Rostlinné nukleasy ze skupiny nukleasa / (E.C.3.1.30.1) jsou enzymy schopné štěpit jednořetězcovou RNA a DNA a tudíž nejsou specifické k cukerné složce nukleové kyseliny. Najde se mnoho dalších nukleových kyselin, které mohou sloužit jako substráty, např. polymery obsahující jednu bázi (poly(C), poly(A), poly(U) atd.). Někteří členové této skupiny efektivně štěpí i dvouřetězcovou DNA a RNA. Tato supstratová nespecificita dává prostor pro různé působení nukleas uvnitř nádorové buňky, jehož výsledkem bude buněčná smrt.
Plant nucleases from nuclease / family (E.C.3.1.30.1) cleave both single-stranded DNA and RNA, therefore they are called sugar nonspecific nucleases. Moreover, some other molecules are cleavable by these nucleases, such as poly(C), poly(A), poly(U) etc. Some members of this family effectively cleave also both double-stranded DNA and RNA. This enzyme non-specificity leads to a degradation of various target molecules inside a tumor cell, resulting in a cell death.
UNLABELLED: Chemotherapy is an important modality of treatment for non-small cell lung cancer (NSCLC). Recent studies have shown that assessment of predictive molecular markers could be helpful for estimation of the response rate to chemotherapy. The aim of our study was to assess the relation of mRNA levels of DNA repair genes excision repair cross-complementary group 1 (ERCC1), ribonucleotide reductase subunit M1 (RRM1) and breast cancer 1 (BRCA1), in surgically-resected tumor tissues from patients who underwent adjuvant chemotherapy, to the disease-free interval (DFI) and overall survival (OS). We investigated if potential residual tumor cells after resection reflect properties of the primary tumor and response to chemotherapy according to the level of predictive markers with respect to current knowledge. PATIENTS AND METHODS: We studied a group of 90 patients with NSCLC who had undergone curative lung resection; 59 of them were subsequently treated with adjuvant chemotherapy, DFI and OS were evaluated only in this subgroup. Quantitative estimation of mRNA of selected genes in paired (tumor and control)-lung tissue samples was performed by real-time reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: We found a significantly lower mRNA expression of ERCC1 (p<0.001) and RRM1 (p=0.023) in NSCLC tumor tissues compared to normal lung tissues. Comparing expression in histological subtypes, we recorded higher mRNA expression of ERCC1 (p=0.021), RRM1 (p=0.011) and BRCA1 (p=0.011) in adenocarcinoma than in squamous cell carcinoma (SCC). Differences in DFI and OS were found only in specific subgroups according to tumor type and stage. We found longer OS for patients with adenocarcinoma with higher expression of the RRM1 mRNA (p=0.002), and for patients with SCC with higher expression of the BRCA1 mRNA (p=0.041). In patients with NSCLC of stage III, we found longer DFI in those with higher expression of RRM1 (p=0.004) and ERCC1 (p=0.038). CONCLUSION: Patients who had been treated with adjuvant chemotherapy and had shown lower expression of repair genes had adverse prognosis. We observed that the assessment of DNA repair gene level in primary tumors treated by surgical resection had prognostic significance and did not predict response to adjuvant chemotherapy.
- MeSH
- DNA vazebné proteiny analýza biosyntéza MeSH
- endonukleasy analýza biosyntéza MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- lidé MeSH
- messenger RNA analýza MeSH
- nádorové biomarkery analýza MeSH
- nádorové supresorové proteiny analýza biosyntéza MeSH
- nádory plic metabolismus mortalita patologie MeSH
- nemalobuněčný karcinom plic metabolismus mortalita patologie MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- prognóza MeSH
- proporcionální rizikové modely MeSH
- protein BRCA1 analýza biosyntéza MeSH
- protokoly protinádorové kombinované chemoterapie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- staging nádorů MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
