Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.23 (MMP)
 4,246 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present study the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in acute lymphatic leukemia (ALL) is studied with immunocytochemical staining in bone marrow aspirate smears from 75 patients. The material included 20 adult and 55 pediatric ALL patients. In 65% of the adult ALL cases the immunoreactive protein for either MMP-2 or MMP-9 or for both the enzymes was seen. A statistically significant correlation (P 0.027) with MMP-2 positivity and appearance of extramedullary infiltrates was found in adult ALL, suggesting that the gelatinase activity could be related with increased extravasation of the leukemic cells in ALL. This has to be confirmed in a larger patient population. In pediatric patients there were only seven cases (12.7%) out of 55 with positive immunostaining for either of these metalloproteinases. MMP expression correlated with L2 FAB class, high-risk tumor group and T-cell immunophenotype, but not with extramedullary presentation in pediatric patients with ALL indicating basic biological differences between adult and childhood ALL.
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PMID:MMP-2 and MMP-9 expression in adult and childhood acute lymphatic leukemia (ALL). 1116 27

Extracellular proteolytic enzymes of the urokinase-type plasminogen activator (uPA) and metalloproteinase (MMP) family play a crucial role in the matrix degradation and tissue remodeling process characteristic of malignant disorders. The receptor for urokinase plasminogen activator (uPAR) serves to localize and intensify the action of UPA and is expressed on the surface of malignant cells. Although the biological significance of MMP-9 and soluble urokinase receptor in growth and progression of lymphoid neoplasm is understood, its clinical significance in acute myeloid leukemia (AML) has not been fully elucidated. In this study, we determined the levels of soluble urokinase-type plasminogen activator receptor (suPAR), cellular uPAR and sMMP-9 in 43 newly diagnosed AML patients at diagnosis, before chemotherapy, and also studied 10 normal subjects served as a control group. After chemotherapy suPAR and MMP-9 were determined at remission and relapse. The levels of suPAR, cellular PAR were significantly higher (P= 0.001, 0.001) and MMP-9 was significantly lower (P=0.001) in AML patients at diagnosis as compared to controls. suPAR and MMP-9 levels were significantly lower in AML patients who achieved complete remission (CR) as compared to those who did not (P= 0.001 for both). Levels of suPAR and MMP-9 were significantly correlated to peripheral blood blast cells (r= 0.88, P= 0.001; r= 0.65, P= 0.001, respectively) and blast cell distribution ratio (BCDR, r= 0.84, P= 0.001; r=65, P= 0.001, respectively). suPAR, cellular PAR and MMP-9 were significantly higher in patients with extramedullary infiltration as compared with those without (P= 0.001, 0.001, <0.05). The suPAR, cellular uPAR, and MMP-9 levels were uneven in AML FAB subtypes being highest in M5(P<0.05 for all). MMP-9 and suPAR levels were correlated with the disease status. In AML survivors, MMP-9, cellular uPAR and suPAR were significantly lower as compared to non-survivors (P= 0.001 for all). In conclusion, MMP-9 and su PAR levels might be used as a marker for disease activity and may contribute to blast cell dissemination. MMP-9 and suPAR may be target molecules in the strategy of treatment of AML.
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PMID:Urokinase plasminogen activator receptor and soluble matrix metalloproteinase-9 in acute myeloid leukemia patients: a possible relation to disease invasion. 1466 33

Cognitive impairment (CI) and dementia are frequent and debilitating features associated with Parkinson's disease (PD). Formal neuropsychological examination is required to ascertain the degree and pattern of CI over the course of the disease. The use of different tools may explain heterogeneous data obtained from studies to date. Normative data for extensively used scales [Mattis Dementia Rating Scale (MDRS), Mini-Mental State Examination (MMSE)] is incomplete in PD populations. According to sample characteristics, statistical analyses, and methodological quality, 33 studies using scales not specific to PD (MDRS, MMSE, Cambridge Cognitive Assessment, FAB) or PD-specific scales (Mini-Mental Parkinson, Scales for Outcomes of Parkinson's disease-Cognition, Parkinson's Disease-Cognitive Rating Scale, and Parkinson Neuropsychometric Dementia Assessment) were eligible for the critical analysis of their appropriateness to assess cognition in PD. Of the four scales specifically designed for PD, the SCOPA-COG and the PD-CRS have undergone extensive and rigorous validation processes. While the SCOPA-COG mainly assesses "frontal-subcortical" cognitive defects, the PD-CRS also assesses "instrumental-cortical" functions, allowing better characterization of the different patterns of CI that may be present in PD from the earliest stages. The MMP and PANDA scales were designed as brief screening tests for CI and have not yet been subjected to extensive clinimetric evaluations. Further research on PD-specific tools seems mandatory to help establish accurate cut-off scores for the diagnosis of mild PDD, detect cognitive profiles more prone to the future development of dementia, and allow comparisons between different descriptive or interventional studies.
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PMID:Cognitive impairment in Parkinson's disease: tools for diagnosis and assessment. 1935 27

The frequency of extramedullary infiltration (EMI) in acute myeloblastic leukemia (AML) is reported up to 40% and most prevalent in myelo-monoblastic and monoblastic subtypes of AML (M4 and M5 according to FAB classification). The majority of patients with EMI suffered poor prognosis. To explore mechanism underlying EMI, we analyzed SHI-1 cells, a highly invasive human acute monocytic leukemia cell line, and found their strong expression of matrix metalloproteinase 2 (MMP-2), membrane type 1 MMP (MT1-MMP) and tissue inhibitor of metalloproteinase 2 (TIMP-2). SHI-1 cells showed higher invasive ability to traverse reconstituted basement membranes (Matrigel) and stronger activation of proMMP-2 than other leukemia cell line such as NB4, K562, U937 and THP-1 cells. When co-cultured with bone marrow stromal cells (BMSCs), the invasive capacity and proMMP-2 activation of SHI-1 cells enhanced remarkably. Furthermore, the inhibition of MMP-2, MT1-MMP, or TIMP-2 by small interfering RNA (siRNA) substantially impaired SHI-1 cells invasion and decreased proMMP-2 activation. In the contrast, up-regulated expression of TIMP-2 for 2-3 folds level increased cell invasion and proMMP-2 activation. These results demonstrated that constitutively high expression of MMP-2, MT1-MMP and TIMP-2 in SHI-1 cells facilitated cell invasion by promoting proMMP-2 activation. Moreover, up-regulation of TIMP-2 exhibited not a repressive but an activating effect on SHI-1 cells invasion. Our study indicated that increasing TIMP-2 in AML patients with EMI may potentially cause adverse effects, particularly in patients containing high levels of MMP-2 and MT1-MMP.
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PMID:The essential roles of matrix metalloproteinase-2, membrane type 1 metalloproteinase and tissue inhibitor of metalloproteinase-2 in the invasive capacity of acute monocytic leukemia SHI-1 cells. 2013 66