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  • Drug resistance is the major obstacle to successful cancer therapy. Our study focuses on resistance to Aurora kinase inhibitors tested as anti-cancer drugs in clinical trials. We have used 2D electrophoresis in the pH ranges of 4? 7 and 6?11 followed by protein identification using MALDITOF/ TOF to compare the protein composition of HCT116 colon cancer cells either sensitive to CYC116 and ZM447439 inhibitors or resistant toward these drugs. The analysis also included p53+/+ and p53?/? phenotypes of HCT116 cells. Our findings demonstrate that platelet-activating factor acetylhydrolase and GTP-binding nuclear protein Ran contribute to the development of resistance to ZM447439 only where resistance is related to p53. On the other hand, serine hydroxymethyltransferase was found to promote the tumor growth in cells resistant to CYC116 without the influence of p53. Computer modeling of interaction networks highlighted a direct link of the p53-independent mechanism of resistance to CYC116 with autophagy. Importantly, serine hydroxymethyltransferase, serpin B5, and calretinin represent the target proteins that may help overcome resistance in combination therapies. In addition, serpin B5 and calretinin appear to be candidate biomarkers that may be accessible in patients for monitoring of cancer therapy with ease.
  • Drug resistance is the major obstacle to successful cancer therapy. Our study focuses on resistance to Aurora kinase inhibitors tested as anti-cancer drugs in clinical trials. We have used 2D electrophoresis in the pH ranges of 4? 7 and 6?11 followed by protein identification using MALDITOF/ TOF to compare the protein composition of HCT116 colon cancer cells either sensitive to CYC116 and ZM447439 inhibitors or resistant toward these drugs. The analysis also included p53+/+ and p53?/? phenotypes of HCT116 cells. Our findings demonstrate that platelet-activating factor acetylhydrolase and GTP-binding nuclear protein Ran contribute to the development of resistance to ZM447439 only where resistance is related to p53. On the other hand, serine hydroxymethyltransferase was found to promote the tumor growth in cells resistant to CYC116 without the influence of p53. Computer modeling of interaction networks highlighted a direct link of the p53-independent mechanism of resistance to CYC116 with autophagy. Importantly, serine hydroxymethyltransferase, serpin B5, and calretinin represent the target proteins that may help overcome resistance in combination therapies. In addition, serpin B5 and calretinin appear to be candidate biomarkers that may be accessible in patients for monitoring of cancer therapy with ease. (en)
Title
  • Cancer cell resistance to aurora kinase inhibitors: identification of novel targets for cancer therapy
  • Cancer cell resistance to aurora kinase inhibitors: identification of novel targets for cancer therapy (en)
skos:prefLabel
  • Cancer cell resistance to aurora kinase inhibitors: identification of novel targets for cancer therapy
  • Cancer cell resistance to aurora kinase inhibitors: identification of novel targets for cancer therapy (en)
skos:notation
  • RIV/61989592:15110/13:33143581!RIV14-MSM-15110___
http://linked.open...avai/riv/aktivita
http://linked.open...avai/riv/aktivity
  • I, P(ED0030/01/01), P(LC07017), S
http://linked.open...iv/cisloPeriodika
  • 1
http://linked.open...vai/riv/dodaniDat
http://linked.open...aciTvurceVysledku
http://linked.open.../riv/druhVysledku
http://linked.open...iv/duvernostUdaju
http://linked.open...titaPredkladatele
http://linked.open...dnocenehoVysledku
  • 64202
http://linked.open...ai/riv/idVysledku
  • RIV/61989592:15110/13:33143581
http://linked.open...riv/jazykVysledku
http://linked.open.../riv/klicovaSlova
  • calretinin; serpin B5; serine hydroxymethyltransferase; Ran; platelet-activating factor acetylhydrolase; autophagy; apoptosis; p53; resistance; Aurora kinase inhibitors (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • US - Spojené státy americké
http://linked.open...ontrolniKodProRIV
  • [976CE85E527C]
http://linked.open...i/riv/nazevZdroje
  • Journal of Proteome Research
http://linked.open...in/vavai/riv/obor
http://linked.open...ichTvurcuVysledku
http://linked.open...cetTvurcuVysledku
http://linked.open...vavai/riv/projekt
http://linked.open...UplatneniVysledku
http://linked.open...v/svazekPeriodika
  • 12
http://linked.open...iv/tvurceVysledku
  • Halada, Petr
  • Hajdúch, Marián
  • Hrabáková, Rita
  • Kovářová, Hana
  • Tylečková, Jiřina
  • Gadher, Suresh Jivan
  • Kollareddy, Madhusudhan Reddy
http://linked.open...ain/vavai/riv/wos
  • 000313156300046
issn
  • 1535-3893
number of pages
http://bibframe.org/vocab/doi
  • 10.1021/pr300819m
http://localhost/t...ganizacniJednotka
  • 15110
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