8 results on '"Vascellari M."'
Search Results
2. Transcriptomic analysis identified up-regulation of a solute carrier transporter and UDP glucuronosyltransferases in dogs with aggressive cutaneous mast cell tumours.
- Author
-
Giantin M, Baratto C, Marconato L, Vascellari M, Mutinelli F, Dacasto M, and Granato A
- Subjects
- Amino Acid Transport Systems, Neutral metabolism, Animals, Dogs, Female, Gene Expression Profiling veterinary, Glucuronosyltransferase metabolism, Male, Mast Cells metabolism, Mastocytoma, Skin genetics, Transcriptome, Up-Regulation, Amino Acid Transport Systems, Neutral genetics, Dog Diseases genetics, Gene Expression Regulation, Neoplastic, Glucuronosyltransferase genetics, Mastocytoma, Skin veterinary, Skin Neoplasms genetics
- Abstract
Gene expression analyses have been recently used in cancer research to identify genes associated with tumorigenesis and potential prognostic markers or therapeutic targets. In the present study, the transcriptome of dogs that had died because of mast cell tumours (MCTs) was characterised to identify a fingerprint having significant influence on prognosis determination and treatment selection. A dataset (GSE50433) obtained using a commercial canine DNA microarray platform was used. The transcriptome of seven biopsies obtained from dogs with histologically confirmed, surgically removed MCTs, treated with chemotherapy, and dead for MCT-related causes, was compared with the transcriptional portrait of 40 samples obtained from dogs with histologically confirmed, surgically removed MCTs and that were still alive at the end of the follow-up period. Among the differentially expressed genes (DEGs), eight transcripts were validated by quantitative real time PCR and their mRNA levels were measured in a cohort of 22 additional MCTs. Statistical analysis identified 375 DEGs (fold change 2, false discovery rate 5%). The functional annotation analysis indicated that the DEGs were associated with drug metabolism and cell cycle pathways. Particularly, members of solute carrier transporter (SLC) and UDP glucuronosyltransferase (UGT) gene families were identified as dysregulated. Principal component analysis (PCA) of the 22 additional MCTs identified the separate cluster dogs dead for MCT-related causes. SLCs and UGTs have been recently recognised in human cancer as important key factors in tumour progression and chemo-resistance. An in-depth analysis of their roles in aggressive canine MCT is warranted in future studies., (Copyright © 2016 Elsevier Ltd. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
3. Global gene expression analysis of canine cutaneous mast cell tumor: could molecular profiling be useful for subtype classification and prognostication?
- Author
-
Giantin M, Granato A, Baratto C, Marconato L, Vascellari M, Morello EM, Vercelli A, Mutinelli F, and Dacasto M
- Subjects
- Animals, Cluster Analysis, Dog Diseases diagnosis, Dog Diseases mortality, Dogs, Reproducibility of Results, Dog Diseases genetics, Gene Expression Profiling, Mastocytosis, Cutaneous veterinary, Skin Neoplasms veterinary, Transcriptome
- Abstract
Prognosis and therapeutic management of dogs with cutaneous mast cell tumors (MCTs) depend on clinical stage and histological grade. However, the prognostic value of this latter is still questionable. In the present study, MCT transcriptome was analyzed to identify a set of candidate genes potentially useful for predicting the biological behavior of MCTs. Fifty-one canine MCT biopsies were analyzed. Isolated and purified total RNAs were individually hybridized to the Agilent Canine V2 4x44k DNA microarray. The comparison of reference differentiated and undifferentiated MCT transcriptome revealed a total of 597 differentially expressed genes (147 down-regulated and 450 up-regulated). The functional analysis of this set of genes provided evidence that they were mainly involved in cell cycle, DNA replication, p53 signaling pathway, nucleotide excision repair and pyrimidine metabolism. Class prediction analysis identified 13 transcripts providing the greatest accuracy of class prediction and divided samples into two categories (differentiated and undifferentiated), harboring a different prognosis. The Principal Component Analysis of all samples, made by using the selected 13 markers, confirmed MCT classification. The first three components accounted for 99.924% of the total variance. This molecular classification significantly correlated with survival time (p = 0.0026). Furthermore, among all marker genes, a significant association was found between mRNA expression and MCT-related mortality for FOXM1, GSN, FEN1 and KPNA2 (p<0.05). Finally, marker genes mRNA expression was evaluated in a cohort of 22 independent samples. Data obtained enabled to identify MCT cases with different prognosis. Overall, the molecular characterization of canine MCT transcriptome allowed the identification of a set of 13 transcripts that clearly separated differentiated from undifferentiated MCTs, thus predicting outcome regardless of the histological grade. These results may have clinical relevance and warrant future validation in a prospective study.
- Published
- 2014
- Full Text
- View/download PDF
4. Expression of Ki67, BCL-2, and COX-2 in canine cutaneous mast cell tumors: association with grading and prognosis.
- Author
-
Vascellari M, Giantin M, Capello K, Carminato A, Morello EM, Vercelli A, Granato A, Buracco P, Dacasto M, and Mutinelli F
- Subjects
- Animals, Biomarkers, Tumor metabolism, Cyclooxygenase 2 genetics, Cyclooxygenase 2 metabolism, Dog Diseases metabolism, Dogs, Female, Follow-Up Studies, Gene Expression Regulation, Neoplastic, Immunohistochemistry veterinary, Ki-67 Antigen genetics, Ki-67 Antigen metabolism, Male, Mast Cells metabolism, Mast Cells pathology, Mast-Cell Sarcoma metabolism, Mast-Cell Sarcoma pathology, Mastocytosis, Cutaneous metabolism, Mastocytosis, Cutaneous pathology, Mitotic Index, Neoplasm Grading veterinary, Prognosis, Prospective Studies, Proto-Oncogene Proteins c-bcl-2 genetics, Proto-Oncogene Proteins c-bcl-2 metabolism, Skin metabolism, Skin pathology, Skin Neoplasms metabolism, Skin Neoplasms pathology, Biomarkers, Tumor genetics, Dog Diseases pathology, Mast-Cell Sarcoma veterinary, Mastocytosis, Cutaneous veterinary, Skin Neoplasms veterinary
- Abstract
The expression of Ki67, BCL-2, and COX-2 was investigated in 53 canine cutaneous mast cell tumors (MCTs) by immunohistochemistry and quantitative real time polymerase chain reaction (qPCR) to evaluate their prognostic significance and the association with the histologic grading and the mitotic index (MI). MCTs were graded according to the Patnaik grading system and the novel 2-tier grading system proposed by Kiupel. The numbers of mitotic figures/10 high-power fields (MI) were counted. Both grading systems were significantly associated with prognosis. The Patnaik grading was of limited prognostic value for grade 2 MCTs, with 23% being associated with mortality. The concordance among pathologists was strongly improved by the application of the 2-tier grading system, and 71% of high-grade MCTs were associated with a high mortality rate. MI and Ki67 protein expression were significantly associated with grading and survival. No significant association between BCL-2 protein expression and either grading system or health status was observed. BCL-2 mRNA expression was significantly higher in grade 2 than in grade 1 MCTs, while no statistically significant differences were detected between low- and high-grade MCTs. The increased BCL-2 mRNA level was significantly associated with increased mortality rate. The COX-2 protein expression was detected in 78% of the MCTs investigated. However, neither association with the tumor grade nor with the health status was observed. COX-2 mRNA was significantly up-regulated in MCTs compared to surgical margins and control skin tissue, but it was neither associated with tumor grade nor with survival.
- Published
- 2013
- Full Text
- View/download PDF
5. Expression of matrix metalloproteinases, tissue inhibitors of metalloproteinases and vascular endothelial growth factor in canine mast cell tumours.
- Author
-
Giantin M, Aresu L, Benali S, Aricò A, Morello EM, Martano M, Vascellari M, Castagnaro M, Lopparelli RM, Zancanella V, Granato A, Mutinelli F, and Dacasto M
- Subjects
- Animals, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, DNA, Neoplasm analysis, Dog Diseases metabolism, Dog Diseases pathology, Dogs, Female, Immunohistochemistry, Male, Mast-Cell Sarcoma genetics, Mast-Cell Sarcoma metabolism, Mast-Cell Sarcoma pathology, Matrix Metalloproteinases metabolism, Polymerase Chain Reaction veterinary, RNA, Messenger metabolism, Skin Neoplasms genetics, Skin Neoplasms metabolism, Skin Neoplasms pathology, Tissue Inhibitor of Metalloproteinases metabolism, Vascular Endothelial Growth Factor A metabolism, Dog Diseases genetics, Gene Expression Regulation, Neoplastic physiology, Mast-Cell Sarcoma veterinary, Matrix Metalloproteinases genetics, Skin Neoplasms veterinary, Tissue Inhibitor of Metalloproteinases genetics, Vascular Endothelial Growth Factor A genetics
- Abstract
Degradation of the extracellular matrix and angiogenesis are associated with tumour invasion and metastasis in human and canine neoplasia. Matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs) and vascular endothelial growth factor-A (VEGF-A) are key mediators of these respective processes. Mast cell tumour (MCT) is the most common malignant cutaneous tumour in dogs. MCTs are always considered potentially malignant, but their true metastatic potential is unknown. In the present study, samples from seven grade 1, 22 grade 2 and six grade 3 MCTs were subjected to quantitative real-time polymerase chain reaction and immunohistochemistry (IHC) to evaluate MMP-2, MMP-9, membrane-type 1 MMP (MT1-MMP), TIMP-2 and VEGF-A mRNA and protein expression. Gelatin zymography (GZ) was also performed to evaluate MMP-2 and MMP-9 activity. MMP-9 and VEGF-A mRNA increased with histological grade, while TIMP-2 decreased with increasing grade. Gene expression data obtained for MMP-9, VEGF-A and TIMP-2 were confirmed by IHC for evaluation of the respective proteins. In contrast, MMP-2 and MT1-MMP had variable, but similar, expression for both mRNA and protein. Despite the high variability observed, there was correlation between MMP-2 and MT1-MMP mRNA expression (r=+0.91, P<0.0001). The MMP-2:TIMP-2 and MMP-9:TIMP-1 mRNA ratios showed an imbalance between MMPs and their specific inhibitors in MCTs, which increased with the histological grade. Finally, the activities of both latent and active forms of MMP-2 and MMP-9 were evaluated by GZ and there were significant increases in their activities with increasing histological grade and immunohistochemical expression. This study demonstrates that MMP-9, TIMP-2 and VEGF-A expression is related to histological grade and suggests that these markers are possible indicators of malignancy and targets for therapeutic strategies., (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Published
- 2012
- Full Text
- View/download PDF
6. Metastatic hepatocellular carcinoma and subcutaneous fibrosarcoma in a black-headed gull (Larus ridibundus).
- Author
-
Mutinelli F, Carminato A, Schiavon E, Melchiotti E, Trevisan L, and Vascellari M
- Subjects
- Animals, Autopsy veterinary, Carcinoma, Hepatocellular pathology, Carcinoma, Hepatocellular secondary, Fatal Outcome, Fibrosarcoma pathology, Liver Neoplasms pathology, Male, Pancreatic Neoplasms secondary, Pancreatic Neoplasms veterinary, Peritoneal Neoplasms secondary, Peritoneal Neoplasms veterinary, Skin Neoplasms pathology, Bird Diseases pathology, Carcinoma, Hepatocellular veterinary, Charadriiformes, Fibrosarcoma veterinary, Liver Neoplasms veterinary, Skin Neoplasms veterinary
- Published
- 2009
- Full Text
- View/download PDF
7. Transcriptomic analysis identified up-regulation of a solute carrier transporter and UDP glucuronosyltransferases in dogs with aggressive cutaneous mast cell tumours
- Author
-
Marta Vascellari, Franco Mutinelli, Mauro Dacasto, Mery Giantin, Chiara Baratto, Laura Marconato, Anna Granato, Giantin M., Baratto C., Marconato L., Vascellari M., Mutinelli F., Dacasto M., and Granato A.
- Subjects
0301 basic medicine ,Male ,Pathology ,medicine.medical_specialty ,Skin Neoplasms ,Biology ,medicine.disease_cause ,Transcriptome ,03 medical and health sciences ,0302 clinical medicine ,Dogs ,dog, mast cell tumour, solute carrier transporter, transcriptome, UDP glucuronosyltransferase, genomics ,Gene expression ,medicine ,genomics ,Mast Cell ,Animals ,Skin Neoplasm ,Dog Diseases ,Mast Cells ,Glucuronosyltransferase ,Mastocytoma, Skin ,General Veterinary ,Animal ,Gene Expression Profiling ,UDP glucuronosyltransferase ,solute carrier transporter ,Cell cycle ,mast cell tumour ,Fold change ,Solute carrier family ,Up-Regulation ,Gene expression profiling ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,Amino Acid Transport Systems, Neutral ,030220 oncology & carcinogenesis ,dog ,Genomic ,Animal Science and Zoology ,Female ,Dog Disease ,DNA microarray ,Carcinogenesis ,transcriptome - Abstract
Gene expression analyses have been recently used in cancer research to identify genes associated with tumorigenesis and potential prognostic markers or therapeutic targets. In the present study, the transcriptome of dogs that had died because of mast cell tumours (MCTs) was characterised to identify a fingerprint having significant influence on prognosis determination and treatment selection. A dataset (GSE50433) obtained using a commercial canine DNA microarray platform was used. The transcriptome of seven biopsies obtained from dogs with histologically confirmed, surgically removed MCTs, treated with chemotherapy, and dead for MCT-related causes, was compared with the transcriptional portrait of 40 samples obtained from dogs with histologically confirmed, surgically removed MCTs and that were still alive at the end of the follow-up period. Among the differentially expressed genes (DEGs), eight transcripts were validated by quantitative real time PCR and their mRNA levels were measured in a cohort of 22 additional MCTs.Statistical analysis identified 375 DEGs (fold change 2, false discovery rate 5%). The functional annotation analysis indicated that the DEGs were associated with drug metabolism and cell cycle pathways. Particularly, members of solute carrier transporter (SLC) and UDP glucuronosyltransferase (UGT) gene families were identified as dysregulated. Principal component analysis (PCA) of the 22 additional MCTs identified the separate cluster dogs dead for MCT-related causes. SLCs and UGTs have been recently recognised in human cancer as important key factors in tumour progression and chemo-resistance. An in-depth analysis of their roles in aggressive canine MCT is warranted in future studies. (C) 2016 Elsevier Ltd. All rights reserved.
- Published
- 2016
8. Global gene expression analysis of canine cutaneous mast cell tumor: could molecular profiling be useful for subtype classification and prognostication?
- Author
-
Emanuela Maria Morello, Marta Vascellari, Laura Marconato, Chiara Baratto, Mery Giantin, Mauro Dacasto, Franco Mutinelli, Anna Granato, A. Vercelli, Giantin M., Granato A., Baratto C., Marconato L., Vascellari M., Morello E.M., Vercelli A., Mutinelli F., and Dacasto M.
- Subjects
Candidate gene ,Pathology ,Skin Neoplasms ,Cellular differentiation ,Mastocytosis, Cutaneou ,Gene Expression ,Transcriptome ,Gene expression ,Dog ,Cluster Analysis ,Dog Diseases ,Multidisciplinary ,Genomics ,mast cell tumours ,DNA microarray ,prognosis ,classification ,Medicine ,Dog Disease ,Transcriptome Analysis ,Research Article ,Veterinary Medicine ,medicine.medical_specialty ,Mastocytosis, Cutaneous ,Science ,Reproducibility of Result ,Biology ,Dogs ,Genetics ,medicine ,Animals ,canine cutaneous mast cell tumors ,Skin Neoplasm ,Gene ,Cluster Analysi ,Animal ,Gene Expression Profiling ,Biology and Life Sciences ,Computational Biology ,Reproducibility of Results ,Genome Analysis ,Gene expression profiling ,FOXM1 ,Cancer research ,Veterinary Oncology ,Veterinary Science ,Genome Expression Analysis - Abstract
Prognosis and therapeutic management of dogs with cutaneous mast cell tumors (MCTs) depend on clinical stage and histological grade. However, the prognostic value of this latter is still questionable. In the present study, MCT transcriptome was analyzed to identify a set of candidate genes potentially useful for predicting the biological behavior of MCTs. Fifty-one canine MCT biopsies were analyzed. Isolated and purified total RNAs were individually hybridized to the Agilent Canine V2 4x44k DNA microarray. The comparison of reference differentiated and undifferentiated MCT transcriptome revealed a total of 597 differentially expressed genes (147 down-regulated and 450 up-regulated). The functional analysis of this set of genes provided evidence that they were mainly involved in cell cycle, DNA replication, p53 signaling pathway, nucleotide excision repair and pyrimidine metabolism. Class prediction analysis identified 13 transcripts providing the greatest accuracy of class prediction and divided samples into two categories (differentiated and undifferentiated), harboring a different prognosis. The Principal Component Analysis of all samples, made by using the selected 13 markers, confirmed MCT classification. The first three components accounted for 99.924% of the total variance. This molecular classification significantly correlated with survival time (p = 0.0026). Furthermore, among all marker genes, a significant association was found between mRNA expression and MCT-related mortality for FOXM1, GSN, FEN1 and KPNA2 (p
- Published
- 2014
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.