Examinando por Autor "Rincón, Raul"

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Active angiogenesis in metastatic renal cell carcinoma predicts clinical benefit to sunitinib-based therapy
(Nature Publishing Group, 2014-05-27) del Puerto-Nevado, Laura; Rojo, Federico; Zazo, Sandra; Carames, Cristina; Rubio, Gustavo; Vega, Ricardo; Chamizo, Cristina; Casado, Victoria; Martinez-Useros, Javier; Rincón, Raul; Rodríguez-Remírez, Maria; Borrero-Palacios, Aurea; Cristobal, Ion; Madoz-Gúrpide, Juan; Aguilera, Oscar; García-Foncillas, Jesus
Background: Sunitinib represents a widely used therapy for metastatic renal cell carcinoma patients. Even so, there is a group of patients who show toxicity without clinical benefit. In this work, we have analysed pivotal molecular targets involved in angiogenesis (vascular endothelial growth factor (VEGF)-A, VEGF receptor 2 (KDR), phosphorylated (p)KDR and microvascular density (MVD)) to test their potential value as predictive biomarkers of clinical benefit in sunitinib-treated renal cell carcinoma patients. Methods: Vascular endothelial growth factor-A, KDR and pKDR-Y1775 expression as well as CD31, for MVD visualisation, were determined by immunohistochemistry in 48 renal cell carcinoma patients, including 23 metastatic cases treated with sunitinib. Threshold was defined for each biomarker, and univariate and multivariate analyses for progression-free survival (PFS) and overall survival (OS) were carried out. Results: The HistoScore mean value obtained for VEGF-A was 121.6 (range, 10–300); for KDR 258.5 (range, 150–300); for pKDRY1775 10.8 (range, 0–65) and the mean value of CD31-positive structures for MVD visualisation was 49 (range, 10–126). Statistical differences for PFS (P = 0.01) and OS (P = 0.007) were observed for pKDR-Y1775 in sunitinib-treated patients. Importantly, pKDRY1775 expression remained significant after multivariate Cox analysis for PFS (P = 0.01; HR: 5.35, 95% CI, 1.49–19.13) and for OS (P = 0.02; HR: 5.13, 95% CI, 1.25–21.05). Conclusions: Our results suggest that the expression of phosphorylated (i.e., activated) KDR in tumour stroma might be used as predictive biomarker for the clinical outcome in renal cell carcinoma first-line sunitinib-treated patients.
UNR/ CSDE1 Expression Is Critical to Maintain Invasive Phenotype of Colorectal Cancer through Regulation of c-MYC and Epithelial-to-Mesenchymal Transition
(MDPI, 2019-04-25) Martinez-Useros, Javier; Garcia-Carbonero, Nuria; Li, Weiyao; Fernández-Aceñero, María Jesús; Cristobal, Ion; Rincón, Raul; Rodríguez-Remírez, Maria; Borrero-Palacios, Aurea; García-Foncillas, Jesus
CSDE1 (cold shock domain containing E1) gene is located upstream of the N-RAS locus, and codes for an RNA-binding protein named Upstream of N-Ras (UNR). In cancer, CSDE1 has been shown to regulate c-Fos, c-Myc, Pten, Rac1, or Vimentin. UNR/CSDE1 has been studied in breast, melanoma, pancreatic and prostate cancer. Then, the aim of this study is to evaluate the role of CSDE1/UNR in colorectal cancer progression and maintenance of aggressive phenotype. We firstly evaluated UNR/CSDE1 expression in human colon cancer derived cell lines and patient samples. Subsequently, we performed functional experiments by UNR/CSDE1 downregulation. We also evaluated UNR/CSDE1 prognostic relevance in two independent sets of patients. Not only was UNR/CSDE1 expression higher in tumor samples compared to untransformed samples, but also in colonospheres and metastatic origin cell lines than their parental and primary cell lines, respectively. Downregulation of UNR/CSDE1 reduced cell viability and migration throughout a restrain of epithelial-to-mesenchymal transition and increases sensitivity to apoptosis. Interestingly, high UNR/CSDE1 expression was associated with poor prognosis and correlated positively with c-MYC expression in colorectal cancer samples and cell lines. Here, we show for the first time compelling data reporting the oncogenic role of UNR/CSDE1 in human colorectal cancer.