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Author Derose, K.P.; Payan, D.D.; Fulcar, M.A.; Terrero, S.; Acevedo, R.; Farias, H.; Palar, K. url  doi
openurl 
  Title Factors contributing to food insecurity among women living with HIV in the Dominican Republic: A qualitative study Type Journal Article
  Year 2017 Publication PloS one Abbreviated Journal PLoS One  
  Volume 12 Issue 7 Pages e0181568  
  Keywords Adolescent; Adult; Domestic Violence; Dominican Republic/epidemiology; Female; *Food Supply; HIV/isolation & purification; HIV Infections/*epidemiology; Humans; Middle Aged; Qualitative Research; Social Stigma; Social Support; Socioeconomic Factors; Young Adult  
  Abstract (up) BACKGROUND: Food insecurity contributes to poor health outcomes among people living with HIV. In Latin America and the Caribbean, structural factors such as poverty, stigma, and inequality disproportionately affect women and may fuel both the HIV epidemic and food insecurity. METHODS: We examined factors contributing to food insecurity among women living with HIV (WLHIV) in the Dominican Republic (DR). Data collection included in-depth, semi-structured interviews in 2013 with 30 WLHIV with indications of food insecurity who resided in urban or peri-urban areas and were recruited from local HIV clinics. In-person interviews were conducted in Spanish. Transcripts were coded using content analysis methods and an inductive approach to identify principal and emergent themes. RESULTS: Respondents identified economic instability as the primary driver of food insecurity, precipitated by enacted stigma in the labor and social domains. Women described experiences of HIV-related labor discrimination in formal and informal sectors. Women commonly reported illegal HIV testing by employers, and subsequent dismissal if HIV-positive, especially in tourism and free trade zones. Enacted stigma in the social domain manifested as gossip and rejection by family, friends, and neighbors and physical, verbal, and sexual abuse by intimate partners, distancing women from sources of economic and food support. These experiences with discrimination and abuse contributed to internalized stigma among respondents who, as a result, were fearful and hesitant to disclose their HIV status; some participants reported leaving spouses and/or families, resulting in further isolation from economic resources, food and other support. A minority of participants described social support by friends, spouses, families and support groups, which helped to ameliorate food insecurity and emotional distress. CONCLUSIONS: Addressing food insecurity among WLHIV requires policy and programmatic interventions to enforce existing laws designed to protect the rights of people living with HIV, reduce HIV-related stigma, and improve gender equality.  
  Address Division of HIV, ID and Global Medicine, School of Medicine, University of California – San Francisco, San Francisco, California, United States of America  
  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 1932-6203 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28742870 Approved no  
  Call Number ref @ user @ Serial 98011  
Permanent link to this record
 

 
Author Jensen, S.S.; Petterson, S.A.; Halle, B.; Aaberg-Jessen, C.; Kristensen, B.W. url  doi
openurl 
  Title Effects of the lysosomal destabilizing drug siramesine on glioblastoma in vitro and in vivo Type Journal Article
  Year 2017 Publication BMC Cancer Abbreviated Journal BMC Cancer  
  Volume 17 Issue 1 Pages 178  
  Keywords Brain slice cultures; Cancer stem cell; Glioblastoma; Lysosomes; Siramesine; Spheroids  
  Abstract (up) BACKGROUND: Glioblastoma is the most frequent and most malignant brain tumor with the patients having a median survival of only 14.6 months. Although glioblastoma patients are treated with surgery, radiation and chemotherapy recurrence is inevitable. A stem-like population of radio- and chemoresistant brain tumor-initiating cells combined with the invasive properties of the tumors is believed to be critical for treatment resistance. In the present study, the aim was to investigate the effect of a novel therapeutic strategy using the lysosomotropic detergent siramesine on glioblastomas. METHODS: Standard glioma cell lines and patient-derived spheroids cultures with tumor-initiating stem-like cells were used to investigate effects of siramesine on proliferation and cell death. Responsible mechanisms were investigated by inhibitors of caspases and cathepsins. Effects of siramesine on migrating tumor cells were investigated by a flat surface migration assay and by implanting spheroids into organotypic rat brain slice cultures followed by confocal time-lapse imaging. Finally the effect of siramesine was investigated in an orthotopic mouse glioblastoma model. Results obtained in vitro and in vivo were confirmed by immunohistochemical staining of histological sections of spheroids, spheroids in brain slice cultures and tumors in mice brains. RESULTS: The results showed that siramesine killed standard glioma cell lines in vitro, and loss of acridine orange staining suggested a compromised lysosomal membrane. Co-treatment of the cell lines with inhibitors of caspases and cathepsins suggested differential involvement in cell death. Siramesine caused tumor cell death and reduced secondary spheroid formation of patient-derived spheroid cultures. In the flat surface migration model siramesine caused tumor cell death and inhibited tumor cell migration. This could not be reproduced in the organotypic three dimensional spheroid-brain slice culture model or in the mice xenograft model. CONCLUSIONS: In conclusion the in vitro results obtained with tumor cells and spheroids suggest a potential of lysosomal destabilizing drugs in killing glioblastoma cells, but siramesine was without effect in the organotypic spheroid-brain slice culture model and the in vivo xenograft model.  
  Address Institute of Clinical Research, University of Southern Denmark, Winslowparken 19.3, 5000, Odense C, Denmark. bjarne.winther.kristensen@rsyd.dk  
  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 1471-2407 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28270132 Approved no  
  Call Number ref @ user @ Serial 96603  
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Author Spencer, D.A.; Auffinger, B.M.; Murphy, J.P.; Muroski, M.E.; Qiao, J.; Gorind, Y.; Lesniak, M.S. url  doi
openurl 
  Title Hitting a Moving Target: Glioma Stem Cells Demand New Approaches in Glioblastoma Therapy Type Journal Article
  Year 2017 Publication Current Cancer Drug Targets Abbreviated Journal Curr Cancer Drug Targets  
  Volume 17 Issue 3 Pages 236-254  
  Keywords Brain Neoplasms/drug therapy/pathology; Drug Resistance, Neoplasm/drug effects; Glioblastoma/*drug therapy/pathology; Glioma/drug therapy/*pathology; Humans; Molecular Targeted Therapy/*methods; Neoplastic Stem Cells/drug effects/*pathology/radiation effects; Chemotherapy; drug targets; glioblastoma multiforme; glioma stem cells; niches; recurrence; resistance  
  Abstract (up) BACKGROUND: Glioblastoma multiforme (GBM) continues to devastate patients and outfox investigators and clinicians despite the preponderance of research directed at its biology, pathogenesis and therapeutic advances. GBM routinely outlasts multidisciplinary treatment protocols, almost inevitably recurring in a yet more aggressive and resistant form with distinct genetic differences from the original tumor. Attempts to glean further insight into GBM point increasingly toward a subpopulation of cells with a stem-like phenotype. These cancer stem cells, similar to those now described in a variety of malignancies, are capable of tumorigenesis from a population of susceptible cells. CONCLUSIONS: Glioma stem cells have thus become a prevalent focus in GBM research for their presumed role in development, maintenance and recurrence of tumors. Glioma stem cells infiltrate the white matter surrounding tumors and often evade resection. They are uniquely suited both biochemically and environmentally to resist the best therapy currently available, intrinsically and efficiently resistant to standard chemo- and radiotherapy. These stem cells create an extremely heterogenous tumor that to date has had an answer for every therapeutic question, with continued dismal patient survival. Targeting this population of glioma stem cells may hold the long-awaited key to durable therapeutic efficacy in GBM.  
  Address Neuro-Oncology Laboratory, Department of Neurosurgery, Northwestern University, 676 N. St. Clair Street, Suite 2210, Chicago, IL60611, United States  
  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 1568-0096 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:27993114 Approved no  
  Call Number ref @ user @ Serial 96616  
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Author Gersey, Z.C.; Rodriguez, G.A.; Barbarite, E.; Sanchez, A.; Walters, W.M.; Ohaeto, K.C.; Komotar, R.J.; Graham, R.M. url  doi
openurl 
  Title Curcumin decreases malignant characteristics of glioblastoma stem cells via induction of reactive oxygen species Type Journal Article
  Year 2017 Publication BMC Cancer Abbreviated Journal BMC Cancer  
  Volume 17 Issue 1 Pages 99  
  Keywords Acetylcysteine/pharmacology; Adult; Antineoplastic Agents/*pharmacology; Cell Proliferation/drug effects; Cell Survival/drug effects; Curcumin/*pharmacology; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Free Radical Scavengers; Glioblastoma/drug therapy/pathology; Humans; Inhibitor of Apoptosis Proteins/metabolism; Inhibitory Concentration 50; Mitogen-Activated Protein Kinases/metabolism; Neoplastic Stem Cells/*drug effects; Oxidative Stress; Reactive Oxygen Species/*metabolism; STAT3 Transcription Factor/metabolism; Tumor Cells, Cultured; Brain tumor; Curcumin; Glioblastoma; Natural product; Reactive oxygen species; Stat3; Stem cell  
  Abstract (up) BACKGROUND: Glioblastoma Multiforme (GBM) is the most common and lethal form of primary brain tumor in adults. Following standard treatment of surgery, radiation and chemotherapy, patients are expected to survive 12-14 months. Theorized cause of disease recurrence in these patients is tumor cell repopulation through the proliferation of treatment-resistant cancer stem cells. Current research has revealed curcumin, the principal ingredient in turmeric, can modulate multiple signaling pathways important for cancer stem cell self-renewal and survival. METHODS: Following resection, tumor specimens were dissociated and glioblastoma stem cells (GSCs) were propagated in neurosphere media and characterized via immunocytochemistry. Cell viability was determined with MTS assay. GSC proliferation, sphere forming and colony forming assays were conducted through standard counting methods. Reactive oxygen species (ROS) production was examined using the fluorescent molecular probe CM-H2DCFA. Effects on cell signaling pathways were elucidated by western blot. RESULTS: We evaluate the effects of curcumin on patient-derived GSC lines. We demonstrate a curcumin-induced dose-dependent decrease in GSC viability with an approximate IC50 of 25 muM. Treatment with sub-toxic levels (2.5 muM) of curcumin significantly decreased GSC proliferation, sphere forming ability and colony forming potential. Curcumin induced ROS, promoted MAPK pathway activation, downregulated STAT3 activity and IAP family members. Inhibition of ROS with the antioxidant N-acetylcysteine reversed these effects indicating a ROS dependent mechanism. CONCLUSIONS: Discoveries made in this investigation may lead to a non-toxic intervention designed to prevent recurrence in glioblastoma by targeting glioblastoma stem cells.  
  Address Department of Neurological Surgery, University of Miami Brain Tumor Initiative (UMBTI) Research Laboratory, Lois Pope LIFE Center, 2nd Floor, 1095 NW 14th Terrace, Miami, Florida, 33136, USA. rgraham@med.miami.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 1471-2407 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28160777 Approved no  
  Call Number ref @ user @ Serial 96610  
Permanent link to this record
 

 
Author 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 (up) 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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