The microbiome and cancer: creating friendly neighborhoods and removing the foes within

Alexandros G.Sfakianakis shared this article with you from Inoreader The microbiome and cancer: creating friendly neighborhoods and removing the foes within Μέσω Cancer Research Online First Articles The human body is colonized by the microbial cells that are estimated to be as abundant as human cells, yet their genome is roughly 100 times the human genome, providing significantly more genetic diversity. The past decade has observed an explosion of interest in examining the existence of microbiota in the human body and understanding its role in various diseases including inflammatory bowel disease, neurologic diseases, cardiovascular disorders, and cancer. Many studies have demonstrated differential community composition between normal tissue and cancerous tissue, paving the way for investigations focused on deciphering the cause-and-effect relationships between specific microbes and initiation and progression of various cancers. Also, evolving are the strategies to alter tumor-associated dysbiosis and move it towards eubiosis with holistic approaches to change the entire neighborhood or to neutralize pathogenic strains. In this review, we discuss important pathogenic bacte ria and the underlying mechanisms by which they impact cancer progression. We summarize key microbiota alterations observed in multiple tumor niches, their association with clinical stages, and their potential use in cancer diagnosis and management. Finally, we discuss microbiota-based therapeutic approaches. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Single-cell transcriptomic heterogeneity in invasive ductal and lobular breast cancer cells

Alexandros G.Sfakianakis shared this article with you from Inoreader Single-cell transcriptomic heterogeneity in invasive ductal and lobular breast cancer cells Μέσω Cancer Research Online First Articles Invasive lobular breast carcinoma (ILC), one of the major breast cancer histological subtypes, exhibits unique features compared to the well-studied ductal cancer subtype (IDC). The pathognomonic feature of ILC is loss of E-cadherin, mainly caused by inactivating mutations, but the contribution of this genetic alteration to ILC-specific molecular characteristics remains largely understudied. To profile these features transcriptionally, we conducted single-cell-RNA-sequencing on a panel of IDC and ILC cell lines, and an IDC cell line (T47D) with CRISPR-Cas9-mediated E-cadherin knock out (KO). Inspection of intra-cell line heterogeneity illustrated genetically and transcriptionally distinct subpopulations in multiple cell lines and highlighted rare populations of MCF7 cells highly expressing an apoptosis-related signature, positively correlated with a pre-adaptation signature to estrogen deprivation. Investigation of E-cadherin KO-induced alterations showed transcriptomic membran ous systems remodeling, elevated resemblance to ILCs in regulon activation, and increased sensitivity to IFN-γ mediated growth inhibition via activation of IRF1. This study reveals single cell transcriptional heterogeneity in breast cancer cell lines and provides a resource to identify drivers of cancer progression and drug resistance. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Radiomic detection of EGFR mutations in NSCLC

Alexandros G.Sfakianakis shared this article with you from Inoreader Radiomic detection of EGFR mutations in NSCLC Μέσω Cancer Research Online First Articles Radiomics is defined as the use of automated or semi-automated post-processing and analysis of multiple features derived from imaging exams. Extracted features might generate models able to predict the molecular profile of solid tumors. The aim of this study was to develop a predictive algorithm to define the mutational status of epidermal growth factor receptor (EGFR) in treatment-naïve patients with advanced non-small cell lung cancer (NSCLC). Computed tomography (CT)-scans from 109 treatment-naïve NSCLC patients (21 EGFR-mutant and 88 EGFR-wild type) underwent radiomics analysis in order to develop a machine learning model able to recognize EGFR-mutant from EGFR-WT patients via CT scans. A "test-retest" approach was used to identify stable radiomics features. The accuracy of the model was tested on an external validation set from another Institution and on a dataset from the Cancer Imaging Archive (TCIA). The machine learning model that considered both radiomic and clinica l features (gender and smoking status) reached a diagnostic accuracy of 88.1% in our dataset with an AUC at the ROC curve of 0.85, while the accuracy in the datasets from TCIA and the external Institution were 76.6% and 83.3%, respectively. Furthermore, 17 distinct radiomics features detected at baseline CT scan were associated with subsequent development of T790M during treatment with an EGFR inhibitor. In conclusion, our machine learning model was able to identify EGFR-mutant patients in multiple validation sets with globally good accuracy, especially after data optimization. More comprehensive training sets might result in further improvement of radiomics-based algorithms. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Ear Cartilage Reconstruction Combining Induced Pluripotent Stem Cell-Derived Cartilage and Three-Dimensional Shape-Memory Scaffold

Alexandros G.Sfakianakis shared this article with you from Inoreader Ear Cartilage Reconstruction Combining Induced Pluripotent Stem Cell-Derived Cartilage and Three-Dimensional Shape-Memory Scaffold Μέσω Tissue Engineering Part A - Table of Contents Tissue Engineering Part A, Ahead of Print. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Facial Nerve Repair by Muscle-Vein Conduit in Rats: Functional Recovery and Muscle Reinnervation

Alexandros G.Sfakianakis shared this article with you from Inoreader Facial Nerve Repair by Muscle-Vein Conduit in Rats: Functional Recovery and Muscle Reinnervation Μέσω Tissue Engineering Part A - Table of Contents Tissue Engineering Part A, Ahead of Print. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Glycosyltransferase ST6Gal-I promotes the epithelial to mesenchymal transition in pancreatic cancer cells [Cell Biology]

Alexandros G.Sfakianakis shared this article with you from Inoreader Glycosyltransferase ST6Gal-I promotes the epithelial to mesenchymal transition in pancreatic cancer cells [Cell Biology] Μέσω JBC Papers in Press ST6Gal-I, an enzyme upregulated in numerous malignancies, adds α2-6-linked sialic acids to select membrane receptors, thereby modulating receptor signaling and cell phenotype. In this study, we investigated ST6Gal-I's role in epithelial to mesenchymal transition (EMT) using the Suit2 pancreatic cancer cell line, which has low endogenous ST6Gal-I and limited metastatic potential, along with two metastati c Suit2-derived subclones, S2-013 and S2-LM7AA, which have upregulated ST6Gal-I. RNA-Seq results suggested that the metastatic subclones had greater activation of EMT-related gene networks than parental Suit2 cells, and forced overexpression (OE) of ST6Gal-I in the Suit2 line was sufficient to activate EMT pathways. Accordingly, we evaluated expression of EMT markers and cell invasiveness (a key phenotypic feature of EMT) in Suit2 cells with or without ST6Gal-I OE, as well as S2-013 and S2-LM7AA cells with or without ST6Gal-I knockdown (KD). Cells with high ST6Gal-I expression displayed enrichment in mesenchymal markers (N-cadherin, slug, snail, fibronectin) and cell invasiveness, relative to ST6Gal-I-low cells. Contrarily, epithelial markers (E-cadherin, occludin) were suppressed in ST6Gal-I-high cells. To gain mechanistic insight into ST6Gal-I's role in EMT, we examined the activity of EGFR, a known EMT driver. ST6Gal-I-high cells had greater α2-6 sialylation and activation of EGFR than ST6Gal-I-low cells. The EGFR inhibitor, erlotinib, neutralized ST6Gal-I-dependent differences in EGFR activation, mesenchymal marker expression and invasiveness in Suit2 and S2-LM7AA, but not S2-013, lines. Collectively, these results advance our understanding of ST6Gal-I's tumor-promoting function by highlighting a role for ST6Gal-I in EMT, which may be mediated, at least in part, by α2-6-sialylated EGFR. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Human genetic variants disrupt RGS14 nuclear shuttling and regulation of LTP in hippocampal neurons [Neurobiology]

Alexandros G.Sfakianakis shared this article with you from Inoreader Human genetic variants disrupt RGS14 nuclear shuttling and regulation of LTP in hippocampal neurons [Neurobiology] Μέσω JBC Papers in Press The human genome contains vast genetic diversity as naturally occurring coding variants, yet the impact of these variants on protein function and physiology is poorly understood. RGS14 is a multifunctional signaling protein that suppresses synaptic plasticity in dendritic spines of hippocampal neurons. RGS14 also is a nucleocytoplasmic shuttling protein, suggesting that balanced nuclear import/export and d endritic spine localization are essential for RGS14 functions. We identified genetic variants L505R (LR) and R507Q (RQ) located within the nuclear export sequence (NES) of human RGS14. Here we report that RGS14 encoding LR or RQ profoundly impacts protein functions in hippocampal neurons. RGS14 membrane localization is regulated by binding Gαi-GDP, whereas RGS14 nuclear export is regulated by Exportin 1 (XPO1). Remarkably, LR and RQ variants disrupt RGS14 binding to Gαi1-GDP and XPO1, nucleocytoplasmic equilibrium, and capacity to inhibit LTP. Variant LR accumulates irreversibly in the nucleus, preventing RGS14 binding to Gαi1, localization to dendritic spines, and inhibitory actions on LTP induction, while variant RQ exhibits a mixed phenotype. When introduced into mice by CRISPR/Cas9, RGS14-LR protein expression was detected predominantly in the nuclei of neurons within hippocampus, central amygdala, piriform cortex, and striatum, brain regions associated with learning and syna ptic plasticity. Whereas mice completely lacking RGS14 exhibit enhanced spatial learning, mice carrying variant LR exhibit normal spatial learning, suggesting that RGS14 may have distinct functions in the nucleus independent from those in dendrites and spines. These findings show that naturally occurring genetic variants can profoundly alter normal protein function, impacting physiology in unexpected ways. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.