Nejvíce citovaný článek - PubMed ID 19469651
The Role of PPARs in MDR - a lesson from embryonic development
Embryonic and tumour cells are able to protect themselves against various harmful compounds. In human pathology, this phenomenon exists in the form of multidrug resistance (MDR) that significantly deteriorates success of anticancer treatment. Cytochromes P450 (CYPs) play one of the key roles in the xenobiotic metabolism. CYP expression could contribute to resistance of cancer cells to chemotherapy. CYP epoxygenases (CYP2C and CYP2J) metabolize about 20% of clinically important drugs. Besides of drug metabolism, CYP epoxygenases and their metabolites play important role in embryos, normal body function, and tumors. They participate in angiogenesis, mitogenesis, and cell signaling. It was found that CYP epoxygenases are affected by peroxisome proliferator-activated receptor α (PPARα). Based on the results of current studies, we assume that PPARs ligands may regulate CYP2C and CYP2J and in some extent they may contribute to overcoming of MDR in patients with different types of tumours.
- MeSH
- biologické modely MeSH
- chemorezistence * MeSH
- lidé MeSH
- mnohočetná léková rezistence * MeSH
- receptory aktivované proliferátory peroxizomů metabolismus MeSH
- systém (enzymů) cytochromů P-450 metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- receptory aktivované proliferátory peroxizomů MeSH
- systém (enzymů) cytochromů P-450 MeSH
Three ABC transporters (MDR1, MRP1, BCRP), belonging to the family of multidrug resistance (MDR) proteins, play a crucial role in the protection mechanisms during embryogenesis and mediate drug resistance in cancer cells. The distribution of these transporters in the series of human embryonal/fetal intestine, liver and kidneys of various stages of intrauterine development (IUD) by indirect two-step immunohistochemical method was investigated. The organ- and age-specific expression patterns of these transporters were depicted and compared with the expression in adult organs. The evaluation of intestine and liver samples demonstrate differences in expression pattern of ABC transporters during IUD. On the contrary, in kidneys the age-specific localization was not observed. However, the increasing positivity from the kidney surface towards deeper, more differentiated parts was found. Hopefully, our study may contribute to elucidation of the role of multidrug resistance (MDR) pathways during IUD in man.
- MeSH
- ABC transportéry biosyntéza genetika metabolismus MeSH
- embryonální vývoj genetika fyziologie MeSH
- exprese genu MeSH
- játra embryologie MeSH
- ledviny embryologie MeSH
- lidé MeSH
- mnohočetná léková rezistence MeSH
- P-glykoproteiny biosyntéza genetika metabolismus MeSH
- střeva embryologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- ABC transportéry MeSH
- P-glykoproteiny MeSH