Id |
Subject |
Object |
Predicate |
Lexical cue |
T1 |
0-116 |
Sentence |
denotes |
Metallothionein-1 as a biomarker of altered redox metabolism in hepatocellular carcinoma cells exposed to sorafenib. |
T2 |
117-128 |
Sentence |
denotes |
BACKGROUND: |
T3 |
129-294 |
Sentence |
denotes |
Sorafenib, a kinase inhibitor active against various solid tumours, induces oxidative stress and ferroptosis, a new form of oxidative necrosis, in some cancer cells. |
T4 |
295-417 |
Sentence |
denotes |
Clinically-applicable biomarkers that reflect the impact of sorafenib on the redox metabolism of cancer cells are lacking. |
T5 |
418-426 |
Sentence |
denotes |
METHODS: |
T6 |
427-637 |
Sentence |
denotes |
We used gene expression microarrays, real-time PCR, immunoblot, protein-specific ELISA, and gene reporter constructs encoding the enzyme luciferase to study the response of a panel of cancer cells to sorafenib. |
T7 |
638-796 |
Sentence |
denotes |
Tumour explants prepared from surgical hepatocellular carcinoma (HCC) samples and serum samples obtained from HCC patients receiving sorafenib were also used. |
T8 |
797-805 |
Sentence |
denotes |
RESULTS: |
T9 |
806-926 |
Sentence |
denotes |
We observed that genes of the metallothionein-1 (MT1) family are induced in the HCC cell line Huh7 exposed to sorafenib. |
T10 |
927-1096 |
Sentence |
denotes |
Sorafenib increased the expression of MT1G mRNA in a panel of human cancer cells, an effect that was not observed with eight other clinically-approved kinase inhibitors. |
T11 |
1097-1375 |
Sentence |
denotes |
We identified the minimal region of the MT1G promoter that confers inducibility by sorafenib to a 133 base pair region containing an Anti-oxidant Response Element (ARE) and showed the essential role of the transcription factor NRF2 (Nuclear factor erythroid 2-Related Factor 2). |
T12 |
1376-1522 |
Sentence |
denotes |
We examined the clinical relevance of our findings by analysing the regulation of MT1G in five tumour explants prepared from surgical HCC samples. |
T13 |
1523-1692 |
Sentence |
denotes |
Finally, we showed that the protein levels of MT1 increase in the serum of some HCC patients receiving sorafenib, and found an association with reduced overall survival. |
T14 |
1693-1704 |
Sentence |
denotes |
CONCLUSION: |
T15 |
1705-1847 |
Sentence |
denotes |
These findings indicate that MT1 constitute a biomarker adapted for exploring the impact of sorafenib on the redox metabolism of cancer cells. |