FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W398075761> ?p ?o ?g. }

• W398075761 abstract "Author(s): Alhiyari, Yazeed | Advisor(s): Pajonk, Frank | Abstract: Gamma secretase (GS) is an intramembraneous protease that cleaves over 91 different membrane substrates. GS is responsible for the final S3 cleavage of the notch receptor, thereby releasing the notch intracellular domain (NICD) into the cytoplasm. Upon translocation into the nucleus NICD activates the transcription of notch effector proteins that maintain cell stemness. Due to GS activity on the notch pathway, it has become an attractive target for cancer stem cells. The cancer stem cell (CSC) hypothesis states that cancers are generated and maintained by a group of cells that share similarities with normal adult stem cells. CSCs have been shown to be resistant to most current anti-cancer treatment approaches, including radiation therapy, thus contributing to tumor repopulation after therapy. A combinational therapy that targets both cancer cells and inhibits cancer stem cell growth is highly desirable. Unfortunately, there is inconsistent data determining the combinational effects of GS inhibitors (GSI) with radiation. In this study, the efficacy of GSI treatment with radiation therapy in reducing the cancer stem cell population in glioblastoma multiforme (GBM) was evaluated. Utilizing a panel of GBM cell lines varying in PTEN, p53, and EGFR status, we evaluated the effects of GSI plus radiation treatment on the cancer stem cell population, using sphere-forming capacity assays, cell cycle analysis, and γH2AX and Hoechst/PY staining. Our data demonstrates that PTEN status plays a role in the sensitivity to GSI treatment in combination with radiation treatment. In addition, we observed that treating PTEN-wt cell lines with GSI improved survival among the stem cell population while PTEN-mutant lines showed a reduced survival. We believe this glioma stem cell protection is mediated through FOXO, or the Forkhead class O transcription factors, which is positively regulated by functioning PTEN. In conclusion, this study demonstrates that the effectiveness of combinational treatment of GSI and radiation on glioma stem cells depends on the genetic background of the tumor. Specifically, PTENwt neurosphere cell lines are radioprotected under GSI treatment while PTEN-null neurosphere cell lines become more radiosensitivecycle analysis, and γH2AX and Hoechst/PY staining. Our data demonstrates that PTEN status plays a role in the sensitivity to GSI treatment in combination with radiation treatment. In addition, we observed that treating PTEN-wt cell lines with GSI improved survival among the stem cell population while PTEN-mutant lines showed a reduced survival. We believe this glioma stem cell protection is mediated through FOXO, or the Forkhead class O transcription factors, which is positively regulated by functioning PTEN. In conclusion, this study demonstrates that the effectiveness of combinational treatment of GSI and radiation on glioma stem cells depends on the genetic background of the tumor. Specifically, PTENwt neurosphere cell lines are radioprotected under GSI treatment while PTEN-null neurosphere cell lines become more radiosensitive." @default.
• W398075761 created "2016-06-24" @default.
• W398075761 creator A5022091778 @default.
• W398075761 date "2014-01-01" @default.
• W398075761 modified "2023-09-27" @default.
• W398075761 title "The Combinational Effects of Gamma Secretase Inhibition and Radiation on the Cancer Stem Cell Population in Glioblastoma" @default.
• W398075761 hasPublicationYear "2014" @default.
• W398075761 type Work @default.
• W398075761 sameAs 398075761 @default.
• W398075761 citedByCount "1" @default.
• W398075761 countsByYear W3980757612016 @default.
• W398075761 crossrefType "journal-article" @default.
• W398075761 hasAuthorship W398075761A5022091778 @default.
• W398075761 hasConcept C121608353 @default.
• W398075761 hasConcept C185592680 @default.
• W398075761 hasConcept C2777609662 @default.
• W398075761 hasConcept C2780546549 @default.
• W398075761 hasConcept C28328180 @default.
• W398075761 hasConcept C2908647359 @default.
• W398075761 hasConcept C502942594 @default.
• W398075761 hasConcept C54355233 @default.
• W398075761 hasConcept C55427017 @default.
• W398075761 hasConcept C62478195 @default.
• W398075761 hasConcept C71924100 @default.
• W398075761 hasConcept C86554907 @default.
• W398075761 hasConcept C86803240 @default.
• W398075761 hasConcept C95444343 @default.
• W398075761 hasConcept C96232424 @default.
• W398075761 hasConcept C99454951 @default.
• W398075761 hasConceptScore W398075761C121608353 @default.
• W398075761 hasConceptScore W398075761C185592680 @default.
• W398075761 hasConceptScore W398075761C2777609662 @default.
• W398075761 hasConceptScore W398075761C2780546549 @default.
• W398075761 hasConceptScore W398075761C28328180 @default.
• W398075761 hasConceptScore W398075761C2908647359 @default.
• W398075761 hasConceptScore W398075761C502942594 @default.
• W398075761 hasConceptScore W398075761C54355233 @default.
• W398075761 hasConceptScore W398075761C55427017 @default.
• W398075761 hasConceptScore W398075761C62478195 @default.
• W398075761 hasConceptScore W398075761C71924100 @default.
• W398075761 hasConceptScore W398075761C86554907 @default.
• W398075761 hasConceptScore W398075761C86803240 @default.
• W398075761 hasConceptScore W398075761C95444343 @default.
• W398075761 hasConceptScore W398075761C96232424 @default.
• W398075761 hasConceptScore W398075761C99454951 @default.
• W398075761 hasLocation W3980757611 @default.
• W398075761 hasOpenAccess W398075761 @default.
• W398075761 hasPrimaryLocation W3980757611 @default.
• W398075761 hasRelatedWork W1487697307 @default.
• W398075761 hasRelatedWork W1963554305 @default.
• W398075761 hasRelatedWork W1984244761 @default.
• W398075761 hasRelatedWork W2037306308 @default.
• W398075761 hasRelatedWork W2040538271 @default.
• W398075761 hasRelatedWork W2104902048 @default.
• W398075761 hasRelatedWork W2147860834 @default.
• W398075761 hasRelatedWork W2314126010 @default.
• W398075761 hasRelatedWork W2315212357 @default.
• W398075761 hasRelatedWork W2340034170 @default.
• W398075761 hasRelatedWork W2461661219 @default.
• W398075761 hasRelatedWork W2520598456 @default.
• W398075761 hasRelatedWork W2550451908 @default.
• W398075761 hasRelatedWork W2795827433 @default.
• W398075761 hasRelatedWork W2811282511 @default.
• W398075761 hasRelatedWork W2903490238 @default.
• W398075761 hasRelatedWork W3033922807 @default.
• W398075761 hasRelatedWork W3037920123 @default.
• W398075761 hasRelatedWork W3159488815 @default.
• W398075761 hasRelatedWork W3186014957 @default.
• W398075761 isParatext "false" @default.
• W398075761 isRetracted "false" @default.
• W398075761 magId "398075761" @default.
• W398075761 workType "article" @default.