Promising targets in renal cell cancer: Met and ron-beta

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 20119-20119
Author(s):  
J. J. Lambea ◽  
I. Alvarez ◽  
R. Lastra ◽  
M. Ortega ◽  
E. Aguirre ◽  
...  

20119 Background: The activation of Tyrosin Kinase Receptors (RTKs) produces several effects about cellular response. These are membrane receptors that bind differentiation signals, grow factors and cellular mediators. The interaction with their ligand causes the phosphorilation and internalization in the endosome. By a metabolic way, these receptors are degradated into the proteasome to small peptides that are expressed over the cellular surface joined to MHC class I mollecules, getting a better immunogenic recognition of the tumor cells. It is known that the bigger expression of the tyrosin kinase receptors in tumors is associated with an aggressive phenotype. For example overexpression of ephA2 or EGFR. Our study is based in the demostration of the overexpression of other receptors in renal cell cancer, a tumour with a disappointing response with treatment in advanced stages. On this way we can use them as targets for monoclonal antibodies and for citotoxic lymphocites CD8 stimulated that will join to peptides presented in MHC class I after the proteasomic degradation. Methods: We use Western-Blot for identifying the overexpressed RTKs in relation to normal tissue and as a reference the expression of beta-actin, that is present in every cells. The cells are from 5 murine renal cell cancer lines, (thanks to Hillman Cancer Center Institute, University of Pittsburgh. Pennsylvania. USA). The control is a murine cell line that is very similar to normal renal tissue (HK). We calculate the ratio of expression compared with the expression of normal tissue with an statistical analysis. Results: HER-2, VEGFR-2, Met, Ron-beta are overexpresed in renal cell cancer in a murine model, as EGFR (epidermic growing factor receptor). Conclusions: Met may be excellent therapeutic and inmunologic target and in selected cases of renal cell cancer. It’s known that EGFR and VEGFR are also good targets. Future research about these targets will get new options of combined immunotherapy (vaccines and monoclonal antibodies). No significant financial relationships to disclose.

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4606-4606
Author(s):  
G. Hennig ◽  
H. Paus ◽  
D. Atkins ◽  
S. Störkel

4606 Background: It would be a substantial progress if gene expression of tumor markers could be accurately analyzed on RNA isolated from formalin fixed paraffin-embedded (FFPE) tumor tissue which is routinely collected. To prove equivalence between fresh frozen and archived FFPE tissue RNA profiles, we quantified 12 different genes with kinetic RT-PCR in renal tumor and paired adjacent normal tissue archived for 8–14 years. Methods: We had access to a set of 32 clear cell renal cell cancers and its adjacent normal tissue (HELIOS Clinic, Wuppertal). Each sample existed as a FFPE tissue block and as paired fresh frozen tissue both stored over 8–14 years at RT or -80oC, respectively. RNA from FFPE tissue was isolated with a Bayer HealthCare internal silica bead-based isolation method. Each sample was analyzed with kinetic one-step RT-PCR for the gene expression of 3 housekeepers (RPL37A, GAPDH, CD63) and 9 candidate genes (EGFR, Her2/neu, Her3, Her4, EGF, TGFα, NRG1, HIF1α, VEGFα). Results: The comparative FFPE/fresh frozen expression data showed a good correlation over all data points (r = 0.87 for Ct values) and the tumor specific up- and down regulation of EGFR family genes and its ligands could be detected in both tissue types equally. We could clearly demonstrate the tumor specific up-regulation of EGFR (2-fold), TGFα (2-fold), VEGFα (4-fold) and down-regulation of EGF (60-fold), Her2/neu (4-fold), Her3 (2-fold) and Her4 (30-fold) in renal cell cancer for both tissue entities (fixed and fresh frozen). In addition a 3-dimensional Principal Component Analysis completely separated the renal tumor population from paired normal tissue in both tissue entities based on the differential gene expression. Conclusions: Here we demonstrate that a small set of genes from the EGFR family and their ligands is specifically up-/down-regulated in renal cell cancer tissue and therefore can be clearly distinguished from normal renal tissue. Furthermore, these data prove that the internal Bayer HealthCare isolation/kinetic RT-PCR detection protocol for RNA from FFPE tissue allows accurate retrospective expression profiling and validation of marker panels in archived tissue material stored for more than a decade. [Table: see text]


BMC Cancer ◽  
2008 ◽  
Vol 8 (1) ◽  
Author(s):  
Florian R Fritzsche ◽  
Wilko Weichert ◽  
Annika Röske ◽  
Volker Gekeler ◽  
Thomas Beckers ◽  
...  

2005 ◽  
Vol 173 (4S) ◽  
pp. 175-175
Author(s):  
Axel S. Merseburger ◽  
Joerg Hennenlotter ◽  
Perikles Simon ◽  
Marcus Horstmann ◽  
Arnulf Stenzl ◽  
...  

2005 ◽  
Vol 173 (4S) ◽  
pp. 178-178
Author(s):  
Stephen O. Ikuerowo ◽  
Stefan A. Machtens ◽  
Markus A. Kuczyk ◽  
Udo Jonas ◽  
Juergen Serth

2005 ◽  
Vol 173 (4S) ◽  
pp. 99-99 ◽  
Author(s):  
Marcus Horstmann ◽  
Axel S. Merseburger ◽  
Markus A. Kuczyk ◽  
Arnulf Stenzl ◽  
Karl-Horst Bichler ◽  
...  

1998 ◽  
Vol 6 (1) ◽  
pp. 51-72
Author(s):  
Allan J. Pantuck ◽  
Kenneth B. Cummings

2006 ◽  
Vol 37 (S 1) ◽  
Author(s):  
J Jones ◽  
H Otu ◽  
D Spentzos ◽  
S Kolia ◽  
R Blaheta ◽  
...  

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