| Records |
| Author |
Momeny, M.; Moghaddaskho, F.; Gortany, N.K.; Yousefi, H.; Sabourinejad, Z.; Zarrinrad, G.; Mirshahvaladi, S.; Eyvani, H.; Barghi, F.; Ahmadinia, L.; Ghazi-Khansari, M.; Dehpour, A.R.; Amanpour, S.; Tavangar, S.M.; Dardaei, L.; Emami, A.H.; Alimoghaddam, K.; Ghavamzadeh, A.; Ghaffari, S.H. |
| Title |
Blockade of vascular endothelial growth factor receptors by tivozanib has potential anti-tumour effects on human glioblastoma cells |
Type |
Journal Article |
| Year |
2017 |
Publication |
Scientific Reports |
Abbreviated Journal |
Sci Rep |
| Volume |
7 |
Issue |
|
Pages  |
44075 |
| Keywords |
|
| Abstract |
Glioblastoma (GBM) remains one of the most fatal human malignancies due to its high angiogenic and infiltrative capacities. Even with optimal therapy including surgery, radiotherapy and temozolomide, it is essentially incurable. GBM is among the most neovascularised neoplasms and its malignant progression associates with striking neovascularisation, evidenced by vasoproliferation and endothelial cell hyperplasia. Targeting the pro-angiogenic pathways is therefore a promising anti-glioma strategy. Here we show that tivozanib, a pan-inhibitor of vascular endothelial growth factor (VEGF) receptors, inhibited proliferation of GBM cells through a G2/M cell cycle arrest via inhibition of polo-like kinase 1 (PLK1) signalling pathway and down-modulation of Aurora kinases A and B, cyclin B1 and CDC25C. Moreover, tivozanib decreased adhesive potential of these cells through reduction of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Tivozanib diminished GBM cell invasion through impairing the proteolytic cascade of cathepsin B/urokinase-type plasminogen activator (uPA)/matrix metalloproteinase-2 (MMP-2). Combination of tivozanib with EGFR small molecule inhibitor gefitinib synergistically increased sensitivity to gefitinib. Altogether, these findings suggest that VEGFR blockade by tivozanib has potential anti-glioma effects in vitro. Further in vivo studies are warranted to explore the anti-tumour activity of tivozanib in combinatorial approaches in GBM. |
| Address |
Haematology/Oncology and Stem Cell Transplantation Research Centre, Shariati Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran |
| 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 |
2045-2322 |
ISBN |
|
Medium |
|
| Area |
|
Expedition |
|
Conference |
|
| Notes |
PMID:28287096 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
96601 |
| Permanent link to this record |
| |
|
| |
| Author |
Oliva, C.R.; Zhang, W.; Langford, C.; Suto, M.J.; Griguer, C.E. |
| Title |
Repositioning chlorpromazine for treating chemoresistant glioma through the inhibition of cytochrome c oxidase bearing the COX4-1 regulatory subunit |
Type |
Journal Article |
| Year |
2017 |
Publication |
Oncotarget |
Abbreviated Journal |
Oncotarget |
| Volume |
8 |
Issue |
23 |
Pages |
37568-37583 |
| Keywords |
chlorpromazine; cytochrome c oxidase; glioblastoma; inhibitor; stem cells |
| Abstract |
Patients with glioblastoma have one of the lowest overall survival rates among patients with cancer. Standard of care for patients with glioblastoma includes temozolomide and radiation therapy, yet 30% of patients do not respond to these treatments and nearly all glioblastoma tumors become resistant. Chlorpromazine is a United States Food and Drug Administration-approved phenothiazine widely used as a psychotropic in clinical practice. Recently, experimental evidence revealed the anti-proliferative activity of chlorpromazine against colon and brain tumors. Here, we used chemoresistant patient-derived glioma stem cells and chemoresistant human glioma cell lines to investigate the effects of chlorpromazine against chemoresistant glioma. Chlorpromazine selectively and significantly inhibited proliferation in chemoresistant glioma cells and glioma stem cells. Mechanistically, chlorpromazine inhibited cytochrome c oxidase (CcO, complex IV) activity from chemoresistant but not chemosensitive cells, without affecting other mitochondrial complexes. Notably, our previous studies revealed that the switch to chemoresistance in glioma cells is accompanied by a switch from the expression of CcO subunit 4 isoform 2 (COX4-2) to COX4-1. In this study, chlorpromazine induced cell cycle arrest selectively in glioma cells expressing COX4-1, and computer-simulated docking studies indicated that chlorpromazine binds more tightly to CcO expressing COX4-1 than to CcO expressing COX4-2. In orthotopic mouse brain tumor models, chlorpromazine treatment significantly increased the median overall survival of mice harboring chemoresistant tumors. These data indicate that chlorpromazine selectively inhibits the growth and proliferation of chemoresistant glioma cells expressing COX4-1. The feasibility of repositioning chlorpromazine for selectively treating chemoresistant glioma tumors should be further explored. |
| Address |
Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, 35294 Alabama, 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 |
1949-2553 |
ISBN |
|
Medium |
|
| Area |
|
Expedition |
|
Conference |
|
| Notes |
PMID:28455961 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
96587 |
| Permanent link to this record |
| |
|
| |
| Author |
Brodie, S.; Lee, H.K.; Jiang, W.; Cazacu, S.; Xiang, C.; Poisson, L.M.; Datta, I.; Kalkanis, S.; Ginsberg, D.; Brodie, C. |
| Title |
The novel long non-coding RNA TALNEC2, regulates tumor cell growth and the stemness and radiation response of glioma stem cells |
Type |
Journal Article |
| Year |
2017 |
Publication |
Oncotarget |
Abbreviated Journal |
Oncotarget |
| Volume |
8 |
Issue |
19 |
Pages |
31785-31801 |
| Keywords |
Talnec2; glioblastoma; glioma stem cells; long non-cording RNAs; mesenchymal transformation |
| Abstract |
Despite advances in novel therapeutic approaches for the treatment of glioblastoma (GBM), the median survival of 12-14 months has not changed significantly. Therefore, there is an imperative need to identify molecular mechanisms that play a role in patient survival. Here, we analyzed the expression and functions of a novel lncRNA, TALNEC2 that was identified using RNA seq of E2F1-regulated lncRNAs. TALNEC2 was localized to the cytosol and its expression was E2F1-regulated and cell-cycle dependent. TALNEC2 was highly expressed in GBM with poor prognosis, in GBM specimens derived from short-term survivors and in glioma cells and glioma stem cells (GSCs). Silencing of TALNEC2 inhibited cell proliferation and arrested the cells in the G1\S phase of the cell cycle in various cancer cell lines. In addition, silencing of TALNEC2 decreased the self-renewal and mesenchymal transformation of GSCs, increased sensitivity of these cells to radiation and prolonged survival of mice bearing GSC-derived xenografts. Using miRNA array analysis, we identified specific miRNAs that were altered in the silenced cells that were associated with cell-cycle progression, proliferation and mesenchymal transformation. Two of the downregulated miRNAs, miR-21 and miR-191, mediated some of TALNEC2 effects on the stemness and mesenchymal transformation of GSCs. In conclusion, we identified a novel E2F1-regulated lncRNA that is highly expressed in GBM and in tumors from patients of short-term survival. The expression of TALNEC2 is associated with the increased tumorigenic potential of GSCs and their resistance to radiation. We conclude that TALNEC2 is an attractive therapeutic target for the treatment of GBM. |
| Address |
Davidson Laboratory of Cell Signaling and Tumorigenesis, Hermelin Brain Tumor Center, Department of Neurosurgery, Detroit, MI, 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 |
1949-2553 |
ISBN |
|
Medium |
|
| Area |
|
Expedition |
|
Conference |
|
| Notes |
PMID:28423669 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
96594 |
| Permanent link to this record |
| |
|
| |
| Author |
Roy, A.; Attarha, S.; Weishaupt, H.; Edqvist, P.-H.; Swartling, F.J.; Bergqvist, M.; Siebzehnrubl, F.A.; Smits, A.; Ponten, F.; Tchougounova, E. |
| Title |
Serglycin as a potential biomarker for glioma: association of serglycin expression, extent of mast cell recruitment and glioblastoma progression |
Type |
Journal Article |
| Year |
2017 |
Publication |
Oncotarget |
Abbreviated Journal |
Oncotarget |
| Volume |
8 |
Issue |
15 |
Pages |
24815-24827 |
| Keywords |
Cd44; Zeb1; glioma; mast cell; serglycin |
| Abstract |
Serglycin is an intracellular proteoglycan with a unique ability to adopt highly divergent structures by glycosylation with variable types of glycosaminoglycans (GAGs) when expressed by different cell types. Serglycin is overexpressed in aggressive cancers suggesting its protumorigenic role. In this study, we explored the expression of serglycin in human glioma and its correlation with survival and immune cell infiltration. We demonstrate that serglycin is expressed in glioma and that increased expression predicts poor survival of patients. Analysis of serglycin expression in a large cohort of low- and high-grade human glioma samples reveals that its expression is grade dependent and is positively correlated with mast cell (MC) infiltration. Moreover, serglycin expression in patient-derived glioma cells is significantly increased upon MC co-culture. This is also accompanied by increased expression of CXCL12, CXCL10, as well as markers of cancer progression, including CD44, ZEB1 and vimentin.In conclusion, these findings indicate the importance of infiltrating MCs in glioma by modulating signaling cascades involving serglycin, CD44 and ZEB1. The present investigation reveals serglycin as a potential prognostic marker for glioma and demonstrates an association with the extent of MC recruitment and glioma progression, uncovering potential future therapeutic opportunities for patients. |
| Address |
Uppsala University, Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala, Sweden |
| 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 |
1949-2553 |
ISBN |
|
Medium |
|
| Area |
|
Expedition |
|
Conference |
|
| Notes |
PMID:28445977 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
96590 |
| Permanent link to this record |
| |
|
| |
| Author |
Gredilla, A.; Fdez-Ortiz de Vallejuelo, S.; Gomez-Nubla, L.; Carrero, J.A.; de Leao, F.B.; Madariaga, J.M.; Silva, L.F.O. |
| Title |
Are children playgrounds safe play areas? Inorganic analysis and lead isotope ratios for contamination assessment in recreational (Brazilian) parks |
Type |
Journal Article |
| Year |
2017 |
Publication |
Environmental Science and Pollution Research International |
Abbreviated Journal |
Environ Sci Pollut Res Int |
| Volume |
24 |
Issue |
31 |
Pages |
24333-24345 |
| Keywords |
Chemometric analysis; Human health; Icp-Ms; Lead isotopic ratio; Metals; Normalized-and-Weighted Average Concentration; Playgrounds |
| Abstract |
In city playgrounds, there is a potential risk of harming children's health by contamination coming from anthropogenic activities. With the aim to determinate the sources and the risk of hazardous elements, soil samples were collected in 19 selected playgrounds of different urban and rural areas from the Rio Grande do Sul state (Brazil). The concentration of 23 metals and metalloids and lead isotopic ratios were determined by ICP-MS. The methodology proposed here, firstly, classified the parks according to the average metal content by means of the NWACs (Normalized-and-Weighted Average Concentrations) and assess the contamination risk determining the Contamination Factors (CFs). Finally, statistical tools (correlation analysis and principal component analysis) were used to identify the most important contamination sources. The statistical tools used, together with lead isotopic composition analysis of the samples, revealed that coal combustion is the main source of contamination in the area. Vegetation was identified as a barrier for the contamination coming from the city. Nonetheless, some of the soils present a possible toxicological risk for humans. In fact, Cr, Sb, and Pb concentrations were higher than the Residential Intervention Values (VIRs) defined by the Environmental Protection Agency of the State of Sao Paulo, also in Brazil. |
| Address |
Research Group in Environmental Management and Sustainability, Faculty of Environmental Sciences, Universidad De la Costa, Calle 58, No. 55-56, 080002, Barranquilla, Atlantico, Colombia |
| 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 |
0944-1344 |
ISBN |
|
Medium |
|
| Area |
|
Expedition |
|
Conference |
|
| Notes |
PMID:28889400 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
97629 |
| Permanent link to this record |
