Biology subjects

Stachtea, X.

Publications and source records attributed to Stachtea, X..

3 recordsLinked to original sources

bioRxiv2021

An atlas of inter- and intra-tumor heterogeneityof apoptosis competency in colorectal cancertissue at single cell resolution

Cancer cells ability to inhibit apoptosis is key to malignant transformation and limits response to therapy. Here, we performed multiplexed immunofluorescence analysis on tissue microarrays with 373 cores from 168 patients, segmentation of 2.4 million individual cells and quantification of 20 cell lineage and apoptosis proteins. Ordinary differential equation-based modelling of apoptosis sensitivity at single cell resolution was conducted and an atlas of inter- and intra-tumor heterogeneity in apoptosis susceptibility generated. We identified an enrichment for BCL2 in immune, and BAK, SMAC and XIAP in cancer cells. ODE-based modelling at single cell resolution identified an enhanced sensitivity of cancer cells to mitochondrial permeabilization and executioner caspase activation compared to immune and stromal cells, with significant inter- and intra-tumor heterogeneity. However, we did not find increased spatial heterogeneity of apoptosis signaling in cancer cells, suggesting that such heterogeneity is an intrinsic, non-genomic property not increased by the process of malignant transformation.

cancer biology↗

bioRxiv2021

Stratification Of Chemotherapy-Treated Stage III Colorectal Cancer Patients Using Multiplexed Imaging And Single Cell Analysis Of T Cell Populations

Colorectal cancer (CRC) has one of the highest cancer incidences and mortality rates. In stage III, postoperative chemotherapy benefits <20% of patients, while more than 50% will develop distant metastases. Predictive biomarkers for identification of patients with increased risk for disease recurrence are currently lacking, with progress in biomarker discovery hindered by the diseases inherent heterogeneity. The immune profile of colorectal tumors has previously been found to have prognostic value. The aims of this study were to evaluate immune signatures in the tumor microenvironment (TME) using an in situ multiplexed immunofluorescence imaging and single cell analysis technology (Cell DIVE). Tissue microarrays (TMAs) with up to three 1mm diameter cores per patient were prepared from 117 stage III CRC patients treated with adjuvant fluoropyrimidine/oxaliplatin chemotherapy. Single sections underwent multilplexed immunofluorescence with Cy3- and Cy5-conjugated antibodies for immune cell markers (CD45, CD3, CD4, CD8, FOXP3, PD1) and cell segmentation markers (DAPI, pan-cytokeratin, AE1, NaKATPase and S6). We applied a probabilistic multi-class, multi-label classification algorithm based on multi-parametric models to build statistical models of protein expression to classify immune cells. Expert annotations of immune cell markers were made on a range of images, and Support Vector Machines (SVM) were used to derive a statistical model for cell classification. Images were also manually scored independently by a Pathologist as high, moderate or low, for stromal and total immune cell content. Excellent agreement was found between manual and total automated scores (p<0.0001). Higher levels of multi-marker classified regulatory T cells (CD3+CD4+FOXP3+PD1-) were significantly associated with disease-free survival (DFS) and overall-survival (OS) (p=0.049 and 0.032), compared to FOXP3 alone. Our results also showed that PD1- Tregs rather than PD1+ Tregs were associated with improved survival. Overall, compared to single markers, multi-marker classification provided more accurate quantitation of immune cells with greater potential for predicting patient outcomes.

cancer biology↗

bioRxiv2020

Time Perception through the Processing of Verb Tenses: An ERP study regarding Mental Time Travel

Humans are equipped with the so-called Mental Time Travel (MTT) ability, which allows them to consciously construct and elaborate past or future scenes. The mechanisms underlying MTT remain elusive. This study focused on the late positive potential (LPP) and alpha oscillations, considering that LPP covaries with the temporal continuity whereas the alpha oscillations index the temporal organization of perception. To that end, subjects were asked to focus on performing two mental functions engaging working memory, which involved mental self-projection into either the present-past (PP) border or the present-future (PF) border. To evaluate underlying mechanisms, the evoked frontal late positive potentials (LPP) as well as their cortical sources were analyzed via the standardized low-resolution brain electromagnetic tomography (sLORETA) technique. The LPP amplitudes - in the left lateral prefrontal areas that were elicited during PF tasks - were significantly higher than those associated with PP, whereas opposite patterns were observed in the central and right prefrontal areas. Crucially, the LPP activations of both the PP and PF self-projections overlapped with the brains default mode network and related interacting areas. Finally, we found enhanced alpha-related activation with respect to PP in comparison to PF, predominantly over the right hemisphere central brain regions (specifically, the precentral gyrus). These findings confirm that the two types of self-projection, as reflected by the frontally-distributed LPP, share common cortical resources that recruit different brain regions in a balanced way. This balanced distribution of brain activation might signify that biological time tends to behave in a homeostatic way.

neuroscience↗