BACKGROUND/AIM: Tumor biomarkers are used for diagnostics and follow-up monitoring of patients with non-small cell lung cancer (NSCLC). We focused on the predictive role of neuron-specific enolase (NSE) and thymidine [corrected] kinase (TK) in patients with advanced-stage NSCLC treated with epidermal growth factor tyrosine kinase inhibitors (EGFR-TKIs). PATIENTS AND METHODS: In a total of 163 patients with advanced-stage (IIIB or IV) NSCLC treated with EGFR-TKIs (erlotinib or gefitinib), pre-treatment levels of NSE and TK were measured. RESULTS: We observed significantly shorter progression-free (PFS) and overall survival (OS) in patients with high NSE levels (p=0.002; p=0.003) and also in those with high TK levels (p=0.026; p=0.020). The multivariate Cox proportional hazards model confirmed that high NSE is a strong independent predictive factor for short PFS (hazard ratio; HR=2.36; p=0.003). CONCLUSION: High pre-treatment serum levels of NSE is an independent biomarker predicting poor outcome of patients with NSCLC treated with EGFR-TKIs.
- MeSH
- antitumorózní látky terapeutické užití MeSH
- dospělí MeSH
- erbB receptory antagonisté a inhibitory MeSH
- fosfopyruváthydratasa metabolismus MeSH
- inhibitory proteinkinas terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory plic farmakoterapie enzymologie mortalita patologie MeSH
- nemalobuněčný karcinom plic farmakoterapie enzymologie mortalita patologie MeSH
- prognóza MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- staging nádorů MeSH
- thymidinkináza metabolismus MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Growth inhibition of the DNA virus vaccinia (VACV) by NO is known to occur at the level of DNA synthesis. This inhibition is partially reversed by addition of deoxyribonucleosides, suggesting that NO or NO-related species inhibit viral ribonucleotide reductase (RR). However, the effect of NO on VACV-encoded RR or other DNA-synthesizing enzymes has not been demonstrated. In order to study the effects of NO on VACV-encoded RR, DNA polymerase (DNA pol) and thymidine kinase (TK), we generated a VACV recombinant expressing murine macrophage iNOS under control of a VACV early/late promoter p7.5. Using this recombinant, we demonstrate that expression of iNOS and the resulting production of NO inhibit activity of the viral RR, but not of viral DNA pol and TK. This NO-mediated inhibition of viral RR occurred around the same time as the increase of ADP levels, while it preceded the block in VACV DNA synthesis and the decrease of ATP levels. In addition, we tested the effects of DPTA/NONOate on the growth of different VACV mutants. Fold-inhibition of the growth of VACV deletion mutant for TK was comparable to that of wild-type VACV. VACV containing amplification of the gene for the small subunit of RR appeared to be least sensitive to DPTA/NONOate, while VACV deletion mutant for the large subunit of RR was most sensitive. The results provide a direct evidence for NO-mediated inhibition of VACV-encoded RR.
- MeSH
- adenosindifosfát metabolismus MeSH
- adenosintrifosfát metabolismus MeSH
- alkeny metabolismus MeSH
- buněčné linie MeSH
- Cercopithecus aethiops MeSH
- DNA virů metabolismus MeSH
- DNA-dependentní DNA-polymerasy metabolismus MeSH
- financování organizované MeSH
- mutace MeSH
- myši MeSH
- oxid dusnatý metabolismus MeSH
- rekombinantní fúzní proteiny genetika metabolismus MeSH
- ribonukleotidreduktasy antagonisté a inhibitory metabolismus MeSH
- synthasa oxidu dusnatého, typ II genetika metabolismus MeSH
- thymidinkináza metabolismus MeSH
- virové proteiny antagonisté a inhibitory metabolismus MeSH
- virus vakcinie enzymologie metabolismus růst a vývoj MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- MeSH
- hepatektomie MeSH
- játra chirurgie metabolismus MeSH
- krysa rodu rattus MeSH
- ornithindekarboxylasa fyziologie metabolismus MeSH
- prolaktin metabolismus MeSH
- regenerace jater MeSH
- thymidinkináza fyziologie metabolismus MeSH
- trijodthyronin metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- MeSH
- atropin metabolismus MeSH
- epidermální růstový faktor metabolismus MeSH
- karbachol metabolismus MeSH
- krysa rodu rattus MeSH
- štítná žláza metabolismus růst a vývoj účinky léků MeSH
- techniky in vitro MeSH
- thymidinkináza fyziologie metabolismus účinky léků MeSH
- thyreotropin metabolismus MeSH
- vazoaktivní intestinální peptid metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- MeSH
- časové faktory MeSH
- erytrocyty imunologie MeSH
- fosfotransferasy metabolismus MeSH
- imunizace MeSH
- injekce intraperitoneální MeSH
- izotopy uhlíku MeSH
- myši MeSH
- ovce MeSH
- papírová chromatografie MeSH
- sérový albumin MeSH
- slezina enzymologie MeSH
- thymidin metabolismus MeSH
- thymidinkináza metabolismus MeSH
- tkáňové extrakty MeSH
- ultracentrifugace MeSH
- uridin metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
