Proteomic changes driven by urban pollution suggest particulate matter as a deregulator of energy metabolism, mitochondrial activity, and oxidative pathways in the rat brain.

The adverse effects of air pollution have been long studied in the lung and respiratory systems, but the molecular changes that this causes at the central nervous system level have yet to be fully investigated and understood. To explore the evolution with time of protein expression levels in the brain of rats exposed to particulate matter of different sizes, we carried out two-dimensional gel electrophoresis followed by determination of dysregulated proteins through Coomassie blue staining-based densities (SameSpots software) and subsequent protein identification using MALDI-based mass spectrometry. Expression differences in dysregulated proteins were found to be statistically significant with p-value <0.05. A systems biology-based approach was utilized to determine critical biochemical pathways involved in the rats' brain response. Our results suggest that rats' brains have a particulate matter size dependent-response, being the mitochondrial activity and the astrocyte function severely affected. Our proteomic study confirms the dysregulation of different biochemical pathways involving energy metabolism, mitochondrial activity, and oxidative pathways as some of the main effects of PM exposure on the rat brain. SIGNIFICANCE: Rat brains exposed to particulate matter with origin in car engines are affected in two main areas: mitochondrial activity, by the dysregulation of many pathways linked to the respiratory chain, and neuronal and astrocytic function, which stimulates brain changes triggering tumorigenesis and neurodegeneration.

Genetic and molecular alterations in rhabdomyosarcoma: mRNA overexpression of MCL1 and MAP2K4 genes.

Rhabdomyosarcoma, the most common soft tissue sarcoma in childhood, belongs to the small round cell tumor family and is classified according to its histopathological features as embryonal, alveolar and pleomorphic. In this study we propose to explore genetic alterations involved in rhabdomyosarcoma tumorigenesis and assess the level of mRNA gene expression of controlling survival signalling pathways. For genetic and molecular analysis, array-based comparative genomic hybridization, combined with Real Time PCR using the comparative method, was performed on 14 primary well-characterized human primary rhabdomyosarcomas. Multiple changes affecting chromosome arms were detected in all cases, including gain or loss of specific regions harbouring cancer progression-associated genes. Evaluation of mRNA levels showed in the majority of cases overexpression of MCL1 and MAP2K4 genes, both involved in cell viability regulation. Our findings on rhabdomyosarcoma samples showed multiple copy number alterations in chromosome regions implicated in malignancy progression and indicated a strong expression of MAP2K4 and MCL1 genes, both involved in different biological functions of complicated signalling pathways.

Altered expression of urokinase-type plasminogen activator and plasminogen activator inhibitor in high-risk soft tissue sarcomas.

In recent years, classification of soft-tissue sarcomas (STS) has improved with cytogenetic analyses, but their clinical behavior is still not easily predictable. The aim of this study was to detect alterations in the urokinase-type plasminogen system, involved in tumor growth and invasion, by comparing mRNA levels of its components with those of paired normal tissues, and relating them with patient clinical course. Real-time PCR was performed on human STS cell lines and tissues from highly malignant STS, including leiomyosarcomas and malignant fibrous histiocytomas, to evaluate the expression of urokinase-type plasminogen activator (uPA), uPA receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1). Immunohistochemistry of gene products was also performed. Median mRNA values of all genes studied were higher in tumors than in paired normal tissues. In agreement with data on STS cell lines, significant up-regulation for uPA and PAI-1 genes compared to reference values was seen. Moreover, different levels of expression were related to histotype and metastatic phenotype. There was accordance between uPA mRNA and protein expression, while immunodetection of PAI-1 product was weak and scattered. Clearly, the controversial role of PAI-1 protein requires further biological analyses, but evident involvement of uPA/PAI-1 gene overexpression in STS malignancy may highlight a molecular defect useful in discriminating STS high-risk patients.

Molecular alterations of monophasic synovial sarcoma: loss of chromosome 3p does not alter RASSF1 and MLH1 transcriptional activity.

Differential diagnosis of monophasic synovial sarcoma requires the detection of specific biological markers. In this study we evaluated the presence of molecular alterations in 15 monophasic synovial sarcomas. Multiple changes affecting chromosome arms were detected by CGH-array in all microdissected cases available, and an association between gain or loss of specific regions harbouring cancer progression-associated genes and aneuploid status was found. The most frequent alteration was loss of 3p including 3p21.3-p23 region that, however, did not involve the promoter regions of the corresponding genes, RASSF1 and MLH1. Using Real-Time PCR, mRNA levels of both resulted moderately high compared to normal tissue; however, the weak to absent protein expression suggests RASSF1 and MLH1 post-transcription deregulation. Moreover, immunohistochemical analysis revealed that both mesenchymal and epithelial antigens were present in diploid tumours. These findings confirm the genetic complexity of monophasic synovial sarcoma and underline the need to integrate different analyses for a better knowledge of this tumour, essential to investigate new diagnostic and prognostic markers.

[Tridimensional ultrasonography in andrology]. / L'ecografia tridimensionale in andrologia.

Three-dimensional ultrasound has already been employed to improve detection and characterization of the masses in various organs. The system can also be expected to improve qualitative evaluation of vessel pathology. Three-dimensional ultrasound could offer an additional contribution even in Andrology, in at least three fields: in the best evaluation of the anatomical structures; in most accurate measurement of the volumes of the organs; in the study of the Peyronie's disease, for the availability of the coronal plain.