86 research outputs found
Preclinical Implementation of matRadiomics: A Case Study for Early Malformation Prediction in Zebrafish Model
No full textRadiomics provides a structured approach to support clinical decision-making through key steps; however, users often face difficulties when switching between various software platforms to complete the workflow. To streamline this process, matRadiomics integrates the entire radiomics workflow within a single platform. This study extends matRadiomics to preclinical settings and validates it through a case study focused on early malformation differentiation in a zebrafish model. The proposed plugin incorporates Pyradiomics and streamlines feature extraction, selection, and classification using machine learning models (linear discriminant analysis—LDA; k-nearest neighbors—KNNs; and support vector machines—SVMs) with k-fold cross-validation for model validation. Classifier performances are evaluated using area under the ROC curve (AUC) and accuracy. The case study indicated the criticality of the long time required to extract features from preclinical images, generally of higher resolution than clinical images. To address this, a feature analysis was conducted to optimize settings, reducing extraction time while maintaining similarity to the original features. As a result, SVM exhibited the best performance for early malformation differentiation in zebrafish (AUC = 0.723; accuracy of 0.72). This case study underscores the plugin’s versatility and effectiveness in early biological outcome prediction, emphasizing its applicability across biomedical research fields
TGF-β/VEGF-A Genetic Variants Interplay in Genetic Susceptibility to Non-Melanocytic Skin Cancer
No full textDifferential genetically determined expression of transforming growth factor-β (TGF-β pathway and of vascular endothelial growth factor-A (VEGF-A) might modulate the molecular “milieu” involved in the etio-pathogenesis of non-melanoma skin cancer (NMSC). We have evaluated the frequency of some functionally relevant SNPs of TGF-β and VEGF-A genes in 70 NMSC patients and 161 healthy controls, typed for TGF-β1 rs1800471, TGF-β2 rs900, TGF-βR1 rs334348 and rs334349, TGF-βR2 rs4522809 and VEGF-A rs3025039 SNPs. TGF-βR2 rs1800629G allele and related genotypes were found to be associated with a possible protective role against NMSC, whereas VEGF-A rs3025039T was associated with an increased risk. To evaluate the effect of genotype combinations on NMSC susceptibility, we determined the frequencies of 31 pseudo-haplotypes due to non-random linkage among alleles of loci not lying on the same chromosome. Two pseudo-haplotypes that imply a minor allele of TGF-βR2 or minor allele of VEGF-A SNPs combined with major alleles of the other SNPs were, respectively, associated with a protective effect, and susceptibility to NMSC. In addition, a pseudo-haplotype involving minor alleles of TGF-β2 rs900, TGF-βR1 rs334348 and rs4522809 SNPs might be a susceptibility marker for NMSC. In conclusion, our data suggest that a complex interplay among the genetic polymorphisms of TGF-β, TGF-β receptors and VEGF-A genes might influence the net effect of genetic background of the patients on NMSC development. This might be relevant in the risk evaluation, diagnosis and treatment of NMSC
“Omics” of HER2-Positive Breast Cancer
No full textHER2/neu amplification/overexpression is the only somatic mutation widely considered to be a marker of
disease outcome and response to treatment in breast cancer. Pathologists have made large efforts to achieve
accuracy in characterizing HER2/neu status. The introduction of transtuzumab contributed to development of
additional measures to identify sensitive and resistant subclasses of HER2/neu-positive tumors. In this article,
we describe the latest advances in HER2/neu status diagnostic assessment and the most relevant research
emerging from ‘‘Omics’’ (genomics, epigenetics, transcriptomics, and proteomics) studies on HER2/neu-positive
breast cancer. A large quantity of biomarkers from different studies highlighted HER2/neu-positive specific
proliferation, cell cycle arrest, and apoptosis mechanisms, as well as immunological and metabolic behavior.
Major driver genes of tumor progression have had a candidate status (GRB7, MYC, CCND1, EGFR, etc.), even
though the main role for HER2/neu is largely recognized. Nonetheless, existing omics data and HER2/neupositive
molecular profiles seem to suggest that few proteogenomic alterations in HER2, EGFR, and PI3K
networks could significantly affect the effectiveness of transtuzumab. The systematic search of molecular alterations
in and across these pathways can help to select the most appropriate drug for a given patient based on
in-depth understanding of complexity in tumor biology
Cytokine profile of breast cell lines after different radiation doses
No full textPurpose: Ionizing radiation (IR) treatment activates inflammatory processes causing the release of a great amount of molecules able to affect the cell survival. The aim of this study was to analyze the cytokine signature of conditioned medium produced by non-tumorigenic mammary epithelial cell line MCF10A, as well as MCF7 and MDA-MB-231 breast cancer cell lines, after single high doses of IR in order to understand their role in high radiation response. Materials and methods: We performed a cytokine profile of irradiated conditioned media of MCF10A, MCF7 and MDA-MB-231 cell lines treated with 9 or 23 Gy, by Luminex and ELISA analyses. Results: Overall, our results show that both 9 Gy and 23 Gy of IR induce the release within the first 72 h of cytokines and growth factors potentially able to influence the tumor outcome, with a dose-independent and cell-line dependent signature. Moreover, our results show that the cell-senescence phenomenon does not correlate with the amount of ‘senescence-associated secretory phenotype’ (SASP) molecules released in media. Thus, additional mechanisms are probably involved in this process. Conclusions: These data open the possibility to evaluate cytokine profile as useful marker in modulating the personalized radiotherapy in breast cancer care
A new method for the mapping of 5' ends of RNAs
No full textIn this article, we describe a new procedure to map 5′ ends of RNAs. The procedure consists in the use of specific RNase H digestion of a hybrid formed by the RNA and a complementary DNA oligonucleotide. Northern blot hybridization of the resulting RNA fragment allows an accurate measurement of its length. Although we generally use this procedure as a control of previously performed primer extension analyses, the absence of nonspecific bands, which often occur in primer extensions on RNA templates with extended secondary structures, suggests that our method may be preferable when these difficult templates are analyzed
Analysis of functionally relevant single nucleotide polymorphisms of TNF alfa and of IFN gamma in celiac disease
No full text
Analysis of functionally Relevant Single nucleotide polymorphisms of TNFα and of IFN-gamma in Celiac Disease
No full text
Mung Bean nuclease mapping of RNAs 3' end
No full textA method is described that allows an accurate mapping of 3' ends of RNAs. In this method a labeled
DNA probe, containing the presumed 3' end of the RNA under analysis is allowed to anneals to
the RNA itself. Mung-bean nuclease is then used to digest single strands of both RNA and DNA.
Electrophoretic fractionation of "protected" undigested, labeled DNA is than performed using a
sequence reaction of a known DNA as length marker. This procedure was applied to the analysis
of both a polyA RNA (Interleukin 10 mRNA) and non polyA RNAs (sea urchin 18S and 26S
rRNAs). This method might be potentially relevant for the evaluation of the role of
posttrascriptional control of IL-10 in the pathogenesis of the immune and inflammatory mediated
diseases associated to ageing. This might allow to develop new strategies to approach to the
diagnosis and therapy of age related disease
- …
