Tubulocystic renal cell carcinoma: is there a rational reason for targeted therapy using angiogenic inhibition? Analysis of seven cases
Jazyk angličtina Země Německo Médium print-electronic
Typ dokumentu kazuistiky, časopisecké články, práce podpořená grantem
- MeSH
- cílená molekulární terapie metody MeSH
- dospělí MeSH
- faktor 1 indukovatelný hypoxií - podjednotka alfa metabolismus MeSH
- fosforylace MeSH
- inhibitory angiogeneze farmakologie terapeutické užití MeSH
- karcinom z renálních buněk krevní zásobení farmakoterapie metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorový supresorový protein VHL metabolismus MeSH
- nádory ledvin krevní zásobení farmakoterapie metabolismus MeSH
- patologická angiogeneze farmakoterapie genetika MeSH
- senioři MeSH
- signální transdukce účinky léků genetika MeSH
- TOR serin-threoninkinasy metabolismus MeSH
- transkripční faktory bHLH metabolismus MeSH
- vaskulární endoteliální růstový faktor A metabolismus MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
- Názvy látek
- endothelial PAS domain-containing protein 1 MeSH Prohlížeč
- faktor 1 indukovatelný hypoxií - podjednotka alfa MeSH
- HIF1A protein, human MeSH Prohlížeč
- inhibitory angiogeneze MeSH
- MTOR protein, human MeSH Prohlížeč
- nádorový supresorový protein VHL MeSH
- TOR serin-threoninkinasy MeSH
- transkripční faktory bHLH MeSH
- vaskulární endoteliální růstový faktor A MeSH
- VEGFA protein, human MeSH Prohlížeč
- VHL protein, human MeSH Prohlížeč
Generally, patients with renal cell carcinoma (RCC) are viewed as potential candidates for antiangiogenic targeted therapy. Tubulocystic RCC (TCRC) is a recently described entity which may behave aggressively, and the rationale for antiangiogenic therapy in this group of renal tumors has yet to be determined. Seven TCRCs and five non-tumor tissue samples from seven patients were subjected to relative expression analysis of mRNA levels of 16 genes involved in three angiogenic signal pathways: (1) VHL/HIF, (2) RTK/mitogen-activated protein kinase (MAPK), and (3) PI3K/Akt/mTOR. Two of them, pathways (2) and (3), are often targeted by antiangiogenic agents. We also determined the mutation and methylation status of the VHL gene. Finally, the levels of vascular endothelial growth factor A (VEGFA), HIF-1α, HIF-2α proteins, and phosphorylated mTOR protein were also determined. The comparison of tumor and control samples revealed no changes of mRNA levels of the following genes: VHL, HIF-1α, HIF-2α, PTEN, Akt2, Akt3, mTOR, VEGFA, KDR, HRas, C-Jun, EGFR, and FGF2. Significantly elevated mRNA level of TP53 was found, while the mRNA levels of FLT1 and C-FOS were reduced in tumor samples. No mutations or methylation in the VHL gene were found. Changes in levels of studied proteins VEGFA, HIF-1α, HIF-2α, and increased phosphorylation of mTOR protein were not found. Three studied angiogenic pathways (VHL/HIF, RTK/MAPK, and PI3K/Akt/mTOR) seem not to be upregulated in TCRC samples, so there appears to be no rationale for a general recommendation of antiangiogenic targeted therapeutic protocols for patients with these tumors.
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