Alberto Moran

Publications (22) View all

• Article: Differential expression of factors related to senescence and cell death pathways in non-small cell lung and colorectal tumours showing telomere attrition

  Tamara Fernández-Marcelo, Alberto Morán, Carmen de Juan, Irene Pascua, Jacqueline Head, Ana Gómez, Florentino Hernando, Jose A. López-Asenjo, Susana Hernández, Andrés Sánchez-Pernaute, Antonio J. Torres, Manuel Benito, Pilar Iniesta
  Oncology 03/2012; 82(153):164. · 2.27 Impact Factor
• Source

  Available from: Manuel Benito

  Article: Differential expression of senescence and cell death factors in non-small cell lung and colorectal tumors showing telomere attrition.

  Tamara Fernández-Marcelo, Alberto Morán, Carmen de Juan, Irene Pascua, Jacqueline Head, Ana Gómez, Florentino Hernando, Jose A López-Asenjo, Susana Hernández, Andrés Sánchez-Pernaute, Antonio J Torres, Manuel Benito, Pilar Iniesta
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  ABSTRACT: The main aim of this work is to investigate the expression of factors related to senescence and cell death pathways in non-small cell lung cancers (NSCLCs) and colorectal cancers (CRCs) in relation to telomere status. We analyzed 158 tissue samples, 36 NSCLCs, 43 CRCs, and their corresponding control tissues obtained from patients submitted to surgery. Telomere function was evaluated by determining telomerase activity and telomere length. Expression of factors related to senescence, cell death pathways, transformation and tumorigenesis was investigated using arrays. Results were validated by real-time quantitative PCR. Considering tumors with telomere shortening, expression for BNIP3, DAPK1, NDRG1, EGFR, and CDKN2A was significantly higher in NSCLC than in CRC, whereas TP53 was overexpressed in CRC with respect to NSCLC. Moreover, compared to nontumor samples, DAPK1, GADD45A, SHC1, and TP53 were downregulated in the group of NSCLCs with telomere shortening, and no significant differences were found in CRC. In NSCLC, the failure of pathways which involve factors such as DAPK1, GADD45A, SHC1, and TP53, in response to short telomeres, could promote tumor progression. In CRC, the viability of these pathways in response to short telomeres could contribute to limiting tumorigenesis.
  Oncology 03/2012; 82(3):153-64. · 2.27 Impact Factor
• Article: MMP-7 and SGCE as distinctive molecular factors in sporadic colorectal cancers from the mutator phenotype pathway.

  Paloma Ortega, Alberto Moran, Tamara Fernandez-Marcelo, Carmen De Juan, Cristina Frias, José-Antonio Lopez-Asenjo, Andrés Sanchez-Pernaute, Antonio Torres, Eduardo Diaz-Rubio, Pilar Iniesta, Manuel Benito
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  ABSTRACT: Colorectal cancers (CRCs) from the suppressor and the mutator carcinogenic pathways display distinctive pathological and clinical features that remain not completely understood. In this context, the aim of this work was to study the differential expression of metalloproteinases and adhesion molecules related to cancer invasiveness in both groups of tumours. We analyzed 84 tissue specimens, 42 primary sporadic CRCs obtained from patients who underwent radical surgery, and its corresponding control tissues. According to microsatellite instability, 31 cancers showed low or null microsatellite instability (MSI-L/MSS) and 11 tumours displayed high microsatellite instability (MSI-H). Expression assays were established using the Oligo GEArray(R) human extracellular matrix and adhesion molecules microarray containing 114 genes. Real-time quantitative PCR (RT-qPCR) confirmed expression data from arrays, using TaqMan probes. Results from oligoarray expression analyses indicated that ITGA3, ITGA9, ITGB4, ITGB7 and MMP15 had significantly higher expression levels in MSI-H tumours versus MSS/MSI-L cancers, whereas COL12A1, CSPG2, FN1, MMP-7 and SGCE were down-regulated in tumours with high microsatellite instability when compared to the stable group. After RT-qPCR validation, two of these genes, MMP-7 and SGCE, were confirmed to have statistical differences between the two groups of tumours studied. In both cases, MSI-H tumours displayed significant lower expression levels than MSI-L/MSS tumours. In conclusion, these two distinctive molecular markers could be related to a diminished invasion in colorectal tumours from the mutator pathway, this may contribute to the understanding of the better patient prognosis conferred by this type of tumours.
  International Journal of Oncology 05/2010; 36(5):1209-15. · 2.40 Impact Factor
• Source

  Available from: Manuel Benito

  Article: Methylation profiling in non-small cell lung cancer: clinical implications.

  Alberto Morán, Tamara Fernández-Marcelo, Juan Carro, Carmen De Juan, Irene Pascua, Jacqueline Head, Ana Gómez, Florentino Hernando, Antonio-José Torres, Manuel Benito, Pilar Iniesta
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  ABSTRACT: The aim of this study was to identify a panel of methylation markers that distinguish non-small cell lung cancers (NSCLCs) from normal lung tissues. We also studied the relation of the methylation profile to clinicopathological factors in NSCLC. We collected a series of 46 NSCLC samples and their corresponding control tissues and analyzed them to determine gene methylation status using the Illumina GoldenGate Methylation bead array, which screens up to 1505 CpG sites from 803 different genes. We found that 120 CpG sites, corresponding to 88 genes were hypermethylated in tumor samples and only 17 CpG sites (16 genes) were hypomethylated when compared with controls. Clustering analysis of these 104 genes discriminates almost perfectly between tumors and normal samples. Global hypermethylation was significantly associated with a worse prognosis in stage IIIA NSCLC patients (P=0.012). Moreover, hypermethylation of the CALCA and MMP-2 genes were statistically associated to a poor clinical evolution of patients, independently of TNM tumor stage (P=0.06, RR=2.64; P=0.04, RR=2.96, respectively). However, hypermethylation of RASSF1 turned out to be a protective variable (P=0.02; RR=0.53). In conclusion, our results could be useful for establishing a gene methylation pattern for the detection and prognosis of NSCLC.
  International Journal of Oncology 11/2011; 40(3):739-46. · 2.40 Impact Factor
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  Available from: Alberto Moran

  Article: Differential colorectal carcinogenesis: Molecular basis and clinical relevance.

  Alberto Morán, Paloma Ortega, Carmen de Juan, Tamara Fernández-Marcelo, Cristina Frías, Andrés Sánchez-Pernaute, Antonio José Torres, Eduardo Díaz-Rubio, Pilar Iniesta, Manuel Benito
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  ABSTRACT: Colorectal cancer (CCR) is one of the most frequent cancers in developed countries. It poses a major public health problem and there is renewed interest in understanding the basic principles of the molecular biology of colorectal cancer. It has been established that sporadic CCRs can arise from at least two different carcinogenic pathways. The traditional pathway, also called the suppressor or chromosomal instability pathway, follows the Fearon and Vogelstein model and shows mutation in classical oncogenes and tumour suppressor genes, such as K-ras, adenomatous polyposis coli, deleted in colorectal cancer, or p53. Alterations in the Wnt pathway are also very common in this type of tumour. The second main colorectal carcinogenesis pathway is the mutator pathway. This pathway is present in nearly 15% of all cases of sporadic colorectal cancer. It is characterized by the presence of mutations in the microsatellite sequences caused by a defect in the DNA mismatch repair genes, mostly in hMLH1 or hMSH2. These two pathways have clear molecular differences, which will be reviewed in this article, but they also present distinct histopathological features. More strikingly, their clinical behaviours are completely different, having the "mutator" tumours a better outcome than the "suppressor" tumours.
  World journal of gastrointestinal oncology. 03/2010; 2(3):151-8.