Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.3.4.6 (urease)
 7,490 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ferrimagnetic materials can be expected to be useful as thermal seeds for hyperthermic treatment of cancer, especially where the cancer is located in deep parts of body, as they can generate heat by magnetic hysteretic loss when they are placed in an alternating magnetic field. In this study, hollow magnetite (Fe(3)O(4)) particles were prepared using an enzymatic reaction of urease. A hollow particle was obtained by using a Pasteur pipette. The particle was 500 microm in size and was composed of Fe(3)O(4). Its saturation magnetization and coercive force were 57 emuxg(-1) and 183 Oe, respectively. Its heat generation under an alternating magnetic field of 300 Oe at 100 kHz was estimated to be 45 Wxg(-1). Microspheres 30 microm in diameter were also successfully obtained by using a spray gun.
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PMID:Enzymatic preparation of hollow magnetite microspheres for hyperthermic treatment of cancer. 1677 May 44

Pituitary transforming gene (PTTG) is frequently expressed at high levels in malignant tumors. We report high levels of expression of PTTG in various lung tumors and tumor-derived cell lines. For a better understanding of its role in maintaining the cancer phenotype, we used RNA interference (RNAi) directed against PTTG. Transfection of H1299 cells with PTTG siRNA duplex (5'-UGG GAG AUC UCA AGU UUC A-3') to a final concentration of 100 nmol/l resulted in almost complete depletion of PTTG mRNA within 24 and 48 h when compared to expression in untransfected cells or cells transfected with control siRNA. Western blot analysis showed nearly a 60% reduction in PTTG protein within 48 h of transfection. In phenotype analysis, we investigated the effect of PTTG siRNA on colony formation on soft agar, and tumor development in nude mice. Transfection of H1299 cells with PTTG siRNA duplex significantly reduced colony formation compared to untransfected cells or cells transfected with control siRNA. Mice injected with H1299 cells transfected with PTTG siRNA followed by injection of siRNA developed no tumors within two weeks of injection, but developed small tumors (67.85+/-45.87 mg) within 4 weeks of injection, whereas untransfected cells, or cells transfected with control siRNA developed large tumors (232.12+/-102.78 and 231.57+/-83.76 mg respectively). Suppression of PTTG as well as Ki67, bFGF and CD34 was observed in H1299 tumors treated with PTTG siRNA compared to untreated and control-treated siRNA in nude mice. In conclusion, decreasing PTTG expression through PTTG siRNA inhibits tumor growth both in vitro and in vivo. Future studies are needed to test whether PTTG expression can be efficiently depleted by siRNA expressed from a DNA-based expression vector combined with a specific-promoter, such that RNAi can specifically target PTTG in cancer cells without affecting normal cells.
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PMID:Suppression of lung cancer with siRNA targeting PTTG. 1682 Aug 81

Ureases are enzymes from plants, fungi and bacteria that catalyze the hydrolysis of urea to form ammonia and carbon dioxide. While fungal and plant ureases are homo-oligomers of 90-kDa subunits, bacterial ureases are multimers of two or three subunit complexes. We showed that some isoforms of jack bean urease, canatoxin and the classical urease, bind to glycoconjugates and induce platelet aggregation. Canatoxin also promotes release of histamine from mast cells, insulin from pancreatic cells and neurotransmitters from brain synaptosomes. In vivo it induces rat paw edema and neutrophil chemotaxis. These effects are independent of ureolytic activity and require activation of eicosanoid metabolism and calcium channels. Helicobacter pylori, a Gram-negative bacterium that colonizes the human stomach mucosa, causes gastric ulcers and cancer by a mechanism that is not understood. H. pylori produces factors that damage gastric epithelial cells, such as the vacuolating cytotoxin VacA, the cytotoxin-associated protein CagA, and a urease (up to 10% of bacterial protein) that neutralizes the acidic medium permitting its survival in the stomach. H. pylori whole cells or extracts of its water-soluble proteins promote inflammation, activate neutrophils and induce the release of cytokines. In this paper we review data from the literature suggesting that H. pylori urease displays many of the biological activities observed for jack bean ureases and show that bacterial ureases have a secretagogue effect modulated by eicosanoid metabolites through lipoxygenase pathways. These findings could be relevant to the elucidation of the role of urease in the pathogenesis of the gastrointestinal disease caused by H. pylori.
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PMID:Ureases display biological effects independent of enzymatic activity: is there a connection to diseases caused by urease-producing bacteria? 1686 75

Results of clinical and instrumental-laboratory study of 17 cases are presented. According to the rapid urease test (CLO) and histological studies, the helicobacter infection was found in 12 (70.6%) cases out of the group of 17 suffering from chronic atrophic gastritis, gastric ulcer adenomatous polyposis. Analyses of Helicobacter pylori dissemination over the gastric mucosa manifested the I (weak) degree (up to 20 microbes within field of vision) prevailing in 8 (66.7%) of 12 cases, while the II (medium) degree (up to 50 microbes within field of vision) and III (high) degree (over 50 microbes within field of vision) occurred only in 4 cases (33.3%). By comparative cytogenetic research of the peripheral blood lymphocytes we found the immunogenetic markers and characteristic features of cytogenetic disturbances in the immunocompetent cells in cases of pre-cancer Helicobacter pylori-associated diseases (chronic atrophic gastritis, gastric ulcer, adenomatous polyposis). Statistical data confirmed an increase in the percentage of cells with chromosomal aberrations, which amounted to 4.25+/-0.51 in the chronic atrophic gastritis cases, 3.5+/-0.46 in the gastric ulcer cases, 5.75+/-0.60 in the adenomatous polyposis cases for 100 analyzed metaphases. Considering the questionable role of Helicobacter pylori as a direct initiator of mutagenesis, the immune disturbances may be caused by the damage of DNA of lymphocytes resulting from the genotoxic effect of some intermediates of inflammation.
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PMID:[Chromosomal instability of peripheral blood lymphocytes in patients with precancer gastric cases]. 1698 Jul 44

Helicobacter pylori, a gram-negative, microaerophilic, motile, spiral-shaped bacterium, has been established as the etiologic agent of gastritis and peptic ulcers and is a major risk factor for gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma (MALT). The ability of H. pylori to cause this spectrum of diseases depends on host, bacterial, and environmental factors. Bacterial factors critical for H. pylori colonization of the gastric mucosa include urease, flagella, adhesins, and delta-glutamyltranspeptidase. Lipopolysaccharide, urease, and vacuolating cytotoxin are among the factors that allow H. pylori to persist for decades and invoke an intense inflammatory response, leading to damaged host cells. Genes in the cag pathogenicity island also contribute to the inflammatory response by initiating a signal transduction cascade, resulting in interleukin-8 production. Proinflammatory cytokines and a Th-1 cytokine response further exacerbates the inflammation. Products of the enzymes nitric oxide synthase (iNOS) and cyclooxygenase may perturb the balance between gastric epithelial cell apoptosis (ulcer formation) and proliferation (cancer). The host Th-1 response and antibodies directed against H. pylori do not eliminate the organism, which presents challenges to vaccine development. Vaccines that include urease have shown some promise, but improved adjuvants and animal models should hasten progress in vaccine research. H. pylori is the most genetically diverse organism known, and the panmictic population structure may contribute to the varying ranges of disease severity produced by different strains. The complete genome sequence of two strains of H. pylori has propelled this field forward, and numerous groups are now using genomic, proteomic, and mutagenetic approaches to identify new virulence genes. Discovered only in 1982, H. pylori is now among the most intensely investigated organisms. This review summarizes recent progress in this rapidly moving field.
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PMID:Pathogenesis of Helicobacter pylori infection. 1702 12

The diagnosis of cancer by examination of the urine has the potential to improve patient outcomes by means of earlier detection. Due to the fact that the urine contains metabolic signatures of many biochemical pathways, this biofluid is ideally suited for metabolomic analysis, especially involving diseases of the kidney and urinary system. In this pilot study, we test three independent analytical techniques for suitability for detection of renal cell carcinoma (RCC) in urine of affected patients. Hydrophilic interaction chromatography (HILIC-LC-MS), reversed-phase ultra performance liquid chromatography (RP-UPLC-MS), and gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) all were used as complementary separation techniques. The combination of these techniques is best suited to cover a very large part of the urine metabolome by enabling the detection of both lipophilic and hydrophilic metabolites present therein. In this study, it is demonstrated that sample pretreatment with urease dramatically alters the metabolome composition apart from removal of urea. Two new freely available peak alignment methods, MZmine and XCMS, are used for peak detection and retention time alignment. The results are analyzed by a feature selection algorithm with subsequent univariate analysis of variance (ANOVA) and a multivariate partial least squares (PLS) approach. From more than 2000 mass spectral features detected in the urine, we identify several significant components that lead to discrimination between RCC patients and controls despite the relatively small sample size. A feature selection process condensed the significant features to less than 30 components in each of the data sets. In future work, these potential biomarkers will be further validated with a larger patient cohort. Such investigation will likely lead to clinically applicable assays for earlier diagnosis of RCC, as well as other malignancies, and thereby improved patient prognosis.
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PMID:A comprehensive urinary metabolomic approach for identifying kidney cancerr. 1731 36

This study assessed the prevalence of Helicobacter pylori in symptomatic Bulgarian adults by means of culture, Gram's stain and an in-house rapid urease test (RUT), and also assessed the H. pylori density by culture. In total, 1441 non-treated and 270 treated patients were evaluated. Most non-treated patients with ulcers (87.7%), gastric malignancy (79.2%) and other gastroduodenal diseases (73.4%) were H. pylori-positive. Among non-treated and treated patients, 75.3% and 54.8%, respectively, of elderly patients, and 78.3% and 56.1%, respectively, of other adults were H. pylori-positive. Two (0.1%) non-treated adults were Helicobacter heilmannii-positive. The accuracy of direct Gram's stain and the in-house RUT were 74.8% and 64.2% in non-treated patients, and 73.7% and 63.0% in treated patients, respectively. Culture was highly accurate (>95%) in both groups. Older age decreased the sensitivity of the RUT in non-treated patients by 10.7% and that of all tests in treated patients by 6.9-8.1%. Incubation for 11 days was required for the growth of 2% and 4% of the strains from treated patients on selective and non-selective medium, respectively. There were no differences in isolation rates between positive fresh (74.2%) and frozen (75.2%) specimens. In non-treated adults, a high H. pylori density (growth in all quadrants of the plates) was more common (43.1%) in ulcer patients than in other patients (25.4%). In conclusion, H. pylori infection was common in Bulgarian patients, and at a high density in >40% of ulcer patients, while H. heilmannii infection was uncommon. Culture provided a highly accurate diagnostic approach. Stomach biopsies from non-treated patients can be frozen for several days. The benefit of reporting H. pylori density, as determined by culture, requires further evaluation.
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PMID:Detection of Helicobacter pylori infection in symptomatic Bulgarian adults. 1768 40

Recent epidemiological studies have demonstrated that consumption of certain natural products can lower cancer risk in humans. For example, plant-derived lignans have been shown to exert chemopreventive effects against cancer in vitro and in vivo. In the present study, the effects of three such lignans, termed arctiin, arctigenin, and nordihydroguaiaretic acid (NDGA), on the proliferation of Helicobacter pylori and the prevention of H. pylori-associated gastric cancer were investigated in Mongolian gerbils. To examine the effects of arctigenin and NDGA on stomach carcinogenesis, specific pathogen-free male, 5-week-old gerbils were infected with H. pylori, administered 10 p.p.m. N-methyl-N-nitrosourea in their drinking water and fed diets containing various concentrations of lignans until they were killed after 52 weeks. At a dietary level of 0.25%, NDGA significantly decreased the incidence of gastric adenocarcinomas. Arctigenin, in contrast, failed to attenuate neoplasia at a level of 0.1%. Both NDGA and arctigenin significantly reduced serum 8-hydroxy-2'-deoxyguanosine levels at doses of 0.25 and 0.05% (NDGA), and 0.1% (arctigenin). Administration of 0.25% NDGA significantly suppressed the formation of intestinal metaplasia both in the antrum and the corpus. Although all three lignans dose-dependently inhibited the in vitro proliferation of H. pylori, there were no differences in the titers of anti-H. pylori antibodies or the amount of the H. pylori-specific urease A gene among all H. pylori-infected groups. These results suggest that NDGA might be effective for prevention of gastric carcinogenesis. The possible mechanisms appear to be related to inhibitory effects on progression of gastritis and antioxidative activity rather than direct antimicrobial influence.
Cancer Sci 2007 Nov
PMID:Inhibitory effect of nordihydroguaiaretic acid, a plant lignan, on Helicobacter pylori-associated gastric carcinogenesis in Mongolian gerbils. 1789 52

Oxidative DNA damage is thought to play an important part in the pathogenesis of H. pylori-induced mucosal damage. 8-OHdG is a sensitive marker of DNA oxidation and is repaired by a polymorphic glycosylase (OGG1) more effectively than by OGG1-Cys(326). The aims of this study were to ascertain the respective roles of H. pylori, cagA status and OGG1 polymorphism in determining 8-OHdG levels in benign and premalignant stomach diseases and in gastric cancer (GC). The study involved 50 GC patients (for whom both neoplastic tissue and surrounding mucosa were available), 35 with intestinal metaplasia and atrophy (IMA) and 43 controls. H. pylori and cagA status were determined by histology and polymerase chain reaction for urease and cagA. 8-OHdG was assayed using HPLC with an electrochemical detector (HPLC-ED). The OGG1 1245C-->G transversion was identified using RFLP analyses. 8-OHdG levels were significantly higher in GC, with no differences in relation to H. pylori or cagA status. OGG1 polymorphism was documented in 34% of GC (15 Ser/Cys, 2 Cys/Cys). OGG1 1245C-->G polymorphism was detected in 54% of IMA patients, but only 16% of controls (p = 0.0004) and coincided with significantly higher 8-OHdG levels. In the multivariate analysis, 8-OHdG levels were predicted by histotype and OGG1 status. OGG1 1245C-->G polymorphism was common in both GC and IMA, but very rare in controls, and correlated more closely with 8-OHdG levels than do H. pylori infection or cagA status.
Int J Cancer 2008 Jul 01
PMID:Oxidative DNA damage in gastric cancer: CagA status and OGG1 gene polymorphism. 1836 59

The biosynthesis of the active metal-bound form of the nickel-dependent enzyme urease involves the formation of a lysine-carbamate functional group concomitantly with the delivery of two Ni(2+) ions into the precast active site of the apoenzyme and with GTP hydrolysis. In the urease system, this role is performed by UreG, an accessory protein belonging to the group of homologous P-loop GTPases, often required to complete the biosynthesis of nickel-enzymes. This study is focused on UreG from Helicobacter pylori (HpUreG), a bacterium responsible for gastric ulcers and cancer, infecting large part of the human population, and for which urease is a fundamental virulence factor. The soluble HpUreG was expressed in E. coli and purified to homogeneity. On-line size exclusion chromatography and light scattering indicated that apo-HpUreG exists as a monomer in solution. Circular dichroism, which demonstrated the presence of a well-defined secondary structure, and NMR spectroscopy, which revealed a large number of residues that appear structured on the basis of their backbone amide proton chemical shift dispersion, indicated that, at variance with other UreG proteins so far characterized, this protein is significantly folded in solution. The amino acid sequence of HpUreG is 29% identical to that of HypB from Methanocaldococcus jannaschii, a dimeric zinc-binding GTPase involved in the in vivo assembly of [Ni,Fe]-hydrogenase. A homology-based molecular model of HpUreG was calculated, which allowed us to identify structural and functional features of the protein. Isothermal titration microcalorimetry demonstrated that HpUreG specifically binds 0.5 equivalents of Zn(2+) per monomer (K(d) = 0.33 +/- 0.03 microM), whereas it has 20-fold lower affinity for Ni(2+) (K(d) = 10 +/- 1 microM). Zinc ion binding (but not Ni(2+) binding) causes protein dimerization, as confirmed using light scattering measurements. The structural rearrangement occurring upon Zn(2+)-binding and consequent dimerization was evaluated using circular dichroism and fluorescence spectroscopy. Fully conserved histidine and cysteine residues were identified and their role in zinc binding was verified by site-directed mutagenesis and microcalorimetry. The results are analyzed and discussed with respect to analogous examples of GTPases in nickel metabolism.
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PMID:Zn2+-linked dimerization of UreG from Helicobacter pylori, a chaperone involved in nickel trafficking and urease activation. 1876 50


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