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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
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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
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ABSTRACT: The WHO grading scheme distinguishes benign (grade I), atypical (grade II) and anaplastic (grade III) meningiomas. Both atypical and anaplastic meningiomas exhibited an overall increased rate of recurrence, but between 15-20% benign meningiomas will also exhibit an unfavourable clinical course with recurrence before 10 years despite aggressive surgery. We investigated 247 cases of meningiomas grade I and II. The immunohistochemical expression of 30 different molecular biomarkers of cell adhesion molecules, cell-cycle and apoptosis regulators and checkpoints was analyzed. We also determined apoptosis by in-situ hybridization (APOPDETEKTM) and loss of chromosome 1p36 by FISH. The study revealed a statistically significant co-variation (p<0.05) between meningiomas grade II associated with several clinicopathological features (Simpson grade of clinical resection, necrosis, nuclear atypia, macronucleoli, transition to small cell, sheet-like growth, high cellularity), increased expression of several biomarkers of tumour proliferation (Cyclin A, Cyclin E, MIB-1 or MDM2), proteases (Cathepsin D) or cell-adhesion (CD44) and lower expression of progesterone receptors than meningiomas grade I. The presence of Psammoma bodies or the location at convexity were protective prognostic factors for tumour recurrence while high cellularity and early age of onset (<57 year-old) were indicators of increased recurrence risk. The expression of COX-2, gamma-catenin, Topoisomerase IIa, VEGF and MIB-1 was significantly higher in the cohort of recurrent meningiomas. Meningiomas with chromosome 1p36 loss showed a higher recurrence rate (33.3%) than meningiomas with normal chromosome 1p36 (18%). Increased COX-2 expression in recurrent meningioma may also suggest a putative role of COX-2 inhibitors as a chemopreventive treatment for recurrence.
Histology and histopathology 03/2010; 25(3):341-9. · 2.48 Impact Factor
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ABSTRACT: Alterations in the Wnt pathway play a major role in colorectal cancer with high (MSI-H) or low microsatellite instability (MSS/MSI-L). However, the differential impact of the Wnt pathway components on these tumors is poorly understood. MMP-3 (stromelysin-1) promoter is a target of the mutator phenotype in sporadic colorectal cancer. Among MMP-3 targets, we investigated E-cadherin integrity status in both groups of tumors. Because beta-catenin is the main effector of the Wnt pathway, we have also investigated the differential cellular status of beta-catenin.
Expression profiles of 114 genes related to the Wnt pathway were analyzed by oligo microarrays in 48 tumors classified by their MSI status. In addition, we analyzed 48 sporadic colorectal cancers for E-cadherin integrity status. We performed investigation of beta-catenin and cyclin D1 by immunohistochemistry using tissue arrays containing 96 tumors.
Our data show that a group of genes that negatively regulate Wnt signaling are downregulated in MSS/MSI-L as compared with MSI-H colorectal tumors. E-cadherin truncation was significantly higher in MSS/MSI-L as compared with MSI-H tumors. Moreover, MSI-H tumors showed low or null beta-catenin nuclear presence, whereas the group of tumors classified as MSS or MSI-L displayed a high content of the nuclear beta-catenin location.
Our results suggest that the differential expression of genes that negatively regulate the Wnt pathway, as well as the status of E-cadherin and beta-catenin in MSI-H or MSS/MSI-L colorectal tumors, shed some light on the different clinical behavior showed by the two groups.
Clinical Cancer Research 03/2008; 14(4):995-1001. · 7.74 Impact Factor
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Juan Julián González-García,
Beatriz Mahillo, Susana Hernández,
Raquel Pacheco,
Sergio Diz,
Paz García,
Herminia Esteban,
José Ramón Arribas,
Carmen Quereda,
Rafael Rubio,
Jesús Díez,
Santiago Moreno,
Juan José Vázquez-Rodríguez
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ABSTRACT: The aims of this study were to estimate the prevalence of HIV and hepatitis virus coinfection in the Spanish population and to determine the percentage of patients who are candidates for chronic hepatitis C virus (HCV) treatment and liver transplantation within this population.
A cross-sectional study was performed in 2002 in two Spanish populations of HIV-infected patients: 1,260 patients from 39 centers throughout Spain (P1) and 1,560 patients from three tertiary teaching hospitals in Madrid (P2).
The following hepatitis A virus (HAV), hepatitis B virus (HBV) and HCV serological prevalence were found in the P1 and P2 groups, respectively: HAV-IgG antibodies: 74% and 78%; HBsAg1: 4.9% and 4.8%; HBsAg-, anti-HBc1, anti-HBs1: 39% and 39%; HBsAg-, anti-HBc1, anti-HBs-: 25% and 31%; HBsAg-, anti-HBc-, anti-HBs1: 7% and 8%; HBsAg-, anti-HBc-, anti-HBs-: 22% and 16%. Anti-HCV1: 61% and 65%, respectively. Of the patients with positive HCV serology, 88.8% and 84.6% of each group were positive for HCV-RNA by polymerase chain reaction. Multiple coinfections with hepatitis viruses were found in 3.2% and 2.8%, respectively; of these, 70% and 78% had coinfection with HBV, HCV and HDV. Liver cirrhosis was found in 5.8% and 9.6% of the patients coinfected with HIV and HCV, respectively. Liver transplant was indicated in approximately one out of every six coinfected patients with liver cirrhosis. The 43 and 37% of the HCV coinfected patients were good candidates for anti-HCV treatment, but only 14% and 15% of patients had initiated it.
A high percentage of HIV-infected patients in Spain were coinfected with hepatitis viruses, especially HCV. The number of possible candidates for liver transplantation is rising and could increase in the next few years. In the future, greater efforts to treat HIV-and hepatitis virus-coinfected patients will be required.
Enfermedades Infecciosas y Microbiología Clínica 23(6):340-8. · 1.49 Impact Factor
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ABSTRACT: A common genetic abnormality detected in Barrett's adenocarcinoma is LOH (loss of heterozygosity) at the sites of known or putative tumor suppressor genes. Thus, some deletions have also been determined in peritumoral Barrett's epithelium. These findings suggest that a tissue field of somatic genetic alterations precede the histopathological phenotypic changes of carcinoma. We investigated 32 cases of Barrett's esophagus with no evidence of dysplasia for LOH at 5q21 (APC), 3p21, 9p21 (p16) and 17p13.1 (p53) chromosomal regions.
Two groups were randomly selected and compared: 16 cases of Barrett's epithelium adjacent to adenocarcinoma and 16 cases of Barrett's epithelium with no evidence of malignant transformation in a 5-10 years follow-up period. In three adenocarcinomas cases several previous endoscopic biopsies of Barrett's esophagus were available.
We determined frequent allelic losses in adenocarcinomas at p53 (54%), p16 (50%), 3p21 (40%) and 5q21 (33%). Identical LOH was present in most cases in the Barrett's epithelium adjacent to adenocarcinoma. LOH at these loci was unusual in Barrett's epithelium with no evidence of malignant transformation. However, in cases where sequential endoscopic biopsies were performed in advance to the adenocarcinoma diagnosis LOH was already present in the Barrett's epithelium.
We suggest that LOH at these loci may be present before the onset of the malignant growth and LOH studies may supplement the histopathological evaluation of Barrett's epithelium. LOH at 3p21, 5q21, 9p21 and 17p13 chromosomal regions in cells of Barrett's epithelium without dysplasia may have a role as a potential marker for individuals with a high risk of developing adenocarcinoma.
Hepato-gastroenterology 50(50):404-7. · 0.66 Impact Factor
