Aung, Thiha

[["dc.bibliographiccitation.firstpage","362"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Oncology"],["dc.bibliographiccitation.lastpage","370"],["dc.bibliographiccitation.volume","84"],["dc.contributor.author","Overbeck, Tobias R."],["dc.contributor.author","Hupfeld, Timo"],["dc.contributor.author","Krause, Doris"],["dc.contributor.author","Waldmann-Beushausen, Regina"],["dc.contributor.author","Chapuy, Björn"],["dc.contributor.author","Guedenzoph, Bjoern"],["dc.contributor.author","Aung, Thiha"],["dc.contributor.author","Inagaki, Nobuya"],["dc.contributor.author","Schoendube, Friedrich Albert"],["dc.contributor.author","Danner, Bernhard Christoph"],["dc.contributor.author","Truemper, Lorenz H."],["dc.contributor.author","Wulf, Gerald G."],["dc.date.accessioned","2018-11-07T09:29:56Z"],["dc.date.available","2018-11-07T09:29:56Z"],["dc.date.issued","2013"],["dc.description.abstract","Patients with advanced-stage bronchial cancer benefit from systemic cytostatic therapy, in particular from regimens integrating cisplatin and taxanes. However, eventual disease progression leads to a fatal outcome in most cases, originating from tumor cells resisting chemotherapy. We here show that the intracellular ATP-binding cassette transporter A3 (ABCA3), previously recognized as critical for the secretion of surfactant components from type 2 pneumocytes, is expressed in non-small-cell lung cancer (NSCLC) cells. With some heterogeneity in a given specimen, expression levels detected immunohistochemically in primary cancer tissue were highest in adenocarcinomas and lowest in small cell lung cancers. Genetic silencing of ABCA3 in the NSCLC cell line models A549, NCI-H1650 and NCI-H1975 significantly increased tumor cell susceptibility to the cytostatic effects of both cisplatin (in all cell lines) and paclitaxel (in two of three cell lines). Taken together, ABCA3 emerges as a modulator of NSCLC cell susceptibility to cytostatic therapy. Copyright (c) 2013 S. Karger AG, Basel"],["dc.description.sponsorship","Faculty of Medicine, Georg August University Gottingen, Germany"],["dc.identifier.doi","10.1159/000348884"],["dc.identifier.isi","000320219100007"],["dc.identifier.pmid","23689165"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10826"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/31175"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.relation.issn","0030-2414"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Intracellular ATP-Binding Cassette Transporter A3 is Expressed in Lung Cancer Cells and Modulates Susceptibility to Cisplatin and Paclitaxel"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e0200343"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","PLOS ONE"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Blesinger, Hannah"],["dc.contributor.author","Kaulfuß, Silke"],["dc.contributor.author","Aung, Thiha"],["dc.contributor.author","Schwoch, Sonja"],["dc.contributor.author","Prantl, Lukas"],["dc.contributor.author","Rößler, Jochen"],["dc.contributor.author","Wilting, Jörg"],["dc.contributor.author","Becker, Jürgen"],["dc.date.accessioned","2019-07-09T11:45:49Z"],["dc.date.available","2019-07-09T11:45:49Z"],["dc.date.issued","2018"],["dc.description.abstract","Lymphatic malformations (LM) are characterized by the overgrowth of lymphatic vessels during pre- and postnatal development. Macrocystic, microcystic and combined forms of LM are known. The cysts are lined by lymphatic endothelial cells (LECs). Resection and sclerotherapy are the most common treatment methods. Recent studies performed on LM specimens in the United States of America have identified activating mutations in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene in LM. However, whole tissue but not isolated cell types were studied. Here, we studied LM tissues resected at the University Hospitals Freiburg and Regensburg, Germany. We isolated LECs and fibroblasts separately, and sequenced the commonly affected exons 8, 10, and 21 of the PIK3CA gene. We confirm typical monoallelic mutations in 4 out of 6 LM-derived LEC lines, and describe two new mutations i.) in exon 10 (c.1636C>A; p.Gln546Lys), and ii.) a 3bp in-frame deletion of GAA (Glu109del). LM-derived fibroblasts did not possess such mutations, showing cell-type specificity of the gene defect. High activity of the PIK3CA-AKT- mTOR pathway was demonstrated by hyperphosphorylation of AKT-Ser473 in all LM-derived LECs (including the ones with newly identified mutations), as compared to normal LECs. Additionally, hyperphosphorylation of ERK was seen in all LM-derived LECs, except for the one with Glu109del. In vitro, the small molecule kinase inhibitors Buparlisib/BKM-120, Wortmannin, and Ly294002, (all inhibitors of PIK3CA), CAL-101 (inhibitor of PIK3CD), MK-2206 (AKT inhibitor), Sorafenib (multiple kinases inhibitor), and rapamycin (mTOR inhibitor) significantly blocked proliferation of LM-derived LECs in a concentration-dependent manner, but also blocked proliferation of normal LECs. However, MK-2206 appeared to be more specific for mutated LECs, except in case of Glu109 deletion. In sum, children that are, or will be, treated with kinase inhibitors must be monitored closely."],["dc.identifier.doi","10.1371/journal.pone.0200343"],["dc.identifier.pmid","29985963"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15320"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59313"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1932-6203"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.title","PIK3CA mutations are specifically localized to lymphatic endothelial cells of lymphatic malformations"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e0164964"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Hasselhof, Viktoria"],["dc.contributor.author","Sperling, Anastasia"],["dc.contributor.author","Buttler, Kerstin"],["dc.contributor.author","Strobel, Philipp"],["dc.contributor.author","Becker, Juergen"],["dc.contributor.author","Aung, Thiha"],["dc.contributor.author","Felmerer, Gunther"],["dc.contributor.author","Wilting, Joerg"],["dc.date.accessioned","2018-11-07T10:06:56Z"],["dc.date.available","2018-11-07T10:06:56Z"],["dc.date.issued","2016"],["dc.description.abstract","Millions of patients suffer from lymphedema worldwide. Supporting the contractility of lymphatic collectors is an attractive target for pharmacological therapy of lymphedema. However, lymphatics have mostly been studied in animals, while the cellular and molecular characteristics of human lymphatic collectors are largely unknown. We studied epifascial lymphatic collectors of the thigh, which were isolated for autologous transplantations. Our immunohistological studies identify additional markers for LECs (vimentin, CCBE1). We show and confirm differences between initial and collecting lymphatics concerning the markers ESAM1, D2-40 and LYVE-1. Our transmission electron microscopic studies reveal two types of smooth muscle cells (SMCs) in the media of the collectors with dark and light cytoplasm. We observed vasa vasorum in the media of the largest collectors, as well as interstitial Cajal-like cells, which are highly ramified cells with long processes, caveolae, and lacking a basal lamina. They are in close contact with SMCs, which possess multiple caveolae at the contact sites. Immunohistologically we identified such cells with antibodies against vimentin and PDGFR alpha, but not CD34 and cKIT. With Next Generation Sequencing we searched for highly expressed genes in the media of lymphatic collectors, and found therapeutic targets, suitable for acceleration of lymphatic contractility, such as neuropeptide Y receptors 1, and 5; tachykinin receptors 1, and 2; purinergic receptors P2RX1, and 6, P2RY12, 13, and 14; 5-hydroxytryptamine receptors HTR2B, and 3C; and adrenoceptors alpha(2A),(B),(C). Our studies represent the first comprehensive characterization of human epifascial lymphatic collectors, as a prerequisite for diagnosis and therapy."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2016"],["dc.identifier.doi","10.1371/journal.pone.0164964"],["dc.identifier.isi","000386204500086"],["dc.identifier.pmid","27764183"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13797"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/39190"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Morphological and Molecular Characterization of Human Dermal Lymphatic Collectors"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","96697"],["dc.bibliographiccitation.firstpage","96697"],["dc.bibliographiccitation.issue","57"],["dc.bibliographiccitation.journal","Oncotarget"],["dc.bibliographiccitation.lastpage","96709"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Sperling, Swetlana"],["dc.contributor.author","Aung, Thiha"],["dc.contributor.author","Martin, Sabine"],["dc.contributor.author","Rohde, Veit"],["dc.contributor.author","Ninkovic, Milena"],["dc.date.accessioned","2018-10-09T07:07:52Z"],["dc.date.available","2018-10-09T07:07:52Z"],["dc.date.issued","2017-11-14"],["dc.description.abstract","A small subpopulation of tumor stem-like cells has the capacity to initiate tumors and mediate radio- and chemoresistance in diverse cancers hence also in glioblastoma (GBM). It has been reported that this capacity of tumor initiation in the brain is mainly dependent on the body's nutrient supply. This population of so-called brain tumor initiating or brain tumor stem-like cells (BTSCs) is able to extract nutrients like glucose with a higher affinity. Riluzole, a drug approved for treating amyotrophic lateral sclerosis (ALS), was reported to possess anticancer properties, affecting the glutamate metabolism. We report that riluzole treatment inhibits the growth of brain tumor stem-like cells enriched cultures isolated from two human glioblastomas. The effects of riluzole on these cells were associated with an inhibition of a poor prognostic indicator: glucose transporter 3 (GLUT3). A decrease in GLUT3 is associated with a decrease in the p-Akt/HIF1α pathway. Further, downregulation of the DNA (Cytosine-5-)-methyltransferase 1 (DNMT1) gene that causes hypermethylation of various tumor-suppressor genes and leads to a poor prognosis in GBM, was detected. Two hallmarks of cancer cells-proliferation and cell death-were positively influenced by riluzole treatment. Finally, we observed that riluzole reduced the tumor growth in in vivo CAM assay, suggesting it could be a possible synergistic drug for the treatment of glioblastoma."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2017"],["dc.fs.pkfprnr","86427"],["dc.identifier.doi","10.18632/oncotarget.18043"],["dc.identifier.fs","633522"],["dc.identifier.pmid","29228563"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14509"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/15891"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation.eissn","1949-2553"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Riluzole: a potential therapeutic intervention in human brain tumor stem-like cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]