Nanobioingeniería de sistemas terapéuticos y diagnósticos inteligentes

Lineas de Investigación

1. Desarrollo de terapias antitumorales inteligentes basadas en pares toxina-antitoxina.

2. Desarrollo de nanosistemas para la vehiculización dirigida de fármacos antitumorales y agentes de contraste in vivo.

3. Desarrollo de terapias antitumorales que actúen activando o inhibiendo las diferentes poblaciones celulares que conforman el microambiente inmune del tumor.

4. Búsqueda de factores/eventos biológicos predictivos de eventos clínicos (extensión de la enfermedad, marcadores de eficacia o toxicidad del tratamiento, marcadores de progresión/recidiva), especialmente en pacientes con cáncer sometidos a las nuevas terapias antitumorales de base inmunológica.



Publicaciones científicas

  • Todo
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Targeted cancer cell killing by highly selective miRNA-triggered activation of a prokaryotic toxin-antitoxin system.

Turnbull A, Bermejo-Rodríguez C, Preston MA, Garrido-Barros M, Pimentel B, de la Cueva-Méndez G.
ACS Synth Biol. 2019 Jul 26.

Although not evolved to function in eukaryotes, prokaryotic toxin Kid induces apoptosis in human cells, and this is avoided by co-expression of its neutralizing antitoxin, Kis. Inspired by the way Kid becomes active in bacterial cells we had previously engineered a synthetic toxin-antitoxin system bearing a Kis protein variant that is selectively degraded in cells expressing viral oncoprotein E6, thus achieving highly selective killing of cancer […]

Repurposing a Prokaryotic Toxin-Antitoxin System for the Selective Killing of Oncogenically Stressed Human Cells.

Preston MA, Pimentel B, Bermejo-Rodríguez C, Dionne I, Turnbull A, de la Cueva-Méndez G.
ACS Synth Biol. 2016 Jul 15;5(7):540-6.

Prokaryotes express intracellular toxins that pass unnoticed to carrying cells until coexpressed antitoxin partners are degraded in response to stress. Although not evolved to function in eukaryotes, one of these toxins, Kid, induces apoptosis in mammalian cells, an effect that is neutralized by its cognate antitoxin, Kis. Here we engineered this toxin-antitoxin pair to create a synthetic system that becomes active in human cells suffering a spec […]

‘Smartening’ anticancer therapeutic nanosystems using biomolecules.

Núñez-Lozano R, Cano M, Pimentel B, de la Cueva-Méndez G.
Curr Opin Biotechnol. 2015 Dec;35:135-40.

To be effective, anticancer agents must induce cell killing in a selective manner, something that is proving difficult to achieve. Drug delivery systems could help to solve problems associated with the lack of selectivity of classical chemotherapeutic agents. However, to realize this, such systems must overcome multiple physiological barriers. For instance, they must evade surveillance by the immune system, attach selectively to target cells, and […]

International Symposium: Trailblazing in Cancer Immunotherapy, October 29-31, 2017, Pamplona, Spain.

Berraondo P, Aznar MA, Perez-Ruiz E, Rodriguez-Ruiz ME, Castañon E, Perez-Gracia JL, Melero I.
Cancer Immunol Immunother. 2018 Nov;67(11):1809-1813.

[…]

Management of Hodgkin lymphoma in the era of brentuximab vedotin: real-world data from five European countries.

Collins GP, Rueda A, Salles G, von Tresckow B, Zaja F.
Leuk Lymphoma. 2018 Sep;59(9):2113-2120.

We examined real-world data on management of relapsed/refractory Hodgkin lymphoma (R/R HL) in five European countries and the consistency of these data with guideline recommendations. Retrospective clinical and epidemiologic data for 509 patients with R/R HL treated between January 2014 and March 2015 were collected at centers in France, Germany, Italy, Spain, and the United Kingdom. Mean age was 46.3 years; 73.3% were receiving second-line thera […]

Expression and Prognostic Value of Oestrogen Receptor Beta in Colorectal Cancer.

Pérez-Ruiz E, Rueda A, Pérez L, Rivas-Ruiz F, Torres E, de Luque V, Álvarez M, Sevilla I, Redondo M, Padilla-Ruiz M, Alba E, Alonso L.
Pathol Oncol Res. 2018 Oct;24(4):871-879.

Differences between men and women in the incidence and biological mechanisms of colorectal cancer (CRC) suggest that estrogens may play a role in the pathogenesis of this disease. The identification of the human estrogen receptor beta (ERβ) and its expression in the intestinal mucosa led to further studies that revealed that estrogens have a protective function against CRC mediated by the activation of ERβ. However, ERβ expression and its role […]

Bcl-2 Inhibition to Overcome Resistance to Chemo- and Immunotherapy.

García-Aranda M, Pérez-Ruiz E, Redondo M.
Int J Mol Sci. 2018 Dec 8;19(12).

Abstract: According to the World Health Organization (WHO), cancer is a leading cause of death worldwide. The identification of novel targets for cancer treatment is an area of intense work that has led Bcl-2 over-expression to be proposed as one of the hallmarks of cancer and Bcl-2 inhibition as a promising strategy for cancer treatment. In this review, we describe the different pathways related to programmed cell death, the role of Bcl-2 family […]

Correction to: Efficacy of fulvestrant in the treatment of postmenopausal women with endocrine-resistant advanced breast cancer in routine clinical practice.

Blancas I, Fontanillas M, Conde V, Lao J, Martínez E, Sotelo MJ, Jaen A, Bayo JL, Carabantes F, Illarramendi JJ, Gordon MM, Cruz J, García-Palomo A, Mendiola C, Pérez-Ruiz E, Bofill JS, Baena-Cañada JM, Jáñez NM, Esquerdo G, Ruiz-Borrego M.
Clin Transl Oncol. 2018 Dec;20(12):1631-1632.

A sentence under ‘Results’ heading in the Abstract section was published incorrectly. The correct sentence should read as follows. […]

SEOM clinical guidelines for the treatment of head and neck cancer (2017).

Iglesias Docampo LC, Arrazubi Arrula V, Baste Rotllan N, Carral Maseda A, Cirauqui Cirauqui B, Escobar Y, Lambea Sorrosal JJ, Pastor Borgoñón M, Rueda A, Cruz Hernández JJ.
Clin Transl Oncol. 2018 Jan;20(1):75-83.

Head and neck cancer (HNC) is defined as malignant tumours located in the upper aerodigestive tract and represents 5% of oncologic cases in adults in Spain. More than 90% of these tumours have squamous histology. In an effort to incorporate evidence obtained since 2013 publication, Spanish Society of Medical Oncology (SEOM) presents an update of HNC diagnosis and treatment guideline. The eighth edition of TNM classification, published in January […]

Protein phosphorylation is a well-known mechanism by which extracellular molecules or factors transduce their signals into intracellular effects. In the context of myelin assembly, phosphorylation of major myelin proteins affects the electrostatic repulsion between adjacent proteins within myelin structure and therefore constitutes one of the mechanisms by which myelin stability is regulated. We report here that arachidonic acid (AA) decreases th […]

High serum vascular endothelial growth factor C predicts better relapse-free survival in early clinically node-negative breast cancer.

Maañón J, Perez D, Rhode A, Callejón G, Rivas-Ruiz F, Perez-Ruiz E, Rodrigo I, Ramos B, Medina F, Villatoro R, Redondo M, Rueda A.
Oncotarget. 2018 Jun 15;9(46):28131-28140.

A recent meta-analysis indicated that higher tumoral expression of vascular endothelial growth factor C (VEGF-C) was related to poorer relapse-free and overall survival in breast cancer patients. However, a retrospective study found that higher circulating VEGF-C levels were associated with better survival in breast cancer patients. In 2009, we initiated a prospective study to determine the utility of preoperative serum VEGF-C levels for predicti […]

Association between PD1 mRNA and response to anti-PD1 monotherapy across multiple cancer types.

Paré L, Pascual T, Seguí E, Teixidó C, Gonzalez-Cao M, Galván P, Rodríguez A, González B, Cuatrecasas M, Pineda E, Torné A, Crespo G, Martin-Algarra S, Pérez-Ruiz E, Reig Ò, Viladot M, Font C, Adamo B, Vidal M, Gaba L, Muñoz M, Victoria I, Ruiz G, Viñolas N, Mellado B, Maurel J, Garcia-Corbacho J, Molina-Vila MÁ, Juan M, Llovet JM, Reguart N, Arance A, Prat A.
Ann Oncol. 2018 Oct 1;29(10):2121-2128.

We hypothesized that the abundance of PD1 mRNA in tumor samples might explain the differences in overall response rates (ORR) observed following anti-PD1 monotherapy across cancer types. […]

Efficacy of the combination of rituximab-bendamustine as a second-line treatment in patients with follicular lymphoma who progress after immunochemotherapy: a phase II trial of the Spanish Lymphoma Oncology Group.

Rueda A, Calvo V, Casanova M, Rodriguez-Abreu D, Aguiar D, Llanos M, Alvarez R, Martinez-Banaclocha N, Alfaro J, Quero C, Blasco A, de la Cruz Merino L, Herrero J, García-Arroyo FR, Provencio M.
Leuk Lymphoma. 2019 Jun;60(6):1576-1579.

[…]

Nutritional risk and malnutrition rates at diagnosis of cancer in patients treated in outpatient settings: Early intervention protocol.

Álvaro Sanz E, Garrido Siles M, Rey Fernández L, Villatoro Roldán R, Rueda Domínguez A, Abilés J.
Nutrition. 2019 Jan;57:148-153.

Malnutrition is frequent in patients with cancer and is associated with a higher rate of morbidity and mortality. However, a significant number of patients at nutritional risk remain undetected due to the lack of a routine screening procedure during diagnosis. Costa del Sol Hospital in Marbella (Málaga), Spain has implemented a protocol for outpatients with cancer aimed at identifying and treating malnutrition at an early stage. The aim of this […]

Genetic Susceptibility in Head and Neck Squamous Cell Carcinoma in a Spanish Population.

Fernández-Mateos J, Seijas-Tamayo R, Adansa Klain JC, Pastor Borgoñón M, Pérez-Ruiz E, Mesía R, Del Barco E, Salvador Coloma C, Rueda Dominguez A, Caballero Daroqui J, Fernández Ruiz E, Ocana A, González-Sarmiento R, Cruz-Hernández JJ.
Cancers (Basel). 2019 Apr 7;11(4).

Despite classical environmental risk factors like tobacco, alcohol or viral infection, not all individuals develop head and neck cancer. Therefore, identification of the genetic susceptibility produced by single nucleotide polymorphisms (SNPs) is an important task. A total of 296 human papillomavirus negative head and neck cancer (HNC) patients (126 laryngeal, 100 pharyngeal and 70 oral cavity) were included in the study, involving 29 candidate S […]

Unraveling transformation of follicular lymphoma to diffuse large B-cell lymphoma.

González-Rincón J, Méndez M, Gómez S, García JF, Martín P, Bellas C, Pedrosa L, Rodríguez-Pinilla SM, Camacho FI, Quero C, Pérez-Callejo D, Rueda A, Llanos M, Gómez-Codina J, Piris MA, Montes-Moreno S, Bárcena C, Rodríguez-Abreu D, Menárguez J, de la Cruz-Merino L, Monsalvo S, Parejo C, Royuela A, Kwee I, Cascione L, Arribas A, Bertoni F, Mollejo M, Provencio M, Sánchez-Beato M.
PLoS One. 2019 Feb 25;14(2):e0212813.

Follicular lymphoma (FL) is an indolent but largely incurable disease. Some patients suffer histological transformation to a more aggressive subtype with poorer prognosis. This study aimed to improve our understanding of the genetics underlying FL histological transformation, and to identify genetic drivers or promoters of the transformation by elucidating the differences between FL samples from patients who did and did not transform. We conducte […]

Transformed follicular lymphoma in the rituximab era: A report from the Spanish Lymphoma Oncology Group.

Méndez M, Torrente M, Sánchez-Beato M, González-Rincón J, Royuela A, Gómez-Codina J, de la Cruz-Merino L, Rueda A, Llanos M, Quero C, Rodríguez-Abreu D, Gumá J, Monsalvo S, Sabin P, Provencio M.
Hematol Oncol. 2019 Apr;37(2):143-150.

Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma (NHL) subtype. The histological transformation (HT) of FL is an event considered frequent in the natural history of this tumor. We studied the transformation rates, predictive factors, and treatment characteristics that may impact in the survival of patients with FL and HT. A total of 1074 patients diagnosed with FL were prospectively enrolled from 1990 to 2016 in a Spanish r […]

Clinical and sociodemographic factors that may influence the resilience of women surviving breast cancer: cross-sectional study.

Padilla-Ruiz M, Ruiz-Román C, Pérez-Ruiz E, Rueda A, Redondo M, Rivas-Ruiz F.
Support Care Cancer. 2019 Apr;27(4):1279-1286.

Breast cancer is one of the most common diseases, affecting many thousands of women. Although more than 80% of women survive the experience, very few studies have been conducted to examine the question of resilience among long-term survivors of breast cancer. The aim of this study is to describe the clinical and sociodemographic factors that correlate with greater resilience in women survivors of breast cancer, in the Costa del Sol Health Area (S […]

Consolidation treatment with yttrium-90 ibritumomab tiuxetan after new induction regimen in advanced stage follicular lymphoma: update results from the Spanish Lymphoma Oncology Group trial after a median follow-up of 8.5-years.

Provencio M, Franco F, Gómez-Codina J, Quero Blanco C, Llanos M, Garcia-Arroyo F, de la Cruz L, Gumá J, Delgado JR, Álvarez R, Chacón JI, Royuela A, Rueda A.
Leuk Lymphoma. 2019 Mar;60(3):856-859.

[…]

Clinical-pathological characteristics and short-term follow-up associated with proliferation, apoptosis and angiogenesis in a prospective cohort of patients with colorectal tumours.

Redondo M, Abitei C, Téllez T, Fúnez R, Pereda T, Rodrigo I, Betancourt AM, García-Aranda M, Rueda A, Martínez García RC, Morales Suarez-Varela MM, Zabalza I, Sánchez Del Charco M, Borrero Martín JJ, García Del Moral R, Escobar A, Quintana J, Rivas-Ruiz F; REDISSEC-CARESS/CCR group.
Tumour Biol. 2019 Apr;42(4):1010428319835684.

We investigate the clinical and pathological features related to variations in colorectal tumour apoptosis, proliferation and angiogenesis and the influence of the latter in short-term mortality (2 years); 551 tumour samples from a prospective cohort of patients with colorectal cancer were examined and tumour biology markers were determined as follows: percentage of apoptotic cells, by the terminal deoxynucleotidyl transferase (TdT) dUTP Nick-E […]

Impact of prophylactic TNF blockade in the dual PD-1 and CTLA-4 immunotherapy efficacy and toxicity.

Alvarez M, Otano I, Minute L, Ochoa MC, Perez-Ruiz E, Melero I, Berraondo P.
Cell Stress. 2019 Jun 27;3(7):236-239.

The TNF blockade therapy is currently a well-established treatment option for a variety of autoimmune diseases such as rheumatoid arthritis (RA), psoriasis or Crohn’s disease, given the proinflammatory role of TNF in the course of these diseases. Importantly, TNF neutralization is also used for the treatment of corticosteroid-refractory immune-related adverse events (irAEs) induced by the combined anti-PD-1 and anti-CTLA-4 immunotherapy. The mani […]

Daratumumab in combination with urelumab to potentiate anti-myeloma activity in lymphocyte-deficient mice reconstituted with human NK cells.

Ochoa MC, Perez-Ruiz E, Minute L, Oñate C, Perez G, Rodriguez I, Zabaleta A, Alignani D, Fernandez-Sendin M, Lopez A, Muntasell A, Sanmamed MF, Paiva B, Lopez-Botet M, Berraondo P, Melero I.
Oncoimmunology. 2019 Apr 13;8(7):1599636.

Daratumumab is an anti-CD38 fully human IgG1 mAb approved for multiple myeloma treatment. One of the proposed mechanisms of action is the induction of antibody-dependent cellular cytotoxicity (ADCC) mediated by NK cells. NK cells acquire surface CD137 expression in the presence of solid-phase-attached daratumumab and when encountering a daratumumab-coated CD38+ tumor cell line. In this setting, addition of the agonist anti-CD137 mAb urelumab enha […]

Prophylactic TNF blockade uncouples efficacy and toxicity in dual CTLA-4 and PD-1 immunotherapy.

Perez-Ruiz E, Minute L, Otano I, Alvarez M, Ochoa MC, Belsue V, de Andrea C, Rodriguez-Ruiz ME, Perez-Gracia JL, Marquez-Rodas I, Llacer C, Alvarez M, de Luque V, Molina C, Teijeira A, Berraondo P, Melero I.
Nature. 2019 May;569(7756):428-432.

Combined PD-1 and CTLA-4-targeted immunotherapy with nivolumab and ipilimumab is effective against melanoma, renal cell carcinoma and non-small-cell lung cancer1-3. However, this comes at the cost of frequent, serious immune-related adverse events, necessitating a reduction in the recommended dose of ipilimumab that is given to patients4. In mice, co-treatment with surrogate anti-PD-1 and anti-CTLA-4 monoclonal antibodies is effective in transpla […]


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