About: Tubulocystic renal cell carcinoma: is there a rational reason for targeted therapy using angiogenic inhibition? Analysis of seven cases     Goto   Sponge   NotDistinct   Permalink

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  • 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 CFOS 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.
  • 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 CFOS 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. (en)
Title
  • Tubulocystic renal cell carcinoma: is there a rational reason for targeted therapy using angiogenic inhibition? Analysis of seven cases
  • Tubulocystic renal cell carcinoma: is there a rational reason for targeted therapy using angiogenic inhibition? Analysis of seven cases (en)
skos:prefLabel
  • Tubulocystic renal cell carcinoma: is there a rational reason for targeted therapy using angiogenic inhibition? Analysis of seven cases
  • Tubulocystic renal cell carcinoma: is there a rational reason for targeted therapy using angiogenic inhibition? Analysis of seven cases (en)
skos:notation
  • RIV/00669806:_____/13:10134274!RIV14-MZ0-00669806
http://linked.open...avai/predkladatel
http://linked.open...avai/riv/aktivita
http://linked.open...avai/riv/aktivity
  • I, P(NT12010)
http://linked.open...iv/cisloPeriodika
  • 2
http://linked.open...vai/riv/dodaniDat
http://linked.open...aciTvurceVysledku
http://linked.open.../riv/druhVysledku
http://linked.open...iv/duvernostUdaju
http://linked.open...titaPredkladatele
http://linked.open...dnocenehoVysledku
  • 111995
http://linked.open...ai/riv/idVysledku
  • RIV/00669806:_____/13:10134274
http://linked.open...riv/jazykVysledku
http://linked.open.../riv/klicovaSlova
  • mRNA expression . Protein expression; Angiogenic pathways; Antiangiogenic targeted therapy; Tubulocystic renal cell carcinoma (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • DE - Spolková republika Německo
http://linked.open...ontrolniKodProRIV
  • [CC2629C541F6]
http://linked.open...i/riv/nazevZdroje
  • Virchows Archiv : an international journal of pathology
http://linked.open...in/vavai/riv/obor
http://linked.open...ichTvurcuVysledku
http://linked.open...cetTvurcuVysledku
http://linked.open...vavai/riv/projekt
http://linked.open...UplatneniVysledku
http://linked.open...v/svazekPeriodika
  • 462
http://linked.open...iv/tvurceVysledku
  • Hes, Ondřej
  • Hora, Milan
  • Korabečná, Marie
  • Michal, Michal
  • Petersson, Fredrik
  • Trávníček, Ivan
  • Vaněček, Tomáš
  • Stehlík, Jan
  • Martínek, Petr
  • Steiner, Petr
http://linked.open...ain/vavai/riv/wos
  • 000314724300007
issn
  • 0945-6317
number of pages
http://bibframe.org/vocab/doi
  • 10.1007/s00428-012-1367-z
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