An Outlook on Ovarian Cancer and Borderline Ovarian Tumors: Focus on Genomic and Proteomic Findings

Among the gynaecological malignancies, ovarian cancer is one of the neoplastic forms with the poorest prognosis and with the bad overall and disease-free survival rates than other gynaecological cancers. Ovarian tumors can be classified on the basis of the cells of origin in epithelial, stromal and germ cell tumors. Epithelial ovarian tumors display great histological heterogeneity and can be further subdivided into benign, intermediate or borderline, and invasive tumors. Several studies on ovarian tumors, have focused on the identification of both diagnostic and prognostic markers for applications in clinical practice. High-throughput technologies have accelerated the process of biomolecular study and genomic discovery; unfortunately, validity of these should be still demonstrated by extensive researches on sensibility and sensitivity of ovarian cancer novel biomarkers, determining whether gene profiling and proteomics could help differentiate between patients with metastatic ovarian cancer and primary ovarian carcinomas, and their potential impact on management. Therefore, considerable interest lies in identifying molecular and protein biomarkers and indicators to guide treatment decisions and clinical follow up. In this review, the current state of knowledge about the genoproteomic and potential clinical value of gene expression profiling in ovarian cancer and ovarian borderline tumors is discussed, focusing on three main areas: distinguishing normal ovarian tissue from ovarian cancers and borderline tumors, identifying different genotypes of ovarian tissue and identifying proteins linked to cancer or tumor development. By these targets, authors focus on the use of novel molecules, developed on the proteomics and genomics researches, as potential protein biomarkers in the management of ovarian cancer or borderline tumor, overlooking on current state of the art and on future perspectives of researches

Ovarian Cancer Biomarkers: A Focus on Genomic and Proteomic Findings

Among the gynaecological malignancies, ovarian cancer is one of the neoplastic forms with the poorest prognosis and with the bad overall and disease-free survival rates than other gynaecological cancers; several studies, analyzing clinical data and pathological features on ovarian cancers, have focused on the identification of both diagnostic and prognostic markers for applications in clinical practice. High-throughput technologies have accelerated the process of biomarker discovery, but their validity should be still demonstrated by extensive researches on sensibility and sensitivity of ovarian cancer novel biomarkers, determining whether gene profiling and proteomics could help differentiate between patients with metastatic ovarian cancer and primary ovarian carcinomas, and their potential impact on management

Silencing of ATI genes involved in adverse reactions to wheat by RNAi and CRISPR-Cas9 technologies

Although wheat is consumed worldwide as a staple food, it can give rise to different adverse reactions, some of which have not been deeply characterized. They are caused mainly by wheat proteins, both gluten and non-gluten proteins. Structural and metabolic proteins, like \u3b1amylase/trypsin inhibitors (ATI) are involved in the onset of wheat allergies (bakers\u2019 asthma) and probably non-coeliac wheat sensitivity (NCWS). The ATI are encoded by a multigene family dispersed over several. Notably, WTAI-CM3 and WTAI-CM16 subunits are involved in the onset of bakers\u2019 asthma and are likely to contribute to NCWS. In this study we report the RNAi silencing of WTAI-CM3, WTAI-CM16 and WMAI-0.28 genes in the bread wheat cultivar Bobwhite and the CRISPR/Cas9 mediated gene knockout of WTAI-CM3 and WTAI-CM16 in the durum wheat cultivar Svevo. We have obtained different RNAi transgenic lines showing an effective decrease in the expression in the targeted genes. These lines do not show differences in terms of yield, but have unintended effects on the accumulation of the high molecular weight glutenin subunits which play a crucial role in the technological performances of wheat flour. Furthermore, the editing of WTAI-CM3 and WTAI-CM16 genes was obtained through a CRISPR-Cas9 multiplexing strategy in the Italian durum wheat cultivar Svevo with a marker-free approach. The regeneration of plants without selection agents allowed T0 homozygous mutant plants to be obtained without the integration in the wheat genome of CRISPR/Cas9 vectors, demonstrating the capability of CRISPR technology to produce wheat lines in a reduced time compared to conventional breeding approaches. The possibility to develop new wheat genotypes accumulating a lower amount of proteins effectively involved in such pathologies, not only offers the possibility to use them as a basis for the creation of wheat varieties with a lower impact on adverse reactions, but also to test if these proteins are actually implicated in those pathologies for which the triggering factor has yet to be established

Biomechanical and proteomic analysis of INF- β-treated astrocytes

Astrocytes have a key role in the pathogenesis of several diseases including multiple sclerosis and were proposed as the designed target for immunotherapy. In this study we used atomic force microscopy (AFM) and proteomics methods to analyse and correlate the modifications induced in the viscoleastic properties of astrocytes to the changes induced in protein expression after interferon- beta (IFN-beta) treatment. Our results indicated that IFN-beta treatment resulted in a significant decrease in the Young's modulus, a measure of cell elasticity, in comparison with control cells. The molecular mechanisms that trigger these changes were investigated by 2DE (two-dimensional electrophoresis) and confocal analyses and confirmed by western blotting. Altered proteins were found to be involved in cytoskeleton organization and other important physiological processes

Biomechanical and proteomic analysis of INF- beta-treated astrocytes

Astrocytes have a key role in the pathogenesis of several diseases including multiple sclerosis and were proposed as the designed target for immunotherapy. In this study we used atomic force microscopy (AFM) and proteomics methods to analyse and correlate the modifications induced in the viscoleastic properties of astrocytes to the changes induced in protein expression after interferon-β (IFN-β) treatment. Our results indicated that IFN-β treatment resulted in a significant decrease in the Young’s modulus, a measure of cell elasticity, in comparison with control cells. The molecular mechanisms that trigger these changes were investigated by 2DE (two-dimensional electrophoresis) and confocal analyses and confirmed by western blotting. Altered proteins were found to be involved in cytoskeleton organization and other important physiological processes

IFN-beta reverses the lipopolysaccharide-induced proteome modifications in treated astrocytes

Astrocytes have a key role in the pathogenesis of several diseases, including multiple sclerosis, and are proposed as a possible target for immunotherapy. Our earlier study reported that astrocytes treated with IFN-β modified their biomechanical properties possibly due to changes in the expression of the proteins involved in cytoskeleton organization and other important physiological processes. To gain insight into the mechanism underlying IFN-β action during inflammation, we stimulated astrocytes with LPS, a bacterial wall component used as a model for both in vitro and in vivo immunological stimulation of microglia and astrocytes. We showed that IFN-β reverses the effects of LPS on the proteome of astrocytes. To better examine this result, we performed a proteomic analysis of astrocytes treated with LPS or LPS plus IFN-β. Treatment with LPS caused increases both in a series of proteins mainly involved in cytoskeletal changes and in protein degradation, as well as protective enzymes like superoxide dismutase. IFN-β reverses LPS effects on astrocyte proteome, supporting its protective role during inflammatory insults

Avaliação comparativa dos efeitos da terapia de fotobiomodulação com laser infravermelho e vermelho na atrofia muscular esquelética em modelo de imobilização em ratos

Não se aplic