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Author (down) Shahar, T.; Rozovski, U.; Hess, K.R.; Hossain, A.; Gumin, J.; Gao, F.; Fuller, G.N.; Goodman, L.; Sulman, E.P.; Lang, F.F. url  doi
openurl 
  Title Percentage of mesenchymal stem cells in high-grade glioma tumor samples correlates with patient survival Type Journal Article
  Year 2017 Publication Neuro-Oncology Abbreviated Journal Neuro Oncol  
  Volume 19 Issue 5 Pages 660-668  
  Keywords *glioblastoma; *mesenchymal stem cells; *microenvironment; *prognosis  
  Abstract Background: Human mesenchymal stem cells (hMSCs) have been shown to reside as stromal cells in human gliomas as glioma-associated hMSCs (GA-hMSCs), but their biological role remains unclear. Because recent evidence indicates that GA-hMSCs drive tumor cell proliferation and stemness, we hypothesized that a higher percentage of GA-hMSCs in tumors predicts poor patient prognosis. Method: We determined the percentage of cells coexpressing GA-hMSC markers CD105+/CD73+/CD90+ from patients with newly diagnosed high-grade glioma and analyzed the association between this percentage and overall survival (OS) in 3 independent cohorts: fresh surgical glioblastoma specimens (cohort 1, N = 9), cultured tumor specimens at passage 3 (cohort 2, N = 28), and The Cancer Genome Atlas (TCGA) database. Results: In all cohorts, patient OS correlated with the percentages of GA-hMSCs in tumors. For cohort 1, the median OS of patients with tumors with a low percentage of triple-positive cells was 46 months, and for tumors with a high percentage of triple-positive cells, it was 12 months (hazard ratio [HR] = 0.24; 95% CI: 0.02-0.5, P = .02). For cohort 2, the median OS of patients with tumors with a low percentage of GA-hMSCs was 66 months, and for tumors with a high percentage, it was 11 months (HR = 0.38; 95% CI: 0.13-0.9, P = .04). In the database of TCGA, the median OS times in patients with high and low coexpression levels of CD105/CD73/CD90 were 8.4 months and 13.1 months (HR = 0.4; 95% CI: 0.1-0.88; P = .04), respectively. Conclusions: The percentage of GA-MSCs inversely correlates with OS, suggesting a role for GA-MSCs in promoting aggressive behavior of gliomas.  
  Address Brain Tumor Center, Unit 442, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, 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 1522-8517 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28453745 Approved no  
  Call Number ref @ user @ Serial 96589  
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Author (down) Saunders, M.J.; Wingfield, T.; Tovar, M.A.; Baldwin, M.R.; Datta, S.; Zevallos, K.; Montoya, R.; Valencia, T.R.; Friedland, J.S.; Moulton, L.H.; Gilman, R.H.; Evans, C.A. url  doi
openurl 
  Title A score to predict and stratify risk of tuberculosis in adult contacts of tuberculosis index cases: a prospective derivation and external validation cohort study Type Journal Article
  Year 2017 Publication The Lancet. Infectious Diseases Abbreviated Journal Lancet Infect Dis  
  Volume 17 Issue 11 Pages 1190-1199  
  Keywords  
  Abstract BACKGROUND: Contacts of tuberculosis index cases are at increased risk of developing tuberculosis. Screening, preventive therapy, and surveillance for tuberculosis are underused interventions in contacts, particularly adults. We developed a score to predict risk of tuberculosis in adult contacts of tuberculosis index cases. METHODS: In 2002-06, we recruited contacts aged 15 years or older of index cases with pulmonary tuberculosis who lived in desert shanty towns in Ventanilla, Peru. We followed up contacts for tuberculosis until February, 2016. We used a Cox proportional hazards model to identify index case, contact, and household risk factors for tuberculosis from which to derive a score and classify contacts as low, medium, or high risk. We validated the score in an urban community recruited in Callao, Peru, in 2014-15. FINDINGS: In the derivation cohort, we identified 2017 contacts of 715 index cases, and median follow-up was 10.7 years (IQR 9.5-11.8). 178 (9%) of 2017 contacts developed tuberculosis during 19 147 person-years of follow-up (incidence 0.93 per 100 person-years, 95% CI 0.80-1.08). Risk factors for tuberculosis were body-mass index, previous tuberculosis, age, sustained exposure to the index case, the index case being in a male patient, lower community household socioeconomic position, indoor air pollution, previous tuberculosis among household members, and living in a household with a low number of windows per room. The 10-year risks of tuberculosis in the low-risk, medium-risk, and high-risk groups were, respectively, 2.8% (95% CI 1.7-4.4), 6.2% (4.8-8.1), and 20.6% (17.3-24.4). The 535 (27%) contacts classified as high risk accounted for 60% of the tuberculosis identified during follow-up. The score predicted tuberculosis independently of tuberculin skin test and index-case drug sensitivity results. In the external validation cohort, 65 (3%) of 1910 contacts developed tuberculosis during 3771 person-years of follow-up (incidence 1.7 per 100 person-years, 95% CI 1.4-2.2). The 2.5-year risks of tuberculosis in the low-risk, medium-risk, and high-risk groups were, respectively, 1.4% (95% CI 0.7-2.8), 3.9% (2.5-5.9), and 8.6%. (5.9-12.6). INTERPRETATION: Our externally validated risk score could predict and stratify 10-year risk of developing tuberculosis in adult contacts, and could be used to prioritise tuberculosis control interventions for people most likely to benefit. FUNDING: Wellcome Trust, Department for International Development Civil Society Challenge Fund, Joint Global Health Trials consortium, Bill & Melinda Gates Foundation, Imperial College National Institutes of Health Research Biomedical Research Centre, Foundation for Innovative New Diagnostics, Sir Halley Stewart Trust, WHO, TB REACH, and Innovation for Health and Development.  
  Address Section of Infectious Diseases and Immunity, Imperial College London, London, UK; Wellcome Trust Imperial College Centre for Global Health Research, London, UK; Innovation for Health and Development (IFHAD), Laboratory of Research and Development, Universidad Peruana Cayetano Heredia, Lima, Peru; Innovacion Por la Salud Y Desarrollo (IPSYD), Asociacion Benefica PRISMA, Lima, Peru  
  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 1473-3099 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28827142 Approved no  
  Call Number ref @ user @ Serial 97505  
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Author (down) Sareddy, G.R.; Viswanadhapalli, S.; Surapaneni, P.; Suzuki, T.; Brenner, A.; Vadlamudi, R.K. url  doi
openurl 
  Title Novel KDM1A inhibitors induce differentiation and apoptosis of glioma stem cells via unfolded protein response pathway Type Journal Article
  Year 2017 Publication Oncogene Abbreviated Journal Oncogene  
  Volume 36 Issue 17 Pages 2423-2434  
  Keywords Animals; Apoptosis/*drug effects; Cell Differentiation/*drug effects; Cell Line, Tumor; Cell Survival/drug effects; Cell Transformation, Neoplastic; Disease Progression; Enzyme Inhibitors/*pharmacology; Gene Expression Regulation, Neoplastic/drug effects; Glioma/*pathology; Histone Demethylases/*antagonists & inhibitors; Mice; Neoplastic Stem Cells/*drug effects/metabolism/pathology; Signal Transduction/drug effects; Survival Analysis; Transcription, Genetic/drug effects; Unfolded Protein Response/*drug effects  
  Abstract Glioma stem cells (GSCs) have a central role in glioblastoma (GBM) development and chemo/radiation resistance, and their elimination is critical for the development of efficient therapeutic strategies. Recently, we showed that lysine demethylase KDM1A is overexpressed in GBM. In the present study, we determined whether KDM1A modulates GSCs stemness and differentiation and tested the utility of two novel KDM1A-specific inhibitors (NCL-1 and NCD-38) to promote differentiation and apoptosis of GSCs. The efficacy of KDM1A targeting drugs was tested on purified GSCs isolated from established and patient-derived GBMs using both in vitro assays and in vivo orthotopic preclinical models. Our results suggested that KDM1A is highly expressed in GSCs and knockdown of KDM1A using shRNA-reduced GSCs stemness and induced the differentiation. Pharmacological inhibition of KDM1A using NCL-1 and NCD-38 significantly reduced the cell viability, neurosphere formation and induced apoptosis of GSCs with little effect on differentiated cells. In preclinical studies using orthotopic models, NCL-1 and NCD-38 significantly reduced GSCs-driven tumor progression and improved mice survival. RNA-sequencing analysis showed that KDM1A inhibitors modulate several pathways related to stemness, differentiation and apoptosis. Mechanistic studies showed that KDM1A inhibitors induce activation of the unfolded protein response (UPR) pathway. These results strongly suggest that selective targeting of KDM1A using NCL-1 and NCD-38 is a promising therapeutic strategy for elimination of GSCs.  
  Address Cancer Therapy and Research Center, University of Texas Health Science Center at San Antonio, San Antonio, TX, 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 0950-9232 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:27893719 Approved no  
  Call Number ref @ user @ Serial 96621  
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Author (down) Saleh, H.M.; Tawfik, M.M.; Abouellail, H. url  doi
openurl 
  Title Prospective, randomized study of long-term hemodialysis catheter removal versus guidewire exchange to treat catheter-related bloodstream infection Type Randomized Controlled Trial
  Year 2017 Publication Journal of Vascular Surgery Abbreviated Journal J Vasc Surg  
  Volume 66 Issue 5 Pages 1427-1431.e1  
  Keywords Aged; Anti-Bacterial Agents/therapeutic use; Catheter-Related Infections/blood/diagnosis/microbiology/*therapy; Catheterization, Central Venous/*adverse effects/*instrumentation; Catheters, Indwelling/*adverse effects; Central Venous Catheters/*adverse effects; *Device Removal/adverse effects; Disease-Free Survival; Egypt; Equipment Design; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Prospective Studies; Renal Dialysis; Risk Factors; Time Factors; Treatment Outcome  
  Abstract BACKGROUND: Long-term (tunneled cuffed) hemodialysis catheters are frequently used vascular access in renal failure patients. Catheter-related bloodstream infection (CRBSI) is a common complication of long-term hemodialysis catheters, with severe morbidities and high risk of mortality. Management of CRBSI by systemic antibiotics while keeping the catheter in place is not effective. Among the different modalities of CRBSI management are catheter removal (CR) and guidewire exchange (GE) of the catheter. The aim of this study was to compare the clinical outcome of CRBSI treated with two different strategies: GE vs CR with new catheter insertion 3 to 7 days later. METHODS: This prospective randomized study analyzed the outcomes of all cases of long-term hemodialysis CRBSI during a 5-year period. The catheter infection-free survival time was analyzed in the two groups of patients (GE group, 339 patients; CR group, 339 patients). Three weeks of systemic antibiotic therapy was used according to culture in both groups. The catheter infection-free survival was analyzed using Kaplan-Meier analysis. RESULTS: No statistically significant difference was found in catheter infection-free survival time for GE and CR groups (P = .69), which is not affected by age, sex, presence of diabetes mellitus, or type of causative organism. CONCLUSIONS: Our study did not demonstrate a difference in the clinical outcome of CRBSI treated with GE or CR with new catheter insertion 3 to 7 days later. However, guidewire catheter exchange saves veins for future access, reduces the cost and number of procedures, and avoids complications of new venipuncture.  
  Address Department of Nephrology, Ain Shams University, El Demerdash Hospital, Cairo, Egypt  
  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 0741-5214 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28822660 Approved no  
  Call Number ref @ user @ Serial 99317  
Permanent link to this record
 

 
Author (down) Saleh, H.M.; Tawfik, M.M.; Abouellail, H. url  doi
openurl 
  Title Prospective, randomized study of long-term hemodialysis catheter removal versus guidewire exchange to treat catheter-related bloodstream infection Type Randomized Controlled Trial
  Year 2017 Publication Journal of Vascular Surgery Abbreviated Journal J Vasc Surg  
  Volume 66 Issue 5 Pages 1427-1431.e1  
  Keywords Aged; Anti-Bacterial Agents/therapeutic use; Catheter-Related Infections/blood/diagnosis/microbiology/*therapy; Catheterization, Central Venous/*adverse effects/*instrumentation; Catheters, Indwelling/*adverse effects; Central Venous Catheters/*adverse effects; *Device Removal/adverse effects; Disease-Free Survival; Egypt; Equipment Design; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Prospective Studies; Renal Dialysis; Risk Factors; Time Factors; Treatment Outcome  
  Abstract BACKGROUND: Long-term (tunneled cuffed) hemodialysis catheters are frequently used vascular access in renal failure patients. Catheter-related bloodstream infection (CRBSI) is a common complication of long-term hemodialysis catheters, with severe morbidities and high risk of mortality. Management of CRBSI by systemic antibiotics while keeping the catheter in place is not effective. Among the different modalities of CRBSI management are catheter removal (CR) and guidewire exchange (GE) of the catheter. The aim of this study was to compare the clinical outcome of CRBSI treated with two different strategies: GE vs CR with new catheter insertion 3 to 7 days later. METHODS: This prospective randomized study analyzed the outcomes of all cases of long-term hemodialysis CRBSI during a 5-year period. The catheter infection-free survival time was analyzed in the two groups of patients (GE group, 339 patients; CR group, 339 patients). Three weeks of systemic antibiotic therapy was used according to culture in both groups. The catheter infection-free survival was analyzed using Kaplan-Meier analysis. RESULTS: No statistically significant difference was found in catheter infection-free survival time for GE and CR groups (P = .69), which is not affected by age, sex, presence of diabetes mellitus, or type of causative organism. CONCLUSIONS: Our study did not demonstrate a difference in the clinical outcome of CRBSI treated with GE or CR with new catheter insertion 3 to 7 days later. However, guidewire catheter exchange saves veins for future access, reduces the cost and number of procedures, and avoids complications of new venipuncture.  
  Address Department of Nephrology, Ain Shams University, El Demerdash Hospital, Cairo, Egypt  
  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 0741-5214 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28822660 Approved no  
  Call Number ref @ user @ Serial 100347  
Permanent link to this record
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