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Author (up) Luedi, M.M.; Singh, S.K.; Mosley, J.C.; Hatami, M.; Gumin, J.; Sulman, E.P.; Lang, F.F.; Stueber, F.; Zinn, P.O.; Colen, R.R. url  doi
openurl 
  Title A Dexamethasone-regulated Gene Signature Is Prognostic for Poor Survival in Glioblastoma Patients Type Journal Article
  Year 2017 Publication Journal of Neurosurgical Anesthesiology Abbreviated Journal J Neurosurg Anesthesiol  
  Volume 29 Issue 1 Pages 46-58  
  Keywords Animals; Antineoplastic Agents, Hormonal/*pharmacology; Apoptosis; Blotting, Western; Brain Neoplasms/*mortality; Cell Line, Tumor; Cell Survival; Dexamethasone/*pharmacology; Flow Cytometry; Gene Expression Regulation, Neoplastic/*drug effects; Glioblastoma/*mortality; Humans; Mice; Prognosis; Stem Cells/drug effects; Survival Analysis  
  Abstract BACKGROUND: Dexamethasone is reported to induce both tumor-suppressive and tumor-promoting effects. The purpose of this study was to identify the genomic impact of dexamethasone in glioblastoma stem cell (GSC) lines and its prognostic value; furthermore, to identify drugs that can counter these side effects of dexamethasone exposure. METHODS: We utilized 3 independent GSC lines with tumorigenic potential for this study. Whole-genome expression profiling and pathway analyses were done with dexamethasone-exposed and control cells. GSCs were also co-exposed to dexamethasone and temozolomide. Risk scores were calculated for most affected genes, and their associations with survival in The Cancer Genome Atlas and Repository of Molecular Brain Neoplasia Data databases. In silico Connectivity Map analysis identified camptothecin as antagonist to dexamethasone-induced negative effects. RESULTS: Pathway analyses predicted an activation of dexamethasone network (z-score: 2.908). Top activated canonical pathways included “role of breast cancer 1 in DNA damage response” (P=1.07E-04). GSCs were protected against temozolomide-induced apoptosis when coincubated with dexamethasone. Altered cellular functions included cell movement, cell survival, and apoptosis with z-scores of 2.815, 5.137, and -3.122, respectively. CCAAT/enhancer binding protein beta (CEBPB) was activated in a dose dependent manner specifically in slow-dividing “stem-like” cells. CEBPB was activated in dexamethasone-treated orthotopic tumors. Patients with high risk scores had significantly shorter survival. Camptothecin was validated as potential partial neutralizer of dexamethasone-induced oncogenic effects. CONCLUSIONS: Dexamethasone exposure induces a genetic program and CEBPB expression in GSCs that adversely affects key cellular functions and response to therapeutics. High risk scores associated with these genes have negative prognostic value in patients. Our findings further suggest camptothecin as a potential neutralizer of adverse dexamethasone-mediated effects.  
  Address *Department of Anesthesiology, Bern University Hospital Inselspital, Bern, Switzerland Departments of daggerCancer Systems Imaging double daggerDiagnostic Imaging section signNeurosurgery and Brain Tumor Center parallelRadiation Oncology, Division of Radiation Oncology #Neurosurgery, Cancer Systems Imaging, and Cancer Biology **Cancer Systems Imaging, and Diagnostic Imaging, The University of Texas MD Anderson Cancer Center paragraph signDepartment of Neurosurgery, Baylor College of Medicine, Houston, TX  
  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 0898-4921 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:27653222 Approved no  
  Call Number ref @ user @ Serial 96635  
Permanent link to this record
 

 
Author (up) Ma, H.X.; He, L.; Cai, S.W.; Xin, X.L.; Shi, H.D.; Zhou, L.; Shi, X.J. url  openurl
  Title [Analysis of the spectrum and resistance of pathogen causing sepsis in patients with severe acute pancreatitis] Type Journal Article
  Year 2017 Publication Zhonghua wai ke za zhi [Chinese Journal of Surgery] Abbreviated Journal Zhonghua Wai Ke Za Zhi  
  Volume 55 Issue 5 Pages 378-383  
  Keywords Adult; Aged; Anti-Bacterial Agents/*therapeutic use; Cross Infection; *Drug Resistance, Bacterial; Escherichia coli; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Pancreatitis/*complications; Retrospective Studies; Sepsis/*drug therapy; Vancomycin/therapeutic use; Young Adult; Bacteria spectrum; Drug resistance; Pancreatitis, acute necrotizing; Sepsis  
  Abstract Objective: To investigate the characteristics of spectrum and drug resistance of pathogens causing sepsis in patients with severe acute pancreatitis(SAP). Methods: The clinical data of 63 SAP patients with sepsis admitted in Department of Hepatobiliary, People's Liberation Army General Hospital from January 2014 to December 2015 were retrospectively studied. There were 47 males and 16 females, aged from 22 to 73 years, with an average age of (52+/-11)years. Samples were collected mainly from: (1)pancreatic and peripancreatic necrosis and abdominal drainage; (2)bile; (3) blood or deep venous catheter; (4) sputum and tracheal catheter and thoracic drainage; (5) urine. Strain identification and drug-resistance test were preformed on positive specimens. Results: Of 244 pathogenic isolates, mainly derived from abdominal cavity(36.0%), blood stream (14.0%), central venous catheter(11.8%), necrotic tissue(9.1%) and sputum(8.1%); 154(63.1%) were gram-negative bacteria, 68 cases(27.9%) were gram-positive bacteria and 22 cases(9.0%) were fungi respectively. The top six common pathogens isolated were E. coli(16.0%), E.faecium and faecalis(15.2%), P.aeruginosa(10.7%), K.pneumonia(9.8%), Acinetobacter baumanni(8.2%), Stenotrophomonas maltophilia(5.3%)respectively. The detection rate of E. coli and K. pneumonia extended-spectrum beta-lactamases(ESBL) was 84.6%(33/39) and 70.8%(17/24), the resistance rate to imipeniem was 12.8% and 25.0%, to cefperazone-sulbactam was 28.2% and 29.2%. As to P. aeruginosa and Acinetobacter bacillus, the resistance rate to imipeniem was 50.0% and 75.0%, to cefperazone-sulbactam was 42.3% and 70.0%; Stenotrophomonas maltophilia was completely resistant to cefperazone-sulbactam, but sensitive to minocycline, SMZ-TMP with the resistance rate less than 40.0%. Gram-positive bacterium strains mainly included E. faecium(38.2%, 26/68), E.faecalis(16.2%, 11/68) and Staphylococcus(35.3%, 24/68) which maintained high sensitivity to vancomycin, teicoplanin and linezolid, there was only one isolate resistant to vancomycin. Candida were the sole pathogens of fungal infections, sensitive to common antifungal drugs overall. Conclusions: The gram-negative bacteria are the predominant pathogens mainly including ESBL-producing isolates(E.coli and K. pneumonia) and non-fermentation bacteria(P.aeruginosa and Acinetobacter bacillus) causing sepsis in SAP. The infection rate and drug-resistance rate of these two kinds of pathogens are relatively higher.  
  Address Department of Hepatobiliary, People's Liberation Army General Hospital, Beijing 100853, China  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language Chinese Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0529-5815 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28464580 Approved no  
  Call Number ref @ user @ Serial 99094  
Permanent link to this record
 

 
Author (up) Ma, H.X.; He, L.; Cai, S.W.; Xin, X.L.; Shi, H.D.; Zhou, L.; Shi, X.J. url  openurl
  Title [Analysis of the spectrum and resistance of pathogen causing sepsis in patients with severe acute pancreatitis] Type Journal Article
  Year 2017 Publication Zhonghua wai ke za zhi [Chinese Journal of Surgery] Abbreviated Journal Zhonghua Wai Ke Za Zhi  
  Volume 55 Issue 5 Pages 378-383  
  Keywords Adult; Aged; Anti-Bacterial Agents/*therapeutic use; Cross Infection; *Drug Resistance, Bacterial; Escherichia coli; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Pancreatitis/*complications; Retrospective Studies; Sepsis/*drug therapy; Vancomycin/therapeutic use; Young Adult; Bacteria spectrum; Drug resistance; Pancreatitis, acute necrotizing; Sepsis  
  Abstract Objective: To investigate the characteristics of spectrum and drug resistance of pathogens causing sepsis in patients with severe acute pancreatitis(SAP). Methods: The clinical data of 63 SAP patients with sepsis admitted in Department of Hepatobiliary, People's Liberation Army General Hospital from January 2014 to December 2015 were retrospectively studied. There were 47 males and 16 females, aged from 22 to 73 years, with an average age of (52+/-11)years. Samples were collected mainly from: (1)pancreatic and peripancreatic necrosis and abdominal drainage; (2)bile; (3) blood or deep venous catheter; (4) sputum and tracheal catheter and thoracic drainage; (5) urine. Strain identification and drug-resistance test were preformed on positive specimens. Results: Of 244 pathogenic isolates, mainly derived from abdominal cavity(36.0%), blood stream (14.0%), central venous catheter(11.8%), necrotic tissue(9.1%) and sputum(8.1%); 154(63.1%) were gram-negative bacteria, 68 cases(27.9%) were gram-positive bacteria and 22 cases(9.0%) were fungi respectively. The top six common pathogens isolated were E. coli(16.0%), E.faecium and faecalis(15.2%), P.aeruginosa(10.7%), K.pneumonia(9.8%), Acinetobacter baumanni(8.2%), Stenotrophomonas maltophilia(5.3%)respectively. The detection rate of E. coli and K. pneumonia extended-spectrum beta-lactamases(ESBL) was 84.6%(33/39) and 70.8%(17/24), the resistance rate to imipeniem was 12.8% and 25.0%, to cefperazone-sulbactam was 28.2% and 29.2%. As to P. aeruginosa and Acinetobacter bacillus, the resistance rate to imipeniem was 50.0% and 75.0%, to cefperazone-sulbactam was 42.3% and 70.0%; Stenotrophomonas maltophilia was completely resistant to cefperazone-sulbactam, but sensitive to minocycline, SMZ-TMP with the resistance rate less than 40.0%. Gram-positive bacterium strains mainly included E. faecium(38.2%, 26/68), E.faecalis(16.2%, 11/68) and Staphylococcus(35.3%, 24/68) which maintained high sensitivity to vancomycin, teicoplanin and linezolid, there was only one isolate resistant to vancomycin. Candida were the sole pathogens of fungal infections, sensitive to common antifungal drugs overall. Conclusions: The gram-negative bacteria are the predominant pathogens mainly including ESBL-producing isolates(E.coli and K. pneumonia) and non-fermentation bacteria(P.aeruginosa and Acinetobacter bacillus) causing sepsis in SAP. The infection rate and drug-resistance rate of these two kinds of pathogens are relatively higher.  
  Address Department of Hepatobiliary, People's Liberation Army General Hospital, Beijing 100853, China  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language Chinese Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0529-5815 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28464580 Approved no  
  Call Number ref @ user @ Serial 100124  
Permanent link to this record
 

 
Author (up) Magrath, J.W.; Kim, Y. url  doi
openurl 
  Title Salinomycin's potential to eliminate glioblastoma stem cells and treat glioblastoma multiforme (Review) Type Journal Article
  Year 2017 Publication International Journal of Oncology Abbreviated Journal Int J Oncol  
  Volume 51 Issue 3 Pages 753-759  
  Keywords  
  Abstract Glioblastoma multiforme (GBM) is the most common and deadliest form of primary brain tumor. Despite treatment with surgery, radiotherapy, and chemotherapy with the drug temozolomide, the expected survival after diagnosis remains low. The median survival is only 14.6 months and the two-year survival is a mere 30%. One reason for this is the heterogeneity of GBM including the presence of glioblastoma cancer stem cells (GSCs). GSCs are a subset of cells with the unique ability to proliferate, differentiate, and create tumors. GSCs are resistant to chemotherapy and radiation and thought to play an important role in recurrence. In order to effectively treat GBM, a drug must be identified that can kill GSCs. The ionophore salinomycin has been shown to kill cancer stem cells and is therefore a promising future treatment for GBM. This study focuses on salinomycin's potential to treat GBM including its ability to reduce the CSC population, its toxicity to normal brain cells, its mechanism of action, and its potential for combination treatment.  
  Address Department of Chemical and Biological Engineering, The University of Alabama, Tuscaloosa, AL 35487-0203, USA  
  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 1019-6439 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28766685 Approved no  
  Call Number ref @ user @ Serial 96573  
Permanent link to this record
 

 
Author (up) McCloskey, M.L.; Tarazona-Meza, C.E.; Jones-Smith, J.C.; Miele, C.H.; Gilman, R.H.; Bernabe-Ortiz, A.; Miranda, J.J.; Checkley, W. url  doi
openurl 
  Title Disparities in dietary intake and physical activity patterns across the urbanization divide in the Peruvian Andes Type Journal Article
  Year 2017 Publication The International Journal of Behavioral Nutrition and Physical Activity Abbreviated Journal Int J Behav Nutr Phys Act  
  Volume 14 Issue 1 Pages 90  
  Keywords 24-h recall; Chronic diseases; Low- and middle income countries; Nutrition transition; Overweight; Urbanization  
  Abstract BACKGROUND: Diet and activity are thought to worsen with urbanization, thereby increasing risk of obesity and chronic diseases. A better understanding of dietary and activity patterns across the urbanization divide may help identify pathways, and therefore intervention targets, leading to the epidemic of overweight seen in low- and middle-income populations. Therefore, we sought to characterize diet and activity in a population-based study of urban and rural residents in Puno, Peru. METHODS: We compared diet and activity in 1005 (503 urban, 502 rural) participants via a lifestyle questionnaire. We then recruited an age- and sex-stratified random sample of 50 (25 urban, 25 rural) participants to further characterize diet and activity. Among these participants, diet composition and macronutrient intake was assessed by three non-consecutive 24-h dietary recalls and physical activity was assessed using Omron JH-720itc pedometers. RESULTS: Among 1005 participants, we found that urban residents consumed protein-rich foods, refined grains, sugary items, and fresh produce more frequently than rural residents. Among the 50 subsample participants, urban dwellers consumed more protein (47 vs. 39 g; p = 0.05), more carbohydrates (280 vs. 220 g; p = 0.03), more sugary foods (98 vs. 48 g, p = 0.02) and had greater dietary diversity (6.4 vs 5.8; p = 0.04). Rural subsample participants consumed more added salt (3.1 vs 1.7 g, p = 0.006) and tended to consume more vegetable oil. As estimated by pedometers, urban subsample participants burned fewer calories per day (191 vs 270 kcal, p = 0.03). CONCLUSIONS: Although urbanization is typically thought to increase consumption of fat, sugar and salt, our 24-h recall results were mixed and showed lower levels of obesity in rural Puno were not necessarily indicative of nutritionally-balanced diets. All subsample participants had relatively traditional lifestyles (low fat intake, limited consumption of processed foods and frequent walking) that may play a role in chronic disease outcomes in this region.  
  Address Biomedical Research Unit, A.B. PRISMA, Lima, Peru. wcheckl1@jhmi.edu  
  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 1479-5868 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28693514 Approved no  
  Call Number ref @ user @ Serial 97446  
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