mesenchymal differentiation. Genetically, initiation of the tumor is similar to that of usual ductal adenocarcinoma, but progression might be rather different. The peculiar histologic and biologic features of this tumor would be the result of changes in other functional genes.
Pancreas 1999 Apr
PMID:Immunohistochemical and molecular analysis of giant cell carcinoma of the pancreas: a report of three cases. 1020 90

Pancreatic cancer requires many genetic mutations. Combinations of underlying germline variants and environmental factors may increase the risk of cancer and accelerate the oncogenic process. We systematically reviewed, annotated, and classified previously reported pancreatic cancer-associated germline variants in established risk genes. Variants were scored using multiple criteria and binned by evidence for pathogenicity, then annotated with published functional studies and associated biological systems/pathways. Twenty-two previously identified pancreatic cancer risk genes and 337 germline variants were identified from 97 informative studies that met our inclusion criteria. Fifteen of these genes contained 66 variants predicted to be pathogenic (APC, ATM, BRCA1, BRCA2, CDKN2A, CFTR, CHEK2, MLH1, MSH2, NBN, PALB2, PALLD, PRSS1, SPINK1, TP53). Pancreatic cancer risk genes were organized into key biological mechanisms that promote pancreatic oncogenesis within an oncogenic model. Development of precision medicine approaches requires updated variant information within the framework of an oncogenic progression model. Complex risk modeling may improve interpretation of early biomarkers and guide pathway-specific treatment for pancreatic cancer in the future. Precision medicine is within reach.
Pancreas 2018 09
PMID:Germline Variants and Risk for Pancreatic Cancer: A Systematic Review and Emerging Concepts. 3011 27