Home About us Contact
|
Home About us Contact | ||
|
|
||
Elevated Activity (elevated + activity)
Selected AbstractsElevated activities of MMP-2 in the non-tumorous lung tissues of curatively resected stage I NSCLC patients are associated with tumor recurrence and a poor survival,JOURNAL OF SURGICAL ONCOLOGY, Issue 4 2007Sang-Hui Kim Abstract Background and Objectives We wanted to assess whether the level of enzyme activity for a particular matrix metalloproteinase (MMP), and not the amount of expressed protein, in lung tissue could be used as a reliable prognostic biomarker for tumor recurrence leading to poorer survival in a certain subgroup of patients who have undergone curative resection for stage I human NSCLC. Methods We determined what type of MMP was significant for tumor recurrence by using a mouse model of pulmonary metastasis with inoculating the footpad with H460 human cancer cells. We then looked for any association between tumor recurrence and the level of enzyme activities for the selected MMP in the tumor and also in the pathologically non-tumorous tissues from 34 stage I lung cancer patients. Results We obtained H460/PM6 cells having a highly metastatic potential after six repeated cycles of pulmonary metastasis by using the mouse footpad inoculated with the metastasized cancer cells in the previous cycle. We started with human lung cancer cells, H460, and we found that among the tested MMPs we tested for, the level of MMP-2 mRNA was elevated. No significant difference was seen in the level of enzyme activity of the MMP-2 cells from the curatively resected tumor tissues of the stage I NSCLC patients who were later found with or without recurrence. However, the level of MMP-2 enzyme activity was found to be significantly different between the non-tumorous lung tissues from patients later found with and without recurrence, and it was associated with the 5-year survival rate. Conclusions This observation suggests that the higher level of MMP-2 enzyme activity in the non-tumorous tissues from the patients could be used as a prognostic biomarker to predict post-operative tumor recurrence and survival for patients with stage I NSCLC. The elevated enzyme activity of MMP-2 in the non-tumorous tissue resected from stage I NSCLC could be used as a prognostic indicator for post-operative tumor recurrence and the patients' poor survival. Further, this could be an important aid for physicians' making decision on whether to subject particular patients to post-operative adjunct chemotherapy. J. Surg. Oncol. 2007;95:337,346. © 2007 Wiley-Liss, Inc. [source] Elevated activity of the oxidative and non-oxidative pentose phosphate pathway in (pre)neoplastic lesions in rat liverINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 4 2008Wilma M. Frederiks Summary (Pre)neoplastic lesions in livers of rats induced by diethylnitrosamine are characterized by elevated activity of the first irreversible enzyme of the oxidative branch of the pentose phosphate pathway (PPP), glucose-6-phosphate dehydrogenase (G6PD), for production of NADPH. In the present study, the activity of G6PD, and the other NADPH-producing enzymes, phosphogluconate dehydrogenase (PGD), isocitrate dehydrogenase (ICD) and malate dehydrogenase (MD) was investigated in (pre)neoplastic lesions by metabolic mapping. Transketolase (TKT), the reversible rate-limiting enzyme of the non-oxidative branch of the PPP, mainly responsible for ribose production, was studied as well. Activity of G6PD in (pre)neoplastic lesions was highest, whereas activity of PGD and ICD was only 10% and of MD 5% of G6PD activity, respectively. Glucose-6-phosphate dehydrogenase activity in (pre)neoplastic lesions was increased 25 times compared with extralesional parenchyma, which was also the highest activity increase of the four NADPH-producing dehydrogenases. Transketolase activity was 0.1% of G6PD activity in lesions and was increased 2.5-fold as compared with normal parenchyma. Transketolase activity was localized by electron microscopy exclusively at membranes of granular endoplasmic reticulum in rat hepatoma cells where G6PD activity is localized as well. It is concluded that NADPH in (pre)neoplastic lesions is mainly produced by G6PD, whereas elevated TKT activity in (pre)neoplastic lesions is responsible for ribose formation with concomitant energy supply by glycolysis. The similar localization of G6PD and TKT activity suggests the channelling of substrates at this site to optimize the efficiency of NADPH and ribose synthesis. [source] Polyamine metabolism in barley reacting hypersensitively to the powdery mildew fungus Blumeria graminis f. sp. hordeiPLANT CELL & ENVIRONMENT, Issue 3 2002T. Cowley Abstract Polyamine levels and activities of enzymes of polyamine biosynthesis and catabolism were examined in the barley cultivar Delibes (Ml1al + Ml(Ab)) reacting hypersensitively to the powdery mildew fungus, Blumeria graminis f. sp. hordei (race CC220). Levels of free putrescine and spermine and of conjugated forms of putrescine, spermidine and spermine were greatly increased 1,4 d following inoculation of barley with the powdery mildew. These changes in polyamine levels were accompanied by elevated activities of the polyamine biosynthetic enzymes ornithine decarboxylase (ODC), arginine decarboxylase (ADC) and S -adenosylmethionine decarboxylase (AdoMetDC) and the polyamine catabolic enzymes diamine oxidase (DAO) and polyamine oxidase (PAO). Activities of two enzymes involved in conjugating polyamines to hydroxycinnamic acids, putrescine hydroxycinnamoyl transferase (PHT) and tyramine feruloyl-CoA transferase (TFT) were also examined and were found to increase significantly 1,4 d after inoculation. The possibility that the increased levels of free spermine, increased polyamine conjugates, and increased DAO and PAO activities are involved in development of the hypersensitive response of Delibes to powdery mildew infection is discussed. [source] Hyperfrontality in patients with schizophrenia during saccade and antisaccade tasks: A study with fMRIPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 2 2009Mai Fukumoto-Motoshita mms Aims:, Antisaccadic eye movements, requiring inhibition of a saccade toward a briefly appearing peripheral target, are known to be impaired in schizophrenia. Previous neuroimaging studies have indicated that patients with schizophrenia show diminished activations in the frontal cortex and basal ganglia. These studies used target fixation as a baseline condition. However, if the levels of brain activities at baseline are not compatible between patients and healthy subjects, between-group comparison on antisaccade-related activations is consequently invalidated. One possibility is that patients with schizophrenia may present with greater activation during fixation than healthy subjects. In order to examine this possibility, here we investigated brain activities associated with antisaccade in the two groups without using target fixation at baseline. Methods:, Functional brain images were acquired during prosaccades and antisaccades in 18 healthy subjects and 18 schizophrenia patients using a box-car functional magnetic resonance imaging design. Eye movements were measured during scanning. Results:, In the patient group, the elevated activities in the dorsolateral prefrontal cortex (DLPFC) and thalamus, normally seen in antisaccade tasks relative to saccade tasks, were no longer observed. Moreover, in normal subjects, activities in the DLPFC and thalamus were greater during the antisaccade task than during the saccade task. In patients, no such difference was observed between the two tasks, suggesting that these brain regions are likely to be highly activated even by a simple task such as fixation. In particular, the DLPFC and thalamus in patients were not activated at a level commensurate with the difficulty of the tasks presented. Conclusions:, From these results, it is suggested that schizophrenia entails dysfunctions in the fronto-striato-thalamo-cortical network associated with motor function control. [source] The adaptive response of anaerobically grown Saccharomyces cerevisiae to hydrogen peroxide is mediated by the Yap1 and Skn7 transcription factorsFEMS YEAST RESEARCH, Issue 8 2008Anthony G. Beckhouse Abstract The molecular mechanisms involved in the ability of cells to adapt and respond to differing oxygen tensions are of great interest to the pharmaceutical, medical and fermentation industries. The transcriptional profiles reported in previous studies of cells grown under anaerobic, aerobic and dynamic growth conditions have shown significantly altered responses including induction of genes regulated by the oxidative stress transcription factor Yap1p when oxygen was present. The present study investigated the phenotypic changes that occur in cells when shifted from anaerobic to aerobic growth conditions and it was found through mutant analyses that the elevated activity of Yap1p during the shift was mediated by the phospholipid hydroperoxide-sensing protein encoded by GPX3. Cell viability and growth rate were unaffected even though anaerobically grown cells were found to be hypersensitive to low doses of the oxidative stress-inducing compound hydrogen peroxide (H2O2). Adaptation to H2O2 treatment was demonstrated to occur when anaerobically grown wild-type cells were aerated for a short time that was reliant on the Yap1p and Skn7p transcription factors. [source] Elevated activity of the oxidative and non-oxidative pentose phosphate pathway in (pre)neoplastic lesions in rat liverINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 4 2008Wilma M. Frederiks Summary (Pre)neoplastic lesions in livers of rats induced by diethylnitrosamine are characterized by elevated activity of the first irreversible enzyme of the oxidative branch of the pentose phosphate pathway (PPP), glucose-6-phosphate dehydrogenase (G6PD), for production of NADPH. In the present study, the activity of G6PD, and the other NADPH-producing enzymes, phosphogluconate dehydrogenase (PGD), isocitrate dehydrogenase (ICD) and malate dehydrogenase (MD) was investigated in (pre)neoplastic lesions by metabolic mapping. Transketolase (TKT), the reversible rate-limiting enzyme of the non-oxidative branch of the PPP, mainly responsible for ribose production, was studied as well. Activity of G6PD in (pre)neoplastic lesions was highest, whereas activity of PGD and ICD was only 10% and of MD 5% of G6PD activity, respectively. Glucose-6-phosphate dehydrogenase activity in (pre)neoplastic lesions was increased 25 times compared with extralesional parenchyma, which was also the highest activity increase of the four NADPH-producing dehydrogenases. Transketolase activity was 0.1% of G6PD activity in lesions and was increased 2.5-fold as compared with normal parenchyma. Transketolase activity was localized by electron microscopy exclusively at membranes of granular endoplasmic reticulum in rat hepatoma cells where G6PD activity is localized as well. It is concluded that NADPH in (pre)neoplastic lesions is mainly produced by G6PD, whereas elevated TKT activity in (pre)neoplastic lesions is responsible for ribose formation with concomitant energy supply by glycolysis. The similar localization of G6PD and TKT activity suggests the channelling of substrates at this site to optimize the efficiency of NADPH and ribose synthesis. [source] Importance of forkhead transcription factor Fkhl18 for development of testicular vasculatureMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 9 2008Yuko Sato Abstract Forkhead transcription factors are characterized by a winged helix DNA binding domain, and the members of this family are classified into 20 subclasses by phylogenetic analyses. Fkhl18 is structurally unique, and is classified into FoxS subfamily. We found Fkhl18 expression in periendothelial cells of the developing mouse fetal testis. In an attempt to clarify its function, we generated mice with Fkhl18 gene disruption. Although KO mice developed normally and were fertile in both sexes, we frequently noticed unusual blood accumulation in the fetal testis. Electron microscopic analysis demonstrated frequent gaps, measuring 100,400 nm, in endothelial cells of blood vessels. These gaps probably represented ectopic apoptosis of testicular periendothelial cells, identified by caspase-3 expression, in KO fetuses. No apoptosis of endothelial cells was noted. Fkhl18 suppressed the transcriptional activity of FoxO3a and FoxO4. Considering that Fas ligand gene expression is activated by Foxs, the elevated activity of Foxs in the absence of Fkhl18 probably explains the marked apoptosis of periendothelial cells in Fkhl18 KO mice. Mol. Reprod. Dev. 75: 1361,1371, 2008. © 2008 Wiley-Liss, Inc. [source] | |||||||||||||