Biomedical subjects

Mauro Tognon

Publications and source records attributed to Mauro Tognon.

8 recordsLinked to original sources

PubMed2003

Oncogenic transformation by BK virus and association with human tumors.

BK virus (BKV), a human polyomavirus closely related to JC virus and Simian Virus 40, is ubiquitous in human populations worldwide. After primary infection, BKV establishes a lifelong latent infection in many organs. BKV transforms rodent cells to the neoplastic phenotype and is highly oncogenic in rodents. This review considers the oncogenic potential of BKV in humans and its possible involvement in human tumors. BKV sequences and T antigen (Tag) are detected in several types of human neoplasms, although the viral load is generally low, with less than one copy of the viral genome per cell. The possible causative role of BKV in human oncogenesis rests on the ability of BKV Tag to inactivate the functions of tumor suppressor proteins p53 and pRB family as well as on its ability to induce chromosomal aberrations in human cells. A 'hit and run' mechanism and secretion of paracrine growth factors by BKV Tag-positive cells, recruiting into proliferation neighboring and distant cells, are discussed as possible BKV pathogenic elements in human oncogenesis.

Animals↗

PubMed2003

Recent developments in orofacial cleft genetics.

Nonsyndromic cleft of the lip and/or palate (CLP or orofacial cleft) derives from an embryopathy with consequent failure of the nasal process and/or palatal shelves fusion. This severe birth defect is one of the most common malformations among live births. Nonsyndromic CLP is composed of two separate entities: cleft lip and palate (CL+/-P) and cleft palate only (CPO). Both have a genetic background, and environmental factors probably disclose these malformations. In CL+/-P, several loci have been identified, and, in one case, a specific gene has also been found. In CPO, one gene has been identified, but many more are probably involved. Because of the complexity of the genetics of nonsyndromic CLP as a result of the difference between CL+/-P and CPO, heterogeneity of each group caused by the number of involved genes, type of inheritance, and interaction with environmental factors, we discuss the more sound results obtained with different approaches: epidemiological studies, animal models, human genetic studies, and in vitro studies.

Animals↗

PubMed2003

Simian virus 40 sequences in human lymphoblastoid B-cell lines.

Human Epstein-Barr virus-immortalized lymphoblastoid B-cell lines tested positive by PCR for simian virus 40 (SV40) DNA (22 of 42 cell lines, 52.3%). B lymphocytes or tissues from which B-cell lines derived were also SV40 positive. In situ hybridization showed that SV40 DNA was present in the nucleus of a small fraction (1/250) of cells. SV40 T-antigen mRNA was detected by reverse transcription-PCR. Lymphoblastoid B-cell lines (n = 4) infected with SV40 remained SV40 positive for 4 to 6 months. SV40-positive B-cell lines were more tumorigenic in SCID mice than were SV40-negative cell lines (4 of 5 [80%] SV40-positive cell lines versus 2 of 4 [50%] SV40-negative cell lines). These results suggest that SV40 may play a role in the early phases of human lymphomagenesis.

Animals↗

PubMed2003

Simian virus 40-like sequences from early and late regions in human thyroid tumors of different histotypes.

Simian virus 40 (SV40) sequences were investigated in human thyroid tumors of different histotypes, Graves' disease thyroid specimens, normal thyroid tissues, and peripheral blood mononuclear cells (PBMC) of healthy donors. Specific SV40 large T antigen (Tag) sequences were detected, by PCR and filter hybridization, in human thyroid tumors with a frequency ranging from 66% in papillary thyroid carcinomas (PTC) to 100% in anaplastic thyroid carcinomas (ATC). SV40 was revealed in 60% and 100% of normal thyroid tissues adjacent to PTC and ATC, respectively, but in only 10% of control normal thyroid tissues (NTT) from patients affected by multinodular goiter. Thyroid tissues from patients affected by the Graves' disease were found to be SV40 positive with a frequency of 20%. In agreement with previous investigations, the presence of SV40 sequences was detected in 25% of PBMC of healthy individuals. SV40 Tag mRNA was detected by RT-PCR, whereas the viral oncoprotein was revealed by immunohistochemistry with a specific monoclonal antibody. The high prevalence of SV40 footprints in human thyroid tumors indicates that the oncogenic virus may participate as a cofactor in the onset/progression of specific human thyroid cancers. Detection of SV40 sequences in NTT adjacent to thyroid cancers suggests that the viral infection may spread from transformed cells to normal cells surrounding the tumor. The presence of the SV40 footprint in PBMC implies that blood cells are vectors of the virus in other tissues of the host.

Adult↗

PubMed2002

Different simian virus 40 genomic regions and sequences homologous with SV40 large T antigen in DNA of human brain and bone tumors and of leukocytes from blood donors.

BACKGROUND: Many studies found only a small fragment of the large T-antigen coding sequences in human tumors, raising doubts on authenticity of SV40 sequences detected in these samples. METHODS: Five different regions of SV40 DNA were investigated in 106 fresh human tumor biopsies (25 brain, 69 bone, 12 Wilms' tumors), 71 tumor-derived cell cultures (38 from brain and 33 from bone tumors) and normal tissues (5 fresh bone biopsies and 38 buffy coats) by polymerase chain reaction (PCR) techniques and filter hybridization with specific oligoprobes. Expression of SV40 Tag sequences was analyzed in human tumor specimens by RT-PCR. RESULTS: SV40 large T-antigen sequences were detected at high prevalence, in human biopsies of primary brain (37-44%) and bone (21-37%) tumors, in cell cultures derived from brain (30-54%) and bone (53-80%) tumors. SV40 Tag sequences were detected in 29% of buffy coats of blood donors. However, only four brain tumor cell lines showed all the five regions of the SV40 genome investigated. Expression of SV40 Tag sequences was found in 11 of 27 (41%) human tumor samples. DNA sequence analysis indicated that the PCR-amplified products belong to the SV40 wild type. Polymerase chain reaction products of Tag middle portion from 20 of 78 (26%) samples showed a 97% homology with telomeric sequences of human chromosomes 10 and 11. CONCLUSIONS: Authentic SV40 sequences were detected in human samples. The expression of SV40 Tag sequences indicates that SV40 could play a role, as a cofactor, in the onset/progression of specific human cancers. The inability to detect some regions of the virus genome may suggest that those regions are not required for tumor persistence or growth and have been lost or, alternatively, may be the result of assay conditions that were unable to PCR-amplify those regions in the tumors.

Antigens, Polyomavirus Transforming↗

PubMed2002

Simian virus 40 sequences and expression of the viral large T antigen oncoprotein in human pleomorphic adenomas of parotid glands.

Simian virus 40 (SV40) sequences of the early region coding for the large T antigen (Tag) oncoprotein were investigated in DNA samples from human pleomorphic adenoma (PA) of parotid glands. Specific SV40 sequences were detected, by PCR and filter hybridization with an internal oligoprobe, in 28 of 45 (62%) human PA specimens. None of the DNA samples from 11 normal salivary gland tissues was SV40-positive. DNA sequence analysis, carried out in all PCR amplified products from SV40-positive PA specimens, confirmed the SV40 specificity and indicated that PCR products had a sequence not distinguishable from SV40 DNA wild-type strain 776. SV40 Tag expression was revealed by immunohistochemistry with the specific monoclonal antibody Pab 101 in PA thin sections with a highly sensitive technical approach which retrieved the nuclear viral oncoprotein in 26 out of 28 (93%) samples previously found SV40-positive by PCR. Detection of SV40 sequences and Tag expression in human PA suggests that this oncogenic virus may play a role as a cofactor in the onset and/or progression of this benign neoplasm, or that SV40 DNA could replicate and express the Tag in PA cells.

Adenoma, Pleomorphic↗

PubMed2002

The presence of simian-virus 40 sequences in mesothelioma and mesothelial cells is associated with high levels of vascular endothelial growth factor.

The aim of this study was to evaluate whether the presence of simian virus-40 (SV40) is associated with increased release of vascular endothelial growth factor (VEGF) in human malignant mesothelioma (MM) cells. We studied nine cell lines derived from pleural effusion (PE) of patients with MM, and three different cultures of normal human mesothelial cells (NHMC) derived from pleural fluid of patients with congestive heart failure. NHMC were transfected with full length SV40 (NHMC-FL) or large T antigen (NHMC Tag) DNAs. High levels of VEGF were detected in conditioned media of each of two MM cells that tested positive for SV40 by PCR amplification and Southern blot hybridization and for Tag transcript by reverse transcription- polymerase chain reaction (RT-PCR) and immunoprecipitation. We also found that NHMC-FL released high amounts of VEGF. Conditioned media from SV40-positive MM cells and from FL-NHMC increased proliferation of human umbilical vein cells (HUVEC) and this effect was partially abrogated by adding specific blocking antibodies against VEGF. These results offer the first evidence that SV40 can cause VEGF release in SV40-positive MM cells and that entire viral genome is required for this effect.

Antigens, Polyomavirus Transforming↗

PubMed2001

Linkage disequilibrium between GABRB3 gene and nonsyndromic familial cleft lip with or without cleft palate.

The malformation of nonsyndromic cleft lip with or without cleft palate (CL/P) is a common congenital disease that affects approximately 1/1000 newborns in Caucasian populations. Genetic studies indicate that CL/P has the characteristics of a complex genetic trait. Linkage analysis and mouse-model knockout studies have suggested several candidate genes mapping in different chromosome regions for CL/P malformation. On these grounds, we have investigated, by linkage disequilibrium (LD) and parametric and nonparametric linkage analyses, five different candidate genes, including those for the beta3 subunit of the gamma-aminobutyric acid receptor (GABRB3), glutamic acid decarboxylase 1 (GAD1), retinoic acid receptor alpha (RARA), transforming growth factor beta3 (TGFB3), and msh ( Drosophila) homeobox homolog 1 (MSX1). Interestingly, a significant LD between GABRB3 and CL/P was obtained ( P-value=0.008 in the allele-wise analysis for multiallelic markers), suggesting that the GABRB3 gene is involved in this congenital disease. This new finding in humans is in agreement with previously reported data obtained with the murine model. Indeed, mouse studies indicate a role for gamma-aminobutyric acid (GABA) and its receptor in normal palate development. Exclusion of the GAD1 gene, which encodes the GABA-producing enzyme, in CL/P pathogenesis was obtained in our study. Moreover, we were unable to confirm the involvement of the MSX1 gene in nonsyndromic CL/P. Modest evidence of LD between marker alleles and CL/P was found at the RARA and TGFB3 loci suggesting a minor role for these genes in our family set of nonsyndromic CL/P.

Cleft Lip↗