| Records |
| Author |
Goffart, N.; Lombard, A.; Lallemand, F.; Kroonen, J.; Nassen, J.; Di Valentin, E.; Berendsen, S.; Dedobbeleer, M.; Willems, E.; Robe, P.; Bours, V.; Martin, D.; Martinive, P.; Maquet, P.; Rogister, B. |
| Title |
CXCL12 mediates glioblastoma resistance to radiotherapy in the subventricular zone |
Type |
Journal Article |
| Year |
2017 |
Publication |
Neuro-Oncology |
Abbreviated Journal |
Neuro Oncol |
| Volume |
19 |
Issue |
1 |
Pages |
66-77 |
| Keywords |
Animals; Brain Neoplasms/metabolism/*pathology/radiotherapy; Chemokine CXCL12/*metabolism; Cranial Irradiation/*adverse effects; Gamma Rays/adverse effects; Glioblastoma/metabolism/*pathology/radiotherapy; Humans; Lateral Ventricles/metabolism/*pathology/radiation effects; Mice; Mice, Nude; Neoplastic Stem Cells/metabolism/*pathology/radiation effects; *Radiation Tolerance; Signal Transduction/radiation effects; Tumor Cells, Cultured; Cxcl12; glioblastoma; mesenchymal activation; radioresistance; subventricular zone |
| Abstract |
BACKGROUND: Patients with glioblastoma (GBM) have an overall median survival of 15 months despite multimodal therapy. These catastrophic survival rates are to be correlated to systematic relapses that might arise from remaining glioblastoma stem cells (GSCs) left behind after surgery. In this line, it has recently been demonstrated that GSCs are able to escape the tumor mass and preferentially colonize the adult subventricular zone (SVZ). At a distance from the initial tumor site, these GSCs might therefore represent a high-quality model of clinical resilience to therapy and cancer relapses as they specifically retain tumor-initiating abilities. METHOD: While relying on recent findings that have validated the existence of GSCs in the human SVZ, we questioned the role of the SVZ niche as a potential GSC reservoir involved in therapeutic failure. RESULTS: Our results demonstrate that (i) GSCs located in the SVZ are specifically resistant to radiation in vivo, (ii) these cells display enhanced mesenchymal roots that are known to be associated with cancer radioresistance, (iii) these mesenchymal traits are specifically upregulated by CXCL12 (stromal cell-derived factor-1) both in vitro and in the SVZ environment, (iv) the amount of SVZ-released CXCL12 mediates GBM resistance to radiation in vitro, and (v) interferes with the CXCL12/CXCR4 signalling system, allowing weakening of the tumor mesenchymal roots and radiosensitizing SVZ-nested GBM cells. CONCLUSION: Together, these data provide evidence on how the adult SVZ environment, through the release of CXCL12, supports GBM therapeutic failure and potential tumor relapse. |
| Address |
Laboratory of Developmental Neurobiology, GIGA-Neurosciences Research Center, University of Liege, Liege, Belgium (N.G., A.L., J.N., M.D., E.W., B.R.); Department of Neurosurgery, CHU and University of Liege, Liege, Belgium (A.L., D.M.); Department of Radiotherapy and Oncology, CHU and University of Liege, Liege, Belgium (F.L., P.M.); Laboratory of Tumor and Development Biology, GIGA-Cancer Research Center, University of Liege, Liege, Belgium (F.L.); Cyclotron Research Centre, University of Liege, Liege, Belgium (F.L.); Human Genetics, CHU and University of Liege, Liege, Belgium (N.G., J.K., V.B.); Department of Neurosurgery, Brain Center Rudolf Magnus Institute of Neurosciences and the T&P Bohnenn Laboratory for Neuro-Oncology University Medical Center, Utrecht, The Netherlands (N.G., J.K., S.B., P.R.); GIGA-Viral Vector Plateform, University of Liege, Liege, Belgium (E.D.V.); Department of Neurology, CHU and University of Liege, Liege, Belgium (P.M., B.R.) |
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English |
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| ISSN |
1522-8517 |
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Notes  |
PMID:27370398 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
96647 |
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| Author |
Yu, W.-L.; Lee, M.-F.; Chen, C.-C.; Tang, H.-J.; Ho, C.-H.; Chuang, Y.-C. |
| Title |
Impacts of Hypervirulence Determinants on Clinical Features and Outcomes of Bacteremia Caused by Extended-Spectrum beta-Lactamase-Producing Klebsiella pneumoniae |
Type |
Journal Article |
| Year |
2017 |
Publication |
Microbial Drug Resistance (Larchmont, N.Y.) |
Abbreviated Journal |
Microb Drug Resist |
| Volume |
23 |
Issue |
3 |
Pages |
376-383 |
| Keywords |
Aged; Anti-Bacterial Agents/therapeutic use; Bacteremia/drug therapy/*microbiology; Bacterial Proteins/genetics; Cross Infection/drug therapy/microbiology; Female; Hospital Mortality; Humans; Klebsiella Infections/drug therapy/*microbiology; Klebsiella pneumoniae/*genetics; Male; Middle Aged; Serogroup; Urinary Tract Infections/drug therapy/microbiology; Virulence Factors/*genetics; beta-Lactamases/*genetics; Esbl; Klebsiella pneumoniae; hypermucoviscosity; hypervirulence; rmpA; virulence |
| Abstract |
We investigated the implications of hypervirulence determinants on clinical features of 48 adult patients with bacteremia caused by extended-spectrum beta-lactamase-producing Klebsiella pneumoniae. Isolates in the hypervirulence group included any of the following virulence determinants: K1/K2 capsule serotypes, hypermucoviscosity phenotype, rmpA gene, or rmpA2 gene. Nonhypervirulence group isolates were negative for all of the above virulence factors. In this study, all isolates used were non-K1/K2 strains. Statistically significant differences were observed in clinical features of patients between the two groups. The hypervirulent isolates (n = 19), including 11 isolates with the hypermucoviscosity phenotype, 15 with the rmpA gene, and 16 with the rmpA2 gene, were more commonly recovered from diabetic patients and mainly manifested as secondary bacteremia (such as pneumonia, urinary tract infections, or other localized infections). The nonhypervirulent isolates (n = 29) were more commonly recovered from patients after prolonged hospital stays (>30 days) and mostly manifested as primary bacteremia. The overall in-hospital mortality was 56.3%. Hazard ratio (HR) analysis revealed the following positive predictors for mortality: nosocomial infection, stay in an intensive care unit, no removal of the central venous catheter, Charlson comorbidity score, and APACHE II score (>==15). The negative predictors were initial appropriate antibiotic therapy (HR 0.42) and urinary tract infection (HR 0.19). Charlson score was an independent confounder based on multivariate analysis (HR 1.43, 95% confidence interval 1.04-1.99). In conclusion, hypervirulence determinants played a role in causing secondary infections in diabetic patients; however, the presence of morbidity cofactors could themselves influence mortality, despite the absence of hypervirulence determinants. |
| Address |
6 Department of Internal Medicine, Chi Mei Medical Center-Liou Ying , Tainan City, Taiwan |
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English |
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Abbreviated Series Title |
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Series Issue |
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Edition |
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| ISSN |
1076-6294 |
ISBN |
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Medium |
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Expedition |
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Conference |
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| Notes |
PMID:27380450 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
99505 |
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| Author |
Yu, W.-L.; Lee, M.-F.; Chen, C.-C.; Tang, H.-J.; Ho, C.-H.; Chuang, Y.-C. |
| Title |
Impacts of Hypervirulence Determinants on Clinical Features and Outcomes of Bacteremia Caused by Extended-Spectrum beta-Lactamase-Producing Klebsiella pneumoniae |
Type |
Journal Article |
| Year |
2017 |
Publication |
Microbial Drug Resistance (Larchmont, N.Y.) |
Abbreviated Journal |
Microb Drug Resist |
| Volume |
23 |
Issue |
3 |
Pages |
376-383 |
| Keywords |
Aged; Anti-Bacterial Agents/therapeutic use; Bacteremia/drug therapy/*microbiology; Bacterial Proteins/genetics; Cross Infection/drug therapy/microbiology; Female; Hospital Mortality; Humans; Klebsiella Infections/drug therapy/*microbiology; Klebsiella pneumoniae/*genetics; Male; Middle Aged; Serogroup; Urinary Tract Infections/drug therapy/microbiology; Virulence Factors/*genetics; beta-Lactamases/*genetics; Esbl; Klebsiella pneumoniae; hypermucoviscosity; hypervirulence; rmpA; virulence |
| Abstract |
We investigated the implications of hypervirulence determinants on clinical features of 48 adult patients with bacteremia caused by extended-spectrum beta-lactamase-producing Klebsiella pneumoniae. Isolates in the hypervirulence group included any of the following virulence determinants: K1/K2 capsule serotypes, hypermucoviscosity phenotype, rmpA gene, or rmpA2 gene. Nonhypervirulence group isolates were negative for all of the above virulence factors. In this study, all isolates used were non-K1/K2 strains. Statistically significant differences were observed in clinical features of patients between the two groups. The hypervirulent isolates (n = 19), including 11 isolates with the hypermucoviscosity phenotype, 15 with the rmpA gene, and 16 with the rmpA2 gene, were more commonly recovered from diabetic patients and mainly manifested as secondary bacteremia (such as pneumonia, urinary tract infections, or other localized infections). The nonhypervirulent isolates (n = 29) were more commonly recovered from patients after prolonged hospital stays (>30 days) and mostly manifested as primary bacteremia. The overall in-hospital mortality was 56.3%. Hazard ratio (HR) analysis revealed the following positive predictors for mortality: nosocomial infection, stay in an intensive care unit, no removal of the central venous catheter, Charlson comorbidity score, and APACHE II score (>==15). The negative predictors were initial appropriate antibiotic therapy (HR 0.42) and urinary tract infection (HR 0.19). Charlson score was an independent confounder based on multivariate analysis (HR 1.43, 95% confidence interval 1.04-1.99). In conclusion, hypervirulence determinants played a role in causing secondary infections in diabetic patients; however, the presence of morbidity cofactors could themselves influence mortality, despite the absence of hypervirulence determinants. |
| Address |
6 Department of Internal Medicine, Chi Mei Medical Center-Liou Ying , Tainan City, Taiwan |
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English |
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1076-6294 |
ISBN |
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Conference |
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| Notes |
PMID:27380450 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
100535 |
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| Author |
Li, M.; Zhao, H.; Ananiev, G.E.; Musser, M.T.; Ness, K.H.; Maglaque, D.L.; Saha, K.; Bhattacharyya, A.; Zhao, X. |
| Title |
Establishment of Reporter Lines for Detecting Fragile X Mental Retardation (FMR1) Gene Reactivation in Human Neural Cells |
Type |
Journal Article |
| Year |
2017 |
Publication |
Stem Cells (Dayton, Ohio) |
Abbreviated Journal |
Stem Cells |
| Volume |
35 |
Issue |
1 |
Pages |
158-169 |
| Keywords |
Drug discovery; Fmr1; Fmrp; Fragile X syndrome; High throughput; Induced pluripotent stem cells; Luciferase |
| Abstract |
Human patient-derived induced pluripotent stem cells (hiPSCs) provide unique opportunities for disease modeling and drug development. However, adapting hiPSCs or their differentiated progenies to high throughput assays for phenotyping or drug screening has been challenging. Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability and a major genetic cause of autism. FXS is caused by mutational trinucleotide expansion in the FMR1 gene leading to hypermethylation and gene silencing. One potential therapeutic strategy is to reactivate the silenced FMR1 gene, which has been attempted using both candidate chemicals and cell-based screening. However, molecules that effectively reactivate the silenced FMR1 gene are yet to be identified; therefore, a high throughput unbiased screen is needed. Here we demonstrate the creation of a robust FMR1-Nluc reporter hiPSC line by knocking in a Nano luciferase (Nluc) gene into the endogenous human FMR1 gene using the CRISPR/Cas9 genome editing method. We confirmed that luciferase activities faithfully report FMR1 gene expression levels and showed that neural progenitor cells derived from this line could be optimized for high throughput screening. The FMR1-Nluc reporter line is a good resource for drug screening as well as for testing potential genetic reactivation strategies. In addition, our data provide valuable information for the generation of knockin human iPSC reporter lines for disease modeling, drug screening, and mechanistic studies. Stem Cells 2017;35:158-169. |
| Address |
Department of Neuroscience, University of Wisconsin-Madison, Madison, Wisconsin, USA |
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English |
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1066-5099 |
ISBN |
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| Notes |
PMID:27422057 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
95937 |
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Rocha, G. da S.; Mello Jorge, M.H.P. de; Grembek, O. |
| Title |
After-effects and disabilities in traffic crash victims in northern Brazil |
Type |
Journal Article |
| Year |
2017 |
Publication |
Traffic Injury Prevention |
Abbreviated Journal |
Traffic Inj Prev |
| Volume |
18 |
Issue |
4 |
Pages |
412-419 |
| Keywords |
Accidents, Traffic/*statistics & numerical data; Adolescent; Adult; Aged; Brazil/epidemiology; Child; Cities; Cross-Sectional Studies; *Disabled Persons; Facial Injuries/epidemiology/mortality/pathology; Female; Humans; Injury Severity Score; Logistic Models; Male; Middle Aged; Motorcycles; Odds Ratio; Risk Factors; Wounds and Injuries/*epidemiology/mortality/pathology; Young Adult; Crashes; after-effects; severity of trauma; traffic; victims |
| Abstract |
OBJECTIVES: The objective of this study was to identify the characteristics related to crash and victim, as well as the after-effects/disabilities and consequences arising from traffic crashes occurring in the city of Rio Branco-Acre. METHODS: This is an analytical descriptive cross-sectional study conducted in the City of Rio Branco-Acre. The study population consisted of 405 residents of the city who were victims of traffic crashes, of all age groups and genders, who were hospitalized for the first time as a result of the crash in public hospitals and the health system network, as recorded in the Hospital Information System, and who were discharged between January 1 and December 31, 2010. The data sources included hospital record consultations and active searches for the victims. Hierarchical logistic regression was performed to evaluate the factors associated with the after-effects. RESULTS: The majority of the study population was motorcycle victims (68.6%), male, and young (20-39 years). Concerning the after-effects, the following were significantly associated: factors related to the presence of a postcrash activity limitation (odds ratio [OR] = 2.39; 95% confidence interval [CI], 2.39-6.76), length of hospital stay in days (OR = 1 03; 95% CI, 1.01-1.06), and surgical treatment (OR = 1.82; 95% CI, 1.03-3.21). Those who suffered damage to soft tissue and nerves or facial injury showed an odds ratio of 2 to 4 times of having an after-effect/disability, independent of the victim's personal attributes. CONCLUSION: The mechanism, such as the origin of the pattern of injuries, explains the exposure factors shown by each attribute of the victim and their characteristics. Many of the injuries were precursors to after-effects/disabilities, which, due to their nature and extent, result in the modification of the apparently healthy living standards of young victims who are routinely injured in traffic crashes. Therefore, public policies for prevention should be formulated, reformulated, and implemented, taking into account each attribute of the victims and their social conditions, because these are closely related to their habits and customs. This is a starting point for promoting changes to the current reality that traffic crashes present in the morbidity and mortality of the population. |
| Address |
c University of California , Berkeley , Safe Transportation Research and Education Center , Berkeley , California |
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English |
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Abbreviated Series Title |
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Series Issue |
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Edition |
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1538-9588 |
ISBN |
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| Notes |
PMID:27575383 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
97666 |
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