| Records |
| Author |
Bijangi-Vishehsaraei, K.; Reza Saadatzadeh, M.; Wang, H.; Nguyen, A.; Kamocka, M.M.; Cai, W.; Cohen-Gadol, A.A.; Halum, S.L.; Sarkaria, J.N.; Pollok, K.E.; Safa, A.R. |
| Title |
Sulforaphane suppresses the growth of glioblastoma cells, glioblastoma stem cell-like spheroids, and tumor xenografts through multiple cell signaling pathways |
Type |
Journal Article |
| Year |
2017 |
Publication  |
Journal of Neurosurgery |
Abbreviated Journal |
J Neurosurg |
| Volume |
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Issue |
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Pages |
1-12 |
| Keywords |
CCCP = carbonyl cyanide m-chlorophenylhydrazone; DMSO = dimethyl sulfoxide; DSB = double-strand break; EGF = epidermal growth factor; FACS = fluorescence-activated cell sorting; FGF = fibroblast growth factor; GBM = glioblastoma; GSC = glioblastoma stem cell; IC50 = 50% inhibition of cell survival; MRC = mitochondrial respiratory chain; MSC = mesenchymal stromal cell; NAC = N-acetylcysteine; NSG = nonobese diabetic scid gamma; PE = phycoerythrin; ROS = reactive oxygen species; SFN = sulforaphane; SSB = single-strand break; apoptosis; cancer stem cells; glioblastoma; oncology; sulforaphane |
| Abstract |
OBJECTIVE Defects in the apoptotic machinery and augmented survival signals contribute to drug resistance in glioblastoma (GBM). Moreover, another complexity related to GBM treatment is the concept that GBM development and recurrence may arise from the expression of GBM stem cells (GSCs). Therefore, the use of a multifaceted approach or multitargeted agents that affect specific tumor cell characteristics will likely be necessary to successfully eradicate GBM. The objective of this study was to investigate the usefulness of sulforaphane (SFN)-a constituent of cruciferous vegetables with a multitargeted effect-as a therapeutic agent for GBM. METHODS The inhibitory effects of SFN on established cell lines, early primary cultures, CD133-positive GSCs, GSC-derived spheroids, and GBM xenografts were evaluated using various methods, including GSC isolation and the sphere-forming assay, analysis of reactive oxygen species (ROS) and apoptosis, cell growth inhibition assay, comet assays for assessing SFN-triggered DNA damage, confocal microscopy, Western blot analysis, and the determination of in vivo efficacy as assessed in human GBM xenograft models. RESULTS SFN triggered the significant inhibition of cell survival and induced apoptotic cell death, which was associated with caspase 3 and caspase 7 activation. Moreover, SFN triggered the formation of mitochondrial ROS, and SFN-triggered cell death was ROS dependent. Comet assays revealed that SFN increased single- and double-strand DNA breaks in GBM. Compared with the vehicle control cells, a significantly higher amount of gamma-H2AX foci correlated with an increase in DNA double-strand breaks in the SFN-treated samples. Furthermore, SFN robustly inhibited the growth of GBM cell-induced cell death in established cell cultures and early-passage primary cultures and, most importantly, was effective in eliminating GSCs, which play a major role in drug resistance and disease recurrence. In vivo studies revealed that SFN administration at 100 mg/kg for 5-day cycles repeated for 3 weeks significantly decreased the growth of ectopic xenografts that were established from the early passage of primary cultures of GBM10. CONCLUSIONS These results suggest that SFN is a potent anti-GBM agent that targets several apoptosis and cell survival pathways and further preclinical and clinical studies may prove that SFN alone or in combination with other therapies may be potentially useful for GBM therapy. |
| Address |
Departments of 2 Pharmacology and Toxicology and |
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English |
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0022-3085 |
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| Notes |
PMID:28059653 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
96613 |
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| Author |
Luedi, M.M.; Singh, S.K.; Mosley, J.C.; Hatami, M.; Gumin, J.; Sulman, E.P.; Lang, F.F.; Stueber, F.; Zinn, P.O.; Colen, R.R. |
| Title |
A Dexamethasone-regulated Gene Signature Is Prognostic for Poor Survival in Glioblastoma Patients |
Type |
Journal Article |
| Year |
2017 |
Publication |
Journal of Neurosurgical Anesthesiology |
Abbreviated Journal |
J Neurosurg Anesthesiol |
| Volume |
29 |
Issue |
1 |
Pages |
46-58 |
| Keywords |
Animals; Antineoplastic Agents, Hormonal/*pharmacology; Apoptosis; Blotting, Western; Brain Neoplasms/*mortality; Cell Line, Tumor; Cell Survival; Dexamethasone/*pharmacology; Flow Cytometry; Gene Expression Regulation, Neoplastic/*drug effects; Glioblastoma/*mortality; Humans; Mice; Prognosis; Stem Cells/drug effects; Survival Analysis |
| Abstract |
BACKGROUND: Dexamethasone is reported to induce both tumor-suppressive and tumor-promoting effects. The purpose of this study was to identify the genomic impact of dexamethasone in glioblastoma stem cell (GSC) lines and its prognostic value; furthermore, to identify drugs that can counter these side effects of dexamethasone exposure. METHODS: We utilized 3 independent GSC lines with tumorigenic potential for this study. Whole-genome expression profiling and pathway analyses were done with dexamethasone-exposed and control cells. GSCs were also co-exposed to dexamethasone and temozolomide. Risk scores were calculated for most affected genes, and their associations with survival in The Cancer Genome Atlas and Repository of Molecular Brain Neoplasia Data databases. In silico Connectivity Map analysis identified camptothecin as antagonist to dexamethasone-induced negative effects. RESULTS: Pathway analyses predicted an activation of dexamethasone network (z-score: 2.908). Top activated canonical pathways included “role of breast cancer 1 in DNA damage response” (P=1.07E-04). GSCs were protected against temozolomide-induced apoptosis when coincubated with dexamethasone. Altered cellular functions included cell movement, cell survival, and apoptosis with z-scores of 2.815, 5.137, and -3.122, respectively. CCAAT/enhancer binding protein beta (CEBPB) was activated in a dose dependent manner specifically in slow-dividing “stem-like” cells. CEBPB was activated in dexamethasone-treated orthotopic tumors. Patients with high risk scores had significantly shorter survival. Camptothecin was validated as potential partial neutralizer of dexamethasone-induced oncogenic effects. CONCLUSIONS: Dexamethasone exposure induces a genetic program and CEBPB expression in GSCs that adversely affects key cellular functions and response to therapeutics. High risk scores associated with these genes have negative prognostic value in patients. Our findings further suggest camptothecin as a potential neutralizer of adverse dexamethasone-mediated effects. |
| Address |
*Department of Anesthesiology, Bern University Hospital Inselspital, Bern, Switzerland Departments of daggerCancer Systems Imaging double daggerDiagnostic Imaging section signNeurosurgery and Brain Tumor Center parallelRadiation Oncology, Division of Radiation Oncology #Neurosurgery, Cancer Systems Imaging, and Cancer Biology **Cancer Systems Imaging, and Diagnostic Imaging, The University of Texas MD Anderson Cancer Center paragraph signDepartment of Neurosurgery, Baylor College of Medicine, Houston, TX |
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0898-4921 |
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| Notes |
PMID:27653222 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
96635 |
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| Author |
Monge-Rojas, R.; Fuster-Baraona, T.; Garita-Arce, C.; Sanchez-Lopez, M.; Colon-Ramos, U.; Smith-Castro, V. |
| Title |
How Self-Objectification Impacts Physical Activity Among Adolescent Girls in Costa Rica |
Type |
Journal Article |
| Year |
2017 |
Publication |
Journal of Physical Activity & Health |
Abbreviated Journal |
J Phys Act Health |
| Volume |
14 |
Issue |
2 |
Pages |
123-129 |
| Keywords |
Adolescent; *Adolescent Behavior; Body Image/*psychology; Costa Rica; Cultural Characteristics; *Exercise; Female; Focus Groups; Humans; Male; Women's Health; Latin America; female identity; machismo; sexual harassment |
| Abstract |
BACKGROUND: In Latin America, more than 80% of adolescent girls are physically inactive. Inactivity may be reinforced by female stereotypes and objectification in the Latin American sociocultural context. METHODS: We examined the influence of objectification on the adoption of an active lifestyle among 192 adolescents (14 and 17 years old) from urban and rural areas in Costa Rica. Analyses of 48 focus-groups sessions were grounded in Objectification Theory. RESULTS: Vigorous exercises were gender-typed as masculine while girls had to maintain an aesthetic appearance at all times. Adolescents described how girls were anxious around the prospect of being shamed and sexually objectified during exercises. This contributed to a decrease in girls' desire to engage in physical activities. Among males, there is also a budding tolerance of female participation in vigorous sports, as long as girls maintained a feminine stereotype outside their participation. CONCLUSION: Self-objectification influenced Costa Rican adolescent girls' decisions to participate in physical activities. Interventions may include: procuring safe environments for physical activity where girls are protected from fear of ridicule and objectification; sensitizing boys about girl objectification and fostering the adoption of a modern positive masculine and female identities to encourage girls' participation in sports. |
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1543-3080 |
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| Notes |
PMID:27775480 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
97269 |
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Del Campo Vega, C.; Tutte, V.; Bermudez, G.; Parra, D.C. |
| Title |
Impact on Area-Level Physical Activity Following the Implementation of a Fitness Zone in Montevideo, Uruguay |
Type |
Journal Article |
| Year |
2017 |
Publication |
Journal of Physical Activity & Health |
Abbreviated Journal |
J Phys Act Health |
| Volume |
14 |
Issue |
11 |
Pages |
883-887 |
| Keywords |
Soparc; observation; parks |
| Abstract |
BACKGROUND: The aim of the study was to measure the level of physical activity (PA) of the users of an urban park before and after the installation of 2 fitness zones (FZs) and to assess the impact of that intervention on the users' level of PA. METHODS: The System for Observing Play and Recreation in Communities method was applied in the urban plaza Liber Seregni in Montevideo (Uruguay): 14 different areas were mapped and then recategorized as fitness (for PAs, including sports), green, and paved zones. Observations were made in the spring (Sep-Oct) of 2011 and 2014, before and after placing 2 FZs. Participation was analyzed by gender, year, mapped areas, and zones, and significant differences were assessed using the chi2 test. RESULTS: In total, 7342 individuals (4091 men and 3251 women) were observed. A greater number of people with intense PA could be seen in the FZ, with significant differences between 2011 (45%) and 2014 (70%; P < .05). CONCLUSION: This is the first longitudinal study on the impact of an intervention to increase the level of PA in public spaces in Uruguay. Higher intensity levels of PA and fewer sedentary people were observed after the installation of the FZ. |
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1543-3080 |
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| Notes |
PMID:28556669 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
98022 |
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| Author |
Monge-Rojas, R.; Fuster-Baraona, T.; Garita-Arce, C.; Sanchez-Lopez, M.; Colon-Ramos, U.; Smith-Castro, V. |
| Title |
How Self-Objectification Impacts Physical Activity Among Adolescent Girls in Costa Rica |
Type |
Journal Article |
| Year |
2017 |
Publication |
Journal of Physical Activity & Health |
Abbreviated Journal |
J Phys Act Health |
| Volume |
14 |
Issue |
2 |
Pages |
123-129 |
| Keywords |
Adolescent; *Adolescent Behavior; Body Image/*psychology; Costa Rica; Cultural Characteristics; *Exercise; Female; Focus Groups; Humans; Male; Women's Health; Latin America; female identity; machismo; sexual harassment |
| Abstract |
BACKGROUND: In Latin America, more than 80% of adolescent girls are physically inactive. Inactivity may be reinforced by female stereotypes and objectification in the Latin American sociocultural context. METHODS: We examined the influence of objectification on the adoption of an active lifestyle among 192 adolescents (14 and 17 years old) from urban and rural areas in Costa Rica. Analyses of 48 focus-groups sessions were grounded in Objectification Theory. RESULTS: Vigorous exercises were gender-typed as masculine while girls had to maintain an aesthetic appearance at all times. Adolescents described how girls were anxious around the prospect of being shamed and sexually objectified during exercises. This contributed to a decrease in girls' desire to engage in physical activities. Among males, there is also a budding tolerance of female participation in vigorous sports, as long as girls maintained a feminine stereotype outside their participation. CONCLUSION: Self-objectification influenced Costa Rican adolescent girls' decisions to participate in physical activities. Interventions may include: procuring safe environments for physical activity where girls are protected from fear of ridicule and objectification; sensitizing boys about girl objectification and fostering the adoption of a modern positive masculine and female identities to encourage girls' participation in sports. |
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English |
Summary Language |
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Abbreviated Series Title |
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Series Issue |
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1543-3080 |
ISBN |
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Conference |
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| Notes |
PMID:27775480 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
98041 |
| Permanent link to this record |
