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)

Risk or presence of metastasis in medulloblastoma causes substantial treatment-related morbidity and overall mortality. Through the comparison of cytokines and growth factors in the cerebrospinal fluid (CSF) of metastatic medulloblastoma patients with factors also in conditioned media of metastatic MYC amplified medulloblastoma or leptomeningeal cells, we were led to explore the bioactivity of IGF1 in medulloblastoma by elevated CSF levels of IGF1, IGF-sequestering IGFBP3, IGFBP3-cleaving proteases (MMP and tPA), and protease modulators (TIMP1 and PAI-1). IGF1 led not only to receptor phosphorylation but also accelerated migration/adhesion in MYC amplified medulloblastoma cells in the context of appropriate matrix or meningothelial cells. Clinical correlation suggests a peri-/sub-meningothelial source of IGF-liberating proteases that could facilitate leptomeningeal metastasis. In parallel, studies of key factors responsible for cell autonomous growth in MYC amplified medulloblastoma prioritized IGF1R inhibitors. Together, our studies identify IGF1R as a high value target for clinical trials in high risk medulloblastoma.
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PMID:IGF1R as a Key Target in High Risk, Metastatic Medulloblastoma. 2725 63

Radiofrequency machines for medical use are known to produce moderate clinical improvement of skin laxity without invasive procedures. Numerous equipment with different characteristics have been proposed after the introduction in 2002 of the first FDA approved device. This report is aimed to test if RF treatment is effective when performed at low frequency and low energy level. Two RF treatments were performed unilaterally 7 and 2 days before a planned eyebrow lifting surgery, with a radiofrequency device with 0.52 to 0.7 MHz frequencies, maximum energy of 200 W, used at 40% of its power. A bipolar handpiece with a diameter of 30 mm and a maximum power of 9-9.5 W was massaged along the temporal area for 10 min. Skin samples of treated and untreated sides were collected during surgery and processed for histologic examination and RT-PCR analysis, to test differences in gene activation in a panel of proteins that are relevant in extracellular matrix of dermal connective tissue. The histological examination of the samples showed that the treatment induced a loss of the typical oriented structure in the reticular dermis. The study through RT-PCR evidenced that ELN, the gene codifying for Elastine was strongly enhanced. Some collagen-tested genes (COL1A1, COL3A1 and COL9A1) were inhibited by the treatment, whereas COL2A1 and COL11 were activated. The genes responsible for Metallo-proteases (MMP) 2, 3 and 13 were depressed, while the MMP9 was stimulated. Gene codifying for Hyaluronic synthase 1 (HAS1), Hyluronidase 1 (HYAL1), Neutrophyl elastase (Elane), Desmoplakin (DSP) and GDF6 were inhibited. Insulin like growth factor (IGF1) gene activity was enhanced. RF treatment, with the tested non-ablative equipment, produced histological effects and change in DNA expression of some extracellular matrix related genes, confirming the biostimulatory role of this procedure.
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PMID:Non-ablative radio-frequency rejuvenation: a histological and bio-molecular report. 2746 72