Examinando por Autor "Borrero-Palacios, Aurea"

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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.
DEK is a potential marker for aggressive phenotype and irinotecan-based therapy response in metastatic colorectal cancer
(Springer-Nature, 2014-12-16) Martínez-Useros, Javier; Rodríguez-Remírez, Maria; Borrero-Palacios, Aurea; Moreno, Irene; Cebrian, Arancha; Gomez del Pulgar, Teresa; del Puerto-Nevado, Laura; Vega-Bravo, Ricardo; Puime-Otin, Alberto; Perez, Nuria; Zazo, Sandra; Senin, Clara; Fernández-Aceñero, María Jesús; Soengas, Marisol; Rojo, Federico; García-Foncillas, Jesus
Background: DEK is a transcription factor involved in stabilization of heterochromatin and cruciform structures. It plays an important role in development and progression of different types of cancer. This study aims to analyze the role of DEK in metastatic colorectal cancer. Methods: Baseline DEK expression was firstly quantified in 9 colorectal cell lines and normal mucosa by WB. SiRNA-mediated DEK inhibition was carried out for transient DEK silencing in DLD1 and SW620 to dissect its role in colorectal cancer aggressiveness. Irinotecan response assays were performed with SN38 over 24 hours and apoptosis was quantified by flow cytometry. Ex-vivo assay was carried out with 3 fresh tumour tissues taken from surgical resection and treated with SN38 for 24 hours. DEK expression was determined by immunohistochemistry in 67 formalin-fixed paraffin-embedded tumour samples from metastatic colorectal cancer patients treated with irinotecan-based therapy as first-line treatment. Results: The DEK oncogene is overexpressed in all colorectal cancer cell lines. Knock-down of DEK on DLD1 and SW620 cell lines decreased cell migration and increased irinotecan-induced apoptosis. In addition, low DEK expression level predicted irinotecan-based chemotherapy response in metastatic colorectal cancer patients with KRAS wild-type. Conclusions: These data suggest DEK overexpression as a crucial event for the emergence of an aggressive phenotype in colorectal cancer and its potential role as biomarker for irinotecan response in those patients with KRAS wild-type status.
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.
UNR/CDSE1 expression as prognosis biomarker in resectable pancreatic ductal adenocarcinoma patients: A proof-of-concept
(PLOS, 2017-08-01) Martinez-Useros, Javier; Georgiev-Hristov, Tihomir; Fernández-Aceñero, María Jesús; Borrero-Palacios, Aurea; Indacochea, Alberto; Guerrero, Santiago; Li, Weiyao; Cebrian, Arancha; Gomez del Pulgar, Teresa; Puime-Otin, Alberto; del Puerto-Nevado, Laura; Rodríguez-Remírez, Maria; Perez, Nuria; Celdrán, Ángel; Gebauer, Fatima; García-Foncillas, Jesus
Pancreatic ductal adenocarcinoma is an aggressive form of pancreatic cancer and the fourth leading cause of cancer-related death. When possible, curative approaches are based on surgical resection, though not every patient is a candidate for surgery. There are clinical guidelines for the management of these patients that offer different treatment options depending on the clinical and pathologic characteristics. However, the survival rates seen in this kind of patients are still low. The CDSE1 gene is located upstream of NRAS and encodes an RNA-binding protein termed UNR. The aim of this study was to analyze UNR expression and its correlation with outcome in patients with resectable pancreatic ductal adenocarcinoma (PDAC). For this, samples from resectable PDAC patients who underwent duodenopancreatectomy were used to evaluate UNR protein expression by immunohistochemistry using a tissue microarray. Here, we observed that low UNR expression was significantly associated with shorter progression-free survival after surgery (P = 0.010). Moreover, this prognostic marker remained significant after Cox proportional hazards model (P = 0.036). We further studied the role of CDSE1 expression in patient's prognosis using data from public repositories (GEO and TGCA), confirming our results. Interestingly, CDSE1 expression correlated with that of genes characteristic of an immunogenic molecular subtype of pancreatic cancer. Based on these findings, UNR may be considered a potential prognostic biomarker for resectable PDAC and may serve to guide subsequent adjuvant treatment decisions.