Encío Martínez, Ignacio

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https://academica-e.unavarra.es/handle/2454/48954

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Encío Martínez

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Ignacio

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Ciencias de la Salud

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IMAB. Research Institute for Multidisciplinary Applied Biology

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0000-0003-1732-1989

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88436

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455

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2001 - 20093
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    PublicationOpen Access
    Synthesis and pharmacological screening of several aroyl and heteroaroyl selenylacetic acid derivatives as cytotoxic and antiproliferative agents
    (MDPI, 2009) Sanmartín, Carmen; Plano, Daniel; Domínguez, Enrique; Font, María; Calvo, Alfonso; Prior, Celia; Encío Martínez, Ignacio; Palop, Juan Antonio; Ciencias de la Salud; Osasun Zientziak
    The synthesis and cytotoxic activity of a series of twenty six aroyl and heteroaroyl selenylacetic acid derivatives of general formula Ar-CO-Se-CH(2)-COOH or Heterar-CO-Se-CH(2)-COOH are reported. The synthesis was carried out by reaction of acyl chlorides with sodium hydrogen selenide, prepared in situ, and this led to the formation of sodium aroylselenides that subsequently reacted with alpha-bromoacetic acid to produce the corresponding selenylacetic acid derivatives. All of the compounds were tested against a prostate cancer cell line (PC-3) and some of the more active compounds were assessed against a panel of four human cancer cell lines (CCRF-CEM, HTB-54, HT-29, MCF-7) and one mammary gland-derived non-malignant cell line (184B5). Some of the compounds exhibited remarkable cytotoxic and antiproliferative activities against MCF-7 and PC-3 that were higher than those of the reference compounds doxorubicin and etoposide, respectively. For example, in MCF-7 when Ar = phenyl, 3, 5-dimethoxyphenyl or benzyl the TGI values were 3.69, 4.18 and 6.19 mu M. On the other hand, in PC-3 these compounds showed values of 6.8, 4.0 and 2.9 mu M. Furthermore, benzoylselenylacetic acid did not provoke apoptosis nor did it perturb the cell cycle in MCF-7.
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    PublicationOpen Access
    Frequent promoter hypermethylation of RASSF1A and CASP8 in neuroblastoma
    (BioMed Central, 2006) Lázcoz Ripoll, Paula; Muñoz, Jorge; Nistal, Manuel; Pestaña, Ángel; Encío Martínez, Ignacio; Sáez Castresana, Javier; Ciencias de la Salud; Osasun Zientziak
    Background: Epigenetic alterations and loss of heterozygosity are mechanisms of tumor suppressor gene inactivation. A new carcinogenic pathway, targeting the RAS effectors has recently been documented. RASSF1A, on 3p21.3, and NORE1A, on 1q32.1, are among the most important, representative RAS effectors. Methods: We screened the 3p21 locus for the loss of heterozygosity and the hypermethylation status of RASSF1A, NORE1A and BLU ( the latter located at 3p21.3) in 41 neuroblastic tumors. The statistical relationship of these data was correlated with CASP8 hypermethylation. The expression levels of these genes, in cell lines, were analyzed by RT-PCR. Results: Loss of heterozygosity and microsatellite instability at 3p21 were detected in 14% of the analyzed tumors. Methylation was different for tumors and cell lines (tumors: 83% in RASSF1A, 3% in NORE1A, 8% in BLU and 60% in CASP8; cell lines: 100% in RASSF1A, 50% in NORE1A, 66% in BLU and 92% in CASP8). In cell lines, a correlation with lack of expression was evident for RASSF1A, but less clear for NORE1A, BLU and CASP8. We could only demonstrate a statistically significant association between hypermethylation of RASSF1A and hypermethylation of CASP8, while no association with MYCN amplification, 1p deletion, and/or aggressive histological pattern of the tumor was demonstrated. Conclusion: 1) LOH at 3p21 appears in a small percentage of neuroblastomas, indicating that a candidate tumor suppressor gene of neuroblastic tumors is not located in this region. 2) Promoter hypermethylation of RASSF1A and CASP8 occurs at a high frequency in neuroblastomas.
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    PublicationOpen Access
    Morphological and biochemical characterization of a cell death process induced by E3, a new synthetic diarylsulfonilurea analogue
    (Hindawi, 2001) Alonso Roldán, Marta; Miglaccio, M.; Encío Martínez, Ignacio; Asumendi, A.; Martínez Merino, Víctor; Hilario, E.; García, M.; Ciencias de la Salud; Química Aplicada; Osasun Zientziak; Kimika Aplikatua
    With a view to finding new compounds with improved antitumoral activity and reduced secondary effects, our group, using theoretical structure-activity studies, has designed several analogues and derivatives of diarylsulfonilureas. These compounds have been synthesized and tested “in vitro” on a panel of human tumor cell lines and showed an antitumoral activity. In the present work, we have characterized the mechanisms involved in the cell death process induced by one of these products called E3 in a CCRF-CEM cell line.