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Author Celiku, O.; Tandle, A.; Chung, J.-Y.; Hewitt, S.M.; Camphausen, K.; Shankavaram, U. url  doi
openurl 
  Title Computational analysis of the mesenchymal signature landscape in gliomas Type Journal Article
  Year 2017 Publication BMC Medical Genomics Abbreviated Journal BMC Med Genomics  
  Volume (up) 10 Issue 1 Pages 13  
  Keywords Cd44; Computational modeling; Epithelial to mesenchymal transition; Glioma  
  Abstract BACKGROUND: Epithelial to mesenchymal transition, and mimicking processes, contribute to cancer invasion and metastasis, and are known to be responsible for resistance to various therapeutic agents in many cancers. While a number of studies have proposed molecular signatures that characterize the spectrum of such transition, more work is needed to understand how the mesenchymal signature (MS) is regulated in non-epithelial cancers like gliomas, to identify markers with the most prognostic significance, and potential for therapeutic targeting. RESULTS: Computational analysis of 275 glioma samples from “The Cancer Genome Atlas” was used to identify the regulatory changes between low grade gliomas with little expression of MS, and high grade glioblastomas with high expression of MS. TF (transcription factor)-gene regulatory networks were constructed for each of the cohorts, and 5 major pathways and 118 transcription factors were identified as involved in the differential regulation of the networks. The most significant pathway – Extracellular matrix organization – was further analyzed for prognostic relevance. A 20-gene signature was identified as having prognostic significance (HR (hazard ratio) 3.2, 95% CI (confidence interval) = 1.53-8.33), after controlling for known prognostic factors (age, and glioma grade). The signature's significance was validated in an independent data set. The putative stem cell marker CD44 was biologically validated in glioma cell lines and brain tissue samples. CONCLUSIONS: Our results suggest that the differences between low grade gliomas and high grade glioblastoma are associated with differential expression of the signature genes, raising the possibility that targeting these genes might prolong survival in glioma patients.  
  Address Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, 10 Center Drive, Bldg. 10, Rm. B3B70, Bethesda, MD, 20892, USA. uma@mail.nih.gov  
  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 1755-8794 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28279210 Approved no  
  Call Number ref @ user @ Serial 96602  
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Author Howard, C.M.; Valluri, J.; Alberico, A.; Julien, T.; Mazagri, R.; Marsh, R.; Alastair, H.; Cortese, A.; Griswold, M.; Wang, W.; Denning, K.; Brown, L.; Claudio, P.P. url  doi
openurl 
  Title Analysis of Chemopredictive Assay for Targeting Cancer Stem Cells in Glioblastoma Patients Type Journal Article
  Year 2017 Publication Translational Oncology Abbreviated Journal Transl Oncol  
  Volume (up) 10 Issue 2 Pages 241-254  
  Keywords  
  Abstract INTRODUCTION: The prognosis of glioblastoma (GBM) treated with standard-of-care maximal surgical resection and concurrent adjuvant temozolomide (TMZ)/radiotherapy remains very poor (less than 15 months). GBMs have been found to contain a small population of cancer stem cells (CSCs) that contribute to tumor propagation, maintenance, and treatment resistance. The highly invasive nature of high-grade gliomas and their inherent resistance to therapy lead to very high rates of recurrence. For these reasons, not all patients with similar diagnoses respond to the same chemotherapy, schedule, or dose. Administration of ineffective anticancer therapy is not only costly but more importantly burdens the patient with unnecessary toxicity and selects for the development of resistant cancer cell clones. We have developed a drug response assay (ChemoID) that identifies the most effective chemotherapy against CSCs and bulk of tumor cells from of a panel of potential treatments, offering great promise for individualized cancer management. Providing the treating physician with drug response information on a panel of approved drugs will aid in personalized therapy selections of the most effective chemotherapy for individual patients, thereby improving outcomes. A prospective study was conducted evaluating the use of the ChemoID drug response assay in GBM patients treated with standard of care. METHODS: Forty-one GBM patients (mean age 54 years, 59% male), all eligible for a surgical biopsy, were enrolled in an Institutional Review Board-approved protocol, and fresh tissue samples were collected for drug sensitivity testing. Patients were all treated with standard-of-care TMZ plus radiation with or without maximal surgery, depending on the status of the disease. Patients were prospectively monitored for tumor response, time to recurrence, progression-free survival (PFS), and overall survival (OS). Odds ratio (OR) associations of 12-month recurrence, PFS, and OS outcomes were estimated for CSC, bulk tumor, and combined assay responses for the standard-of-care TMZ treatment; sensitivities/specificities, areas under the curve (AUCs), and risk reclassification components were examined. RESULTS: Median follow-up was 8 months (range 3-49 months). For every 5% increase in in vitro CSC cell kill by TMZ, 12-month patient response (nonrecurrence of cancer) increased two-fold, OR=2.2 (P=.016). Similar but somewhat less supported associations with the bulk tumor test were seen, OR=2.75 (P=.07) for each 5% bulk tumor cell kill by TMZ. Combining CSC and bulk tumor assay results in a single model yielded a statistically supported CSC association, OR=2.36 (P=.036), but a much attenuated remaining bulk tumor association, OR=1.46 (P=.472). AUCs and [sensitivity/specificity] at optimal outpoints (>40% CSC cell kill and >55% bulk tumor cell kill) were AUC=0.989 [sensitivity=100/specificity=97], 0.972 [100/89], and 0.989 [100/97] for the CSC only, bulk tumor only, and combined models, respectively. Risk categorization of patients was improved by 11% when using the CSC test in conjunction with the bulk test (risk reclassification nonevent net reclassification improvement [NRI] and overall NRI=0.111, P=.030). Median recurrence time was 20 months for patients with a positive (>40% cell kill) CSC test versus only 3 months for those with a negative CSC test, whereas median recurrence time was 13 months versus 4 months for patients with a positive (>55% cell kill) bulk test versus negative. Similar favorable results for the CSC test were observed for PFS and OS outcomes. Panel results across 14 potential other treatments indicated that 34/41 (83%) potentially more optimal alternative therapies may have been chosen using CSC results, whereas 27/41 (66%) alternative therapies may have been chosen using bulk tumor results. CONCLUSIONS: The ChemoID CSC drug response assay has the potential to increase the accuracy of bulk tumor assays to help guide individualized chemotherapy choices. GBM cancer recurrence may occur quickly if the CSC test has a low in vitro cell kill rate even if the bulk tumor test cell kill rate is high.  
  Address Department of BioMolecular Sciences, National Center for Natural Products Research, University of Mississippi, University, MS; Department of Radiation Oncology, University of Mississippi Medical Center Cancer Institute, Jackson, MS 39216. Electronic address: pclaudio@olemiss.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 1936-5233 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28199863 Approved no  
  Call Number ref @ user @ Serial 96608  
Permanent link to this record
 

 
Author Souza, R.L.; Mugabe, V.A.; Paploski, I.A.D.; Rodrigues, M.S.; Moreira, P.S.D.S.; Nascimento, L.C.J.; Roundy, C.M.; Weaver, S.C.; Reis, M.G.; Kitron, U.; Ribeiro, G.S. url  doi
openurl 
  Title Effect of an intervention in storm drains to prevent Aedes aegypti reproduction in Salvador, Brazil Type Journal Article
  Year 2017 Publication Parasites & Vectors Abbreviated Journal Parasit Vectors  
  Volume (up) 10 Issue 1 Pages 328  
  Keywords Aedes aegypti; Arboviruses; Catch basin; Disease vectors; Entomology; Epidemiology; Insect vectors; Mosquitoes; Storm drain  
  Abstract BACKGROUND: Aedes aegypti, the principal vector for dengue, chikungunya and Zika viruses, is a synanthropic species that uses stagnant water to complete its reproductive cycle. In urban settings, rainfall water draining structures, such as storm drains, may retain water and serve as a larval development site for Aedes spp. reproduction. Herein, we describe the effect of a community-based intervention on preventing standing water accumulation in storm drains and their consequent infestation by adult and immature Ae. aegypti and other mosquitoes. METHODS: Between April and May of 2016, local residents association of Salvador, Brazil, after being informed of water accumulation and Ae. aegypti infestation in the storm drains in their area, performed an intervention on 52 storm drains. The intervention consisted of placing concrete at the bottom of the storm drains to elevate their base to the level of the outflow tube, avoiding water accumulation, and placement of a metal mesh covering the outflow tube to avoid its clogging with debris. To determine the impact of the intervention, we compared the frequency at which the 52 storm drains contained water, as well as adult and immature mosquitoes using data from two surveys performed before and two surveys performed after the intervention. RESULTS: During the pre-intervention period, water accumulated in 48 (92.3%) of the storm drains, and immature Ae. aegypti were found in 11 (21.2%) and adults in 10 (19.2%). After the intervention, water accumulated in 5 (9.6%) of the storm drains (P < 0.001), none (0.0%) had immatures (P < 0.001), and 3 (5.8%) contained adults (P = 0.039). The total number of Ae. aegypti immatures collected decreased from 109 to 0 (P < 0.001) and adults decreased from 37 to 8 (P = 0.011) after the intervention. Collection of immature and adult non-Aedes mosquitoes (mainly Culex spp.) in the storm drains also decreased after the intervention. CONCLUSION: This study exemplifies how a simple intervention targeting storm drains can result in a major reduction of water retention, and, consequently, impact Ae. aegypti larval populations. Larger and multi-center evaluations are needed to confirm the potential of citywide structural modifications of storm drains to reduce Aedes spp. infestation level.  
  Address Instituto de Saude Coletiva, Universidade Federal da Bahia, Salvador, Bahia, Brazil. guilherme.ribeiro@bahia.fiocruz.br  
  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 1756-3305 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28697811 Approved no  
  Call Number ref @ user @ Serial 97633  
Permanent link to this record
 

 
Author Ramke, J.; Petkovic, J.; Welch, V.; Blignault, I.; Gilbert, C.; Blanchet, K.; Christensen, R.; Zwi, A.B.; Tugwell, P. url  doi
openurl 
  Title Interventions to improve access to cataract surgical services and their impact on equity in low- and middle-income countries Type Journal Article
  Year 2017 Publication The Cochrane Database of Systematic Reviews Abbreviated Journal Cochrane Database Syst Rev  
  Volume (up) 11 Issue Pages Cd011307  
  Keywords  
  Abstract BACKGROUND: Cataract is the leading cause of blindness in low- and middle-income countries (LMICs), and the prevalence is inequitably distributed between and within countries. Interventions have been undertaken to improve cataract surgical services, however, the effectiveness of these interventions on promoting equity is not known. OBJECTIVES: To assess the effects on equity of interventions to improve access to cataract services for populations with cataract blindness (and visual impairment) in LMICs. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2017, Issue 3), MEDLINE Ovid (1946 to 12 April 2017), Embase Ovid (1980 to 12 April 2017), LILACS (Latin American and Caribbean Health Sciences Literature Database) (1982 to 12 April 2017), the ISRCTN registry (www.isrctn.com/editAdvancedSearch); searched 12 April 2017, ClinicalTrials.gov (www.clinicaltrials.gov); searched 12 April 2017 and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 12 April 2017. We did not use any date or language restrictions in the electronic searches for trials. SELECTION CRITERIA: We included studies that reported on strategies to improve access to cataract services in LMICs using the following study designs: randomised and quasi-randomised controlled trials (RCTs), controlled before-and-after studies, and interrupted time series studies. Included studies were conducted in LMICs, and were targeted at disadvantaged populations, or disaggregated outcome data by 'PROGRESS-Plus' factors (Place of residence; Race/ethnicity/ culture/ language; Occupation; Gender/sex; Religion; Education; Socio-economic status; Social capital/networks. The 'Plus' component includes disability, sexual orientation and age). DATA COLLECTION AND ANALYSIS: Two authors (JR and JP) independently selected studies, extracted data and assessed them for risk of bias. Meta-analysis was not possible, so included studies were synthesised in table and text. MAIN RESULTS: From a total of 2865 studies identified in the search, two met our eligibility criteria, both of which were cluster-RCTs conducted in rural China. The way in which the trials were conducted means that the risk of bias is unclear. In both studies, villages were randomised to be either an intervention or control group. Adults identified with vision-impairing cataract, following village-based vision and eye health assessment, either received an intervention to increase uptake of cataract surgery (if their village was an intervention group), or to receive 'standard care' (if their village was a control group).One study (n = 434), randomly allocated 26 villages or townships to the intervention, which involved watching an informational video and receiving counselling about cataract and cataract surgery, while the control group were advised that they had decreased vision due to cataract and it could be treated, without being shown the video or receiving counselling. There was low-certainty evidence that providing information and counselling had no effect on uptake of referral to the hospital (OR 1.03, 95% CI 0.63 to 1.67, 1 RCT, 434 participants) and little or no effect on the uptake of surgery (OR 1.11, 95% CI 0.67 to 1.84, 1 RCT, 434 participants). We assessed the level of evidence to be of low-certainty for both outcomes, due to indirectness of evidence and imprecision of results.The other study (n = 355, 24 towns randomised) included three intervention arms: free surgery; free surgery plus reimbursement of transport costs; and free surgery plus free transport to and from the hospital. These were compared to the control group, which was reminded to use the “low-cost” ( USD 38) surgical service. There was low-certainty evidence that surgical fee waiver with/without transport provision or reimbursement increased uptake of surgery (RR 1.94, 95% CI 1.14 to 3.31, 1 RCT, 355 participants). We assessed the level of evidence to be of low-certainty due to indirectness of evidence and imprecision of results.Neither of the studies reported our primary outcome of change in prevalence of cataract blindness, or other outcomes such as cataract surgical coverage, surgical outcome, or adverse effects. Neither study disaggregated outcomes by social subgroups to enable further assessment of equity effects. We sought data from both studies and obtained data from one; the information video and counselling intervention did not have a differential effect across the PROGRESS-Plus categories with available data (place of residence, gender, education level, socioeconomic status and social capital). AUTHORS' CONCLUSIONS: Current evidence on the effect on equity of interventions to improve access to cataract services in LMICs is limited. We identified only two studies, both conducted in rural China. Assessment of equity effects will be improved if future studies disaggregate outcomes by relevant social subgroups. To assist with assessing generalisability of findings to other settings, robust data on contextual factors are also needed.  
  Address School of Population Health, Faculty of Medicine and Health Sciences, University of Auckland, Auckland, New Zealand  
  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 1361-6137 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:29119547 Approved no  
  Call Number ref @ user @ Serial 97501  
Permanent link to this record
 

 
Author Ramke, J.; Petkovic, J.; Welch, V.; Blignault, I.; Gilbert, C.; Blanchet, K.; Christensen, R.; Zwi, A.B.; Tugwell, P. url  doi
openurl 
  Title Interventions to improve access to cataract surgical services and their impact on equity in low- and middle-income countries Type Journal Article
  Year 2017 Publication The Cochrane Database of Systematic Reviews Abbreviated Journal Cochrane Database Syst Rev  
  Volume (up) 11 Issue Pages Cd011307  
  Keywords  
  Abstract BACKGROUND: Cataract is the leading cause of blindness in low- and middle-income countries (LMICs), and the prevalence is inequitably distributed between and within countries. Interventions have been undertaken to improve cataract surgical services, however, the effectiveness of these interventions on promoting equity is not known. OBJECTIVES: To assess the effects on equity of interventions to improve access to cataract services for populations with cataract blindness (and visual impairment) in LMICs. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2017, Issue 3), MEDLINE Ovid (1946 to 12 April 2017), Embase Ovid (1980 to 12 April 2017), LILACS (Latin American and Caribbean Health Sciences Literature Database) (1982 to 12 April 2017), the ISRCTN registry (www.isrctn.com/editAdvancedSearch); searched 12 April 2017, ClinicalTrials.gov (www.clinicaltrials.gov); searched 12 April 2017 and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 12 April 2017. We did not use any date or language restrictions in the electronic searches for trials. SELECTION CRITERIA: We included studies that reported on strategies to improve access to cataract services in LMICs using the following study designs: randomised and quasi-randomised controlled trials (RCTs), controlled before-and-after studies, and interrupted time series studies. Included studies were conducted in LMICs, and were targeted at disadvantaged populations, or disaggregated outcome data by 'PROGRESS-Plus' factors (Place of residence; Race/ethnicity/ culture/ language; Occupation; Gender/sex; Religion; Education; Socio-economic status; Social capital/networks. The 'Plus' component includes disability, sexual orientation and age). DATA COLLECTION AND ANALYSIS: Two authors (JR and JP) independently selected studies, extracted data and assessed them for risk of bias. Meta-analysis was not possible, so included studies were synthesised in table and text. MAIN RESULTS: From a total of 2865 studies identified in the search, two met our eligibility criteria, both of which were cluster-RCTs conducted in rural China. The way in which the trials were conducted means that the risk of bias is unclear. In both studies, villages were randomised to be either an intervention or control group. Adults identified with vision-impairing cataract, following village-based vision and eye health assessment, either received an intervention to increase uptake of cataract surgery (if their village was an intervention group), or to receive 'standard care' (if their village was a control group).One study (n = 434), randomly allocated 26 villages or townships to the intervention, which involved watching an informational video and receiving counselling about cataract and cataract surgery, while the control group were advised that they had decreased vision due to cataract and it could be treated, without being shown the video or receiving counselling. There was low-certainty evidence that providing information and counselling had no effect on uptake of referral to the hospital (OR 1.03, 95% CI 0.63 to 1.67, 1 RCT, 434 participants) and little or no effect on the uptake of surgery (OR 1.11, 95% CI 0.67 to 1.84, 1 RCT, 434 participants). We assessed the level of evidence to be of low-certainty for both outcomes, due to indirectness of evidence and imprecision of results.The other study (n = 355, 24 towns randomised) included three intervention arms: free surgery; free surgery plus reimbursement of transport costs; and free surgery plus free transport to and from the hospital. These were compared to the control group, which was reminded to use the “low-cost” ( USD 38) surgical service. There was low-certainty evidence that surgical fee waiver with/without transport provision or reimbursement increased uptake of surgery (RR 1.94, 95% CI 1.14 to 3.31, 1 RCT, 355 participants). We assessed the level of evidence to be of low-certainty due to indirectness of evidence and imprecision of results.Neither of the studies reported our primary outcome of change in prevalence of cataract blindness, or other outcomes such as cataract surgical coverage, surgical outcome, or adverse effects. Neither study disaggregated outcomes by social subgroups to enable further assessment of equity effects. We sought data from both studies and obtained data from one; the information video and counselling intervention did not have a differential effect across the PROGRESS-Plus categories with available data (place of residence, gender, education level, socioeconomic status and social capital). AUTHORS' CONCLUSIONS: Current evidence on the effect on equity of interventions to improve access to cataract services in LMICs is limited. We identified only two studies, both conducted in rural China. Assessment of equity effects will be improved if future studies disaggregate outcomes by relevant social subgroups. To assist with assessing generalisability of findings to other settings, robust data on contextual factors are also needed.  
  Address School of Population Health, Faculty of Medicine and Health Sciences, University of Auckland, Auckland, New Zealand  
  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 1361-6137 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:29119547 Approved no  
  Call Number ref @ user @ Serial 97624  
Permanent link to this record
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