Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.27.1 (RNase)
 16,360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) have been implicated in the immense invasive potential and neovascularization of primary brain tumors. We investigated the gene expression profiles of MMPs 1, 2, 3, 7, 9, 12, 13, 14, 16 and of TIMPs 1, 2, 3, and 4 in various primary brain tumors (astrocytoma WHO grade I-III, glioblastoma, PNET, ependymoma III and oligoastrocytoma II) using novel RNase protection assay probe sets. In addition, we determined the level and cellular source of gelatinolytic activity and localized gelatinase B and TIMP-1 RNA. Distinct expression patterns of the MMP and TIMP genes were found in the various brain tumors tested. While the WHO grade I and II tumors had MT1/MT3 ratios below 1, the malignant (grade III and IV) tumors had ratios above 1. Strong expression of TIMP-1 RNA was observed in all malignant tumors and in grade I pilocytic astrocytomas and localized to the walls of neovessels. Quantitative analysis of enzymatic activity in the soluble fraction of protein extracts revealed that in most tumors gelatinases remained in the inactive pro-form. In situ zymography revealed net gelatinolytic activity in neurons of normal brain and in tumor cells and vessel walls of all tumors tested. Immunohistochemistry demonstrated that gelatinase B was localized to vessel walls, to neutrophils in areas of hemorrhage, and in glioblastomas to macrophages. Together these data demonstrate that the different primary brain tumors show distinct regulation of MMP and TIMP genes. The localization of the soluble gelatinase B indicates an association with neovascularization, whereas membrane-bound MMPs may account for the invasive potential of the glial tumor cells.
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PMID:Distinct expression patterns and levels of enzymatic activity of matrix metalloproteinases and their inhibitors in primary brain tumors. 1139 36

We report a case of a DICER1-associated EWSR1-rearranged malignant primitive neuroectodermal tumor (PNET) arising in a patient with DICER1 tumor predisposition syndrome. A 16-yr-old female with a history of multinodular goiter presented with a widely metastatic abdominal small round blue cell tumor with neuroectodermal differentiation. EWSR1 gene rearrangement was identified in the tumor by fluorescence in situ hybridization (FISH). Genetic analysis revealed biallelic pathogenic DICER1 variation. The patient was treated with an aggressive course of chemotherapy, surgery, and radiation with complete pathologic response. We believe this case to represent a new expression of the DICER1 tumor predisposition syndrome, an entity caused by deleterious germline mutations in the DICER1 gene, encoding a ribonuclease active in the processing of miRNA. Patients with germline mutations in DICER1 develop a diverse group of benign and malignant tumors. Some of these tumors have been noted to have immature neuroepithelium as a component, including the ciliary body medulloepithelioma and the recently described DICER1-associated presacral malignant teratoid neoplasm. To our knowledge, abdominal sarcomas that resemble PNET histology with an EWSR1 rearrangement have not previously been described as a classical expression of the DICER1 syndrome phenotype.
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PMID:DICER1-associated metastatic abdominopelvic primitive neuroectodermal tumor with an EWSR1 rearrangement in a 16-yr-old female. 3302 42