Novel insights into the biology of brain metastasis

The incidence of brain metastases is on the rise due to improved cancer treatments, affecting patient morbidity and survival rates. Despite therapeutic advancements, treating brain metastases remains challenging due to the blood-brain barrier limitations. Understanding the unique biological and immunological characteristics of brain metastases is crucial for developing targeted therapies. Bioinformatics and data analysis play a key role in identifying molecular signatures and expression patterns related to brain metastasis. To address these challenges, we performed comparative analysis of brain metastases from lung adenocarcinoma (BM-LUAD) and breast cancer (BM-BC). We found differences in immune response, higher immune infiltration, and higher expression of immune checkpoint molecules in BM-LUAD. Through the analysis of matched-paired samples, we identified the molecular mechanisms and druggable targets in BM-LUAD and BM-BC. We additionally investigated differences in immune- and cancer-related genes in non-small cell lung cancer (NSCLC) patients who developed brain metastasis and those who developed metastasis to other organ than the brain. We found differences in immune response in primary NSCLC samples in relation to subsequent brain-specific metastasis. Spatial profiling revealed specific organization of immune cells across the tissue.Furthermore, we explored the association between gut microbiota, inflammatory immune markers, white blood cell counts, and risk of cancer development. We found a positive association between gut microbiota, higher SII levels, and higher lymphocyte and granulocyte counts, contributing to an increased risk of lung cancer development.<br/

Novel insights into the biology of brain metastasis

The incidence of brain metastases is on the rise due to improved cancer treatments, affecting patient morbidity and survival rates. Despite therapeutic advancements, treating brain metastases remains challenging due to the blood-brain barrier limitations. Understanding the unique biological and immunological characteristics of brain metastases is crucial for developing targeted therapies. Bioinformatics and data analysis play a key role in identifying molecular signatures and expression patterns related to brain metastasis. To address these challenges, we performed comparative analysis of brain metastases from lung adenocarcinoma (BM-LUAD) and breast cancer (BM-BC). We found differences in immune response, higher immune infiltration, and higher expression of immune checkpoint molecules in BM-LUAD. Through the analysis of matched-paired samples, we identified the molecular mechanisms and druggable targets in BM-LUAD and BM-BC. We additionally investigated differences in immune- and cancer-related genes in non-small cell lung cancer (NSCLC) patients who developed brain metastasis and those who developed metastasis to other organ than the brain. We found differences in immune response in primary NSCLC samples in relation to subsequent brain-specific metastasis. Spatial profiling revealed specific organization of immune cells across the tissue.Furthermore, we explored the association between gut microbiota, inflammatory immune markers, white blood cell counts, and risk of cancer development. We found a positive association between gut microbiota, higher SII levels, and higher lymphocyte and granulocyte counts, contributing to an increased risk of lung cancer development.<br/

Continuum Line-of-Sight Percolation on Poisson-Voronoi Tessellations

In this work, we study a new model for continuum line-of-sight percolation in a random environment driven by the Poisson-Voronoi tessellation in the $d$-dimensional Euclidean space. The edges (one-dimensional facets, or simply 1-facets) of this tessellation are the support of a Cox point process, while the vertices (zero-dimensional facets or simply 0-facets) are the support of a Bernoulli point process. Taking the superposition $Z$ of these two processes, two points of $Z$ are linked by an edge if and only if they are sufficiently close and located on the same edge (1-facet) of the supporting tessellation. We study the percolation of the random graph arising from this construction and prove that a 0-1 law, a subcritical phase as well as a supercritical phase exist under general assumptions. Our proofs are based on a coarse-graining argument with some notion of stabilization and asymptotic essential connectedness to investigate continuum percolation for Cox point processes. We also give numerical estimates of the critical parameters of the model in the planar case, where our model is intended to represent telecommunications networks in a random environment with obstructive conditions for signal propagation.Comment: 30 pages, 4 figures. Accepted for publication in Advances in Applied Probabilit

Unlocking molecular mechanisms and identifying druggable targets in matched-paired brain metastasis of breast and lung cancers

Introduction: The incidence of brain metastases in cancer patients is increasing, with lung and breast cancer being the most common sources. Despite advancements in targeted therapies, the prognosis remains poor, highlighting the importance to investigate the underlying mechanisms in brain metastases. The aim of this study was to investigate the differences in the molecular mechanisms involved in brain metastasis of breast and lung cancers. In addition, we aimed to identify cancer lineage-specific druggable targets in the brain metastasis. Methods: To that aim, a cohort of 44 FFPE tissue samples, including 22 breast cancer and 22 lung adenocarcinoma (LUAD) and their matched-paired brain metastases were collected. Targeted gene expression profiles of primary tumors were compared to their matched-paired brain metastases samples using nCounter PanCancer IO 360™ Panel of NanoString technologies. Pathway analysis was performed using gene set analysis (GSA) and gene set enrichment analysis (GSEA). The validation was performed by using Immunohistochemistry (IHC) to confirm the expression of immune checkpoint inhibitors. Results:Our results revealed the significant upregulation of cancer-related genes in primary tumors compared to their matched-paired brain metastases (adj. p ≤ 0.05). We found that upregulated differentially expressed genes in breast cancer brain metastasis (BM-BC) and brain metastasis from lung adenocarcinoma (BM-LUAD) were associated with the metabolic stress pathway, particularly related to the glycolysis. Additionally, we found that the upregulated genes in BM-BC and BM-LUAD played roles in immune response regulation, tumor growth, and proliferation. Importantly, we identified high expression of the immune checkpoint VTCN1 in BM-BC, and VISTA, IDO1, NT5E, and HDAC3 in BM-LUAD. Validation using immunohistochemistry further supported these findings. Conclusion: In conclusion, the findings highlight the significance of using matched-paired samples to identify cancer lineage-specific therapies that may improve brain metastasis patients outcomes.</p

Influence de la modélisation spectrale sur les performances d'un système de conversion de voix

- La conversion de voix est une technique qui consiste à modifier le signal de parole d'un locuteur de référence appelé aussi locuteur source, d'une façon telle qu'il semble, à l'écoute, être prononcé par le locuteur désiré. Dans ce papier, nous étudions l'influence de la modélisation spectrale sur la qualité de la conversion du timbre. Nous comparons, dans le cadre de la conversion par GMM, les modélisations par cepstre discret et par paramètres LSF. Des tests objectifs montrent que l'utilisation des paramètres LSF conduit à de meilleurs résultats de conversion

Non-Small Cell Lung Cancer Brain Metastasis: The Link between Molecular Mechanisms and Novel Therapeutic Approaches

The prognosis of patients suffering from non-small cell lung carcinomas (NSCLC) worsens significantly when brain metastasis occurs. Seeding to the brain usually happens relatively early in the course of disease and therefore, new therapies anticipating this complication would result in considerable improvement in outcomes. In this review, we address recent molecular data of NSCLC with a focus on the risk of the formation of brain metastasis. Included is new data on the involvement of miRNAs and lncRNAs in the rise of the cerebral seeding of NSCLC. We summarize novel therapeutic approaches developed in the light of these recent molecular discoveries

Unraveling Differences in Molecular Mechanisms and Immunological Contrasts between Squamous Cell Carcinoma and Adenocarcinoma of the Cervix

This study aims to refine our understanding of the inherent heterogeneity in cervical cancer by exploring differential gene expression profiles, immune cell infiltration dynamics, and implicated signaling pathways in the two predominant histological types of cervix carcinoma, Squamous Cell Carcinoma (SCC) and Adenocarcinoma (ADC). Targeted gene expression data that were previously generated from samples of primary cervical cancer were re-analyzed. The samples were grouped based on their histopathology, comparing SCC to ADC. Each tumor in the study was confirmed to be high risk human papilloma virus (hrHPV) positive. A total of 21 cervical cancer samples were included, with 11 cases of SCC and 10 of ADC. Data analysis revealed a total of 26 differentially expressed genes, with 19 genes being overexpressed in SCC compared to ADC (Benjamini–Hochberg (BH)-adjusted p-value &lt; 0.05). Importantly, the immune checkpoint markers CD274 and CTLA4 demonstrated significantly higher expression in SCC compared to ADC. In addition, SCC showed a higher infiltration of immune cells, including B and T cells, and cytotoxic cells. Higher activation of a variety of pathways was found in SCC samples including cytotoxicity, interferon signaling, metabolic stress, lymphoid compartment, hypoxia, PI3k-AKT, hedgehog signaling and Notch signaling pathways. Our findings show distinctive gene expression patterns, signaling pathway activations, and trends in immune cell infiltration between SCC and ADC in cervical cancer. This study underscores the heterogeneity within primary cervical cancer, emphasizing the potential benefits of subdividing these tumours based on histological and molecular differences.</p

PPrate: A Passive Capacity Estimation Tool

Knowledge of link capacities is essential, e.g., for ISPs to troubleshoot paths outside the boundaries of their networks. However, the vast majority of capacity measurement tools are based on active probing, which is not suitable for large scale studies of Internet paths characteristics. In this paper we present PPrate, a completely passive tool, that can extract capacity information of a path from the packet trace of a TCP connection. We validate PPrate using synthetic traces and real traces collected on PlanetLab. We compare PPrate with Pathrate, which is very accurate active tool, and show that they perform comparably. We finally apply PPrate on a large publicly available ADSL trace