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Author Yin, J.; Oh, Y.T.; Kim, J.-Y.; Kim, S.S.; Choi, E.; Kim, T.H.; Hong, J.H.; Chang, N.; Cho, H.J.; Sa, J.K.; Kim, J.C.; Kwon, H.J.; Park, S.; Lin, W.; Nakano, I.; Gwak, H.-S.; Yoo, H.; Lee, S.-H.; Lee, J.; Kim, J.H.; Kim, S.-Y.; Nam, D.-H.; Park, M.-J.; Park, J.B. url  doi
openurl 
  Title Transglutaminase 2 Inhibition Reverses Mesenchymal Transdifferentiation of Glioma Stem Cells by Regulating C/EBPbeta Signaling Type Journal Article
  Year 2017 Publication Cancer Research Abbreviated Journal Cancer Res  
  Volume (down) 77 Issue 18 Pages 4973-4984  
  Keywords  
  Abstract Necrosis is a hallmark of glioblastoma (GBM) and is responsible for poor prognosis and resistance to conventional therapies. However, the molecular mechanisms underlying necrotic microenvironment-induced malignancy of GBM have not been elucidated. Here, we report that transglutaminase 2 (TGM2) is upregulated in the perinecrotic region of GBM and triggered mesenchymal (MES) transdifferentiation of glioma stem cells (GSC) by regulating master transcription factors (TF), such as C/EBPbeta, TAZ, and STAT3. TGM2 expression was induced by macrophages/microglia-derived cytokines via NF-kappaB activation and further degraded DNA damage-inducible transcript 3 (GADD153) to induce C/EBPbeta expression, resulting in expression of the MES transcriptome. Downregulation of TGM2 decreased sphere-forming ability, tumor size, and radioresistance and survival in a xenograft mouse model through a loss of the MES signature. A TGM2-specific inhibitor GK921 blocked MES transdifferentiation and showed significant therapeutic efficacy in mouse models of GSC. Moreover, TGM2 expression was significantly increased in recurrent MES patients and inversely correlated with patient prognosis. Collectively, our results indicate that TGM2 is a key molecular switch of necrosis-induced MES transdifferentiation and an important therapeutic target for MES GBM. Cancer Res; 77(18); 4973-84. (c)2017 AACR.  
  Address Specific Organs Cancer Branch, Research Institute and Hospital, National Cancer Center, Goyang, Korea  
  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 0008-5472 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28754668 Approved no  
  Call Number ref @ user @ Serial 96575  
Permanent link to this record
 

 
Author Yan, H.; Romero-Lopez, M.; Benitez, L.I.; Di, K.; Frieboes, H.B.; Hughes, C.C.W.; Bota, D.A.; Lowengrub, J.S. url  doi
openurl 
  Title 3D Mathematical Modeling of Glioblastoma Suggests That Transdifferentiated Vascular Endothelial Cells Mediate Resistance to Current Standard-of-Care Therapy Type Journal Article
  Year 2017 Publication Cancer Research Abbreviated Journal Cancer Res  
  Volume (down) 77 Issue 15 Pages 4171-4184  
  Keywords Brain Neoplasms/*pathology; Cell Transdifferentiation/physiology; Endothelial Cells/*pathology; Glioblastoma/*pathology; Humans; *Models, Theoretical; Neoplastic Stem Cells/*pathology  
  Abstract Glioblastoma (GBM), the most aggressive brain tumor in human patients, is decidedly heterogeneous and highly vascularized. Glioma stem/initiating cells (GSC) are found to play a crucial role by increasing cancer aggressiveness and promoting resistance to therapy. Recently, cross-talk between GSC and vascular endothelial cells has been shown to significantly promote GSC self-renewal and tumor progression. Furthermore, GSC also transdifferentiate into bona fide vascular endothelial cells (GEC), which inherit mutations present in GSC and are resistant to traditional antiangiogenic therapies. Here we use three-dimensional mathematical modeling to investigate GBM progression and response to therapy. The model predicted that GSCs drive invasive fingering and that GEC spontaneously form a network within the hypoxic core, consistent with published experimental findings. Standard-of-care treatments using DNA-targeted therapy (radiation/chemo) together with antiangiogenic therapies reduced GBM tumor size but increased invasiveness. Anti-GEC treatments blocked the GEC support of GSCs and reduced tumor size but led to increased invasiveness. Anti-GSC therapies that promote differentiation or disturb the stem cell niche effectively reduced tumor invasiveness and size, but were ultimately limited in reducing tumor size because GECs maintain GSCs. Our study suggests that a combinatorial regimen targeting the vasculature, GSCs, and GECs, using drugs already approved by the FDA, can reduce both tumor size and invasiveness and could lead to tumor eradication. Cancer Res; 77(15); 4171-84. (c)2017 AACR.  
  Address Center for Complex Biological Systems, University of California, Irvine, California  
  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 0008-5472 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28536277 Approved no  
  Call Number ref @ user @ Serial 96585  
Permanent link to this record
 

 
Author 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 (down) 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 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 (down) 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
 

 
Author Liu, Y.; Shen, Y.; Sun, T.; Yang, W. url  doi
openurl 
  Title Mechanisms regulating radiosensitivity of glioma stem cells Type Journal Article
  Year 2017 Publication Neoplasma Abbreviated Journal Neoplasma  
  Volume (down) 64 Issue 5 Pages 655-665  
  Keywords glioma stem cells; radiosensitivity signaling pathways.  
  Abstract Malignant glioblastoma (GBM) has become a very common and difficult brain tumor given its low cure rate and high recurrence rate. GBMs are resistant to treatments because glioma stem cells (GSCs)/glioma-initiating cells (GICs), a specific subpopulation of GBM, possess properties of tumor stem cells, such as unlimited proficiency, self-renewal, differentiation and resistance to chemotherapy and radiotherapy, and exhibit a very strong DNA repair capability. Radiotherapy has become a preponderant treatment, and researchers have found many significant tumor microenvironmental factors and valuable signaling pathways regulating the GSC radioresistance, including NOTCH, Wnt/beta-catenin, Hedgehog, STAT3, and PI3K/AKT/mTOR. Therefore, we seek to boost GSC radiosensitivity through activating or inactivating pathways alone or together to eliminate the likely source of glioma and prolong survival of patients.  
  Address  
  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 0028-2685 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28592117 Approved no  
  Call Number ref @ user @ Serial 96582  
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