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)

Although debates still exist whether Helicobacter pylori infection is really class I carcinogen or not, H. pylori has been known to provoke precancerous lesions like gastric adenoma and chronic atrophic gastritis with intestinal metaplasia as well as gastric cancer. Chronic persistent, uncontrolled gastric inflammations are possible basis for ensuing gastric carcinogenesis and H. pylori infection increased COX-2 expressions, which might be the one of the mechanisms leading to gastric cancer. To know the implication of long-term treatment of antiinflammatory drugs, rebamipide or nimesulide, on H. pylori-associated gastric carcinogenesis, we infected C57BL/6 mice with H. pylori, especially after MNU administration to promote carcinogenesis and the effects of the long-term administration of rebamipide or nimesulide were evaluated. C57BL/6 mice were sacrificed 50 weeks after H. pylori infection. Colonization rates of H. pylori, degree of gastric inflammation and other pathological changes including atrophic gastritis and metaplasia, serum levels and mRNA transcripts of various mouse cytokines and chemokines, and NF-kappaB binding activities, and finally the presence of gastric adenocarcinoma were compared between H. pylori infected group (HP), and H. pylori infected group administered with long-term rebamipide containing pellet diets (HPR) or nimesulide mixed pellets (HPN). Gastric mucosal expressions of ICAM-1, HCAM, MMP, and transcriptional regulations of NF-kappaB binding were all significantly decreased in HPR group than in HP group. Multi-probe RNase protection assay showed the significantly decreased mRNA levels of apoptosis related genes and various cytokines genes like IFN-gamma, RANTES, TNF-alpha, TNFR p75, IL-1beta in HPR group. In the experiment designed to provoke gastric cancer through MNU treatment with H. pylori infection, the incidence of gastric carcinoma was not changed between HP and HPR group, but significantly decreased in HPN group, suggesting the chemoprevention of H. pylori-associated gastric carcinogenesis by COX-2 inhibition. Long-term administration of antiinflammatory drugs should be considered in the treatment of H. pylori since they showed the molecular and biologic advantages with possible chemopreventive effect against H. pylori-associated gastric carcinogenesis. If the final concrete proof showing the causal relationship between H. pylori infection and gastric carcinogenesis could be obtained, that will shed new light on chemoprevention of gastric cancer, that is, that gastric cancer could be prevented through either the eradication of H. pylori or lessening the inflammation provoked by H. pylori infection in high risk group.
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PMID:Chemoprevention of Helicobacter pylori-associated gastric carcinogenesis in a mouse model: is it possible? 1254 79

The neurotrophin nerve growth factor (NGF) regulates neuronal growth, differentiation, and survival during development. However, the precursor of NGF, proNGF, is a potent apoptotic ligand for the p75 neurotrophin receptor (p75(NTR))-sortilin complex. The mechanisms that regulate cleavage of proNGF, therefore, are critical determinants of whether this factor promotes neuronal survival or death. In this study, we demonstrate that, following kainic acid-induced seizures, the proNGF processing enzyme matrix metalloproteinase 7 (MMP-7) and its inhibitor TIMP-1 (tissue inhibitor of matrix metalloproteinase 1) are regulated in a manner that prevents proneurotrophin cleavage and leads to increased proNGF in the extracellular milieu. Furthermore, we demonstrate both in vitro and in vivo that exogenous MMP-7 enhances proNGF cleavage and provides neuroprotection following kainic acid treatment. These data demonstrate that increased extracellular proNGF levels following seizures are stabilized by altered MMP-7 enzymatic activity, leading to increased neuronal death via activation of p75(NTR).
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PMID:Matrix metalloproteinase-7 regulates cleavage of pro-nerve growth factor and is neuroprotective following kainic acid-induced seizures. 2259 20

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer without effective targeted drugs. While breast cancer patients often use acupuncture for the relief of cancer-induced pain or the side effects of chemo- or radiation therapy, little information is known regarding the direct effects of electroacupuncture on TNBC tumor and its potential mechanisms. Here, we created a mice model of TNBC and electroacupuncture with encircled needling around the tumors was given to the animals daily for 3 weeks at 15-20 Hz (3 min, each time). For sham electroacupuncture control, the skin was punctured to a depth of 5 mm and then the needle was quickly withdrawn without electrical stimulation or manual needle manipulation. We found that electroacupuncture significantly inhibited TNBC tumor growth and the inhibitory rate increased gradually overtime. Mechanistic analysis showed that electroacupuncture inhibited tumor angiogenesis by reducing the expression of vascular endothelial growth factor A (VEGF-A), its receptor VEGF-R and neuropilin 1 (NRP-1). Electroacupuncture also led to a significant decrease of matrix metalloproteinase-2 (MMP-2) expression and an increase of tissue inhibitor of MMP (TIMP-2) expression. Additionally, the expression of semaphorin 3A (Sema3A) and nerve growth factor receptor (NGFR) p75 in TNBC tissue was significantly upregulated in response to electroacupuncture. Furthermore, tumor necrosis factor (TNF)-alpha level in the serum was dramatically reduced after electroacupuncture. These results showed that electroacupuncture could directly inhibit TNBC tumor growth through the inhibition of proteins related to tumor angiogenesis and extracellular matrix, the suppression of TNBC-induced inflammation and the upregulation of nerve growth factor receptors.
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PMID:Inhibition of Triple-Negative Breast Cancer Tumor Growth by Electroacupuncture with Encircled Needling and Its Mechanisms in a Mice Xenograft Model. 3183 52