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Author Tahara, T.; Hirata, I.; Nakano, N.; Nagasaka, M.; Nakagawa, Y.; Shibata, T.; Ohmiya, N. url  doi
openurl 
  Title Comprehensive DNA Methylation Profiling of Inflammatory Mucosa in Ulcerative Colitis Type Journal Article
  Year 2017 Publication Inflammatory Bowel Diseases Abbreviated Journal Inflamm Bowel Dis  
  Volume 23 Issue 1 Pages 165-173  
  Keywords  
  Abstract INTRODUCTION: Aberrant DNA methylation frequently occurs in the inflammatory mucosa in ulcerative colitis (UC) and is involved in UC-related tumorigenesis. We performed comprehensive DNA methylation profiling of the promoter regions of the inflamed rectal mucosae of patients with UC. DESIGN: The methylation status of the promoter CpG islands (CGIs) of 45 cancer/inflammation or age-related candidate genes and the LINE1 repetitive element were examined in the colonic mucosae of 84 cancer-free patients with UC by bisulfite pyrosequencing. Methylation status of selected genes (DPYS, N33, MIR1247, GSTP1, and SOX11) was also determined in 14 neoplastic lesions (5 with high-grade dysplasia and 9 with carcinoma) and 8 adjacent tissues derived from 12 patients. An Infinium HumanMethylation450 BeadChip array was used to characterize the methylation status of >450,000 CpG sites for 10 patients with UC. RESULTS: Clustering analysis based on the methylation status of the candidate genes clearly distinguished the inflammatory samples from the noninflammatory samples. The hypermethylation of the promoter CGIs strongly correlated with increased disease duration, which is a known risk factor for the development of colon cancer. Genome-wide methylation analyses revealed a high rate of hypermethylation in the severe phenotype of UC, particularly at the CGIs. Exclusively hypermethylated promoter CGIs in the severe phenotypes were significantly related to genes involved in biosynthetic processes, the regulation of metabolic processes, and nitrogen compound metabolic processes. CONCLUSION: Our findings suggest the potential utility of DNA methylation as a molecular marker and therapeutic target for UC-related tumorigenesis.  
  Address *Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Japan; and daggerDepartment of Gastroenterology, Tanimukai Hospital Japan, Nishinomiya, Japan  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language (up) English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1078-0998 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:27930411 Approved no  
  Call Number ref @ user @ Serial 96375  
Permanent link to this record
 

 
Author Heffernan, J.M.; McNamara, J.B.; Borwege, S.; Vernon, B.L.; Sanai, N.; Mehta, S.; Sirianni, R.W. url  doi
openurl 
  Title PNIPAAm-co-Jeffamine(R) (PNJ) scaffolds as in vitro models for niche enrichment of glioblastoma stem-like cells Type Journal Article
  Year 2017 Publication Biomaterials Abbreviated Journal Biomaterials  
  Volume 143 Issue Pages 149-158  
  Keywords Brain tumor initiating cells; Cancer stem cells; Radioresistance; Temperature responsive polymer scaffolds; Tissue engineering  
  Abstract Glioblastoma (GBM) is the most common adult primary brain tumor, and the 5-year survival rate is less than 5%. GBM malignancy is driven in part by a population of GBM stem-like cells (GSCs) that exhibit indefinite self-renewal capacity, multipotent differentiation, expression of neural stem cell markers, and resistance to conventional treatments. GSCs are enriched in specialized niche microenvironments that regulate stem phenotypes and support GSC radioresistance. Therefore, identifying GSC-niche interactions that regulate stem phenotypes may present a unique target for disrupting the maintenance and persistence of this treatment resistant population. In this work, we engineered 3D scaffolds from temperature responsive poly(N-isopropylacrylamide-co-Jeffamine M-1000(R) acrylamide), or PNJ copolymers, as a platform for enriching stem-specific phenotypes in two molecularly distinct human patient-derived GSC cell lines. Notably, we observed that, compared to conventional neurosphere cultures, PNJ cultured GSCs maintained multipotency and exhibited enhanced self-renewal capacity. Concurrent increases in expression of proteins known to regulate self-renewal, invasion, and stem maintenance in GSCs (NESTIN, EGFR, CD44) suggest that PNJ scaffolds effectively enrich the GSC population. We further observed that PNJ cultured GSCs exhibited increased resistance to radiation treatment compared to GSCs cultured in standard neurosphere conditions. GSC radioresistance is supported in vivo by niche microenvironments, and this remains a significant barrier to effectively treating these highly tumorigenic cells. Taken in sum, these data indicate that the microenvironment created by synthetic PNJ scaffolds models niche enrichment of GSCs in patient-derived GBM cell lines, and presents tissue engineering opportunities for studying clinically important behaviors such as radioresistance in vitro.  
  Address Barrow Brain Tumor Research Center, Barrow Neurological Institute, 350 W Thomas Ave, Phoenix, AZ, 85013, USA; School of Biological and Health Systems Engineering, Arizona State University, PO Box 879709, Tempe, AZ, 85287, USA. Electronic address: rachael.sirianni@dignityhealth.org  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language (up) English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0142-9612 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28802102 Approved no  
  Call Number ref @ user @ Serial 96570  
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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 (up) English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1570-159X ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28786347 Approved no  
  Call Number ref @ user @ Serial 96571  
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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 (up) English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0950-9232 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28783169 Approved no  
  Call Number ref @ user @ Serial 96572  
Permanent link to this record
 

 
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  
  Publisher Place of Publication Editor  
  Language (up) English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1019-6439 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28766685 Approved no  
  Call Number ref @ user @ Serial 96573  
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