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Author Klumpp, L.; Sezgin, E.C.; Skardelly, M.; Eckert, F.; Huber, S.M. url  doi
openurl 
  Title KCa3.1 channels and glioblastoma: in vitro studies Type Journal Article
  Year 2017 Publication Current Neuropharmacology Abbreviated Journal Curr Neuropharmacol  
  Volume Issue Pages  
  Keywords γH2AX foci; Aldh1a3; Gbm; GSCs; IKCa; Kcnn4; Sk4; radioresistance  
  Abstract Several tumor entities including brain tumors aberrantly overexpress intermediate conductance Ca2+ activated KCa3.1 K+ channels. These channels contribute significantly to the transformed phenotype of the tumor cells. By modulating membrane potential, cell volume, Ca2+ signals and the respiration chain, KCa3.1 channels in both, plasma and inner mitochondrial membrane, have been demonstrated to regulate many cellular processes such as migration and tissue invasion, metastasis, cell cycle progression, oxygen consumption and metabolism, DNA damage response and cell death of cancer cells. Moreover, KCa3.1 channels have been shown to crucially contribute to resistance against radiotherapy suggesting KCa3.1 channels as promising new targets of future anti-cancer therapies. The present article summarizes our current knowledge of the molecular signaling upstream and downstream and the effector functions of KCa3.1 channel activity in tumor cells in general and in glioblastoma cells in particular. In addition, it presents original in vitro data on KCa3.1 channel expression in subtypes of glioblastoma stem(-like) cells proposing KCa3.1 as marker for the mesenchymal subgroup of cancer stem cells. Moreover, the data suggest that KCa3.1 contributes to the therapy resistance of mesenchymal glioblastoma stem cells.  
  Address (up) Department of Radiation Oncology University of Tubingen Hoppe-Seyler-Str. 3 72076 Tubingen. Germany  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1570-159X ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28786347 Approved no  
  Call Number ref @ user @ Serial 96571  
Permanent link to this record
 

 
Author Bijangi-Vishehsaraei, K.; Reza Saadatzadeh, M.; Wang, H.; Nguyen, A.; Kamocka, M.M.; Cai, W.; Cohen-Gadol, A.A.; Halum, S.L.; Sarkaria, J.N.; Pollok, K.E.; Safa, A.R. url  doi
openurl 
  Title Sulforaphane suppresses the growth of glioblastoma cells, glioblastoma stem cell-like spheroids, and tumor xenografts through multiple cell signaling pathways Type Journal Article
  Year 2017 Publication Journal of Neurosurgery Abbreviated Journal J Neurosurg  
  Volume Issue Pages 1-12  
  Keywords CCCP = carbonyl cyanide m-chlorophenylhydrazone; DMSO = dimethyl sulfoxide; DSB = double-strand break; EGF = epidermal growth factor; FACS = fluorescence-activated cell sorting; FGF = fibroblast growth factor; GBM = glioblastoma; GSC = glioblastoma stem cell; IC50 = 50% inhibition of cell survival; MRC = mitochondrial respiratory chain; MSC = mesenchymal stromal cell; NAC = N-acetylcysteine; NSG = nonobese diabetic scid gamma; PE = phycoerythrin; ROS = reactive oxygen species; SFN = sulforaphane; SSB = single-strand break; apoptosis; cancer stem cells; glioblastoma; oncology; sulforaphane  
  Abstract OBJECTIVE Defects in the apoptotic machinery and augmented survival signals contribute to drug resistance in glioblastoma (GBM). Moreover, another complexity related to GBM treatment is the concept that GBM development and recurrence may arise from the expression of GBM stem cells (GSCs). Therefore, the use of a multifaceted approach or multitargeted agents that affect specific tumor cell characteristics will likely be necessary to successfully eradicate GBM. The objective of this study was to investigate the usefulness of sulforaphane (SFN)-a constituent of cruciferous vegetables with a multitargeted effect-as a therapeutic agent for GBM. METHODS The inhibitory effects of SFN on established cell lines, early primary cultures, CD133-positive GSCs, GSC-derived spheroids, and GBM xenografts were evaluated using various methods, including GSC isolation and the sphere-forming assay, analysis of reactive oxygen species (ROS) and apoptosis, cell growth inhibition assay, comet assays for assessing SFN-triggered DNA damage, confocal microscopy, Western blot analysis, and the determination of in vivo efficacy as assessed in human GBM xenograft models. RESULTS SFN triggered the significant inhibition of cell survival and induced apoptotic cell death, which was associated with caspase 3 and caspase 7 activation. Moreover, SFN triggered the formation of mitochondrial ROS, and SFN-triggered cell death was ROS dependent. Comet assays revealed that SFN increased single- and double-strand DNA breaks in GBM. Compared with the vehicle control cells, a significantly higher amount of gamma-H2AX foci correlated with an increase in DNA double-strand breaks in the SFN-treated samples. Furthermore, SFN robustly inhibited the growth of GBM cell-induced cell death in established cell cultures and early-passage primary cultures and, most importantly, was effective in eliminating GSCs, which play a major role in drug resistance and disease recurrence. In vivo studies revealed that SFN administration at 100 mg/kg for 5-day cycles repeated for 3 weeks significantly decreased the growth of ectopic xenografts that were established from the early passage of primary cultures of GBM10. CONCLUSIONS These results suggest that SFN is a potent anti-GBM agent that targets several apoptosis and cell survival pathways and further preclinical and clinical studies may prove that SFN alone or in combination with other therapies may be potentially useful for GBM therapy.  
  Address (up) Departments of 2 Pharmacology and Toxicology and  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0022-3085 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28059653 Approved no  
  Call Number ref @ user @ Serial 96613  
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Author Jara-Samaniego, J.; Perez-Murcia, M.D.; Bustamante, M.A.; Paredes, C.; Perez-Espinosa, A.; Gavilanes-Teran, I.; Lopez, M.; Marhuenda-Egea, F.C.; Brito, H.; Moral, R. url  doi
openurl 
  Title Development of organic fertilizers from food market waste and urban gardening by composting in Ecuador Type Journal Article
  Year 2017 Publication PloS one Abbreviated Journal PLoS One  
  Volume 12 Issue 7 Pages e0181621  
  Keywords Analysis of Variance; Carbon/analysis; *Cities; Ecuador; Feasibility Studies; *Fertilizers/analysis/economics; *Food; *Gardening/economics/methods; Nitrogen/analysis; Plants; Recycling/economics/methods; *Soil/chemistry; Temperature; Waste Management/economics/*methods  
  Abstract Currently, the management of urban waste streams in developing countries is not optimized yet, and in many cases these wastes are disposed untreated in open dumps. This fact causes serious environmental and health problems due to the presence of contaminants and pathogens. Frequently, the use of specific low-cost strategies reduces the total amount of wastes. These strategies are mainly associated to the identification, separate collection and composting of specific organic waste streams, such as vegetable and fruit refuses from food markets and urban gardening activities. Concretely, in the Chimborazo Region (Ecuador), more than 80% of municipal solid waste is dumped into environment due to the lack of an efficient waste management strategy. Therefore, the aim of this study was to develop a demonstration project at field scale in this region to evaluate the feasibility of implanting the composting technology not only for the management of the organic waste fluxes from food market and gardening activities to be scaled-up in other developing regions, but also to obtain an end-product with a commercial value as organic fertilizer. Three co-composting mixtures were prepared using market wastes mixed with pruning of trees and ornamental palms as bulking agents. Two piles were created using different proportions of market waste and prunings of trees and ornamental palms: pile 1 (50:33:17) with a C/N ratio 25; pile 2: (60:30:10) with C/N ratio 24 and pile 3 (75:0:25) with C/N ratio 33), prepared with market waste and prunings of ornamental palm. Throughout the process, the temperature of the mixtures was monitored and organic matter evolution was determined using thermogravimetric and chemical techniques. Additionally, physico-chemical, chemical and agronomic parameters were determined to evaluate compost quality. The results obtained indicated that all the piles showed a suitable development of the composting process, with a significant organic matter decomposition, reached in a shorter period of time in pile 3. At the end of the process, all the composts showed absence of phytotoxicity and suitable agronomic properties for their use as organic fertilizers. This reflects the viability of the proposed alternative to be scaled-up in developing areas, not only to manage and recycle urban waste fluxes, but also to obtain organic fertilizers, including added value in economic terms related to nutrient contents.  
  Address (up) Dept. of Agrochemistry and Environment, Miguel Hernandez University, Orihuela, Alicante, Spain  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1932-6203 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28727757 Approved no  
  Call Number ref @ user @ Serial 98013  
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Author Hudgins, J.D.; Goldberg, V.; Fell, G.L.; Puder, M.; Eisenberg, M.A. url  doi
openurl 
  Title Reducing Time to Antibiotics in Children With Intestinal Failure, Central Venous Line, and Fever Type Journal Article
  Year 2017 Publication Pediatrics Abbreviated Journal Pediatrics  
  Volume 140 Issue 5 Pages  
  Keywords Anti-Bacterial Agents/*administration & dosage; Bacteremia/diagnosis/drug therapy/epidemiology; Central Venous Catheters/microbiology; Child, Preschool; Cohort Studies; Female; Fever/diagnosis/*drug therapy/*epidemiology; Humans; Intestinal Diseases/diagnosis/drug therapy/epidemiology; Length of Stay/*trends; Male; Short Bowel Syndrome/diagnosis/*drug therapy/*epidemiology; Time-to-Treatment  
  Abstract BACKGROUND: Children with intestinal failure (IF) on parenteral nutrition (PN) are at high risk for bacteremia, and delays in antibiotic administration have been associated with increased morbidity and mortality. We designed an emergency department (ED) quality improvement (QI) initiative to reduce time to administration of intravenous antibiotics in febrile children with IF on PN. METHODS: Our aim was to decrease the mean time for febrile children with IF on PN to receive intravenous antibiotics by 50% to <60 minutes over a 12-month period. Secondary outcome measures were ED, hospital, and ICU length of stay (LOS). Our process measure was the rate of ordering recommended antibiotics, and our balancing measure was the rate of hypoglycemia. Interventions included increasing provider knowledge of IF, streamlining order entry, providing individualized feedback, and standardizing the triage process. Results were analyzed by using statistical process control methodology and time series analysis. RESULTS: We identified 149 eligible ED patients, of which 62 (41.6%) had bacteremia. The mean time to antibiotics decreased after the onset of the QI initiative from 112 to 39 minutes, and the ED LOS decreased from 286 to 247 minutes, but the total length of hospital and ICU stays were unchanged. The rate of hypoglycemia was also unchanged. CONCLUSIONS: Our QI intervention for febrile children with IF on PN shortened the time to receive antibiotics. Larger studies are needed to demonstrate the impact on overall LOS and mortality.  
  Address (up) Division of Emergency Medicine and  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0031-4005 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:29066581 Approved no  
  Call Number ref @ user @ Serial 98935  
Permanent link to this record
 

 
Author Hudgins, J.D.; Goldberg, V.; Fell, G.L.; Puder, M.; Eisenberg, M.A. url  doi
openurl 
  Title Reducing Time to Antibiotics in Children With Intestinal Failure, Central Venous Line, and Fever Type Journal Article
  Year 2017 Publication Pediatrics Abbreviated Journal Pediatrics  
  Volume 140 Issue 5 Pages  
  Keywords Anti-Bacterial Agents/*administration & dosage; Bacteremia/diagnosis/drug therapy/epidemiology; Central Venous Catheters/microbiology; Child, Preschool; Cohort Studies; Female; Fever/diagnosis/*drug therapy/*epidemiology; Humans; Intestinal Diseases/diagnosis/drug therapy/epidemiology; Length of Stay/*trends; Male; Short Bowel Syndrome/diagnosis/*drug therapy/*epidemiology; Time-to-Treatment  
  Abstract BACKGROUND: Children with intestinal failure (IF) on parenteral nutrition (PN) are at high risk for bacteremia, and delays in antibiotic administration have been associated with increased morbidity and mortality. We designed an emergency department (ED) quality improvement (QI) initiative to reduce time to administration of intravenous antibiotics in febrile children with IF on PN. METHODS: Our aim was to decrease the mean time for febrile children with IF on PN to receive intravenous antibiotics by 50% to <60 minutes over a 12-month period. Secondary outcome measures were ED, hospital, and ICU length of stay (LOS). Our process measure was the rate of ordering recommended antibiotics, and our balancing measure was the rate of hypoglycemia. Interventions included increasing provider knowledge of IF, streamlining order entry, providing individualized feedback, and standardizing the triage process. Results were analyzed by using statistical process control methodology and time series analysis. RESULTS: We identified 149 eligible ED patients, of which 62 (41.6%) had bacteremia. The mean time to antibiotics decreased after the onset of the QI initiative from 112 to 39 minutes, and the ED LOS decreased from 286 to 247 minutes, but the total length of hospital and ICU stays were unchanged. The rate of hypoglycemia was also unchanged. CONCLUSIONS: Our QI intervention for febrile children with IF on PN shortened the time to receive antibiotics. Larger studies are needed to demonstrate the impact on overall LOS and mortality.  
  Address (up) Division of Emergency Medicine and  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0031-4005 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:29066581 Approved no  
  Call Number ref @ user @ Serial 99965  
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