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Author Klumpp, L.; Sezgin, E.C.; Skardelly, M.; Eckert, F.; Huber, S.M. url  doi
openurl 
  Title KCa3.1 channels and glioblastoma: in vitro studies Type Journal Article
  Year 2017 Publication Current Neuropharmacology Abbreviated Journal Curr Neuropharmacol  
  Volume Issue Pages  
  Keywords γH2AX foci; Aldh1a3; Gbm; GSCs; IKCa; Kcnn4; Sk4; radioresistance  
  Abstract Several tumor entities including brain tumors aberrantly overexpress intermediate conductance Ca2+ activated KCa3.1 K+ channels. These channels contribute significantly to the transformed phenotype of the tumor cells. By modulating membrane potential, cell volume, Ca2+ signals and the respiration chain, KCa3.1 channels in both, plasma and inner mitochondrial membrane, have been demonstrated to regulate many cellular processes such as migration and tissue invasion, metastasis, cell cycle progression, oxygen consumption and metabolism, DNA damage response and cell death of cancer cells. Moreover, KCa3.1 channels have been shown to crucially contribute to resistance against radiotherapy suggesting KCa3.1 channels as promising new targets of future anti-cancer therapies. The present article summarizes our current knowledge of the molecular signaling upstream and downstream and the effector functions of KCa3.1 channel activity in tumor cells in general and in glioblastoma cells in particular. In addition, it presents original in vitro data on KCa3.1 channel expression in subtypes of glioblastoma stem(-like) cells proposing KCa3.1 as marker for the mesenchymal subgroup of cancer stem cells. Moreover, the data suggest that KCa3.1 contributes to the therapy resistance of mesenchymal glioblastoma stem cells.  
  Address Department of Radiation Oncology University of Tubingen Hoppe-Seyler-Str. 3 72076 Tubingen. Germany  
  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 1570-159X ISBN Medium (down)  
  Area Expedition Conference  
  Notes PMID:28786347 Approved no  
  Call Number ref @ user @ Serial 96571  
Permanent link to this record
 

 
Author Guerrero, P.A.; Tchaicha, J.H.; Chen, Z.; Morales, J.E.; McCarty, N.; Wang, Q.; Sulman, E.P.; Fuller, G.; Lang, F.F.; Rao, G.; McCarty, J.H. url  doi
openurl 
  Title Glioblastoma stem cells exploit the alphavbeta8 integrin-TGFbeta1 signaling axis to drive tumor initiation and progression Type Journal Article
  Year 2017 Publication Oncogene Abbreviated Journal Oncogene  
  Volume Issue Pages  
  Keywords  
  Abstract Glioblastoma (GBM) is a primary brain cancer that contains populations of stem-like cancer cells (GSCs) that home to specialized perivascular niches. GSC interactions with their niche influence self-renewal, differentiation and drug resistance, although the pathways underlying these events remain largely unknown. Here, we report that the integrin alphavbeta8 and its latent transforming growth factor beta1 (TGFbeta1) protein ligand have central roles in promoting niche co-option and GBM initiation. alphavbeta8 integrin is highly expressed in GSCs and is essential for self-renewal and lineage commitment in vitro. Fractionation of beta8high cells from freshly resected human GBM samples also reveals a requirement for this integrin in tumorigenesis in vivo. Whole-transcriptome sequencing reveals that alphavbeta8 integrin regulates tumor development, in part, by driving TGFbeta1-induced DNA replication and mitotic checkpoint progression. Collectively, these data identify the alphavbeta8 integrin-TGFbeta1 signaling axis as crucial for exploitation of the perivascular niche and identify potential therapeutic targets for inhibiting tumor growth and progression in patients with GBM.Oncogene advance online publication, 7 August 2017; doi:10.1038/onc.2017.248.  
  Address Department of Neurosurgery, M. D. Anderson Cancer Center, Houston, TX, 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 0950-9232 ISBN Medium (down)  
  Area Expedition Conference  
  Notes PMID:28783169 Approved no  
  Call Number ref @ user @ Serial 96572  
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Author Magrath, J.W.; Kim, Y. url  doi
openurl 
  Title Salinomycin's potential to eliminate glioblastoma stem cells and treat glioblastoma multiforme (Review) Type Journal Article
  Year 2017 Publication International Journal of Oncology Abbreviated Journal Int J Oncol  
  Volume 51 Issue 3 Pages 753-759  
  Keywords  
  Abstract Glioblastoma multiforme (GBM) is the most common and deadliest form of primary brain tumor. Despite treatment with surgery, radiotherapy, and chemotherapy with the drug temozolomide, the expected survival after diagnosis remains low. The median survival is only 14.6 months and the two-year survival is a mere 30%. One reason for this is the heterogeneity of GBM including the presence of glioblastoma cancer stem cells (GSCs). GSCs are a subset of cells with the unique ability to proliferate, differentiate, and create tumors. GSCs are resistant to chemotherapy and radiation and thought to play an important role in recurrence. In order to effectively treat GBM, a drug must be identified that can kill GSCs. The ionophore salinomycin has been shown to kill cancer stem cells and is therefore a promising future treatment for GBM. This study focuses on salinomycin's potential to treat GBM including its ability to reduce the CSC population, its toxicity to normal brain cells, its mechanism of action, and its potential for combination treatment.  
  Address Department of Chemical and Biological Engineering, The University of Alabama, Tuscaloosa, AL 35487-0203, USA  
  Corporate Author Thesis  
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  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1019-6439 ISBN Medium (down)  
  Area Expedition Conference  
  Notes PMID:28766685 Approved no  
  Call Number ref @ user @ Serial 96573  
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Author Miranda, A.; Blanco-Prieto, M.; Sousa, J.; Pais, A.; Vitorino, C. url  doi
openurl 
  Title Breaching barriers in glioblastoma. Part I: Molecular pathways and novel treatment approaches Type Journal Article
  Year 2017 Publication International Journal of Pharmaceutics Abbreviated Journal Int J Pharm  
  Volume 531 Issue 1 Pages 372-388  
  Keywords Glioblastoma; Molecular mechanisms; Temozolomide; Therapeutic advances; Therapeutic resistance  
  Abstract Glioblastoma multiforme (GBM) is the most common primary brain tumour, and the most aggressive in nature. The prognosis for patients with GBM remains poor, with a median survival time of only 1-2 years. The treatment failure relies on the development of resistance by tumour cells and the difficulty of ensuring that drugs effectively cross the dual blood brain barrier/blood brain tumour barrier. The advanced molecular and genetic knowledge has allowed to identify the mechanisms responsible for temozolomide resistance, which represents the standard of care in GBM, along with surgical resection and radiotherapy. Such resistance has motivated the researchers to investigate new avenues for GBM treatment intended to improve patient survival. In this review, we provide an overview of major obstacles to effective treatment of GBM, encompassing biological barriers, cancer stem cells, DNA repair mechanisms, deregulated signalling pathways and autophagy. New insights and potential therapy approaches for GBM are also discussed, emphasizing localized chemotherapy delivered directly to the brain, immunotherapy, gene therapy and nanoparticle-mediated brain drug delivery.  
  Address Faculty of Pharmacy, University of Coimbra, Portugal; Pharmacometrics Group of the Centre for Neurosciences and Cell Biology (CNC), University of Coimbra, Portugal. Electronic address: csvitorino@ff.uc.pt  
  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 0378-5173 ISBN Medium (down)  
  Area Expedition Conference  
  Notes PMID:28755993 Approved no  
  Call Number ref @ user @ Serial 96574  
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Author Yin, J.; Oh, Y.T.; Kim, J.-Y.; Kim, S.S.; Choi, E.; Kim, T.H.; Hong, J.H.; Chang, N.; Cho, H.J.; Sa, J.K.; Kim, J.C.; Kwon, H.J.; Park, S.; Lin, W.; Nakano, I.; Gwak, H.-S.; Yoo, H.; Lee, S.-H.; Lee, J.; Kim, J.H.; Kim, S.-Y.; Nam, D.-H.; Park, M.-J.; Park, J.B. url  doi
openurl 
  Title Transglutaminase 2 Inhibition Reverses Mesenchymal Transdifferentiation of Glioma Stem Cells by Regulating C/EBPbeta Signaling Type Journal Article
  Year 2017 Publication Cancer Research Abbreviated Journal Cancer Res  
  Volume 77 Issue 18 Pages 4973-4984  
  Keywords  
  Abstract Necrosis is a hallmark of glioblastoma (GBM) and is responsible for poor prognosis and resistance to conventional therapies. However, the molecular mechanisms underlying necrotic microenvironment-induced malignancy of GBM have not been elucidated. Here, we report that transglutaminase 2 (TGM2) is upregulated in the perinecrotic region of GBM and triggered mesenchymal (MES) transdifferentiation of glioma stem cells (GSC) by regulating master transcription factors (TF), such as C/EBPbeta, TAZ, and STAT3. TGM2 expression was induced by macrophages/microglia-derived cytokines via NF-kappaB activation and further degraded DNA damage-inducible transcript 3 (GADD153) to induce C/EBPbeta expression, resulting in expression of the MES transcriptome. Downregulation of TGM2 decreased sphere-forming ability, tumor size, and radioresistance and survival in a xenograft mouse model through a loss of the MES signature. A TGM2-specific inhibitor GK921 blocked MES transdifferentiation and showed significant therapeutic efficacy in mouse models of GSC. Moreover, TGM2 expression was significantly increased in recurrent MES patients and inversely correlated with patient prognosis. Collectively, our results indicate that TGM2 is a key molecular switch of necrosis-induced MES transdifferentiation and an important therapeutic target for MES GBM. Cancer Res; 77(18); 4973-84. (c)2017 AACR.  
  Address Specific Organs Cancer Branch, Research Institute and Hospital, National Cancer Center, Goyang, Korea  
  Corporate Author Thesis  
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  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0008-5472 ISBN Medium (down)  
  Area Expedition Conference  
  Notes PMID:28754668 Approved no  
  Call Number ref @ user @ Serial 96575  
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