PubMed | University of Porto, Molecular Oncology Group and Institute Biologia Molecular e Celular Immunobiology Research Group
Type: Journal Article | Journal: Future oncology (London, England) | Year: 2015
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.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.Serum levels of Ang-2 and VEGF are correlated (p < 0.0001). High serum levels of Ang-2 and VEGF isolated and both combined (high(Ang-2/VEGF)) correlate with likelihood of presenting NSCLC (p = 0.016; p = 0.003; p < 0.0001, respectively). Serum levels of Ang-2 and high(Ang-2/VEGF) but not VEGF alone are independent prognostic factors (p = 0.001; p = 0.619; p = 0.005). High(Ang-2/VEGF) serum levels could be exploited as a new valuable integral biomarker in NSCLC.
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.
PubMed | University of Barcelona, Vall dHebron Institute of Oncology VHIO, University of Malaga, Hospital Universitari Of La Vall Dhebron and 3 more.
Type: Journal Article | Journal: Clinical cancer research : an official journal of the American Association for Cancer Research | Year: 2016
Most hormone receptor (HR)(+)/HER2(-) breast cancer patients respond unfavorably to neoadjuvant chemotherapy (NAC); however, genomic tests may identify those patients who are likely to benefit. Using the Prosigna assay, we first evaluated the technical performance of core needle biopsy (CNB) tissues. We then determined whether Prosigna risk of relapse (ROR) score and intrinsic subtype predicted response to NAC in HR(+)/HER2(-) patients using CNB samples.Using the NanoStrings nCounter Dx analysis system and a development tissue sample set, we established tissue requirements and assay output variance. We then evaluated the concordance in subtype and correlation in ROR between CNBs and corresponding surgical resection specimens (SRS) in a second independent sample set. Finally, we analyzed 180 independent CNB samples from HR(+)/HER2(-) patients who were treated with NAC and correlated ROR and intrinsic subtype with pathologic response.Intra- and interbiopsy variabilities were 2.2 and 6.8 ROR units, respectively. Subtype concordance within multiple CNBs was high for the 4- and 3-subtype classifications (k = 0.885 and 0.889, respectively). Correlation in Prosigna ROR score observed between paired CNBs and SRS was high (r 0.90), and subtype concordance was also high for the 4- and 3-subtype classifications (kappa = 0.81 and 0.91, respectively). Prosigna results obtained from the HR(+)/HER2(-) patient samples showed that both ROR (P = 0.047) and intrinsic subtype (OR LumA vs. non-LumA = 0.341, P = 0.037) were significant predictors of response to NAC.Prosigna ROR and intrinsic subtype are readily obtained from CNB samples in normal practice and reliably predict response to NAC in HR(+)/HER2(-) patients.
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.
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.
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.
PubMed | Cancer Research UK Research Institute and Molecular Oncology Group
Type: Case Reports | Journal: Annals of oncology : official journal of the European Society for Medical Oncology | Year: 2015
Chronic myeloid leukaemia (CML) is characterised by the presence of a fusion driver oncogene, BCR-ABL1, which is a constitutive tyrosine kinase. Tyrosine kinase inhibitors (TKIs) are the central treatment strategy for CML patients and have significantly improved survival rates, but the T315I mutation in the kinase domain of BCR-ABL1 confers resistance to all clinically approved TKIs, except ponatinib. However, compound mutations can mediate resistance even to ponatinib and remain a clinical challenge in CML therapy. Here, we investigated a ponatinib-resistant CML patient through whole-genome sequencing (WGS) to identify the cause of resistance and to find alternative therapeutic targets.We carried out WGS on a ponatinib-resistant CML patient and demonstrated an effective combination therapy against the primary CML cells derived from this patient in vitro.Our findings demonstrate the emergence of compound mutations in the BCR-ABL1 kinase domain following ponatinib treatment, and chromosomal structural variation data predicted amplification of BCL2. The primary CD34(+) CML cells from this patient showed increased sensitivity to the combination of ponatinib and ABT-263, a BCL2 inhibitor with a negligible effect against the normal CD34(+) cells.Our results show the potential of personalised medicine approaches in TKI-resistant CML patients and provide a strategy that could improve clinical outcomes for these patients.
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.