onr:"20186294"
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| Fältnamn | Indikatorer | Metadata |
|---|---|---|
| 000 | 04180naa a22005413a 4500 | |
| 001 | 20186294 | |
| 003 | SE-LIBR | |
| 005 | 20170322161326.0 | |
| 007 | cr|||||||||||| | |
| 008 | 170322s2015 sw |||| o |||| ||eng c | |
| 024 | 7 | a http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-2522302 uri |
| 024 | 7 | a urn:nbn:se:uu:diva-2522302 urn |
| 024 | 7 | a 10.1371/journal.pone.01195552 doi |
| 040 | a S | |
| 041 | 0 | a eng |
| 042 | 9 EPLK | |
| 100 | 1 | a Bogaerts, Eliene4 aut |
| 245 | 1 0 | a Time-Dependent Effect of Hypoxia on Tumor Progression and Liver Progenitor Cell Markers in Primary Liver Tumorsh [Elektronisk resurs] |
| 260 | c 2015 | |
| 500 | a Published | |
| 506 | 0 | a gratis |
| 520 | a Background & Aims Expression of liver progenitor cell (LPC) characteristics has been proposed as a negative prognostic marker in primary liver tumors. Hypoxia has been linked to activation of the Notch pathway which is responsible for activation and proliferation of LPCs and hypoxia- induced LPC activation has been shown in hepatocellular carcinoma. Our aim was to elucidate the time-dependent effects of hypoxia on the LPC niche in hepatocellular carcinoma which could aid in determining a safe time frame for use of hypoxia inducing therapies. Methods We used dimethyloxaloylglycine to mimic a hypoxic reaction in mice by stabilizing hypoxia-inducible factor 1 alpha at three distinct time points in diethylnitrosamine induced hepatocarcinogenesis. LPC, metastasis and Notch pathway markers were determined by quantitative PCR and (immune) histochemistry (heamatoxillin-eosin, reticulin, Sirius red and cytokeratin 19 staining). Results Activating the hypoxia inducible pathway early in hepatocarcinogenesis resulted in an increased incidence of both cholangioma and hepatocellular lesions, associated with high expression of LPC, metastatic and Notch pathway markers. Adversely, activating the hypoxic response during tumor development resulted in decreased incidence of hepatocellular lesions and increased cholangioma incidence, with an unaltered gene expression profile of LPC-, Notch pathway-and metastatic markers. A hypoxic insult at advanced stages of hepatocarcinogenesis severely increased the expression of LPC characteristics, however without increased expression of actors of the Notch pathway and metastatic markers and minor changes in incidence of hepatocellular and cholangioma lesions. Conclusion Our results indicate that increased hypoxia at the onset of tumor development has detrimental effects on tumor progression; patients with HCC developed in a background of fibrosis/cirrhosis might therefore represent a more difficult treatment group. In contrast, hypoxia during tumor development appears to favor tumor outcome, highlighting the importance of early detection. Finally, hypoxia in advanced stages resulted in increased expression of LPC characteristics indicating poor outcome. | |
| 650 | 7 | a Medical and Health Sciences2 hsv |
| 650 | 7 | a Clinical Medicine2 hsv |
| 650 | 7 | a Cancer and Oncology2 hsv |
| 650 | 7 | a Medicin och hälsovetenskap2 hsv |
| 650 | 7 | a Klinisk medicin2 hsv |
| 650 | 7 | a Cancer och onkologi2 hsv |
| 700 | 1 | a Heindryckx, Femke4 aut |
| 700 | 1 | a Devisscher, Lindsey4 aut |
| 700 | 1 | a Paridaens, Annelies4 aut |
| 700 | 1 | a Vandewynckel, Yves-Paul4 aut |
| 700 | 1 | a Van den Bussche, Anja4 aut |
| 700 | 1 | a Verhelst, Xavier4 aut |
| 700 | 1 | a Libbrecht, Louis4 aut |
| 700 | 1 | a van Grunsven, Leo A.4 aut |
| 700 | 1 | a Geerts, Anja4 aut |
| 700 | 1 | a Van Vlierberghe, Hans4 aut |
| 710 | 1 2 | a Uppsala universitetb Medicinska och farmaceutiska vetenskapsområdet4 pbl |
| 772 | 1 8 | i channel recordw 19753896 |
| 773 | 0 8 | i Värdpublikationt PLoS ONEg 10:3x 1932-6203 |
| 856 | 4 0 | u http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-252230 |
| 856 | 4 0 | u http://dx.doi.org/10.1371/journal.pone.0119555 |
| 856 | 4 0 | u http://uu.diva-portal.org/smash/get/diva2:810037/FULLTEXT01 |
| 841 | 5 APISa x ab 170322||0000|||||001||||||000000e 1 | |
| 024 | 7 | 5 APISa urn:nbn:se:uu:diva-2522302 urn |
| 852 | 5 APISb APIS | |
| 856 | 4 0 | 5 APISu http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-252230 |
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