Aranda, E. (E.)

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2010 - 20192

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    Pharmacological impairment of s-nitrosoglutathione or thioredoxin reductases augments protein S-Nitrosation in human hepatocarcinoma cells
    (International Institute of Anticancer Research, 2010) Rodriguez-Ariza, A. (Antonio); Corrales, F.J. (Fernando José); Lopez-Pedrera, C. (Chary); Lopez-Sanchez, L.M. (Laura M.); Aranda, E. (E.)
    BACKGROUND/AIM: S-Nitrosoglutathione reductase (GSNOR) and thioredoxin enzyme systems participate in cellular defence against nitrosative stress. Pharmacological interventions against these enzyme systems might represent valuable strategies to impair S-nitrosothiol (SNO) homeostasis in tumour cells. MATERIALS AND METHODS: Human HepG2 cells were pre-treated with mithramycin A or auranofin and exposed to S-nitroso-L-cysteine. GSNOR mRNA levels were analyzed by quantitative real-time reverse transcriptase-polymerase chain reaction and S-nitrosated proteins were detected and purified using the biotin-switch approach. Proteins were identified using electrospray ionization tandem mass spectrometry. RESULTS: Mithramycin interfered with GSNOR induction resulting in an increased cellular sensitivity to protein S-nitrosation. Moreover, the thioredoxin reductase inhibitor auranofin also increased cellular susceptibility to S-nitrosoprotein formation. The impairment of these two cellular defense systems against nitrosative stress resulted in different sets of S-nitrosated proteins, as revealed by the proteomics approach. CONCLUSION: Our results suggest that pharmacological intervention with mithramycin or auranofin may constitute promising tools for altering SNO homeostasis in tumour cells.
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    Combination of KIR2DS4 and FcγRIIa polymorphisms predicts the response to cetuximab in KRAS mutant metastatic colorectal cancer
    (Nature Publishing Group, 2019) Hernandez, I. (I.); Cervantes, A. (Andrés); Rodríguez, J. (J.); Puime-Otin, A. (A.); Valladares, M. (M.); Vega-Bravo, R. (R.); Cebrián, A. (A.); Borrero-Palacios, A. (A.); Garcia-Alfonso, P. (P.); Vieitez, J.M. (J. M.); Rodríguez-Remírez, M. (M.); Garcia-Foncillas, J. (Jesús); López-López, R. (Rafael); García-Carbonero, R. (R.); Martinez-Useros, J. (Javier); García, J.L. (J. L.); Nadal, C. (C.); Guillén-Ponce, C. (C.); Rincón, R. (R.); Rojo-Todo, F. (Federico); Elez, E. (E.); Puerto-Nevado, L. (L.) del; Aranda, E. (E.)
    Cetuximab is a standard-of-care treatment for RAS wild-type metastatic colorectal cancer (mCRC) but not for those harbor a KRAS mutation since MAPK pathway is constitutively activated. Nevertheless, cetuximab also exerts its effect by its immunomodulatory activity despite the presence of RAS mutation. The aim of this study was to determine the impact of polymorphism FcγRIIIa V158F and killer immunoglobulin-like receptor (KIR) genes on the outcome of mCRC patients with KRAS mutations treated with cetuximab. This multicenter Phase II clinical trial included 70 mCRC patients with KRAS mutated. We found KIR2DS4 gene was significantly associated with OS (HR 2.27; 95% CI, 1.08-4.77; P = 0.03). In non-functional receptor homozygotes the median OS was 2.6 months longer than in carriers of one copy of full receptor. Multivariate analysis confirmed KIR2DS4 as a favorable prognostic marker for OS (HR 6.71) in mCRC patients with KRAS mutation treated with cetuximab. These data support the potential therapeutic of cetuximab in KRAS mutated mCRC carrying non-functional receptor KIR2DS4 since these patients significantly prolong their OS even after heavily treatment. KIR2DS4 typing could be used as predictive marker for identifying RAS mutated patients that could benefit from combination approaches of anti-EGFR monoclonal antibodies and other immunotherapies to overcome the resistance mediated by mutation in RAS.