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Malho P.,Comparative Ophthalmology Unit | Dunn K.,FOCUS EyePathLab | Donaldson D.,Comparative Ophthalmology Unit | Dubielzig R.R.,University of Wisconsin - Madison | And 2 more authors.
Journal of Small Animal Practice | Year: 2013

Objective: To evaluate if 14 genes that discriminate metastasising and non-metastasising human uveal melanomas can differentiate metastasising and non-metastasising uveal melanomas in dogs. Methods: Nineteen archival biopsies of eyes with a histopathological classification of primary benign (n=9) and malignant (n=10) uveal melanoma were selected. Thoracic and/or abdominal metastases confirmed metastatic spread of the primary tumour in seven dogs during the follow-up period. Gene expression was assayed by Reverse Transcription-quantitative Polymerase Chain Reaction. Genes displaying statistically significant differences in expression between the metastasising and non-metastasising tumours were identified. Results: Four genes (HTR2B, FXR1, LTA4H and CDH1) demonstrated increased expression in the metastasising uveal melanomas. Clinical Significance: This preliminary study illustrates the potential utility of gene expression markers for predicting canine uveal melanoma metastasis. The genes displaying elevated expression in the metastasising tumours are part of a 12-discriminating gene set used in a routine assay, performed on fine needle aspirate biopsies collected without enucleation, for predicting human uveal melanoma metastasis. Further work is required to validate the results. © 2013 British Small Animal Veterinary Association. Source


Pereira C.,Molecular Oncology Group | Pimentel-Nunes P.,Portuguese Institute of Oncology | Brandao C.,Portuguese Institute of Oncology | Moreira-Dias L.,Portuguese Institute of Oncology | And 4 more authors.
European Journal of Gastroenterology and Hepatology | Year: 2010

Objective: COX-2, the inducible isoenzyme, was found to be overexpressed in approximately 85% of colorectal adenocarcinomas, contributing to key steps in tumor development. COX-2 polymorphisms that might modify the levels of protein expression would be anticipated to have a substantial influence on disease phenotype. Therefore, we sought to understand the role of three COX-2 polymorphisms (-1195A>G, -765G>C, and 8473T>C) in colorectal cancer (CRC) onset. Material and Methods: We conducted a hospital-based case-control study involving 117 consecutively enrolled CRC patients and 256 healthy individuals without any clinical evidence of cancer. The COX-2 polymorphisms genotypes were characterized by PCR-restriction fragment length polymorphism or real-time PCR techniques. Results: The -1195A>G polymorphism was associated with a 1.73-fold increased predisposition to CRC onset. In a stratified analysis, men and ever-smokers carrying -1195G allele (AG+GG) had an increased risk for CRC development (odds ratio: 2.58; 95% confidence intraval: 1.29-5.15 and odds ratio: 10.3; 95% confidence intraval: 3.37-31.2, respectively). More interestingly, men ever-smokers carrying -1195G allele appeared to have a nine-fold increased risk for CRC onset (95% CI: 2.94-27.6). No difference in the genotype's distribution was noticed between cases and controls for the remaining two polymorphisms. Conclusion: The -1195A>G COX-2 polymorphism seems to modulate the genetic susceptibility for CRC onset, especially in men ever-smokers. This genetically based higher-risk group definition may help shift the balance between risk and benefits for the use of COX-2 inhibitors in chemoprevention that is currently hampered by the adverse gastrointestinal and cardiovascular side-effects. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source


Nunez de Villavicencio-Diaz T.,Bioinformatics Group | Mazola Y.,Bioinformatics Group | Perera Negrin Y.,Molecular Oncology Group | Cruz Garcia Y.,National Institute of Oncology and Radiobiology of Cuba | And 2 more authors.
Biochemistry and Biophysics Reports | Year: 2015

CK2 is a constitutively active Ser/Thr protein kinase deregulated in cancer and other pathologies, responsible for about the 20% of the human phosphoproteome. The holoenzyme is a complex composed of two catalytic (α or αD') and two regulatory (β) subunits, with individual subunits also coexisting in the cell. In the holoenzyme, CK2β is a substrate-dependent modulator of kinase activity. Therefore, a comprehensive characterization of CK2 cellular function should firstly address which substrates are phosphorylated exclusively when CK2β is present (class-III or beta-dependent substrates). However, current experimental constrains limit this classification to a few substrates. Here, we took advantage of motif-based prediction and designed four linear patterns for predicting class-III behavior in sets of experimentally determined CK2 substrates. Integrating high-throughput substrate prediction, functional classification and network analysis, our results suggest that beta-dependent phosphorylation might exert particular regulatory roles in viral infection and biological processes/pathways like apoptosis, DNA repair and RNA metabolism. It also pointed, that human beta-dependent substrates are mainly nuclear, a few of them shuttling between nuclear and cytoplasmic compartments. © 2015 The Authors. Source


Watrowski R.,University Hospital Freiburg | Watrowski R.,Molecular Oncology Group | Castillo-Tong D.C.,Molecular Oncology Group | Wolf A.,Molecular Oncology Group | And 4 more authors.
Anticancer Research | Year: 2015

Background: The overexpression of the human epidermal growth factor receptor 2 (HER2) in breast cancer (BC) is associated with impaired prognosis. Data concerning the HER2 codon 655 polymorphism (Ile/Val) and BC risk are conflicting. Materials and Methods: We studied the HER2 codon 655 (rs1136201) polymorphism in 80 Austrian patients with BC and 100 healthy volunteers by pyrosequencing and polymerase chain reaction. Associations between codon 655 allelic variants and clinicopathological variables (e.g. age, stage of disease, tumor type, grading, and receptor status) were studied with 22 tables. Results: The genotypic distributions in patients with BC (AA: 63.75%, AG: 32.5%, GG: 3.75%) and controls (AA: 63%, AG: 34%, GG: 3.7%) were virtually identical (odds ratio=1.03, 95% confidence interval=0.56-1.90). A non-significant link between carrying at least one G allele and more aggressive tumor type (estrogen receptor-negative p=0.08, G3 tumor p=0.19) was observed. Conclusion: Genotypic variation within the codon 655 of HER2 does not alter the BC risk in Caucasian Austrian women. The association between the G allele and more aggressive tumor types requires further investigation. Source


Coelho A.L.,Molecular Oncology Group | Coelho A.L.,University of Porto | Araujo A.M.,Centro Hospitalar do Porto | Araujo A.M.,Abel Salazar Biomedical Sciences Institute | And 9 more authors.
Future Oncology | Year: 2015

Aim: Evaluate if serum levels of VEGF and Ang-2 are correlated in non-small-cell lung cancers (NSCLCs) and its implications in the diagnostic and prognostic of the disease. Patients & methods: Unselected cohort of 145 NSCLC patients and 30 control individuals. The serum levels of Ang-2 and VEGF of each patient were measured by ELISA prior to treatment. Results & conclusions: Serum levels of Ang-2 and VEGF are correlated (p < 0.0001). High serum levels of Ang-2 and VEGF isolated and both combined (highAng-2/VEGF) correlate with likelihood of presenting NSCLC (p = 0.016; p = 0.003; p < 0.0001, respectively). Serum levels of Ang-2 and highAng-2/VEGF but not VEGF alone are independent prognostic factors (p = 0.001; p = 0.619; p = 0.005). HighAng-2/VEGF serum levels could be exploited as a new valuable integral biomarker in NSCLC. © 2015 Future Medicine Ltd. Source

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