Esperanza Feijoó

Publications (6)46.97 Total impact

• Article: Therapeutic effect of a peptide inhibitor of TGF-β on pulmonary fibrosis.

  Laura Arribillaga, Javier Dotor, María Basagoiti, José Ignacio Riezu-Boj, Francisco Borrás-Cuesta, Juan José Lasarte, Pablo Sarobe, María Eugenia Cornet, Esperanza Feijoó
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  ABSTRACT: Pulmonary fibrosis encompasses several respiratory diseases characterized by epithelial cell injury, inflammation and fibrosis. Transforming growth factor (TGF)-β1 is one of the main profibrogenic cytokines involved in the pathogenesis of lung fibrosis. It induces fibroblast differentiation into myofibroblasts, which produce high levels of collagen and concomitantly loss of lung elasticity and reduction of the respiratory function. In the present study, we have investigated the effects of P17 (a TGF-β inhibitor peptide) on IMR-90 lung fibroblast differentiation in vitro, as well as on the inhibition of the development of bleomycin-induced pulmonary fibrosis in mice. It was found that in IMR-90 cells, P17 inhibited TGF-β1-induced expression of connective tissue growth factor and α-smooth muscle actin. In vivo, treatment of mice with P17 2days after bleomycin administration decreased lung fibrosis, areas of myofibroblast-like cells and lymphocyte infiltrate. P17 also reduced mRNA expression of collagen type I, fibronectin and the fibronectin splice isoform EDA in the lung, and increased the expression of IFN-γ mRNA. Finally, therapeutic treatment with P17 in mice with already established fibrosis was able to significantly attenuate the progression of lung fibrosis. These results suggest that P17 may be useful in the treatment of pulmonary fibrosis.
  Cytokine 03/2011; 53(3):327-33. · 3.02 Impact Factor
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  Available from: Fernando Aranda

  Article: Induction of monocyte chemoattractant protein-1 and interleukin-10 by TGFbeta1 in melanoma enhances tumor infiltration and immunosuppression.

  Nancy Díaz-Valdés, María Basagoiti, Javier Dotor, Fernando Aranda, Iñaki Monreal, José Ignacio Riezu-Boj, Francisco Borrás-Cuesta, Pablo Sarobe, Esperanza Feijoó
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  ABSTRACT: Melanoma progression is associated with the expression of different growth factors, cytokines, and chemokines. Because TGFβ1 is a pleiotropic cytokine involved not only in physiologic processes but also in cancer development, we analyzed in A375 human melanoma cells, the effect of TGFβ1 on monocyte chemoattractant protein-1 (MCP-1) and interleukin-10 (IL-10) expression, two known factors responsible for melanoma progression. TGFβ1 increased the expression of MCP-1 and IL-10 in A375 cells, an effect mediated by the cross-talk between Smad, PI3K (phosphoinositide 3-kinase)/AKT, and BRAF-MAPK (mitogen activated protein kinase) signaling pathways. Supernatants from TGFβ1-treated A375 cells enhanced MCP-1-dependent migration of monocytes, which, in turn, expressed high levels of TGF,β1, bFGF, and VEGF mRNA. Moreover, these supernatants also inhibited functional properties of dendritic cells through IL-10-dependent mechanisms. When using in vitro, the TGFβ1-blocking peptide P144, TGFβ1-dependent Smad3 phosphorylation, and expression of MCP-1 and IL-10 were inhibited. In vivo, treatment of A375 tumor-bearing athymic mice with P144 significantly reduced tumor growth, associated with a lower macrophage infiltrate and decreased intratumor MCP-1 and VEGF levels, as well as angiogenesis. Finally, in C57BL/6 mice with B16-OVA melanoma tumors, when administered with immunotherapy, P144 decreased tumor growth and intratumor IL-10 levels, linked to enhanced activation of dendritic cells and natural killer cells, as well as anti-OVA T-cell responses. These results show new effects of TGFβ1 on melanoma cells, which promote tumor progression and immunosuppression, strongly reinforcing the relevance of this cytokine as a molecular target in melanoma.
  Cancer Research 02/2011; 71(3):812-21. · 7.86 Impact Factor
• Article: Identification of peptide inhibitors of transforming growth factor beta 1 using a phage-displayed peptide library.

  Javier Dotor, Ana B López-Vázquez, Juan J Lasarte, Pablo Sarobe, Marta García-Granero, José I Riezu-Boj, Alfonso Martínez, Esperanza Feijoó, Jacinto López-Sagaseta, José Hermida, Jesús Prieto, Francisco Borrás-Cuesta
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  ABSTRACT: Pathologies such as liver fibrosis and scleroderma are characterized by harmful levels of transforming growth factor beta 1 (TGFbeta1). These levels could be neutralized if inhibitors of this cytokine were available. With this aim we searched for peptides with binding affinity for TGFbeta1 using a phage-displayed random 15-mer peptide library. Some peptides thus identified blocked activity of TGFbeta1 in vitro, as measured by their capacity to restore growth of Mv-1-Lu cells in presence of added TGFbeta1. Also, they inhibited TGFbeta1-dependent expression of collagen type I mRNA in liver of mice orally insulted with CCl(4). Intraperitoneal administration of 50 microg of peptide P17 (the most active 15-mer peptide, also referred to as P17(1-15)) inhibited expression of collagen type I mRNA by almost 100%. Interestingly, titration experiments showed that P17(1-12) (a peptide encompassing the first 12 amino acids of P17) was approximately four times more active than P17. These results suggest that both peptides, as well as others reported here, may be of therapeutic interest in processes requiring control of undesired high levels of TGFbeta1.
  Cytokine 09/2007; 39(2):106-15. · 3.02 Impact Factor
• Article: Dendritic cells delivered inside human carcinomas are sequestered by interleukin-8.

  Esperanza Feijoó, Carlos Alfaro, Guillermo Mazzolini, Patricia Serra, Iván Peñuelas, Ainhoa Arina, Eduardo Huarte, Iñigo Tirapu, Belén Palencia, Oihana Murillo, Juan Ruiz, Bruno Sangro, José A Richter, Jesús Prieto, Ignacio Melero
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  ABSTRACT: In the course of a clinical trial consisting of intratumoral injections of dendritic cells (DCs) transfected to produce interleukin-12, the use of (111)In-labeled tracing doses of DCs showed that most DCs remained inside tumor tissue, instead of migrating out. In search for factors that could explain this retention, it was found that tumors from patients suffering hepatocellular carcinoma, colorectal or pancreatic cancer were producing IL-8 and that this chemokine attracted monocyte-derived dendritic cells that uniformly express both IL-8 receptors CXCR1 and CXCR2. Accordingly, neutralizing antihuman IL-8 monoclonal antibodies blocked the chemotactic attraction of DCs by recombinant IL-8, as well as by the serum of the patients or culture supernatants of human colorectal carcinomas. In addition, tissue culture supernatants of colon carcinoma cells inhibited DC migration induced by MIP-3beta in an IL-8-dependent fashion. IL-8 production in malignant tissue and the responsiveness of DCs to IL-8 are a likely explanation of the clinical images, which suggest retention of DCs inside human malignant lesions. Impairment of DC migration toward lymphoid tissue could be involved in cancer immune evasion.
  International Journal of Cancer 09/2005; 116(2):275-81. · 5.44 Impact Factor
• Article: Intratumoral injection of dendritic cells engineered to secrete interleukin-12 by recombinant adenovirus in patients with metastatic gastrointestinal carcinomas.

  Guillermo Mazzolini, Carlos Alfaro, Bruno Sangro, Esperanza Feijoó, Juan Ruiz, Alberto Benito, Iñigo Tirapu, Ainhoa Arina, Josu Sola, Maite Herraiz, Felipe Lucena, Cristina Olagüe, José Subtil, Jorge Quiroga, Ignacio Herrero, Belén Sádaba, Maurizio Bendandi, Cheng Qian, Jesús Prieto, Ignacio Melero
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  ABSTRACT: To evaluate the feasibility and safety of intratumoral injection of autologous dendritic cells (DCs) transfected with an adenovirus encoding interleukin-12 genes (AFIL-12) for patients with metastatic gastrointestinal carcinomas. Secondarily, we have evaluated biologic effects and antitumoral activity. Seventeen patients with metastatic pancreatic (n = 3), colorectal (n = 5), or primary liver (n = 9) malignancies entered the study. DCs were generated from CD14+ monocytes from leukapheresis, cultured and transfected with AFIL-12 before administration. Doses from 10 x 10(6) to 50 x 10(6) cells were escalated in three cohorts of patients. Patients received up to three doses at 21-day intervals. Fifteen (88%) and 11 of 17 (65%) patients were assessable for toxicity and response, respectively. Intratumoral DC injections were mainly guided by ultrasound. Treatment was well tolerated. The most common side effects were lymphopenia, fever, and malaise. Interferon gamma and interleukin-6 serum concentrations were increased in 15 patients after each treatment, as well as peripheral blood natural killer activity in five patients. DC transfected with AFIL-12 stimulated a potent antibody response against adenoviral capsides. DC treatment induced a marked increase of infiltrating CD8+ T lymphocytes in three of 11 tumor biopsies analyzed. A partial response was observed in one patient with pancreatic carcinoma. Stable disease was observed in two patients and progression in eight patients, with two of the cases fast-progressing during treatment. Intratumoral injection of DC transfected with an adenovirus encoding interleukin-12 to patients with metastatic gastrointestinal malignancies is feasible and well tolerated. Further studies are necessary to define and increase clinical efficacy.
  Journal of Clinical Oncology 03/2005; 23(5):999-1010. · 18.37 Impact Factor
• Article: MAGE antigens: therapeutic targets in hepatocellular carcinoma?

  Pablo Sarobe, Esperanza Feijoó, Carlos Alfaro, Guillermo Mazzolini, Ignacio Melero
  Journal of Hepatology 02/2004; 40(1):155-8. · 9.26 Impact Factor